Oxazole rings construction

The oxazole ring can be constructed on a quinoline ring such as 589 by alkylation to give 590 which upon treatment with halogen in CHCI3 gave the corresponding oxazoloquinolinium derivative 591 that upon treatment with... 

One of the most reliable methods for constructing the oxazole ring is the cyclodehydration of a-acylamino ketones, the Robinson-Gabriel synthesis (1909/1910) (equation 93). The reaction is usually conducted in the presence of sulfuric add or phosphorus pentachloride and more recently polyphosphoric add, phosgene or anhydrous hydrogen fluoride have... 

N—C—O + C—C. The construction of the oxazole ring by the condensation of a-halogeno ketones with primary amides (equation 122) is the Bliimlein-Lewy synthesis (1884/1888). The method succeeds best when the resulting oxazole contains one or more aryl substituents. The use of formamide leads to oxazoles with a free 2-position and in this case it is possible that the reaction proceeds as in equation (113). 2-Aminooxazoles are produced by the action of a-halogeno ketones on urea and its derivatives (equation 123) or on cyanamide (80ZOR2185). The mercury(II) sulfate-catalyzed condensation of alkynic alcohols or their esters with primary amides leads to trisubstituted oxazoles (equation 124). 

A new synthesis of (-)-ulapualide A was completed by the group of Pattenden following a previous synthesis of a different diastereisomer whose chiroptical and H NMR spectroscopic data were identical with those of the natural product <07 AG(E)4359>. The first synthesis of siphonazole 119 was completed. Both the oxazole rings were constructed using rhodium carbene chemistry <07CC1508>. 

Heathcock and Parsons pursued a synthetic strategy to 1187 wherein the terminal oxazole ring was constructed in the presence of the tris-thiazoline array. 

Ehrler and Farooq" prepared 1187 via a stepwise construction of the three thiazoline rings, introduction of the styryl group, and preparation of the oxazole ring (Scheme 1.333). Condensation of L-cysteine ethyl ester hydrochloride 1284 (R = C2H5) with an imino ether derived from cinnamamide was unsuccessful, owing to complications from Michael addition. This necessitated a strategy in which the styryl double bond was introduced after assembly of thiazoline rings. 

Pattenden and co-workers " proposed a convergent alternative strategy to the ulapualide core, wherein suitably functionalized monooxazoles would be coupled first. Construction of the final, central oxazole ring would then complete the macrocyclization process. 

Several different strategies [94, 96, 97, 98, 99, 100] for the elaboration of a suitable substituted 1,3-oxazole ring as precursors for the fragments (38) or (41) have been described in the literature since the pioneering work of A.I. Meyers and co-workers [101]. Construction of fragments (38) was achieved by the same authors [94,95,102]. They proposed a unique pathway differing only in the last step as indicated by the following retrosynthetic analysis (Scheme 9). 

As shown in Scheme 2, two heteroatom-carbon bonds are constructed in such a way that one component provides both heteroatoms for the resultant heterocycle. By variation of X and Z entry is readily obtained into thiazoles, oxazoles, imidazoles, etc. and by the use of the appropriate oxidation level in the carbonyl-containing component, further oxidized derivatives of these ring systems result. These processes are analogous to those utilized in the formation of five-membered heterocycles containing one heteroatom, involving cyclocondensation utilizing enols, enamines, etc. 

First the styrene function is generated (52 53). Now only the construction of the oxazole remains to be accomplished. In contrast to the ideas of Fukuyama, Ehrler decides to prepare the oxazole in the presence of the other thiazoline rings. The conversion of the ester 53 into the amide 54 succeeds with 76 % yield well enough. But the yields drop in the following cyclocondensation with the bromoketoester 55. After conversion of the ester to the methylamide (56 4), thiangazole is isolated in only 20 %... 

Considerable parallelism emerges from an examination of the major methods for the construction of oxazole, thiazole and imidazole ring systems. 

The construction of an amide using aminomalononitrile and a carboxylic acid under typical peptide coupling conditions is accompanied by ring closure and thus the production of 5-amino-oxazoles. " °... 

Meyers and co-workers" completed the first synthesis of (—)-griseoviridin 1184. In this case, the authors envisioned an unprecedented olefin metathesis reaction of 1269 would construct the macrocycle (Scheme 1.325). Amide bond disconnection of 1269 then led to the key intermediate fragments, an oxazole diene moiety 1270, and the sulfur-containing nine-membered ring lactone 1271. 

Selnick and Brookes prepared a series of thiopyrans as carbonic anhydrase 11 inhibitors via intramolecular oxazole-alkyne cycloadditions. The starting 4-methyl-2-thiooxazole-alkyne 215 was readily constructed from 2-mercapto-4-methyloxazole (Fig. 3.62). Refluxing 215 in toluene afforded an 88% yield of the furanothiopyran 216. Varying the length of the oxazole-acetylene linker provided furans fused to 5- and 7-membered rings as well. 

Oxalactims, for exanple 5//-methyl-2-phenyl-oxazol-4-one, were investigated as synthetically powerful synthons for the construction of a-hydroxy acids via o -deprotonation followed by molybdenum-catalyzed asymmetric allylation and a subsequent hydrolysis of the oxalactim rings. Among the series of the HMDS bases used in tbe Mo-catalyzed asymmetric allylation, LHMDS was found to be tbe base of choice providing better yields, regio- (branched/Unear), diastereo- andenantioselectivity than the corresponding allylation reactions mediated by KHMDS (eq 63). ... 

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