Conjugate Addition to an a,3-Unsaturated Ketone

Michael-type addition, whereas the combination of this addition followed by an aldol reaction to form the six-membered ring of 29 is called the Robinson annula-tion. The names honor the chemists who discovered the two types of reactions. 

The dehydration of 34 to 29 is a reversible process that is driven to completion by removing the water from the reaction mixture. This is conveniently done by using toluene as the solvent for the reaction. Water and toluene form an azeotrope (Sec. 4.4), so azeotropic distillation allows the continuous separation of water as dehydration occurs. To minimize the amount of solvent that is required for distillations of this type, a Dean-Stark trap (Fig. 18.15) is commonly used. Because such traps are often not available in the undergraduate laboratory, an operational equivalent may be devised by assembling the apparatus in a way such that water, but not toluene, can be prevented from returning to the reaction flask (Fig. 18.16). 

The choice of an aldehyde such as 2-methylpropanal (26) having only one a-hydrogen atom is important to the success of this crossed-aldol condensation because its dimerization is of no consequence. For example, aldehyde 26 can readily react with another molecule of itself to give 35 (Eq. 18.13), but this process is reversible under the reaction conditions. Moreover, unlike the aldol product 34,35 is incapable of dehydrating to give an a,p-unsaturated product and water, which would drive the equilibrium leading to the dimerization product. It is left to you to consider the possibility of self-condensation of 3-buten-2-one (27) and of the reaction of enol 30 with the carbon atom of the protonated carbonyl function in 31 (see Exercises 12 and 13 at the end of this section). 

Dean-Stark trap for removal of water by azeotropic distillation. 

Rubber septum or stopper Round-bottom flask 

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The first step of the Robinson annulation is simply a Michael reaction. An enamine or an enolate ion from a jS-keto ester or /3-diketone effects a conjugate addition to an a-,/3-unsaturated ketone, yielding a 1,5-diketone. But as we saw in Section 23.6,1,5-diketones undergo intramolecular aldol condensation to yield cyclohexenones when treated with base. Thus, the final product contains a six-membered ring, and an annulation has been accomplished. An example occurs during the commercial synthesis of the steroid hormone estrone (figure 23.9). 

Conjugate addition to an a,(3-unsaturated ketone followed by silylation may be used to generate a regiochemically-pure silyl enol ether (Equation Si3.2). 

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