Intramolecular conjugate addition of α,β-unsaturated lactones having an alkanenitrile side chain: Stereocontrolled construction of carbocycles with quaternary carbon atoms

Abstract

An efficient method for constructing carbocycles with all-carbon quaternary stereocenters has been developed on the basis of a stereoselective cyclization reaction of ,-unsaturated lactones having an alkanenitrile side chain. Treatment of the substrate with lithium hexamethyldisilazide (LiHMDS) in the presence of triisopropylsilyl chloride (TIPSCl) led to the generation of the corresponding -cyano carbanion species which readily underwent an intramolecular conjugate addition reaction. It was found that thecombined use of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and triethylamine is also effective for the cyclization reaction without using a strong base. Interestingly, different ste-reochemical outcomes were observed in the two cyclization methods. © Georg Thieme Verlag Stuttgart - New York.