Reactions at the a-carbon

Reactions at the a-carbons have been of considerable kiterest because it is at these positions that enzymatic oxidation, which is beheved to initiate the events leading to carcinogenic metaboUtes, generally occurs (5,7,8,73). The a-hydrogens exchange readily as shown in the following where D represents H. This exchange apparentiy results from stabilization of an anionic intermediate by electron delocalization (74,75). 

Reactions at the a-Carbon of Substituents Attached to Ring Carbons 1110... 

Reactions at the a-Carbon Atom of Carbonyl Groups Alkylation of Imino- and Enamino Compounds ... 

Bistriflyl amines constitute a rare class of amino derivatives which undergo SN2 reactions at the a-carbon [50], The presence of two strong acceptor groups in the p position of this carbon greatly facilitate the C-N bond cleavage. 

Reactions at the a-carbon atom of the a-amino acids can be divided into three classes. 

Reactions at the a-carbon atom are affected by the presence of 02. First, by rapidly removing the reducing species, it blocks reductive deamination. This is thought to explain the protective effect of 02 on alanine destruction 26). Secondly, 02 also probably alters the mechanism of oxidative deamination though the products (NH3 and the carbonyl group) are the same 39). 

The increase in double bond character is assumed to increase the intrinsic barrier for reaction at the a-carbon atom. As this increase is greatest for the thermodynamically least stable (CF3-substituted) carbocation, changes in thermodynamic driving force and intrinsic barrier oppose each other. The constancy of the values of kn2o thus reflects a change in intrinsic barrier overriding the second and third terms in the Marcus expression of Equation (20). This is a more radical effect than the lesser variation preserving the linearity of the plots for the reaction families in Fig. 3 (p. 77), for which only the third term is overridden. 

Carbonyl compounds such as acetone 10 exist predominantly in the keto form 10 but are in equilibrium with the enol form 11. We shall be more interested in the formation of the enolate anion 13 with base 12 and its reactions at the a-carbon with carbon electrophiles. 

Scheme I. General mechanism of PLP-catalyzed reactions at the a-carbon atom of amino acids and amines.

V. AMIDES, ELECTROPHILIC REGIO AND STEREOSELECTIVE REACTIONS AT THE a-CARBON.1514... 

Replacing the O atom of the aldehyde 9 by an N—R affords the simplest nitrogen carbonyl analog—the aldimine 10. In trying to overcome a few of the problems in alkylation reactions at the a-carbons of aldehydes and ketones (for example 9 13 ... 

VI. AMIDOESTERS. STEREOSELECTIVE, REGIOSELECTIVE AND ELECTROPHILIC REACTIONS AT THE a-CARBON... 

Review Unit 9 Carbonyl Compounds II Reaction at the a Carbon Amines... 

A second general reaction of aldehydes and ketones involves reaction at the a carbon. A C-H bond on the a carbon to a carbonyl group is more acidic than many other C-H bonds, because reaction with base forms a resonance-stabilized enolate anion. 

Chapters 23 and 24 are devoted to reactions at the a carbon to a carbonyl group. 

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. 

The carbocation that is formed upon protonation of a carbonyl compound can lose H+ from the a-carbon to give an enol. Enols are good nucleophiles. Thus, under acidic conditions, carbonyl compounds are electrophilic at the carbonyl C and nucleophilic at the a-carbon and on oxygen, just like they are under basic conditions. Resonance-stabilized carbonyl compounds such as amides and esters are much less prone to enolize under acidic conditions than less stable carbonyl compounds such as ketones, aldehydes, and acyl chlorides in fact, esters and amides rarely undergo reactions at the a-carbon under acidic conditions. 

However, aromatic amine hydrochlorides and weakly basic aromatic amines effect selective reactions at the a-carbon atom to give derivatives of the type CCl3C(=NAr)N=PCl3. Products of closely related structure were also obtained on reaction with AW-dichloro-amines ... 

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