A-Acyloxyketones

Base-catalyzed acyl transfer reaction that converts a-acyloxyketones to (3-diketones. 

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). 

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). ... 

This unusual reduction by halide ion of the vinylog of an a-acyloxyketone, presumably via an -haloketone intermediate, finds analogy in the reduction of simple a-haloketones by halogen acid (Newman, 1951 Meyer, 1911 Backes et al., 1921). 

Shrnada, T., Kawakami, T., Sakai, H., Takada, I., and Ohfune, Y., An efficient synthesis of a-acyloxyketone by Cufacacfj-catalyzed insertion reaction of a-diazoketone to carboxylic acid. Tetrahedron Lett., 39, 3757, 1998. 

The enediol-monoesters initally formed by 1,4-addition of aldehydes to a-diketones tautomerize to the more stable keto-form so that the observed products are a-acyloxyketones. In reaction of camphorqui-none 15>130)j the acyloxy group had the more stable, endo configuration... 

The synthesis of oxazoles via cyclization of a-acyloxyketones with ammonium acetate or urea was described 65 years ago. The yields of this reaction can vary significantly, and the yield can be complicated by formation of imidazoles. Nonetheless, it is still a useM method for preparing oxazoles given the ready availability of starting materials. 

Shridhar and co-workers used this method to prepare 2,4-diaryloxazoles that were intermediates for potential hypolipidemic agents (Scheme 1.114). The a-acyloxyketones 419 were readily prepared from 418 in modest to good yield. Cyclization of 419 to 420 was achieved using anhydrous ammonium acetate in refluxing acetic acid. 

TABLE 1.33 2,4-DIARYLOXAZOLES EROM CYCEIZATION OF a-ACYLOXYKETONES WITH ACETAMIDE-BF3 OEtz, 93... 

Various methods for the a-hydroxylation of carbonyl compounds have appeared. lodosobenzene shows a high degree of selectivity in the preparation of acyloins, and benzeneseleninic anhydride appears to be an excellent reagent for the hydroxylation at the tertiary centre in a-alkylcycloalkanones. Enol silyl ethers give acyloins with osmium tetroxide and V-methylmorpholine V-oxide,and a-acyloxycarbonyl compounds with silver acetate and iodine. a-Acyloxyketones may also be prepared conveniently by treatment of oximes with acid chlorides [equation (42)]. ... 

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