Synthesis of [n,5]-Spiroketals by Ring Enlargement of Donor-Acceptor-Substituted Cyclopropane Derivatives

摘要

Exocyclic enol ethers served as starting materials for the synthesis of [n,5]-spiroketals (n = 5, 6).A metal-mediated cyclopropanation using ethyl diazoacetate afforded spiroannelated cyclopropane deriva-tives bearing an ester group. A reduction of the corresponding ester by followed by subsequentoxidation using hypervalent iodine reagents, produced [n,5]-spiroketals in moderate to good yields. The keystep within this three-step sequence is the ring enlargement of the three-membered ring with an oxygen donorand a carbonyl acceptor group into the five-membered enol ether system. Catalytic amounts of the Lewis acidYb(OTf)3 facilitate the ring enlargement and increase the yield of the corresponding spiroketal in many cases.When Yb(OTf)3 was used, our experiments revealed an open transition state rather than a concertedmechanism because the stereochemistry of the spirocenter was not conserved during the ring enlargement. Asa result, the thermodynamically more favored anomeric [n,5]-spiroketal was observed as the major product.All the structures were established unambiguously by NOESY experiments.