Hydroxycarbonyl compound

In this and the next chapter we consider disconnection with participation of two oxygen functionalities, called the dioxygenated pattern. The rationale behind this selection rests in the fact that oxygen functionalities can be conveniently transformed into functional groups with other heteroatoms. Schematic stmctures of the 1,3-dioxygenated pattern are presented as TM I-III (Fig. 4.3). 

The synthetic reaction in which two carbonyl components are connected to a more complex molecule with a 1,3-hydroxycarbonyl pattern as in TM II is the well-known aldol reaction, which takes place between the enolate and carbonyl form of aldehydes or ketones. The mechanism of this reaction and its stereochemical course will be discussed later in this chapter. The examples that follow serve to suggest the decision concerning which internal C-C bond in 1,3-dioxygenated compounds to disconnect. 

Example 4.1 Propose the preferred disconnection for TM 4.1 and then the synthesis from easily available starting materials. Suggest how to use TM 4.1 for the 

The result of disconnection is a pleasant surprise TM 4.1a repeats in two molecules of n-butanal. 

Some technological aspects of the process are worth comment. Formylation (a) is catalyzed by the Rh(I) complex of tris(3-sulfophenyl)phosphine trisodium salt (TPPTS). Ligand solubilizes the Rh(I) complex in water because of the presence of three sulfonyl sodium groups, and its high stability enables high turnover of the catalytic cycle. n-Butanal is insoluble in water and separates as the upper layer, while the aqueous layer that contains catalysts can be reused in the process. 

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The parallel synthesis of furans from a-hydroxycarbonyl compounds is frequently conducted using aldoses or ketoses as readily available sources of this functional grouping, especially as the resulting polyhydroxyalkyl side-chain can be removed easily by oxidative degradation (Schemes 67d and 67e) 56MI30300). 

Within this section, the term aldol reaction includes additions of enols and enolates to carbonyl compounds. This section concentrates on aldol additions which deliver nonracemic, /i-hydroxycarbonyl compounds. The chiral information can be located ... 

In aldol reactions, especially Mukaiyama aldol reactions, TiIV compounds are widely employed as efficient promoters. The reactions of aldehydes or ketones with reactive enolates, such as silyl enol ethers derived from ketones, proceed smoothly to afford /3-hydroxycarbonyl compounds in the presence of a stoichiometric amount of TiCl4 (Scheme 17).6, 66 Many examples have been reported in addition to silyl enol ethers derived from ketones, ketene silyl acetals derived from ester derivatives and vinyl ethers can also serve as enolate components.67-69... 

A convenient procedure was developed for transformations of /V-siloxyisoxa-zolidines into functionalized p-hydroxycarbonyl compounds with aqueous titanium trichloride (185, 189) (Scheme 3.164). 

Main Rearrangements of BENA In previous Sections (3.5.4.1. and 3.5.4.2.), a-hydroxy oximes (503) and their bis-silyl derivatives (504) were considered as undesired by-products, formed in the synthesis and chemical transformations of BENA. The aim was to minimize the amount of these impurities. On the other hand, oximes (503) are convenient precursors of various useful products, such as p-amino alcohols (530), amino acids (531), a-hydroxycarbonyl compounds (532) and various heterocyclic systems (533). 

Metallic tin, Sn(0), is even more effectively employed. For example, in the presence of Sn(0), allyl bromide and a-halocarbonyl compounds afford nucleophilic organometallic species, which add to aldehydes in good yields to give homoallylic alcohols (12) and g-hydroxycarbonyl compounds (13,14) respectively. a-Diketones could be reduced by activated Sn(0), to give tin(II) enediolates which in turn undergo aldol reaction to form a,g-dihydroxyketones (15,16). This reaction was successfully applied to a stereoselective synthesis of methyl D-glucosaminate (17). 

Oxidation of chiral sulfonimines (R"S02N=CHAr)and chiral sulfamyl-imines (R RNS02N=CHAr)affords optically active 2-sulfonyloxaziridines and 2-sulfamyloxaziridines, respectively. These chiral, oxidizing reagents have been used in the asymmetric oxidation of sulfides to sulfoxides (15-68% ee), 11-13 selenides to selenoxides (8-9% ee] enolates to a-hydroxycarbonyl compounds (8-37% ee) and in the asymmetric epoxidation of alkenes (15-40% ee)... 

In the third series, aj-dimethyl- -hydroxycarbonyl compounds, there is no pronounced trend for any carbon. 

Reaction of a-Dicarbonyl or a-Hydroxycarbonyl Compounds with Ammonia in the Presence of Formaldehyde... 

The imidazoles formed in the reaction of aqueous ammonia with other a-hydroxycarbonyl compounds, for example, the triose DL-glyceraldehyde, and such a-dicarbonyl compounds as 3-deoxy-D-glycero-pentosulose (59), and the 3,6-dideoxy-L-erythro-, D-arabino-, and 3-deoxy-D-erytforo-hexosuloses (60, 61, and 62), respectively, are summarized in Table VIII for reactions in which formaldehyde was added, and in Table IX for reactions in which it was not added. 

To develop new electrophilic reagents, Ricci and coworkers have described the synthesis of trimethylsilyloxy and hydroxy compounds from magnesium enolates and bis(trimethyl-silyl)peroxide. Magnesium enolates, generated using magnesium diisopropylamide, (DA)2Mg, give the hydroxycarbonyl compounds in excellent yields (equation 72, Table 8). 

The addition of the nucleophilic carbanion-enolate, usually of an aldehyde, to the C=0 group of its parent compound is called an aldol condensation. The product is a /3-hydroxycarbonyl compound. In a mixed aldol condensation the carbanion-enolate of an aldehyde or ketone adds to the 0=0 group of a molecule other than its parent. The more general condensation diagramed above is termed an aldol-type condensation. Since the C, not the O, is the more reactive site in the hybrid, the enolate contributing structure is usually omitted when writing equations for these reactions. This is done even though the enolate is the more stable and makes the major contribution. 

Aldol condensations are reversible, and with ketones the equilibrium is unfavorable for the ondensation product. To effect condensations of ketones, the product is continuously removed from he basic catalyst. )3-Hydroxycarbonyl compounds are readily dehydrated to give a,j3-unsaturated arbonyl compounds. With Ar on the carbon, only the dehydrated product is isolated. 

Write structural formulas for the )3-hydroxycarbonyl compounds and their dehydration products formed by aldol condensations of (a) butanal, (6) phenylacetaldehyde, (c) diethyl ketone, (d) cyclohexanone, (e) benzaldehyde. 

A further variation on this general method for preparing quinoxaline dioxides is the use of o-quinone dioximes (54) rather than benzofurazan 1-oxides. The dioxime undergoes cycloaddition with cr-dicarbonyl and a-hydroxycarbonyl compounds, and hydroxamic acids of type 55 are particularly easily prepared by this method.56... 

Dioxotetrahydropteridines are reduced analogously400 to the 2,3-di-oxoquinoxalines a reduction scheme was proposed in Part I and substantiated later.401 The primary two-electron reduction product is an enediol that isomerizes to a hydroxycarbonyl compound. After loss of water, the double bond is saturated with the uptake of two electrons and protons and a monooxytetrahydropyrazine ring is formed. 

The aldol reaction is well established in organic chemistry as a remarkably useful synthetic tool, providing access to p-hydroxycarbonyl compounds and related building blocks. Intensive efforts have raised this classic process to a highly enantioselective transformation employing only catalytic amounts of chiral promoters, as reviewed in the previous section (Chap. 29.1). While some effective applications have been reported, most of the methodologies necessarily involve the preformation of latent enolates 2, such as ketene silyl acetals, using... 

The oxidation of 1,4- and 1,5-diols with many oxidants leads to intermediate hydroxycarbonyl compounds that equilibrate with lactols, which are transformed in situ into lactones. This side reaction is very uncommon during Swern oxidations, due to the sequential nature of alcohol activation versus base-induced transformation of the activated alcohol into a carbonyl compound. Thus, during the oxidation of a diol, normally when the first alcohol is transformed into an aldehyde or ketone, the second alcohol is already protected by activation, resulting in the impossibility of formation of a lactol that could lead to a lactone. 

The Corey Kim procedure is the oxidation method of choice for the transformation of (3-hydroxycarbonyl compounds into 1,3-dicarbonyl compounds. Treatment of (3-hydroxycarbonyl compounds under Corey Kim conditions leads to an intermediate 1,3-dicarbonyl compound 33 that reacts in situ with activated DMSO, resulting in the generation of a stable sulfur ylide 34. This sulfur compound can be transformed into the desired 1,3-dicarbonyl compound by reduction with zinc in acetic acid.254... 

Tricarbonyl compounds can also be obtained by treatment of (3-hydroxycarbonyl compounds—without a sulfur atom at the a—position— with Dess-Martin periodinane.38... 

Diols are sometimes transformed with Fetizon s reagent into an intermediate (3-hydroxycarbonyl compound, which suffers water elimination resulting in the formation of an enone.6a... 

From the temperature dependence of the substantial kinetic isotope effect (KIE) observed in the oxidation of diols to hydroxycarbonyl compounds by 2,2/-bipyridinium chlorochromate (BPCC), it is proposed that hydride transfer occurs in a chromate ester intermediate, involving a six-electron Hiickel-type transition state.9 A similar conclusion is drawn for the oxidation of substituted benzyl alcohols by quinolinium chlorochromate.10... 

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