Kinetic Investigation of a Ligand‐Accelerated Sub‐mol % Copper‐Catalyzed CN Cross‐Coupling Reaction

Abstract

Unique ligand acceleration: A kinetic investigation of the copper‐catalyzed CN cross‐coupling in the sub‐mol % range reveals an exceptional ligand dependence. Dimethylethylenediamine (DMEDA) is unique in promoting this reaction, and even at a ratio of >2000:1 relative to the catalyst, the reaction order is still positive in DMEDA. This discovery allowed the development of milder reaction conditions. The reaction order in copper becomes zero at very low concentration.

Synthesis of 2‐Aminobenzothiazoles via Copper(I)‐Catalyzed Cross‐Coupling with Part‐Per‐Million Catalyst Loadings

“…Very recently, a similar result was also found in the copper-catalyzed cross-coupling reaction of pyrazole and iodobenzene. [10] These research works pioneered the efficient cross-coupling reactions catalyzed by sub-mol% amounts of copper catalyst loadings, although a high reaction temperature and large amount of ligand (usually 20 mol%) are still necessary. Issues yet to be developed are, therefore, the generality and facility of these cross-coupling reactions with very low catalyst loadings.…”

New efficient ligand for sub-mol % copper-catalyzed C–N cross-coupling reactions running under air

“…This is different from DMEDA, where the order was found to be 1 at Cu concentrations below ca. 1 mM, and 0 at higher concentrations [77]. A value lower than 1 indicates that an active monomeric catalyst is in equilibrium with inactive dimers or higher oligomers.…”

“…DMDETA, together with DMEDA, is one of the few reported ligands that work at sub-mol % levels of copper catalyst [23,45,77–78 88]. DMDETA proved to be at least as efficient as DMEDA and in addition has the ability to render the catalyst tolerant to air.…”

“…With a few exceptions [23,45], the catalytic loading is still in the range of 5–20 mol %. We have shown recently that in many cases sub-mol % of copper is enough to catalyze several transformations [76–77]. By keeping the ligand (DMEDA) concentration high (>20 mol %) the cross-coupling reactions can be run with copper concentrations down to 0.001 mol % (10 ppm).…”

Sunlight‐Driven Copper‐Catalyst Activation Applied to Photolatent Click Chemistry

“…[32] It is noteworthy that the copper(II) ions of a laccase protein could be effectively reduced through a Zn-porphyrin photosensitized process, the generated copper(I) species could then mediate the four-electron reduction of O 2 into water. [34][35][36][37][38] The DMEDA ligand is structurally simple, commercially available, and inexpensive, making it valuable from a practical point of view. We describe herein the synthesis, full characterization, photoreduction properties, and catalytic activity for the CuAAC reaction of the copper(II)-DMEDA complex 1 (Scheme 1).…”