Small-molecule compounds aldol reactions

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... 

Condensations are some of the most important enolate reactions of carbonyl compounds. Condensations combine two or more molecules, often with the loss of a small molecule such as water or an alcohol. Under basic conditions, the aldol condensation involves the nucleophilic addition of an enolate ion to another carbonyl group. The product, a /3-hydroxy ketone or aldehyde, is called an aldol because it contains both an aldehyde group and the hydroxy group of an alcoho/. The aldol product may dehydrate to an a,/3-unsaturated carbonyl compound. 

The influence of inorganic compounds on polysaccharide pyrolysis has been extensively investigated. More detailed information is further provided in connection to the description of pyrolysis of each polymeric carbohydrate. As a general rule, inorganic compounds increase the formation of small molecules generated in pyrolysis, thereby reducing the number of larger molecules that would provide better structural information. In Py-MS, addition of KOH to the initial polysaccharide results in a loss of information. Also addition of calcium ions (as CaCb) increases the decarboxylation. At the same time retro-aldolization reactions are diminished. 

A number of combinatorial-based syntheses have been reported. Andrus et al. prepared a solution-phase indexed combinatorial library of nonnatural polyenes such as 291 for multidrug resistance reversal.298 This library was formed by modification of R and R. Ellman and co-workers reported a combinatorial library of synthetic receptors targeting vancomycin-resistant bacteria,209 and Paterson et al. prepared polyketide-type libraries by iterative asymmetric aldol reactions on solid support.2l0 Rieser et al. used combinatorial liquid-phase synthesis to prepare [1,4]-oxazepine-7-ones by the Baylis-Hillman reaction (see sec. 9.7.B).2H Schreiber and co-workers reported the synthesis and evaluation of a library of polycyclic small molecules for use in chemical genetic assays.2 2 Bauer et al. reported a library of N-substituted 2-pyrazoline compounds... 

Contrary to some reports, electrophilic addition reactions may occur in other multiple-bond systems. In many of the reactions of aldehydes and ketones the first stage involves the addition of some entity across the carbon-oxygen bond, e.g., the formation of oximes, semicarbazones, hydrazones, hydrates (1,1-diols) and their ethers, and the aldol condensation. Most of these reactions entail a subsequent loss (elimination) of a small molecule e.g. water, ammonia, ethanol) and, while one must be careful to determine whether the rate-determining stage involves attack on the carbonyl compound or elimination from the adduct , there are some systems in which it is evident that electrophilic attack is involved in the slow stage of the reaction sequence. Examples of such reactions are the acid-catalysed formation of oximes of aliphatic - and aromatic carbonyl compounds, of furfural semi-carbazone , and of 1,1-diols from aldehydes or ketones . 

In acid, a second reaction, the dehydration of the p-hydroxy carbonyl compound to the a,P unsaturated aldehyde or ketone is very common, and it is generally the dehydrated products that are isolated (Fig. 19.69). In the overall reaction, two carbonyl compounds condense to produce a larger carbonyl compound and give off a small molecule— water in this case. Thus, the aldol reaction is often called the aldol condensation. 

Reviews have featured recent applications of organocatalysts to asymmetric aldol reactions, including particular focus on catalysis by small molecules. The effects of introduction of a diaryl (oxy)methyl group into chiral auxiliaries, catalysts, and dopants have been discussed and applications of amidine-, isothiourea-, and guanidine-based nucleophilic catalysts for a range of reactions of carbonyl compounds have been highlighted. " ... 

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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