Acyclic stereocontrol via the claisen rearrangement: a formal synthesis of (+) tirandamycic acid

✍ Scribed by Frederick E. Ziegler; Ronald T. Wester

• Publisher: Elsevier Science
• Year: 1984
• Tongue: French
• Weight: 205 KB
• Volume: 25
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)99953-2

✦ Synopsis

The unique bicyclic ring systen of tirandamycin (8&),' an acyltetramic acid antibiotic, has inspired several synthetic efforts directed towards its total synthesis. Tirandamycic acid (a), a degradation product of tirandamycin, has been synthesized by Ireland in optically active form frolrl D-glucose.2 We have reported3 the applicability of furan chemistry to the construction of models for the bicyclic portion of tirandamycic acid. Subsequently, DeShong reported4 similar studies and, more recently, has employed the furan approach, in conjunction with tested aldol methodology, in a synthesis of the racemate of Ireland's alcohol 7b.5 This Letter details a -Claisen rearrangement-based methodology for acyclic diastereoselection which employs the furan approach in the synthesis of Ireland's chiral intermediate 70. -Lactone 3, both diastereomerically and enantiomerically pure, is produced through the Claisen rearrangement of S-3-methylbutyrolactone (as its diethoxy ortholactone) and R-(E)-2-octen-4-01.6 Exposure of lactone la to Tebbe's reagent7 (Cp2TiCH2C1AlMe2, -1.1 equiv; toluene/Tt!F/pyridine; 45 min -55"C, + 25"C, 3h) provided the crude enol ether lb (6 3.84 and 4.32 (2xlH, br. s, -=CH2)), which was immediately transformed into the hydroperoxides & (30% H202, THF/HOAc, -l@"C, 72 h) in 82% overall yield.8 Criegee rearrangelnent of the hydroperoxides' (Ac20/Et3N/DMAP; CH2Cl2; 0' + 25'; 30 min) via acylperoxides 2b afforded a mixture of hydroxy acetates which was -