Robinson annulation 1,5-diketone cyclization

In this example, the /3-diketone 2-methyJ-l,3-cyclopentanedione is used to generate the enolate ion required for Michael reaction and an aryl-substituted a,/3-unsaturated ketone is used as the acceptor. Base-catalyzed Michael reaction between the two partners yields an intermediate triketone, which then cyclizes in an intramolecular aldol condensation to give a Robinson annulation product. Several further transformations are required to complete the synthesis of estrone. 

The Robinson annulation is a combination of two reactions covered in this chapter. First, a Michael reaction takes place between a nucleophilic donor (the diketone in this problem) and an a,(3-unsaturated carbonyl compound (the enone shown). The resulting product can cyclize in an aldol reaction. The base catalyzes both reactions. 

Carbonyl condensation reactions are widely used in synthesis. One example of their versatility is the Robinson annulation reaction, which leads to the formation of substituted cyclohexenones. Treatment of a /8-diketone or fi-keto ester with an a,p-unsaturated ketone leads first to a Michael addition, which is followed by intramolecular aldol cyclization. Condensation reactions are also used widely in nature for the biosynthesis of such molecules as fats and steroids. 

A popular and useful application of the conjugate addition reaction is the combined conjugate addition-intramolecular aldol strategy, commonly known as the Robinson annulation. When the Michael donor is a ketone and the Michael acceptor an a,p-unsaturated ketone, the product is a 1,5-diketone which can readily undergo cyclization to a six-membered ring. Typical Michael donor substrates are 2-substituted cyclohexanones, which condense with alkyl vinyl ketones to give the intermediate conjugate addition products 42 (1.52). The subsequent intramolecular... 

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