Page 254 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

234 NH 2 NH 2
N N
CHAPTER 2 N N
HOCH N
Stereochemistry, 2 N N HOCH 2 O N
Conformation, O
and Stereoselectivity
HO HO OH
OH
pseudo-axial pseudo-equatorial

Topic 2.4. Polar Substituent Effects in Reduction of Carbonyl
Compounds

The stereoselectivity of hydride reduction was discussed in terms of steric
approach and torsional effects in Section 2.4.1.2. Two additional factors have to be
considered when polar substituents are present. The polar substituents enhance the
importance of hyperconjugation involving and orbitals. Polar substituents also
∗
introduce bond dipoles and the potential for electrostatic interactions. Both the hyper-
conjugative and dipolar interactions depend on the equatorial or axial orientation of
the substituent. There are two contrasting views of the nature of the hyperconjugative
effects. One is the Felkin-Ahn model, which emphasizes stabilization of the devel-
∗
oping negative charge in the forming bond by interaction with the orbital of the
substituent. The preferred alignment for this interaction is with an axial position and
the strength of the interaction should increase with the electron-accepting capacity
of the substituent. 262 The Cieplak model 263 emphasizes an alternative interaction in
which the orbital of the C−X bond acts as a donor to the developing antibonding
orbital. 264 It has been pointed out that both of these interactions can be present, since
they are not mutually exclusive, although one should dominate. 265 Moreover, hydride
reductions involve early transition states. The electronic effects of substituents on the
reactant should be more prominent than effects on the TS.

Nu – Nu –
O O

:
X X
hyperconjugation hyperconjugation
in Felkin-Ahn model in Cieplak model

There have been computational efforts to understand the factors controlling axial
and equatorial approaches. A B3LYP/6-31G calculation of the TS for addition of
∗
lithium hydride to cyclohexanone is depicted in Figure 2.34. 266 The axial approach is

262
N. T. Ahn, Top. Current Chem., 88, 145 (1980).
263
A. S. Cieplak, J. Am. Chem. Soc., 103, 4540 (1981).
264 Both the Felkin-Ahn and Cieplak models are also applied to alkyl substituents.
265 H. Li and W. J. le Noble, Recl. Trav. Chim. Pays-Bas, 111, 199 (1992).
266
T. Senju, and S. Tomoda, Chem. Lett., 431 (1997).