Theoretical insight into the activity and selectivity in palladium/Ming-Phos-catalyzed three-component asymmetric synthesis of gem-diarylmethine silanes

Recently, a three-component coupling reaction for efficient construction of gem-diarylmethine silanes was developed, utilizing a Pd-Ming-Phos catalyst. To explore the underlying mechanism governing this intriguing reaction, we have conducted comprehensive density functional theory (DFT) computations (M06-L/SDD/6-311++G(d,p)/SMD//B3LYP-D3/lanl2dz/6-31G(d,p)). DFT calculations reveal that the oxidative addition of ArBr to Pd(0) is the rate-determining step, and the carbenation process of PhCHN 2 to Pd(II) is the enantioselectivity-determining step. Moreover, the Ming-Phos ligand exhibits a self-adaptive nature, allowing it to dynamically adapt its coordination patterns with the metal center in different elementary steps, thereby enhancing the overall reactivity. The enantioselectivity is determined by both the trans effect and the side-arm effect of the ligand. This mechanism nicely explains why TY-Phos with P- t Bu 2 instead of the Ming-Phos with P-Ph 2 results in poor reactivity and much reduced enantioselectivity. This study not only provides deeper insights into the functioning principles of SadPhos ligands but also offers valuable guidance for future ligand modifications and optimizations.