Beta-keto ester synthesis

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... 

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. 

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. 

Keto ester 67 was converted to the unsaturated nitrile 70 in a routine manner. The latter proved to be an exceptionally useful intermediate. Concern that the significant steric demands which are associated with the formation of a sigma bond to the fully substituted beta carbon of the unsaturated nitrile would prevent reaction from occurring, were allayed by the discovery that the controlled potential reduction of 70 at —2.4 V in the presence of dimethyl malonate as the proton donor, alforded a 90% isolated yield of the requisite [3.2.1] adduct 71. This material was subsequently converted to enone 72 [42], a convergent point with an existing synthesis of quadrone (59). 

The Pechmann synthesis of coumarins via condensation of phenols with keto esters also involves an intramolecular hydroxyalkylation, following initial transesterification, and subsequent dehydration. It was found that H-Beta could successfully replace the sulfuric acid conventionally used as catalyst. For example, reaction of resorcinol with ethyl acetoacetate afforded methylumbelliferone (Figure 11.9), a perfumery ingredient and insecticide... 

The Knorr Pyrrole Synthesis. In this process, the starting materials are an alpha-amino ketone, or less commonly an alpha-amino aldehyde, and a beta-ketoester. In the latter, the protons on the alpha carbon are activated both by the keto and the ester carbonyls and are especially easily removed. The Knorr process starts with the condensation of the amino group with the keto group in the usual way to tie the two molecules together as in 4.29 of the example shown in Scheme 4.31. This species then undergoes intramolecular aldol-type condensation to form a reduced pyrrole derivative 4.30. 

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