Cooperative Palladium/Isothiourea Catalyzed Enantioselective Formal (3+2) Cycloaddition of Vinylcyclopropanes and α,β‐Unsaturated Esters

Abstract

A protocol for the enantioselective synthesis of substituted vinylcyclopentanes has been realised using cooperative palladium and isothiourea catalysis. Treatment of vinylcyclopropanes with Pd(PPh3)4 generates a zwitterionic π‐allyl palladium intermediate that intercepts a catalytically generated α,β‐unsaturated acyl ammonium species prepared from the corresponding α,β‐unsaturated para‐nitrophenyl ester and the isothiourea (R)‐BTM. Intermolecular formal (3+2) cycloaddition between these reactive intermediates generates functionalised cyclopentanes in generally good yields and excellent diastereo‐ and enantiocontrol (up to >95 : 5 dr, 97 : 3 er), with the use of LiCl as an additive proving essential for optimal stereocontrol. To the best of our knowledge a dual transition metal/organocatalytic process involving α,β‐unsaturated acyl ammonium intermediates has not been demonstrated previously.