Significant effects of nonconjugated remote substituents in catalytic asymmetric epoxidation

Full text of DOI:10.1021/ja980435a

J. Am. Chem. Soc. 1998, 120, 7659-7660
7659
Under our previously reported in situ conditions,5,11 epoxidation
of symmetrical, meta- or para-substituted trans-stilbenes 6 and
7 catalyzed by chiral (2S,5R)-ketones 1-5 all gave the (S,S)-
epoxides as the major products. As suggested by the X-ray
structure of ketone 2 (Figure 1), (2S,5R)-dioxiranes 1a-5a adopt
the most stable chair conformations with alkyl substituents at the
equatorial positions and a 2-chloro atom at the axial position
(Figure 2). Approach by bulky substrates 6 and 7 from the axial
face is considered unlikely due to the steric hindrance of axial
protons H-3 and H-5. For the equatorial approach, there are two
possible spiro TS. The sterically favored one (TSf) has phenyl
groups of trans-stilbenes positioned away from the 2-chloro atom
of dioxiranes 1a-5a, leading to (S,S)-epoxides. The disfavored
one (TSd), giving rise to the (R,R)-epoxides, has steric clash
between the 2-chloro atom and the phenyl groups. The free
energy difference between TSf and TSd determines the enantio-
selectivity.12
Significant Effects of Nonconjugated Remote
Substituents in Catalytic Asymmetric Epoxidation
Dan Yang,* Yiu-Chung Yip, Jian Chen, and
Kung-Kai Cheung
Department of Chemistry, The UniVersity of Hong Kong
Pokfulam Road, Hong Kong
ReceiVed February 9, 1998
Since Jacobsen’s report on electronic effects of remote sub-
stituents in asymmetric epoxidation catalyzed by chiral (salen)-
Mn(III) complexes,1 the electronic tuning has been recognized
as an important tool in catalyst design. While the origin of
electronic effects is poorly understood, a great deal of success in
asymmetric catalysis has been achieved by changing conjugated
remote substituents.2,3 Here we report that electronic properties
of nonconjugated remote substituents on the catalysts have sig-
nificant effects in asymmetric epoxidation by chiral dioxiranes.
We also propose an electrostatic model to account for the elec-
tronic effects of those substituents.
Chiral dioxiranes, generated in situ from chiral ketones and
Oxone, are excellent reagents for asymmetric epoxidation of un-
functionalized trans-olefins and trisubstituted olefins.4-7 As
Molecular models13 suggested that the 2-chloro atom is very
close to the dioxirane group in 1a-5a and therefore is unlikely
to have steric interactions with the remote para- or meta-
substituents of trans-stilbenes 6 and 7 in either TSf or TSd. This
implies that the enantioselectivities of epoxidation are not sensitive
to the steric sizes but possibly to the electronic properties of those
remote substituents. Indeed, by using ketone 2 as the catalyst,
higher ee’s were obtained for the more electron-rich olefins, and
the Hammett plot of log(er) against either σm or σp showed a
linear relation (Figure 3: F ) -0.84 and r ) 0.989 for plot A;
F ) -0.86 and r ) 0.985 for plot B).14 The negative slope of
plot A or plot B could be understood by considering the
unfavorable n-π electronic repulsion, present in TSd but not in
TSf, between the 2-chloro atom of dioxiranes and the phenyl
groups of trans-stilbenes (Figure 2). The evidence for the n-π
electronic repulsion came from the observation that, despite of
smaller steric size of Cl atom compared to the methyl group,
ketone 2 gave much higher ee (85%) than its C2 epimer ketone
8 (32% ee) for epoxidation of trans-stilbene under the same
reaction conditions. For trans-stilbenes with stronger electron-
donating substituents (smaller σm or σp values), the n-π electronic
repulsion in TSd becomes more severe, thereby giving higher ee’s.
Note that the slope of plot A or plot B (the apparent reaction
constant F) is equal to Ff - Fd, where reaction constants Ff and
Fd represent charge distributions of TSf and TSd, respectively.15
The negative value of F in plot A thus means that Ff is more
negative or less positive than Fd, suggesting that more positive
reactions between dioxiranes and olefins follow a concerted one-
step process with a spiro transition state (TS),5b,6a,8-10 chiral
dioxirane epoxidation offers an ideal system for understanding
the electronic effects of remote substituents on enantioselectivity.
To probe the effect of nonconjugated remote substituents, a new
series of chiral ketone catalysts 1-5, prepared from (R)-carvone,
was selected. Ketones 1-5 all have a quaternary carbon at C2
position, but they differ in the remote substituent at C8 position.
(1) (a) Jacobsen, E. N.; Zhang, W.; Gu¨ler, M. L. J. Am. Chem. Soc. 1991,
113, 6703. (b) Palucki, M.; Finney, N. S.; Pospisil, P. J.; Gu¨ler, M. L.; Ishida,
T.; Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120, 948.
(2) For recent examples of catalyst electronic effects on enantioselectivity,
see: (a) Nishiyama, H.; Yamaguchi, S.; Kondo, M.; Itoh, K. J. Org. Chem.
1992, 57, 4306. (b) Park, S. B.; Murata, K.; Matsumoto, H.; Nishiyama, H.
Tetrahedron: Asymmetry 1995, 6, 2487. (c) RajanBabu, T. V.; Casalnuovo,
A. L. J. Am. Chem. Soc. 1992, 114, 6265. (d) RajanBabu, T. V.; Ayers, T.
A.; Casalnuovo, A. L. J. Am. Chem. Soc. 1994, 116, 4101. (e) RajanBabu, T.
V.; Casalnuovo, A. L. J. Am. Chem. Soc. 1996, 118, 6325. (f) Schnyder, A.;
Hintermann, L.; Togni, A. Angew. Chem., Int. Ed. Engl. 1995, 34, 931.
(3) For recent examples of substrate electronic effects on enantioselectivity,
see: (a) Corey, E. J.; Helal, C. J. Tetrahedron Lett. 1995, 36, 9153. (b) Zhang,
H.; Xue, F.; Mak, T. C. W.; Chan, K. S. J. Org. Chem. 1996, 61, 8002.
(4) (a) Curci, R.; Fiorentino, M.; Serio, M. R. J. Chem. Soc., Chem.
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Tetrahedron Lett. 1995, 36, 5831.
(5) (a) Yang, D.; Yip, Y.-C.; Tang, M.-W.; Wong, M.-K.; Zheng, J.-H.;
Cheung, K.-K. J. Am. Chem. Soc. 1996, 118, 491. (b) Yang, D.; Wang, X.-
C.; Wong, M.-K.; Yip, Y.-C.; Tang, M.-W. J. Am. Chem. Soc. 1996, 118,
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Zheng, J.-H.; Cheung, K.-K. J. Am. Chem. Soc. 1998, 120, 5943.
(6) (a) Tu, Y.; Wang, Z.-X.; Shi, Y. J. Am. Chem. Soc. 1996, 118, 9806.
(b) Wang, Z.-X.; Tu, Y.; Frohn, M.; Shi, Y. J. Org. Chem. 1997, 62, 2328.
(c) Wang, Z.-X.; Tu, Y.; Frohn, M.; Zhang, J.-R.; Shi, Y. J. Am. Chem. Soc.
1997, 119, 11224. (d) Wang, Z.-X.; Shi, Y. J. Org. Chem. 1997, 62, 8622.
(7) Denmark, S. E.; Wu, Z.; Crudden, C. M.; Matsuhashi, H. J. Org. Chem.
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(11) Yang, D.; Wong, M.-K.; Yip, Y.-C. J. Org. Chem. 1995, 60, 3887.
(12) Theoretical studies by Houk et al. showed that the spiro transition
state of dioxirane epoxidation could be asynchronous (ref 10a). However, for
epoxidation of trans-stilbenes 6 and 7 by dioxiranes 1a-5a, the extent of
asynchronicity is determined by the unsymmetrical structures of the dioxiranes
but not by the remote substituents of symmetrical trans-stilbenes.
(13) MacroModel version 4.5: Mohamadi, F.; Richards, N. G. J.; Guida,
W. C.; Liskamp, R.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. J.
Comput. Chem. 1990, 11, 440.
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O. Acc. Chem. Res. 1989, 22, 205. (b) Murray, R. W. Chem. ReV. 1989, 89,
1187.
(9) Baumstark, A. L.; McCloskey, C. J. Tetrahedron Lett. 1987, 28, 3311.
(10) For computational studies on dioxirane chemistry, see: (a) Houk, K.
N.; Liu, J.; DeMello, N. C.; Condroski, K. R. J. Am. Chem. Soc. 1997, 119,
10147. (b) Bach, R. D., Andre´s, J. L.; Owensby, A. L.; Schlegel, H. B.;
McDouall, J. W. J. Am. Chem. Soc. 1992, 114, 7207.
(14) (a) Exner, O. In Correlation Analysis in Chemistry; Chapman, N. B.,
Shorter, J., Eds.; Plenum Press: New York, 1978. Chapter 10. (b) Hansch,
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(15) See Supporting Information. Also: Palucki, M. Ph.D. Thesis, Harvard
University, December, 1995.
S0002-7863(98)00435-1 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/18/1998

7660 J. Am. Chem. Soc., Vol. 120, No. 30, 1998
Communications to the Editor
Figure 1. X-ray structure of ketone 2 (ORTEP view).
Figure 3. Hammett plots: A, asymmetric epoxidation of olefins 6 by
catalyst 2 (ee range: 74-89%); B, asymmetric epoxidation of olefins 7
by catalyst 2 (ee range: 72-87%); C, asymmetric epoxidation of trans-
stilbene by catalysts 1-5 for 22 h in DME-H2O (3:2 v/v) (ee range:
42-87%); D, asymmetric epoxidation of trans-stilbene by catalysts 1-3
and 5 for 1 h in DME-H2O (3:2 v/v; 9) and CH3CN-H2O (2:3 v/v; b),
respectively (ee range: 42-88%).
This implies that, in both TSf and TSd, the negative ends of polar
C-X bonds are closer to the olefin double bond than their positive
ends. By favorable field effects, more polar substituents (higher
F values) should stabilize TSf more than TSd and thus give higher
ee’s, which explains the positive slope of plot C in Figure 3.
Furthermore, the Hammett plot of log(er) against F was found to
have a larger slope when a lower polarity solvent (e.g., 40% water
in DME) was used (Figure 3: plot D).22 The observed solvent
effect on enantioselectivity lends additional support to the
electrostatic model. The strong electrostatic effect in aqueous
solutions23 is not surprising because in water the transition state
for dioxirane epoxidation is much more polarized than the
reactants.17,24
Figure 2. Spiro transition states for dioxirane epoxidation.
Our results represent the first report on electronic effects
imparted by nonconjugated remote substituents in asymmetric
catalysis. The significant effect of C8 substituents of chiral
ketones 1-5 on enantioselectivity (42-87% ee, ∆∆G‡ ca. 1 kcal
mol-1) demonstrates the importance of this new type of electronic
tuning. The proposed electrostatic model should provide a rational
approach to catalyst design.
charges or less negative charges are developed on the olefin
double bond of TSf than that of TSd.16,17
Molecular models also revealed that nonconjugated remote
substituents at the C8 position of dioxiranes 1a-5a were too
remote from the dioxirane group to have steric interactions with
trans-stilbenes 6 and 7 in either TSf or TSd. However, given the
different charge distributions in TSf and TSd, those substituents
may affect the enantioselectivity of epoxidation by through-space
electrostatic interactions, i.e., the field effects.18,19 Indeed, a linear
Hammett plot of log(er) against substituent field constant F14 was
observed for epoxidation of trans-stilbene20 (Figure 3: F ) 1.72
and r ) 0.999 for plot C). As shown in Figure 2, small
substituents F, Cl, OH, OEt, and H at C8 position prefer the axial
orientation, i.e., pointing to the R-face of dioxiranes 1a-5a.21
Acknowledgment. This work was supported by the Hong Kong
Research Grants Council, postdoctoral fellowship to Y.C.Y., and the Hui
Pun Hing Scholarship for Postgraduate Research to J.C. from the
University of Hong Kong. We thank Professors Edwin Vedejs and Yun-
Dong Wu for helpful discussions.
Supporting Information Available: Hammett equations for enan-
tioselective reactions; preparation and characterization data of ketones
1-5 and 8; experimental details for catalytic asymmetric epoxidation
reactions; determination of enantiomeric excess of epoxides, and X-ray
structural analysis of ketones 2 and 8 containing tables of atomic
coordinates, thermal parameters, bond lengths, and angles (57 pages, print/
PDF). See any current masthead page for ordering information and Web
access instructions.
(16) Epoxidation reactions with ketones 1-5 were found to be faster for
more electron-rich substrates, which implies that both Ff and Fd should be
negative and the olefin double bond bears more positive charges in TSf than
in TSd.
(17) For epoxidation of para-substituted styrenes by dimethyldioxirane, a
F value of -0.90 was obtained, indicating the electrophilic nature of the oxygen
transfer process. Baumstark, A. L.; Vasquez, P. C. J. Org. Chem. 1988, 53,
3437.
(18) For a recent review of electronic field effects on chemical reactivity
in organic reactions, see: Bowden, K.; Grubbs, E. J. Chem. Soc. ReV. 1996,
171.
(19) Houk and co-workers reported that electrostatic effects influence the
diastereoselectivities of hydride addition to cyclohexanones carrying remote
polar groups. Wu, Y.-D.; Tucker, J. A.; Houk, K. N. J. Am. Chem. Soc. 1991,
113, 5018.
JA980435A
(21) The axial orientation of C8-Cl atom was also observed in the X-ray
structure of ketone 8.
(22) The in situ epoxidation reactions catalyzed by ketones 1-5 took place
in only two solvent systems, i.e., CH3CN-H2O and DME-H2O. The dielectric
constants for DME, CH3CN, and H2O are 6, 36, and 78, respectively.
(23) For a recent report of the electrostatic effect in water, see: Conroy, J.
L.; Sanders, T. C.; Seto, C. T. J. Am. Chem. Soc. 1997, 119, 4285.
(24) Jenson, C.; Liu, J.; Houk, K. N.; Jorgensen, W. L. J. Am. Chem. Soc.
1997, 119, 12982.
(20) C8 substituted ketones 1-3 gave faster epoxidation reactions and higher
ee’s than unsubstituted ketone 5 (see Supporting Information for details). This
result cannot be explained by Jacobsen’s model (ref 1), which is built upon
the Hammond Postulate argument.