Divergent Synthesis of Anisidines by Controlling Cu‐Catalyzed [1,3]‐Methoxy Rearrangement

Abstract

AbstractA divergent synthesis of ortho‐anisidines was achieved by controlling Cu‐catalyzed [1,3]‐methoxy rearrangement. The reactions of N‐alkoxyanilines having an electron‐donating group (EDG), such as an alkyl or anisyl group, at the ortho position and a pivaloyl group on the nitrogen atom in the presence of catalytic amounts of IPrMeCuCl and AgNTf2 afforded the corresponding 6‐substituted 2‐anisidines with good product selectivity through a [1,3]‐rearrangement of the methoxy group to the unsubstituted ortho position. In contrast, the reactions of N‐ methoxyanilines having a benzyloxycarbonyl group on the nitrogen atom using IPrCuBr and AgBF4 as catalysts afforded 3‐substituted 2‐anisidines via a domino process involving a [1,3]‐rearrangement of the methoxy group to the EDG‐substituted ortho position followed by a [1,2]‐rearrangement of the EDG of the resulting ortho‐quinol imine intermediate.