Mechanistic investigation of Rh(i)-catalysed asymmetric Suzuki-Miyaura coupling with racemic allyl halides


van Dijk L., Ardkhean R., Sidera M., Karabiyikoglu S., Sari O., Claridge T. D. W. , ...More

NATURE CATALYSIS, vol.4, no.4, pp.284-292, 2021 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 4 Issue: 4
  • Publication Date: 2021
  • Doi Number: 10.1038/s41929-021-00589-y
  • Title of Journal : NATURE CATALYSIS
  • Page Numbers: pp.284-292

Abstract

Understanding how catalytic asymmetric reactions with racemic starting materials can operate would enable new enantioselective cross-coupling reactions that give chiral products. Here we propose a catalytic cycle for the highly enantioselective Rh(i)-catalysed Suzuki-Miyaura coupling of boronic acids and racemic allyl halides. Natural abundance C-13 kinetic isotope effects provide quantitative information about the transition-state structures of two key elementary steps in the catalytic cycle, transmetallation and oxidative addition. Experiments with configurationally stable, deuterium-labelled substrates revealed that oxidative addition can happen via syn- or anti-pathways, which control diastereoselectivity. Density functional theory calculations attribute the extremely high enantioselectivity to reductive elimination from a common Rh complex formed from both allyl halide enantiomers. Our conclusions are supported by analysis of the reaction kinetics. These insights into the sequence of bond-forming steps and their transition-state structures will contribute to our understanding of asymmetric Rh-allyl chemistry and enable the discovery and application of asymmetric reactions with racemic substrates.