Multifunctional aldehydes

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. 

The DKR of functionalized alcohols such as diols, hydroxy esters, hydroxy aldehydes, azido alcohols and hydroxy nitriles was also taken up as the synthetic uhlity of the products is very high besides such a study will bring out the effect of multifunctional substrates under these reaction conditions to broaden the scope of DKR. Initially, the DKR of diols was achieved with diruthenium catalyst 1... 

As shown in Scheme 8-49, this multifunctional catalyst can be applied in direct aldol reactions between an aldehyde R CHO and a ketone R2COCH3."... 

Some successful attempts to immobilize catalysts for the oxidation of alcohols to carbonyl compounds involve the attachment of TEMPO-derivatives to a solid phase. Bolm et al. were the first to immobilize l-hydroxy-2,2,6,6-tetramethylpiperi-dine to modified silica gel (SG-TMP-OH) (11) and applied in the oxidation of multifunctional alcohols [68]. Other groups further investigated the use of polymer-supported TEMPO [69]. This system allowed the oxidation of alcohols to aldehydes and ketones, respectively, using bleach to regenerate the immobilized ni-troxyl radical (Scheme 4.6). 

Multifunctional acids containing a carbonyl group such as pyruvic acid [CH3C(0)C00H] are typically measured using the derivatization techniques used for aldehydes and ketones, such as the DNPH method (e.g., see Lee et al., 1995). 

The syntheses of dithioacetals are generally straightforward [43]. Standard methods may be unselective for multifunctional molecules. Therefore, new procedures have been developed. It has thus been reported that 1,3-dithianes are readily synthesized by reaction of aldehydes, ketones or acetals with 2-stanna-l,3-dithianes under catalysis of organotin triflates [45]. These odourless reagents are prepared from dialkyldichlorotin and 1,3-propanedithiol. 

A range of methods has been developed for the protection of the carbonyl group in multifunctional aliphatic and alicyclic aldehydes and ketones. This has been necessary because in many multistage syntheses, modification of other functionalities (e.g. oxidation, reduction, hydrolysis, nucleophilic and electrophilic additions and displacements, etc.) requires a differing range of experimental conditions, and that protective group must be selected which is stable in the presence of the reaction medium. A further feature that should be noted is that... 

The asymmetric catalytic nitroaldol reaction, also known as the asymmetric Henry reaction, is another example of an aldol-related synthesis of high general interest. In this reaction nitromethane (or a related nitroalkane) reacts in the presence of a chiral catalyst with an aldehyde, forming optically active / -nitro alcohols [122], The / -nitro alcohols are valuable intermediates in the synthesis of a broad variety of chiral building blocks, e.g. / -amino alcohols. A highly efficient asymmetric catalytic nitroaldol reaction has been developed by the Shibasaki group, who used multifunctional lanthanoid-based complexes as chiral catalysts [122-125],... 

Bronsted base [the lithium binaphthoxides] and of a Lewis acid [La(UI)] sitting side by side at the heart of the LLB multifunctional catalyst evokes the active site of aldolases and probably explains why simple unmodified ketones and primary aldehydes can be used504. The examples in Scheme 132 illustrate the performance of this system612. 

A wide array of compounds undergo the Nef reaction. These include simple nitro compounds, as well as complex multifunctional species. For example, the carbohydrate in equation (2) was isolated as its hy-drazone derivative in 72% yield. Nitronate anions generated in situ can be acidified to give good yields of aldehydes and ketones. As an illustration, Michael addition of the dianion of hexanoic acid to 2-nitro-propene gives the expected keto acid after acidification (equation 3). ... 

Another atom-efficient process that has been studied solvent free is the Baylis-Hillman reaction.This reaction affords useful multifunctional products from an addition reaction between an electrophile (often an aldehyde) and an electron-deficient olefin. Unfortunately, under most conditions it has the significant drawback of a slow rate of reaction. However, this has been overcome through a solvent free approach that uses a high-speed ball mill (HSBM) (Figure 2.9). Previous solvent free studies of this reaction took 3-4 days to achieve completion. In contrast, using an HSBM, the reaction is complete in 30 min. Unfortunately, a chlorinated solvent was chosen for reaction work up clearly, it would be desirable to use a less hazardous VOC here. 

The Dess-Martin oxidation of alcohols has proven to be an efficient method for the conversion of primary and secondary alcohol to aldehydes and ketones, respectively. The rate of oxidation is markedly accelerated in the presence of water. The oxidation proceeds under mild reaction conditions and is especially suitable for multifunctional substrates containing acid-sensitive groups, as exemplified below. 

Functionalized allylic systems are not only often part of target molecules but also have potential as versatile synthetic intermediates. They can frequently be used to generate multifunctional compounds by further elaboration of the C=C bond, namely by reduction (e.g. hydrogenation) or oxidation (e.g. to alcohols, diols, oxiranes, aldehydes or ketones) or by diverse addition reactions. As such reactions can very often be performed with remarkable stereocontrol by means of the allylic functionality, especially in intramolecular reactions, the potential of functionalized allylic systems is immense. 

If progesterone is directly acted on by 2l-hydroxylu.se (Cyp21). 11 -deoxycorticosterone is produced, a precursor lo the mineralocorticoid aldosterone. In tissues where aldosterone is synthesized, the multifunctional enzyme aldosterone synthase (Cypl IB2) mediates the hydroxylalion at Cl i as well as the two-step oxidation ofCIS lo an aldehyde, providing aldo.sicronc. which exists predominantly in the cyciic hcmiacclal form. 

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