Oxazoles 5-acyloxy

Die einzige bisher bekannte Reaktion dieses Typs ist die Acylierung der A2-Oxazolinone 169-171> und 2-Trifluormethyl-A3-oxazolinone 172> mit aliphatischen Carbonsaurehalogeniden oder Chlorameisensaureestern und Triathylamin, bei der in hohen Ausbeuten 5-Acyloxy-oxazole (84) ent-stehen. Mit aromatischen Saurehalogeniden werden Gemische von 84 und... 

Besonders gut untersucht wurden in letzter Zeit 4-alkylsubstituierte 4-Acyl-A2-oxazolinone-(5) (85), die durch Acylierung der A2-Oxazolinone mit aliphatischen Carbonsaurehalogeniden/Pyridin (171) oder durch Um-lagerung der 5-Acyloxy-oxazole 84 mit Pyridin i69,i7i) allgemein zugang-lich sind. Dabei konnen 4-[N-Acyl-1.4-dihydro-pyridyl]-A2-oxazoli-none-(5) (98) als Zwischenstufen nachgewiesen und in einigen Fallen isoliert werden 17 3>. 

Davidson s synthesis consists of the cydization of a-acyloxyketones with ammonia or ammonium acetate to give 2,4,5-trisubstituted oxazoles. The Passerini reaction between arylglyoxals, carboxylic acids, and isocyanides afforded N-substituted 2-acyloxy-3-aryl-3-oxopropionamides 83 in high yields. Upon heating with an excess of ammonium acetate in acetic acid, compounds 83 were cydized to N,2,4-trisubstituted oxazole-5-carboxamides 84 in fair yields [59]. A large number of a-acyloxy-jS-ketoamides can be prepared by changing the reaction components, so the method provides straightforward access to a variety of oxazole-5-carboxamides (Scheme 2.30). 

An oxidative route to 1,3-thiazoles (39) and oxazoles, which bear the requisite functionality, such as amino groups and stereocenters, for incorporation into a variety of natural products was reported. Treatment of 1,3-thiazolines (36) with CuBr (l.leq), Cu(OAc)2 (l.leq) and t-butyl perbenzoate (1.5eq) under benzene reflux gave 1,3-thiazoles (39) in about 80% yield. A plausible mechanism included generation of a Cu (III) species (37) via oxidative addition, reductive elimination to the acyloxy thiazoline (38), and syn elimination on warming to produce the thiazole (39). [94TL6803]... 

C—C—O—C+N. The formation of oxazoles from a-acyloxy ketones and ammonium salts was discovered in 1937 when it was found that treatment of benzoin benzoate with ammonium acetate in hot acetic acid gave triphenyloxazole in excellent yield. It has been shown that the reaction proceeds by way of intermediate enamines (equation 113). The synthesis is quite general and it is only.limited by the difficulty of obtaining the starting keto esters, particularly formates. The latter are probably intermediates in the preparation of cycloalkenooxazoles from acyloins and formamide in hot sulfuric acid (equation 114). Another variation is to heat a mixture of an a-bromo ketone, the sodium salt of a carboxylic acid and ammonium acetate in acetic acid (equation 115). 

It is usual for the reaction of or-acyloxy ketones with ammonium acetate to give mixtures of oxazoles and imidazoles, with the result that the method may not be the one of choice if the product mixture complexity can become too great (Scheme 77) (70AHC(12)103). Excess ammonia may help depress oxazole formation, although the oxazoles can be converted into imidazoles (Section 4.08.2.2). 

A new synthesis of 2,5-di- and 2,4,5-trisbustituted oxazoles begins with -(acyloxy)vinyl azides... 

Application of the Davidson oxazole synthesis to products of the Passerini reaction has expanded the usefulness of this well-known route <91LAll07>. The a-acyloxy ketones or a-acyloxy -keto esters employed in the Davidson synthesis are not readily available. However, the use of arylglyoxals as the carbonyl component of the Passerini reaction, along with cyclohexyl isocyanide and carboxylic acids, gives a wide variety of iV-cyclohexyl-2-acyloxy-3-aryl-3-oxopropionamides (151). Reaction of these intermediates with ammonium formate in acetic acid affords A -cyclohexyl-2,4-diaryl-5-oxazolecarboxamides (152) in fair yields (Scheme 69). 

Eguchi and co-workers ° developed a general synthesis of 2,5-disubstituted and 2,4,5-trisubstituted oxazoles from an intramolecular Aza-Wittig reaction of (Z)-p-(acyloxy)vinyl azides (Scheme 1.74). An a-bromoketone 277 was converted to an a-azidoketone 278, which was O-acylated at 78°C to give, exclusively, a (Z)-p-(acyloxy)vinyl azide 279. This was attributed to intramolecular chelation of lithium by the enol oxygen and the a-nitrogen atom of the azide. 

TABLE 1.22. 2,5-DISUBSnTUTED- AND 2,4,5-TRISUBSTITUTED-OXAZOLES FROM INTRAMOLECULAR AZA-WITTIG REACTION OF (Z)-P-(ACYLOXY)VINYL AZIDES"... 

Previously, these authors reported a general synthesis of 2,4,5-trisubstituted oxazoles 561 from 558 (Scheme 1.153). Addition of an alkyUithium reagent to 558 generated a lithium p-bis(trimethylsilyl)amino enolate 559 that was acylated in situ to produce a p-(acyloxy)-A,A-bis-(trimethylsilyl) enamine 560. Cyclization of 560 to 561 was accomplished using FVP or TMSOTf. 

According to route II, FGA d (addition of H2O at C-4) gives rise to hydroxyoxazoHne 26, which by disconnection e leads to the iminoester 28 and FGI f to the (a-acyloxy)carbonyl compound 29 and two sets of components, namely 31/33 (via disconnection h) and 34/carboxylate (via disconnection i). Alternatively, 28 can be disconnected according to g leading to components (a-halogeno)carbonyl compound 32/carboxamide. Thus, retrosynthesis proposes systems 27-29 to be suitable educts for approaches to oxazole synthesis [262]. 

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