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 -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 SN2 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 -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.

A novel stereocontrolled synthesis of cis-fused bicyclic lactams via [3 + 2]-cycloaddition of alkynyltungsten complexes with tethered aziridines.

Treatment of alkynyltungsten complexes with tethered aziridines in the presence of BF(3).Et(2)O led to [3 + 2]-cycloaddition reactions, affording bicyclic tungsten-enamine species stereoselectively. The stereochemistry of the resulting product reveals that ring opening of aziridine is initiated by S(N)2 attack of the tungsten fragment. Decomplexation of these organometallics with I(2) in CH(2)Cl(2), followed by hydrolysis, afforded only cis-fused bicyclic lactams efficiently. [reaction: see text]