Pd-catalysed ortho-alkoxylation of benzamides N-protected with an iminophosphorane functionality

Abstract

The oxidative coupling of keto-stabilised iminophosphoranes (IPs) Ph₃PNC(O)C₆H_xR_y with alcohols R′OH affords the alkoxylated species Ph₃PNC(O)C₆H_x−1R_y-2-OR′. The process is catalysed by 10% PdCl₂(NCMe)₂, uses oxone® as an oxidant and alcohol R′OH as a source of OR′ groups and reaction solvent. The reaction takes place at room temperature regioselectively at the ortho-position of the benzamide ring, gives only the mono-alkoxylated derivatives, and shows tolerance to a variety of functional groups and different primary and secondary alcohols. Better yields were obtained when the aryl ring contains electron-releasing substituents (OMe, Me). The iminophosphorane moiety plays a dual role as the protecting/directing group, and can be hydrolysed to give the corresponding free benzamide.