Asymmetric Synthesis of Cα‐Substituted Prolines through Curtin–Hammett‐Controlled Diastereoselective N‐Alkylation. Issue 10 (21st January 2019)

• Record Type: Journal Article
• Authors: Cho, Hyunkyung; Jeon, Hongjun; Shin, Jae Eui; Lee, Seokwoo; Park, Soojun; Kim, Sanghee
• Is Part Of: Chemistry. Volume 25:Issue 10(2019)
• Page Start: 2447
• Page End: 2451
• Publication Date: 2019-01-21
• Subjects: chirality transfer -- Curtin–Hammett principle -- proline derivatives -- rearrangement -- stereoselectivity; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201804965
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: 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. Abstract : 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.