Aldol type condensation of aldehydes

For synthetic purposes, aldol-type condensations of aldehydes with esters or amides are potentially of great utility because the carbonyl group is easily transformed either by further additions or by oxidation or reduction. Deprotonation of an ester [18, 19, 20] or amide of fluoroacetic acid [9, 21] has led to aldol condensations in high yields (equation 17) (Table 7)... 

Direct aldol-type condensations of aldehydes with ethyl diazoacetate to give /S-hydroxy-a-diazocarbonyl compounds, R-CH(0H)-C(=N2)-C02Et, are catalysed by tetrabutylammonium hydroxide.155... 

Scheme 7.13 Aldol-type condensation of aldehydes with TBS ketene acetals.

Table 7.4 Aldol-type condensation of aldehydes 1 with silyl ketenes 69a (r2 = H, R3 = Me), catalyzed by 60 (Scheme 7.13) [67].

Several a-btomo-a,/3-olefinic ketones and esters have been prepared by an interesting cleavage of S-acyl or )3-carbethoxy-a-ketolactones. It is unnecessary to isolate the bromolactone. Bromination and cleavage take place readily at 0-20° over-all yields are 60-85%. The /6-acyl and /6-catbethoxy-a-ketolactones are prepared by aldol-type condensations of aldehydes with the active methylene groups of ethyl )3-acetyl-pyruvate, CHjCOCHjCOCO CjHs, and ethyl oxalacetate,... 

The aldol type condensation of aldehydes with the o-position of enones can be achieved directly using... 

The aldol-type condensation of aldehydes and ketones with ketenimines and ketones can be catalyzed by titanium alkox-ides and, in appropriate cases, useful levels of stereocontrol can be achieved (eq 22). 

Demailly and coworkers195 found that the asymmetric induction increased markedly when optically active methyl pyridyl sulfoxide was treated with an aldehyde. They also synthesized (S)-chroman-2-carboxylaldehyde 152, which is the cyclic ring part of a-tocopherol, by aldol-type condensation of the optically active lithium salt of a,/3-unsaturated sulfoxide. Although the diastereomeric ratio of allylic alcohol 151 formed from lithium salt 149 and 150 was not determined, the reaction of 149 with salicylaldehyde gave the diastereomeric alcohol in a ratio of 28 72196. 

The heteroatom version of the vinylcyclopropane rearrangement serves to facilitate alkaloid construction. Scheme 13 outlines a strategy for the pyrrolizidine alkaloid isoretronecanol 211 90). Use of a carboxaldehyde (i.e. 213) as a synthon for the primary alcohol provides an ability to adjust stereochemistry. It also sets up formation of the pyrrolidine ring bearing the aldehyde by an aldol-type condensation of an enol of the aldehyde onto an imine derived from 214. Because of the lability of such systems, introduction of X=PhS imparts stability. The resultant azacyclopentene translates to an imine 215 using the iminocyclopropane rearrangement methodology. Simple condensation of the primary amine 216 with aldehyde 37a then initiates this... 

The methodology of the catalytic asymmetric aldol reaction has been further extended to the aldol-type condensation of (isocyanomethyl)phosphonates (12) with aldehydes, providing a useful method for the synthesis of optically active (l-aminoalkyl)phosphonic acids, which are a class of biologically interesting phosphorous analogs of a-amino acids (Scheme 8B1.6) [21,22], Higher enantioselectivity and reactivity are obtained with diphenyl ester 12b than with diethyl ester 12a (Table 8B1.6). 

It is interesting that aldol-type condensation of tosylmethyl isocyanide (16) with aldehydes is catalyzed by the silver catalyst more stereoselectively than that catalyzed by the gold catalyst under the standard reaction conditions (Scheme 8B1.9) [26], Elucidation of the mechanistic differences between the gold and silver catalysts in the asymmetric aldol reaction of 16 needs further study. Oxazoline 17 can be converted to optically active a-alkyl-p-(A-methyl-amino)ethanols. 

Chiral lactones. The aldol type condensation of this reagent with an aldehyde has been used to synthesize two chiral five- and six-membered lactones in > 80% ee. The synthesis of the six-membered lactone (R)-( + )-d-n-hexadecanolactone (5), a pheromone of the Oriental hornet, from the /-butyl ester (1) of the sulfoxide is formulated in equation (I).1... 

Scheme 33 MgBr2/Et3N-promoted aldol-type condensation of a 6-bromopenem with aldehydes.

Nitroalkanes having an a-hydrogen atom undergo aldol-type condensation with aldehydes and ketones in the presence of a base to give p-hydroxy nitro compounds or nitroethylene compounds. The reaction is known as the Henry reaction " or nitroaldol reaction. 

Aldol-Type Condensation. The aldol-type condensation of the enolate anion of sulfinylpropionate, which was prepared as usual with the base t-butylmagnesium bromide, with aldehydes afforded after desulfurization with Aluminum Amalgam the corresponding 3-hydroxy esters in high yield (90%) and, with aliphatic aldehydes, high diastereoselectivity (eq 3). The amount of asymmetric induction was determined by transformation of the 3-hydroxy esters to the corresponding isopropyl-substituted alcohols. 

General Discussion. Aldol-type condensation of the magnesium enolate of (R)-(+)-phenyl (p-toluenesulfinyl)acetate, prepared with f-butylmagnesium bromide, with the aldehyde precursor of maytansine afforded, after desulfurization with Aluminum Amalgam, the desired 4,5-unsaturated 3-(5)-hydroxy ester in high yield and high diastereoselectivity (eq 3). ... 

Aldol-iype Condensation. Aldol-type condensation of the lithium enolate of ethyl (/ )-(p-tolylsulfinyl)-A-methoxy-acetimidate (prepared with n-Butyllithium) with aldehydes affords, after desulfurization with Raney Nickel, P-hydroxy esters with high enantioselectivity (eq 2). ... 

The enhanced activity of alkyl groups attached to the pyrazine nucleus is illustrated by methylpyrazine, which undergoes aldol type condensations with aldehydes and ketones. Methylpyrazine (14) formed an adduct (IS) with chloral in pyridine solution (405) with paraformaldehyde at 165°, it gave 2-hydroxyethylpyrazine (470) (which was subsequently dehydrated with molten potassium hydroxide to 2-vinylpyrazine) and with benzophenone and sodamide it gave the corresponding carbinol (705). 

Aldol-type condensation of chiral a-sulfinyl hydrazones with aldehydes also provides a route leading to chiral 3-hydroxy ketones. - This is exemplified by the synthesis of (-)-(/ )-[6]-gingerol (98 equation 24). ... 

Gardner and co-workers found Triton B a superior catalyst for the aldol-type condensation of aromatic aldehydes with ethylidenemalonic esters, one step in a new synthesis of benzosuberones. 

Henry reaction. Formation of nitroalcohols by an aldol-type condensation of nitroparaffins with aldehydes in the presence of base (Henry) or by the condensation of sodium salts of aci nitroparaffi ns with the sodium bisulfite addition products of aldehydes in the presence of a trace of alkali or weak acid (Kamlet). Widely used in sugar chemistry. 

Aldol-type condensation of enol silyl ethers and acetals or orthoesters can be accontplished by the use of trimethylsilyl trifluoromethanesulfonate (TMSOTf). In these reactions, TMSOTf acts as a true catalyst and is required in 1-S ntol %. The reactions show interesting chemoselectivity in that acetals are highly reactive receptors of enol silyl ethers but the parent aldehydes and ketones do not react under these conditions (Scheme 37). Similarly, trityl perchlorate is found to be an efficient catalyst to promote the reaction between enol silyl ethers and acetals. 

The pinwheel shape of a f-butyl propionate derived silylketene acetal (see Section 2.4.2.1) was revealed by a single-crystal X-ray diffraction analysis. Several different catalysts were reported to promote the aldol-type condensation of alkyl enol ethersand silyl enol ethers with aldehydes, acetals and various other electrophiles. In some cases the reaction proceeded with high simple stereoselection. The mechanism of the Lewis acid mediated additions to acetals (see Section 2.4.2.3) was investigated in detail, as well as the uncatalyzed aldol reaction of silyl enol ethers with aldehydes promoted by the hydrophobic effect (see Section 2.4.2.1). 

This route depends on the samarium-catalysed aldol-type condensation of nitroalkanes with imines generated from amines and aldehydes, all three components being... 

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