Tin(IV) Hydride-Mediated Intramolecular Reductive Head-to-Tail Michael Reaction of Enones with Activated Alkene Tethers

Intramolecular reductive coupling of enones bearing an unsaturated ketone, ester or nitrile was carried out under radical conditions. Upon exposure of these enone derivatives to tri-n-butyltin hydride in presence of AIBN, tin enolates were generated via 1,4-hydrostannation and then added to the internal activated alkenes in a Michael fashion to produce 1,2-disubstituted cyclopentane products. The reaction of bisenones smoothly produced the desired products in good to excellent yields under optimized conditions using 1.3 equivalents of n-Bu3SnH in benzene solution. On the other hand, the coupling of enones to a,b-unsaturated esters or nitriles, which is a thermodynamically disfavorable process, was accomplished by addition of a catalytic amount of tetrabutylammonium bromide after 1,4-hydrostannation. Coordination of the bromide ion to the tin enolate enhanced its nucleophilicity and promoted the reaction. This work represents the first examples of intramolecular reductive head-to-tail coupling of enones bearing a,b-unsaturated esters or nitriles as a Michael acceptor.