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A one pot, three‐step cascade reaction to provide functionalized proline derivatives was developed. The Michael addition reaction of N‐allylated proline and activated alkyne forms a zwitterionic intermediate that further undergoes cyclization and [2,3]‐rearrangement to provide Cα‐alkylated proline bicyclic derivatives. This transformation was highly stereoselective and the chirality of the N‐allylated prolines was completely transferred to the product via a C−N−C chirality transfer process. The developed reaction is operationally simple and does not require any reagents other than the substrates. [ABSTRACT FROM AUTHOR]

Asymmetric synthesis of α‐substituted proline derivatives has been accomplished by an efficient chirality‐transfer method. High diastereoselectivity of the N‐alkylation of the proline ester (C→N chirality transfer) was achieved when a 2,3‐disubstituted benzyl group was used as the N‐substituent. DFT calculations provided a mechanistic rationale for the high degree of stereoselectivity. The generated N‐chirality of the quaternary ammonium salt was transferred back to the α‐carbon through a stereoselective [2,3]‐Stevens rearrangement (N→C chirality transfer) to give α‐substituted proline ester. C→N→C chirality transfer: An efficient chirality‐transfer process was established for the asymmetric synthesis of α‐substituted proline derivatives. Using a 2,3‐disubstituted benzyl group as the N‐substituent, a high level of C→N chirality transfer was achieved, which enabled the enantioselective synthesis of the α‐substituted prolines through [2,3]‐Stevens rearrangement (N→C chirality transfer). DFT calculations suggested that this selective N‐alkylation follows Curtin–Hammett kinetics. [ABSTRACT FROM AUTHOR]