C O M M U N I C A T I O N S
Figure 1. Reaction heat flow vs time for the alkylation of p-(trifluorom-
ethyl)benzaldehyde (0.1 M) with Et2Zn (0.28 M) using 1.9 mol % MIB of
varying enantiopurity at 298 K in toluene: black: 100% ee (-)-MIB;
blue: 40% ee MIB; red: 20% ee MIB. Inset shows rate vs fraction
conversion.
Blackmond recently discussed theoretical models for systems
exhibiting nonlinear effects in which the Curtin-Hammett condition
for equilibrium exchange between species is not met.2c A limiting
case of strong substrate binding may be envisioned where none of
the heterochiral dimer dissociates while all of the homochiral dimer
enters the catalytic cycle via dissociation to the monomer. In this
strong binding limit, the enantiomeric excess of the reaction product
for the reaction using any nonenantiopure catalyst mixture will be
given by eq 3. Equation 2, which may be considered as giving the
product ee for the limit of weak substrate binding, may be compared
with eq 3 to reveal that a greater asymmetric amplification will be
achieved for the strong binding limit, as was observed in the Walsh
study.6 Reaction rates may also be predicted for the weak and strong
binding limits as given by eqs 4 and 5, where r0 is the rate expected
for the enantiopure catalyst [R]0.7
Figure 2. Experimental eeprod (a) and reaction rate (b) data for substituted
benzaldehydes. Weak binding limits for ee and rate are given by eqs 2 and
5, respectively. Strong binding limits for ee and rate are given by eqs 3
and 4, respectively. (b) benzaldehyde; (9) p-tolualdehyde; ([) p-(trifluo-
romethyl)benzaldaldehyde; (2) m-(trifluoromethyl)benzaldehyde.
the Noyori model to allow for nonthermodynamically controlled
monomer/dimer partitioning. This work also highlights an important
point4c concerning nonlinear effects in systems exhibiting this type
of dynamic monomer/dimer interaction: catalyst composition may
be a function of the substrate properties. While in many cases the
observation of nonlinear effects in a reaction is used as a diagnostic
probe of the reaction mechanism, perturbation of the catalyst by
the reaction itself may introduce additional complexity into such a
mechanistic tool.
ee
)
strong binding
limit:
prod
Acknowledgment. Funding from the EPSRC, Merck Research
Laboratories and Pfizer Global Research (D.G.B.) and the National
Institutes of Health (P.J.W.) is gratefully acknowledged.
([R] + 2Khomo[R]2) - ([S] + 2Khomo[S]2)
0([R] + 2Khomo[R]2) + ([S] + 2Khomo[S]2)
ee
(3)
Supporting Information Available: Details of the model calcula-
tions determining the strong and weak binding limits and experimental
details (PDF). This material is available free of charge via the Internet
([R] + 2Khomo[R]2 + [S] + 2Khomo[S]2)
r
r0
)
strong binding
limit:
([R]0 + 2Khomo[R] 20)
(4)
References
([R] + [S])
[R]0
r
r0
)
(5)
weak binding
limit:
(1) (a) Puchot, C.; Samuel, O.; Dun˜ach, E.; Zhao, S.; Agami, C.; Kagan, H.
B. J. Am. Chem. Soc. 1986, 108, 2353. (b) Guillaneux, D.; Zhao, S. H.;
Samuel, O.; Rainford, D.; Kagan, H. B. J. Am. Chem. Soc. 1994, 116,
9430.
Thus, experimental rate and ee data may combined to test the
predictions of eqs 2-5 for weak and strong substrate binding.
Reaction calorimetry5b,8 was used to measure rates for a series of
reactions of substituted benzaldehydes with diethylzinc using the
amino alcohol MIB of varying enantiopurity. Figure 1 shows the
reaction heat flow curves for the reaction using p-(trifluoromethyl)-
benzaldehyde for three different eecat. The inset of the figure shows
the data plotted as reaction rate (mM-1 min1) versus fraction
conversion, where the slopes of the curves give the relative reaction
rates. Product ee’s were also measured for these reactions, and both
rate and ee were then compared to the kinetic model as given in
eqs 2-5 (Figure 2). The experimental data for both rate and ee
fall approximately within the boundaries for weak and strong
binding limits when the ratio Khetero/Khomo ) 30.
(2) Recent reviews: (a) Girard, C.; Kagan, H. B. Angew. Chem., Int. Ed.
1998, 37, 2922. (b) Avalos, M.; Babiano, R.; Cintas, P.; Jimenez, J. L.;
Palacios, J. C. Tetrahedron: Asymmetry 1997, 8, 2997. (c) Blackmond,
D. G. Acc. Chem. Res. 2000, 33, 402.
(3) Oguni, N.; Matsuda, Y.; Kaneko, T. J. Am. Chem Soc. 1988, 110, 7877.
(4) (a) Noyori, R.; Kitamura, M. Angew. Chem., Int. Ed. 1991, 30, 49. (b)
Yamakawa, M.; Noyori, R. J. Am. Chem. Soc. 1995, 117, 6327. (c)
Kitamura, M.; Suga, S.; Oka, H.; Noyori, R. J. Am. Chem. Soc. 1998,
120, 9800.
(5) (a) Nugent, W. A. Chem. Commun. 1999, 1369. (b) Rosner, T., Sears, P.
J., Nugent, W. A.; Blackmond, D. G. Org. Lett. 2000, 2, 2511.
(6) Chen, Y. K.; Costa, A. M.; Walsh, P. J. J. Am. Chem. Soc. 2001, 123,
5378.
(7) The product ee and reaction rates for the strong and weak binding limits
in eqs 2-5 refer to the effect that strongly or weakly binding substrates
have on the monomer-dimer distribution established in Scheme 1b in
the absence of substrate.
(8) (a) Rosner, T.; Le Bars, J.; Pfaltz, A.; Blackmond, D. G. J. Am. Chem.
Soc. 2001, 123, 1848. (b) Blackmond, D. G.; McMillan, C. R.; Ramdeheel,
S.; Schorm, A.; Brown, J. M. J. Am. Chem. Soc. 2001, 123, 10103.
Thus, this model rationalizes the apparently anomalous results
observed by Walsh and co-workers through a simple extension of
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