Cyclohexanone crossed aldol reaction

It is thus possible to look at a molecule such as A below and recognize that it is a ft-hydroxy ketone and thus could be formed in a crossed-aldol reaction between enolate B and aldehyde C. Likewise D could potentially be produced by dehydration of the aldol product of cyclohexanone... 

Draw the product of the crossed aldol reaction between furfural and cyclohexanone and the product formed by its base-catalyzed dehydration. 

Direct asymmetric cross-aldol reactions of ketones with aromatic aldehydes proceed in the presence of an l-proline-derived tertiary diamine and additives using water as a solvent (Scheme 26). L-Proline-derived diamines give racemic product in the absence of an acid cocatalyst. While trifluoroacetic acid (TFA) is the most effective additive for the aldol addition of cyclohexanone to 4-nitrobenzaldehyde in the presence of L-proline-derived diamine, addition of scandium triflate is also effective for the reaction with similar enantioselectivity. 

On the other hand, a number of asymmetric aldol reactions have been performed in the last year in the presence of variously substituted prolines as the organocatalysts. As an example, Zhao et al. reported excellent results for the cross-aldol reaction of cyclohexanone with p,y-unsaturated keto esters catalysed by a tra i-siloxy-L-proline (Scheme 2.3). This practical and highly efficient protocol could be extended to other ketones, albeit with lower enantioselectivities (<93% ee). 

Cross-aldol reactions of cyclohexanone with P,y-unsaturated keto esters catalysed by trans-siloxy-L-proline. 

Pioneering work in this field has been independently reported based on two distinct strategies. Designed small diamine catalyst 54 (10mol%) in the presence of trifluoroacetic acid in an emulsion system catalyzes the direct cross-aldol reaction of cyclohexanone (51, 2 equiv.) with p-nitrobenzaldehyde (52) in bulk water (111 equiv.), giving the anti-aldol product 53 in quantitative yield with 94% ee... 

The aldol reaction is synthetically useful because it forms new carbon-carbon bonds, generating products with two functional groups. Moreover, the P-hydroxy carbonyl compounds formed in aldol reactions are readily transformed into a variety of other compounds. Figure 24.3 illustrates how the crossed aldol product obtained from cyclohexanone and formaldehyde (CH2=0) can be converted to other compounds by reactions learned in earlier chapters. 

Dibenz[c,e]azepine salt (57) - derived fromfranj-l,2-diaminocyclohexane -promotes highly diastereo- and enantio-selective crossed-aldols of cyclohexanone and aromatic aldehydes. Chiral l-amino-2-sulfonamidocyclohexanes catalyse syn-aldols of benzaldehydes and hydroxyacetone. A chiral l°-3° diamine promotes 0 aldol reactions of acetone and -unsaturated a-ketoesters in yields up to 99% and (g) ees up to 96%. ... 

The other two unenolizable esters we mentioned on p. 728 undergo cross-condensations with ketones. Unlike formaldehyde, formate esters are well behaved—no special method is necessary to correspond with the Mannich reaction in aldol chemistry, Here is what happens with cyclohexanone. 

Reduction. The familiar preparation of pentaerythritol from acetaldehyde and formaldehyde involves aldolization and crossed Cannizzaro reduction. In the same way, cyclohexanone reacts with 5 moles of formaldehyde to give the pentaol (3). The reaction is conducted by adding calcium oxide (1,25 moles) to a stirred mixture O OH... 

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