The origins of reactivity and regioselectivity in nickel-catalyzed reductive coupling reactions of alkynes and aldehydes were investigated with density functional calculations. The regioselectivities of reactions of simple alkynes are controlled by steric effects, while conjugated enynes and diynes are predicted to have increased reactivity and very high regioselectivities, placing alkenyl or alkynyl groups distal to the forming C-C bond. The reactions of enynes and diynes involve 1,4-attack of the Ni-carbonyl complex on the conjugated enyne or diyne. The consequences of these conclusions on reaction design are discussed.

Origins of Regioselectivity and Alkene-Directing Effects in Nickel- Catalyzed Reductive Couplings of Alkynes and Aldehydes

Herein, we describe an efficient method to prepare polysubstituted pyrroles via a copper hydride (CuH)-catalyzed enyne–nitrile coupling reaction. This protocol accommodates both aromatic and alipha...

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Synthesis of Pyrroles through the CuH-Catalyzed Coupling of Enynes and Nitriles.

Iron-Catalyzed Dehydrative Alkylation of Propargyl Alcohol with Alkyl Peroxides To Form Substituted 1,3-Enynes.

A quantitative description for the interaction of Cu(I) with poly(styrene-co-maleic anhydride) modified with 4-aminopyridine (denoted as CuI/SMI complex) is presented using density functional theory (DFT) and quantum theory of atoms in molecules (QTAIM) approaches. Topological analysis of electron density revealed the existence of effective interactions between Cu(I) ions and the nitrogen in the pyridine ring. Interestingly, the results also showed that there is considerable interaction between Cu(I) and the oxygen of the carbonyl motif in the SMI ligand. Thus, CuI/SMI was examined as a heterogeneous and recyclable catalyst in Hantzsch pyridine synthesis under solvent-free conditions, affording diverse 1,4-dihydropyridines (1,4-DHPs) in excellent yields with relatively short reaction times.

Computational investigations on structural and electronic properties of CuI nanoparticles immobilized on modified poly(styrene-co-maleic anhydride), leading to an unexpected but efficient catalyzed synthesis of 1,4-dihydropyridine via Hantzsch pyridine synthesis

A computational study using the B3LYP density functional was carried out to explore the effects of counterions and solvents on the Au(I)-catalyzed cyclization reaction of indole-allenoate to form dihydrocyclopenta[b]indole derivatives. The optimal reaction path includes intramolecular cyclization and proton transfer steps. In the first process, the counterions Cl−, BF4− and OTf− act as hydrogen-bond acceptors to promote the intramolecular cyclization between the C1 and C5 atoms. In the proton transfer step, the anions greatly reduce the energy barrier of proton migration, in the form of a proton-transfer shuttle. More importantly, the Bronsted/Lewis basicity of the counterions (Cl− > OTf− > BF4−) turns out to be the primary reason for the difference in the counterion catalytic activity in the proton-transfer process. During the protonation of the counterion, the catalytic capacities of the counterions show significant differences according to the series Cl− > OTf− > BF4−, and the order of the catalytic ability of the counterions was found to be Cl− < OTf− < BF4− in the deprotonation of the counterion-H. Interestingly, the strong coordinating capability of the solvents (DMF and DMSO vs. PhCH3) was found to be another important factor that critically affects the reaction yield (0%, 0% and 95% yield, respectively). Overall, our calculations not only explain the experimental phenomena well, but also put forward some guidance and advice for the selection of counterions and solvents for transition metal-catalyzed reactions, including proton-transfer processes.

DFT study on the Au(I)-catalyzed cyclization of indole-allenoate: counterion and solvent effects

A computational study with the BhandHLYP density functional is conducted to elucidate the mechanisms of Cu(I)- and Cu(II)-catalyzed reactions of o-alkynylbenzaldehydes with a nucleophile (MeOH). Our calculations suggest the following. (a) The use of CuCl as a catalyst deceases significantly the energy barrier and promotes intramolecular cyclization. (b) Solvent DMF is critical in the stepwise hydrogen-transport process involved in an intermolecular nucleophilic addition because it can greatly reduce the free energy barrier of the hydrogen-transfer process as a proton shuttle. In addition, we find that substrate MeOH also plays a role similar to that of DMF in the hydrogen-transport reaction. (c) The 6-endo product P1 is formed exclusively using a catalytic system consisting of CuCl and DMF, whereas a mixture of 6-endo product P1 and 5-exo product P2 in a ratio of ∼1:1 is produced using CuCl2 and DMF as a catalytic system. Our theoretical calculations reproduce the experimental results very well. This study is expected to improve our understanding of Cu(I)- and Cu(II)-catalyzed reactions involving Lewis base solvents and to provide guidance for the future design of new catalysts and new reactions.

Mechanistic Insights into the Cu(I)- and Cu(II)-Catalyzed Cyclization of o-Alkynylbenzaldehydes: The Solvent DMF and Oxidation State of Copper Affect the Reaction Mechanism.

Density functional theory (DFT) was utilized to elucidate the reaction mechanisms of and the key factors that influence the Ni(0)-catalyzed cross-dimerization and -trimerization of trimethylsilylacetylene (R1) and diphenylacetylene (R2). Calculated results revealed that the electron-donating ability of the ligand plays a crucial role in determining the regionselectivity of this tandem reaction. The use of strongly electron-donating ligands favors the formation of cross-dimer intermediates, whereas cross-trimer products can easily be synthesized using weakly electron-donating ligands. A simple method of estimating the electron-donating abilities of different ligands based on the Mulliken charge distribution of the ligand–ligand pair was employed. The present theoretical results allow us to elucidate the reaction mechanisms for and to identify the factors that exert the greatest influence on the ligand-controlled cross-dimerization and -trimerization of trimethylsilylacetylene and diphenylacetylene. Guidelines for the design of novel ligand systems with Ni(0) catalysts are also proposed.

Mechanisms for the synthesis of conjugated enynes from diphenylacetylene and trimethylsilylacetylene catalyzed by a nickel(0) complex: DFT study of ligand-controlled selectivity

Cheng Huang

Papers

Mechanistic Insights into the Cu(I)- and Cu(II)-Catalyzed Cyclization of o-Alkynylbenzaldehydes: The Solvent DMF and Oxidation State of Copper Affect the Reaction Mechanism.

Mechanisms for the synthesis of conjugated enynes from diphenylacetylene and trimethylsilylacetylene catalyzed by a nickel(0) complex: DFT study of ligand-controlled selectivity