Lithium 3-Lithio-3-tosylalkanoates: .beta.-Acylvinyl Anion Equivalents of .beta.-Lithiated .alpha.,.beta.-Unsaturated Carboxylic Acids

Abstract

The dilithiation of β-tosylated propanoic, 2-methylpropanoic, and butanoic acid 10 with n-butyllithium at -78 o C leads to the corresponding lithium 3-lithio-3-tosylalkanoates 11. They react with different electrophilic reagents (deuterium oxide, iodine, trimethylchlorosilane, alkyl halides, and acyl chlorides) to give the corresponding 3-substituted tosylated alkanoic acids 12. When carbonyl compounds are allowed to react with intermediates 11 followed by in situ lactonization with trifluoroacetic anhydride and base-promoted elimination α,β-butenolides are obtained. This methodology is applied to the direct synthesis of the rosefuran lactone precursor 14cg, the O-benzyl derivative of (±)-umbelactone (14ch), and (±)-andirolactone (14ci). The alkylation and acylation reactions of organolithium compounds 11 followed by esterification with hydrogen chloride in methanol and treatment with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) afford α,β- and/or β,γ-unsaturated esters 17 and/or 18 and unsaturated 4-keto esters 19, respectively. The last methodology has been applied to the synthesis of the unsaturated 4-keto ester 19ae precursor of the seco acid of (±)-pyrenophorin (22)