Stereocontrolled synthesis of bicyclic lactone derivatives via tungsten-mediated [3+2] cycloaddition of epoxides with a tethered alkynyl group

In the presence of BF3.Et2O, alkynyltungsten complexes underwent [3 + 2] cycloaddition with tethered epoxides to give bicyclic gamma-lactones efficiently. Only one diastereomeric product was formed despite the presence of three stereogenic centers. A mechanism is proposed that involves formation of a tungsten-vinylidenium species via an S(N)2 attack of the epoxide carbon by an alkynyltungsten group to give a tungsten-enol ether species via counterattack at the central tungsten-vinylidenium carbon by the OBF3_ terminus. Most of the tungsten enol ether species were too unstable for isolation and underwent hydrolysis to give only cis-fused gamma-bicyclic lactones. This cyclization works for both cis- and trans-epoxides and tolerates various functional groups. In the case of trans-phenyl epoxide, the reaction led to an addition product via a 6-endo attack of epoxide by the tungsten fragment. This method provides a simple enantiospecific synthesis of complex bicyclic lactones if a chiral epoxide is used in the cyclization. It is also applicable to the one-pot synthesis of bicyclic unsaturated gamma-lactones if a suitable alkynyltungsten functionality is used.