s-Block Metal Catalysts for the Hydroboration of Unsaturated Bonds

The addition of a B–H bond to an unsaturated bond (polarized or unpolarized) is a powerful and atom-economic tool for the synthesis of organoboranes. In recent years, s-block organometallics have appeared as alternative catalysts to transition-metal complexes, which traditionally catalyze the hydroboration of unsaturated bonds. Because of the recent and rapid development in the field of hydroboration of unsaturated bonds catalyzed by alkali (Li, Na, K) and alkaline earth (Mg, Ca, Sr, Ba) metals, we provide a detailed and updated comprehensive review that covers the synthesis, reactivity, and application of s-block metal catalysts in the hydroboration of polarized as well as unsaturated carbon–carbon bonds. Moreover, we describe the main reaction mechanisms, providing valuable insight into the reactivity of the s-block metal catalysts. Finally, we compare these s-block metal complexes with other redox-neutral catalytic systems based on p-block metals including aluminum complexes and f-block metal complexes of lanthanides and early actinides. In this review, we aim to provide a comprehensive, authoritative, and critical assessment of the state of the art within this highly interesting research area.


INTRODUCTION
Hydroborationthe addition of a boron−hydrogen bond to an unsaturated bondis a useful and atom-economic transformation for the synthesis of organoboranes. The addition of boranes (HBR 2 ) to CO or CN bonds (Scheme 1) results in formation of a boron−oxygen or nitrogen bond, which, along with hydrolysis, constitutes a two-step process equivalent to reduction. 1,2 Furthermore, the addition of boranes to carbon− carbon unsaturated bonds (e.g., alkenes or alkynes) results in the synthesis of a carbon−boron bond suitable for sequential transformations such as C−C couplings 3 (i.e., Suzuki coupling reaction 4,5 ).
In 1956, Brown et al. discovered the direct addition of a B−H bond across a CC bond using sodium borohydride-aluminum chloride mixtures. 6 This pioneering discovery marked a substantial breakthrough in the hydroboration reaction. 7 Using the simplest borane (BH 3 ), the transformation occurs spontaneously without the need for a catalyst to provide the anti-Markovnikov product. In this regard, the regioselectivity observed is rationalized as follows: (i) B−H addition occurs in a cis-fashion; (ii) the boryl moiety prefers the least sterically hindered carbon; and (iii) the hydridic character of the H−B bond favors interactions with an electropositive carbon in the transition state of the reaction. 8,9 Catecholborane (HBcat) and pinacolborane (HBpin) have emerged as alternatives to highly reactive BH 3 . Groundbreaking work by Kono and Ito et al. revealed that Wilkinson's catalyst, Rh(PPh 3 ) 3 Cl, underwent oxidative addition with HBcat (Scheme 2), 10 which led to the first example of metal-catalyzed hydroboration of alkenes and alkynes by Mannig and Noẗh et al. 11 Since then, research on transition-metal-based catalytic systems capable of providing hydroboration chemo-and regioselectively has increased exponentially. 12,13 Early-transition-metal, 14,15 first-row metal, 16,17 and lanthanide complexes 18−20 have also shown excellent activity and selectivity toward the hydroboration of polarized and unpolarized bonds. However, these materials have the drawbacks of high cost and toxicity. To overcome these problems, s-block metals have been applied as more sustainable alternatives.
In the past decade, the application of alkaline earth metals and, more recently, alkali metals has evolved rapidly. 21 Among the latest discoveries, the use of these metal complexes in catalysis, which was not thought to be possible merely two decades ago, stands out. With these breakthroughs, interest in the catalytic activity of group 1 and group 2 metals has increased tremendously. 22,23 Although some alkaline earth metals, such as magnesium and calcium, are among the most abundant metals in the Earth's crust (Figure 1), 24 their use in catalysis is still underdeveloped compared to, for instance, that of transition metals.
Organometallic complexes derived from early main group elements are known to be very reactive and difficult to isolate. Their high nucleophilic character and Brønsted basicity make them strong polar reagents. This high reactivity gives them high potential as catalysts for organic transformations that are traditionally catalyzed by transition-metal complexes. In terms of environmental hazards and toxicity, the replacement of expensive and harmful transition metals for abundant and nontoxic alkali and alkaline earth metals is highly desirable, particularly with regard to applications in the pharmaceutical industry or materials synthesis, where residual transition metals must be avoided.
Although the use of early main group metals in hydrofunctionalization catalysis has increased in the past decade, 25 their application is still fairly limited due to their tendency to undergo Schlenk-type equilibrium (section 2.3). 26 Whereas group 1 early metals (Li, Na, K) have been mostly limited to hydroboration reactions, group 2 metals (Mg, Ca, Sr, and Ba) have been widely studied and applied in a variety of hydrofunctionalizations of unsaturated bonds. 27−30 In terms of standard reactivity toward hydrofunctionalization of unsaturated bonds, alkaline earth metal catalytic systems differ depending on the polarization of the Y−H bond in the reactant. While hydridic Y−H bonds undergo σ-bond metathesis, protic Y−H bonds undergo protonolysis. Therefore, two general catalytic cycles can be distinguished (Scheme 3).
The year 2016 brought a breakthrough in the area of alkali and alkaline earth metal hydrofunctionalization of unsaturated bonds, specifically, with regard to the hydroboration reaction. Therefore, herein, we will disclose in detail all s-block (group 1 and group 2) metal complexes and their application in the hydroboration of polarized and unpolarized unsaturated bonds. First, we will briefly describe the different synthetic approaches for the synthesis of alkali-and alkaline earth metal catalysts and their reactivity toward hydroboration reactions (Section 2). Regarding the catalytic applicability, we have organized this section by reactions depending on the nature of the reduced bond: polarized (section 3) and nonpolarized (section 4). As the hydroboration of polarized bonds has been the most studied field, we have organized it in order of applicability: aldehydes and ketones (section 3.1) followed by main CN bonds such as N-heterocycles and imines (sections 3.2 and 3.3, respectively). Then we will disclose the hydroboration of more stable and thus less reactive compounds such as esters and amides (section 3.4) as well as carbonates and carbamates (section 3.5).
To close the section on polarized unsaturated bonds, we will focus on the hydroboration of other unsaturated systems, such as nitriles and isonitriles (section 3.6), isocyanates and carbodiimides (section 3.7), carbon dioxide (section 3.8), carboxylic acids (section 3.9), and sulfoxides (section 3.10). Finally, we will include hydroboration of C−C double and triple bonds: alkenes (section 4.1), alkynes (section 4.2), and strained ring systems such as epoxides (section 5). For each transformation, we will include and explain in detail all known examples of group 1 and group 2 metal catalysts in chronological order.
Over the past years, aluminum-and lanthanide-based catalysts have been used for hydroboration of organic compounds. Given the similarities in reactivity (Section 6), we decided to provide a comparison of s-block metal-based catalysts with those derived from aluminum (section 6.1) and lanthanides (section 6.2).
Very recently, Thomas et al. reported the decomposition of the previously perceived stable hydride source HBPin, a borane most often used in hydroboration reactions. This decomposition results in the formation of BH 3 which then may act as a "hidden" catalyst (see section 7). 31,32 We recommend the readers to be aware of this issue while reading our manuscript.
Finally, protocols utilizing a catalyst-free hydroboration approach are briefly discussed in section 7.2.
Please note that the use of heterobimetallic complexes that contain alkali or alkaline earth metals as counterions will be excluded from this review, as they have been recently reviewed by Mulvey et al. 33

S-BLOCK ORGANOMETALLIC COMPLEXES: SYNTHESIS AND REACTIVITY
In this section, we briefly describe the synthesis and representative examples of alkali and alkaline earth metal complexes applied to the hydroboration of unsaturated bonds. Moreover, the general reactivity trend and catalytic behavior of these complexes will also be discussed.

Synthesis of Alkali Metal Complexes
Although simple and commercially available compounds (e.g., n-BuLi, NaOH, and KOt-Bu) have been successfully applied in the hydroboration of unsaturated bonds, several alkali metal complexes have also been effectively synthesized and applied in this transformation. In this regard, there are two main synthetic approaches to afford alkali metal complexes: (i) the use of neutral N,N,N,N-ligands to form ion-pair complexes (Scheme 4a) and (ii) the formation of neutral alkali metal complexes by either deprotonation of a ligand containing an acidic proton or 1,2-addition of organolithium compounds to pyridines (Scheme 4b).
The first important route (Scheme 4a), explored by Okuda et al., consists of ligand coordination to easily accessible tetramethyl disilazides 34 followed by BPh 3 -mediated β-SiH abstraction. An alternative route provides group 1 metal complexes after treating the corresponding hydridotriphenylborates with a neutral N,N,N,N-ligand (tris{2-(dimethylamino)-ethyl}amine). These routes developed by Okuda and coworkers led to the successful synthesis of Li, Na, and K solventseparated ion pairs. 35−37 The second approach, which is most commonly used for the synthesis of alkali metal complexes, is based on a deprotonation strategy (Scheme 4b-1). Due to the high basicity of LiN-(SiMe 3 ) 2 (pK a ∼ 30), lithium diisopropylamide (pK a ∼ 35), and n-BuLi (pK a ∼ 50), 38,39 these lithium precursors can effectively remove acidic protons from phenol 40 and pyrrole derivatives, 41 among others. 42 In addition, β-diketiminate lithium complexes have been synthesized following the same strategy. 43 Finally, 1-lithio-2-alkyl-1,2-dihydropyridine complexes can easily be synthesized by nucleophilic addition of alkyl lithium to pyridines, forming soluble and active lithium complexes (Scheme 4b-2). In this regard, Mulvey et al. were able to successfully isolate and comprehensively characterize this type of Li complexes. 44 All of the above-mentioned strategies were applied to the synthesis of active alkali metal catalysts for the hydroboration of unsaturated bonds. All group 1 metal complexes will be presented, and their application will be discussed in section 3.

Synthesis of Alkaline Earth−Metal Complexes
The application of alkaline earth metal complexes in the hydroboration reaction has gained more attention than the application of group 1 metal complexes. For this reason, there are several examples of effective group 2 metal catalysts in the literature. As already described for alkali metal complexes (section 2.1), two main types of alkaline earth metal catalysts can be distinguished: (1) cationic complexes and (2) neutral complexes containing monoanionic or dianionic ligands.
The first type, developed by Okuda et al., relies on the synthesis of magnesium hydridotriphenylborate complexes 1 where a coordinative solvent, such as THF, provides the complex as a solvent-separated ion pair (Scheme 5a-1). 45 amidinates, 54 which have been applied in the hydroboration of polarized and unpolarized unsaturated bonds ( Figure 2).
The use of monoanionic ligands results in the corresponding stable alkaline earth metal complex bearing a reactive site (e.g., alkyl or silylamide ligands) that reacts with HBpin via σ-bond metathesis to afford an active metal hydride species. Moreover, this strong ligand−metal interaction prevents any kind of ligand redistribution, known as Schlenk-type equilibrium, 26 which would lead to a less reactive species. Although dianionic ligands, such as diols, have been widely used in group 2 metal catalysis, 55−57 examples of applications in hydroboration reactions are scarce.
In section 3, all group 2 metal catalysts and their application in hydroboration will be discussed in more detail.

Reactivity of s-Block Organometallic Complexes toward Hydroboration of Unsaturated Bonds
As previously mentioned, the chemistry of s-block organometallics is marked by their stable +1 (for alkali metals) and +2 (for alkaline earth metals) oxidation states. 65 In this regard, the ionic radii of the corresponding ions (groups 1 and 2) 66 increase as the group number decreases, leading to a decrease in electronic density and an increase in polarizability ( Figure 3).
These inherent variations influence the nature of metal-toligand bonding. In the case of heavier alkaline earth metals (Ca, Sr, and Ba), the nondirectional ionic interactions affect metal-toligand binding. Therefore, heteroleptic complexes tend to undergo Schlenk-type equilibrium, 26 leading to homoleptic metal complexes, which mostly differ in reactivity (Scheme 6). Concerning enantioselective catalysis, this ligand redistribution can also lead to nonchiral and more reactive homoleptic complexes, which would provide low or no enantioinduction (Scheme 6). To avoid ligand redistribution, considerable efforts have been made in ligand and catalyst design. In this regard, bior polydentate monoanionic ligands presenting hard donor sites and steric bulk provide efficient kinetic stability to avoid any kind of ligand redistribution. Alkaline earth metal complexes designed for catalytic hydroboration reactions are frequently based on a spectator ligand (and most of the cases, monoanionic ligand, L) and a reactive ligand (usually silylamide or an alkyl group).
In contrast to transition metals, which usually show reversible oxidation states, 67 s-block metals generally favor only one oxidation state, a fact that excludes catalytic pathways with redox features such as oxidative addition and reductive elimination. 68 Therefore, the catalytic steps are simplified and built around basic dipolar transformations.
As described in the Introduction, the nature of the hydrofunctionalizing agent determines the elemental catalytic steps (Scheme 3) of the transformation. 69 In this case, hydroboranes such as HBpin present a hydridic H−B bond; therefore, a general catalytic cycle (Scheme 7) is based on metal hydride 70,71 bond formation and its addition to an unsaturated bond, as follows: (i) σ-bond metathesis occurs between the polarized catalyst precursor, which bears a reactive labile ligand, and a polarized hydride reagent (H−Bpin). In this first step, a reactive L−Ae−H species is formed. (ii) The metal hydride species is inserted into an unsaturated bond via hydrometalation. (iii) Finally, the polarized hydride reagent H−B undergoes σ-bond metathesis to regenerate the active L−Ae−H catalyst and release the corresponding hydroborated product. 72 This general catalytic cycle, which is based on metal hydride formation and subsequent hydrometalation, can vary depending on the nature of the ligand and the metal. For alkali metal catalysts, which have either spectator monoanionic ligands or reactive ligands, HBpin activation and the catalytic cycle can differ from those described in Scheme 7. Moreover, the hydroboration catalyzed by metal catalysts bearing a dianionic ligand or by a cationic complex also occurs via different

Scheme 6. Schlenk-Type Equilibrium
Chemical Reviews pubs.acs.org/CR Review pathways. Different HBpin activations and mechanisms will be discussed in detail in section 3.

Aldehydes and Ketones
The first example of s-block metal-catalyzed hydroboration of carbonyl compounds was reported in 2011 by Clark et al. and involved the use of sodium tert-butoxide 4 as the precatalyst (Scheme 8). The authors demonstrated that sodium alkoxide can catalytically activate pinacolborane toward the addition to CO bonds in ketones. In this regard, the initial activation of pinacolborane by NaOt-Bu forms hydride species I, which adds to the CO bond. The formed alkoxide II activates pinacolborane to generate species III, which subsequently adds to the CO bond, generating the corresponding product and sodium alkoxide II, which enters the new catalytic cycle. Since the active hydride species could not be isolated or characterized by means of NMR spectroscopy, the authors postulated an equilibrium between sodium trialkoxyborohydride and other boron alkoxy and hydride species, which can also act as hydride sources. 73 β-Diketiminate magnesium complex 5, as reported by Hill et al., showed catalytic activity toward the hydroboration of aldehydes and ketones. 74 Excellent yields were afforded for a wide range of carbonyl compounds for the first time using magnesium-based catalysts under mild reaction conditions (ambient temperature) and at low catalyst loadings (0.05−0.5 mol %). Mechanistically, the addition of HBpin to a solution of 5 leads, via σ-bond metathesis, to stoichiometric formation of n-BuBpin and heteroleptic magnesium hydride species 6, which exists in equilibrium with labile magnesium borohydride species of the anion [n-BuHBpin] − . Next, the addition of the substrate leads to the formation of a heteroleptic magnesium species resulting from the insertion of the carbonyl group into the magnesium hydride bond. Finally, σ-bond metathesis with HBpin releases a boronic ester and recovers the catalyst (Scheme 9).
As described in section 2, Stasch et al. developed phosphinoamido−magnesium−hydride complexes 7−10 (Scheme 10) to investigate whether a ligand that favors bridging and terminal coordination modes can be beneficial in terms of activity compared to magnesium complexes such as 5. 75 Complexes 7−9 were shown to be very active for the hydroboration of ketones, providing quantitative conversions under mild reaction conditions, short reaction times, and low catalyst loadings (0.05 mol %). The authors, however, limited the substrate scope to only two ketonesbenzophenone and 2adamantanone.
The addition of Li−H species to the carbonyl group was first reported in 2012 by Stasch et al., who showed that a hydrocarbon-soluble lithium hydride complex can effectively undergo hydrometalation to benzophenone. 51 It was not until 2016, however, that the first catalytic application of light alkali metal complexes was reported. Okuda et al. employed a series of lithium, sodium, and potassium hydridotriphenylborate complexes 11−13 for the selective hydroboration of benzophenone as a model substrate (Scheme 11). 35 Compared to sodium and potassium complexes 12 and 13, respectively, lithium complex 11 exhibited superb activity, exhibiting a remarkably high TOF of 66.6 × 10 3 h −1 or 18 s −1 .
Complex 11, the most active catalyst, was applied for the hydroboration of several ketones and aldehydes. Mechanistically, the authors postulate that lithium hydridotriphenylborate 11 reacts rapidly with the carbonyl compound to give intermediate [(L)M][R 1 R 2 CHOBPh 3 ] (I), whereas no reaction between 11 and HBpin or BPh 3 and HBpin was observed. Finally, intermediate I reacts further with HBpin to give the desired product and regenerated 11. The insertion step appears to be equally fast for all metals (Li, Na, and K), but the catalyst regeneration (or group transfer) is faster for Li complex 11 than for Na and K 12 and 13, respectively. The authors suggested that the group-transfer step is rate determining. The group-transfer step through a direct hydride−alkoxide exchange via σ-bond metathesis was discarded, and regeneration of the active species 11 was suggested to occur by hydride abstraction from HBpin to generate LiH and BiPh 3 (Scheme 11). Moreover, coordination of Me 6 TREN is crucial for high activity; in the absence of the coordinating ligand, the catalyst activity significantly decreased. The Me 6 TREN ligand offers a unique combination of flexible coordination and retention of the Lewis acidity of the lithium cation to become a highly active catalyst. Thus, the high activity of the Li catalyst is thus explained by the higher degree of polarization of lithium in the [(L)Li][R 1 R 2 CHOBPh 3 ] intermediate compared with sodium and potassium. Moreover, this chelation most likely prevents lithium from forming aggregates. 36 Similarly, macrocyclic Me 4 TACD has also been used as an N,N,N,N-type neutral ligand to afford complexes 14− 16. 37 When applied for hydroboration of benzophenone, these complexes exhibited much lower activity than their Me 6 TREN analogues. Nevertheless, the reactivity trend of Li ≫ Na ≥ K was also observed in this case.
Lin et al. reported a simple strategy to stabilize heteroleptic magnesium alkyl species by a TPHN-metal−organic framework (TPHN = 4,4′-bis(carboxyphenyl)-2-nitro-1,1′-biphenyl), thus avoiding any kind of Schlenk equilibrium that could lead to inactive Mg species. The authors succeeded in a straightforward metalation of secondary building units of Zr-MOF with MgMe 2 and the application of this magnesium-supported catalyst 17 (Scheme 12) for the hydroboration of a wide range of carbonyl compounds, such as aldehydes and ketones. Impressively, Mg-functionalized MOF 17 displayed high turnover numbers and could be reused more than 10 times with no loss of activity. 76 In addition, Okuda et al. developed magnesium hydrotriphenylborate complex 1 (Scheme 13), which proved to be an active catalyst for the hydroboration of various polarized bonds. 45 Although complex 1 was active for the hydroboration of aldehydes with as low as 0.05 mol % catalyst loading, lower conversions and longer reaction times were required when ketones were used in the reaction. Moreover, since the reactions were carried out in DMSO, the authors observed competition between the reduction of carbonyls and sulfoxides (see section 3.10).
To expand the catalyst versatility, Okuda et al. designed a new molecular magnesium complex 18 containing an N,N,N,N-type macrocyclic ligand (Scheme 13). Interestingly, the basic amido function is blocked by the Al(iBu) 3 coordination in order to avoid the formation of large clusters. 77 Complex 18 was subsequently applied for the catalytic hydroboration of a wide range of substrates, including ketones. Compared to its ligandfree analogue 1, magnesium complex 18 showed lower catalytic activity toward the hydroboration of ketones which may be explained by the oversaturated, sterically encumbered fivecoordinate magnesium center.
It was not until 2017 that the first calcium-catalyzed hydroboration of carbonyl compounds appeared. Sen et al. designed a benzamidinato calcium complex 19 that was active toward the hydroboration of aldehydes and ketones (Scheme 14). By using complex 19, excellent yields could be obtained under mild reaction conditions, short reaction times, and low catalyst loadings. 78 Moreover, this catalytic system showed good functional group tolerance toward OH and NH groups as well as C−C double bonds.
Wu, Liu, and Zhao et al. showed that a catalytic hydroboration of carbonyl compounds could be initiated simply by NaOH 20 (Scheme 15). 79 The authors postulated that the reaction is possible due to the formation of an anionic borodihydride species from the reaction of borane and NaOH, which then acts as a precatalyst. The formation of the anionic borodihydride was corroborated when the authors used 9-BBN as a hydride source to isolate and characterize the dihydride species, as the attempt to obtain such dihydride from HBpin resulted in the formation of unanalyzable species.
Taking advantage of the excellent hydrogen-transfer ability of dihydropyridines, Mulvey and Roberston et al. described the successful application of lithium tert-butyldihydropyridine complex 21 in the hydroboration of aldehydes and ketones. 80 This highly hydrocarbon-soluble catalyst exhibited excellent activities, providing quantitative conversions in less than 30 min, in almost all cases. On the basis of the NMR studies, the authors suggested that complex 21 undergoes hydrometalation of the CO bond, releasing rearomatized t-BuPy and Li alkoxide. Finally, the Li alkoxide species activates HBpin via a 6membered transition state with t-BuPy to regenerate the Li-1,2-dihydropyridine 21 and the desired boronic ester (Scheme 16).
Ma et al. designed a series of bulky amido magnesium complexes 22−25 ( Figure 4), which could be easily prepared by treating the corresponding secondary amine and 2 equiv of the Grignard reagent (MeMgI). 81 All complexes exhibited excellent activities toward ketone hydroboration, although complex 25 provided the best results. However, when sterically hindered ketones were used, elevated temperature and prolonged time were necessary to achieve good conversion.
In 2018, Sen et al. reported a wide range of accessible and active lithium compounds (26−28, Scheme 17). 82 2,6-Di-tertbutyl phenolate lithium 26, 1,1′-dilithioferrocene 27, and βdiketiminate lithium 28 and exhibited excellent activities toward aldehyde and ketone hydroboration. Based on the results of NMR spectroscopy and DFT calculations, the authors provided mechanistic insight into the reaction catalyzed by complex 26. A comparative study of the hydroboration of p-methoxybenzaldehyde using N-adamantyliminopyrrolyl complexes 29−33 with Group 1 and Group 2 metals was carried out by Panda et al. (Scheme 18). 41 The results showed that group 1 complexes rapidly led to the formation of the corresponding product within 30 min for lithium and sodium complexes 29 and 30, respectively. The potassium analogue showed the highest activity, and the reaction was finished in less than 20 min. Thus, potassium complex 31 was applied for the hydroboration of aldehydes and ketones, showing good functional group tolerance. Moreover, the authors found that magnesium complex 32 and calcium complex 33 exhibited similar reactivity and were less active than the corresponding group 1 metal complexes 29−31.  Xue and Bao et al. demonstrated that readily available n-BuLi 34 is able to effectively catalyze the hydroboration of aldehydes and ketones. With as little as 0.1 mol % precatalyst, the authors were able to reduce aromatic and aliphatic aldehydes and ketones, showing excellent functional group tolerance, under mild reaction conditions: in most cases in just 20 min. On the basis of DFT calculations, the authors proposed that n-BuLi 34 reacts with pinacolborane to provide a Li-butylborate species I which upon reduction of the aldehyde leads to the lithium alkoxide, which presumably binds to the n-BuBpin, forming adduct II. Adduct II then undergoes ligand exchange with pinacolborane, affording species III to form the active catalytic species. A thermodynamically favored nucleophilic attack of the alkoxide to the boron atom affords Li boronate species V, in which a carbonyl compound binds to the lithium cation, favoring the hydride attack (TS VII). The obtained species VIII finally reacts with another molecule of pinacolborane, affording the desired compound and the regenerated active species III (Scheme 19). 83 A similar study was reported at the same time by An et al., who showed the excellent reactivity of n-BuLi 34 toward the hydroboration of aldehydes and ketones. Varying the reaction conditions compared to those used by Xue and Bao et al., 83 such as performing reactions with higher catalyst loading but lower temperature (0°C) and using THF as a solvent, resulted in formation of the desired product in just 5 min. Remarkably, α,βunsaturated ketones and aldehydes underwent selective 1,2hydroboration, affording the corresponding allylic alcohols. 84 Moreover, the same authors also reported the catalytic application of NaH 35 for the hydroboration of aldehydes and ketones (Scheme 20). 85 This NaH-catalyzed hydroboration of α,β-unsaturated substrates was completely regioselective, affording the corresponding allylic alcohols in excellent yields.
The concept of magnesium(I) complexes was first presented in 2007 by Stasch et al.; 86,87 however, their first application in catalytic hydroboration was reported by Ma et al., who applied a series of unsymmetrical β-diketiminatomagnesium(I) complexes 36−38 as precatalysts (Scheme 21) for the hydroboration of aldehydes and ketones, among others. 88 The reduction of CO bonds was performed under mild reaction conditions and at low catalyst loadings. From a mechanistic point of view, the authors proposed that dimeric Mg(I) complex 38 reacts with HBpin to form dimeric magnesium boryloxide complex 39, arising from the decomposition of HBpin. Compound 39 reacts with another molecule of HBpin, forming catalytically active Mg(II) complex 40. Although catalytically active Mg(II) 40 has been reported as a well-defined species active toward hydroboration of unsaturated bonds, it is worth mentioning that the combination of Mg(I) dimers with pinacolborane provides additional reactive boron-containing species, which could also be considered active in hydroboration (see section 7.1).
An interesting use of magnesium and calcium complexes for the hydroboration of aldehydes and ketones has been reported by Vanka and Sen et al. Here, β-diketiminatomagnesium and -calcium complexes 41 and 42 allowed formation of the desired products under mild reaction conditions, short reaction times, and low catalyst loadings (Scheme 22). On the basis of the hemilabile bond between the pyridyl group and the metal center as well as the results of DFT calculations, the authors postulated that the metallic center does not partake in any activation, but rather binds two ligands, each of which is capable of acting as a catalytic site for the hydroboration. Thus, the calcium enables the formation of a dual site catalyst, which would be more efficient than just employing a pyridine moiety as a single site catalyst in the reaction. It should be noted, however, that the authors did not conduct any control experiments with just a ligand or pyridine to confirm the proposal. 89 The presented work could therefore be considered as an example of organocatalytic transformation.
Following the trend of Xue and Bao, who used readily available n-BuLi as a precatalyst, 83 Kucinśki and Hreczycho reported that commercially available and inexpensive LiHBEt 3 43 shows high activity toward the catalytic hydroboration of a wide range of aldehydes and ketones. 90 Under solvent-free conditions, with as little as 0.1 mol % precatalyst, quantitative conversions were reported for a wide range of substrates.
Furthermore, An et al. reported the successful hydroboration of aldehydes and ketones using lithium tert-butoxide 44 91 and potassium carbonate 45 92 as precatalysts. Excellent yields were obtained under mild reaction conditions and catalyst loadings of 0.5−1 mol %. Interestingly, lithium tert-butoxide 44 showed higher activity than its sodium analogue 4, which was studied by Clark et al. 73 Although commercially available lithium complexes were tested as efficient precatalysts, commercially available magnesium compounds were not applied for the hydroboration of carbonyl compounds until Rueping et al. applied readily available Mg(n-Bu) 2 46 for the chemoselective hydroboration of α,β-unsaturated ketones (Scheme 23). For the first time, this simple and readily available precatalyst was successfully applied for the highly 1,2-selective hydroboration of α,β-unsaturated ketones, achieving excellent yields and chemoselectivities for a wide range of enones and ynones with low catalyst loadings, short times, and mild reaction conditions. 93 Compared to other Mg complexes previously applied for hydroboration of α,β− unsaturated compounds, 45,76 precatalyst 46 provides better conversions in shorter times.
Moreover, Grignard reagents have been applied by Ma et al. in the hydroboration of aldehydes and ketones. The high concentration of the reaction mixture ensured excellent conversions in the presence of MeMgI 47 (aldehydes: 0.05 mol %, ketones: 0.5 mol %) in 20 min. 94 Very recently, Harder et al. reported the use of calcium amidinate complexes 48−51 with various anionic ligands or counterions for the hydroboration of ketones 95 and compared their activity with that of previously reported complex 19 (Scheme 24). 78 The authors concluded that complex 48 exhibited far better activity than complex 19. The authors attribute this observation to the different amidinate spectator ligands' bulkiness (buried volume V B = 34.0% for 48 and V B = 28.1% for 19), both in N,N-coordination mode, and the presence of aryl substituents in complex 48, making calcium more electrophilic. Further increasing the metal center electrophilicity by introducing the [B(C 6 F 5 ) 4 ] − anion (complex 49) led to an improvement in the catalytic performance. Finally, catalysts 50 and 51 outperformed all the other catalysts, which led to the proposal of two different mechanistic pathways depending on the ligand.
Mechanistically, for hydridic complexes 50 and 51 the authors proposed that in similar metal−hydride hydroboration reactions, Ca−H I undergoes hydrometalation to provide calcium alkoxide II, which via nucleophilic attack to the boron atom forms zwitterionic species III. Finally, after hydride transfer, complex IV is obtained, the product is released, and the catalyst regenerates the catalysts. Alternatively, a pathway in which Scheme 23. Mg-Catalyzed Regioselective Hydroboration of α,β-Unsaturated Ketones, Developed by Rueping et al.

Scheme 24. Calcium Catalysts for Hydroboration of Ketones
Chemical Reviews pubs.acs.org/CR Review hydride is not transferred from the metal to the ketone, but directly from the borate (species V), cannot be excluded.
In the case of catalysts 48 and 49, no metal hydride formation was observed, as activation of HBpin occurs via Ca−O interactions. This behavior is in agreement with the increasing reaction rates and Lewis acidity of the calcium center. Thus, the authors postulated a mechanism for 48 and 49 in which the metal catalyst activates HBpin to form adduct VI. Substrate coordination ensures polarization of the CO bond (VII), thus making it reactive toward hydride addition via direct B−H/C O addition. Lastly, species VIII releases the corresponding boronic ester product and the catalyst is regenerated.
Kucinśki and Hreczycho reported the first example of a catalytic hydroboration in the presence of easily available potassium fluoride (KF) 52. Thus, ketones and aldehydes, bearing a wide range of functional groups, were successfully reduced to the corresponding primary and secondary alcohols under mild reaction conditions (DMF, room temperature) and short reaction times (30−60 min). 96 Similarly, An et al. applied lithium bromide (LiBr) 53 for hydroboration of various organic compounds, such as aldehydes and ketones, acid chlorides, esters, amides, nitriles, alkenes, and alkynes as well as epoxides. Out of all tested substrates, only hydroboration of aldehydes and ketones provided the desired products. With as little as 0.5−1 mol % of LiBr, various substrates bearing aliphatic and aromatic substituents were reduced under mild reaction conditions and in short reaction times. 97 Very recently, Maron, Venugopal, and co-workers reported (Me 6 TREN)−magnesium alkoxide complex 54 and magnesium dialkoxide 55 as active catalysts for the hydroboration of ketones. 98 The sterically hindered magnesium complex 54 was employed as a model catalyst to explore the role of magnesium alkoxides for ketone hydroboration (Scheme 25). Control experiments and DFT calculations suggest that the hydride transfer from pinacolborane to the CO bond occurs in a concerted reaction pathway through a six-membered ring transition state (TS-1). On the basis of these results, the authors discarded the possibility of the formation of any magnesium hydride intermediate (cf. Scheme 28). The authors explored the substrate scope by using homoleptic dialkoxide 55 as a simplified version of 54. Excellent yields were obtained for a wide range of dialkyl ketones, enones, and acetophenone derivatives, showing good functional group tolerance. It is important to highlight the excellent activities of 55, competing favorably with the other Group 1 and Group 2 metal catalysts.
Recently, Liu and Cui reported the activity of dinuclear magnesium hydride 56 stabilized by a phosphinimino amide ligand. 99 Under mild reaction conditions and in short reaction times, complex 56 was able to successfully catalyze the hydroboration of a wide range of aldehydes, acetophenonederived ketones, and enones (Scheme 26).
Asymmetric Hydroboration of Ketones. Although the catalytic hydroboration of carbonyl compounds has been widely studied using magnesium catalysts, the catalytic enantioselective version has been exclusively limited to transition-metal catalysts. 100 104,105 there are only two examples of enantioselective magnesiumcatalyzed hydroborations. 106 The first example of enantioselective magnesium hydroboration of prochiral ketones was reported by Rueping et al. using Mg-(R)-BINOL derived complex 57. 107 With this in situ formed catalyst, 108 excellent yields and enantioselectivities could be obtained for a wide range of acetophenone and 1-indanone derivatives (Scheme 27). Moreover, catalyst 57 was applied for the hydroboration of α,β-unsaturated ketones, with exclusive 1,2-addition, achieving excellent enantioselectivities for a wide range of enones and ynones. The authors suggested a cooperative magnesium−ligand activation mode of HBpin, which is supported by the results of NMR spectroscopy and DFT calculations (Scheme 28). NMR experiments showed that, in contrast to other magnesium hydroboration examples, no Mg−H species was observed when 57 and HBpin were mixed. NMR spectroscopy measurements also showed that in stoichiometric experiments only one molecule of HBpin is necessary for the quantitative reduction of ketone, in agreement act as a noninnocent ligand and is involved in HBpin activation. In this regard, when HBPin coordinates to the O atom of 57, it becomes more electron rich and facilitates hydride transfer to CO bond. This hydride transfer is also favored not only by the increase of the hydridic character of HBpin but presumably also by the increased electrophilic character of the substrate upon coordination to the Mg center. The computed energy profile reveals that the hydride-transfer step is predicted to be the ratelimiting and enantiodetermining step. In this case, the origin of enantioselectivity arises from the steric repulsion between the substituent at the 3′-position of the BINOL skeleton and the aryl substituent of the ketone. Thus, the energy difference of 2.5 kcal mol −1 between both transition states in the hydride transfer step and the absolute configuration of the products are in agreement with the experimental results. Similarly, Gade et al. developed magnesium−boxmi complex 58 (boxmi = bis(oxazolinylmethylidene)isoindoline) for the hydroboration of a wide range of acetophenone derivatives (Scheme 29). 109 On the basis of the results of NMR spectroscopy and DFT calculations, the authors suggest a mechanistic pathway that involves a reactive borohydride intermediate (59) formed via metathesis with a simultaneous release of Me 3 SiCH 2 BPin. Although complex 58 showed excellent enantioselectivity toward acetophenone derivatives, competing favorably with Rueping's catalyst 57 (Scheme 26), complex 58 showed a narrower substrate scope.
Very recently, Melen et al. developed the enantioselective lithium-catalyzed hydroboration of aryl alkyl ketones (Scheme 30). Lithium complex 60 formed in situ between LDA and a chiral BINOL-derived ligand generated secondary alcohols in good to excellent yields; however, the optical purities of the obtained products were rather low and did not exceed 60% ee. Mechanistically, the authors showed that the phenolic proton in the ligand is deprotonated with LDA and that subsequent addition of HBpin leads to the formation of reactive trialkoxyborohydride species 61, which is responsible for the hydride transfer to the CO bond. 110

Pyridines
In 2010, Hill et al. found that β-diketiminate magnesium complex 5 promoted the dearomatization of pyridine. By singlecrystal X-ray diffraction analysis and NMR spectroscopy, they observed that upon mixing of 5 and pyridine coordination takes place rather than alkyl addition. Treatment of the pyridyl complex with phenylsilane, a reagent known for the synthesis of well-defined magnesium hydrides, resulted the formation of nbutylphenylsilane. However, no evidence of a Mg−H species was found. Instead, the formation of a mixture of 1,2-and 1,4dihydropyridines was observed (Scheme 31a). 111,112 The product distribution was in agreement with the seminal work from Ashby who demonstrated MgH 2 addition to pyridine. 113,114 These stoichiometric studies led to the development of the first catalytic system based on magnesium hydride species for the hydroboration of unsaturated bonds. In this case, magnesium complex 5 was shown to catalyze the hydroboration of a wide range of pyridines, leading to mixtures of 1,2-and 1,4dihydropyridine products (Scheme 31b), with a preference for the latter. 115,116 Mechanistically, the magnesium-catalyzed hydroboration of pyridine derivatives did not differ from the stepwise stoichiometric studies previously accomplished by the same group. The authors postulate that the precatalyst 5 reacts with pinacolbor-  117 Focusing first on stoichiometric reactivity, a tetranuclear cluster 62 showed exceptional selectivity toward hydride transfer to the 2-position of the pyridine, with no isomerization even at elevated temperatures and prolonged heating. On the other hand, the octanuclear cluster analogue showed temperature-dependent mixtures with 1,2-and 1,4-selectivity. Because of the exceptional 1,2-selectivity, the authors applied 62 in the catalytic hydroboration of a wide range of pyridine derivatives. Whereas the use of stoichiometric Mg−H addition to pyridine led to the formation of a 1,2-regioisomer exclusively, the use of catalytic amounts of 62 resulted in lower regioselectivity. The inactivity observed for 2,6-lutidine supported the mechanistic hypothesis of an initial hydride transfer to the 2-position prior to the isomerization to the 4-position. The difference in regioselectivity of the stoichiometric and catalytic reactions led the authors to hypothesize that the two metallic centers of the catalysts might be operating in different catalytic stages of the cycle, which could potentially result in the preference of regioselectivity. The  which could directly transfer a hydride from boron to either the 2-or 4-position of a pyridine ligand, resulting in the formation of a magnesium 1,2-DHP or 1,4-DHP mixture (V). Importantly, multinuclear magnesium 62 showed slightly better performance than the mononuclear magnesium complex 5. 115,116 In 2016, Stasch et al. developed phosphinoamido−magnesium−hydride complex 8 ( Figure 5), which was shown to be very active for the hydroboration of ketones. 75 When applied to the hydroboration of pyridine, complex 8 did not lead to full conversion due to decomposition of HBpin under harsh reaction conditions, thus showing lower catalytic activity than the previously developed magnesium complexes 5 and 62 developed by Hill 115 and Harder,117 respectively.
In the same year, Okuda et al. applied magnesium complex 18, containing an N,N,N,N-type macrocyclic ligand ( Figure 5), for the hydroboration of pyridine, which regioselectively afforded the 1,4-insertion product. 77 Similarly, Parkin et al. developed [Tism PriBenz ]MgMe complex 63 ( Figure 5). 118 Although the precatalyst provided the 1,4addition product with high regioselectivity, the authors did not further investigate the substrate scope.
Tetranuclear siloxide/amide strontium complex 64, which is active for the hydroboration of pyridine and its derivatives (Scheme 33), was reported by Harder et al. 119 In terms of activity and 1,4-regioselectivity, complex 64 competes favorably with the magnesium catalysts reported to date. The authors also developed tetranuclear siloxide/amide barium complex 65, which is an analogue of 64, for the hydroboration of pyridines. Compared to strontium complex 64, barium complex 65 was slightly more active, although in some cases, this increase in activity occurred at the expense of regioselectivity. It is important to highlight the excellent activity and good selectivity of complex 65 when chlorinated pyridine was tested, which thus far has been converted only with the use of an iron catalyst. 120 Okuda  117 Okuda et al. also reported the synthesis of cationic magnesium hydride species 3 (Figure 7) stabilized by an N,N,N,N-type macrocycle. 46 When 3 was treated with pyridine, complex 70 was obtained. Remarkably, complex 70, which contains a 1,2dihydropyridine as a ligand, did not isomerize to the 1,4regioisomer 71, even at high temperature, in excess pyridine, and after a long time. The conversion of 70 to 71 was achieved by adding catalytic amounts of complex 72. The authors speculated that the strong Lewis acidic Mg 2+ complex 72 accelerated the transformation of 70 to 71. These three magnesium complexes were further applied for the catalytic hydroboration of pyridine. Whereas complexes 70 and 71 provided a mixture of 1,2-and 1,4-regioisomers (ratio 1:3 and 1:9, respectively), complex 72 exclusively provided the 1,4-regioisomer. Interestingly, Park and Chang et al. found that potassiumbased precatalysts not only are active for the hydroboration of CO bonds but also provide excellent regioselectivities for the hydroboration of pyridines and their derivatives. Potassium tertbutoxide 73 together with 18-crown-6 showed excellent activities and regioselectivities for the hydroboration of a range of N-heteroarenes (Scheme 34), achieving N-boryl-1,4dihydropyridines in excellent yields. Mechanistic studies revealed that in situ formed BH 3 forms an adduct with Nheteroarenes to which HBpin is selectively added to break the Naromaticity. Mechanistic investigations supported by NMR spectroscopy, DFT calculations, and kinetic studies revealed that initially KO-t-Bu reacts with HBpin to rapidly produce borohydrides species I, which are in equilibrium (including BH 3 ). The pyridine substrate then reacts with BH 3 to generate a pyridine·BH 3 adduct II that undergoes nucleophilic hydride attack by a borohydride species, forming 1,4-dihydropyridyl borohydride III, which is a resting intermediate. Then a hydride transfer from III to HBpin slowly regenerates the reactive borohydrides I and 1,4-dihydropyridyl borane IV, which finally reacts with a second molecule of pinacolborane to afford the N-Bpin-1,4-dihydropyridine product and BH 3 , probably via σbond metathesis. 122 Recently, He and Zhang et al. reported the regioselective 1,2hydroboration of N-heteroarenes using potassium tert-butoxide 73. 123 The authors found that replacing THF with a nonpolar solvent, such as benzene, completely changed the regioselectivities observed by Chang et al. 122 toward selective 1,2-addition. Therefore, a range of N-heteroarenes could be selectively hydroborated, affording the corresponding N-boryl-1,2-dihydropyridine derivatives in excellent yields and selectivity. When KO-t-Bu 73 and HBpin were mixed a white precipitate was obtained together with t-BuOBpin. The authors suggested that the white precipitate is KH, which indeed in subsequent experiments performed the same way as KO-t-Bu 73 (Scheme 35). Interestingly, other alkali metal hydrides (LiH and NaH) provided lower regioselectivity. These findings corroborated the hypothesis that KH is formed after mixing 73 and HBpin and that KH was the active hydride species.
Regarding the regioselectivity, the authors propose that the 1,2-regioselectivity relies on the reaction between K-compound I with HBpin, which is faster than the isomerization of I to II. Therefore, once I is formed, the 1,2-regiosomer will be afforded together with KH. Control experiments confirmed that the isomerization from I to II occurs due to stability of N-boryl-1,2hydropyridine (Scheme 35). 123 Hence, polar and coordinative solvents such as THF favor the isomerization toward intermediate II, whereas C 6 D 6 suppresses it.
A comparison of the KO-t-Bu-catalyzed hydroboration of Nheterocycles reported by Park and Chang et al. 122

and He and
Zhang et al. 123 shows that the active hydride species (and thus, the regioselectivity) depends on the nature of the solvent. Whereas reactions carried out in THF and in the presence of 18crown-6 provide BH 3 as active hydride species and 1,4regioisomers, the reactions carried out in C 6 D 6 and in the absence of 18-crown-6 form KH as a hydride donor, and 1,2regioisomers are obtained.
Bai and Lan and co-workers performed DFT calculations to investigate the mechanism of the alkaline earth metal catalyzed hydroboration of pyridines with pinacolborane. 124 The authors

Imines
Imines, which are easily accessible from carbonyl compounds and primary amines, are suitable precursors for the preparation of secondary amines. In 2013, Hill et al. reported the excellent catalytic activity of magnesium complex 5 for the hydroboration of N-aryl and N-alkyl aldimines and ketimines (Scheme 37). 125 For reactions that required temperatures higher than 60°C and prolonged times, poor yields were obtained due to the decomposition of catalyst. The authors observed in several reactions B 2 pin 3 as a decomposition pathway byproduct. By means of NMR spectroscopy, the authors established that when complex 5 is mixed with HBpin, dimeric species 6 is formed together with n-BuBpin, which exist in equilibrium with Kinetic studies displayed a second-order rate in [imine] and a zero order in [HBpin], and in the excess of pinacolborane, a decrease of the reaction rate was observed, consistent with HBpin acting as an inhibitor. On the contrary, the excess of imine substrate showed no catalyst inhibition at higher initial concentrations. Finally, kinetic studies showed that the reaction is first order in [catalyst], which is consistent with the monomeric nature of the insertion intermediate.
Lin et al. applied magnesium-functionalized Zr-MOF 17 for the hydroboration of imines to give N-borylamines. 76 Although the complete conversion of N-benzylideneaniline was observed with a catalyst loading of 0.05 mol %, rather long reaction times were reported for other aldimines and ketimines, limiting the applicability of the catalyst (Scheme 38a).
Magnesium hydrotriphenylborate complex 1 applied for the reduction of a variety of polarized bonds was used for Nbenzylideneaniline as a model substrate (Scheme 38b). 45 Similar to Lin's finding, 76 harsher reaction conditions and a long reaction time were necessary to afford full conversion of this relatively reactive imine.
N-benzylideneaniline was hydroborated by Okuda et al. in the presence of magnesium complex 18 containing an N,N,N,N-type macrocyclic ligand (Scheme 34c). 77 The authors suggested that the presence of a bulky Al(iBu) 3 group made the reaction difficult, and full conversion was achieved after 48 h.
The catalytic hydroboration of N-methyl-1-phenylmethanimine could be initiated simply by NaOH 20 (Scheme 34d), as shown by Wu, Liu, and Zhao et al. 79 The reaction proceeded within 6 h at 90°C, affording the product in good yield. The  126 For the first time, a lithium catalyst was shown to be active toward the hydroboration of imines. A wide range of N-aryl and N-alkyl aldimines and ketimines were hydroborated under mild reaction conditions. Additionally, this catalytic system showed excellent chemoselectivity toward the hydroboration of N-propargylic aldimines.
Panda and co-workers applied potassium benzyl (KCH 2 Ph) 74 for the hydroboration of aldimines. 127 Although low catalyst loadings (5 mol %) and mild reaction conditions were required for the successful hydroboration of aldimines, no examples of less reactive N-alkyl aldimines and ketimines were presented. Thus, excellent yields were obtained for a wide range of N-aryl ketimines. Furthermore, after successfully applying lithium bromide for hydroboration of aldehydes and ketones in the presence of cheap and readily available lithium bromide 53, 97 An et al. utilized this catalytic system for hydroboration of imines. Various aryl-protected aldimines and ketimines were hydroborated to afford the corresponding amines under mild reaction conditions and in remarkably short reaction times. 128

Esters and Amides
Due to their higher stability compared to ketones and imines, the reduction of esters and amides is a more challenging task. 129 The existing protocols often employ either transition-metal catalysts 130 or very reactive metal hydrides, 131 which are rather undesired, as they tend to react with other functional groups. The s-block metal-catalyzed hydroboration of esters and amides has been reported using only magnesium-based catalysts.
The  One year later, in 2015, the same authors applied complex 75 to the hydroboration of amides (Scheme 41). The presented catalytic system allowed the reduction of secondary and tertiary amides to the corresponding amines via deoxygenative C−O bond cleavage. 133 Although reduction of N,N-dimethylformamide was completed within minutes under mild reaction conditions, hydroboration of acetamides, benzamides, and secondary formamides required much longer reaction times of up to 48 h. Mechanistically, the authors postulate that the magnesium species A (in Scheme 40), formed by mixing 75 and HBpin, is not a plausible catalytically relevant species as it provides a mixture of several products from C−N, C−O, and C−C bond cleavages. Alternatively, 75 decomposes in the presence of amides, ruling out the possibility that 75 is a catalytically relevant species. Moreover, no reactivity of amide with HBpin (in the absence of 75) is observed.
Spectroscopy data suggest that 75 reacts with both amide and HBpin simultaneously, forming formimidate boronic ester I (at higher concentrations of HBpin) and diborylated compound II (at lower concentration of HBpin); the latter being obtained via a NH/BH dehydrocoupling pathway from a possible i-II species. Kinetic studies showed that conversion of amide to I and II is fast, whereas the reductive deoxygenation pathway (from I and II to give the desired product) is the turnoverlimiting step.
Okuda et al. also applied magnesium hydrotriphenylborate complex 1 and complex 18 for the hydroboration of esters and amides (Scheme 42). 45,77 In all cases, however, the reactions required harsher conditions and longer times than those needed for Sadow's precatalyst 75. 132,133 The authors concluded that in the case of complex 18, the presence of a bulky Al(iBu) 3 134 Whereas magnesium diamide 76 showed excellent selectivity toward ester hydroboration, more sterically hindered complex 77 was less active. From a catalytic perspective, quantitative conversions at ambient temperature and low catalyst loadings (0.1−0.5 mol %) were achieved in 10− 45 min for a wide range of linear and cyclic esters bearing functional groups, competing favorably with Sadow's precatalyst. 132 Ma et al. applied dimeric Mg(I) complex 78 (Figure 8) for the reduction of various carbonyl compounds, including esters. 135 Under mild reaction conditions, full conversions were obtained for a variety of substrates, showing the high effectiveness of this low-valent magnesium(I) complexes, comparable to the best results obtained with divalent magnesium(II) complexes.
Mandal and co-workers reported the use of abnormal NHCbased potassium complex 79 for the catalytic hydroboration of primary amides. 136 Low catalyst loading and mild reaction temperatures allowed the reduction of several aryl and alkyl primary amides in excellent yields. It is important to highlight that control experiments showed that in the absence of precatalyst 79 or with the presence of only NHC or KN(TMS) 2 no conversion was observed. Isolation of reaction intermediates and single-crystal XRD analysis as well as DFT calculations led Later, Yao and co-workers reported that simple and commercially available KO-t-Bu 73 in combination with BEt 3 could selectively reduce amides to amines (Scheme 44). 137 Interestingly, and contrary to the previously reported K-based precatalyst 79, KO-t- Bu 138 On the basis of control experiments and DFT calculations, the authors reported that a plausible mechanism would involve the reaction of I with the amide, providing ion-pair intermediate II, which subsequently reacts with pinacolborane to afford borane III and regenerate active species I. Intermediate III then provides iminium IV species, which in the case of 3°amides is reduced to afford the desired product. On the contrary, with 1°and 2°amines an imine intermediate V is obtained via intermediate IV and HBpin. Finally, imine V undergoes reduction, affording the corresponding primary and secondary amines.
Finally, Sen and co-workers reported high efficiency of lithium phenolate 26 as catalyst for the deoxygenative hydroboration of primary, secondary, and tertiary amides (Scheme 45). 139 In this regard, excellent yields for a wide range of amides could be obtained. In agreement with the previous reports from Sadow, 133 Mandal, 136   Finally, hydrogen evolution and reduction of N-borylated imine VI provides the corresponding compound. It is important to highlight that direct reactivity of 26 with amide, and the subsequent reaction with HBpin is discarded due to the higher energy barrier required.
Recently, Liu and Cui and co-workers reported the catalytic activity of dimeric magnesium hydride stabilized by phosphinimino 56 toward ester hydroboration, although in comparison with most of the other catalyst, lower activity was observed. 99

Carbonates and Carbamates
The reduction of carbonates leads to methanol and value-added diols or their derivatives. However, carbonates are known to be inert toward reduction due to their high stability. 140 Thus, the hydroboration of carbonates remains fairly underdeveloped, and the first example was reported recently. Rueping et al. applied readily available Mg(n-Bu) 2 46 to the hydroboration of linear and cyclic carbonates. 141 For the first time, an s-block metalbased catalyst showed activity toward carbonate reduction. This efficient Mg-catalyzed reduction of carbonates provides an efficient indirect route for the conversion of CO 2 into valuable alcohols (Scheme 46). Moreover, magnesium 46 could also be applied for the depolymerization of polycarbonates. Based on control experiments and NMR spectroscopy, the authors suggest a mechanism for the magnesium-catalyzed hydroboration of carbonates which involves a n-BuMgH species obtained by σ-bond metathesis of HBpin and Mg(n-Bu) 2 46. This active n-BuMgH species then participates in three sequential catalytic cycles. After the first hydromagnesiation of carbonate and the subsequent σ-bond metathesis with one  Similarly, Ma et al. continued their research on the application of dimeric Mg(I)-based precatalysts for the hydroboration of carbonyl compounds. Just recently, they reported an efficient protocol for the reduction of cyclic and linear carbonates, among other compounds. By performing the reaction under neat conditions, the authors were able to prepare the corresponding Bpin-protected alcohols and diols in the presence of 1 mol % catalyst 78 at ambient temperature. 135 Rueping et al. also applied commercially available Mg(n-Bu) 2 46 for the hydroboration of a wide range of secondary and tertiary linear and cyclic carbamates (Scheme 47). 142 In this case, the hydroboration of methyl and tert-butyl carbamates provided the corresponding N-methyl amines in excellent yields. It is important to highlight that one of the most applied Nprotecting groups, the N-Boc group, could be used as a C1building block. Similarly, by using DBpin, the corresponding Ntrideuteromethyl amines could be obtained. On the basis of the

Nitriles and Isonitriles
The reduction of nitriles and isonitriles, compared to the reduction of other unsaturated compounds, is a fairly underdeveloped field of research, as the only existing example of catalytic hydroboration of this class of compounds was described by Hill et al. in 2015. 143 The reduction of N-alkylsubstituted isonitriles to form 1,2-diborylated amines proceeded smoothly in 1 h at a moderate temperature in the presence of βdiketiminato magnesium alkyl complex 5 (Scheme 48). The reduction of N-aryl substrates, on the other hand, required much harsher conditions and did not lead to complete consumption of the substrate. The low conversions were attributed not only to the change in electronic properties of the substrates and hence their higher stability but also to the decomposition of the reducing agent at elevated temperature. Mechanistic studies revealed that the first Mg−H addition occurs on the polarized CN bond. Then HBpin coordination takes place, leading to an intramolecular hydride transfer from HBpin to the Mg− formimidoyl intermediate. Finally, a σ-bond metathesis of the second molecule of HBpin regenerates the catalyst and provides the corresponding 1,2-diborylated amine products. On the basis of NMR spectroscopy studies, the authors proposed a mechanism in which precatalyst 5 reacts with HBpin to form LMg-H species I. After substrate coordination, the first Mg-H addition to the polarized CN bond occurs, providing intermediate III. Then HBpin coordination takes place, affording species IV, which undergoes intramolecular hydride transfer from HBpin to the Mg-formimidoyl intermediate III to afford magnesium species V. Analysis of the reaction rates indicate a pre-equilibria between I and II and between III and IV, which regulates the assembly of a magnesium formimidoylhydroborate IV. The intramolecular hydride transfer in IV is proposed to be the turnover-limiting step. Finally, a σ-bond metathesis of the second molecule of HBpin regenerates the catalyst and provides the corresponding 1,2-diborylated amine products. It is worth mentioning that the authors did not find enough experimental evidence to rule out the possibility that the formidoyl reduction (intermediate IV) and borane metathesis occur in a concerted fashion. Therefore, the product could be obtained through a pathway which would not contemplate intermediate V.
Hill et al. showed that complex 5 is also an active and selective precatalyst for the reductive dihydroboration of organic nitriles and is a useful tool for the synthesis of primary amine derivatives 144 (Scheme 49). Similar to the reduction of isonitriles, substrates with aliphatic substituents could be reduced in shorter times and under milder reaction conditions compared to aryl nitriles. Mechanistic investigations indicated that the magnesium-catalyzed processes are likely to demonstrate previously unappreciated mechanistic diversity, as follows: (i) Stoichiometric experiments showed that the reaction proceeds through the generation of magnesium aldimido II, magnesium aldimidoborate III, and magnesium borylamido IV intermediates formed via sequential intra-and intermolecular σ-bond metathesis of HBpin.
(ii) Mechanistic differences may depend on the substrate; alkyl nitriles versus electron-rich aryl nitriles versus electron poor aryl nitriles. (iii) KIE indicates that B−H bond cleavage and C−H bond formation are involved in the rate-determining process during the dihydroboration of alkyl and electron poor aryl nitriles. With all that information, the authors suggested a common mechanism in which the rate-determining steps vary based on the formation of several pre-equilibria. Thus, for alkyl nitriles (which exhibit more basic character) the monomer/dimer equilibrium favors the monomeric species II. After HBpin coordination, magnesium aldimido hydroborate III is obtained. A facile subsequent hydride transfer follows, affording magnesium borylamide IV. Finally, Mg−N metathesis with a second equivalent of pinacolborane provides the corresponding bis(boryl) amine product via intermediate V.
The catalytic hydroboration of alkyl nitriles is determined by the pre-equilibria of II and III and its consumption though a B−H transfer to the coordinated CN bond. Thus, the observed rate is dictated by not only the ability of HBpin to replace the nitrile substrate but also by the intramolecular CN reduction. For electron-rich aryl nitriles, the conjugative stability of III toward intramolecular reduction would discard the reaction pathway via intermediate IV. Although only one substrate has been tested (Scheme 50), the authors proved the high activity of both complexes, as the reduction of tert-butyl nitrile was completed in a very short time using 10 times less catalyst than that used by Hill et al. 144 Finally, Ma et al. applied an unsymmetrical β-diketiminatomagnesium(I) complex 37 (Scheme 51) for the hydroboration of nitriles. 88 Although the reaction required high catalyst loadings (10 mol %), the reduction of both aliphatic and aromatic nitriles could be achieved. Notably, the higher activity of complex 37 in the hydroboration of aromatic nitriles than of the initial precatalyst 5 developed by Hill et al. 144 was attributed to the better accessibility of the metal center due to the smaller steric hindrance of one of the aryl moieties of the unsymmetrical ligand.
Findlater and co-workers showed the high catalytic activity of NaHBEt 3 80 toward nitrile hydroboration (Scheme 52). 145 In this regard, excellent yields in short reaction times were obtained for a wide range of aryl and alkyl nitriles, competing favorably with the previous magnesium catalysts reported by Hill,144 Okuda, 45,77 and Ma. 88 At the same time, Wangelin and co-workers applied lithium amide 81 precatalyst for the hydroboration of nitriles (Scheme 53). 146 Excellent yields for a wide range of substrates were obtained, although slightly higher catalyst loadings and longer reaction times were required when compared to other previously

Isocyanates and Carbodiimides
The application of magnesium 5 to the hydroboration of carbodiimides was first presented by Hill et al. in 2016. 148 Interestingly, only partial reduction took place, affording the corresponding N-boryl formamidine products. Attempts to induce the second reduction led only to HBpin decomposition. Therefore, a wide range of (E)-formamidine derivatives could be obtained under relatively mild reaction conditions (Scheme 55). On the basis of kinetic studies, the authors showed that catalytic turnover is dependent on the cooperative assembly of further carbodiimides and HBpin to affect the formation of the (E)formamidine product.
In the same year, Okuda et al. developed magnesium hydrotriphenylborate complex 1, which was applied for the hydroboration of polarized bonds, including carbodiimides and isocyanates (Scheme 56). 45 Although the authors limited the application of the catalytic system to only model substrates, it has been proven that the catalyst exhibits high activity toward the reduction of CN bonds (cf. Hill's monohydroboration on Scheme 55), as the dihydroboration of N,N-diisopropyl carbodiimide and tert-butyl isocyanate was complete within 12 and 0.5 h, respectively, in the presence of just 1 mol % catalyst.
Furthermore, Hill et al. confirmed the excellent versatility of complex 5 by its application in the reductive hydrodeoxygenation of isocyanates. 149 Organic isocyanates were easily converted to methyl amines via a magnesium-catalyzed hydroboration process (Scheme 57). On the basis of the results of control experiments, NMR spectroscopy, and DFT calculations, the authors suggest that the mechanism involves two hydride additions to isocyanate (cycle I) and formamide intermediate (cycle II) and a third hydride addition that cleaves a C−O bond (cycle III), affording the corresponding N-methyl amine. Thus,   118 The authors claim that complex 63 shows the highest activity in the hydroboration of carbodiimides among all the magnesium catalysts reported thus far, as the reaction proceeds in a short time at room temperature. It should be pointed out, however, that a large excess of reducing agent was used. Panda et al. applied KCH 2 Ph 74 as precatalyst in the hydroboration of carbodiimides as earlier studies showed 74 to be an active precatalyst for the aldimine hydroboration (Scheme 59). 127 Although higher catalyst loadings were required when compared to magnesium complex 1 developed by Okuda, 45 precatalyst 74 compares well with magnesium precatalyst 5 applied by Hill et al. 148 Recently, Yang and Ma and co-workers showed that readily available n-BuLi 34 can also be used in the hydroboration of dialkyl-and diarylcarbodiimides. 147 In this regard, precatalyst 34 showed similar activities to magnesium 5 and 1, previously reported by Hill 148 and Okuda. 45

Carbon Dioxide
Hydroboration of carbon dioxide is a convenient approach for conversion of this rather thermally and kinetically stable gas to C1 building blocks. 151 Although several transition-metal complexes have shown to be active toward carbon dioxide reduction, it was only very recently when alkali-or alkalineearth-abundant metals were applied. 152 In 2014, Hill et al. showed that B(C 6 F 5 ) 3 -activated magnesium and calcium hydride complexes 83 and 84 are active for the catalytic hydroboration of CO 2 (Scheme 60a). 153 This catalytic system allowed the unprecedented complete and selective reduction of CO 2 to the methanol equivalent (CH 3 OBpin), although for both catalysts, full conversion was observed only after long reaction times at elevated temperature.
Later, Okuda et al. employed a series of alkali metal hydridotriphenylborate complexes 11−13 for the selective hydroboration of CO 2 to primarily reduce formoxyborane (Scheme 60b). 35 In this case, all complexes promoted hydroboration at very low catalyst loadings following the reactivity trend Li > Na > K, similar to when carbonyl compounds were reduced (section 3.1).
Okuda et al. applied magnesium hydrotriphenylborate complex 1 (Scheme 60c) for the hydroboration of carbon dioxide at ambient temperature. 45 Notably, the complex showed higher activity than magnesium and calcium complexes 83 and 84.  (Scheme 60d). This precatalyst, however, showed much lower activity than previously reported complexes, as harsh reaction conditions and long reaction times were necessary for complete consumption of the substrate. 141 This observation was also reported by Ma et al., who applied Mg(I) complex 78 for hydroboration of CO 2 and other carbonyl compounds (Scheme 60e). 135

Carboxylic Acids
Reduction of carboxylic acids can be performed using stoichiometric amounts of LiAlH 4 . The application of HBpin in combination with metal catalysts is very rare, and the only example of a main group metal catalyzed hydroboration of carboxylic acids was reported by Ma et al. in 2020. 154 Sterically bulky amino magnesium methyl complex 85 was applied for hydroboration of various aliphatic and aromatic carboxylic acids (Scheme 61). Remarkably, the reported catalytic system turned out to be more efficient than the previously reported protocols based on Ru 155 and Mn. 156 On the basis of DFT calculations, NMR analysis, and control experiments, the authors proposed a mechanism which involves formation of RCOOBpin II via a noncatalytic reaction of carboxylic acid with HBpin with simultaneous liberation of hydrogen or via a Mg-catalyzed pathway. The so-obtained RCOOBpin is then reduced in the presence of in situ formed magnesium hydride I (pathway A) to to generate a magnesium complex V and eventually the desired product. Alternatively (pathway B), the first step obtained boryl ester could react with LMgH I to form an aldehyde and magnesium boryloxide species V. The formation of an aldehyde as a plausible intermediate was confirmed via NMR experiments. The boryloxide species V reacts then with HBpin to regenerate the magnesium hydride with elimination byproduct pinBOBpin. At the same time, the aldehyde is reduced to the corresponding borylated alcohol via alkoxide intermediate VI. Although the authors reported high activity of their complex, it should be noted that recent studies on catalyst-free hydroboration of carboxylic acids demonstrated that this reaction may in fact proceed efficiently without the presence of any catalyst (see section 7.2).

Sulfoxides
During studies on the hydroboration of carbonyl compounds in the presence of magnesium hydrotriphenylborate complex 1, Okuda et al. found that when the reactions were carried out in DMSO, catalytic deoxygenation of DMSO occurred as a side reaction (Section 3.1). The authors further investigated the reactivity of complex 1 for the hydroboration of sulfoxide, and thus, the only existing protocol of such a reaction in the presence of an alkaline earth metal-based catalyst was reported (Scheme 62). 45 Catalytic deoxygenation proceeded even under mild reaction conditions and low catalyst loadings; however, longer reaction times were required, and the substrate scope was limited to only three examples.

Alkenes
Although the transition-metal-catalyzed hydroboration of alkenes has been widely studied, 157−160 studies of the hydroboration of alkenes catalyzed by s-block metals have been limited. 161 The first example of the s-block metal-catalyzed hydroboration of unsaturated C−C bonds was reported by Harder et al. in 2012. Calcium-based complexes 86−88 ( Figure   9) were investigated as potential catalysts in the hydroboration of 1,1-diphenylethylene using HBcat (catecholborane) as reducing agent. Surprisingly, the product of the reaction was not the expected Ph 2 CHCH 2 Bcat; instead, (Ph 2 CHCH 2 ) 3 B was formed. By means of NMR spectroscopy, the authors proved that organocalcium complexes 86−88 decompose HBcat to BH 3 or B 2 H 6 , which are the actual active species in the reaction. By using less reactive HBpin, they found that the organocalcium complexes decompose even at room temperature. 162 Several years later, Wu, Liu, and Zhao et al. showed that a catalytic hydroboration of nonpolarized unsaturated compounds, such as alkenes, could be carried out in the presence of NaOH 20 as a precatalyst (Scheme 63). 79 The authors postulated that the reaction is possible due to the formation of an anionic borodihydride species from the reaction of borane and NaOH, which then acts as a catalyst (see Scheme 15).
The only example of magnesium-catalyzed hydroboration of alkenes reported thus far was reported in 2017 by Parkin et al., who applied magnesium complex 63 for the hydroboration of styrene (Scheme 64). 118 Remarkably, in contrast to the anti-Markovnikov regioselectivity observed when transition-metal catalysts were used, the hydroboration in the presence of 63 as a precatalyst proceeded in a Markovnikov manner. Although only styrene was tested, this was the first example of such a transformation in the presence of a magnesium catalyst.
In 2019, Xu and Shi et al. showed that n-BuLi 34 may also be active for the reductive relay hydroboration of allylic alcohols (Scheme 65). 163 Mechanistic studies revealed that this process involves a onepot three-step process involving: Scheme 62. Magnesium-Catalyzed Reduction of Sulfoxides afford the desired product. Although the authors report that n-BuLi 34 species are regenerated within the proposed catalytic cycle (Scheme 65), no experimental evidence is reported. Because of the high reaction temperatures (130°C) and the presence of allylic alcohol as substrates, alternative regenerated Li species should be considered.
The same authors reported an efficient and general n-BuLipromoted anti-Markovnikov selective hydroboration of various terminal αand 1,1-disubstituted alkenes, providing the corresponding alkyl boronic esters bearing various functional groups as single regioisomers with very good yields (Scheme 66). 164 Similarly, Sen et al. reported that lithium complexes 26 and 27, which were previously employed for the hydroboration of polarized unsaturated compounds such as ketones and aldehydes (Scheme 17), 82 could also be applied for the hydroboration of alkenes. 165 Interestingly, when 2-substituted 1,3-diene was used in the reaction, the 3,4-selective hydroboration product was obtained exclusively. Finally, An et al. discovered that potassium carbonate 45 was an active precatalyst for the hydroboration of a wide range of terminal alkenes. 92 This method employing inexpensive, readily available, and air-stable potassium salts afforded products with moderate to very good yields.

Alkynes
Vinylboranes are versatile precursors that have been widely used in organic synthesis, for instance, in the Suzuki−Miyaura reaction. Although in recent years the catalytic hydroboration of alkynes has increasingly gained attention, 166−169 the application of main group metal catalyst is at its early career stage. 170 Wu, Liu, and Zhao et al. showed that catalytic hydroboration alkynes could be initiated by simple sodium hydroxide 20 (Scheme 67). 79 The desired products were isolated, in most cases, in moderate to good yields with anti-Markovnikov regioselectivity and (E)-stereoselectivity; however, the authors limited the substrate scope to only aryl-terminal alkynes.
One year later, Ma et al. applied unsymmetrical β-diketiminate magnesium(I) complex 37 for the hydroboration of terminal alkynes. 88 Although harsh reaction conditions were required, excellent yields of aryl-and alkyl-terminal alkynes were obtained. Only one example of an internal alkyne was reported, although with moderate regioselectivity.
Xue and Bao et al. extended the application of n-BuLi 34 as a precatalyst for the hydroboration of alkynes under mild reaction conditions (Scheme 68). 126 Although the authors described the reaction conditions as "neat", some solvent from n-BuLi stock solution has been involved. For the first time, a lithium catalyst was shown to be active toward the hydroboration of nonpolarized unsaturated bonds; however, relatively high catalyst loading was necessary. Unfortunately, this catalytic system failed when internal alkynes were tested.
Rueping et al. applied commercially available Mg(n-Bu) 2 46 for the hydroboration of a wide range of terminal and internal alkynes. 171 Low-cost and readily available magnesium species 46 provided the corresponding (E)-vinyl boranes in excellent yields (Scheme 69).
Moreover, precatalyst 46 showed excellent functional group tolerance, and the hydroboration of alkynes bearing hydroxyl and free amino groups proceeded with excellent yields and with syn-stereoselectivities. It is important to highlight the good to excellent regioselectivities obtained for a wide range of internal unsymmetrical alkynes. The authors provided insight into the reaction mechanism, and based on the results of NMR spectroscopy and DFT calculations, they proposed the catalytic cycle, based on catalytically active magnesium hydride species, which involves: (i) The formation of active n-BuMgH species: By means of NMR spectroscopy and DFT calculations, the authors suggested that mixing commercially available 46 with pinacolborane, n-BuMgH I, and n-BuBpin were formed via a σ-bond metathesis pathway (8.9 kcal mol −1 ). (ii) Alkyne hydromagnesiation step: In situ formed magnesium hydride species I, which contains one molecule of coordinated HBpin, undergoes hydrometalation of alkyne (20.2 kcal mol −1 ) to afford the corresponding vinyl magnesium II. (iii) Nucleophilic migration: The next step is the nucleophilic migration of the vinyl group to the boron atom of the coordinated pinacolborane (8.2 kcal mol −1 ), forming a zwitterionic intermediate III, which is more stable than vinyl magnesium II species. (iv) Hydride migration: Finally, a reverse hydride migration of anionic borohydride to magnesium center (5.8 kcal mol −1 ) provides the corresponding (E)-vinyl borane and regenerates the active n-BuMgH I species. The significantly lower energy barriers of nucleophilic migration and hydride migration steps (8.2 and 5.9 kcal mol −1 , respectively) suggest that the rate-limiting step in the catalytic cycle is the hydromagnesiation step (20.2 kcal mol −1 ).
Xu and Shi et al. reported an efficient and general n-BuLipromoted anti-Markovnikov selective hydroboration of various terminal and internal alkynes (Scheme 70). 164 When nonsymmetrical internal alkynes were tested, moderate to excellent regioselectivities were observed. Moreover, harsher reaction conditions than those reported by Xue and Bao et al. 126 were required to make the hydroboration of internal alkynes possible.
At the same time, Sen et al. reported that lithium complexes 23 and 24, which were active for the hydroboration of polarized unsaturated bonds such as ketones and aldehydes, 82 were also active toward alkyne hydroboration. 165 Smooth hydroboration of different aromatic terminal alkynes with electron-donating or electron-withdrawing substituents at the o/m/p-positions was reported, providing the corresponding products with very good conversions. On the other hand, when internal alkynes were tested, only moderate yields and stereoselectivities were achieved.

HYDROBORATION OF STRAINED SYSTEMS:
EPOXIDES AND OXETANES The ring opening of strained systems such as epoxides and oxetanes is a powerful tool to obtain alcohols. In this regard, the ring opening of nonsymmetrical substrates afford mixtures of regioisomers; traditionally dependent on the reducing agent employed. 172 Generally, the catalytic C−O bond cleavage is fairly limited due to the high stability of the metal−alkoxide products, which hampers the regeneration of the metal hydride intermediate.
In the recent years, the transition-metal-catalyzed hydroboration of epoxides has emerged as a good method for the synthesis of alcohols. The use of mild pinacolborane as a reducing agent resulted in good-to-excellent selectivities, however, exclusively toward linear alcohols. 172 In 2020, Rueping et al. reported the first main group metal catalyzed hydroboration of epoxides and oxetanes to obtain the  173 The authors demonstrated that readily available Mg(n-Bu) 2 46 was able to catalyze the ring opening of terminal and internal epoxides and oxetanes to afford the corresponding branched alcohol, the opposite regioselectivity compared to transition-metal-catalyzed hydroboration of epoxides. 174 In addition, enantiopure tertiary alcohols were also Chemical Reviews pubs.acs.org/CR Review obtained as a result of the enantiospecific ring opening of optically pure epoxides and epoxides derived from natural products, showing excellent functional group tolerance (Scheme 71). Interestingly, the good performance of 46 could be also extended to the hydroboration of less reactive oxetanes which had not even been reported with transition-metal catalysts. In addition, the authors found that replacing the Mg(n-Bu) 2 46 precatalyst with readily available Mg(NTf 2 ) 2 81 completely reversed the regioselectivity. In this regard, magnesium catalyst 81 provided the corresponding linear alcohol in excellent yields and regioselectivities for a wide range of terminal epoxides. Mechanistically, based on control experiments and DFT calculations, the authors elucidated two different mechanisms for magnesium 46 and magnesium 89 catalyzed reactions (Scheme 72 and Scheme 73 respectively).
For the Mg(n-Bu) 2 46-catalyzed procedure (Scheme 72), the authors suggest that after epoxide coordination to active n-BuMgH species a bimolecular ring-opening mechanism occurs in which epoxide activation and hydride addition to the least substituted carbon take place simultaneously (5.2 kcal mol −1 difference between TS1 and TS1-R) to provide the corresponding magnesium alkoxide intermediate. Then HBpin activation occurs, followed by alkoxide migration to pinacolborane (TS3), and the resulting zwitterionic species undergoes hydride transfer (TS4) to liberate the branched pinacol ester product with the regeneration of active n-BuMgH. Thus, the overall reaction profile (Scheme 72) shows that the bimetallic hydride transfer via TS1 is the rate-controlling step. Regarding the regioselectivity, as mentioned before, differences in energy of 5.2 kcal mol −1 (TS1 vs TS1-R) and 3.8 kcal mol −1 (TS2 vs TS2-R) are consistent with the high regioselectivity observed.
On the other hand, by means of DFT calculations, the authors elucidated the mechanism for Mg(NTf 2 ) 2 89-catalyzed ring opening of terminal epoxides (Scheme 73). Here, magnesium 89 catalyzes the hydroboration of epoxides to afford the linear product (opposite to magnesium 46). First, the authors ruled out the possibility of a magnesium hydride intermediate. However, they established that the epoxide coordinates to highly Lewis acidic 89, which results in isomerization (TS1 and TS2) to afford the corresponding aldehyde. Finally, after HBpin coordination to 89, the aldehyde is reduced, affording the linear isomer product. Moreover, the authors also demonstrated a loss of enantioselectivities when enantiopure epoxide was tested with 89, corroborating the epoxide isomerization via carbocation intermediate. Very

COMPARISON OF ALKALI-AND ALKALINE-EARTH-ABUNDANT CATALYSTS WITH ALUMINUM AND LANTHANIDE AND EARLY-ACTINIDE ANALOGUES
The application of main group metal catalysts in reactions that have been traditionally been associated with transition-metal complexes has increased exponentially in the past decade. Thus, p-block metals such as aluminum (and to a lesser extent, Sn and Ge) and f-block metal complexes such as lanthanides have been successfully applied for the hydroboration of a wide range of unsaturated systems.
Alkali-and alkaline-earth-abundant metals (s-block) share several similarities with p-and f-block metals, including: (i) generally redox neutral catalytic activity; (ii) metal hydride as active catalytic species; (iii) mechanisms based on similar catalytic steps. As such, it is interesting to compare alkali-and alkaline-earthabundant metal catalysts (presented in this review) with their aluminum, lanthanide, and early actinide catalyst analogues. It is important to highlight that this section is not intended to provide a detailed description of the mechanisms and scope of the different p-and f-block metals. We will simply illustrate the best catalysts of each block and compare them with the best of sblock catalysts. The comparison with Sn-and Ge-based catalysts will not be discussed due to their limited scope as almost all examples are based on the hydroboration of aldehydes and ketones. 176,177 However, it is worth mentioning that since the first example of low-valent Sn(II) and Ge(II) complexes applied in hydroboration of CO bonds 178 promising advances have been made on low-valent p-block metal hydroborations. 179−182

s-Block Metals versus Aluminum Complexes
Group 13 hydrides have been widely used in various organic transformations, but their catalytic use has been rather scarce. 183 Many efforts have been made to investigate the catalytic activity of aluminum hydrides as main group catalysts based on the principles of transition-metal catalysts. 184 6.1.1. Aldehydes and Ketones. The hydroboration of aldehydes and ketones has become a benchmark reaction to test the activity of catalysts. In this regard, several aluminum-based catalysts active for the reduction of CO bonds have been developed (Scheme 75). 185−191 Compared with Group 1 and Group 2 catalysts, however, application of aluminum catalysts (group 13) is still in its infancy. A comparison of β-diketiminate magnesium 5 with its aluminum analogue 93 185 demonstrates that the magnesium complex 5 showed higher activities toward aldehyde and ketone hydroboration. This behavior can be attributed to the electronically difference of the metal centers but also to the fact that, whereas complex 5 contains an alkyl group as reactive side, aluminum 93 contains a hydride and a OTf group, which influences the reactivity. Although recent  194 and a recent aluminum−ammonium salt 97 developed by Kastner, Peters, and co-workers. 195 The different reactivity observed between Al-BINOL 96 and Mg-BINOL 57 can be attributed to the different active species formed in the presence of pinacolborane. In the reaction with 96, the authors report the formation of active aluminum hydride species, while for 57, the authors suggest a metal−ligand cooperative activation of pinacolborane. In the case of aluminum 97, the ammonium salt activates the borane while the aluminum center activates the carbonyl compound. As such, very different active species and mechanisms are reported, thus making the comparison difficult. Nevertheless, main group metal complexes mimicking the dual activation mode of 57 and 97 can be excellent candidates for active and selective catalysts toward enantioselective hydroboration of ketones. 6 198 However, cationic magnesium complex 1 developed by Okuda is still the most active catalytic system for the hydroboration of nitriles and carbodiimides. 45 6.1.3. Carbon Dioxide. The hydroboration of carbon dioxide has not been studied as much as the hydroboration of other CO bonds. Although recent advances have been made in aluminum catalysis by Inoue et al. 200 and Meźailles, So, et al. 201 dicationic magnesium catalyst 1 developed by Okuda exhibits the highest activity (Scheme 78). 45 One can attribute the higher catalytic activity of magnesium 1 to its different reactivity. Whereas the aluminum complexes 102 and 103 undergo 1,2-hydroalumination, in the case of cationic magnesium 1, the hydroborated anion plays a crucial role via direct B−H addition (Scheme 12).
6.1.4. Alkenes. Contrary to the hydroboration of highly polarized CO and CN bonds, there are more active aluminum complexes reported for hydroboration of CC bonds than the s-block analogues. 202 In this regard, Cowley and Thomas applied commercially available LiAlH 4 105 for the hydroboration of a wide range of terminal alkenes to obtain the anti-Markovnikov regioisomer. 203 Similarly and independently, Panda 204 and Shi 205 applied active aluminum precatalyst 104 and 106 (Scheme 79). A comparison of commercially available alkyl metals such as AlEt 3 106 and n-BuLi 46, 164 shows that both provide similar activities and regioselectivities. Interestingly, magnesium 63, developed by Parkin, is the only main group metal catalyst that affords the Markovnikov product to date, most likely due to the ligand backbone. 118 6.1.5. Alkynes. Similarly than hydroboration of CC bonds, the hydroboration of alkynes has been widely studied using aluminum catalysts (Scheme 80). 204−206 In fact, the first application of aluminum catalysts was reported by Roesky in 2016, two years before the first magnesium complex. 168 Interestingly, Thomas and Cowley applied commercially available alkyl aluminum 107 and 108 for the hydroboration of terminal and internal alkynes. However, the functional group tolerance was limited. 169 Comparison of 99 with 107 and 108 shows that the latter precatalysts can catalyze the hydroboration of internal alkynes, probably due to the lower steric hindrance around the metal center. On the other hand, magnesium complexes developed by Ma (37) and Rueping (46) showed broader substrate scope with excellent functional group tolerance, probably due to the milder reaction conditions used, when compared to its aluminum analogue 108 (80°C for 46 vs 110°C for 108).

s-Block Metals versus Lanthanide and Early-Actinide Complexes
Because of their low cost and toxicity and high catalytic activity, f-block elements, which are relatively highly abundant in the Earth's crust, have been widely used in catalytic hydrofunctionalization of unsaturated bonds. 207,208 Similar to s-block metals and aluminum, organolanthanide and early actinide catalysts engage in redox-neutral processes. Thus, in hydroboration reactions the mechanism resembles the one presented for alkali-and alkaline-earth-abundant metals. Another similarity is the σ-bond metathesis pathway occurring in the presence of hydridic reagents such as pincacolborane. As such, organolanthanides and early actinides form catalytically Thus, for f-block metal-catalyzed hydroelementations, larger metal ions bearing a less sterically hindered coordination sphere show higher activity. 211,212 However, due to the high oxophilicity of the Ln-and An-centers, thermodynamically stable and catalytically inactive Ln−O and An−O bonds are preferred, making the hydroboration of CO bonds rather challenging. 213,214 In this part, we will compare the most active and selective fblock metal-based complexes with s-block metal catalysts in the hydroboration of unsaturated systems.
6.2.1. Aldehydes and Ketones. The wider exploration of lanthanide-based catalyst for the hydroboration of aldehydes and ketones started later than s-block metal complexes. 215 Simple La−amide, 215 −cyclopentadienyl, 216,217 and −alkoxide 218 complexes were found to be very active, competing favorably with the best group 1 and group 2 metal complexes (Scheme 81). However, Okuda's Li complex 11 remains the most active catalyst reported to date. 35 Generally, metal complexes that form metal hydrides upon reaction with boranes show lower activity than those that, for instance, activate pinacolborane via nucleophilic attack or Lewis acid-type coordination (1, 11, and 55).
Regarding Ln reactivity, La-amide 109, which bears a Nligand, has been shown to be the most active Ln catalyst.
Enantioselective Hydroboration of Ketones. As described above the successful applications of chiral alkali-and alkalineearth-abundant metals for the enantioselective hydroboration of ketones are rare. 107 220 Probably, due to the milder reaction conditions when compared to Mg precatalyst 5, the kinetically favored 1,2product remains in favor over the thermodynamically controlled 1,4-hydroborated product. It is important to highlight that comparable 1,2-regioselectivity was observed by He and Zhang when KO-t- Bu 222 Comparing Ln- (117) and An-based complexes (118 and 119) with s-block metal catalysts (1, 5, and 17), one can see that, whereas for the hydroboration of imines, long reaction times are needed in all cases, for the nitrile hydroboration magnesium complex 1 is the most active metal complex (Scheme 84). 45 6.2.4. Esters and Amides. While the first s-block magnesium-catalyzed hydroboration of esters 132 and amides 133 was reported by Sadow in 2014 and 2015 (75), the first example using a lanthanum-based precatalyst (120) was reported in 2019 by the same author. 20 Since then, other La-based complexes have been reported as active precatalyst toward esters and amides. 223 18 In this case, HBcat was used to hydroborate terminal and internal alkenes. With the recent application of s-block metal catalytic systems, broader substrate scope is tolerated under milder reaction conditions and shorter reaction times. Similar to aluminum-based complexes and most of the s-block metal complexes, Ln-based catalysts ensure the anti-Markovnikov regioselectivity (Scheme 86). 227 6.2.6. Epoxides. In 2019, Sadow et al. reported the use of tris(alkyl)lanthanum 120 for the hydroboration of epoxides. 20 One year later, Rueping et al. reported the use of commercially available dialkylmagnesium Mg(n-Bu) 2 46 as a precatalyst. 173 Interestingly, while the lanthanide-based precatalyst provided Recently reported enantioselective and regiodivergent hydroboration of unsaturated systems in the presence of well-defined alkali-and alkaline-earth-metal complexes, however, show that BH 3 does not always have to be the "hidden" catalyst. If BH 3 indeed acted as a hidden catalyst background reaction then racemic product formation would have been expected. Nevertheless, careful control experiments must be conducted when HBpin activation by group 1 and group 2 metals is studied.
Thomas also points out that commercially available HBpin may contain BH 3 impurities which may compete with a catalyst. In this context, it is worth mentioning that some commonly occurring impurities may promote hydroboration as well. For instance, Speed reported that water or methanol impurities promoted hydroboration of imines. 229 Very recently, Jones and co-workers reported that Mg(I) dimers also react with HBpin to provide derivatives in which the γ-carbon of the β-diketiminate ligand is activated by boron hydride. Additionally, different reactive boron-containing species such as boryloxides (OBpin), borates ([B(pin) 2 ] − or [(pin)BH 2 ] − ), B−O bond ruptured [pinBH 2 ] − , or BH 3 have been observed. These results suggest that magnesium(I) dimers are not catalysts in the hydroboration of unsaturated bonds and that there are many potential precatalysts or hydride sources that are generated when Mg(I) dimers and HBpin are mixed. 230 Additionally, Jin and co-workers discovered that carboxylic acids may promote hydroboration of alkynes. However, in this case, elevated temperatures were required, and thus, acid impurities must also be taken into consideration. 231 As such, as for any catalytic reaction, it is of great importance to consider all side products as potential catalysts.

Catalyst-Free Hydroboration
In 1992, Knochel introduced a catalyst-free approach for selective hydroboration of alkynes and alkenes (Scheme 88a). 232 In the presence of superstoichiometric quantities of HBpin (2 equiv), hydroboration of alkenes and alkynes proceeded in high yields under ambient reaction conditions. Since his discovery, catalyst-free approaches have been utilized for many functional group transformations. In 2018, Hreczycho et al. performed a solvent-free and catalyst-free hydroboration of aldehydes. The reaction proceeded rapidly at ambient temperature (Scheme 88b). 233 The authors suggested that the reaction occurs through the formation of Lewis adducts with a weakened boron−hydrogen bond that facilitates the hydride transfer and reduction of the carbonyl bond. Leung et al. performed the reduction of ketones to achieve high conversion to the corresponding secondary alcohols at elevated temperature and long reaction times (Scheme 88c) 234 and Rit et al. applied catalyst-free conditions for the hydroboration of aldimines and ketimines (Scheme 88d). The authors observed trends similar to those observed for the reduction of aldehydes and ketones. Whereas aldimines were hydroborated at room temperature, ketimines required elevated temperature and long reaction times. 235 Very recently, Vanka, Sen et al. reported deoxygenative hydroboration of primary and secondary amides (Scheme 88e). 236 The corresponding N-Bpin-protected amines were obtained with good to excellent yields; however, harsh reaction conditions, and in the case of secondary amides prolonged reaction times, were necessary. DFT calculations showed an energy barrier of 47.9 kcal mol −1 (ΔG ⧧ value) which explains the need for elevated temperatures (100°C). The groups of Panda, 237 Ma,238 and Xue 239 almost simultaneously reported hydroboration of carboxylic acids in the absence of any catalyst (Scheme 88f). All three groups suggested their own mechanisms; however, all start with a reaction between the acid and HBpin to form a boronic ester with concomitant release of hydrogen. Ma et al. suggest that this first step has an energy barrier of 56.8 kcal/mol. However, because the reaction is highly exothermic, this barrier is surpassed. Interestingly, the abovementioned results contradict the paper on magnesium-based hydroboration of carboxylic acid by Ma et al. (see section 3.9). In the optimization table, the authors show that in the case of the absence of the catalyst very poor conversion for the reduction of model benzoic acid is observed (3.1 equiv of HBpin, 60°C, 1 h, 40% yield). 154 The same group, however, reports full conversion of the same model substrate under solvent-free and catalyst-free conditions (4 equiv of HBpin, 60°C, 1 h, 99% yield). 238 Similarly, Xue et al. reported full conversion already at room temperature, although after a slightly longer time (3.3 equiv of HBpin, rt, 4 h, 95% yield). 239 As such, further studies are required to understand the reaction pathway. Finally, An et al. reported a catalyst-free hydroboration of alkynes (Scheme 88g). The authors postulate that hydroboration of alkynes proceeded in a general syn-addition to afford the trans hydroboration product as a result of thermal activation (110°C). 240 Overall, most of the above-mentioned hydroborations under catalyst-free and solvent-free conditions using HBpin as a reducing agent require elevated temperatures, long reaction times, or superstoichiometric amounts of HBpin to achieve full conversions. On the other hand, catalytic systems based on sblock metals usually present milder reaction conditions and shorter reaction times. For example, when two papers reported by Hreczycho on hydroboration of aldehydes are compared, the one that utilizes a catalyst (LiHBEt 3 ) 90 shows much better results than its catalyst-free analogue. 233 Another example is the Mg-based catalytic system reported by Rueping which requires 80°C for the hydroboration of alkynes, 171 while the catalyst-free protocol requires 110°C. 240 However, comparison of the activity of the catalyst-free approach for the reduction of amides 236 shows similar efficiency to s-block metals. 133,136,137,139 In this context, it is worth mentioning, that reduction of tertiary amides was not possible when a catalystfree system was utilized, whereas in the case of some of the sblock metal catalysts, this reaction was possible. 133,136,137 Therefore, to further improve the efficiency of catalyst-free systems, more reactive boranes may be introduced. In this context, Himmel et al. reported the use of nucleophilic diborane [HB(hpp)] 2 for the hydroboration of carbon dioxide. 241 The first hydroboration takes place at remarkably low temperature and short reaction time (Scheme 89). Further reduction of the so-obtained products was possible, when 9-BBN was added. The results obtained for CO 2 reduction utilizing HBpin and the most active alkaline-earth-metal-based catalysts (see Section 3.8) compete favorably with the catalyst-free variant.

CONCLUSIONS AND OUTLOOK
In the past decade, alkali and alkaline earth metals have emerged as redox-neutral alternatives to transition-metal catalysts for the hydrofunctionalization of unsaturated bonds. In this Review, we describe the Group 1 and Group 2 metal catalysts applied for the hydroboration of various polarized unsaturated CX as well as C−C multiple bonds. We discussed the synthesis of different sblock metal complexes, the scope of the hydroborations, and the proposed outcome. Finally, the comparison of these s-block metal complexes with other redox-neutral catalytic systems based on p-block metals such as aluminum and f-block metal complexes such as lanthanides and early actinides has been also presented.
Since the first example of an s-block metal-catalyzed hydroboration reaction, the evolution of this topic of research has been exponential. Regarding achiral hydroborations, alkaliand alkaline-earth metals bearing neutral and monoanionic ligands have been successfully reported as active and selective catalysts. The ligand design principles can be summarized as (i) the use of monoanionic or dianionic ligands to favor a strong metal−ligand binding, thus avoiding ligand redistribution, and (ii) bulky substituents in a close proximity to the metal center to avoid side-reactivity such as polymerization, catalyst decomposition, and/or ligand redistribution.
Moreover, in recent years, the use of commercially and readily available s-block metal precatalysts has become a focus of interest due to their low cost, simplicity, and thus, the avoidance of tedious ligand synthesis. The recent reports of the application of simple s-block organometallics in the hydroboration of a wide range of unsaturated systems have shown that these simple reagents are very active and selective and can be seen as good alternatives to those s-block metal complexes bearing elaborated ligands.
However, one has to take into consideration that some of the readily available organometallic can decompose pinacolborane (or other organic boranes) to form BH 3 , which has been shown to be an active hydroborating agent. Thus, careful control experiments must be conducted when the HBpin activation by sblock metals is studied.
Concerning the metals of interest, lithium and magnesium complexes have been the most studied catalytic precursors for the hydroboration of unsaturated polarized and unpolarized bonds, which has been the most studied hydrofunctionalization reaction. The combination of experimental and theoretical studies has provided insight into different mechanisms for alkali and alkaline earth metal complexes, all involving redox-neutral pathways. Whereas some mechanisms are based on σ-bond metathesis for precatalyst activation, leading to the formation of active metal hydride species, other mechanisms discard the formation of metal hydrides and rely on the formation of zwitterionic species from the reaction of catalyst precursor and HBpin. Hence, different mechanisms need to be considered: (i) in some cases, s-block metals act as active precatalysts due to the formation of active metal hydrides (via σ-bond metathesis with pinacolborane) and undergo 1,2-hydrometalation with the unsaturated bond; (ii) in other cases, the s-block metals activate the borane (via nucleophilic attack) and the newly formed borate is the active species, transferring the hydride to the unsaturated substrate. Here the question arises if the s-block metal is just a counterion of the nucleophile or if it also has a role in the activation of the unsaturated system via coordination. Given the early stage of s-block metal-catalyzed hydroborations of unsaturated systems, more efforts have to be made to fully understand the respective mechanisms.
Moreover, whereas the addition of H−B bonds to reactive CO and CN bonds has been widely studied, more recently, the hydroboration of less reactive bonds such as carbon dioxides and derivatives (carbonates and carbamates), alkenes, and alkynes, and strained systems such as epoxides and oxetanes has also been accomplished. Thus, the hydroboration reaction has Scheme 89. Catalyst-Free Reduction of Carbon Dioxide Chemical Reviews pubs.acs.org/CR Review become a useful tool for the synthesis of fine chemicals and the conversion of greenhouse gas to C1 building blocks. Although the use of s-block metal catalysts for achiral hydroboration has evolved exponentially and can already been seen as a real alternative to transition-metal catalysts, the application of alkali-and alkaline-earth-abundant metal catalysts to asymmetric hydroboration is still underexplored. In this regard, there are only a few chiral catalysts reported which so far only focus on the hydroboration of ketones and which show lower catalytic activity and functional group tolerance if compared to the best transition-metal-based catalysts. Thus, the development of efficient chiral s-block metal catalysts is greatly desirable. For this purpose, an efficient ligand design is of high interest to avoid any kind of ligand redistribution, known as Schlenk-type equilibrium, which leads to very reactive but nonchiral species and, consequently, no enantioselective induction.
Comparing s-block metal catalysts with their p-and f-block analogues, we can observe several similarities: (i) Simple organometallic compounds have appeared as precatalyst that can be an attractive alternative to catalysts with complex ligand architectures. They show excellent activities toward the hydroboration of several unsaturated bonds and high functional group tolerance.
(ii) Whereas for some unsaturated bonds s-, p-, and f-block metal catalysts show similar activities and selectivities, for other CX bonds (such as aldehydes and ketones) lithium and magnesium complexes show higher activities than their aluminum and lanthanide analogues. (iii) Regarding enantioselective hydroborations, chiral aluminum magnesium complexes display similar reactivity.
However, chiral f-block metal complexes are still underdeveloped. Furthermore, new catalyst-free protocols have recently appeared in the literature for the hydroboration of several unsaturated compounds. However, in almost all cases, excess of pinacolborane, elevated temperatures, or longer reaction times are required.
Given that only very few examples of enantioselective s-block metal-catalyzed hydroboration reactions are known, there are many opportunities for further developments in this field, and we anticipate that future directions will focus on enantioselective hydroboration of other unsaturated bonds, such as imines and alkenes, to achieve chiral amines and alkyl boranes. Moreover, we foresee that new research will also be directed toward other enantioselective hydrofunctionalizations.
Apart from the hydrofunctionalization of unsaturated bonds, and due to the high reactivity of s-block metals (and their lowvalent analogues), we also expect the application of alkali and alkaline earth metal catalysts to further cutting-edge catalytic transformations such as C−H or C−X bond activation and functionalization. In this regard, to date, only stoichiometric use has been reported, and the need for catalytic transformations will provide important impetus for this area of research. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

Funding
This work was financially supported by the King Abdullah University of Science and Technology.

Notes
The authors declare no competing financial interest.