EVALUATION OF PHENOXYTHIAZOLINE-COBALT CATALYSTS FOR C(sp2)–C(sp3) SUZUKI-MIYAURA CROSS-COUPLING REACTIONS

Abstract

Suzuki-Miyaura cross-coupling reactions have widespread applications in the synthesis of pharmaceuticals, fine chemicals, and organic materials. Cross-coupling reactions to form C–C bonds are typically catalyzed by precious metals such as palladium, which significantly contributes to the cost and environmental impact of important synthetic routes. Consequently, there is large motivation to use more earth-abundant first-row transition metals such as cobalt in catalysis, which can provide both chemical and environmental advantages. However, the mechanistic understanding of cobalt catalysis largely remains in its infancy, particularly as applied to C(sp2)–C(sp3) couplings. In this work, a reproducible protocol for a cobalt-catalyzed C(sp2)–C(sp3) Suzuki-Miyaura cross-coupling with phenoxyimine (FI) ligands was established by finetuning previously reported experimental and analytical procedures. Cobalt(II) halides in combination with phenoxythiazoline (FTz) ligands were then used to catalyze a C(sp2)–C(sp3) Suzuki-Miyaura cross-coupling between alkyl bromides and a pharmaceutically relevant indole-containing boronic ester. This reaction was then optimized by exploring the influence of various reaction parameters. Finally, the relevant coordination chemistry of the catalyst was explored by forming various FTz-Co complexes and examining their reactivity, revealing that mono and bis-ligand Co(II) compounds were effective in producing high yields of the desired product, while a tris-ligand Co(III)–Co(III) complex was ineffective.