A,p-Epoxy carbonyl

A powerful approach to the synthesis of a,p-epoxy carbonyls and related compounds is found in the Darzens reaction (Scheme 11.18b). In this context, the groups of and Arai " have investigated the asymmetric PTC-... 

The oxidative rearrangement of allylic alcohols to a -unsaturated kelmies or alddiydes is one of the most widely used synthetic reactions in this group, and forms part of a 1,3-carbonyl tran sition sequence. Scheme 7 shows this reaction and the related conversion of the allylic alcdiol to an a,p-epoxy carbonyl compound. Chromate reagents induce some allylic alcohol substrates to undergo a directed qmxidation of the alkene without rearrangement, but this reaction is beyond the scope of the present discussion. 

Hydroxy carbonyl compounds The oxirane ring of a,P-epoxy carbonyl compounds undergo reductive cleavage (29 examples, 80-100%). 

The Darzens reaction (tandem aldol-intramolecular cyclization sequence reaction) is a powerful complementary approach to epoxidation (see Chapter 5) that can be used for the synthesis of a,P-epoxy carbonyl and a,p-epoxysulfonyl compounds (Scheme 8.32). Currently, all catalytic asymmetric variants of the Darzens reactions are based on chiral phase-transfer catalysis using quaternary ammonium salts as catalysts. 

Chemoselective reduction of a,p-epoxy carbonyl compounds to aldols and their analogs by organoseleniums and its application to natural product synthesis 98YGK736. 

Another calixarene-based phase-transfer catalyst was designed by Srivastava and Srivastava [20]. In that study, two different quaternary ammonium salts of calix [4]arene (Calix[4]arene 2a and 2b) were employed as a catalyst in the Darzens condensation to synthesize a,p-epoxy carbonyl compounds (see Fig. 27.5). It was found that these phase-transfer catalysts exhibited significant catalytic activity, especially when the calix[4]arene with long aUcyl chain ( -butyl) was chosen (see Table 27.3). 

The Darzens condensation is an old methodology for the construction of a,p-epoxy carbonyl compounds 49 with control of two formed stereogenic centers. This reaction includes an aldol reaction (C-C bond formation), which normally requires stoichiometric amounts of base to achieve good yields. Only phase transfer catalysts, usually chiral ammonium halides have shown to be efQdent to perform this transformation in a catalytic and enantioselective form. 

The Darzens Reaction is the condensation of a carbonyl compound with an a-halo ester in the presence of a base to form an a,p epoxy ester. 

In the past, Darzens methodology was primarily used for the synthesis of aldehydes and ketones, as a homologation reaction without any consideration of stereocontrol in the epoxide formation. For this sequence, saponification of the a,P-epoxy ester followed by decarboxylation gives the substituted carbonyl compound ... 

The double bond of an unsaturated ketone is deactivated towards electrophilic attack by the electron-withdrawing carbonyl group but is susceptible to nucleophilic addition. Base-catalysed epoxidation with alkaline hydrogen peroxide provides a useful method for the synthesis of a,P-epoxy ketones. 

Schreiber, J., et al. Synthesis of acetylenic carbonyl compounds by fragmentation of a,P-epoxy ketones with p-tolylsulfonylhydrazine. Helv. Chim. Acta 1967, 50, 2101-2108. 

Epoxides. Allylstannanes react under the influence of Pbl -HMPA with carbonyl compounds such as a,P-epoxy ketones and a-bromoketones give epoxy products. On the other hand, the reaction of l-chloro-3-tributylstannyl-l-propene with aldehydes leads to vinyl-epoxides. 

The a,p-epoxy sulfoxides available using this protocol are important intermediates for several synthetic methodologies. For example, they give upon thermal rearrangement a, -unsaturated aldehydes and thus represent the pivotal intermediate in a two-step procedure for the one-carbon homologation of carbonyl compounds (Scheme 8). °... 

Modeling the inhibition activity of peptides and peptidomimetics containing epoxide ring against the cysteine protease Helter and co-workers explored the potential energy surface for interaction of oxirane (1), a, 3-epoxy carbonyl compounds (22,23) with methylthiolate-anion at BLYP/6-311 + G(d) and BLYP/TZV+P levels of theory [46, 47]. 

The formation of a,P-epoxy carboxylic esters from carbonyl compounds and a-halo esters is not just an undesired side reaction, but is also an important synthetic method known as Darzens reaction. 

P-Trimethylsilylstyrenes are formed by reaction of alka-nesulfonyl chlorides with TMSCHN2 in the presence of triethy-lamine (eq 13). TMSC(Li)N2 reacts with carbonyl compounds to give a-diazo-p-hydroxy silanes which readily decompose to give a,p-epoxy silanes (eq 14). However, benzophenone gives diphenylacetylene under similar reaction conditions (eq 15). ... 

The epoxyketone 3 is a versatile precursor for a variety of tricycloundecane systems having a p,y-unsaturated carbonyl chromophore, which are not so readily accessible. The contiguous epoxy ketone functionality and the double bond present in the five-membered ring provide opportunities for further manipulation. Adduct 3 may be transformed into a variety of molecular frameworks such as linearly fused cis anti cis tricyclopentanoids, protoilludanes, and marasmanes in a stereoselective fashion after suitable chemical and photochemical manipulation.13... 

Rearrangement of epoxy silyl ethers. When treated with 1 equiv. of TiCl4, a-silyloxy epoxides rearrange to p-hydroxy carbonyl compounds. 

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