Development of highly enantioselective new Lewis basic N-formamide organocatalysts for hydrosilylation of imines with an unprecedented substrate profile

l-Pipecolinic acid derived N-formamides have been developed as new Lewis basic organocatalysts that promote the asymmetric reduction of N-aryl ketimines using trichlorosilane as the reducing agent. The substituent on N4 of the piperazinyl backbone and the 2-carboxamide group both proved to have profound effects on the efficacy of the catalyst. The reductions of both N-aryl acyclic methyl ketimines and non-methyl ketimines were catalyzed to afford the desired amines in good to high yield and enantioselectivity. In particular, catalyst 6e enabled the reduction of the difficult bulky ketimines to be highly efficient and enantioselective, affording up to 99% yield and 97% ee. This catalyst proved to prefer the relatively bulkier non-methyl acyclic ketimines to the methyl ketimines as substrate, which is so far unprecedented in catalytic asymmetric reduction of imines.