Highly Regio- and Enantioselective Formal [3 + 2]-Annulation of Indoles with Electrophilic Enol Carbene Intermediates

Changcheng Jing; Qing-Qing Cheng; Yongming Deng; Hadi Arman; Michael P Doyle

doi:10.1021/acs.orglett.6b02192

Highly Regio- and Enantioselective Formal [3 + 2]-Annulation of Indoles with Electrophilic Enol Carbene Intermediates

Org Lett. 2016 Sep 16;18(18):4550-3. doi: 10.1021/acs.orglett.6b02192. Epub 2016 Sep 2.

Authors

Changcheng Jing¹, Qing-Qing Cheng², Yongming Deng², Hadi Arman², Michael P Doyle²

Affiliations

¹ Shanghai Engineering Research Centre of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200062, P.R. China.
² Department of Chemistry, The University of Texas at San Antonio , San Antonio, Texas 78249, United States.

PMID: 27589203
DOI: 10.1021/acs.orglett.6b02192

Abstract

Chiral cyclopentane-fused indolines are synthesized with high regio- and enantiocontrol by formal [3 + 2]-annulation reactions of indoles and electrophilic enol carbenes. High enantioselectivity and exclusive regiocontrol occurred with enoldiazoacetamides using a less sterically encumbered prolinate-ligated dirhodium(II) catalyst in reactions with N-substituted indoles without substituents at the 2- or 3-positions via a selective vinylogous addition process. In this transformation, donor-acceptor cyclopropenes generated from enoldiazoacetamides serve as the carbene precursors to form metal carbene intermediates.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't