Retroaldol/aldol reactions

The synthesis started with the known hydrindenone derivative, 154 (Scheme 15) (177). Surprisingly, the group transformation of the secondary alcohol to the cyanide 155 via the tosylate occurred under retention of configuration in 64% yield. The authors were able to exclude a retroaldol-aldol reaction sequence as the reason for the unusual stereochemistry but did not further elaborate. To form the annelated pyrrolidinone, the enone was chemo- and stereoselectively reduced by... 

A stereoselective intramolecular aldol reaction of thiazolidinecarboxylate (39) proceeds with retention of configuration to give fused heterocycles (40a,b separable) and (41), the product of a retroaldol-acylation reaction. The selectivity is suggested to be directed by self-induced axial chirality, in which the enolate generated in the reaction has a stereochemical memory, being generated in an axially chiral form (42). The retroaldol step also exemplifies a stereoretentive protonation of an enolate. 

Direct aldol reactions on building block 49 appear to be much more straightforward, but are problematic because of the retroaldol problem. Nevertheless, two successful non-basic methods... 

An example of a retrograde aldol reaction (retroaldolization) is probably the pyrolytic decomposition of cellulose with formation of hydroxyacetaldehyde (see Section 7.2), Other mechanisms for pyrolysis of cellulose are also possible [3]. More paths for the same process is a common occurrence in pyrolysis, and more than one mechanism is frequently needed to explain the variety of reaction products. 

The use of lanthanide metal enolates in the aldol reaction has, to date, only been developed to a synthetically useful level in the case of cerium (Scheme S and Table 7). Stereoselectivities are no better than those of lithium enolates, but the cerium enolates of ketones woik well in crossed aldol additions to ketones (Table 7, entries 1-7) and sterically hindered aldehydes (Table 7, entries 9 and 10). Such crossed aldol reactions do not often work well with lithium enolates as enolate equilibration, retroaldolization and steric retardation of addition occur. Imamoto et al. have shown that cerium enolates (44), formed from anhydrous CeCb (1.2 equiv.) and the preformed lithium enolates of ketones in THF at -78 C, undergo such aldol reactions to give the corresponding p-hydroxy ketones (46), usually in high yield. The cerium suppresses the retroaldol reaction by efficient chelation of the aldolate (45). A similar effect is known for zinc halide mediated aldol reactions (Volume 2, (Chapter 1.8). The stereoselectivity of the... 

Besides the cleavage of C-T/C-2 bond of the substrate, the DHNA of E. coli can also catalyze the epimerization of the 1 position of dihydroneopterin. That reaction is believed to proceed through bond cleavage followed by religation, that is, a retroaldol/aldol mechanism. ... 

The general class of enzymes catalyzing aldol or retroaldol condensation reactions are the aldolases (Table VI) (156-161). In principle, there are four possible stereochemical routes to product depending on whether C-C bond formation involves retention or inversion of configuration at the methyl or methylene carbon atom a to the ketonic carbonyl (Eq. (30)] ... 

In contrast to phase-transfer catalytic allgrlation, aldol reactions are somewhat less common because it is difficult to control more than one concurrently generated stereocentre, and the retroaldol reaction leads to low chemical yields. In 1991, the first catalytic asymmetric synthesis of P-hydrmg -a-amino acids via aldol condensation under PTC reaction conditions in the presence of catalyst 7a was reported by the Miller group. The moderately optically enriched diastereomeric aldol adducts 77 obtained from heptanal and 5 were derivatised to 78 (Scheme 16.23). °... 

The versatile reactivity of the minor isomer 13 has been further explored by Fleet s group. When the azide is reduced and the acetal removed, dte resulting amino compound 17 presumed to be less susceptible to reversible aldol reaction) is opened to give the anticipated 18, but a minor product 19 is obtained via reversible aldol cleavage of the C2-C3 bond. The isomeric amino compound 20 undergoes lactone hydrolysis to 16 and 21, with 21 as the major product derived from retroaldol-reclosure (Scheme 4). 

Scheme 87.3 Suggested mechanisms for the IspC reaction, (a) Stepwise retroaldol-aldol mechanism, (b) concerted a-ketol-iearrangement mechanism, and (c) postulated mechanism for the enzymatic formation of the DXP epimer 18...

Retinal pigment epithelium (RPE), 3925, 3927-3929, 3937, 3939 3941, 3943-3947 Retinoids, 2675, 2695 Retinol, 3369 Retinopathy, 1450 Retroaldol-aldol mechanism, 2700 Retrochalcones, 1869, 1874, 1875 Retrograde amnesia, 292 Retronecine, 1058, 1064 Retro-Prince reaction, 3075, 3076 Retrorsine, 1061, 1063, 1385 Reversed phase... 

C. Schwarzinger, On the mechanism of thermally assisted hydrolysis and methylation of carbohydrates the contribution of aldol and retroaldol reactions, J. Anal. Appl. Pyrol., 68 69, 137 149 (2003). 

Diastereomer ratios were determined by gas chromatography. Since the aldol adduct undergoes retroaldol reaction on the column, it must be silylated prior to injection. Approximately 5 mg of the crude adduct is filtered through a short plug of silica gel to remove any trace metals. The material is taken up into 1-2 mL of dichloromethane in a 2-raL flask or small test tube. To this solution are added 4-5 drops of N,N-diethyl-1,1,1-trimethylsilylamine and a small crystal of 4-(N,N-dimethylamino)pyridine (Note 11), The solution is stirred for 2 hr and injected directly onto the column. (Column conditions 30 m x 0.32 mm fused silica column coated with OB 5, 14 psi hydrogen carrier gas, oven temperature 235°C). 

Formulate this reaction as a reversal of an aldol condensation (retroaldol condensation). ... 

Knowledge of the Maillard reaction is being extended very actively in many different ways. The participation of free radicals has already been dealt with in Chapter 2 and work on colour and flavour aspects is being deferred to Chapters 4 and 5, respectively. This chapter deals with a number of relatively disparate topics, namely, the effects of pH, high pressure, 7g, and the use as reactants of amines other than amino acids, of lipids, and of oligo- and polysaccharides, as well as the determination of a-dicarbonyl intermediates, control of aldol/retroaldol reactions, fluorescence, kinetic aspects, and sites of protein glycation. 

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