Triarylmethanes are important structural motifs with wide applications in natural products, drug discovery, and materials science. Chiral triarylmethanes are particularly noteworthy due to their unique three-dimensional architectures, which facilitate interactions with biological targets. Current enantioselective syntheses primarily rely on strategies such as enantioselective desymmetrization, asymmetric dehydroxylation, and stereocontrolled C-C bond formation. However, these methods often depend on preconstructed frameworks, posing challenges for synthesizing unfunctionalized triarylmethanes. Herein, we present a one-pot cascade reaction that enables the modular and enantioselective synthesis of triarylmethanes from aldehyde-derived hydrazones, aryl halides, and aryl nucleophiles. This method achieves excellent step and pot economies by simultaneously forming two distinct C-C bonds. Notably, the enantiodetermining step is strategically relocated to the transition metal-carbene migratory insertion event, overcoming limitations of conventional approaches. Our results demonstrate robust yields and excellent enantioselectivity across a diverse range of substrates. This modular strategy also allows for facile access to both enantiomers by simply switching the aromatic rings. DFT calculations reveal that the transmetalation step is the rate-determining step and the carbenation process is the enantioselectivity-determining step, also demonstrating the self-adaptive nature of the SadPhos ligand.
Zhu et al. (Tue,) studied this question.