Aldehydes from glycide esters

Synthesis of glycidic esters (amides) from an aldehyde or ketone and an a-haloester (amide). 

Geranyl chloride can be prepared from geraniol by the careful use of triphenylphosphine in carbon tetrachloride. Tris(dimethylamino)phosphine reacts with carbon tetrachloride to form the complex (42) which can be used to form the enol esters (43) from acid anhydrides. Similarly, aldehydes form the alkenes (44), and esters or amides of trichloroacetic acid are converted to glycidic esters. ... 

Early work on the asymmetric Darzens reaction involved the condensation of aromatic aldehydes with phenacyl halides in the presence of a catalytic amount of bovine serum albumin. The reaction gave the corresponding epoxyketone with up to 62% ee.67 Ohkata et al.68 reported the asymmetric Darzens reaction of symmetric and dissymmetric ketones with (-)-8-phenylmenthyl a-chloroacetate as examples of a reagent-controlled asymmetric reaction (Scheme 8-29). When this (-)-8-phenyl menthol derivative was employed as a chiral auxiliary, Darzens reactions of acetone, pentan-3-one, cyclopentanone, cyclohexanone, or benzophenone with 86 in the presence of t-BuOK provided dia-stereomers of (2J ,3J )-glycidic ester 87 with diastereoselectivity ranging from 77% to 96%. 

The methoxy derivatives may be treated directly o-methoxyphenyl-acetone, heated with hydrobroniic acid in acetic acid, gives 2-methyl-benzofuran.326 o-Methoxylated phenylacetones are readily prepared by glycidic synthesis from o-methoxylated aromatic aldehydes the intermediate glycidic ester (127) can be directly converted by pyridine hydrochloride into a 2-alkylbenzofuran in 40-80% yield.105... 

Aromatic and aliphatic aldehydes have been prepared in good yields by the decarboxylation and isomerization of the corresponding glycidic acids. Esters of the latter are obtained by treating a ketone with ethyl chloro-acetate in the presence of sodium amide (method 127). The glycidic esters are first converted to the sodium salts with sodium ethoxide and then treated with aqueous hydrochloric acid under gentle reflux. By this procedure, a-phenylpropionaldehyde has been prepared from acetophenone in an over-all yield of 38%. Other details have been discussed. ... 

Since glycidic esters can usually be prepared from carbonyl compounds and chloroacetic esters, hydrolysis of the ester group and decarboxylation of the resulting glycidic acid gives as end-product the aldehyde containing one carbon atom more than those in the aldehyde or ketone ... 

The Cl 4-aldehyde 7 is also a key intermediate in the technical synthesis of vitamin A. It can be prepared from p-ionone f7J in a Darzens glycidic ester condensation by the reaction with ethyl chloroacetate (16) via 17 as intermediate. The chain elongation to the Ci9-aldehyde 72 was achieved by reaction with the acetylenic Cs-compound 18 (Scheme 4). 

The final common intermediate for the syntheses of vitamin A and P,p-carotene (3) is the Ci4-aldehyde 23, which is obtained from p-ionone f/7) by glycidic ester synthesis. Grignard coupling of the C6-unit (Z)-19 yields the C2o-diol 24, which has the carbon skeleton of vitamin A (22). The four conjugated double bonds in the side chain are formed by selective acetylation, partial hydrogenation to give 25 [19], and acid-catalysed elimination of water results in vitamin A acetate (26) (Scheme 4) [8]. 

Modified Darzens-Claisen reaction Aldehydes from ketones via glycidic acid tertAmiyX esters Synthesis with addition of 1 -atom... 

Sodium alcohol (s. a. under Cu and Ni(CO)J Darzens-Claisen reaction Synthesis of ketones from aldehydes via glycidic acid esters... 

Darzens reaction. Typical among the many types of glycidic ester recently obtained from the Darzens reaction of aliphatic and aromatic aldehydes and ketones with esters of chloroacetic acid are (110), (111), and (112). ... 

The Darzens Glycidic Ester Condensation. When an aldehyde (or ketone) is allowed to react with the carbanion formed by proton abstraction from a halogenbearing carbon a to the carbonyl of an ester, RCO2R (this Chapter), an oxirane (epoxide) results. These compounds, containing an oxirane (epoxide) a,p to the carbon of the carbonyl of the ester, are known as glycidic esters. An accepted... 

The lipase from Serratia marcescens has a high enantioselectivity (E = 135) for the (2R,3S)-(4-methoxyphenyl) glycidic acid methyl ester, which acts as a competitive inhibitor. The formed acid (hydrolyzed (+)-methoxyphenylglycidate) is unstable and decarboxylates to give 4-methoxyphenylacetaldehyde this aldehyde strongly inhibits and deactivates the enzyme. It is removed by transfer to the aqueous phase by formation of a water-soluble adduct with sodium hydrogen sulfite added to the aqueous phase. The bisulfite acts also as a buffer to maintain constant pH during synthesis. 

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