Synthesis of Highly Functionalized γ-Butyrolactones from Activated Carbonyl Compounds and Dimethyl Acetylenedicarboxylate

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Abstract
A triphenylphosphine-catalyzed cyclization of α-keto esters, α-keto nitriles, or α,α,α-trifluoroacetophenone with dimethyl acetylenedicarboxylate is reported to produce highly functionalized α,β-unsaturated γ-butyrolactones in moderate yields. Thus treating a mixture of methyl 4-nitrophenylglyoxylate and dimethyl acetylenedicarboxylate with 20 mol % of triphenylphosphine afforded 5,5‘-disubstituted 3-methoxy-4-(methoxycarbonyl)-2(3H)-furanone in 94% yield. In the reaction of α-keto esters R1COCOOMe, an electron-withdrawing R1 substituent is required for satisfactory reactivity. On the other hand, electron-donating R1 substituents give higher yields with α-keto nitriles R1COCN. Another electron-deficient carbonyl compound, α,α,α-trifluoroacetophenone, gave the corresponding lactone in good yield. The use of an α-hydroxy ketone as an electrophilic carbonyl compound with more than 1 equiv of triphenylphosphine produced dihydrofuran derivatives. One equivalent of triphenylphosphine oxide was obtained as a major product. An intramolecular Wittig reaction is proposed as a reaction mechanism.