Ketocarbonyl compounds

The use of chiral dirhodium carboxylate, 17 or 18, is preferred over chiral dirhodium carboxamidates for chemical transformations of a-diazo-p-ketocarbonyl compounds primarily because of reactivity considerations, that is, these diazo compounds do not undergo dinitrogen loss with the carboxamidate catalysts even at elevated temperatures. In addition, the orientation of the chiral ligands in 17 and 18 provides closer access to bulky diazo compounds. When the two attachments to the di azomethane unit are vastly unequal in size, high levels of enantiocontrol can result. 

SCHEME 57. Various types of solid-state aggregation of /3-ketocarbonyl compounds (A) unsolvated dimer [(CH3C(OLi)CH-COOEt]2]222 (B) unsolvated hexameric [(CH3C(OLi)CHCOOBu-t]6223 (C) tetrasolvated dimer of 1,3-cyclohexanedione lithium enolate exhibiting both O—Li and O—H coordinations224... 

At first, analogous to the 1,4-dihydropyridine synthesis, in the Hantzsch pyrrole synthesis, a p-ketocarbonyl compound reacts with ammonia or a secondary amine, forming an enamine II. This enamine II reacts with the a-haloketone I in a nucleophilic substitution and gives, after tautomerization and condensation, the pyrroles HI (Scheme 13.130). 

Symmetric 1,4-Dihydropyridines The most common Hantzsch synthesis produces symmetrical 1,4-dihydropyridines by the use of two equivalents of the P-ketocarbonyl compound. For the solvent-free performance, the nitrogen sources are limited to sohd or high boiling ones, like ammonium acetate [220-224, 232, 235], ammonium chlorate [237], ammonium formate [238], or primary aryl amines (Scheme 13.131) [218b]. 

Asymmetric 1,4-Dihydropyridines Instead of two equivalents of one p-ketocarbonyl compound, two different equimolar p-ketocarbonyl compounds with different reactivities can be subjected to the Hantzsch 1,4-dihydropyridine synthesis. The products of those reactions are asymmetric 1,4-dihydropyridines 579. 

Another example deals with the direct synthesis of pyr-rol-2-carbaldehydes 598 and 601 to avoid installation of these moieties into preformed pyrroles. Therefore, it is necessary to change from a normal p-ketocarbonyl compound to a stabilized ketonitrile 596 to ensure only one possible reaction pathway toward the enamine (Scheme 13.150) [270]. 

The unusually high acidity of the methylene hydrogens of j8-ketocarbonyl compounds can be used to synthetic advantage. Their unusually low pK values (ca. 9-13, see Table 23-1) allow alkoxide bases to remove a proton from this methylene group essentially quantitatively, giving an enolate ion that may be alkylated to produce substituted derivatives. For example, treatment of ethyl 3-oxobutanoate (ethyl acetoacetate) with NaOCH2CH3 effects complete deprotonation to the enolate, which reacts via the Sn2 mechanism with iodomethane... 

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