Substitution Reactions of Carbonyl Compounds at the a Carbon

Substitution Reactions of Carbonyl Compounds 23-1 Chapter 23 Substitution Reactions of Carbonyl Compounds at the a Carbon 

The reaction occurs via enol intermediates. Monosubstitution of X for H occurs on the a carbon. 

The reaction occurs with methyl ketones, and results in cleavage of a carbon-carbon a bond. 

Elimination of the elements of Br and H forms a new it bond, giving an a,P-unsaturated carbonyl compound. 

The reaction follows an Sn2 mechanism, generating an a-substituted carbonyl compound. 

Tamoxifen is a potent anticancer drug used widely in the treatment of breast cancer. Tamoxifen binds to estrogen receptors, and in this way inhibits the growth of breast cancers that are estrogen dependent. One method to synthesize tamoxifen forms a new carbon-carbon bond on the a carbon to a carbonyl group using an intermediate enolate. In Chapter 23 we learn about these and other carbon-carbon bond-forming reactions that occur on the a carbon. 

Chapter 23 concentrates on substitution reactions at the a carbon, whereas Chapter 24 concentrates on reactions between two carbonyl compounds, one of which serves as the nucleophile and one of which is the electrophile. Many of the reactions in Chapter 23 form new carbon-carbon bonds, thus adding to your repertoire of reactions that can be used to synthesize more complex organic molecules from simple precursors. As you will see, the reactions introduced in Chapter 23 have been u.sed to prepare a wide variety of interesting and useful compounds. 

Up to now, the discussion of carbonyl compounds has centered on their reactions with nucleophiles at the electrophilic carbonyl carbon. Two general reactions are observed, depending on the structure of the carbonyl starting material. 

Nucleophilic acyl substitution occurs when there is an eiectronegative atom Z on the carbonyl carbon (as with carboxylic acids and their derivatives). 

Reactions can also occur at the a carbon to the carbonyl group. These reactions proceed by way of ends or enolates, two electron-rich intermediates that react with electrophiles, forming a new bond on the a carbon. This reaction results in the substitution of the electrophile E for hydrogen. 

Chapters 23 and 24 focus on reactions that occur at the a carbon to a carbonyl group. These reactions are different from the reactions of Chapters 20-22, all of which involved nucleophilic attack at the electrophilic carbonyl carbon. In reactions at the a carbon, the carbonyl compound serves as a nucleophile that reacts with a carbon or halogen electrophile to form a new bond to the a carbon. 

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