Retro-aldol-type reaction

In antithetical analyses of carbon skeletons the synthon approach described in chapter I is used in the reverse order, e.g. 1,3-difunctional target molecules are "transformed" by imaginary retro-aldol type reactions, cyclohexene derivatives by imaginary relro-Diels-Alder reactions. 

Another example of a [4S+1C] cycloaddition process is found in the reaction of alkenylcarbene complexes and lithium enolates derived from alkynyl methyl ketones. In Sect. 2.6.4.9 it was described how, in general, lithium enolates react with alkenylcarbene complexes to produce [3C+2S] cycloadducts. However, when the reaction is performed using lithium enolates derived from alkynyl methyl ketones and the temperature is raised to 65 °C, a new formal [4s+lcj cy-clopentenone derivative is formed [79] (Scheme 38). The mechanism proposed for this transformation supposes the formation of the [3C+2S] cycloadducts as depicted in Scheme 32 (see Sect. 2.6.4.9). This intermediate evolves through a retro-aldol-type reaction followed by an intramolecular Michael addition of the allyllithium to the ynone moiety to give the final cyclopentenone derivatives after hydrolysis. The role of the pentacarbonyltungsten fragment seems to be crucial for the outcome of this reaction, as experiments carried out with isolated intermediates in the absence of tungsten complexes do not afford the [4S+1C] cycloadducts (Scheme 38). 

Another interesting example is SHMT. This enzyme catalyzes decarboxylation of a-amino-a-methylmalonate with the aid of pyridoxal-5 -phosphate (PLP). This is an unique enzyme in that it promotes various types of reactions of a-amino acids. It promotes aldol/retro-aldol type reactions and transamination reaction in addition to decarboxylation reaction. Although the types of apparent reactions are different, the common point of these reactions is the formation of a complex with PLP. In addition, the initial step of each reaction is the decomposition of the Schiff base formed between the substrate and pyridoxal coenzyme (Fig. 7-3). 

It can be assumed that, upon irradiation, tautomer 5-40-II reacts with the alkene 5-41 in a highly regioselective [2+2] cycloaddition to give the cyclobutane 5-42 as an intermediate. Subsequent retro-aldol-type reaction and hemiacetal formation produces 5-44 via 5-43. After addition of the Lewis acid (BF3-Et20), cyclization takes place to give the desired products. It should be noted that the excess of alkene must be removed under reduced pressure before addition of the Lewis acid in order to avoid polymerization. 

Fig. 10.17. The epoxide-diol pathway in 5-vinylbarbitu.rates such as vinylbital (10.65, R = 1-methylbutyl). The difference with 5-allylbarbiturates is that the diol metabolite of 5-vinylbar-biturates cannot be isolated due to its immediate decomposition via a retro-aldol-type reaction...

A possible origin of this ring-opened alkaloid is from the methyl chanofruticosinate (238) which on oxidation provides the iminium ion 360. Hydrolysis of this iminium ion gives the presumably unstable carbinol amine 361 which could then undergo a retro-aldol-type reaction... 

Aromatic A-TMS-ketene imines undergo efficient aldol-type reaction with O-protected a-hydroxy aldehydes, giving iy -selectivity at ambient temperature, reversing at -78 °C to anti- Transfer of the TMS group from the ketene imine prevents (g) retro-reaction. 

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... 

Enzyme Catalyzed. The enzyme aldolases are the most important catalysts for catalyzing carbon-carbon bond formations in nature.248 A multienzyme system has also been developed for forming C-C bonds.249 Recently, an antibody was developed by Schultz and co-workers that can catalyze the retro-aldol reaction and Henry-type reactions.250 These results demonstrate that antibodies can stabilize the aldol transition state but point to the need for improved strategies for enolate formation under aqueous conditions. 

The Michael reaction is the conjugate addition of a soft enolate, commonly derived from a P-dicarbonyl compound 24, to an acceptor-activated alkene such as enone 41a, resulting in a 1,5-dioxo constituted product 42 (Scheme 8.14) [52]. Traditionally, these reactions are catalyzed by Bronsted bases such as tertiary amines and alkali metal alkoxides and hydroxides. However, the strongly basic conditions are often a limiting factor since they can cause undesirable side- and subsequent reactions, such as aldol cyclizations and retro-Claisen-type decompositions. To address this issue, acid- [53] and metal-catalyzed [54] Michael reactions have been developed in order to carry out the reactions under milder conditions. 

Treatment of cycloprop [c]pyrans 520 with acid leads to chromans 521 with a 5,8-substitution pattern, which is difficult to obtain by other synthetic methods (Scheme 114). This novel reaction is believed to proceed via a retro-hDA opening of the dihydropyran ring to afford 522 followed by an acid-catalyzed aldol-type cyclization and dehydration (Scheme 114) <20040L3191>. 

Hydrolysis of the aldol-type adducts (26) proceeds to form a mixture of products due to retro aldol reactions. 

A similar rearrangement has been observed when the base attacks nitrosarcophaginates, in particular [Co(MENOsar)] + cation. At the first stage, a reaction of the retro-aldol type occurs to decompose the capping fragment. Then the base favours the detachment of an imine species, and the primary amine moiety is formed. The latter reacts... 

It has previously been shown that in the triplet state a nitro group on a benzene ring is highly electron withdrawing at the 3- and 4- positions and induces decarboxylations, retro-Aldol type processes and a novel intramolecular redox-type reaction by way of nitrobenzyl carbanion-type intermediates in all cases. In this context, the irradiation of the three 4-nitrobiphenyl derivatives (217), (218) and (219) has been examined in order to assess the potential of photoexcited nitro groups to induce such processes across the biphenyl system.Indeed analogous reactions are observed in these biphenyls but with enhanced quantum efficiencies to those for the reactions in benzenoid compounds. Thus (217) yields the aldehydes (220) and (221) at pHs of 2 and 7, respectively, and (218) gives (222) and (223) under similar conditions, whereas (223) is also formed from (219) at pH 13 but no reaction is observed in neutral solution. The authors note that these results provide more evidence that the... 

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