4- oxazolone Stille reaction

Displacement of the chlorine atom in 395 by sodium thiomethoxide or other mercaptans was reported recently. The same authors also described an efficient synthesis of 4-arylidene-2-phenyl-5(477)-oxazolones 399 from 395 and organo-stannanes via palladium catalyzed Stille reaction (Scheme 7.128). Selected examples are shown in Table 7.36 (Fig. 7.47). 

TABLE 7.36. SYNTHESIS OE 4-ARYLIDENE-2-PHENYL-5(477)-OXAZOLONES EROM STILLE REACTION OF 4-(CHEOROMETHYEENE)-2-PHENYL-5(4/7)-OXAZOLONE ... 

A facile assembly of 2,4-orthogonally-functionalised oxazoles as useful bidirectional linchpins was achieved by treatment with diazomethane of acyl isocyanates, generated in situ from acyl halides 132 oxazolones 133 were converted to the oxazole triflates 134, useful intermediates for further synthetic elaborations as highlighted by the synthesis of 135 via Wittig and Stille reactions <01SL1739>. This linchpin tactic was used in the stereocontrol led total synthesis of the potent cytostatic agent (+)-phorboxazole A <01JA10942>. 

The 5-methyl-2(37f)-oxazolone sulfonamide derivatives 265 are obtained from the sulfonamides 263 via bromination and subsequent Stille coupling reaction with tetramethyltin in the presence of palladium catalyst (Fig. 5.64). °... 

The first procedure to prepare unsaturated 5(4//)-oxazolones was the Erlenmeyer synthesis" " that was described more than one hundred years ago and is still used extensively with some variations in the experimental conditions. In general, the reaction employs an acylamino acid, for example, A-acetyl- or A-benzoylglycine are the most common, and a carbonyl compound, usually an aldehyde, in the presence of a cyclodehydrating agent such as acetic anhydride (Scheme 7.114). Hundreds of unsaturated oxazolones 363 have been obtained via this procedure and these compounds are valuable intermediates for the synthesis of many interesting organic compounds. 

The synthesis of the side chain was illustrated in Scheme 76. 4-Penten-l-ol 346 was converted into hydroxy ketone 347, which was treated with phosgene, followed by exposiu e to aqueous ammonia to give oxazolone, after acidification. Triflyloxazole 348, which was prepared from the oxazolone by Tf20 and lutidine, was subjected to Sonogashira coupling to provide 349, which was converted into the side chain imit 350 via lindlar hydrogenation, desilylation, oxidation, and the Still s modified Horner-Emmons reaction. 

---