Copper‐Catalyzed Reaction Cascade of Thiophenol Hydroxylation and S‐Arylation through Disulfide‐Directed C−H Activation

Abstract

Copper-catalyzed thiophenol C-H activation is described. Through an initial attempt to conduct C-arylation with arylboronic acid, a rather surprising sequential C-H activation and S-arylation was discovered. Mechanistic investigation revealed the disulfide intermediate as the key component in directing C-H oxidation. The overall reaction proceeded under mild conditions with molecular oxygen as the oxidant. Discovery of disulfide as the directing group provides a potential new direction for catalytic C-H functionalization under mild conditions.

Disulfide‐Directed C–H Hydroxylation for Synthesis of Sulfonyl Diphenyl Sulfides and 2‐(Phenylthio)phenols with Oxygen as Oxidant

“…Furthermore, the competing reaction between the aryl iodide and the arylboronic acid revealed a faster reaction with the arylboronic acid (Scheme D). Therefore, based on these experiments and considering that the reaction could not proceed under N 2 protection (Scheme ), we suggest that the oxygen atom of the product may be from molecular oxygen for both the aryl iodide and arylboronic acid, which was consistent with Shi's work . In order to obtain more information on this reaction, some selectivity experiments with an unsymmetrical disulfide and iodobenzene were carried out.…”

“…Particularly, these compounds were used as pigments, anticancer drugs, dyes and antibiotics on ac count of their special biological activities (Scheme ). Based on the thioether, sulfoxides as the directing group, herein, we report a copper‐catalyzed hydrolytic reaction with disulfide as directing group to prepare sulfonyl diphenyl sulfides and 2‐(phenylthio)phenol derivatives that avoids producing sulfoxides and sulfones at elevated temperatures …”

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…Further exploring the potential of the thioether motif as DG and drawing inspiration from the observation that benzylthioethers are effective in C–H activation reactions, Wang and Shi described an elegant example of disulfide-directed C–H hydroxylation ( Scheme 164 ). 1013 The optimized Cu-based catalytic system allows a sequential transformation involving: (1) thiophenol oxidation to disulfide, (2) disulfide-directed ortho -hydroxylation and (3) S -arylation using boronic acid coupling partner, affording otherwise difficult to access 1,2-thio-phenol derivatives. Remarkably, this complex transformation is rather high-yielding and shows good substrate scope, in particular with regard to halogenated substituents at both coupling partners.…”

Transition-metal-catalyzed synthesis of phenols and aryl thiols

“…In 2016, the Wang and Shi group reported a CuI-catalyzed C–H hydroxylation of thiophenols, in which disulfide directed the hydroxylation [58]. Using aryl thiol and arylboronic acid as starting materials, C–H hydroxylation and C–S coupling sequentially occurred in DMF in the presence of Cs 2 CO 3 and molecular oxygen, affording 2-(phenylthio)phenols as final products (Scheme 29).…”