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

Abstract

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.

Theoretical Investigation on Mechanism of the PPh3-Catalyzed Isomerization of Allenic Sulfones to 2-Arylsulfonyl 1,3-Dienes: Effects of Additive as the Proton-Shuttle

“…Similar effect of solvents has been found by Yamamoto, Xia and Li et al . Besides, the reactance MeOH also prompts the catalytic reactions as the proton‐shuttle reagent, which has been discovered in our previous theoretical studies. Interestingly, Li and co‐workers found that the OTf − ‐assisted 1,2‐H migration required the activation energy of only 9.6 kcal/mol, while the activation energy barrier was much higher (20.2 and 29.0 kcal/mol, respectively) for BF 4 − ‐ and SbF 6 − ‐assisted H‐shift process in the Au(PR 3 ) + ‐catalyzed cycloisomerization of bromoallenyl ketones.…”

“…Yamamoto and co‐workers presented that solvent DMF could not only offer an appropriate catalytic medium for the synthesis of cyclic alkenyl ethers via intramolecular cyclization of o ‐Alkynylbenzaldehydes using Cu(I) salts as the catalysts, but also serve as a cocatalyst to directly participate in the reaction. In this reaction, our previous study showed that DMF molecule played the role of proton‐shuttle to assist proton shift from MeOH to carbon atom of substrate (2‐(1‐alkynyl)‐2‐alken‐1‐ones). Similar effect of solvents has been found by Yamamoto, Xia and Li et al .…”

DFT Study on the Gold(I)‐Catalyzed Dehydrogenative Heterocyclization of 2‐(1‐Alkynyl)‐2‐alken‐1‐ones to form 2,3‐Furan‐Fused Carbocycles: Effects of Additives C5H5NO vs. PhNO

“…In addition, this experimental phenomenon can be explained by the loose scan profile (see Figure S4 in Supporting Information). The method using the loose scan to explain the experimental results has been adopted successfully in the previous theoretical calculations . As shown in Figure S4, the energy curve is sharply rising in energy with the formation of O1‐C1 bond from 1a to in1’ , meaning that the intramolecular cyclization of O1 with C1 cannot be carried out without the participation of Au(I) catalyst.…”

“…The geometric structures of all the intermediates and the transition states are calculated with the Becke three‐parameter hybrid functional (B3LYP) in the framework of density functional theory (DFT) . This computational method has been successfully applied in the mechanistic studies of transition‐metal‐catalyzed reactions . As a further test for the functionals CAM‐B3LYP, M06, BLYP, B3P86, B3PW91 and BHandHLYP are evaluated, and their calculation results are close to those of B3LYP (see Table S1 in Supporting Information).…”

“…The double‐ζ basis set (6‐31G*) is employed for N, C, O, Cl, P and H elements, while Au element is described using the effective core potential double‐ζ basis set (LanL2DZ) . This combination of basis sets (6‐31G* and LanL2DZ) has also been proven to be reliable in numerous theoretical simulations of mechanisms of metal‐catalyzed reactions . As a further test, other basis sets 6‐31G**, 6–31 + G* and 6‐311G* (triple‐zeta) are employed for comparison to avoid the shortcomings of basis sets (see Table S2 in Supporting Information).…”