Selective α-Me–C(sp3)–H borylation of methyl sulfides controlled by substrate–ligand electrostatic interaction

Abstract

An iridium/electron-deficient bipyridine-catalyzed selective α-Me–C(sp³)–H borylation of methyl sulfides was disclosed. The reaction exhibited high site-selectivity at the C(sp³)–H bond of the α-methyl group when aryl methyl sulfides were used as substrates (up to 65% yield with a 99 : 1 rr ratio). In contrast, the borylation mostly occurred at the aryl ring and gave C(sp²)–H borylated products when using 4,4′-di-tert-butyl-2,2′-bipyridine as a ligand (up to 76% yield with a 5 : 95 rr ratio). DFT calculations revealed that the C–H bond cleavage step of this reaction is the rate-determining step; the electrostatic interaction (π–π stacking) between the substrate and the electron-deficient bipyridine ligand contributing to the energy difference between the major sp³ pathway (19.4 kcal mol⁻¹) and the minor sp² pathway (23.7 kcal mol⁻¹) is the key factor for controlling the unique site-selectivity. This selective α-Me-C(sp³)–H borylation was applicable to many aryl methyl sulfides, as well as aliphatic methyl sulfides, displaying high functional group tolerance and good yields. Furthermore, the boryl group of the borylated product was readily transformed into other functional groups, which demonstrates the applicability of this methodology.