Access to Allene-Containing Molecules via Enantioselective Reactions of Azolium Cumulenolate Intermediates

Angew Chem Int Ed Engl. 2021 Jun 25;60(27):14817-14823. doi: 10.1002/anie.202102177. Epub 2021 May 24.

Abstract

Azolium cumulenolates are a special type of intermediates in N-heterocyclic carbene catalysis. They contain elongated linear structures with three contiguous C=C bonds and sterically unhindered α-carbon atoms. These structural features make it difficult to develop enantioselective reactions for these intermediates. Here we disclose the first carbene-catalyzed highly enantioselective addition reactions of azolium cumulenolates. The reaction starts with alkynals as the precursors for azolium cumulenolate intermediates that undergo enantioselective addition to activated ketones. From the same set of substrates, both allene and spirooxindole products can be obtained with high yields and excellent enantioselectivities. The allene moieties in our optically enriched products carry rich reactivities and can be transformed to diverse molecules. The spirooxindole scaffolds in our products are important structural motifs in natural products and medicines.

Keywords: N-heterocyclic carbenes; allenes; asymmetric catalysis; cumulenolate; spirooxindoles.

Publication types

  • Research Support, Non-U.S. Gov't