Suzuki–Miyaura Cross-Couplings of Alkylboranes: Transmetalation Studies and Synthesis of Model Organopalladium Pretransmetalation Species

This report investigates the transmetalation of B-alkyl-9-borabicyclo[3.3.1]nonane (B-alkyl-9-BBN) coupling partners in Csp2–Csp3 Suzuki–Miyaura (SM) reactions. Kinetically stable, model organopalladium(II) SM pretransmetalation intermediates were synthesized, which enabled comprehensive X-ray crystallographic and NMR spectroscopic characterization of these elusive species at last. Computational studies of kinetically relevant systems were consistent with transmetalation proceeding with retention of configuration with respect to the carbon atom via a frontside SE2 (coordination) mechanism. This is proposed to involve a four-membered transition state with electron transfer into the vacant palladium dx2–y2 orbital. Furthermore, integrated theoretical and experimental results indicated that in the presence of hydroxide in THF/water mixtures, catalytic turnover is kinetically favored via anionic transmetalation path A, which involves the initial reaction of [Pd(Ph)(PPh3)2Br] with [B-alkyl-9-BBN(OH)]−, over neutral path B, which requires initial formation of [Pd(Ph)(PPh3)2OH] then reaction with B-alkyl-9-BBN. It is notable that in path A, the conversion of [Pd(Ph)(PPh3)2Br] to the phenylpalladium(II) boronate pretransmetalation species only appears to be feasible if phosphine ligand exchange with [B-alkyl-9-BBN(OH)]− precedes the loss of bromide. It is likely that these nuances derive, at least partly, from the very high Lewis acidity and steric bulk of the boron center within B-alkyl-9-BBN and its derivatives.