Studies of Intermolecular Asymmetric Halofunctionalisations of Alkenes

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Description of the chemistry and potentially issues in the fieldAlkene halofunctionalisations, namely the addition of an electrophilic halogen and a nucleophile across a double bond, are fundamental carbon-heteroatom bond-forming reactions in organic chemistry. These reactions facilitate the conversion of a prochiral alkene moiety into two new stereogenic carbon centres with predictable regiocontrol and diastereoselectivity, and are therefore attractive routes towards a diverse array of enantiopure, heteroatom-bearing vicinal disubstituted compounds. However, although the stereochemical course of alkene halofunctionalisations has been well-established over the past century, developing catalytic, asymmetric variants of these reactions has presented a significant challenge for the modern synthetic community. In the last decade, several examples of enantioselective intramolecular halofunctionalisation (involving capture of a halonium ion by a covalently tethered nucleophile) have emerged, many of which utilise chiral bisalkaloids or BINOL-phosphoric acids as organocatalysts. In contrast, there are very few examples of successful enantioselective intermolecular halofunctionalisation reactions (utilising a nucleophile extraneous to the starting alkene) using either of these organocatalysts. This is because of a generally poor mechanistic understanding of the intermolecular systems relative to their intramolecular counterparts. Inspired by results of Li et al., this project intends to elucidate the mechanisms of organocatalytic intermolecular halofunctionalisation, with comparisons being made between different organocatalytic systems. This will involve thorough optimisation experiments using factorial designs, chemometrics for the analysis of kinetic data, all tied in with a computational approach to develop theories surrounding our experimental data.