Synthesis of alkyl-substituted six-membered lactones through ring-closing metathesis of homoallyl acrylates. An easy route to pyran-2-ones, constituents of tobacco flavor

Article abstract of DOI:10.1021/jo070600h

(Chemical Equation Presented) The ring-closing metathesis (RCM) reactions of homoallylic acrylates bearing alkyl substituents on various positions of their skeleton afford the corresponding pentenolides in the presence of carbene ruthenium catalysts. For R³ = R⁴ = H, or R³ = Me, R⁴ = H, the reactions are catalyzed by complex [RuCl ₂(PCy₃)₂(=CHPh)], while a second-generation Grubbs catalyst is required when R³ = H and R⁴ = Me, R³ = R⁴ = Me, or R³ = i-Pr and R⁴ = H. Alkyl substitution at the homoallylic carbon (R¹, R²) increases the yield of the reaction when both the acrylic and/or homoallylic double bonds are methyl-substituted. The interaction of the catalyst with the substrate in the initiation stage involves the homoallylic double bond rather than the acrylic moiety, and the resulting alkylidene species from the first-generation Grubbs catalyst can be observed by ¹H and ³¹P NMR. The racemic tobacco constituents 4-isopropyl-5,6- dihydropyran-2-one and 4-isopropyltetrahydropyran-2-one are prepared via a short reaction sequence, involving the RCM reaction as the key transformation.