Ni-Catalyzed Synthesis of Thiocarboxylic Acid Derivatives

Abstract

A Ni-catalyzed cross-coupling of readily accessible O-alkyl xanthate esters or thiocarbonyl imidazolides and organozinc reagents for the synthesis of thiocarboxylic acid derivatives has been developed. This method benefits from a fast reaction time, mild reaction conditions, and ease of starting material synthesis. The use of transition-metal catalysis to access a diverse range of thiocarbonyl-containing compounds provides a useful complementary approach when compared with previously established methodologies.

Redox-Active Thiocarbonyl Auxiliaries in Ni-Catalyzed Cross-Couplings of Aliphatic Alcohols

“…Notably, our investigation revealed that this reaction tolerated low nickel and ligand loadings (as low as 1% Ni and 2% ligand), reached completion in less than 5 minutes at room temperature, and was readily performed on larger scales (e.g., reactions on a 10 mmol scale have since been performed with similar efficiency). Notably, the identities of the Ni-precatalyst, bipyridine ligand, and solvent system were found to have a smaller impact on the desired product yield in comparison to our previously developed deoxygenative arylation protocols. − …”

“…A. L. Monteith, J. J. Scotchburn, K. Mills, L. R. Rousseaux, S. A. L. 10.1021/acs.orglett.1c04074202224619624 …”

“…Given the efficiency of thionoester formation under a variety of mild reaction conditions, we wondered if we could develop a method to purposefully access these compounds . This pursuit was further motivated by the varied applications of thionoesters and other thiocarboxylic acid derivatives (e.g., thioamides and dithioesters) as starting materials in both organic and biological chemistry (Scheme a). − Aside from being able to access a new cohort of redox-active thiocarbonyl auxiliaries for subsequent cross-coupling efforts, we thought that the development of a unified synthetic approach to thiocarboxylic acid derivatives would be enabling, given the various drawbacks associated with traditional thionation and thioacylation approaches (malodorous, harsh reaction conditions, challenging purification, etc.)…”

“…3 To accomplish this objective, we focused on activating alcohol, amine, or thiol precursors with commercially available thiocarbonyl sources (carbon disulfide (CS 2 ) or 1,1′thiocarbonyldiimidazole (TCDI)) for the development of a Ni-catalyzed Negishi cross-coupling. 3 For thionoester synthesis, O-alkyl xanthate esters derived from tertiary (79a), secondary (79b, 79c, 79f, 79g), or primary (79d, 79e) aliphatic alcohols could be efficiently coupled to both electron-rich (79h, 79j) and electron-deficient (79i) (hetero)arylzinc reagents (Scheme 14a). As observed with our previous reports, ortho-substituted arylzinc reagents gave low yields of the desired product.…”

Redox-active alkyl xanthate esters enable practical C–S cross-coupling by nickel catalysis

“…1C, path a). 16 c – f Despite the high accessibility of AXEs and the well-established delivery of alkyl radicals as key intermediates in the reactions, noteworthily, utilizing them as cross-coupling handles in transition metal catalysis has been largely excluded from past work, 17 primarily due to the scarcity of suitable activation modes for the xanthate functionality. Although alkyl xanthate esters have been used in C–S bond formation via sequential alcoholysis-substitution, 18 to our knowledge, the employment of AXEs serving as alternative sulfenylating reagents for metal-catalyzed chemo- and regioselective cleavage of the C–S bond followed by cross-coupling with a carbon counterpart to deliver a new C–S bond remains an uncharted exercise (Fig.…”