Page 259 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

These effects are attributed to differences in the -donor character of the C−C bonds 239
resulting from the substituent (Cieplak model). Electron-attracting groups diminish the
PROBLEMS
donor capacity and promote syn addition. An alternative explanation invokes a direct
electrostatic effect arising from the C−X bond dipole. 276

favors syn O
approach

+
X
+
favors anti
approach

The arguments supporting the various substituent effects on stereoselectivity in
cyclic ketones have been discussed by some of the major participants in the field
in a series of review articles in the 1999 issue of Chemical Reviews. 277 While many
of the details are still subject to discussion, several general points are clear. (1) For
cyclohexanones, in the absence of steric effects, the preferred mode of attack by small
hydride reducing agents is from the axial direction. Torsional effects are a major
contributing factor to this preference. (2) When steric factors are introduced, either by
adding substituents to the ketone or using bulkier reducing agents, equatorial approach
is favored. Steric approach control is generally the dominant factor for bicyclic ketones.
(3) In bicyclic ketones, electron donor substituents favor an anti mode of addition and
acceptor substituents favor a syn approach.
The issues that remain under discussion are: (1) the relative importance of the
acceptor (Felkin-Ahn) or donor (Cieplak) hyperconjugation capacity of substituents;
(2) the relative importance of electrostatic effects; and (3) the role of reactant
pyramidalization in transmitting the substituent effects. Arguments have been offered
regarding the importance of electrostatic effects in all the systems we have discussed.
Consideration of electrostatic effects appears to be important in the analysis of stereo-
selective reduction of cyclic ketones. Orbital interactions (hyperconjugation) are also
involved, but whether they are primarily ground state (e.g., reactant pyramidalization)
or transition state (e.g., orbital stabilization) effects is uncertain.

General References

D. Ager and M. B. East, Asymmetric Synthetic Methodology, CRC Press, Boca Raton, FL, 1996.
R. S. Atkinson, Stereoselective Synthesis, John Wiley & Sons, New York, 1995.
J. Dale, Stereochemistry and Conformational Analysis, Verlag Chemie, New York, 1978.
E. L. Eliel, N. L. Allinger, S. J. Angyal, and G. A. Morrison, Conformational Analysis, Wiley-Interscience,
New York, 1965.
E. L. Eliel, S. H. Wilen, and L. N. Mander, Stereochemistry of Organic Compounds, John Wiley & Sons,
New York, 1993.
E. Juaristi and G. Cuevas, The Anomeric Effect, CRC Press, Boca Raton, FL, 1995.
A. J. Kirby, Stereoelectronic Effects, Oxford University Press, Oxford, 1996.
276 W. Adcock, J. Cotton, and N. A. Trout, J. Org. Chem., 59, 1867 (1994).
277
B. W. Gung and W. G. le Noble, eds., Thematic Issue on Diastereoselection, Chemical Reviews, 99,
No. 5, 1999.