Cu-mediated enantioselective C-H alkynylation of ferrocenes with chiral BINOL ligands.

Abstract

A wide range of Cu(II)-catalyzed C-H activation reactions have been realized since 2006, however, whether a C-H metalation mechanism similar to Pd(II)-catalyzed C-H activation reaction is operating remains an open question. To address this question and ultimately develop ligand accelerated Cu(II)-catalyzed C-H activation reactions, realizing the enantioselective version and investigating the mechanism is critically important. With a modified chiral BINOL ligand, we report the first example of Cu-mediated enantioselective C-H activation reaction for the construction of planar chiral ferrocenes with high yields and stereoinduction. The key to the success of this reaction is the discovery of a ligand acceleration effect with the BINOL-based diol ligand in the directed Cu-catalyzed C-H alkynylation of ferrocene derivatives bearing an oxazoline-aniline directing group. This transformation is compatible with terminal aryl and alkyl alkynes, which are incompatible with Pd-catalyzed C-H activation reactions. This finding provides an invaluable mechanistic information in determining whether Cu(II) cleaves C-H bonds via CMD pathway in analogous manner to Pd(II) catalysts.