Topic 2.4. Polar Substituent Effects in Reduction of Carbonyl Compounds

Topic 2.4. Polar Substituent Effects in Reduction of Carbonyl Compounds 

Both the Felkin-Ahn and Cieplak models are also applied to alkyl substituents. 

Polar substituents may also affect stereoselectivity through an electrostatic effect that depends on the size and orientation of the bond dipole. These are relatively easy to determine for the ground state molecule but may be altered somewhat in the TS. The dipole from an electronegative substituent prefers to be oriented anti to the carbonyl substituent. 

Rosenberg and co-workers approached the problem of separating the hyper-conjugative and electrostatic interactions by examining the product ratios for NaBH4 reduction of both axially and equatorially oriented substituents in 4-r-butylcyclohexanones. The product ratios were used to calculate the energy difference, AAG (kcal/mol), for axial and equatorial approach. The results are given in Table 2.10. 

Substituent % Equatorial % Axial AAG (kcal/mol) % Equatorial % Axial AAG (kcal/mol) 

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