Enantioselective Synthesis of Pyrrolidines by Imidodiphosphorimidate (IDPi)-catalysed anti-hydroamination of alkenes

Chiral pyrrolidines are common structural motives in natural products as well as active pharmaceutical ingredients explaining the need for methods for their enantioselective synthesis. While several, often metal-catalyzed, methods do exist, the enantioselective synthesis of pyrrolidines containing quarternary stereocentres remains challenging. Herein, we report a Brønsted acid-catalysed intramolecular hydroamination, which provides such pyrrolidines from simple starting materials in high yield and enantioselectivity. Key to an efficient reaction was the use of an electron-deficient protective group on nitrogen, the common nosyl protecting group, to avoid deactivation of the Brønsted acid by deprotonation. The reaction proceeds as a stereospecific anti-addition suggesting a concerted reaction. Furthermore, kinetic studies show Michaelis-Menten behaviour suggesting the formation of a precomplex similar to those observed in enzymatic catalysis.