Phosphorus Ylide Based Functionalizations of Tetronic and Tetramic Acids

Abstract

The versatility of the ylide (triphenylphosphoranyl­idene)ketene (Ph₃P=C=C=O, 3) in the construction of tetronic and tetramic acids from various carboxylic acid derivatives is demonstrated by new reactions and extensions of known ones. With α-hydroxy or α-amino esters, 3 affords tetronates or tetramates. A two-step synthesis of (-)-epi-blastmycinolactol shows that allyl α-hydroxy esters can be domino Wittig-Claisen reacted to give 3-allyltetronic acids. More extended Wittig-Claisen-Conia cascades can produce 3-alkylidenefuran-2,4-diones, the photooxygenation of which furnishes lactone endoperoxides with antiplasmodial potential. Tetronic acids can be acylated by 3 at C3 to give the corresponding acyl ylides. Their saponification yields the respective 3-acetyl compounds, e.g. the fungal metabolite pesthetoxin. α-Hydroxy acids react with 3 to afford the corresponding 3-phosphoranylidenefuran-2,4-diones. The antibiotic (R)-reutericyclin was built up from benzyl d-leucinate and 3 in four steps by downstream acylation first at C3, then at N1 without racemization.

domino reactions - phosphorus ylides - tetramic acids - lactones - reutericyclin

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Crystallographic data (excluding structure factors) for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Centre (CCDC number 616240). Copies of the data can be obtained free of charge on application to The Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: [phone], e-mail: [e-mail]].

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