Carbon substrates, preferred substitution

Alkyl halides (RX) are good substrates for substitution reactions. The nucleophile (Nu ) displaces the leaving group (X ) from the carbon atom by using its electron parr or lone pair to form a new a bond to the carbon atom. Two different mechanisms for nucleophilic substitution are SnI and 8 2 mechanisms. In fact, the preference between S l and 8 2 mechanisms depends on the structure of the alkyl halide, the reactivity and structure of the nucleophile, the concentration of the nucleophile and the solvent in which reaction is carried out. 

Table 8.5 Preferred Substitution Mechanisms for Various Carbon Substrates...

The classical kinetic resolution of racemic substrate precursors allows only access to a theoretical 50% yield of the chiral ladone product, while the antipodal starting material remains unchanged in enantiomerically pure form. The regioseledivity for the enzymatic oxidation correlates to the chemical readion with preferred and exclusive migration of the more nucleophilic center (usually the higher substituted a-carbon). The majority of cydoketone converting BVMOs (in particular CHMOAdneto)... 

Evaluation of the only appropriate Fukui function is required for investigating an intramolecular reaction, as local softness is merely scaling of Fukui function (as shown in Equation 12.7), and does not alter the intramolecular reactivity trend. For this type, one needs to evaluate the proper Fukui functions (/+ or / ) for the different potential sites of the substrate. For example, the Fukui function values for the C and O atoms of H2CO, shown above, predicts that O atom should be the preferred site for an electrophilic attack, whereas C atom will be open to a nucleophilic attack. Atomic Fukui function for electrophilic attack (fc ) for the ring carbon atoms has been used to study the directing ability of substituents in electrophilic substitution reaction of monosubstituted benzene [23]. In some cases, it was shown that relative electrophilicity (f+/f ) or nucleophilicity (/ /f+) indices provide better intramolecular reactivity trend [23]. For example, basicity of substituted anilines could be explained successfully using relative nucleophilicity index ( / /f 1) [23]. Note however that these parameters are not able to differentiate the preferred site of protonation in benzene derivatives, determined from the absolute proton affinities [24],... 

In all of the reactions with carboxylic acid derivatives, the carbonyl carbon is acting as the substrate in nucleophilic substitution. Rather than memorize all these reactions, you should remember that carboxylic acids and their derivatives undergo nucleophilic substitution aldehydes and ketones prefer nucleophilic addition. 

The first and second HOMO electron densities of parent five-membered heteroaromatics may be directly evaluated from theoretical calculations and are illustrated qualitatively at the left side of Fig. 8. A distinct preference for the a carbons of parent heteroaromatics is therefore predicted for electrophilic species, whose reactivity is regulated by preliminary charge-transfer interactions with the substrate (76JA4361). In an abundant number of cases, predominant a substitution in simple hve-membered heteroaromatics is... 

---