Stereospecific 3‐Aza‐Cope Rearrangement Interrupted Asymmetric Allylic Substitution‐Isomerization

Abstract Transition‐metal catalyzed asymmetric allylic substitution with alkyl and heteroaryl carbon nucleophiles has been well‐established. However, the asymmetric allylic arylation of acyclic internal alkenes with aryl nucleophiles remains challenging and underdeveloped. Herein we report a stereospecific 3‐aza‐Cope rearrangement interrupted asymmetric allylic substitution‐isomerization ( Int‐AASI ) that enables asymmetric allylic arylation. By means of this stepwise strategy, both enantioenriched allylic arylation products and axially chiral alkenes could be readily obtained in high enantioselectivities. Experimental studies support a mechanism involving a cascade of asymmetric allylic amination, stereospecific 3‐aza‐Cope rearrangement and alkene isomerization. Density functional theory studies detailed the reasons of achieving the high chemoselectivity, regioselectivity, stereoselectivity and stereospecificity, respectively.