Enolate anions Dieckmann condensation

The intra-molecular Claisen condensation is called a Dieckmann condensation, and it generates a cyclic compound 58,99,101,118. Malonic esters can be converted to the enolate anion and condensed with aldehydes, ketones, or add derivatives. The reaction of malonic acid with an aldehyde using pyridine as a base is called the Knoevenagel condensation 59, 60, 61, 62, 69, 99,108,110,112, 113,119,124. 

This type of enolate anion reaction occurs among esters in the Claisen (Section 15.3A) and Dieckmann condensations (Section 15.3B). 

Identify the a-carbon for each ester group. Convert one of the a-carbons to an enolate anion and show it adding to the other carbonyl carbon. Because Dieckmann condensations occur with nucleophilic acyl substitution, the —OR group of the carbonyl being attacked Is eliminated from the final product. It often helps to number the atoms in the enolate anion and the ester being attacked. 

Addition of enolate anions derived from aldehydes or ketones (aldol reactions) and esters (Claisen and Dieckmann condensations) to the carbonyl groups of other aldehydes, ketones, or esters. 

We have described what is commonly known as the acetoacetic ester synthesis and have illustrated the use of ethyl acetoacetate as the starting reagent. This same synthetic strategy is applicable to any j8-ketoester, as, for example, those that are available by the Claisen (Section 19.3A) and Dieckmann (Section 19.3B) condensations. For example, following are structural formulas for two jS-ketoesters available from Dieckmann and Claisen condensations that can be made to tmdergo (1) formation of an enolate anion, (2) alkylation or acylation, (3) hydrolysis followed by (4) acidification, and finally (5) decarboxylation just as we have shown for ethyl acetoacetate. 

Note that aldol, Claisen, and Dieckmann condensations all give primary products with oxygens in a 1,3 relationship. The Michael reaction with enolate anions gives products with oxygens in a 1,5 relationship. These relationships are a consequence of the polarization of the reagents. In aldol, Claisen, and Dieckmann condensations, the carbonyl carbon is positive and the a-position is negative. 

The synthesis of the 10-methoxytetracyclic ketone 353 (Scheme 26) started from the readily available 3-methyl-5-methoxyindole 355, which after Boc protection, was brominated, and then condensed with the anion of the Schollkopf auxiliary 356 (from l-valine). Removal of the Boc-protecting group, followed in succession by A -methylation and hydrolysis, gave the required A -methyl-5-methoxy-D-tryptophan ethyl ester 357, which was then transformed into the key 10-methoxytetracyclic ketone 353, via N-benzylation, Pictet-Spengler condensation, and Dieckmann cyclization. Subsequent N-alkylation by the vinyl iodide 358 followed by Pd-catalyzed (enolate-driven)... 

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