Ketones hydroxycarbonyl compounds

Unsaturated Aldehydes and Ketones.— -Hydroxycarbonyl compounds are commonly-considered precursors to o -unsaturated aldehydes and ketones. However, simple aldol reactions often may not be appropriate for the construction of particular enones. Isoxazolines offer ever more attractive routes to hydroxy-ketones, and hence enones, as their chemistry continues to be explored. The... 

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... 

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. 

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. 

A retrosynthetic analysis of an a,/J-unsaturated aldehyde or ketone involves an initial functional group interconversion into a /1-hydroxycarbonyl compound, followed by a disconnection into the carbocation (12) and the carbanion (13) synthons. The reagent equivalents of these two synthons are the corresponding carbonyl compounds. 

The Morita-Baylis-Hillman (MBH) reaction is the formation of a-methylene-/ -hydroxycarbonyl compounds X by addition of aldehydes IX to a,/ -unsaturated carbonyl compounds VIII, for example vinyl ketones, acrylonitriles or acrylic esters (Scheme 6.58) [143-148]. For the reaction to occur the presence of catalytically active nucleophiles ( Nu , Scheme 6.58) is required. It is now commonly accepted that the MBH reaction is initiated by addition of the catalytically active nucleophile to the enone/enoate VIII. The resulting enolate adds to the aldehyde IX, establishing the new stereogenic center at the aldehydic carbonyl carbon atom. Formation of the product X is completed by proton transfer from the a-position of the carbonyl moiety to the alcoholate oxygen atom with concomitant elimination of the nucleophile. Thus Nu is available for the next catalytic cycle. 

Another nucleophilic addition involving a charged nucleophile is the Aldol reaction. This involves the nucleophilic addition of enolate ions to aldehydes and ketones to form p-hydroxycarbonyl compounds ... 

In principle it also is possible to obtain the /3-hydroxycarbonyl compounds directly in neutral form rather than in form of their alkoxides (Figure 13.44, bottom). This is accomplished by the reaction of one carbonyl compound or of a mixture of two carbonyl compounds with a catalytic amount of MOH or MOR. Aldehyde enolates and ketone enolates are then formed in small amounts (see the Rule of Thumb at the beginning of Section 13.1.2). These enolates add to the C=0 double bond of the starting substrate molecules or, if a mixture of carbonyl compounds is employed, they add to the C=0 double bond of the more reactive of the carbonyl compounds. The alkoxides B of the aldol adducts are formed initially but are converted immediately and quantitatively into the aldols by way of protonation. 

It is for good reason that the bulky ketone substituent of enolate A contains a Me3SiO group, which is carried on into the. syw-configured aldol adduct its acid-catalyzed hydrolysis affords an OH group in the a-position of the C=0 double bond. Such an a-hydroxycarbonyl compound can be oxidatively cleaved with sodium periodate to afford a carboxylic acid (cf. Section 9.1.1). The mechanism of this oxidation is described later in connection with Fig-... 

Cyclobutanols oxidize with ring cleavage to 4-hydroxy ketones, 4-hydroxy acids, or 1,4-diones under the influence of chromium(Vl) reagents (Scheme 11). The first formed product is a 4-hydroxycarbonyl compound (31) which exists as the five-membered ring hemiacetal (32). This form will persist in the absence of excess reagent under nonforcing conditions otherwise further oxidation takes place to give a... 

Merino P, Tejero T. Organocafalyzed asymmefric a-aminoxyla-tion of aldehydes and ketones—an efficienl access to enanfiomer-ically pure a-hydroxycarbonyl compounds, diols, and even amino alcohols. Angew. Chem. Inf. Ed. 2004 43 2995-2997. 

Here, the name aldol refers to a /3-hydroxycarbonyl compound which is derived from the nucleophilic additions between enol (or enolate) 13 and ketone (or aldehyde) 14 (O Scheme 5). Sugars, as the chiral polyhydroxy aldehyde or ketone compounds, are natural substrates for these reactions. 

Eliel has extensively studied the 1,3-oxathiane systems (55) as a chiral auxiliary to control the addition of organometallics to ketones (Scheme 3). Following nucleophilic addition, cleavage of the oxathiane group generates chiral a-hydroxycarbonyl compounds (58). The wide variety of carbonyl substituents, as well as Grignard reagents, amenable to this process is illustrated in Table 14. The enantiomeric auxiliary is available, and affords alcohols of opposite chirality in equivalent yields. 

Aldol reaction Addition of an enol/enolate of a carbonyl compound to an aldehyde or ketone to form a (J-hydroxycarbonyl compound. 8... 

The F-alkyl ketone enolates were readily prepared by dephosphorylation of the corresponding 1-substituted F-l-aUcenyl phosphates with DIBAL at 0°C for a few minutes (Scheme 6.29) [50]. The resulting diisobutylaluminum enolate undergoes aldol reaction with benzaldehyde to give fhe -hydroxycarbonyl compound in a reasonable yield. 

The direct asymmetric aldol reaction between unmodified aldehydes and ketones plays an important role in nature as a source of carbohydrates and it is used for the synthesis of chiral p-hydroxycarbonyl compounds. This reaction was performed by using (5)-proline/poly-(diallyldimethylammonium) hexafluorophosphate heterogeneous catalytic system 36. The catalyst was simply prepared by mixing a suspension of the commercially available polyelectrolyte 34 in methanol with a solution of (,S )-prolinc (35) in the same solvent (Scheme 3.11). 

The 2-sulfonyloxaziridine (57) is a more selective oxidant than peracids. The reagent has been employed in the oxidation of sulfides to sulfoxides, disulfides to thiolsulfinates, selenides to selenoxides, thiols to sulfenic acids, organometallic reagents to alcohols and phenols, ketone and ester enolates to a-hydroxycarbonyl compounds (equation 31)41. The oxidation of chiral amide enolates gives optically active a-hydroxy carboxylic acids with 93-99% enantiomeric excess42. 

Route I leads via the retrosynthetic operations a and b to the or-acylamino carbonyl system 2. This suggests NH3 or a primary amine as starting materials. According to route II, addition of H2O (c) leads to intermediate 1 which can be further dissected in line with the usual retroanalytical scheme. Route d points to an or-halo- or a-hydroxycarbonyl compound and amidine, whereas route e suggests an a-amino ketone and acid amide or nitrile as starting materials. 

The required cr-amino aldehydes or ketones are usually prepared in situ because of their instability. They are obtained from a-hydroxycarbonyl compounds and ammonium acetate or by catalytic reduction of (3r-hydroxyimino- or or-azido-carbonyl compounds. 

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