Theoretical Insight into the Au(I)-Catalyzed Intermolecular Condensation of Homopropargyl Alcohols with Terminal Alkynes: Reactant Stoichiometric Ratio-Controlled Chemodivergence

The mechanisms and chemoselectivities on the Au(I)-catalyzed intermolecular condensation between homopropargyl alcohols and terminal alkynes were investigated by performing DFT calculations. The reaction was indicated to involve three stages: transformation of the homopropargyl alcohol (R) via intramolecular cyclization to the cyclic vinyl ether (R'), formation of the C-2-arylalkynyl cyclic ether (P) via hydroalkynylation of R' with phenylacetylene (R), and conversion from P to 2,3-dihydro-oxepine (P). The results revealed the origin of the reaction divergence and rationalized the experimental observations that a 1:3 reactant stoichiometric ratio affords P as the major product, whereas the 1:1.1 ratio results in P in high yield. The reactant stoichiometric ratio-controlled divergent reactivity is attributed to different catalytic activities of the gold catalyst toward different reaction stages. In the 1:3 situation, the excess R induces the Au catalyst toward its dimerization and/or hydration, inhibiting the conversion of P to P and resulting in product P. Without excess R, the Au catalysis follows a general cascade reaction, leading to product P. Theoretical results described a general strategy controlling the reaction divergence by a different reactant stoichiometric ratio. This strategy may be enlightening for chemists who are exploring various synthesis methods with high chemo-, regio-, and enantioselectivities.