Decarboxylative aldol reactions

In PLP-dependent enzymatic reactions, the Schiff base formed by reaction of the substrate with PLP provides an electron sink for stabilization of the negative charge that results from the bond-breaking process required in the reaction (racemization, decarboxylation, aldol reaction, elimination, etc.). The elegant work of Walsh and coworkers provided evidence that, subsequent to Schiff base formation, a common intermediate is formed from several different alanine analogues that are alanine racemase inhibitors. From this they proposed the elimination-Michael addition sequence shown in Figure 14 as the mechanism for inhibition166. 

With a Ph-BOX ligand (e.g., ent-lB) to complex Cu(OTf (2 for decarboxylative aldol reaction of substituted malonic acid monothioesters, yyn-selectivity is observed/ This reaction operates on a different mechanism than enz3mie-catalyzed decarboxylative Claisen condensation. 

Malonic acid half thioesters, H02C-CH(R )-C0-SR (R =H/Me), undergo an enantioselective decarboxylative aldol reaction with aldehydes, using a chiral catalyst bearing a hydrogen-bond donor and acceptor. In situ ESI-MS evidence supports a complex between the conjugate base of the substrate and the conjugate acid of the... 

M. Kapoor, A.B. Majumder, J. Mukherjee, M.N. Gupta, Decarboxylative aldol reaction catalysed by lipases and a protease in organic co-solvent mixtures and nearly anhydrous oi anic solvent media, Biocatal. BioUans. 30 (2012) 399-408. 

Biomimetic decarboxylative aldol reaction of -ketoacids with RCOF3 has been promoted enantioselectively by a chiral tertiary amine (Scheme 15). ... 

The biologically active form of vitamin Bg is pyridoxal-5-phosphate (PEP), a coenzyme that exists under physiological conditions in two tautomeric forms (Figure 18.25). PLP participates in the catalysis of a wide variety of reactions involving amino acids, including transaminations, a- and /3-decarboxylations, /3- and ") eliminations, racemizations, and aldol reactions (Figure 18.26). Note that these reactions include cleavage of any of the bonds to the amino acid alpha carbon, as well as several bonds in the side chain. The remarkably versatile chemistry of PLP is due to its ability to... 

By this concept, a reversible enzymatic aldol reaction generates a mixture of l-threo/erythro aldol diastereomers (133) from which the i-threo isomer is preferentially decomposed by an irreversible decarboxylation to furnish aromatic aminoalcohol (R)-(134) vhth 78% ee in high yield. 

As predicted, l,2,3,4-13C-labeled acetone dicarboxylate (15) provided an intact three-carbon chain into lycopodine. It also helped to explain why two molecules of pelletierine (12) were not incorporated (Scheme 6.3) [12]. As before, lysine (6) is converted to piperideine (8) via a decarboxylation. Then a Mannich reaction of labeled 15 with 8 provides pelletierine 12. The other half of the molecule to be incorporated must be pelletierine-like (12-CC>2Na), still containing one of the carboxylates. An aldol reaction of the two pelletierine fragments and a series of transformations leads to phlegmarine 9. Oxidation of 9 involving imine formation between N-C5, isomerization to the enamine and then cyclization onto an imine (at N-C13), provides lycopodine 10. Phlegmarine 9 and lycopodine 10 are proposed as... 

It is appropriate here to look at the structure of oxaloacetic acid, a critical intermediate in the Krebs cycle, and to discover that it too is a P-ketoacid. In contrast to oxalosuccinic acid, it does not suffer decarboxylation in this enzyme-mediated cycle, but is used as the electrophile for an aldol reaction with acetyl-CoA (see Box 10.4). 

Hence, if the proline-catalyzed aldol reaction between acetone and 4-nitrobenzal-dehyde in DM SO is carried out using 5 mol% proline, decarboxylation occurs and [3 + 2] cycloaddition between the resulting ylide and benzaldehyde gives a 1,3-oxazolidinone as the maj or side product [98]. Therefore, it is important that if catalyst loadings are to be reduced, either the carboxylic acid should be unable to decarbox-ylate (e.g. Appendix 7.B, Entries 12 [97, 98], 35 [99]) or else must be replaced by an isostere [101, 102] (e.g. Appendix 7.B, Entries 7 [103, 104], 8-10 [105], 11 [106], 28 [107]). Alternatively, the relative rate of the aldol reaction can be increased in order to minimize the concentration of iminium ion in solution and remove it from equilibrium before decarboxylation can take place. 

Transketolase removes a two-carbon fragment from ketols such as fructose 6-phosphate (alternatively xylulose 5-phosphate or sedoheptu-lose 7-phosphate) through the participation of thiamine diphosphate. Nucleophilic attack of the thiamine diphosphate anion on to the carbonyl results in an addition product which then fragments by a reverse aldol reaction, generating the chain-shortened aldose erythrose 4-phosphate, and the two-carbon carbanion unit attached to TPP (Figure 8.5) (compare the role of TPP in the decarboxylation of a-keto... 

Several approaches have been developed for the synthesis of 3-deoxy-D-mararao-oct-2-ulosonic acid (Kdo, 123) the most common one involves the coupling of oxaloacetic acid with D-arabinose followed by decarboxylation. This aldol reaction takes place under basic conditions, but above pH 11 side reactions occur. The procedure is simple and Kdo is isolated as the crystalline ammonium salt.316... 

Fig. 10 Why decarboxylation is inherently slower than an analogous retro-aldol reaction (itself a slow reaction). The angular distortion for sp2 to sp geometry is much larger than for sp3 to sp2 geometry, and the energy cost is proportional to the square of the angular distortion. Reproduced with permission from ref.9...

Chalcones such as 80 are very easily made by an aldol reaction between acetophenone and benzaldehyde conjugate addition of the enolate of 81 and cyclisation occur all in the same reaction.15 The ester 82 is formed as a mixture of diastereomers in high yield hydrolysis and decarboxylation give 78. 

You may not want a product with both ester groups present, and we discussed in Chapter 26 how one of two 1,3-related ester groups may be removed by hydrolysis and decarboxylation. There is a simpler route with the aldol reaction. If, instead of the malonate diester, malonic add is used, the... 

Figure 6.8 Proposed mechanism for lactone ring formation. Cardenolides an intermediate malonate ester is involved, and ring formation probably occurs via an aldol addition process giving the cardenolide digitoxigenin, the carboxyl carbon of the malonate ester being lost by decarboxylation. Bufadienolides three carbons from oxaloacetate can be incorporated by a similar esterification/aldol reaction sequence to yield the cumaline ring system. (From Dewick, 2002.)...

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. 

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