Cooperative catalysis by bovine serum albumin–iodine towards cascade oxidative coupling-C(sp2)–H sulfenylation of indoles/hydroxyaryls with thiophenols on water

Abstract

Cooperative cascade catalysis by bovine serum albumin (BSA)–iodine allows for the first time the performance of C(sp²)–H sulfenylation of indole from readily available thiophenol (–SH bond) via in situ generation/cleavage of disulfide (S–S bond) in air under aqueous conditions, whereas BSA or I₂ individually do not permit this two step sequence to occur in the same pot towards C–S bond formation. This green cooperative protocol is extendable to sulfenylation of hydroxyaryls (i.e. 2-naphthol or 4-hydroxycoumarin) with diverse thiols (aryl/heteroaryl) without using any toxic metal catalysts, bases or oxidants, thus rendering the process environmentally and economically reliable. Further, the gram scale synthesis of a COX-2 inhibitor (3-(pyridin-2-ylthio)-1H-indole), regioselectivity and recyclability (up to four cycles) are the additional merits of this cooperative cascade bio-chemocatalytic (BSA–I₂) protocol. Moreover, HPLC and ESI-MS provide powerful insights into the mechanistic aspects of the above cascade sulfenylation reaction.