Photochemical Cross-Organoboron Coupling of Heteroaryl and Alkyl Boronic Acids and Esters.

Abstract

The Suzuki-Miyaura cross-coupling reaction is a cornerstone of C-C bond formation. However, heteroaryl boronic acids such as pyridyl and quinolyl derivatives remain challenging nucleophiles due to facile protodeboronation. Strategies enabling these substrates are limited to C(sp2)-C(sp2) formation. Efficient and modular C(sp2)-C(sp3) cross-coupling methods that directly employ these substrates remain underdeveloped. Here, we report a cross-organoboron platform that enables direct C(sp2)-C(sp3) bond formation from heteroaryl and alkyl organoboron reagents under visible-light irradiation using Ag2O/TiO2 nanoparticles (NPs). The two organoboron reagents undergo distinct Ag2O NP activations: alkyl boronates undergo single-electron photo-oxidation to generate alkyl radicals while arylboronates undergo transmetalation. Importantly, this method tolerates protodeboronation-prone pyridyl, quinolyl, α-heteroaryl boronic acids, and (hetero)aryl halide-containing substrates, including aryl iodides. High-throughput evaluation across 161 pharmaceutically relevant organoboron substrates identified 113 detectable couplings, and representative examples were validated at preparative scale. This work establishes photochemical cross-organoboron coupling as a complementary approach to classical transition-metal-catalyzed coupling and expands the accessible chemical space of heteroaryl organoboron reagents.

Abstract as supplied by the indexing source. © the authors / publisher.