Rearrangement of protected epoxy-alcohols into tetrahydrofuran derivatives: The protecting group matters!

We have explored an interesting rearrangement of protected epoxy-alcohols into tetrahydrofuran derivatives. Our protocol is operationally simple and involves treatment of a substrate with catalytic quantities of boron trifluoride diethyl etherate in methylene chloride without any special precautions to exclude air or ambient moisture. The nature of the protecting group dictates the stereochemical outcome of the cyclization. For example, with <i>trans</i>-di-substituted epoxides bearing pendant esters or carbamates, the rearrangement gives tetrahydrofurans with contiguous stereocenters in a <i>syn</i> configuration. With these substrates, we hypothesize that the transformation initiates upon attack of the epoxide by the carbonyl oxygen of the ester or carbamate. Conversely, with <i>trans</i>-di-substituted epoxides bearing free alcohols or ethers, cyclization gives tetrahydrofurans with contiguous stereocenters in an <i>anti</i> configuration. Here, we believe that a simple S_N2 attack on the epoxide is taking place. We also examined the cyclization with aziridine alcohols and their derivatives and with oxetane esters and found that some of these substrates were compatible with the reaction conditions.