Palladium/GF-Phos-catalyzed asymmetric carbenylative amination to access chiral pyrrolidines and piperidines

The cross-coupling of N-tosylhydrazones has emerged as a powerful method for the construction of structurally diverse molecules, but the development of catalytic enantioselective versions still poses considerable challenges and only very limited examples have been reported. We herein report an asymmetric palladium/GF-Phos-catalyzed carbenylative amination reaction of N-tosylhydrazones and (E)-vinyl iodides pendent with amine, which allows facile access to a range of chiral pyrrolidines and piperidines in good yields (45-93%) with up to 96.5 : 3.5 er. Moreover, mild conditions, general substrate scope, scaled-up preparation, as well as the efficient synthesis of natural product (-)-norruspoline are practical features of this method.

Automated summary

This article reports an efficient method for the synthesis of chiral pyrrolidines and piperidines through a palladium-catalyzed carbenylative amination reaction of N-tosylhydrazones and (E)-vinyl iodides. The reaction shows high selectivity and good yields, and can be easily scaled up. It also enables the efficient synthesis of a natural product (-)-norruspoline.