The understanding and development of rhodium-catalysed asymmetric cross-coupling reactions

This thesis examines the understanding and development of Rh(I)-catalysed cross-couplings with arylboronic acids. Our group has previously developed an asymmetric Rh-catalysed Suzuki-Miyaura cross-coupling of racemic allylic halides and boronic acids. Based on a combination of experimental and computational studies, a mechanism is proposed for this highly enantioselective transformation. The first step in the catalytic cycle is irreversible transmetalation. Oxidative addition can happen via syn- or anti-pathways and, in cases where a diastereomeric starting material is used, the diastereoselectivity is set in this irreversible step. The stereochemistry of the product is set by reductive elimination from a η3 Rh-complex formed from both allyl halide enantiomers. This study has led to a better understanding of our group’s method and we believe it will contribute towards the broader understanding of Rh-allyl chemistry and of asymmetric reactions with racemic substrates in general. Attempts to significantly expand our group’s Rh-catalysed asymmetric Suzuki-Miyaura method, with a particular focus on forming quaternary stereocentres, are next presented. These involve the use of substrates with unsymmetric allyl units which introduces regioselectivity issues. Inspired by our mechanistic insights, these regioselectivity issues can be solved by employing enantioenriched substrates in a regiodivergent transformation. In the final chapter, a regioselective Rh-catalysed hydroarylation of cyclobutenes is discussed. This carbometallation method can be used to synthesise biologically relevant cyclobutane products. Our group, and likely others, will continue to explore the potential and limitations of transition-metal catalysed cross-couplings with cyclobutenes. Overall, this thesis examines the mechanism of Rh-catalysed asymmetric Suzuki-Miyaura transformations with racemic substrates and details the development of a Rh-catalysed regiodivergent Suzuki-Miyaura reaction along with a Rh-catalysed regioselective hydroarylation.