Synthesis of Cyclic Alkenyl Ethers via Intramolecular Cyclization of O-Alkynylbenzaldehydes. Importance of Combination between CuI Catalyst and DMF

An efficient and remarkably general method for the synthesis of cyclic alkenyl ethers via the Cu(I)-catalyzed intramolecular cyclization of O-alkynylbenzaldehydes has been developed. The survey of metal catalysts and solvents revealed that the combination of copper(I) iodide and DMF was the catalytic system of choice. The reaction most probably proceeds via the nucleophilic addition of alcohols 2 to O-alkynylbenzaldehydes 1 to generate the corresponding hemiacetals, and subsequent nucleophilic attack of the hemiacetal oxygen to the copper coordinated alkyne would give the annulation products 3. In all cases, the reaction proceeded in a regiospecific manner leading to the six-membered endocyclic products via 6-endo-dig cyclization.