Cu-catalyzed [1,3]-Alkoxy Rearrangement Reactions of N-Alkoxyaniline Derivatives

Abstract

In recent years, we disclosed that the N-alkoxyanilines underwent [1,3]-alkoxy rearrangement by the action of NHC-ligated cationic copper catalysts. The rearrangement reactions afforded the corresponding ortho-aminophenol derivatives with high compatibility of functional groups, such as bromo, iodo, methoxycarbonyl, and trifluoromethyl groups. The rearrangement reactions were applicable to polyarenes, such as naphthalenes and phenanthlenes and benzene ring of heteroarenes, such as indoles. Since directed C-H oxygenation reactions of 1-naphthylamine derivatives generally occurs at the peri position, the present rearrangement reactions are regarded as a complementary approach to ortho-aminonaphthol derivatives. To our surprise, N-methoxyanilines, which have alkyl and electron-rich aryl groups at the ortho position, underwent domino rearrangement reactions, including [1,3]-rearrangement of the methoxy group to the substituted ortho position followed by [1,2]-rearrangement of the ortho substituent to the meta position. The present rearrangement reactions are quite efficient to generate functionalized ortho-quinol imines, which have been rarely utilized in organic synthesis due to poor accessibility. The reactions of the N-methoxyanilines, which have an electron-donating group at the ortho position, with carbon nucleophiles, such as 1-methylindole, 1,3,5-trimethoxybenzene, and dimethyl malonate, proceeds via [1,3]-methoxy rearrangement followed by Michael addition to the in-situ generated ortho-quinol imines. Moreover, the Cu-catalyzed [1,3]-alkoxy rearrangement / Diels-Alder cascade reactions between the N-methoxyanilines and olefins afforded the corresponding bicyclic compounds in good yields with excellent stereoselectivity.