Potassium Dieckmann reaction

Potassium Amides. The strong, extremely soluble, stable, and nonnucleophilic potassium amide base (42), potassium hexamethyldisilazane [40949-94-8] (KHMDS), KN [Si(CH2]2, pX = 28, has been developed and commercialized. KHMDS, ideal for regio/stereospecific deprotonation and enolization reactions for less acidic compounds, is available in both THF and toluene solutions. It has demonstrated benefits for reactions involving kinetic enolates (43), alkylation and acylation (44), Wittig reaction (45), epoxidation (46), Ireland-Claison rearrangement (47,48), isomerization (49,50), Darzen reaction (51), Dieckmann condensation (52), cyclization (53), chain and ring expansion (54,55), and elimination (56). 

The mercaptals obtained by the acid catalyzed reaction of J3-ketoesters, e.g., ethyl acetoacetate, with methyl thioglycolate (73) undergo the Dieckmann cyclization with alcoholic potassium hydroxide at lower temperatures to give ethyl 3-hydroxy-5-methyl-2-thiophenecarboxylate (74) in 75% yield. ° Besides ethyl acetoacetate, ethyl a-ethylacetoacetate, ethyl benzoyl acetate, and ethyl cyclopentanonecarboxylate were also used in this reaction/ It is claimed that /8-diketones, hydroxy- or alkoxy-methyleneketones, or /8-ketoaldehyde acetals also can be used in this reaction. From acetylacetone and thioglycolic acid, 3,5-dimethyl-2-thiophenecarboxyl-ic acid is obtained. ... 

These side reactions can be minimized by adding trimethylsilyl chloride to the reaction mixture as an alkoxide scavenger. This traps the enediolate dianion as a bis-silyl enol ether, and traps the sodium or potassium alkoxides, which are catalysts for the Dieckmann ring closure, as neutral silyl ethers." The resultant bis-siloxy cycloalkenes are either isolated or converted in situ to a-hydroxy ketones by alcoholysis or by acid hydrolysis. ... 

The key step in a new synthesis of cyclic ketones by House and Babad is cyclization with potassium t-butoxide in f-butanol of a phosphonium salt of type (8) to a cyclophosphorane (9). The reaction is considered to be related to a Dieckmann condensation. When n = 2-4 yields are 52-84%. 

The addition of potassium cyanide to the acid (77) and subsequent acid (not, as before, alkaline) hydrolysis, led to a mixture of the cis- and transisomers from which the pure trans-isomer, forming the trans-diester (80) on esterification, was isolated by crystallization. Reduction of the keto group, Dieckmann cyclization of the hydroxydiester formed, and decarboxylation led to the Z-trans-C/D ketol (79). Resolution of the racemic diacid corresponding to the diester (80) by crystallizing its brucine salts and performing the reactions described above with the optical isomers obtained enabled the tZ-enantiomer of the ketol (79) to be obtained [898], this being identical with the product formed in the oxidation of vitamin D2 [899]. This enantiomer has also been used as the CD fragment in the synthesis of vitamin D (Scheme 90). 

---