Affiliation:
1. Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs Shanghai Frontiers Science Center for Drug Target Identification and Delivery School of Pharmaceutical Science Shanghai Jiao Tong University 800 Dongchuan Road Minhang District, Shanghai 200240 China
2. Laboratory of Synthesis and Natural Products (LSPN) Institute of Chemical Sciences and Engineering Ecole Polytechnique Fédérale de Lausanne, EPFL-SB-ISIC-LSPN, BCH5304 1015 Lausanne Switzerland
Abstract
AbstractAn unprecedent asymmetric catalytic benzilic amide rearrangement for the synthesis of α,α‐disubstituted piperazinones is reported. The reaction proceeds via a domino [4+1] imidazolidination/formal 1,2‐nitrogen shift/1,2‐aryl or alkyl migration sequence, employing readily available vicinal tricarbonyl compounds and 1,2‐diamines as starting materials. This approach provides an efficient access to chiral C3‐disubsituted piperazin‐2‐ones with high enantiocontrol, which are exceedingly difficult to access from the existing synthetic methodologies. The observed enantioselectivity was proposed to be controlled by dynamic kinetic resolution in the 1,2‐aryl/alkyl migration step. The resulting densely functionalized products are versatile building blocks to bioactive natural products, drug molecules and their analogues.
Funder
National Natural Science Foundation of China
China Postdoctoral Science Foundation