A Mechanistic Dichotomy in Ruthenium-Catalyzed Propargyl Alcohol Reactivity:  A Novel Hydrative Diyne Cyclization

The cycloisomerization of diyne-ols catalyzed by [CpRu(CH3CN)3]PF6 to 2-vinyl-1-acylcycloalkenes proceeds via a ruthenacyclopentadiene involving initial ionization of the tertiary or secondary alcohol, followed by readdition. In the case of primary alcohols, a competing pathway wherein water first adds would appear to occur. The feasibility of this proposed minor pathway was tested in the reaction of diynes in the presence of water. Quite excitingly, cyclization comcommittant with addition of water to form 1-acylcycloalkenes occurs. This proves to be general process to form five- and six-membered rings. Interestingly, hydrative cyclization of Z-5-decen-2,8-diyne to 1-acetyl-2-ethyl-cyclohexa-1,4-diene occurs without isomerization of the double bonds. Furthermore, the epoxide of the same substrate cyclizes without opening of the strained epoxide. Unsymmetrically substituted diynes cyclize with remarkable chemoselectivity wherein water attacks the less hindered alkynes. β-branching of any kind gives only a single product. Remarkably, even competing methyl versus ethyl still effects a 2.5:1 selectivity in favoring water addition to the methyl-bearing alkyne. Alcohols can replace water and provide enol ethers. Strong mechanistic evidence suggests two reaction manifolds indeed operate, depending upon the presence of propargyl alcohols and the degree of substitution on the hydroxyl-bearing carbon.