TheDieckmann Condensation (Including theThorpe‐Ziegler Condensation)

Abstract

The Dieckman condensation is an acetoacetic ester condensation in which a dicarboxylic ester is cyclized to a beta‐ketonic ester through the action of a base. The dicarboxylic ester must have at least one alpha‐hydrogen atom and the carbalkoxy groups must be situated that cyclization will result in a 4‐membered ring or larger ring. Discovery and development of the reaction are generally credited to Dieckmann, who found that heating an adipic or a pimelic ester with sodium and a trace alcohol led to cyclization with formation of a cyclopentanone or a cyclohexanone. The Dieckmann condensation has proved useful for the preparation of a variety of carbocyclic and heterocyclic ketones and has been extended to the synthesis of 7 and 8‐membered rings.

Synthetic Approaches to the New Drugs Approved during 2019

“…The chiral pyrrolidine fragment 198 was rapidly synthesized starting from an in situ Michael addition−Dieckmann condensation 122 of Cbz-protected glycine ethyl ester 192 and ethyl acrylate (193) in the presence of NaOt-Bu to afford 194 (Scheme 31). Reaction with trflic anhydride gave enol triflate 195, which underwent a Suzuki−Miyaura reaction with ethylboronic acid to provide 4-ethylpyrrolidine 196 in good yield.…”

Synthesis of a Model Tetracyclic Core Structure of Calyciphylline B-Type Alkaloids

“…The organic layer was concentrated under reduced pressure, and the residue was purified by flash chromatography (hexanes/EtOAc = 90/10) to give the title compound 14 (579 mg, 75% over two steps) as a colorless liquid. (15). Alkene 14 (2 g, 6.7 mmol) was dissolved in a 3:1 mixture of 1,4-dioxane:water (67 mL, 0.1 M), and NaIO 4 (5.8 g, 26.93 mmol) was added.…”

“…4l Elimination to 14 according to Grieco 14 led to the alkene 14, which was converted to 15 in 80% yield over three consecutive steps. Treatment of 15 under Dieckmann conditions 15 using KHMDS in THF provided the corresponding β-ketoester, which was decarboxylated to the aza-bicyclic ketone 16 in 75% yield over two steps. A catalytic amount of acid was necessary to accelerate the decarboxylation process.…”

High-yielding method for preparation of carbocyclic or N-containing heterocyclic β-keto esters using in situ activated sodium hydride in dimethyl sulphoxide

“…The compounds are very often prepared by the acylation of preformed ketone enolate anions using reagents such as Weinreb amides (4), alkyl-cyanoformates (5,6) or 1-Boc-imidazole (7), as well as alkyl carbonates at elevated temperature (8)(9)(10)(11). Dieckmann condensation (12) of various diesters provides good yields of 5-and 6-membered carbocyclic (13)(14)(15) or heterocyclic β-keto esters (16)(17)(18)(19)(20)(21) while acyclic analogues result from Claisen ester condensation (22) typically after prolonged heating in aromatic solvents with alkoxides. Alternatively, the acylation is promoted by Lewis acids (23,24).…”