SYNTHESIS OF HIGHLY FUNCTIONALIZED GAMMA-BUTYROLACTONES FROM ACTIVATED CARBONYL-COMPOUNDS AND DIMETHYL ACETYLENEDICARBOXYLATE

A triphenylphosphine-catalyzed cyclization of alpha-keto esters, alpha -keto nitriles, or alpha,alpha,alpha-trifluoroacetophenone with dimeth yl acetylenedicarboxylate is reported to produce highly functionalized alpha,beta-unsaturated gamma-butyrolactones in moderate yields. Thus treating a mixture of methyl 4-nitrophenylglyoxylate and dimethyl acet ylenedicarboxylate with 20 mol % of triphenylphosphine afforded 5,5'-d isubstituted 3-methoxy-4-(methoxycarbonyl)-2(3H)-furanone in 94% yield . In the reaction of alpha-keto esters R(1)COCOOMe, an electron-withdr awing R(1) substituent is required for satisfactory reactivity. On the other hand, electron-donating R(1) substituents give higher yields wi th alpha-keto nitriles R(1)COCN. Another electron-deficient carbonyl c ompound, alpha,alpha,alpha-trifluoroacetophenone, gave the correspondi ng lactone in good yield. The use of an alpha-hydroxy ketone as an ele ctrophilic carbonyl compound with more than 1 equiv of triphenylphosph ine produced dihydrofuran derivatives. One equivalent of triphenylphos phine oxide was obtained as a major product. An intramolecular Wittig reaction is proposed as a reaction mechanism.