Phosphorus ylide based functionalizations of tetronic and tetramic acids

• Published in: Synthesis (Stuttgart) no. 22; pp. 3902 - 3914
• Main Authors: Schobert, Rainer, Dietrich, Matthias, Mullen, Gillian, Urbina-Gonzalez, Juan-Manuel
• Format: Journal Article
• Language: English
• Published: STUTTGART Thieme Medical Publishers 17.11.2006
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; phosphorus ylides; tetramic acids; ALPHA; CLAISEN REARRANGEMENTS; lactones; METHODOLOGY; domino reactions; PRODUCTS; BIOSYNTHESIS; 3-ACYLTETRAMIC ACIDS; reutericyclin; INHIBITORS; DERIVATIVES; C-ACYLATION
• ISSN: 0039-7881; 1437-210X
• DOI: 10.1055/s-2006-950310

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 a-hydroxy or a-amino esters, 3 affords tetronates or tetramates. A two-step synthesis of (-)-epi-blastmycinolactol shows that allyl a-hydroxy esters can be domino Wittig-Claisen reacted to give 3-al-lyltetronic 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. alpha-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.