Copper-catalyzed asymmetric cascade diyne cyclization/Meinwald rearrangement

Abstract

The Meinwald rearrangement has proven to be one of the most useful tools in organic synthesis. However, examples of asymmetric Meinwald rearrangements are quite scarce, and these reactions have so far been limited to the use of chiral Brønsted acids as catalysts. Here, we report a copper-catalyzed asymmetric cascade cyclization/Meinwald rearrangement reaction, allowing the practical and atom-economic synthesis of a range of chiral tricyclic pyrroles bearing a chiral oxa-quaternary carbon stereocenter in high yields and enantioselectivities. Thus, this protocol not only represents the first transition-metal-catalyzed enantioselective Meinwald rearrangement, but also constitutes the first example of asymmetric formal monocarbon insertion into C–O bond of ester. Moreover, theoretical calculations provide further evidence for this multiple cascade cyclization and elucidate the origin of enantioselectivity.