Photocatalytic C(sp³)–C(sp²) radical-polar crossover cross-coupling of styrenyl boronic acids

Abstract

Organoboron reagents are widely used in organic chemistry due to their versatile reactivity, ubiquity, stability, and low cost. They are commonly employed as coupling partners in cross-coupling reactions, such as the Pd-catalysed Suzuki-Miyaura reaction, which is responsible for 40% of C–C bond formation reactions in the pharmaceutical industry. However, with the development of the photoredox chemistry over the last 15 years, radical-mediated cross-coupling reactions have flourished. Radicals are now easily made from cheap-commercially-available or easy-to-make precursors using visible light irradiation. They can then further react with numerous different coupling partners leading to an extensive range of new cross coupling opportunities, without the requirement for a photocatalyst in some cases. Organoborons have mostly been employed as radical precursors but their use as coupling partners has increased over the past few years.

N-(Acyloxy)phthalimides (NHPI) esters, a class of redox activated ester species, are widely used as alkyl radical precursors owing to their bench-stability and ease of access. Single electron transfer (SET) affords the desired radical through decarboxylation. In this work, we disclose a new method for C–C bond formation between a styrenyl boronic acid and NHPI ester under Ru-mediated photocatalysis. The reaction proceeds smoothly within three hours under blue LED irradiation and affords the desired products in good to excellent yields. The radical addition undergoes unusual polarity-mismatched Giese-type addition to the organoboron coupling partner. A radical polar crossover reaction requires the presence of a redox-active additive to enable the desired bond formation to occur, and proceeds via an unusual boronic acid priming event. This thesis will describe the development and application of this reaction.