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

Lucy van Dijk, Ruchuta Ardkhean, Mireia Sidera, Sedef Karabiyikoglu, Özlem Sari, Timothy D.W. Claridge*, Guy C. Lloyd-Jones, Robert S. Paton, Stephen P. Fletcher

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 13C 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. [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)284–292
JournalNature Catalysis
Volume2021
Issue number4
Early online date5 Apr 2021
DOIs
Publication statusE-pub ahead of print - 5 Apr 2021

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