Synthesis of 2-alkylidene oxetanes and substituted tetrahydrofurans

Date of Completion

January 2007


Chemistry, Organic




Strained heterocycles are useful scaffolds in oerganic synthesis. One class of such heterocycles is 2-alkylidene oxetanes, which contain an oxetane ring, an α-enol ether and an alkyl substituent on the exocyclic double bond. This combination of functionalities makes 2-alkylidene oxetanes potential scaffolds for a variety of organic targets. Some strategies have been reported in the literature for the preparation of 2-alkylidene oxetanes. However, only a limited range of 2-alkylidene oxetanes can be accessed by these approaches with generally low yields and poor stereo- and regioselectivities. In order to study the 2-alkylidene oxetanes, it is important to develop a general strategy to a wide range of 2-alkylidene oxetanes. Several strategies, including alkene isomerization, benzelidenation and mesylate elimination were explored for preparing 2-alkylidene oxetanes, E- and Z-2-alkylidene oxetanes have now been successfully prepared in a stereoselective fashion by β-elimination of mesylates using t-BuOK. A new reaction was discovered in the course of preparing intermediates for accessing 2-alkylidene oxetanes by β-elimination. The transformation involved one pot ring expansion and silyl migration of α-silyloxy epoxides by treatment with trimethylsulfonium methylide to give substituted 3-silyloxy tetrahydrofurans. This ring expansion-silyl migration protocol has been successfully applied to some substituted epoxides to give 1,3- and 2,3-disubstituted tetrahydrofurans. ^