A detailed theoretical investigation to unravel the molecular mechanism of the ligand-free copper-catalyzed Suzuki cross-coupling reaction

Abstract

Suzuki Miyayura Coupling (SMC) represents a very efficacious method for constructing C-C bonds in organic synthesis. The ligand-free variants of SMC have been grabbing attention these days. Despite this momentousness,...

Water-Soluble Copper(I) Hydroxide Catalyst and Its Formation in Ligand-Free Suzuki–Miyaura Cross-Coupling Reactions

“…Carbon–carbon cross-coupling reactions are widely used in designing organic compounds, materials, agrochemicals, and pharmaceuticals. − One type of such reactions is the Suzuki–Miyaura (SM) cross-coupling, which utilizes an organoborane nucleophile coupled with an sp 2 -hybridized aryl halide electrophile. , Due to the mild reaction conditions, compatibility with other functional groups, and readily available organoboron derivatives, SM reactions are particularly common in the pharmaceutical industry. , The record of cross-coupling reactions has been present in the literature since the 1940s when several transition metals were used to catalyze such reactions, including Fe, Ni, and Cu, among others . The first study of Pd-catalyzed SM reactions was reported in 1979, and since then, Pd increasingly became the metal of choice for transition metal-catalyzed SM cross-coupling reactions due to its high stability, C–H activation ability, and the ability to catalyze reactions at trace amounts. ,− However, there are growing concerns about its long-term sustainability due to the low nature abundance, prohibitive costs, and high toxicity of Pd metal. − …”

“…The coupling was assumed to be homogeneous with CuI being the active catalyst, though no experimental evidence was presented . Possible reaction mechanisms involving transmetalation, oxidative addition, and reductive elimination were also reported but without experimental evidence of either active catalysts or reaction intermediates. , …”

“…36 Possible reaction mechanisms involving transmetalation, oxidative addition, and reductive elimination were also reported but without experimental evidence of either active catalysts or reaction intermediates. 18,28 Without using stabilizing ligands, ligand-free metal-catalyzed cross-coupling offers several benefits. They include that precatalysts are readily available and easy to be recovered, reactions can be conducted in air, and products are easily isolated with less contaminations.…”