Dieckman condensation

Related chemistry not covered in this chapter includes the acylation of stabilized organometallics and the broad category of enolate or metalloenamine C-acylation (Volume 2), the Claisen or Dieckman condensations (Chapter 3.6, Volume 2), the acylation of heteroatom-stabilized carbanions (Part 2, Volume... 

Further persuasive evidence in support of the expectation that the mechanism of the ECH-catalyzed reaction involves an Elcb mechanism with a stabilized thioester enolate anion intermediate is obtained from the membership of ECH in the mechanistically diverse enoyl-CoA hydratase superfamily [70]. Such superfamilies are derived from a common ancestor by divergent evolution the members of these share a partial reaction, usually formation of a common intermediate, e.g., an enolate anion. The reactions catalyzed by members of the enoyl-CoA hydratase superfamily (almost) always utilize acyl esters of CoA as substrates the reactions invariably can be rationalized with mechanisms that involve the formation of a thioester enolate anion intermediate, e.g., 1,3-proton transfer, 1,5-proton transfer, Dieckman and reverse Dieckman condensations, and yS-decarboxylation. Although mechanisms with thioester enolate anion intermediates are plausible for each of these reactions, as in the ECH-catalyzed reaction, evidence for their existence on the reaction coordinate is circumstantial because the intermediates do not accumulate, thereby avoiding spectroscopic detection. 

The mechanism involves the formation of a thioacetal followed by a Dieckman condensation to produce the requisite five-membered ring. The reaction is completed with elimination and tautomerization to form the desired product. 

Dieckman condensation reactions of diesters have been carried out in solid state in presence of a base (like Na or NaOEt) using high-dilution conditions in order to avoid intermolecular reaction. It has been found that the Dieckman condensation of diethyl adipate and pimelate proceed very well in absence of the solvent the reaction products were obtained by direct distillation of the reaction mixture. In this method the diester and powdered Bu OK were mixed using a pestle and mortar for 10 min. The solidified reaction mixture was neutralised with P-TSOH.H2O and distilled to give cyclic compounds (Scheme 14). 

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