Mechanisms for nickel(0)/N-heterocyclic carbene-catalyzed intramolecular alkene hydroacylation: insights from a DFT study

Abstract

Density functional calculations have been applied to study and elucidate nickel(0)/N-heterocyclic carbene-catalyzed intramolecular alkene hydroacylation. The calculations showed that nickel(0)-catalyzed intramolecular alkene hydroacylation involved four potential reaction channels (I, II, III, and IV), and pathway IV was predicted to be more favorable than the other three. Two pathways, I and II, had three steps (oxidative addition, hydrogen migration, reductive elimination), and the rate-determining step was hydrogen migration. Pathway III proceeded through oxidative cyclization, β-hydride elimination, and hydrogen migration, and the rate-determining step was β-hydride elimination. Pathway IV included four steps (oxidative cyclization, dimerization, β-hydride elimination, hydrogen migration), and the rate-determining step was again β-hydride elimination. Oxidative cyclization was easy and led to rapid dimerization, greatly reducing the free energy of β-hydride elimination. The binuclear nickelacycle intermediate was observed in Ogoshi's experiments, and it was identified by nuclear magnetic resonance (NMR). The dominant product was the five-membered benzocyclic ketone p1. All results agreed with Ogoshi's experiments. Graphical Abstract Nickel(0)-catalyzed intramolecular alkene hydroacylation involved four potential reaction channels. The binuclear nickelacycle intermediate was important, and the dimerization greatly reduced the free energy of the β-hydride elimination.

Theoretical Studies on the Mechanisms and Origins of Ligand-Controlled Regioselective Hydroacylation of Terminal Alkynes Catalyzed by the Rhodium(I) Complex

“…We also note that this addition process is exergonic and reversible. The facility of C–H oxidative addition has also been found in previous theoretical studies of hydroacylation reactions. , Following, there are four possible pathways: alkyne 1 can directly insert into Rh–H bond via 1,2- (path 1) or 2,1-insertion (path 2) modes, and the insertion pattern determines the regioselectivity. Alternatively, the alkyne can also coordinate with the rhodium center, pushing H downward from two different directions: the Ar substituent of alkyne lies on the same side of the Rh–C­(acyl) bond (path 3) or points away from it (path 4) (the free energy profiles for paths 3 and 4 see Figure S2).…”

N-Heterocyclic carbenes as privileged ligands for nickel-catalysed alkene functionalisation

“…In the seminal work reported by Ogoshi and co-workers in 2012, they developed a Ni 0 /I t Bu catalysed intramolecular alkene hydroacylation reaction to access five/six-membered benzocyclic ketones 128 (Scheme 50). Mechanistic studies involving stoichiometric experiments 128 and DFT calculations 129 provide valuable insights into the plausible reaction mechanism which involves a dioxanickelacycle intermediate in the lowest energy pathway.…”

“…The dimer 328 was isolated in 84% yield in a separate stoichiometric experiment and was characterised with 1 H NMR and X-ray crystallography. A later DFT study 129 delved deeper into the mechanism and revealed that the facile dimerisation of 327 , which results in the formation of 328, significantly reduces the free energy required for the subsequent rate-determining β-hydride elimination step that leads to the formation of intermediate 329 . This is followed by a formal reductive elimination step, which releases the final benzocyclic ketone product and regenerates the active Ni/I t Bu species.…”