Aldehydes, 2-hydroxy synthesis

Living olefin polymerization allows the synthesis of end-functionalized polyolefins if appropriate initiation and/or quenching methods are used. Doi et al. first showed the utility of living olefin-polymerization catalysts for the preparation of end-functionalized polyolefins. They synthesized iodine-, amine-, aldehyde-, hydroxy-, and metha-cryl-terminated PPs using living V-PP species and appropriate reagents. " " ... 

Optically active a-kytbvxy aldehydes. A synthesis of chiral a-hydroxy aldehydes involves reaction of 1 with methyl hydroxymethoxyacetate to form the methoxycarbonyl aminal 2. The product is treated with a Grignard reagent in the presence of MgCl2 to form the keto aminal 3. A second Grignard reaction with 3 forms an intermediate (a), which is hydrolyzed to 1 and an a-hydroxy aldehyde (4) ... 

Hoesch synthesis A variation of the Gattermann synthesis of hydroxy-aldehydes, this reaction has been widely applied to the synthesis of anthocyanidins. It consists of the condensation of polyhydric phenols with nitriles by the action of hydrochloric acid (with or without ZnCl2 as a catalyst). This gives an iminehydrochloride which on hydrolysis with water gives the hydroxy-ketone. 

The 5-oxohexanal 27 is prepared by the following three-step procedure (1) 1,2-addition of allylmagnesium bromide to an a, / -unsaturated aldehyde to give the 3-hydroxy-1,5-diene 25, (2) oxy-Cope rearrangement of 25 to give 26, and (3) palladium catalyzed oxidation to afford 27. The method was applied to the synthesis of A -2-octalone (28), which is difficult to prepare by the Robinson annulation[25]. 

Reactions and Uses. The common reactions that a-hydroxy acids undergo such as self- or bimolecular esterification to oligomers or cycHc esters, hydrogenation, oxidation, etc, have been discussed in connection with lactic and hydroxyacetic acid. A reaction that is of value for the synthesis of higher aldehydes is decarbonylation under boiling sulfuric acid with loss of water. Since one carbon atom is lost in the process, the series of reactions may be used for stepwise degradation of a carbon chain. 

Cyanohydrin Synthesis. Another synthetically useful enzyme that catalyzes carbon—carbon bond formation is oxynitnlase (EC 4.1.2.10). This enzyme catalyzes the addition of cyanides to various aldehydes that may come either in the form of hydrogen cyanide or acetone cyanohydrin (152—158) (Fig. 7). The reaction constitutes a convenient route for the preparation of a-hydroxy acids and P-amino alcohols. Acetone cyanohydrin [75-86-5] can also be used as the cyanide carrier, and is considered to be superior since it does not involve hazardous gaseous HCN and also virtually eliminates the spontaneous nonenzymatic reaction. (R)-oxynitrilase accepts aromatic (97a,b), straight- (97c,e), and branched-chain aUphatic aldehydes, converting them to (R)-cyanohydrins in very good yields and high enantiomeric purity (Table 10). 

The acid catalyzed condensation of benzaldehydes with 2-acetyIpyridine provides access to hydroxy- or amino-indolizines (Scheme 58a) (71CB1629,71CB1645). A remarkable synthesis of fused pyrrolidines in which aldehydes also provide C-2 is exemplified in Scheme 58b... 

Upon heating of a carboxylic ester 1 with sodium in an inert solvent, a condensation reaction can take place to yield a a-hydroxy ketone 2 after hydrolytic workup. " This reaction is called Acyloin condensation, named after the products thus obtained. It works well with alkanoic acid esters. For the synthesis of the corresponding products with aryl substituents (R = aryl), the Benzoin condensation of aromatic aldehydes is usually applied. 

The formylation of a phenol 1 with chloroform in alkaline solution is called the Reimer-Tiemann reaction. It leads preferentially to formation of an ortho-formylated phenol—e.g. salicylic aldehyde 2 —while with other formylation reactions, e.g. the Gattermann reaction, the corresponding /jara-formyl derivative is obtained as a major product. The Reimer-Tiemann reaction is mainly used for the synthesis of o-hydroxy aromatic aldehydes. 

The aldol reaction yields either a /3-hydroxy aldehyde/ketone or an a, 3-unsatu-rated aldehyde/ketone, depending on the experimental conditions. By learning how to think backward, it s possible to predict when the aldol reaction might be useful in synthesis. Whenever the target molecule contains either a /3-hydroxy aldehyde/ketone or a conjugated enone functional group, it might come from an aldol reaction. 

Besides simple alkyl-substituted sulfoxides, (a-chloroalkyl)sulfoxides have been used as reagents for diastereoselective addition reactions. Thus, a synthesis of enantiomerically pure 2-hydroxy carboxylates is based on the addition of (-)-l-[(l-chlorobutyl)sulfinyl]-4-methyl-benzene (10) to aldehydes433. The sulfoxide, optically pure with respect to the sulfoxide chirality but a mixture of diastereomers with respect to the a-sulfinyl carbon, can be readily deprotonated at — 55 °C. Subsequent addition to aldehydes afforded a mixture of the diastereomers 11A and 11B. Although the diastereoselectivity of the addition reaction is very low, the diastereomers are easily separated by flash chromatography. Thermal elimination of the sulfinyl group in refluxing xylene cleanly afforded the vinyl chlorides 12 A/12B in high chemical yield as a mixture of E- and Z-isomers. After ozonolysis in ethanol, followed by reductive workup, enantiomerically pure ethyl a-hydroxycarboxylates were obtained. 

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