Reduction Ester

Perhaps the most notable example of this chemistry is in the production of vitamin A [68-26-8] where the P-ionyUdenacetaldehyde is condensed with the ester-yhd to obtain the polyene ester. Reduction then yields vitamin A (see Vitamins). 

Acetic acid, 3-ethoxycarbonyl-l-methyl-2-pyrrolyl-ethyl ester reduction, 4, 287 Acetic acid, 9-hydroxyethoxy-as metabolite of dioxane, 1, 245... 

Grignard reaction, 3, 711 Chromone-2-carboxylic acid, 7-phenyl-ethyl ester reduction, 3, 704... 

Coumarin-3-carboxylic acid, 6-nitro-ethyl ester reduction, 3, 691 Coumarinic acid synthesis, 3, 685 Coumarinoisocoumarin synthesis, 3, 834 Coumarins acetoxylation, 3, 680 acylation, 3, 689 annelated... 

Isothiazole-4,5-dicarboxylic acid, 3-phenyl-dimethyl ester synthesis, S, 150 Isothiazole-5-glyoxylic acid ethyl ester reduction, 6, 156 Isothiazole-4-mercurioacetate reactions, 6, 164 Isothiazole-5-mercurioacetate reactions, 6, 164 Isothiazoles, 6, I3I-I75 acidity, 6, 141 alkylation, 6, 148 aromaticity, S, 32 6, 144-145 basicity, 6, I4I biological activity, 6, 175 boiling points, 6, I43-I44, 144 bond fixation, 6, 145 bond orders, 6, I32-I34 calculated, 6, 133 bromination, S, 58 6, 147 charge densities, 6, 132-134 cycloaddition reactions, 6, 152 desulfurization, S, 75 6, 152 deuteration, S, 70... 

Claisen ester condensation, 6, 279 Thiazolecarboxylic acid chlorides reactions, 6, 279-280 Thiazolecarboxylic acid hydrazides synthesis, 6, 280 Thiazolecarboxylic acids acidity, 6, 279 decarboxylation, 6, 279 reactions, S, 92 6, 274 Thiazole-2-carboxylic acids decarboxylation, S, 92 Thiazole-4-carboxylic acids stability, S, 92 Thiazole-5-carboxylic acids decarboxylation, S, 92 Thiazole-4,5-dicarboxylic acid, 2-amino-diethyl ester reduction, 6, 279 Thiazole-4,5-dicarboxylic acids diethyl ester saponification, 6, 279 Thiazolediones diazo coupling, 5, 59 Thiazoles, 6, 235-331 ab initio calculations, 6, 236 acidity, S, 49 acylation, 6, 256 alkylation, S, 58, 73 6, 253, 256 analytical uses, 6, 328 antifogging agents... 

McFADYEN - STEVENS Ester Reduction Reduction of esters to aldehyde via hydrazides. 

The stereoselective reactions in Scheme 2.10 include one example that is completely stereoselective (entry 3), one that is highly stereoselective (entry 6), and others in which the stereoselectivity is modest to low (entries 1,2,4, 5, and 7). The addition of formic acid to norbomene (entry 3) produces only the exo ester. Reduction of 4-r-butylcyclohexanone (entry 6) is typical of the reduction of unhindered cyclohexanones in that the major diastereomer produced has an equatorial hydroxyl group. Certain other reducing agents, particularly sterically bulky ones, exhibit the opposite stereoselectivity and favor the formation of the diastereomer having an axial hydroxyl groi. The alkylation of 4-t-butylpiperidine with benzyl chloride (entry 7) provides only a slight excess of one diastereomer over the other. 

An interesting appetite suppressant very distantly related to hexahydroamphetamines is somanta-dine (24). The reported synthesis starts with conversion of 1-adamantanecarboxylic acid (20) via the usual steps to the ester, reduction to the alcohol, transformation to the bromide (21), conversion of the latter to a Grignard reagent with magnesium metal, and transformation to tertiary alcohol 22 by reaction with acetone. Displacement to the fomiamide (23) and hydrolysis to the tertiary amine (24) completes the preparation of somantadine [6]. 

Diels-Alder reaction, 493 El reaction, 391-392 ElcB reaction, 393 E2 reaction, 386 Edman degradation, 1032 electrophilic addition reaction, 147-148. 188-189 electrophilic aromatic substitution, 548-549 enamine formation, 713 enol formation, 843-844 ester hydrolysis, 809-811 ester reduction, 812 FAD reactions. 1134-1135 fat catabolism, 1133-1136 fat hydrolysis, 1130-1132 Fischer esterification reaction, 796 Friedel-Crafts acylation reaction, 557-558... 

The strategy for the construction of 13 from aldehyde 16 with two units of phosphonate 15 is summarized in Scheme 12. As expected, aldehyde 16 condenses smoothly with the anion derived from 15 to give, as the major product, the corresponding E,E,E-tri-ene ester. Reduction of the latter substance to the corresponding primary alcohol with Dibal-H, followed by oxidation with MnC>2, then furnishes aldehyde 60 in 86 % overall yield. Reiteration of this tactic and a simple deprotection step completes the synthesis of the desired intermediate 13 in good overall yield and with excellent stereoselectivity. 

The procedure is outlined in Scheme 8.33, starting from the generic allylic alcohol 125. SAE on 125 would provide epoxide 126, which could easily be transformed into the unsaturated epoxy ester 127 by oxidation/Horner-Emmonds olefmation (two-carbon extension). This operation makes the oxirane carbon adjacent to the double bond more susceptible to nucleophilic attack by a hydride, so reductive opening (DIBAL) of 127 provides, with concomitant ester reduction, diol 128. Pro-... 

Enantiomerically pure /J-keto sulfoxides are prepared easily via condensation of a-lithiosulfinyl carbanions with esters. Reduction of the carbonyl group in such /J-keto sulfoxides leads to diastereomeric /J-hydroxysulfoxides. The major recent advance in this area has been the discovery that non-chelating hydride donors (e.g., diisobutylaluminium hydride, DIBAL) tend to form one /J-hydroxysulfoxide while chelating hydride donors [e.g., lithium aluminium hydride (LAH), or DIBAL in the presence of divalent zinc ions] tend to produce the diastereomeric /J-hydroxysulfoxide. The level of diastereoselectivity is often very high. For example, enantiomerically pure /J-ketosulfoxide 32 is reduced by LAH in diethyl ether to give mainly the (RR)-diastereomer whereas DIBAL produces exclusively the (.S R)-diastereomer (equation 30)53-69. A second example is shown in... 

A representative set of a- and -keto esters was also tested as substrates (total 11) for each purified fusion protein (Figure 8.13b,c) [9bj. The stereoselectivities of -keto ester reductions depended both on the identity of the enzyme and the substrate stmcture, and some reductases yielded both l- and o-alcohols with high stereoselectivities. While a-keto esters were generally reduced with lower enantioselec-tivities, it was possible to identify pairs of yeast reductases that delivered both alcohol antipodes in optically pure form. These results demonstrate the power of genomic fusion protein libraries to identify appropriate biocatalysts rapidly and expedite process development. 

Aldehydes and ketones can be converted to ethers by treatment with an alcohol and triethylsilane in the presence of a strong acid or by hydrogenation in alcoholic acid in the presence of platinum oxide. The process can formally be regarded as addition of ROH to give a hemiacetal RR C(OH)OR", followed by reduction of the OH. In this respect, it is similar to 16-14. In a similar reaction, ketones can be converted to carboxylic esters (reductive acylation of ketones) by treatment with an acyl chloride and triphenyltin hydride. " ... 

The degradation of vinyl chloride and ethene has been examined in Mycobacterium sp. strain JS 60 (Coleman and Spain 2003) and in Nocardioides sp. strain JS614 (Mattes et al. 2005). For both substrates, the initially formed epoxides underwent reaction with reduced coenzyme M and, after dehydrogenation and formation of the coenzyme A esters, reductive loss of coenzyme M acetate resulted in the production of 5-acetyl-coenzyme A. The reductive fission is formally analogous to that in the glutathione-mediated reaction. 

Scheme 7.27. Domino ester reduction/epoxide formation/reductive epoxide-opening reaction.

Rodriguez, S., Kayser, M.M. and Stewart, J.D. (2001) Highly stereoselective reagents for/3-keto ester reductions by genetic engineering of baker s yeast. Journal of the American Chemical Society, 123 (8), 1547-1555. 

Carbon-carbon double bonds alkene to alkane reductions, trisubstituted alkenes, 40 ketone-alcohol reduction, 77, 86-87 a,p-unsaturated ester reduction, 93-96 Carbonyl compounds ... 

Tricarbonyl( 1 -ewrfo-allyltetralin)chromium, stereoselective alcohol to hydrocarbon reduction, 132 1,2,3-Trideoxy-D-r/fco-hex-1 -enopyranose diacetate, allyl ester reduction,... 

Despite the diverse range of documented enzyme-catalyzed reactions, there are only certain types of transformations that have thus far emerged as synthetically useful. These reactions are the hydrolysis of esters, reduction/oxidation reactions, and the formation of carbon-carbon bonds. The first part of this chapter gives a brief overview by describing some examples of various biotransformations that can easily be handled and accessed by synthetic organic chemists. These processes are now attracting more and more attention from nonspecialists of enzymes. 

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