A Acylaminoketones

The Gabriel s synthesis is also applicable when a polysubstituted thiazole is required (381, 550). Thus 2,4,5-trisubstituted thiazoles are obtained by treating the corresponding a-acylaminoketones with phosphorus pentasulfide for a few minutes at 100°C (550) or at higher temperature for heavier substituents (381). (Table 11-31). 

These a-acylaminoketones also provided a convenient synthesis of thiazoles on treatment with phosphorus pentasulfide (Gabriel s method). Although yields range from 45 to 80%, substituents are usually restricted to alkyl, aryl and alkoxy derivatives. Thus, reaction of the a-acylaminoketone (4) with P4S1Q gave the thiazole (5), and thiazole (7) itself was prepared in this manner in 62% yield from formylaminoacetal (6) (14CB3163). The corresponding 5-ethoxy compound was obtained from the a-formamidoester and phosphorus pentasulfide in an inert solvent. 

An alternative method involves reaction of an a-acylaminoketone (12) with a primary amine and subsequent ring closure of the resultant Schiff s base (13) with phosphoryl chloride. This enables the introduction of a 1-substituent as in (14) to be carried out efficiently, and if the amine were replaced with a monosubstituted hydrazine, the imidazole derivative (IS) resulted (78LA1916). 

In the ring-closure reaction of a-acylaminoketones with hydrazines, some dihydro-1,2,4-triazines were obtained. The possible 1,2-, 2,3-, or 5,6-dihydro structures were excluded by IR spectroscopic studies however, this method, as well as the attempted preparation of fixed derivatives, failed to distinguish between... 

Fiir die Umwandlung von a-Aminosauren in a-Acylaminoketone und C02 bei. der Einwirkung von Essigsaureanhydrid in Gegenwart einer... 

A-Acyl AAs, when transformed into a-acylaminoketones by the Dakin-West reaction, react with arylhydrazines, arylsulfonylhydrazines, or some primary amines to give the corresponding ketimines which undergo cyclodehydration with POCI3/PCI5 or TPP (Scheme 21) (78LA1916). 

Multisubstituted five-membered aromatic heterocycles are synthesized via this cascade protocol (equation 34). The cycloadditions of a-acyloxyketones 78a with lithium ynolates afford /3-lactone lithium enolates 79a, which spontaneously cyclize to give bicyclic compounds 80a. These intermediates, which are stable enough to be isolated, are treated with TsOH under heating to provide substituted furans 81a via decarboxylation and dehydration. Thiophenes (e.g. 81b) are also synthesized by the analogous scheme via intermediate 80b using a-acylthioketones (78b) as a substrate. In the synthesis of pyrroles using a-acylaminoketones as a substrate, the cyclization proceeded at —20 °C, and the -lactone was subsequently ring-opened via /3-elimination to furnish pyrroles in one-pot (equation 35). ... 

Alkaline cleavage of 2,4,4-trimethyl-5-phenyl-4//-imidazole 1-oxide gives oximes of a-acylaminoketones as products (80AHC(27)24l). 

TABLE H-31. THIAZOLES FROM a-ACYLAMINOKETONES AND PHOSPHORUS PENTASULFIDE (Gabriel s synthesis)... 

Thiazoles were usually obtained by treating the corresponding a-acylaminoketones with phosphorus pentasulfide for a few minutes at IOO C... 

When primary amines react with a-acylaminoketones the resulting Schiff bases can be cyclized in the presence of phosphoryl chloride, phosphorus pentachloride, or triphenylphosphine and triethylamine in hexachloroethane to give 1-substituted imidazoles (11) (Scheme 2.1.4). The starting a-acyl-aminocarbonyls are readily prepared from a-amino acids by reduction with sodium amalgam [31, 32] or by the Dakin-West reaction [33, 34], which is most conveniently conducted in the presence of 4-(AUV-dimethylamino)pyridine (DMAP) as an acylation catalyst [35 37]. 

Thiazoles can also be derived from 1,4-dicarbonyl compounds, which are available through the N-H insertion reaction of rhodium carbenoids <05JA15644>. For example, the dirhodium(II) carboxylate-catalyzed reaction of diazocarbonyl compound 8 in the presence of primary amide 7 leads to the formation of a-acylaminoketone 9, which is converted into thiazole 10 by treatment with Lawessons reagent. Thiazole 10 serves as one of the six thiazole building blocks in the total synthesis of thiopeptide antibiotic amythiamicin D. 

Via intermediates Acetylenedicarhoxylic acid ester syntheses s. 3, 704 jd-Keto-o-acylaminocarboxylic acid esters and a-acylaminoketones from a-acylaminocarboxylic acids via oxazolones s. 4, 804 v.L -f- <—... 

A convenient route to polysubstituted oxazoles was developed through a variation on the Robinson-Gabriel synthesis in which the key 1,4-dicarbonyl compounds were obtained by a rhodium carbene N-H insertion reaction. Dirhodium tetraacetate catalysed reaction of primary amides 103 and diazocarbonyl compounds 107 gave a-acylaminoketones 108, which were converted into 109 by cyclodehydration using the Wipf and Miller protocol <04T3967>. 

Benzoyl chloride added to an equimolar soln. of N-benzoylalanine azlactone and triethylamine in tetrahydrofuran 5-benzoyloxy-4-methyl-2-phenyloxazole 63-70%) warmed in pyridine and the resulting azlactone allowed to stand at room temp, in methanol -> methyl N,2-dibenzoylalaninate (Y 70-78%). S. H. Pines and M. Sletzinger, Tetrah. Let. 1969,121 prepn. of a-acylaminoketones cf. W. Steglidi and G. Hofle, B. 102, 883, 899 (1969). 

Cobalt carbonyl I potassium hydroxide jpolyethylene glycol-400 a-Acylaminoketones from azomethines Phase transfer catalyzed carbonylation... 

Acylaminoketones ring, closure with ring expansion 28, 935 a-Acylaminoketones ring closure with ring... 

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