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Pd‐Catalyzed Asymmetric 5‐exo‐trig Cyclization/Cyclopropanation/Carbonylation of 1,6‐Enynes for the Construction of Chiral 3‐Azabicyclo[3.1.0]hexanes

Qiuyu Li, Yunchu Zhang, Pengyun Liu, Jing Zhong, Baihui Gong, Hequan Yao, Aijun Lin

2022Angewandte Chemie International Edition31 citationsDOI

Abstract

We herein disclose a mild and efficient access to chiral 3-azabicyclo[3.1.0]hexanes via a Pd-catalyzed asymmetric 5-exo-trig cyclization/cyclopropanation/carbonylation of 1,6-enynes. Various nucleophiles, such as alcohols, phenols, amines and water, are well compatible with the reaction system. This reaction forms three C-C bonds, two rings, two adjacent quaternary carbon stereocenters as well as one C-O/C-N bond with excellent regio- and enantioselectivities. The products could be further functionalized to generate a library of 3-azabicyclo[3.1.0]hexane frameworks.

Topics & Concepts

CyclopropanationStereocenterNucleophileCarbonylationChemistryCatalysisMedicinal chemistryHexaneOrganic chemistryStereochemistryEnantioselective synthesisCarbon monoxideCyclopropane Reaction MechanismsCatalytic C–H Functionalization MethodsAsymmetric Synthesis and Catalysis