Discovery of Zinc Thiolates as the Missing Link in Ni-Catalyzed Reductive C(sp)²–S Coupling

Abstract

Nickel-catalyzed reductive coupling of organic halides with sulfur electrophiles has emerged as a robust strategy for accessing a diverse array of valuable sulfur-containing molecules. However, its mechanism remains incompletely elucidated, primarily due to the lack of studies on characterization of multiple nickel intermediates (e.g., Ni(I)/Ni(II)/Ni(III)), as well as the mechanistic roles of reductive metal additives. Herein, we identify the rapid oxidative addition of zinc to the S–S bond of disulfides as a pivotal step that enables subsequent transmetallation with arylnickel(II) adducts. Furthermore, we discovered that the zinc serves as additional two critical roles: it not only reduces the Ni(II)-precatalyst to active Ni(0) specie, but also mediates the reduction of sulfur electrophiles (e.g., N-thiophthalimides or thiosulfonates) to the corresponding disulfides. We also report the first example of a base-free, nickel-catalyzed Negishi-type thiolation of (hetero)aryl halides using bench-stable zinc dithiolates, thereby furnishing a versatile alternative to established methodologies for the synthesis of structurally diverse C(sp²)-rich sulfides.

Keywords

Organosulfur compounds / Reductive coupling / Zinc insertion / C(sp)²–S coupling / Negishi-type thiolation / Transition-metal catalysis / Zinc thiolate / Sulfur electrophile

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