Aqueous Suzuki couplings mediated by a hydrophobic catalyst

The catalytic activity of [(Ph2P-o-C6H4)2N]PdCl in aerobic aqueous Suzuki couplings is described. Though hydrophobic, this molecular catalyst is competent in cross-coupling reactions of arylboronic acids with a variety of electronically activated, unactivated, and deactivated aryl iodides, bromides, and chlorides upon heating in aqueous solutions under aerobic conditions to give biphenyl derivatives without the necessity of amphiphiles even in the presence of an excess amount of mercury.

Metal nanoparticles 38 differ inherently in size and shape, typically rendering rather undesirable multiple active sites comprising different compositions for catalysis. The constitutions and thus activities of these active sites could be very sensitive to their formation procedures and the presence of traces of usually unnoticed components, particularly those prepared in situ when molecular precatalysts decompose under catalytic conditions. Reproducibility of catalysis of this type could be troublesome. In this regard, there have been several reports addressing this challenge, 39,40 including concerns of commercially available molecular precatalysts. 41,42 The development of well-dened molecular catalysts where leaching of the metal does not occur during catalysis is therefore of interest and benet.
Palladium-catalyzed Suzuki couplings are versatile in the development of biaryl derivatives. 6 We have previously reported the catalytic competence of amido phosphine complexes of palladium, e.g., 1 and 2 in Fig. 1, for Suzuki couplings in organic solvents. 43,44 Of note are reactions conducted under aerobic conditions in the presence of exogenous water, an unusual result considering the inherently high basicity of a Pd-amide bond. 45 Note that water in these attempts is not a major solvent. We were therefore interested in aerobic aqueous Suzuki couplings with these promising catalysts. We report herein the catalytic activity of 2a in this regard without the requirement of any amphiphilic additives despite the hydrophobic nature of this catalyst. Of interest is also its unchanged activity in the presence of mercury, 39,40,46,47 consistent with homogeneous catalysis by a well-dened molecular catalyst that contrasts with the heterogeneous feature of palladium nanoparticles derived in situ from the decomposition of other molecular precatalysts such as commercially available Pd(PPh 3 ) 4 and Pd(OAc) 2 (vide infra).
To gain insights into mechanistic possibilities, we examined a series of competitive reactions of phenylboronic acid with electronically activated, unactivated, and deactivated aryl bromides catalyzed by 2a in H 2 O/nBuOH at 100 C, a Hammett plot of which shows a reaction constant r of 1.54 AE 0.06 (Fig. 2). This value is relatively small as compared with those found for oxidative addition of aryl iodides to Pd(PPh 3 ) 2 (r ¼ 2) 54 and aryl chlorides to Pd(XPhos) (r ¼ 2.3) 55 or Pd(dippp) (r ¼ 5.2). 56 Oxidative addition of aryl bromides in this study is therefore unlikely the rate-determining step. Relatively smaller reaction constants have also been reported for Suzuki couplings catalyzed by 1a (r ¼ 0.48), 43 1b (r ¼ 0.66), 43 or 2a (r ¼ 0.25 in dioxane, r ¼ 1.08 in toluene), 44 Heck olenation by 2a (r ¼ 0.60), 48 and Sonogashira couplings by 2a (r ¼ 0.82) 49 in organic solvents, where transmetallation is proposed to be the slowest. A similar proposition was also suggested in other Suzuki couplings having a small reaction constant. 57,58 The hypothesis regarding transmetallation as the rate-determining step in this aqueous catalysis is also consistent with the consequence that 2a outperforms 2b taking into account that oxidative addition of aryl halides and reductive elimination of biaryl products are more encouraged by the latter given its more electron-releasing and larger P-substituents, respectively.
In summary, the amido PNP complex 2a is a competent catalyst in aqueous Suzuki coupling reactions under aerobic conditions. Of note is the feasibility of this hydrophobic catalyst in aqueous catalysis without the assistance of amphiphiles. A variety of electronically activated, unactivated, and deactivated aryl iodides, bromides, and chlorides are suitable electrophiles, resulting in biaryl products straightforwardly. Mercury poisoning experiments and Hammett reaction constant collectively implicate a molecular mechanism where transmetallation is likely the rate-determining step. All in all, this study demonstrates a facile entry into aerobic aqueous catalysis with a robust hydrophobic catalyst, a rare example contrasting with those requiring amphiphiles [24][25][26] or those transforming into catalytically active nanoparticles. [34][35][36][37] Studies aiming at expanding the territory of 2a in aqueous catalysis are currently underway.

Conflicts of interest
There are no conicts of interest to declare.