Aldol reactions direct small-molecule

McMillan and co-workers [146] have reported the first example of direct enantioselective aldehyde-aldehyde cross-aldol reaction using small molecules as catalysts. Subsequently, they have described the enantioselective dimerization and cross-coupling of a-oxygenated aldehydes to provide eiythrose architecture. A second L-proline-catalyzed aldol reaction generates hexoses (O Scheme 22) [147]. 

Direct Small-molecule-Catalyzed Asymmetric Aldol Reactions Enzymes can catalyze the reaction of unactivated carbonyl donors with aldehyde acceptors. 

Luo, Z.-B., Dai, L.-X. Novel small organic molecules for a highly enantioselective direct Aldol reaction. Chemtracts 2003, 16, 843-847. 

Highly enanttoselecitve direct aldol reaction catalysed by a novel small organic MOLECULE... 

HIGHLY ENANTIOSELECTIYE DIRECT ALDOL REACTION CATALYSED BY A NOVEL SMALL ORGANIC MOLECULE... 

Class II aldolase mimics (Scheme 10.4) were the first small-molecule catalysts that were reported for the direct intermolecular aldol reaction. These catalysts are characterized as bimetallic complexes that contain both Lewis acidic and Brpnsted basic sites. Shibasaki et al. first reported on the use of such a catalyst in the aldol reaction in 1997, demonstrating its potential with the reaction of various acetophenones 52 and aldehydes 53 (Scheme 10.13). Aldols 55 were obtained in good yields and enantioselectivities. A similar approach was used in the direct catalytic asymmetric aldol-Tishchenko reaction.Nevertheless, for the moment, this method does not provide access to true polypropionate fragments. ... 

Small-molecule-Catalyzed Asymmetric Aldol Reactions with Preformed Enol Ethers The methodologies of intermolecular direct asymmetric aldol reactions still tend to give mediocre results when enolizable carbonyl compounds are used. Even if current indirect small-molecule-catalyzed aldol reactions all require preactivation... 

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. 

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