Decarboxylative aldol

Pyrrolo[3,4-c][l,5]-benzothiazepin-3-ones 300 are available from ketoester 299 by a three-step sequence which includes hydrolysis and decarboxylation, aldol condensation and cyclization with o-aminothiophenol (Equation (35) (1993CE773)). 

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. 

Copper(II) catalysed enantioselective decarboxylative aldol-type addition of malonic acid hemithioesters to aldehydes in the presence of tartaric acid-derived bisbenzimidazole and an achiral base was examined. The use of DBU (1) as an achiral base resulted in low enantioselectivity [69]. 

Reactions in plants are of course catalyzed by enzymes, but the reactions are simply those allowed by organic chemical principles. Familiar processes such as methylation, oxidation, reduction, decarboxylation, aldol condensations, and so on, are frequently involved. In many cases it is difficult to determine the exact sequence of events, but the broad outlines of the biosynthesis of many alkaloids have been elucidated. To take a simple case for illustration of a biosynthetic pathway, the synthesis of coniine in the hemlock tree will be presented. Coniine (3.6) is the poison in hemlock that was used to kill Socrates. As found in Scheme 3.5, the amino acid lysine is the precursor of coniine. The use of radioactive isotopic labels is invaluable in proving such pathways. 

Copper Lewis acids have also been used in decarboxylative, aldol-type additions of malonic acid hemithioesters to aldehydes. Cozzi and coworkers reported a catalyst prepared from Cu(OTf)2 and bisbenzimidazole (107) gave low to moderate yields and low enantioselectivities in additions of thioester (107) to 3-phenylpropanal or p-nitrobenzaldehyde (Scheme 17.21) [27]. 

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. 

A.S. Evitt, U.T. Bornscheuer, Lipase CAL-B does not catalyze a promiscuous decarboxylative Aldol addition or knoevenagel reaction. Green Chem. 13 (2011) 1141-1142. 

We successfully developed several amine-catalyzed decarboxylative aldol/oxa-Michael cascade reactions deploying unprotected and unactivated carbohydrates to access glycosides of acetone. Useful substrates for this transformation are acetonedi-carboxylic acid 9 or acetoacetic acid 10 (Eqs. 4 and 5 Scheme 2.1). These reactions are catalyzed by tertiary amines at room temperature. The corresponding C-glycoside 6 was isolated with good yields (60%) and selectivity (p/a 3/1) [26]. 

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

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