Visible-Light-Activated Nickel Thiolates for C–S Couplings

Abstract

Thiolates are known as the inhibitors of metal catalysis due to their strong coordination with the metal. Herein, we reported visible-light-induced homolysis of the Ni–S bond to activate the nickel(II) thiolates for the C–S coupling, obviating the use of exogenous photocatalysts and other additives. Various aryl bromides/iodides can efficiently couple with thiols with a wide range of functional groups under mild conditions. Preliminary mechanistic studies suggested the homolysis of the Ni–S bond is the key step for couplings and nickel(0) is not involved in the process.

A Paradigm Shift in Catalysis: Electro- and Photomediated Nickel-Catalyzed Cross-Coupling Reactions

“…The Ni­(I)­SR complex can then undergo oxidative addition into an aryl iodide to form a Ni­(III)­SR­(X)Ar complex, which, upon reductive elimination, delivers the desired thioether product and a Ni­(I)­X species. This proposed mechanism has since been validated by several groups and invoked in other C–heteroatom cross-coupling reactions. − The electrochemical versions of this Ni-catalyzed C–S cross-coupling reaction have since been reported. , …”

“…This is especially the case in drug discovery, as medicinal chemistry is often performed across electron-rich benzenes and electron-deficient heterocycles with a wide range of alkyl and heteroatomic fragments. Over the past decade, several general strategies toward C­(sp 2 )–C­(sp 3 ), ,,,,,,,,− C­(sp)–C­(sp 3 ), ,,− and C-heteroatom ,,,,,,− cross-couplings have been enabled by photo- and electrochemistry. , Throughout our experience in developing Ni-catalyzed photo- and electrochemically driven C–C and C–heteroatom cross couplings, we, as well as others, have noticed several reactivity trends . To aid the community in discerning the appropriate tactic, we have assembled a user guide to help navigate photo- and electrochemically driven cross-coupling reactions and highlight useful technologies developed by others in the field (Figure ).…”

Nickel-catalyzed cross-electrophile coupling of aryl thiols with aryl bromides via C–S bond activation

“…Normally, the cross-coupling of aryl thiols with organic halides or pseudohalides proceeded via S–H bond cleavage 6 with the aid of a transition metal catalyst ( e.g. , rhodium, 7 copper, 8 palladium, 9 cobalt, 10 and nickel 11,12 ) or a photocatalyst 13 in the presence of a base (Scheme 1a), leading to the corresponding aryl sulfides as the final products while leaving the C–S bond in the thiol substrate intact. It was reported that even under reductive conditions that are commonly employed in cross-electrophile couplings by using nickel or cobalt as the transition metal catalyst and zinc as the reducing metal (Scheme 1b), 10,12 the cross-coupling of aryl thiols with aryl halides still produced the corresponding aryl sulfides instead of biaryls as the target products.…”

Synthesis and Functionalization of Thiophosphonium Salts: A Divergent Approach to Access Thioether, Thioester, and Dithioester Derivatives

“…As part of our overarching strategies to synthesize a diverse range of thio-based bioactive compounds ( I –VI ), encompassing thioether, thioester, and dithioester derivatives, we recognized the potential of thiophosphonium salts as versatile core scaffolds for these molecules (Scheme B). − …”

“…To this end, various representative applications were conceived for these valuable salts 3 as depicted in Scheme and . For instance, we conducted selective reduction and oxidation protocols of the C– + P, enabling the synthesis of the valuable thioether, deuterated-thioether, thioester, and dithioester derivatives. ,,,− …”