Mechanistic investigation of Rh(i)-catalysedasymmetric Suzuki–Miyaura coupling withracemic allyl halides

Journal article

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.

Authors: Van Dijk, LL; Ardkhean, R; Sidera, M; Karabiyikoglu, S; Sari, Ö

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature
• Journal: Nature Catalysis
• Volume: 4
• Issue: 2021
• Pages: 284–292
• Publication date: 2021-04-05
• Acceptance date: 2021-02-15
• DOI: 10.1038/s41929-021-00589-y
• EISSN: 2520-1158
• Language: English
• Keywords: FFR