Secondary carbon centers nucleophilic reactions

The major application of the Mitsunobu reaction is the conversion of a chiral secondary alcohol 1 into an ester 3 with concomitant inversion of configuration at the secondary carbon center. In a second step the ester can be hydrolyzed to yield the inverted alcohol 4, which is enantiomeric to 1. By using appropriate nucleophiles, alcohols can be converted to other classes of compounds—e.g. azides, amines or ethers. 

There is evidence, both experimental and theoretical, that there are intermediates in at least some Sn2 reactions in the gas phase, in charge type I reactions, where a negative ion nucleophile attacks a neutral substrate. Two energy minima, one before and one after the transition state, appear in the reaction coordinate (Fig. 10.1). The energy surface for the Sn2 Menshutkin reaction (p. 499) has been examined and it was shown that charge separation was promoted by the solvent.An ab initio study of the Sn2 reaction at primary and secondary carbon centers has looked at the energy barrier (at the transition state) to the reaction. These minima correspond to unsymmetrical ion-dipole complexes. Theoretical calculations also show such minima in certain solvents, (e.g., DMF), but not in water. "... 

TABLE 4. Rates and selectivity parameters for the nucleophilic reactions of anilines at cycloalkyl secondary carbon centers (c-(CF I2) lCHOSOiCfdLZ) in MeCN at 65.0 °C53... 

The structure of the TS for the nucleophilic reaction of aniline at secondary cycloalkyl carbon centers depends on the size of the cycloalkyl group53. We note in Table 4 that although the rate is fastest with the cyclopentyl and slower with the cyclohexyl compound, the TS shifts successively to a later position along the reaction coordinate (more... 

A common way for the introdnction of azides into carbohydrates is the nucleophilic replacement of leaving groups by the azide ion. These reactions can be divided into three groups substitutions at the anomeric center leading to glycosyl azides, substitutions at primary, and substitutions at secondary carbon atoms. 

The reaction proceeds well with unhindered secondary amines as both nucleophiles and bases. The yield of allylic amine formed depends upon how easily palladium hydride elimination occurs from the intermediate. In cases such as the phenylation of 2,4-pentadienoic acid, elimination is very facile and no allylic amines are formed with secondary amine nucleophiles, while phenylation of isoprene in the presence of piperidine gives 29% phenylated diene and 69% phenylated allylic amine (equation 30).84 Arylation occurs at the least-substituted and least-hindered terminal diene carbon and the amine attacks the least-hindered terminal ir-allyl carbon. If one of the terminal ir-allyl carbons is substituted with two methyl groups, however, then amine substitution takes place at this carbon. The reasons for this unexpected result are not clear but perhaps the intermediate reacts in a a- rather than a ir-form and the tertiary center is more accessible to the nucleophile. Primary amines have been used in this reaction also, but yields are only low to moderate.85 A cyclic version occurs with o-iodoaniline and isoprene.85... 

Bromooctane is a secondary bromoalkane, which undergoes Sn2 substitution. Since SN2 reactions proceed with inversion of configuration, the configuration at the carbon chirality center is inverted. (This does not necessarily mean that all R isomers become S isomers after an Sn2 reaction. The R,S designation refers to the priorities of groups, which may change when the nucleophile is varied.)... 

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