1.2- Cyclohexanedione aldol reaction

The mechanism of the Robinson annulation consists of two parts a Michael addition to the a,p-unsaturated carbonyl compound to form a 1,5-dicarbonyl compound, followed by an intramolecular aldol reaction to form the six-membered ring. The mechanism is written out in two parts (Mechanisms 24.7 and 24.8) for Reaction [2] between methyl vinyl ketone and 2-methyl-1,3-cyclohexanedione. 

Some systems of different structure have shown their ability to catalyze the formation of a new carbon-carbon bond by reaction of two ketones. The enantioselective aldol reaction between 1,3-cyclohexanedione (173) and different a-bromoketo esters 174 followed by final cyclization gave as the main compound cw-configured 176. Several Cinchona alkaloid derivatives were tested in this transformation, with the dimeric catalyst system 175 in the presence of a proton sponge and an ammonium salt affording the best results (Scheme 4.37) [256], Also dimeric cinchona... 

Scheme 4.37 Aldol reaction between 1,3-cyclohexanedione with different a-bromoketo esters...

This is an example of a Robinson annulation. The mechanism for the Robinson annulation involves a sequence of conjugate addition reactions and aldol condensations. As illustrated, the first step is deprotonation of cyclohexanedione with sodium hydride. The resulting anion then participates in a 1,4-addition to methyl vinyl ketone. The resulting enolate anion then tautomerizes through... 

The important intermediate 66 of the steroid synthesis has been prepared by the application of the same reaction sequence to 2-methyl-1,3-cyclohexanedione (65) (Scheme 22). A synthesis of (+) 19-nortestosterone (69) starts with the Michael addition of the optically active oxo ester 67 to 1,7-octadien-3-one (59) catalyzed by sodium hydride, the ester group being removed by heating in aqueous HMPA with sodium iodide to give the dione 68. The aldol condensation catalyzed by sodium hydroxide proceeds in 90% yield. The terminal double bond is oxidized with PdCl2/CuCl to the methyl ketone and the internal olefinic double bond subsequently hydrogenated. The final reaction step involves aldol condensation in refluxing... 

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