Rhodium(I) Carbene-Promoted Enantioselective C-H Functionalization of Simple Unprotected Indoles, Pyrroles and Heteroanalogues: New Mechanistic Insights

Angew Chem Int Ed Engl. 2022 Aug 22;61(34):e202207008. doi: 10.1002/anie.202207008. Epub 2022 Jul 7.

Abstract

A rhodium(I)-diene catalyzed highly enantioselective C(sp2 )-H functionalization of simple unprotected indoles, pyrroles, and their common analogues such as furans, thiophenes, and benzofurans with arylvinyldiazoesters has been developed for the first time. This transformation features unusual site-selectivity exclusively at the vinyl terminus of arylvinylcarbene and enables a reliable and rapid synthetic protocol to access a distinctive class of diarylmethine-bearing α,β-unsaturated esters containing a one or two heteroarene-attached tertiary carbon stereocenter in high yields and excellent enantioselectivities under mild reaction conditions. Mechanistic studies and DFT calculations suggest that, compared to the aniline substrate, the more electron-rich indole substrate lowers the C-C addition barrier and alters the rate-determining step to the reductive elimination, leading to different isotope effect.

Keywords: Asymmetric Catalysis; Carbene Insertion; Chiral Diene; C−H Functionalization; Unprotected Indoles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Indoles
  • Methane / analogs & derivatives
  • Pyrroles
  • Rhodium*
  • Stereoisomerism

Substances

  • Indoles
  • Pyrroles
  • carbene
  • Rhodium
  • Methane