Dimer Involvement and Origin of Crossover in Nickel-Catalyzed Aldehyde–Alkyne Reductive Couplings

Abstract

The mechanism of nickel(0)-catalyzed reductive coupling of aldehydes and alkynes has been studied. Extensive double-labeling crossover studies have been conducted. While previous studies illustrated that phosphine- and N-heterocyclic carbene-derived catalysts exhibited differing behavior, the origin of these effects has now been evaluated in detail. Many variables, including ligand class, sterics of the ligand and alkyne, temperature, and ring size being formed in intramolecular versions, all influence the extent of crossover observed. A computational evaluation of these effects suggests that dimerization of a key metallacyclic intermediate provides the origin of crossover. Protocols that proceed with crossover are typically less efficient than those without crossover given the thermodynamic stability and low reactivity of the dimeric metallacycles involved in crossover pathways.

Mechanistic Basis for Regioselection and Regiodivergence in Nickel-Catalyzed Reductive Couplings

“…30 Additionally, a number of theoretical studies have examined different combinations of metals, ligands, and reductants, with metallacycle formation uniformly being found as a key component of the operative pathway. 31-35 …”

“…33 Most recently, post rate-limiting dimerization of a metallacycle derived from an intramolecular processes using silanes with a nickel(0)-phosphine catalyst was found to be competitive with the simple mononuclear pathway depicted above (Scheme 3), however, in this study as well, metallacycle formation was proposed to be the rate-determining step. 35 In summary, across a broad range of combinations of substrate classes, including inter- and intramolecular processes, phosphine and NHC-derived catalyst systems, and silane and borane reductants, evidence from kinetics and computational studies of the most widely used protocols all pointed towards a metallacycle-based pathway involving a rate-determining oxidative cyclization to produce metallacycle 4 followed by a fast process involving metallacycle consumption by the reductant.…”

Regiodivergent and Stereoselective Hydrosilylation of 1,3‐Disubstituted Allenes

“…To probe the mechanism of the addition process,aseries of double-labeling studies were performed with cyclohexylallene and the Ni or Pd catalyst (Scheme 3) utilizing mixtures of Et 3 SiD and nPr 3 SiH. [12] Additions to am onosubstituted allene were studied to simplify the analysis,a st his substrate permitted the highest regioselectivities using commercially available deuterated silane reagents.F or both the nickel-and palladium-catalyzed reactions,o nly traces of the crossover products were observed, indicating that as ingle molecule of R 3 SiH delivers the SiR 3 and Ht oasingle product molecule, thus ruling out the involvement of metal hydrides that lack the silyl group or metal silyl species that lack the hydride.This outcome stands in contrast to ar ecent study by Schmidt and Tafazolian who observed the crossover products when cationic catalysts were used, thus indicating that the mechanism of allene hydrosilylation is highly catalyst-dependent. [8c] Based on this outcome,alikely mechanism involves coordination of the nickel or palladium catalyst to the sterically least encumbered face of the allene to form complex 22 or 23 ( Figure 2).…”

Highly Enantioselective Nickel‐Catalyzed Intramolecular Reductive Cyclization of Alkynones

“…However, the absorption peak slowly disappeared after the addition of a stoichiometric amount of AntPhos, indicating that the cycloaddition of 1 a with a nickel species bearing an AntPhos ligand has occurred. Based on these results and a kinetic study by Montgomery and co‐workers16 and computational studies by the groups of Houk,17 Jamison,17a and Montgomery17c,d on Ni‐catalyzed intermolecular or intramolecular ynal reductive cyclizations, we propose the catalytic cycle depicted in Figure 4. Cycloaddition of alkynone 1 a with the Ni 0 species I provides Ni II metallacycle II .…”