Cu(I)-Catalyzed ortho-Selective Cross-Coupling of Phenols with Electrophilic Indoles

Abstract

Direct functionalization of inert C-H bonds is an attractive strategy and therefore have drawn intense interest. To implement such a strategy for regioselective functionalization of phenols, we introduced herein N-(acyloxy)indole as electrophilic, umpoled indole derivatives. In this presentation, we developed a new protocol for a general synthesis of N-(acyloxy)indoles, based on the electrophilic cyclization of (o-alkynyl)phenylhydroxylamines. With an easy access to a variety of N-(acyloxy)indoles, we developed a Cu(I) catalyzed ortho-selective coupling of phenols with the umpoled indoles. The [Cu(OTf)]2·C6H6 system was extremely reactive and catalyzed the coupling at a very low loading (0.1 - 0.01 mol%) and at room temperature. The unusual C2-regioselectivity was rationalized by a sequence comprising N-substitution, followed by [3,3]-sigmatropic rearrangement.