Regioselective synthesis of ortho-iodobiphenylboronic acid derivatives: a superior catalyst for carboxylic acid activation

Abstract

An efficient and versatile synthesis of ortho-iodobiphenylboronic acids via the highly regioselective metal–iodine exchange (MIE) of 2,3-diiodobiphenyls is reported. The site-selectivity is very much controlled by the size of the biphenyl fragment, providing only the terminal arylboronic acid derivatives in excellent site-selectivity. The nature of the substituents (R¹ and R²) on the biphenyls is found to have an influence on the reactivity but not on the regioselectivity. The best reactivity and the highest isolated yields were furnished with products bearing electron-donating groups. The synthesized derivatives were also tested for in vitro antimicrobial activity against four strains of bacteria and one fungal strain. This revealed that (2-iodo-4′-isopropyl-[1,1′-biphenyl]-3-yl)boronic acid 6_A and (3-(benzo[d][1,3]dioxol-5-yl)-2-iodo-5-methoxyphenyl)boronic acid 22_A possess the most potent antibacterial and antifungal activity with MICs of 0.10 and 0.3 mg mL⁻¹ for B. cereus and C. albicans respectively. The catalytic activity was also examined towards an amidation reaction at ambient temperature and this revealed a new optimal catalyst, (2-iodo-4′,5-dimethoxy-[1,1′-biphenyl]-3-yl)boronic acid 19_A providing a remarkable increase in the amide yields, including α-aminoacids. This work discloses a protocol for the first synthesis of hitherto unknown ortho-iodobiphenylboronic acid derivatives that is scalable, and general in scope, where no chromatographic purification is necessary and the products are indeed potential organocatalysts.