Page 407 - Advanced Organic Chemistry Part B - Reactions & Synthesis

380 An especially important case is the enantioselective hydrogenation of
29
-amidoacrylic acids, which leads to -aminoacids. A particularly detailed study has
CHAPTER 5
been carried out on the mechanism of reduction of methyl Z- -acetamidocinnamate by
30
Reduction of a rhodium catalyst with a chiral diphosphine ligand DIPAMP. It has been concluded
Carbon-Carbon Multiple
Bonds, Carbonyl that the reactant can bind reversibly to the catalyst to give either of two complexes.
Groups, and Other Addition of hydrogen at rhodium then leads to a reactive rhodium hydride and
Functional Groups
eventually to product. Interestingly, the addition of hydrogen occurs most rapidly in
the minor isomeric complex, and the enantioselectivity is due to this kinetic preference.
OMe

P P
Rh
MeO

DIPAMP

CO Me
2
PhCH C
H 2 NHAc H
2
slower major minor faster
complex complex
Rh
Rh-hydride Rh-hydride
complex complex

minor (R) major (S)
product product

A thorough computational study of this process has been carried out using
31
B3LYP/ONIOM calculations. The rate-determining step is found to be the formation
of the rhodium hydride intermediate. The barrier for this step is smaller for the minor
complex than for the major one. Additional details on this study can be found at:

Visual models and additional information on Asymmetric Hydrogenation can be
found in the Digital Resource available at: Springer.com/carey-sundberg.

29
J. Halpern, in Asymmetric Synthesis, Vol. 5, J. D. Morrison, ed., Academic Press, Orlando, FL, 1985;
A. Pfaltz and J. M. Brown, in Stereoselective Synthesis, G. Helmchen, R. W. Hoffmann, J. Mulzer, and
E. Schauman, eds., Thieme, New York, 1996, Part D, Sect. 2.5.1.2; U. Nagel and J. Albrecht, Catalysis
Lett., 5, 3 (1998).
30 C. R. Landis and J. Halpern, J. Am. Chem. Soc., 109, 1746 (1987).
31
S. Feldgus and C. R. Landis, J. Am. Chem. Soc., 122, 12714 (2000).