Mechanistic Investigation of the Nickel-Catalyzed Metathesis between Aryl Thioethers and Aryl Nitriles

Abstract

Functional group metathesis is an emerging field in organic chemistry with promising synthetic applications. However, no complete mechanistic studies of these reactions have been reported to date, particularly regarding the nature of the key functional group transfer mechanism. Unraveling the mechanism of these transformations would not only allow for their further improvement but would also lead to the design of novel reactions. Herein, we describe our detailed mechanistic studies of the nickel-catalyzed functional group metathesis reaction between aryl methyl sulfides and aryl nitriles, combining experimental and computational results. These studies did not support a mechanism proceeding through reversible migratory insertion of the nitrile into a Ni–Ar bond and provided strong support for an alternative mechanism involving a key transmetalation step between two independently generated oxidative addition complexes. Extensive kinetic analysis, including rate law determination and Eyring analysis, indicated the oxidative addition complex of aryl nitrile as the resting state of the catalytic reaction. Depending on the concentration of aryl methyl sulfide, either the reductive elimination of aryl nitrile or the oxidative addition into the C­(sp2)–S bond of aryl methyl sulfide is the turnover-limiting step of the reaction. NMR studies, including an unusual 31P–2H HMBC experiment using deuterium-labeled complexes, unambiguously demonstrated that the sulfide and cyanide groups exchange during the transmetalation step, rather than the two aryl moieties. In addition, Eyring and Hammett analyses of the transmetalation between two Ni­(II) complexes revealed that this central step proceeds via an associative mechanism. Organometallic studies involving the synthesis, isolation, and characterization of all putative intermediates and possible deactivation complexes have further shed light on the reaction mechanism, including the identification of a key deactivation pathway, which has led to an improved catalytic protocol.

Structural Evidence for Aromatic Heterocycle N–O Bond Activation via Oxidative Addition

“…There have been reports of presumably low-valent Ni complexes activating aromatic N–O bonds . To initiate our studies, we chose the combination of bis­(1,5-cyclooctadiene)­nickel(0) (Ni­(COD) 2 ) and 1,2-bis­(dicyclohexylphosphino)­ethane (dcype), which we have used in the past to activate challenging bonds, such as C–S and C–CN bonds. − Mixing 1,2-benzisoxazole ( BZX I ) with Ni(0)/dcype (Figure a) resulted in a doublet in 31 P­{ 1 H} NMR and immediate formation of orange crystals. When analyzed using scXRD, they revealed the structure of a cationic complex resulting from N–O oxidative addition and protonation of the Ni­(II)-imidate ( OAC I ), with a phenolate (resulting from Kemp rearrangement of BZX I ) as the counterion (Figure b).…”

An efficient direct arylation polycondensation via C-S bond cleavage

“…2a). Note that the oxidative intermediate can be adopted to consolidate the following transmetalation process [40][41][42] . Thus, the stoichiometric reaction (Fig.…”

Structural Evidence for Aromatic Heterocycle N–O Bond Activation via Oxidative Addition

“…31 To initiate our studies, we chose the combination of bis(1,5cyclooctadiene)nickel(0) (Ni(COD)2) and 1,2bis(dicyclohexylphosphino)ethane (dcype), which we have used in the past to activate challenging bonds such as C-S and C-CN bonds. [32][33][34][35][36] Mixing 1,2-benzisoxazole (BZX I) with Ni(0)/dcype (Fig. 2a) resulted in a doublet in 31 P{ 1 H} NMR and immediate formation of orange crystals.…”