Retro-aldol condensation

In systems which preclude retro-aldol condensations, benzilic acid rearrangement of 11,12-diketones affords normal C-norsteroids in fair yields. For example, 11,12-diketotigogenin (82) is converted to the C-nor-(5oc,9(, 22a)-spirostane (83) in 65 % yield by barium oxide in boiling aqueous methyl-cellosolve. ... 

Trimethylsilyl cyanide. This reagent readily silylates alcohols, phenols, carboxylic acids, and, more slowly, thiols and amines. Amides and related compounds do not react with it. The reagent has the advantage that a volatile gas (HCN is highly toxic) is the only by-product. In the following case, the use of added base resulted in retro aldol condensation ... 

The first step in the nonreversible degradation reactions is the formation of a reactive a-dicarbonyl species through the p-elimination of a hydroxide ion. The subsequent reaction pathways to all degradation products can be described by just five reaction types, namely, p-elimination, benzilic acid rearrangement, a-dicarbonyl cleavage, aldol condensation, and retro-aldol condensation (see Fig. 7).31 Retro-aldol condensation and a-dicarbonyl cleavage involve C-C bond... 

For explanation, the example 8 of Fig. 5 is again used (Fig. 7). The essential features of an aldol condensation in its retro-form are the breaking of a CC- and of an OH-bond, and the making of a CO- and of a CH-bond. Alternatively, if this process is considered in an even more general manner, two bonds between atoms I, J and K, L are broken and two new ones between the four atoms involved are made. 

Three-cmbon ring expansionThe cyclic p-keto esters 1 with a 4-oxopentyl group at the a-position do not undergo the expected aldol condensation on treatment with KOC(CH3)3 in DMSO, but undergo ring expansion to medium-size ketones (2). The reaction may involve aldol and retro-aldol condensation. A similar... 

Originally, the term aldol condensation referred specifically to the reaction of an aldehyde (having an a-hydrogen) with an aldehyde/ketone to form a j8-hydroxy aldehyde (the aldol). The reverse reaction is often referred to as a retrograde aldol reaction, a retro-aldol condensation (or reaction), or an aldol cleavage. March categorizes aldol condensations into five classes. The first is condensation between two identical aldehydes... 

Figure 1. Kinetic parameters for the selection of antibody-catalyzed aldol and retro-aldol reactions, reflecting the biocatalyst s ability to accept substrates that differ clearly with respect to their molecular geometry. No background reaction was observed for the self-condensation of cyclopentanone. The indicated value for cyclopentanone addition to pentanal was estimated using the published kuncat value of 2.28 X 10 M s for the aldol addition of acetone to an aldehyde. Reproduced with permission of the authors and the American Association for the Advancement of Science.

Intermediate I contains the tricyclic skeleton of longifolene, shorn of its substituent groups, but containing carbonyl groups suitably placed so that the methyl groups at C-2 and C-6 and the C-ll methylene can eventually be introduced. The retro synthetic step I = II corresponds to an intramolecular aldol condensation. However, II clearly is strained relative to I, so II (with OR=OH) should open to I. 

An Oppenauer reaction produces the selective oxidation of a secondary alcohol, leading to a (3-hydroxyketone that suffers a retro-aldol condensation under the basic reaction conditions, resulting in the evolution of formaldehyde. 

The synthetic method (a) is the regioselective reduction of an a,/ -unsaturated aldehyde or ketone (Section 5.18.2, p. 798), which is most conveniently effected by the Meerwein-Ponndorf-Verley procedure (Section 5.4.1, p. 520). The further disconnection shown of the a, -carbonyl compound is a retro-aldol condensation (Section 5.18.2, p. 799) however it should be emphasised that other routes to the unsaturated carbonyl compound, such as the Horner-Emmons reaction (Section 5.18.2, p. 799), may also be feasible. 

The carbon alpha to the carbonyl of aldehydes and ketones can act as a nucleophile in reactions with other electrophilic compounds or intermolecu-larly with itself. The nucleophilic character is imparted via the keto-enol tau-tomerism. A classic example of this reactivity is seen in the aldol condensation (41), as shown in Figure 23. Note that the aldol condensation is potentially reversible (retro-aldol), and compounds containing a carbonyl with a hydroxyl at the (3-position will often undergo the retro-aldol reaction. The aldol condensation reaction is catalyzed by both acids and bases. Aldol products undergo a reversible dehydration reaction (Fig. 23) that is acid or base catalyzed. The dehydration proceeds through an enol intermediate to form the a,(3-unsaturated carbonyl containing compound. 

The formation of monohydroxy acids having chains of four, three, or two carbons can be rationalized with the same mechanism of oxidation of the corresponding enediol. The 1,2-enediol can rearrange to the 2,3- or 3,4-enolates, which undergo the oxidative cleavage. Alternatively, the enediol may undergo a retro-aldol condensation followed by oxidation. 

Figure 2. Mechanism for the Formation of 2-Pentenal, Propanal, 2-Propanone and Ethanal from the Thermal Degradation and Retro-Aldol Condensation of Linolenic Acid.

The alkadienals could be formed from the autoxidation of PUFA and may contribute desirable arenas to freshly prepared foods (19). Further degradation of alkadienals often increased undesirable flavors. Josephson and Lindsay demonstrated that 2,4-decadienal could produce 2-octenal and ethanal (20) and 2,6-nonadienal could produce 4-heptenal and ethanal (21) via retro-aldol condensation mechanisms. Hsieh et al. (22) reported that iscmers of various alkadienals and alkatrienals gave green, greasy and oxidized fish oil odors in crude menhaden fish oil. 

Although attempts to catalyze bimolecular aldol condensations without resorting to enamine chemistry have not yet been successful, the Schultz group92 has prepared an antibody against the phosphinate hapten 115 that catalyzes the retro aldol reaction of 116 (kcJKm = 125 M-1 s l). The equilibrium in this case strongly disfavors the condensation product, and a histidine induced in response to the phosphinate may be involved in catalysis. Interestingly and in contrast to the previous examples, the stereoselectivity of the antibody is modest. The syn diastereomer of 116 was found to be the better substrate for the antibody by 2 1 over the anti diastereomer, but no evidence of enantioselectivity was observed. 

B as an ester- or lactone-substituted aldehyde enolate. Such enolates undergo condensations with all kinds of aldehydes, including paraformaldehyde. An adduct E is formed initially, acy-lating itself as soon as it is heated. The reaction could proceed intramolecularly via the tetrahedral intermediate D or intermolecularly as a retro-Claisen condensation. In both cases, the result is an acyloxy-substituted ester enolate. In the example given in Figure 13.50, this is the formyloxy-substituted lactone enolate C. As in the second step of an Elcb elimination, C eliminates the sodium salt of a carboxylic acid. The a,/)-unsaturated ester (in Figure 13.50 the 0J,/3-unsaturated lactone) remains as the aldol condensation product derived from the initial ester (here, a lactone) and the added aldehyde (here, paraformaldehyde). 

In the case of (11), retrosynthetic functional group interconversion into the aldol followed by disconnection of the a, /J-bond gives the dipolar synthon (15), of which the reagent equivalent is the 1,4-dicarbonyl compound, hexane-2,5-dione (i.e. a retro-aldol condensation). The action of base on this diketone effects the forward aldol reaction followed by spontaneous dehydration (see Expt 7.4 for formulation). 

The mechanism of Step 4 involves a retro-aldol condensation reaction on the open-chain form of D-fructose 1,6-bisphosphate. This reaction, and the origin of the carbon atoms in the products, is shown below. 

The decomposition or retro aldol condensation of 2-nitro alcohols, as described in Scheme 9.2, has often been observed in the hydrogenation over Raney Ni in neutral or basic medium. The hydrogenation of (1-nitro-l-cyclohexyl)(4-pyridyl)methanol (7) over Raney Ni in ethanol gave a mixture of 4-hydroxymethylpyridine and cyclo-hexylamine in 73% yield, although 2-nitro-l-(4-pyridyl)ethanol (8) gave the undecomposed amino alcohol in 70% yield (Scheme 9.3).15 The presence of carbon... 

When sweet potato (Ipomoea batatas) is infected with the fungus Fusarium solani it produces ipomeamarone (31) and a number of furans (32)—(35) which are pulmonary toxins and which may be degraded mono- or sesqui-terpenoids. The discovery of 4-hydroxymyoporone (36) as a phytoalexin of sweet potato has led to the suggestion72 that the C9 furans may be formed from this by retro-aldol condensation. Radioactive (36) was transformed by F. solani into (32)—(35), and control... 

By analyzing an input molecule, substructures are found which point to chapters in the reaction library. There, descriptions of changes in these substructures are contained which will occur in the course of a certain reaction. Implementing these changes leads to synthetic precursors. Thus, the recognition of the substructure of a /3-hydroxy-carbonyl group would point to the chapter aldol condensation in the reaction library. There the structural changes of a retro-aldol condensation are contained and result in the two carbonyl compounds as precursors (see Fig. 1). As the reac-... 

Fig. 9. Retro-aldol condensation breakable bonds as indicated...

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