Retro-Aldol decomposition

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). 

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...

The next task was to form the C2-C3 aldol bond stereoselectively. However, asymmetric coupling of acetate derivatives to aldehydes is often accompanied by poor / -induction [89]. Moreover, the C3-C4 bond is particularly sensitive to retro-aldol reaction, especially under basic conditions. In the natural products, this was observed to be the main decomposition reaction. The first total syntheses of epothilones circumvented this problem by constructing this part of the molecule in an indirect manner, e.g., by using reduced forms at Cl or C5. We decided to employ our chromium-Reformatsky methodology, which avoids these problems and allows the direct use of reagents in the correct oxidation state. The non-basic reaction conditions, the intermediacy of a chromium(III) aldolate that is resistant to retro-aldol reaction, and the potential of a direct asymmetric carboxymethyl ( acetate ) transfer favor the use of this method [90]. 

Not surprisingly, an attempt at direct Mitsunobu inversion of (3-hydroxyketone 14 led only to elimination, yielding the corresponding a,(3-unsaturated ketone. To circumvent this problem, 14 was converted to homoallylic alcohol 15 by Petasis methylenation via the corresponding TES ether. Attempts to methylenate (3-hydroxyketone 14 directly under Petasis conditions led to substantial decomposition via elimination and retro-aldol pathways. Alcohol 15 underwent smooth Mitsunobu inversion to give, following methanolysis and TES ether formation, the desired 1,4-anti compound 16 (Scheme 3). This was then converted in three straightforward steps to aldehyde 17, ready for the proposed aldol union with ketone 10. 

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... 

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. 

Transition metal catalysis of the Michael reaction of 1,3-dicarbonyl compounds with acceptor activated alkenes has been known since the early 1980 s 2>3 It is a valuable alternative to the classic base catalysis of the reaction. Because of the mild and neutral conditions, the chemoselectivity of these reactions is superior to that provided by base catalysis, since the latter suffers from various unwanted side or subsequent reactions, such as aldol cyclizations, ester solvolyses or retro-Claisen type decompositions. A number of transition metal and lanthanide compounds have been reported to catalyze the Michael reaction, but FeCb 6 H20 is one of the most efficient systems to date. A number of 3-diketones or p-oxo esters and MVK are cleanly converted to the corresponding Michael reaction products within a few hours at room... 

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