3-ketoesters, halogenation

Since analogous ketoesters not containing halide could be hydrogenated in good yield, the acidity of the enolate seems to be the main reason for the replacement of the aminoalcohol ligand by the halogenated acetoacetate. Indeed,... 

The synthesis of furans from /3-ketoesters and a-halogenated aldehydes or ketones under basic conditions is known as the Feist-Benary furan synthesis (Equation 28). In most of the cases, the reaction is initiated by an aldol reaction. If the first step is alkylation, reversed regioselectivity is observed. 

The first group is represented by the alcohol dehydrogenases (ADHs) that can be used for the synthesis of chiral alcohols. There are several commercially available ADHs isolated from yeast or horse liver (NADH dependent), or T. brockii (NADPH-dependent) that can be used for different types of substrates. Lactobacillus kefir produces an (/ )-ADH that accepts a broad variety of ketone substrates (ring halogenated, aliphatic, open-chain ketones, 2- and 3-ketoesters, and cyclic ketones), producing, for example, enantiomerically pure I -l-(2-pyridyl ethanol), / -(l-trimerhylsylyl)-l-butyn-3-ol or 5-phenylbutan-2-ol (Hummel 1990). 

Z3.3. The Feist-Benary Furan Synthesis. In this synthesis, an aldol-type carbonyl-carbanion condensation and a halogen displacement by an enol are employed to bring two molecules together in a ring stmc-ture, and in this sense it resembles the Knorr synthesis. The reactants are an alpha-haloketone and a ketoester (like ethyl acetoacetate). The mechanistic details remain unclear, but a logical mechanism is shown in Scheme 4.34. This assumes the carbonyl condensation occurs first before the halogen displacement, but the reverse may be tme. 

A Lewis acid-catalyzed one-pot sequential transformation of /3-ketoesters, aromatic aldehydes, and NCS was reported. The reaction proceeds by way of JCnoevenagel condensation/Nazarov cyclization/halogenations to give a-chloro-)3-ketoesters in moderate yields with high diastereoselectivities. ... 

Catalytic asymmetric halogenation reactions are still rarely studied. Togni et al. developed the efficiency of [Ti(TADDOLato)] complexes 18 in combination with the fluorinating agent Selectfluor in the catalytic fluorination of P-ketoesters. In 2004, this group executed the asymmetric chlorination of P-ketoesters using titanium complexes 18 with (dichloroiodo)toluene to generate enantiomerically enriched a-chlorinated products 19 (Scheme 5) [35]. 

A French group have described the low-temperature dealkoxycarbonyla-tion of jS-ketoesters by boric anhydride, B2O3. A further example of thermal demethoxycarbonylation of substituted malonate esters has been reported halogen participation in charge dispersal has been invoked to account for the production of methyl bromoacetate from dimethyl bromomalonate (Scheme 26). 

STEREOSELECTIVE SYNTHESIS OE HALOGENATED NATURAL PRODUCTS TABLE 43.2. Enantioselective Halogenation of (J-Ketoesters... 

RECENT PROGRESS IN ENANTIOSELECTIVE BROMINATION, CHLORINATION, AND lODINATION 1335 TABLE 43.3. Enantioselective Halogenation of 3-Ketoesters... 

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