0-Hydroxy carbonyl compounds

4- Hydroxy carbonyl compounds seem available by selective reduction of one carbonyl group in 1,4-dicarbonyl compounds. Such chemoselectivity usually is not workable, and the retrosynthetic step where the hydroxy group in 

4- hydroxycarbonyl compounds is interconverted to a keto group does not suggest 

Synthon II, an analog of I with an oxygen atom at a lower oxidation state, is also conceivable. Here, the positive charge can be compensated intramolecularly by an electron pair from an oxygen atom, i.e., by the formation of epoxide. In other words, epoxides are ideal reagents for illogical synthons II  

When as the nucleophilic component a-carbanion stabilized by a carbonyl group or masked as enamine reacts, the reaction products are 1,4- or Y-hydroxycarbonyl compounds. The next example illustrates the utility of such retrosynthetic considerations. 

Example 5.19 Complete the retrosynthetic analysis and then propose the synthesis of TM 5.21. 

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XXV XXV, 1st 1936 3634-3793 Two Cyclic Nitrogens (continued). 1 Hydroxy-carbonyl compounds, 1 1... 

Aldol additions and ester condensations have always been and still are the most popular reactions for the formation of carbon-carbon bonds (A.T. Nielsen, 1968). The earbonyl group acts as an a -synthon, the enoi or enolate as a d -synthon. Both reactions will be treated together here, and arguments, which are given for aldol additions, are also valid for ester condensations. Many famous name reactions belong to this category ). The products of aldol additions may be either /J-hydroxy carbonyl compounds or, after dehydration, or, -unsaturated carbonyl compounds. 

Cleavage reactions of car bohydrates also occur on treatment with aqueous base for prolonged periods as a consequence of base-catalyzed retro-aldol reactions. As pointed out in Section 18.9, aldol addition is a reversible process, and (3-hydroxy carbonyl compounds can be cleaved to an enolate and either an aldehyde or a ketone. 

Reaction of aldehydes or ketones to give /3-hydroxy carbonyl compounds... 

If the initially formed /3-hydroxy carbonyl compound 3 still has an a-hydrogen, a subsequent elimination of water can take place, leading to an o ,/3-unsaturated aldehyde or ketone 4. In some cases the dehydration occurs already under the aldol reaction conditions in general it can be carried out by heating in the presence of acid ... 

An alkene activated by an electron-withdrawing group—often an acrylic ester 2 is used—can react with an aldehyde or ketone 1 in the presence of catalytic amounts of a tertiary amine, to yield an a-hydroxyalkylated product. This reaction, known as the Baylis-Hillman reaction, leads to the formation of useful multifunctional products, e.g. o -methylene-/3-hydroxy carbonyl compounds 3 with a chiral carbon center and various options for consecutive reactions. 

All three elimination reactions--E2, El, and ElcB—occur in biological pathways, but the ElcB mechanism is particularly common. The substrate is usually an alcohol, and the H atom removed is usually adjacent to a carbonyl group, just as in laboratory reactions. Thus, 3-hydroxy carbonyl compounds are frequently converted to unsaturated carbonyl compounds by elimination reactions. A typical example occurs during the biosynthesis of fats when a 3-hydroxybutyryl thioester is dehydrated to the corresponding unsaturated (crotonyl) thioester. The base in this reaction is a histidine amino acid in the enzyme, and loss of the OH group is assisted by simultaneous protonation. 

The product is a jS-hydroxy carbonyl compound. Sign in atwwvu.thomsonedu.com to see a simulation based on this figure and to take a short quiz. 

The reaction conditions needed for aldol dehydration are often only a bit more vigorous (slightly higher temperature, for instance) than the conditions needed for the aldol formation itself. As a result, conjugated enones are usually obtained directly from aldol reactions without isolating the intermediate jS-hydroxy carbonyl compounds. 

StepS 9-1° of F Sure 29-7 Dehydration and Dephosphorylation Like mos /3-hydroxy carbonyl compounds produced in aldol reactions, 2-phospho glvcerate undergoes a ready dehydration in step 9 by an ElcB mechanism (Section 23.3). The process is catalyzed by enolase, and the product i... 

Aldol reaction (Section 23.1) The carbonyl condensation reaction of an aldehyde or ketone to give a jS-hydroxy carbonyl compound. 

Write disconnections and starting materials forthi.> i-hydroxy carbonyl compounds. 

Supplement 1941 1-161 Derivatives. Methyl alcohol, 273. Ethyl alcohol, 292. Ethyl ether, 314. Glycerol, 502. Carbonyl Compounds Aldehydes, Ketones, Ketencs and Derivatives. Formaldehyde, 558. Acetaldehyde, 635. Acetone, 635. Ketene, 724. Hydroxy-Carbonyl Compounds Aldehyde-Alcohols, Ketone-Alcohols, Monosaccharides and Derivatives. Glycolaldehyde, 817. Aldol, 824. Pentoses, 858. Hexoses, 878. 

The Mukaiyama aldol reaction can provide access to a variety of (3-hydroxy carbonyl compounds and use of acetals as reactants can provide (3-alkoxy derivatives. The issues of stereoselectivity are the same as those in the aldol addition reaction, but the tendency toward acyclic rather than cyclic TSs reduces the influence of the E- or Z-configuration of the enolate equivalent on the stereoselectivity. 

Here the carbanion (87), obtained from the action of base (usually eOH) on an oc-H atom of one molecule of a carbonyl compound (88), adds to the carbonyl carbon of another (88) to yield a -hydroxy-carbonyl compound. Thus with ethanal, CH3CHO, the product is 3-hydroxybutanal (89)—aldol itself ... 

Davis et al.111 developed another method for reagent-controlled asymmetric oxidation of enolates to a-hydroxy carbonyl compounds using (+)-camphor-sulfonyl oxaziridine (147) as the oxidant. This method afforded synthetically useful ee (60-95%) for most carbonyl compounds such as acyclic keto esters, amides, and a-oxo ester enolates (Table 4-20). 

Oxidation of silyl enol ethers. Oxidation of silyl enol ethers to a-hydroxy aldehydes or ketones is usually effected with w-chloroperbenzoic acid (6, 112). This oxidation can also be effected by epoxidation with 2-(phenylsulfonyl)-3-( p-nitrophenyl) oxaziridine in CHC1, at 25-60° followed by rearrangement to a-silyloxy carbonyl compounds, which are hydrolyzed to the a-hydroxy carbonyl compound (BujNF or H,0 + ). Yields are moderate to high. Oxidation with a chiral 2-arene-sulfonyloxaziridine shows only modest enantioselectivity. 

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

Abstract Synthetically useful examples of carbonylations of aldehydes that enable the synthesis of structurally diverse carbonyl compounds such as -amino acids, -hydroxy carbonyl compounds, furanones, and lactones will be highlighted in this chapter. 

Abstract Development in the field of transition metal-catalyzed carbonylation of epoxides is reviewed. The reaction is an efficient method to synthesize a wide range of / -hydroxy carbonyl compounds such as small synthetic synthons and polymeric materials. The reaction modes featured in this chapter are ring-expansion carbonylation, alternating copolymerization, formylation, alkoxycarbonylation, and aminocarbonylation. 

Carbonylation of epoxides provides direct access to a large variety of hydroxy carbonyl compounds, such as /Mac tones, useful synthons in organic synthesis, and poly(3-hydroxyalkanoate), important biodegradable polyesters. Thus, the development of efficient catalysts for such carbonylations has been widely studied. 

The reversible reaction (usually base catalyzed) of two carbonyl compounds (/.e., two aldehydes, two ketones, or one of each), in which at least one compound has an a-hydrogen, to produce a j8-hydroxy carbonyl compound. 

Aldol Reaction The formation of an aldol (P-hydroxy carbonyl compound) through the catalyzed condensation of an enol/enolate with a carbonyl compound. 

The aldol reaction is well-recognized as one of the most powerful synthetic tools for a fast carbon-carbon bond connection. This route provides a rapid access to (5-hydroxy carbonyl compounds, which have attracted many synthetic efforts and... 

A great deal of the interest in isoxazolines stems from their use in the synthesis of acyclic compounds (19). The approach to (3-hydroxy carbonyl compounds via... 

There are very few reactions of real synthetic significance which proceed via condensation of two 1,3-electrophile-nucleophile species. Probably the most important of this latter type of reaction is the synthesis of pyrazines by self-condensation of an a-acylamino compound to the dihydropyrazine followed by aromatization (equation 132). The a-acylamino compounds, which dimerize spontaneously, are normally generated in situ, for example by treatment of a- hydroxy carbonyl compounds with ammonium acetate or by reduction of a-azido, -nitro or -oximino carbonyl compounds. Cyclodimerization of a-amino acids gives 2,5-dioxopiperazines (equation 133), many derivatives of which occur as natural products. Two further reactions which illustrate the 1,3-electrophile-nucleophile approach are outlined in equations (134) and (135), but su i processes are of little general utility. 

Diastereomeric 1,3-amino alcohols 1 have been obtained by reduction of 4,5-dihydroisoxa-zoles350-353. 3C chemical shifts allow a stereochemical differentiation due to the formation of energetically preferred chelated conformations. Similar to /3-hydroxy carbonyl compounds and 1,3-diol derivatives, the chemical shifts of the backbone carbons are larger in the syn 1,3-amino alcohols than in the awn -isomers353. 

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