Gold(I)-Catalyzed Cycloaddition of 1-(1-Alkynyl)cyclopropyl Ketones with Nucleophiles To Yield Substituted Furans: A DFT Study

Abstract

By means of density functional theory (DFT), the mechanism for the synthesis of highly substituted furan (2) from 1-(1-alkynyl)-cyclopropyl ketone (1) with nucleophile (MeOH) catalyzed by Au(I) was investigated. As demonstrated, both the intimate ion-pair [AuL]+ ·[OTf]− (L = PPh3, PMe3, and PH3, OTf = trifluoromethane sulfonate) and the cation [AuL]+ exhibit catalysis, and the former is dominant. Moreover, the bigger the ligand coordinated to gold is, the poorer the catalysis is. The theoretical study reveals that the nucleophiles such as MeOH are important for this reaction, that the reaction between the bicyclo[4.1.0]heptan and the carbinol is a stereospecific addition reaction, and how the proton migration goes through. In the proton migration process, both the anion OTf− and another nucleophile molecule such as MeOH act as a proton shuttle to transport a proton from the nucleophile to the 2-position carbon of alkynyl. The most favorable mechanism includes the activation of the substrate, nucleophile attraction, an addition reaction of the carbonyl triple bond, a stereospecific attack of the nucleophile on the activated cyclopropane, proton migration, and regeneration of the catalyst. The substrate 1 is activated by its combination with Au(I) and a molecule of nucleophile (MeOH), which leads to a decrease in the orbital energy of π*(C1C2) and σ*(C3−C5) and an increase in the dipole moment of the bent bond σ(C3−C5). On the whole, the solvent effects increase the reaction barriers.

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.…”

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

“…This method applied to search the transition state has been adopted successfully in the previous theoretical calculations. 35 In tsa1-3-2, the protonated DMF (as a proton donor) transfers a proton to C2 to produce a complex ia1-5-2 that will decompose into 6-endo product P1 and regenerate DMF and catalyst CuCl. In summary, in the two-step hydrogen-transfer strategy, solvent DMF plays a role as a proton shuttle to assist the transfer of H3 from MeOH to C2 of reactant R1.…”

Silver‐Free Two‐Component Approach in Gold Catalysis: Activation of [LAuCl] Complexes with Derivatives of Copper, Zinc, Indium, Bismuth, and Other Lewis Acids

“…Either way, TfOH could not catalyze the reaction, even when using 10 mol % (entries 13 and 14). The reason why metal chlorides are inactive here (compare entries 4/5 and 6/7) could be due to the ability of the triflate anion to serve as a proton shuttle during the catalytic process 33…”