Carbohydrate‐Functionalized Triazolylidene Iridium Complexes: Hydrogenation Catalysis in Water with Asymmetric Induction

Abstract Two sets of carbohydrate‐NHC hybrid iridium complexes were synthesised in order to combine properties of carbohydrates and triazolylidene (trz) ligands in organometallic catalysis. One set features a direct trz linkage to the anomeric carbohydrate carbon, while the second set is comprised of an ethyl linker between the two functional units. Deprotection of the carbohydrate afforded hybrid complexes that efficiently catalyse the direct hydrogenation of ketones in water. The catalytic activity of the hybrid complexes was influenced by the pH of the aqueous medium and surpassed the activity of carbohydrate‐free or acetyl‐protected analogues (>90 % vs 13 % yield). While no enantiomeric induction was observed for the ethyl‐linked hybrids, a moderate enantiomeric excess (ee) was induced by the directly linked systems. Moreover, these carbohydrate‐trz hybrid complexes displayed mixed inhibitory activity towards a glycosidase from H. orenii that contain a glucose binding site.


Structural analysis
Single crystals suitable for X-ray diffraction analysis were obtained of unprotected triazole 1-Gal-4-Ph-triazole (Scheme S1), acetyl-protected complex 5βGlc and unprotected complex   . Molecular structure of one of the crystallographically independent molecules of complex 5βGlc (50% probability, hydrogen atoms omitted for clarity).

S3
Crystals of 5βGlc grew as yellow plates. The unit cell contained two crystallographically independent molecules with one acetate group disordered over two sites. The quality of the results is low (see Table S1) and as such, discussion of the bonding geometries is not conclusive, however molecular connectivity is proven by this structure and can be seen to be qualitatively analogous to the previously published molecular structure of the deprotected analogue 7βGlc, [4] indicating that the presence of acetyl protecting groups has minimal impact on the solid state geometry of these systems, particularly the geometry of the carbohydrate with respect to the metal centre. Illustration of the hydrogen-bonding network between carbohydrate motifs and CH3OH in crystal structure; for clarity the triazolylidene and metal centre have been replaced by blue spheres.
The molecular structure of 7βGal (Fig. S3a) confirms the expected β-configuration and chair conformation of the carbohydrate entity. A series of hydrogen bonding interactions between the galactosyl alcohol groups of adjacent molecules and a co-crystallised methanol molecule generates a 3D-network (Fig. S3b). No intramolecular hydrogen bonding was identified in the solid state. The unit cell is composed of only one single independent molecule. The bonding geometry about the iridium centre does not deviate significantly from related complex such as 7βGlc, [4] or the analogous complex 9 containing a simple triazolylidene ligand. [5] S4

Crystal structure determination
A single crystal was mounted in air at ambient conditions. All measurements were made on a Oxford Diffraction SuperNova area-detector diffractometer [6] using mirror optics monochromated Mo Kα radiation (λ = 0.71073 Å) and Al filtered. [7] The unit cell constants and an orientation matrix for data collection were obtained from a least-squares refinement of the setting angles of reflections in the following ranges: For 1-Gal-4-Ph-triazole: 2.3 < θ < 27.6°. A total of 566 frames were collected using ω scans, with 15+15 seconds exposure time, a rotation angle of 1.0° per frame, a crystal-detector distance of 65.0 mm, at T = 173(2) K. For 5βGlc: 1.9° < θ < 27.7°. A total of 708 frames were collected using ω scans, with 30+30 seconds exposure time, a rotation angle of 1.0° per frame, a crystal-detector distance of 65.0 mm, at T = 123(2) K. For 7βGal: 2.154° < θ < 26.99°. A total of 680 frames were collected using ω scans, with 60+60 seconds exposure time, a rotation angle of 1.0° per frame, a crystaldetector distance of 65.0 mm, at T = 173(2) K.
Data reduction was performed using the CrysAlisPro [6] program. The intensities were corrected for Lorentz and polarization effects, and an absorption correction based on the multi-scan method using SCALE3 ABSPACK in CrysAlisPro 1 was applied for 7βGal and 1-Gal-4-Ph-triazole, while for 5βGlc a numerical absorption correction based on gaussian integration over a multifaceted crystal model was applied. Data collection and refinement parameters are given in Table S1.
The structure was solved by direct methods using SHELXT [8] , which revealed the positions of all not disordered non-hydrogen atoms of the title compound. The non-hydrogen atoms were refined anisotropically. H-atoms were assigned in geometrically calculated positions and refined using a riding model where each H-atom was assigned a fixed isotropic displacement parameter with a value equal to 1.2Ueq of its parent atom (1.5Ueq for methyl groups).
Refinement of the structure was carried out on F 2 using full-matrix least-squares procedures, which minimized the function Σw(Fo 2 -Fc 2 ) 2 . The weighting scheme was based on counting statistics and included a factor to downweight the intense reflections. All calculations were performed using the SHELXL-2014/7 [9] program.
For 5βGlc, the asymmetric unit of the crystal contains two independent metal complexes. One methylacetate group is disordered about two sites. About 16% of the unit cell volume contains electron density which is very diffuse and could not be modelled by discrete molecules and probably contains a mixture of heavily disordered co-crystallized S5 dichloromethane and diethylether solvent molecules. This electron density was accounted for by the SQUEEZE technique [10] . The quality of the results for 5βGlc is low and doesn't allow a discussion of the bonding geometries. It is however good enough for a proof of the molecular connectivity. Table S1. Selected crystallographic data and structural refinements for 7βGal, 5βGlc and 1-Gal-4-Ph-triazole.

Gas chromatography: ee determination
The enantioselectivity of each catalyst was determined by gas chromatography (GC) at the end point of each reaction. Gas chromatography (GC) was performed on an Agilent 7820A GC System using a CP-Chiralsil-DEXC8 column (25mm × 0.25mm × 0.25μm) as stationary phase and the following method: