Condensation conjugate addition-Dieckmann

Scheme 2.33. Formation of highly substituted chiral cyclohexenone derivatives using a domino conjugate addition/Dieckmann condensation.

Bunce, R. A., Harris, C. R. Six-membered cyclic (i-keto esters by tandem conjugate addition-Dieckmann condensation reactions. J. Org. Chem. 1992, 57, 6981-6985. 

Scheme 14.8 Spring s diversity-oriented synthesis of polycyclic scaffolds via domino depro-tection/double conjugate addition/Dieckmann condensation.

The mechanism of the Fiesselmann reaction between methylthioglycolate and a,P-acetylenic esters proceeds via consecutive base-catalyzed 1,4-conjugate addition reactions to form thioacetal Enolate formation, as a result of treatment with a stronger base, causes a Dieckmann condensation to occur providing ketone 8. Elimination of methylthioglycolate and tautomerization driven by aromaticity provides the 3-hydroxy thiophene dicarboxylate 9. 

Key Mechanism 22-12 The Claisen Ester Condensation 1071 22-13 The Dieckmann Condensation A Claisen Cyclization 1074 22-14 Crossed Claisen Condensations 1074 22-15 Syntheses Using /3-Dicarbonyl Compounds 1077 22-16 The Malonic Ester Synthesis 1079 22-17 The Acetoacetic Ester Synthesis 1082 22-18 Conjugate Additions The Michael Reaction 1085 Mechanism 22-13 1,2-Addition and 1,4-Addition (Conjugate Addition) 1085... 

Carboxylic Acids and their Derivatives.—2,3-Seco-A -unsaturated dicarboxylic acids (443), obtained by ozonolysis of 2-hydroxymethylene-4-en-3-ones, have been considered rather resistant to cyclisation to form the A-nor-3-en-2-one system (444). Two convenient methods for achieving such a reaction are now described. Dieckmann condensation of the dimethyl ester (445) was successful with sodium hydride, in toluene containing a little methanol. The 5-methoxy-carbanion (446), resulting from conjugate addition of methoxide ion, is suggested as a possible activated intermediate. Alternatively, the diacid (in the B-nor-series)... 

Nucleophilic addition to C=0 (contd.) ammonia derivs., 219 base catalysis, 204, 207, 212, 216, 226 benzoin condensation, 231 bisulphite anion, 207, 213 Cannizzaro reaction, 216 carbanions, 221-234 Claisen ester condensation, 229 Claisen-Schmidt reaction, 226 conjugate, 200, 213 cyanide ion, 212 Dieckmann reaction, 230 electronic effects in, 205, 208, 226 electrons, 217 Grignard reagents, 221, 235 halide ion, 214 hydration, 207 hydride ion, 214 hydrogen bonding in, 204, 209 in carboxylic derivs., 236-244 intermediates in, 50, 219 intramolecular, 217, 232 irreversible, 215, 222 Knoevenagel reaction, 228 Lewis acids in, 204, 222 Meerwein-Ponndorf reaction, 215 MejSiCN, 213 nitroalkanes, 226 Perkin reaction, 227 pH and, 204, 208, 219 protection, 211... 

The mechanism of a Dieckmann condensation is identical to the mechanism we described for the Claisen condensation. An anion formed at the a-carbon of one ester in Step 1 adds to the carbonyl of the other ester group in Step 2 to form a tetrahedral carbonyl addition intermediate. This intermediate ejects ethoxide ion in Step 3 to regenerate the carbonyl group. Cyclization is followed by formation of the conjugate base of the j8-ketoester in Step 4, just as in the Claisen condensation. The j8-ketoester is isolated after acidification with aqueous acid. 

---