Synthesis of <i>meta</i>-Substituted Anilines via Copper-Catalyzed [1,3]-Methoxy Rearrangement
Itaru Nakamura, Hiroki Tashiro, Yasuhiro Ishida, Masahiro Terada
Abstract
meta-Substituted anilines were efficiently synthesized via copper-catalyzed [1,3]-methoxy rearrangement of N-methoxyanilines followed by Michael addition of nucleophiles to the in situ generated ortho-quinol imine. The present reaction exhibits excellent applicability of para-substituents, such as vinyl, methylthio, ester, and bromo, and carbon nucleophiles, such as 1,3,5-trimethoxybenzene, N-methylindole, and dimethyl malonate. Thus, the present rearrangement can resolve problems stemming from oxidation reactions, such as the use of stoichiometric amounts of oxidants and low compatibility of electron-withdrawing groups.
Topics & Concepts
ChemistryNucleophileCatalysisMalonateCopperStoichiometryImineMedicinal chemistryDimethyl malonateMichael reactionCombinatorial chemistryOrganic chemistryEnantioselective synthesisCatalytic C–H Functionalization MethodsSulfur-Based Synthesis TechniquesSynthesis and Catalytic Reactions