Convergent synthesis of trans-fused 6/n/6/6 (n=7, 8) tetracyclic ether system via α-cyano ethers

A convergent method for synthesizing 6/n/6/6 (n=7, 8) tetracyclic ether system via two-rings construction of the central n/6 ring system was developed. The key steps of the present synthesis involve a ring-closing metathesis reaction for the construction of the seven- and eight-membered rings, and reductive etherification for the tetrahydropyrans. Unification of the two fragments through acetal formation, followed by regioselective cleavage of the acetal using TMSCN/TMSOTf in the presence of 2,6-di-tert-butyl-4-methylpyridine, afforded the α-cyano ether, of which the nitrile group was manipulated to give the precursors of the ring-closing reactions.