Rearrangement Cornforth

The Cornforth rearrangement involves the thermal interconversion of 4-carbonyl substituted oxazoles, with exchange between the C-C-O side-chain and the C-C-O fragment of the oxazole ring. These reactions generally involve compounds where a heteroatom (-OR, -SR, -Cl) is attached to the 5-position (R2) of the starting oxazole. 

The thermally induced Cornforth rearrangement can be rationalized by postulating the dicarbonylnitrile ylid 103 as intermediate. It is especially the natures of the substituents R and R" that determine the direction of the rearrangement. For example, heating of 5-alkoxy-4-(aminocarbonyl)oxazole (102, R = OAlkyl, R" = NR2) readily gives in a good yield rearrangement into the isomeric 5-(substituted amino)-4-(alkoxycarbonyl) oxazole (104, R = OAlkyl, R" = NR2) (Scheme IV.40). 

UV characteristics of the natural product, while further hydrolysis (under acid conditions) yielded asteroidic acid (190)—the chromophoric fragment—together with e-hydroxylysine (191) and acetic acid (97). For the synthesis of asteroidic acid (190), /V-salicyloylglycine (192) was condensed with triethyl orthoacetate to afford 2-(o-hydroxy)phenyl-4-(l -ethoxy)ethylidene-5-oxazolone (193). This product on treatment with base underwent Cornforth rearrangement,... 

The formation of oxazoles by the Cornforth rearrangement, which is a useful synthetic procedure, is described in Section 4.18.3.1.2(i). Oxazoles are also satisfactorily prepared by reduction of their IV-oxides (see next section) with zinc and acetic acid. Treatment of oxazoles and benzoxazoles with alkylating agents gives quaternary salts. 

Keywords Oxazoles Tandem alkylation/cyclisation Cornforth rearrangement Anti-proliferative agent Antibacterial activity... 

The 2-aryloxazoles have also been synthesized under microwave activation by the direct Stille and Suzuki cross-coupling reactions of 1,3-oxazoline (OXT) [17]. Nolt et al. [18] utilized the microwave-assisted Cornforth rearrangements for the preparation of substituted 5-amino-oxazole-4-carboxylate (v). 

In the laboratory of D.R. Williams, a carbanion methodology for the alkylations and acylations of substituted oxazoles was investigated. The study showed that the monoalkylation of the dianion generated from 2-(5-oxazolyl)-1,3-dithiane exclusively led to the substitution of the carbon adjacent to sulfur. However, acylation reactions of the dianion afforded 4,5-disubstituted oxazoles. These new products presumably arose from carbonyinitrile ylide intermediates, which were generated by the selective C-acylation of a ring-opened dianion tautomer. This is the first example of a base-induced, low-temperature Cornforth rearrangement. 

Williams, D. R., McClymont, E. L. Carbanion methodology for alkylations and acylations in the synthesis of substituted oxazoles. The formation of Cornforth rearrangement products. Tetrahedron Lett. 1993, 34, 7705-7708. 

Dewar, M. J. S., Turchi, I. J. Ground states of molecules. Part 35. MINDO/3 study of the Cornforth rearrangement. J. Chem. Soc., Perkin Trans. 21977, 724-729. 

Although oxazole and its alkyl and aryl derivatives are thermally stable to high temperatures, the introduction of functionalized substituents can lead to reaction at lower temperature. The Cornforth rearrangement, discussed in <84CHEC-I(6)177>, is one example. An application of the Cornforth reaction is the conversion of 4-aminothiocarbonyl-5-ethoxyoxazoles (33) to 5-aminothiazoles (34)... 

It is also interesting to note that MINDO/3 calculations indicate that the Cornforth rearrangement (Eq. 15) proceeds via an intermediate (53) that has been variously described as a carbene and a zwitterionic species.55... 

COREY KIM Oxidizing reagent 79 COREY-WINTERAlkenesynthesis 80 CORNFORTH Rearrangement 81 Crafts 131... 

COREY Oxidizing reagents for alcohols 78 COREY Enantioselective borane reduction 77 COREY Homologatne epaxidation 78 COREY - KIM Oxidizing reagent 79 COREY-WINTERAlkenesynthesis 80 CORNFORTH Rearrangement 81 Crafts 131... 

TABLE 1.62. 2-ALKYL(ARYL)-5-AMlNO-4-CARBOETHOXYTHlAZOLES VIA CORNFORTH REARRANGEMENT OF 2-ALKYL(ARYL)-5-ETHOXY-4-OXAZOLETHIOCARBOXAMIDES ... 

Other references related to the Cornforth rearrangement are cited in the Uterature. ... 

---