Copper and Silver Catalysis in the (3 + 2) Cycloaddition of Neutral Three-Atom Components with Terminal Alkynes

Abstract

The introduction of the copper-catalyzed azide− alkyne coupling (CuAAC) to 1,3-dipolar cycloadditions was pivotal to their popularization in synthetic chemistry and to their application to multiple other domains of science. The reaction rate enhancement observed when coinage metal acetylide intermediates are involved in the cyclization process greatly expanded the structural and conditional range in which (3 + 2) cycloadditions may take place with terminal alkynes. Herein, we report that comparable rate enhancements, in nature and level, are induced by copper and silver catalysts in the intramolecular (3 + 2) cycloaddition of terminal alkynes with "neutral" three-atom components (TACs), specifically alkynyl sulfides. Through careful observations amidst reaction optimization, experimental, and DFT mechanistic studies, a pathway involving a proton-coupled cyclometallation key step is proposed. The sets of catalytic conditions that have been developed allow us to overcome several scope limitations previously presented by the thermally promoted (3 + 2) cycloaddition of "neutral" TACs, thus expanding their synthetic and applicative potential.

An insight, at the atomic level, into the structure and catalytic properties of the isomers of the Cu22 cluster

“…The reaction was conducted in acetonitrile, using 0.06 mol% of Cu 22 -1 and Cu 22 -2 crystals as catalysts suspended in the solvent. 52–56 After 24 hours at 50 °C, Cu 22 -1 achieved a product yield of 92%, while Cu 22 -2 yielded only 36% (Table S6†). A time-dependent kinetic study of the CuAAC reaction was also performed.…”

Sulfur in Waste‐Free Sustainable Synthesis: Advancing Carbon–Carbon Coupling Techniques

“…Among the uncommon reactivity of alkynyl sulfides, cobalt‐catalyzed [4+2] cycloaddition reactions (Scheme 12a) [107,108] and soft Lewis acid (such as Ag + cations)‐promoted [3+2] cycloaddition reactions with migration of the aryl substituent attached to S (Scheme 12b) [109] stand out. More complex cationic cascades are catalyzed by hard Lewis acids (such as BF 3 ), which activate alkynyl sulfides and trigger the formal [3+2] cycloaddition of alkynyl sulfides and alkynyl sulfoxides with the migration of the thiyl moiety (Scheme 12c) [110] …”

Sulfur in Waste‐Free Sustainable Synthesis: Advancing Carbon–Carbon Coupling Techniques

“…[4+2] cycloaddition reactions (Scheme 12a) [107,108] and soft Lewis acid (such as Ag + cations)-promoted [3+2] cycloaddition reactions with migration of the aryl substituent attached to S (Scheme 12b) [109] stand out. More complex cationic cascades are catalyzed by hard Lewis acids (such as BF 3 ), which activate alkynyl sulfides and trigger the formal [3+2] cycloaddition of alkynyl sulfides and alkynyl sulfoxides with the migration of the thiyl moiety (Scheme 12c).…”