Theoretical Elucidation of Au(I)-Catalyzed Cycloisomerizations of Cycloalkyl-substituted 1,5-Enynes: 1,2-alkyl Shift versus C−H Bond Insertion Products

Abstract

The Au(I)-catalyzed cycloisomerization reactions of cycloalkyl-substituted 1,5-enynes (A) have been investigated by performing density functional theory (DFT) calculations. Theoretical calculations suggest that the reaction proceeds via a stepwise mechanism by the initial formation of a Au(I)-carbene intermediate (B), followed by a 1,2-alkyl shift or C-H insertion reaction to form the ring-expanded three-cyclic product (C) or ring-closed four-cyclic product (D) depending on the size of cycloalkyl substitutions. It is found that the formation of intermediate B is the rate-determining step, and the formation of products C or D is controlled by the size (n) of cycloalkyl substitutions in 1,5-enynes. In the situations with n = 1 and 2, the calculated relative free energies and the barriers consistently indicate that the 1,5-enynes prefer to evolve into product C to product D. In contrast, for the situation of n = 4, the barrier forming product C is found to be higher than that forming product D, supporting the experimental observation that a range of the 1,5-enynes with n = 4 isomerize into product D, although it is thermodynamically less favorable than product C. The present theoretical results provide insight into the mechanism details of the catalytic rearrangement of 1,5-enynes and rationalize the early experimental observations well.

Mechanistic insight into water-modulated cycloisomerization of enynyl esters using an Au(i) catalyst

“…In She's experiment, 27 (PPh 3 )AuSbF 6 was used as an efficient catalyst. Previous studies [31][32][33][34][35][36][37] and our primary studies 38 indicated that the phenyls in triphenylphosphine have little influence on the reaction mechanisms as well as the geometric structures of the stationary points located on the potential energy surfaces. Therefore, in the present calculations the real catalyst (PPh 3 )AuSbF 6 is simplified as (PMe 3 )AuSbF 6 to save computational costs.…”

Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular Complexity

“…Thus, cycloalkyl-substituted enyne 203 undergoes a ring expansion by 1,2-alkyl shift to give tricyclic compound 205 , whereas 204 bearing a larger cycloalkyl substituent goes through C–H bond insertion to afford tetracyclic compound 206 (Scheme 65 ). 217 …”

Gold-catalyzed C(sp3)–H bond functionalization

“…Subsequently, to further determine the pathway of gold-catalyzed cycloisomerization of 1,5-enynes, Zhang et al carried out the DFT calculations. 39 It was found that the formation of intermediate 92 was the rate-determining step of the reaction pathway. In addition, theoretical calculations also demonstrated that the size of the cycloalkyl substitutions was crucial for the success of cycloisomerization/C sp 3-H insertion tandem sequence.…”