Stereochemistry nucleophilic aliphatic substitution

Figure 3-22 shows a nucleophilic aliphatic substitution with cyanide ion as a nucleophile, i his reaction is assumed to proceed according to the S f2 mechanism with an inversion in the stereochemistry at the carbon atom of the reaction center. We have to assign a stereochemical mechanistic factor to this reaction, and, clearly, it is desirable to assign a mechanistic factor of (-i-1) to a reaction with retention of configuration and (-1) to a reaction with inversion of configuration. Thus, we want to calculate the parity of the product, of 3 reaction from the parity of the... 

Quite early. Ingold and coworkers (Baker et al., 1928) proposed carbocations as intermediates in these reactions, as the product pattern and the stereochemistry display similarities to those of nucleophilic aliphatic substitutions of molecules with anionic leaving groups like halogenide ions, arenesulfonate ions, etc. (7-2). 

For another classical problem of nucleophilic aliphatic substitution and rearrangement, namely pinacolic deaminations and rearrangements, the use of cyclohexane derivatives with a tert-hvXyX group instead of open-chain alkane derivatives was very helpful. The stereochemistry of these reactions was studied first by Bernstein and Whitmore (1939). Specific labeling with used first by Collins and his coworkers (Benjamin et al., 1957), helped significantly to elucidate the complex pathway of pinacolic deamination. Even summarizing the results would take far too much space here. 

Lund, T. Correlation between inner-sphere stabilization and stereochemistry for the aliphatic nucleophilic substitution. Tetrahedron Lett. 1991, 32,1595-1598. 

Aliphatic R groups are not the only ones that undergo oxidative addition. Vinyl and phenyl groups work also Eqs. 12.25 and 12.26 give examples. Sn2 mechanisms cannot be operative, because nucleophilic substitution does not occur on sp hybridized carbons. With alkenes, the stereochemistry of the double bond is almost always retained. This rules out radical intermediates because a vinyl radical would undergo rapid inversion, thereby scrambling the stereochemistry of the alkene in the product. 

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