Example a,P-Unsaturated Carbonyl

Synthesize the following target molecule, using readily available starting materials and reagents. The synthesis must involve the formation of a new C-C bond. 

Since the target molecule is an a,P-unsaturated carbonyl, one possible approach would be an aldol reaction. A disconnection can be made directly through the C=C double bond, or a stepwise approach can be taken by first imagining the TM as a P-hydroxy structure that can then be disconnected between the alpha and beta carbons. Either approach leads to the same aldol starting materials a nucleophilic alpha carbon (enolate) and an electrophilic carbonyl carbon (benzaldehyde). 

The resulting mixed aldol should be a reasonable one, since benzaldehyde has no alpha protons and the only enolate (Nu ) present would be from methyl acetate. Sodium methoxide is a good choice of base, since it would not give a new product if an addition/elimination (acyl substitution) mechanism were to take place at the ester carbonyl (i.e., no hydrolysis or transesterification will take place if the alkoxide base matches the alkoxy group of the ester). Heat is added to the reaction conditions to imply that the a,P-unsaturated product is desired, rather than the 3-hydroxy product. However, since the resulting alkene is in conjugation with both the carbonyl and the phenyl group, this dehydration is likely to occur spontaneously even at room temperature. 

Another possible approach is to view the TM as the product of a Wittig reaction with a stabilized Wittig reagent (or HWE reagent). 

This synthetic approach begins with the preparation of the Wittig reagent from methyl bromoacetate. Treatment of this reagent with benzaldehyde produces the IM. 

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