Radical Decarboxylative 1,2,3-Trifunctionalization of 3-Enoic Acids via 1,4-Imino-N Shift: A Modular Approach to Functionalized 3,4-Dihydroisoquinolines

Abstract

A novel radical decarboxylative 1,2,3-trifunctionalization of various 3-enoic acids is achieved via 1,4-imino-N shift by using CF3I as trifluoromethylating reagent and the readily available aryl ketoximes as both acid activator and difunctionalization reagent. This reaction is performed by CF3-radical addition on the terminal alkene moiety of in-situ formed aryl ketoxime 3-enoates, followed by a cascade radical 1,4-imino-N shift/decarboxylation/arylation to furnish the N-atom at 2-position of alkenes and to fix the aryl group at 3-position by replacing the carboxyl group. Consequently, a series of 1,2,3-trifunctionalized allyl derivatives are efficient produced in the form of structurally important trifluoromethylated 3,4-dihydroisoquinolines (3,4-DHIQs). Other functional radicals such as diverse fluoroalkyl and azido radicals can also trigger the reaction. This tactic not only provides a new conversion mode for 3-enoic acids and aryl ketoximes, but also affords unprecedent modular method for constructing diverse functionalized 3,4-polysubstituted DHIQs with excellent regio- and diastereoselectivity and bioactive molecules compatibility.