Beta-keto esters

One step synthesis o( substrtuted pyridines from a beta keto ester, an aldehyde arid ammonia. 

Michael reactions and, 895 Beta-keto ester, 851 alkylation of, 859-860 cyclic, 892-893 decarboxylation of, 857, 860 Michael reactions and. 895 pKd of, 852 synthesis of, 892-893 Beta-lactam antibiotics, 824-825 Beta oxidation pathway, 1133-1137 mechanism of, 1133-1136 Beta-pleated sheet (protein), 1038 molecular model of, 1039 secondary protein structure and, 1038-1039 Betaine, 720 Bextra. structure of, 544 BHA, synthesis of, 629 BHT, synthesis of. 629 Bicycloalkane. 129 Bijvoet. J. M., 299 Bimolecular, 363... 

Padhi, S.K., Kaluzna, I.A., Buisson, D. et al. (2007) Reductions of cyclic beta-keto esters by individual Saccharomyces cerevisiae dehydrogenases and a chemo-enzymatic route to (lR,2S)-2-methyl-l-cyclohexanol. Tetrahedron Asymmetry, 18 (18), 2133-2138. 

Kaluzna, I.A., Feske, B.D., Wittayanan, W. et al. (2005) Stereoselective, biocatalytic reductions of alpha-chloro-beta-keto esters. The Journal of Organic Chemistry, 70 (1), 342-345. 

Fujioka H, Murai K, Kubo O, Ohba Y, Kita Y (2007) New three-component reaction novel formation of a seven-membered ring by the unexpected reaction at the gamma-position of the beta-keto ester. Org Lett 9 1687-1690... 

Bromination of Beta Keto Esters. The work of K. A. Pedersen on the bromination of beta keto esters in the presence of copper(II) and other divalent metal ions provides several examples of reactions proceeding via complexes (29), The complexes provide an alternative and much more rapid route for the bromination reaction. These reactions are accelerated by bases which take up a proton from the beta keto esters. For such substrates, e.g. ethyl acetoacetate, the general expression for the pseudo first order rate constant in the presence of copper has the form ... 

Beckman EJ, Munshi P (2011) Ambient caiboxylation on a supported reversible C02 carrier ketone to [beta]-keto ester. Green Chem 13(2) 376-383... 

He, X. C. Wang, B. Yu, G. L. Bai, D. L. Studies on the asymmetric synthesis of huperzine A. Part 2 highly enantioselective palladium-catalyzed bicycloannulation of the beta-keto-ester using new chiral ferrocenylphosphine ligands. Tetrahedron-Asymmetry, 2001, 12(23) 3213-3216. 

In this reaction, sodium metal is reacted with absolute alcohol to make sodium ethoxide (NaOCH2CH3). Ethyl acetoacetate and bromobenzene are then added to this to produce a beta keto ester. Reaction with acid then produces phenylacetone. 

A side reaction which sometimes becomes a problem is bromobenzene reacting with beta keto ester to produce di-phenylacetone. This can be controlled by not using too much bromobenzene, adding it slowly and stirring it well. 

The first results showed that optically active amino acids are not very effective as modifiers and showed that the most effective modifiers are hydroxycarboxylic acids, such as tartaric and malic acids. Also, it was found that the treatment of Raney Ni catalysts with these modifying solutions diminished the catalytic activity for the hydrogenation of the C=0 bonds in beta-keto esters but not for the hydrogenation of C=C bonds in olefinic substrates (Scheme 4.1.). 

In general, the reactions of enantioselective hydrogenations of beta-keto esters on modified Ni or of alpha-ksio esters on modified Pt are structure sensitive reactions. In both reactions, enantioselectivities increase with increasing crystallite size of Ni or Pt. 

Wolfson, A., Vankelekom, I.F.J., Geresh, S. and Jacobs, P.A. (2003) The role of the solvent in the asymmetric hydrogenation of beta-keto esters with Ru-BINAP, J. Mol Catal A. Chem. 198,39-45. 

Another classic method is that known as the Hantzsch pyrrole synthesis (Scheme 9.4). The nitrogen starting material is an enamine (9.2), which is prepared from a beta-keto ester and ammonia. The beta-position of the enamine is electron-rich and is alkylated with an alpha-haloketone. The amino and the carbonyl groups interact in the familiar way to close the ring. 

Trage, C., Schroder, D., and Schwarz, H. (2005) Coordination of iron(lll) cationsto beta-keto esters as studied by electrospray mass spectrometry implications for iron-catalyzed Michael addition reactions. Chem. Eur.J., 11, 619-627. 

Enamine bond formation operates in a similarly dynamic manner. Pomposo, Fulton, and coworkers synthesized reversible SCNPs using enamine chemistry. Initially, enamine-functionalized polymers were synthesized by the condensation of butylamine with a polymer containing beta-keto ester units. Nanoparticles were synthesized by a dynamic exchange reaction with ethylene diamine. The enamine eross-links were cleaved upon addition of phosphoric acid, and reformed with additional ethylene diamine. 

Beta-keto esters can be prepared by treating the enolate of a ketone with diethyl carbonate. Draw a plausible mechanism for this reaction. 

The racemization of the unreacted substrate can be accomplished either by spontaneous equilibration between the two enantiomers or by using a chemical or biological catalyst. The basic requirements for a successful DKR are that (i) the KR conditions must be compatible with the racemization process, (ii) the KR process must be very stereoselective, (iii) the catalyst for the racemization must not react with the product, and (iv) the racemization must be faster than the reaction of the slow reacting enantiomer k c 2> ksiow [la,b]. The concept of DKR has been applied to a variety of compounds such as a-amino acids, hemithioacetal esters, a-(hetero) arylcarboxylic acids, a-substituted nitriles, beta-keto esters, cyanohydrin esters, a-substituted thioesters, 4-substituted oxazolin-5-ones and thiazolin-5-ones [la]. 

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