Synthesis of Diacetal Trioxa-Cage Compounds via a Sequential Cyclization Reaction of Norbornene Derivatives Induced by Electrophiles

Abstract

The synthesis of diacetal trioxa-cage compounds via a sequential cyclization reaction of norbornene derivatives induced by electrophiles in a short sequence is reported. Treatment of the norbornene derivatives 2a−d and 10b with I2 in aqueous THF in the presence of KI at 25 °C regioselectively gave the iodo-cage compounds 3a−d and 11 in 80−90% yields, respectively, via a iodine-induced sequential cyclization reaction. No detectable amount of other regioisomers or monocyclization products was obtained. The synthesis of trioxa-cages 14a−e was accomplished from 3a−d and 11 in a two-step sequence. Treatment of diacylnorbornenes 15a−f with I2 in aqueous THF at 25 °C regioselectively and stereoselectively gave the sequential cyclization products 16a−f, respectively, which were converted in one step to the diacetal trioxa-cages 24a−f in high yields. The structure of these trioxa-cages was proven by X-ray analysis of the crystalline compound 14e. Other electrophiles, such as bromine, m-CPBA, and Hg(OAc)2, were also found to be effective for the sequential cyclization reaction. Oxymercuration of 15a−f and 2a−c with Hg(OAc)2 in aqueous THF followed by reduction with NaBH4 at 25 °C gave compounds 28a−f and 30b,d,c in high yields, respectively.