Enantioselective Synthesis of Axially Chiral Sulfonamides via Atroposelective Hydroamination of Allenes

A Pd-catalyzed atroposelective hydroamination has been developed for the efficient and rapid construction of a family of axially chiral sulfonamides with a wide functional group tolerance. Ortho-groups including undeveloped ester, ketone, nitro, Cl, F, OMe and well-developed Bu-t, I, Br were all applicable in this transformation. Importantly, a simple oxidation of N,O-acetal moiety and gamma-addition to the versatile atropoisomeric iminium ion enabled diversity-synthesis of various valuable axially chiral sulfonamides and anilides. For example, gamma-azidation of the iminium ion opened an opportunity to the synthesis of atropoisomeric non-natural amino acid derivatives and an axially chiral 8-membered cyclic sulfonamide was finally synthesized. Preliminary DFT calculations were performed to explain the origin of asymmetric induction in terms of both stereogenic center and axis.