Studies in Dieckmann Cyclization. I. Cyclization of Triethyl Pentane-1,2,5-tricarboxylate¹

Studies in Dieckmann cyclization and utilization of the products in the synthesis of steroids

“…These workers separated the products on the basis of the difference in their acidities. The more acidic product, which could be extracted with a mixture of equal volumes of saturated aqueous sodium bicarbonate and 2N aqueous sodium carbonate, was identified as 2,3-dicarbethoxycyclopentanone (11), while the other isomer, extractable with 2N sodium carbonate, was found to be 2,4-dicarbethoxycyclopentanone (12). For determination of the structures of these isomers, each of them was separately alkylated with j3-carbethoxyethyl chloride and then subjected to hydrolysis to obtain two sets of tetra acids (13 and 14) and keto diaeids (15 and -16) ; structures of the former set were proved by direct comparison with authentic specimens prepared by unambiguous methods.…”

“…However, using8 just a little over a gram atom of sodium and xylene, the formation of undesirable products could be reduced. It appeared to us that the formation of a considerable quantity of the isomer (12) in spite of the greater acidity of the isomer (11) might have been due D. X. BANERJEE to the hindrance caused by the C2-carbethoxy group to the approach of the C4-carbethoxy group to the C2-methylene anion of the triester (10 a), required for the formation of the carbon-carbon bond in the cyclization and also due to the formation of the insoluble sodium conjugates of the fl-keto esters (11 and 12) in the final step.…”

“…Presumably, the high yield in xylene was due to the relatively greater solubility of the conjugates in the solvent because of its comparatively high boiling point. Requirement of the P-keto ester (11) in large quantities for the synthesis of the urinary steroid, led us to study the conversion of the fl-keto ester (12), which had accumulated in considerably quantity during the cyclization of the triester (10 a), to its isomer (11). In view of the equilibrium nature of the Dieckmann reaction, the isomer (12) was treated 8 with a molar quantity of sodium ethoxide in both refluxing .…”

“…Requirement of the P-keto ester (11) in large quantities for the synthesis of the urinary steroid, led us to study the conversion of the fl-keto ester (12), which had accumulated in considerably quantity during the cyclization of the triester (10 a), to its isomer (11). In view of the equilibrium nature of the Dieckmann reaction, the isomer (12) was treated 8 with a molar quantity of sodium ethoxide in both refluxing . xylene and ethanol, and mixtures of the two isomers (11 and 12) were obtained in approximately the same proportions as those obtained from the triester (10 a) under the same conditions.…”

“…however, suggested the structure (23) for the product, without providing any experimental proof. Later, Sen and Bagchi, 12 utilizing the procedure of Ruzicka, 7 proved it to have the structure (22).…”