A New Type of Ketone Catalyst for Asymmetric Epoxidation

Full text of DOI:10.1021/jo971701q

8622
J . Org. Chem. 1997, 62, 8622-8623
Ch a r t 1
A New Typ e of Keton e Ca ta lyst for
Asym m etr ic Ep oxid a tion
Zhi-Xian Wang and Yian Shi*
Department of Chemistry, Colorado State University,
Fort Collins, Colorado 80523
Received September 12, 1997
Dioxiranes generated in situ from Oxone and chiral
ketones have been shown to be remarkably promising
oxidation reagents for asymmetric epoxidation of olefins.1-4
Our efforts have been focusing on ketones that have
stereogenic centers in the vicinity of the reacting carbonyl
groups and fused ring(s) or a quaternary carbon R to the
carbonyl groups (ketones 1 and 4 in Chart 1). The
closeness of the stereogenic centers to the carbonyl group
(reacting center) was intended to optimize the stereo-
chemical communication between olefin substrates and
the catalyst during the epoxidation. The introduction of
the fused ring(s) and quaternary carbon was intended
to maintain the chiral elements in the ketones by
minimizing the potential epimerization due to the acidity
of the protons R to the carbonyl group. Among the
ketones closely related to 1, we recently found that a
fructose-derived ketone 3 displayed high enantioselec-
tivity for the epoxidation of a wide range of trans- and
trisubstituted olefins.4 In addition to ketone 1, we have
also been actively studying ketone 4, which uses another
fused ring to replace the quaternary center existing in
1.5 As an initial part of our study, ketones 6a -e, as close
analogues of 4, were prepared and tested for asymmetric
epoxidation. Herein, we wish to report our preliminary
results on the epoxidation catalyzed by these ketones.
Ketones 6a -e were prepared from (-)-quinic acid in
a straightforward manner based on the existing proce-
dures.6 The detailed synthesis is outlined in Scheme 1.7
Sch em e 1a
a
Reaction Conditions: (a) 2,2-dimethoxypropane, benzene,
TsOH (cat.), reflux (15 h), 83.8%; (b) MeONa, MeOH, rt, 5 h, 82%;
(c) PCC, 3A MS, pyridine, CH2Cl2, rt, 24 h, 60%; (d) NaBH4,
MeOH, 1 h, 98%; (e) TBSCl, imidazole, DMAP, CH2Cl2, rt, 3 h,
96%; (f) OsO4, NMO, tBuOH, pyridine, H2O, reflux, 4 h, 90-95%;
(g) 2-methoxypropene, CSA (cat.), CH2Cl2, rt, 96-99%; (h) TBAF,
rt, 0.5 h, 70%; (i) DMSO, oxalyl chloride, CH2Cl2, -78 °C, 90-
100%; (j) DIBAL-H (1 M in hexane), THF, -20 to 0 °C, 92-94%;
(k) (1) for 6b Ac2O, Et3N, DMAP, CH2Cl2, rt, then TBAF, rt, 86%
two steps, (2) for 6c BzCl, Et3N, DMAP, CH2Cl2, rt, then TBAF,
rt, 99% two steps, (3) for 6d TsCl, Et3N, DMAP, CH2Cl2, rt, then
TBAF, rt, 82% two steps; (l) NaBH4, EtOH, aq NaCl, rt, 30 h,
100%; (m) TBSCl, imidazole, DMAP, CH2Cl2, 0 °C; (n) PCC, 3A
MS, CH2Cl2, then POCl3, pyridine, 54% two steps; (o) NaBH4,
MeOH, rt, then Ac2O, pyridine, DMAP, CH2Cl2, rt, 96%.
* To whom correspondence should be addressed. Phone: (970) 491-
7424. Fax: (970) 491-1801. E-mail: yian@lamar.colostate.edu.
(1) For general leading references on dioxiranes see: (a) Adam, W.;
Curci, R.; Edwards, J . O. Acc. Chem. Res. 1989, 22, 205-211. (b)
Murray, R. W. Chem. Rev. 1989, 89, 1187-1201. (c) Curci, R.; Dinoi,
A.; Rubino, M. F. Pure Appl. Chem. 1995, 67, 811-822. (d) Adam, W.;
Smerz, A. K. Bull. Soc. Chim. Belg. 1996, 105, 581-599.
(2) For examples of in situ generation of dioxiranes see: (a) Edwards,
J . O.; Pater, R. H.; Curci, R.; Di Furia, F. Photochem. Photobiol. 1979,
30, 63-70. (b) Curci, R.; Fiorentino, M.; Troisi, L.; Edwards, J . O.;
Pater, R. H. J . Org. Chem. 1980, 45, 4758-4760. (c) Gallopo, A. R.;
Edwards J . O. J . Org. Chem. 1981, 46, 1684-1688. (d) Cicala, G.; Curci,
R.; Fiorentino, M.; Laricchiuta, O. J . Org. Chem. 1982, 47, 2670-2673.
(e) Corey, P. F.; Ward, F. E. J . Org. Chem. 1986, 51, 1925-1926. (f)
Denmark, S. E.; Forbes, D. C.; Hays, D. S.; DePue, J . S.; Wilde, R. G.
J . Org. Chem. 1995, 60, 1391-1407 and references therein. (g) Yang,
D.; Wong, M. K.; Yip, Y. C. J . Org. Chem. 1995, 60, 3887-3889 and
references therein.
High yields were obtained in almost all the steps. These
ketones exist partially in hydrate forms, suggesting that
the carbonyl groups are quite electrophilic. The epoxi-
dation of trans-â-methylstyrene as substrate using ketone
6b was initially carried out to determine the solvent effect
on the reaction. Among the solvents tested (Table 1),
dimethoxyethane (DME) was found to be the solvent of
choice for both reactivity and selectivity.
Ketones 6a -e differ from one another in the substit-
uents at the â position to the carbonyl group. To test
whether these substituents have any effect on the ep-
oxidation, three types of olefins, i.e., trans- and cis-olefins
and terminal olefins, were employed as substrates. The
results presented in Table 2 show that the substituents
have some effects on both the conversion of the substrate
and the enantiomeric excess of the epoxides, and the
response of the three olefins to the substituent change
is somewhat different. The effect could result from the
conformational and electronic changes of the catalysts
imposed by the substituents. This observation opens up
the possibilities that substituents on ketone catalysts
could be used as handles to fine-tune the catalyst
reactivity and selectivity.
(3) For examples of asymmetric epoxidation mediated by chiral
ketones see: (a) Curci, R.; Fiorentino, M.; Serio, M. R. J . Chem. Soc.,
Chem. Commun. 1984, 155-156. (b) Curci, R.; D’Accolti, L.; Fiorentino,
M.; Rosa, A. Tetrahedron Lett. 1995, 36, 5831-5834. (c) Reference 2f.
(d) Brown, D. S.; Marples, B. A.; Smith, P.; Walton, L. Tetrahedron
1995, 51, 3587-3606. (e) Yang, D.; Yip, Y. C.; Tang, M. W.; Wong, M.
K.; Zheng, J . H.; Cheung, K. K. J . Am. Chem. Soc. 1996, 118, 491-
492. (f) Yang, D.; Wang, X.-C.; Wong, M.-K.; Yip, Y.-C.; Tang, M.-W.
J . Am. Chem. Soc. 1996, 118, 11311-11312.
(4) (a) Tu, Y.; Wang, Z.-X.; Shi, Y. J . Am. Chem. Soc. 1996, 118,
9806-9807. (b) Wang, Z.-X.; Tu, Y.; Frohn, M.; Shi, Y. J . Org. Chem.
1997, 62, 2328-2329.
(5) For
a related C2-symmetric five-membered ring ketone see:
Armstrong, A.; Hayter, B. R. Tetrahedron Asymmetry 1997, 8, 1677-
1684.
(6) For leading references see: (a) Shing, T. K. M.; Tang, Y.
Tetrahedron 1990, 46, 6575-6584. (b) Shing, T. K. M.; Tang, Y.
Tetrahedron 1991, 47, 4571-4578. (c) White, J . D.; Cammack, J . H.;
Sakuma, K.; Rewcastle, G. W.; Widener, R. K. J . Org. Chem. 1995,
60, 3600-3611.
(7) New compounds have been fully characterized spectroscopically.
Elemental compositions have been established by combustion analysis
and/or high-resolution mass spectrometry.
To further reveal the catalytic features of these ke-
tones, 6b was chosen as a representative to explore the
epoxidation of a variety of olefins. The results are shown
in Table 3. Compared to ketone 3, 6b is less enantiose-
S0022-3263(97)01701-5 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 25, 1997 8623
Ta ble 1. Solven t Effect on Asym m etr ic Ep oxid a tion of
Ta ble 3. Asym m etr ic Ep oxid a tion of Rep r esen ta tive
Olefin s by Keton e 6ba
â-Meth ylstyr en e w ith Keton e 6ba
cntry
solvent
T (° C)
t (h)
convn (%)
ee (%)
1
2
3
4
5
6
7
CH3CN
0
0
-10
0
0
0
0
4
4
4
4
4
4
3
58.4
100
95
43
99.4
91
63
70
73
66
67
67
64
DMEb
DME
DMMb
dioxane
DMM/CH3CN (2/1)
DMF
99
a
All reactions were carried out with trans-â-methylstyrene (0.4
mmol), ketone 6b (0.02 mmol), Oxone (0.55 mmol), and K2CO3
(2.31 mmol) in organic solvent (6 mL) and buffer (0.05
M
Na2B4O7‚10H2O in 4 × 10-4 M aqueous EDTA) (4 mL). The
conversion was determined by GC (HP-17 column), and the
enantioselectivity was determined by Chiral GC (Chiraldex γ-TA
b
column). DME ) dimethoxyethane, DMM ) dimethoxymethane.
Ta ble 2. Ep oxid a tion of Rep r esen ta tive Olefin s w ith
Keton es 6a -e
a
All reactions were carried out with substrate (1 equiv), ketone
(0.05-0.1 equiv), Oxone (1.38 equiv), and K2CO3 (5.8 equiv) in (1.5:
1, v/v) DME-buffer (prepared by mixing 100 mL of 0.1 M aqueous
b
K2CO3 with 0.5 mL of AcOH) except for entries 1 and 6. The
reactions were carried out in (2:1:2, v/v) DME-DMM-buffer (the
same as above). c The epoxides were purified by flash chromatog-
d
raphy and gave satisfactory spectroscopic characterization. Enan-
tioselectivity was determined by chiral HPLC (Chiralcel OD
a
e
The reactions were carried out with trans-stilbene (0.2 mmol),
column). Enantioselectivity was determined by chiral GC (Chiral-
dex γ-TA column). f Enantioselectivity was determined by 1H NMR
ketone (0.02 mmol), Oxone (0.276 mmol), and K2CO3 (1.16 mmol)
in DME/DMM (3 mL, 2/1, v/v) and buffer (prepared by mixing 100
mL of 0.1 M aqueous K2CO3 with 0.5 mL of AcOH) (2 mL) at -10
g
shift analysis of the epoxide product directly with Eu(hfc)3. The
absolute configurations were determined by comparing the mea-
sured optical rotations with the reported ones.
b
°C. The reactions were stopped after 6 h. Everything is the same
except that the reactions were carried out in DME (3 mL). c The
reactions were carried out with styrene (0.4 mmol), ketone (0.02
or 0.04 mmol), Oxone (0.55 mmol), and K2CO3 (2.31 mmol) in DME
(5 mL, 2/1, v/v) and buffer (the same as above) (3.2 mL) at -10
°C. The reactions were stopped after 6 h for ketone 6a and 4 h for
ketones provide a strong stimulus for further studies,
particularly for the epoxidation of terminal olefins, which
is still a challenging problem. Future efforts will be
devoted to the elucidation of the structural requirements
for a ketone to be an effective catalyst for asymmetric
epoxidation. Efficient synthesis of ketone catalysts will
also be pursued.
ketone 6b-e. Isolated yields. e Enantioselectivity was deter-
d
mined by chiral HPLC (Chiralcel OD column). f The conversion
g
was determined by GC (HP-17 column). Enantioselectivity was
determined by chiral GC (Chiraldex γ-TA column).
Ack n ow led gm en t. We are grateful for the generous
financial support from Colorado State University, the
Camille and Henry Dreyfus New Faculty Award Pro-
gram, the General Medical Sciences of the National
Institutes of Health (GM55704-01), Beckman Young
Investigator Award Program, and Hoechst Celanese. We
would like to thank Professors Greenberg, Hegedus,
Meyers, and Williams for the use of their GC, chiral
HPLC apparatuses, and syringe pumps. We also thank
Michael Frohn, J on Lorenz, and Yong Tu for their
helpful discussions.
lective for both trans- and trisubstituted olefins. How-
ever, a few noticeable features of this type of ketone are
worth mentioning: (1) 6a -e are more stable and reactive
than 3, and a smaller amount of catalyst is required to
achieve good conversion. (2) Electron-deficient olefins
can be epoxidized by 6b (entries 2 and 3, Table 3),
indicating that the dioxirane derived from this type of
ketone is very electrophilic.8 The high enantioselectivity
obtained with the enone (entry 3, Table 3) suggests that
the catalyst can effectively compete with the ketones
present in the substrate and the epoxide product. (3) The
enantiomeric excess for the epoxidation of the cis-olefins
and terminal olefins is encouragingly high. The epoxi-
dation of styrene gives up to 67% ee, which is close to
the best reported.9
Su p p or tin g In for m a tion Ava ila ble: Characterizations
of compounds 7-12 and 6a -e along with the NMR spectral,
GC, and HPLC data for the determination of the enantiomeric
excess of the formed epoxides (11 pages).
In summary, a ketone with a fused ring at each side
of the carbonyl group has been shown to be an effective
catalyst for asymmetric epoxidation. The results show
that this type of ketone displays a distinct reaction
pattern. The unique features associated with these
J O971701Q
(9) (a) Collman, J . P.; Lee, V. J .; Kellen-Yuen, C. J .; Zhang, X.; Ibers,
J . A.; Brauman, J . I. J . Am. Chem. Soc. 1995, 117, 692-703. (b) Gross,
Z.; Ini, S. J . Org. Chem. 1997, 62, 5514-5521.
(10) (a) Chang, H.-T.; Sharpless, K. B. J . Org. Chem. 1996, 61,
6456-6457. (b) Cabon, O.; Buisson, D.; Larcheveque, M.; Azerad, R.
Tetrahedron Asymmetry 1995, 6, 2211-2218. (c) Witkop, B.; Foltz, C.
M. J . Am. Chem. Soc. 1957, 79, 197-201. (d) Brandes, B. D.; J acobsen,
E. N. J . Org. Chem. 1994, 59, 4378-4380. (e) Berti, G.; Bottari, F.;
Ferrarini, P. L.; Macchia, B. J . Org. Chem. 1965, 30, 4091-4096. (f)
Solladie-Cavallo, A.; Diep-Vohuule, A. J . Org. Chem. 1995, 60, 3494-
3498. (g) Fujisawa, T.; Takemura, I.; Ukaji, Y. Tetrahedron Lett. 1990,
31, 5479-5482. (h) J acobsen, E. N.; Zhang, W. PCT Int. Appl. W091
14,694, U.S. Appl. 496,992; Chem. Abstr. 1992, 117, 106067f.
(8) For nucleophilic asymmetric epoxidation see: (a) Enders, D.; Zhu,
J .; Raabe, G. Angew. Chem., Int. Ed. Engl. 1996, 35, 1725-1728. (b)
Elston, C. L.; J ackson, R. F. W.; MacDonald, S. J . F.; Murray, P. J .
Angew. Chem., Int. Ed. Engl. 1997, 36, 410-412. (c) Bougauchi, M.;
Watanabe, S.; Arai, T.; Sasai, H.; Shibasaki, M.; J . Am. Chem. Soc.
1997, 119, 2329-2330. (d) Bentley, P. A.; Bergeron, S.; Cappi, M. W.;
Hibbs, D. E.; Hursthouse, M. B.; Nugent, T. C.; Pulido, R.; Roberts, S.
M.; Wu, L. E. J . Chem. Soc., Chem. Commun. 1997, 739-740.