Page 222 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

202 of reactants have been examined, and an empirical model for predicting orientation
has been developed from the data. 173 This model is shown in Figure 2.22. Note that the
CHAPTER 2 DHQD and DHQ ligands have opposite enantioselectivity because they are of opposite
Stereochemistry, absolute configuration.
Conformation,
and Stereoselectivity There have been a several efforts aimed at theoretical modeling and analysis
of the enantioselectivity of osmium-catalyzed dihydroxylation. The system is too
large to be amenable to ab initio approaches, but combinations of quantum chemical
(either MO or DFT) and molecular mechanics make the systems tractable. A hybrid
investigation based on DFT (B3LYP/6-31G) computation and MM3 was applied
to the DHQD PYDZ catalyst PYDZ = 3 5-pyridazinyl). 174 This study examined
2
a number of possible orientations of styrene within the complex and computed
their relative energy. The energies were obtained by combining DFT calculations
on the reaction core of OsO and the double bond, with MM3 calculations on the
4
remainder of the molecule. Two orientations were found to be very close in energy
and these were 2.5–10 kcal/mol more favorable than all the others examined. Both
led to the observed enantioselectivity. The two preferred TS structures are shown in
Figure 2.23.
Most of the differences in energy among the various orientations are due
to differences in the MM portion of the calculation, pointing to nonbonded inter-
actions as the primary determinant of the binding mode. Specifically, attractive
interaction with quinoline ring A ( − stacking, 6.1 kcal/mol), quinoline ring
B (2.3 kcal/mol), and a perpendicular binding interaction with the pyridazine ring
(1.3 kcal/mol) offset the energy required to fit the reactant molecule to the catalytic site.
This is consistent with the view that there is an attractive interaction with the ligand
system.
Norrby, Houk, and co-workers approached the problem by deriving a molecular
mechanics type of force field from quantum chemical calculations. 175 This model,
too, suggests that there are two possible bonding arrangements and that either
might be preferred, depending on the reactant structure. This model was able

Fig. 2.23. Two most favored orientations of styrene for enantioselective dihydroxylation by
(DHQD)PYDZ catalyst. The bridging structure is 3,5-pyridazinyl. Reproduced from J. Am.
Chem. Soc., 121, 1317 (1999), by permission of the American Chemical Society.

173
H. C. Kolb, P. G. Andersson, and K. B. Sharpless, J. Am. Chem. Soc., 116, 1278 (1994).
174 G. Ujaque, F Maseras, and A Lledos, J. Am. Chem. Soc., 121, 1317 (1999).
175
P.-O. Norrby, T. Rasmussen, J. Haller, T. Strassner, and K. N. Houk, J. Am. Chem. Soc., 121, 10186
(1999).