Asymmetric epoxidation of allylic alcohols catalyzed by new chiral vanadium(V) complexes

Article abstract of DOI:10.1016/S0957-4166(02)00741-3

Vanadium catalysts bearing (+)-ketopinic acid-based chiral hydroxamic acids as constituent ligands are investigated in the asymmetric epoxidation of allylic alcohols. Chiral ligands lacking an N-substituent and those having a bulkier aryl group in the bor

Full text of DOI:10.1016/S0957-4166(02)00741-3

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 2625–2628
Asymmetric epoxidation of allylic alcohols catalyzed by new
chiral vanadium(V) complexes
Hsyueh-Liang Wu and Biing-Jiun Uang*
Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 300, People’s Republic of China
Received 6 October 2002; revised 30 October 2002; accepted 31 October 2002
Abstract—Vanadium catalysts bearing (+)-ketopinic acid-based chiral hydroxamic acids as constituent ligands are investigated in
the asymmetric epoxidation of allylic alcohols. Chiral ligands lacking an N-substituent and those having a bulkier aryl group in
the bornane skeleton provided better selectivity. © 2002 Elsevier Science Ltd. All rights reserved.
Chiral epoxides have gained immense importance in the
domain of organic synthesis in view of their wide
applicability as building blocks for many important
chiral compounds including complex organic
molecules.1 Prior to the usage of the titanium-based
catalytic system, the Sharpless group had reported their
first asymmetric epoxidation reactions using chiral
vanadium hydroxamate complexes 1.2 Yamamoto’s
vanadium complexes containing axial-chiral hydrox-
amic acids 23 and Bolm’s vanadium catalyst4 bearing
paracyclophane type planar-chiral ligands 3 are subse-
quent successful catalysts employed in the asymmetric
epoxidation of allylic alcohols. The recent disclosure by
Yamamoto et al. utilizing an amino acid-based hydrox-
amic acid ligand 45 for asymmetric epoxidations is
another significant contribution to the repertoire of
these vanadium catalysts (Fig. 1).
propen-1-ol 7a was conducted as a representative
example by using the hydroxamic acids 6 in combina-
tion with VO(OiPr)3 and tert-butyl hydroperoxide
(tBHP 5.5 M in decane) as oxidant.2–5 Though the
corresponding epoxy alcohol (2S,3S)-8a7 was obtained
in good yield (80–90%), the reaction was not rewarding
in terms of selectivity. Contrary to Yamamoto’s obser-
vations,3,5 we found that increasing the bulk of the
Our ongoing interest in vanadium-catalyzed synthetic
methods6 prompted us to venture into the asymmetric
epoxidation of allylic alcohols using vanadium com-
plexes bearing chiral hydroxamic acids and we present
the results of this work herein.
Figure 1. Chiral hydroxamic acids used in asymmetric epoxi-
dations.
At the outset, we studied the effect of the bulkiness of
the N-substituent of the ligand on the selectivity of the
asymmetric epoxidation reaction. Chiral hydroxamic
acids 6 with different substituents on nitrogen were
accessed from (+)-ketopinic acid 5 by a two-step proce-
dure (Fig. 2). Epoxidation of (E)-2,3-diphenyl-2-
Figure 2. (+)-Ketopinic acid 5 and its derivatives—hydrox-
amic acids 6a–e.
* Corresponding author. Tel.: +886 3 5721224; fax: +886 3 5711082;
e-mail: bjuang@mx.nthu.edu.tw
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00741-3

2626
H.-L. Wu, B.-J. Uang / Tetrahedron: Asymmetry 13 (2002) 2625–2628
Figure 3. (+)-Ketopinic acid-derived C-2-substituted hydrox-
amic acids 9a–f.
Scheme 1.
N-substituent reduced the selectivity (Table 1, entries
1–5).
We sought to illuminate the relevant parameters by
varying the oxidant and the reaction temperature. Three
t
hydroperoxides, BHP, cumene hydroperoxide (CHP)
and triphenylmethyl hydroperoxide (TrOOH) were
tested as oxidants but no significant selectivity was
observed (entries 1, 6 and 7). Among them, tBHP
afforded the epoxide in better yield and selectivity.
Variation of the temperature did not have any apprecia-
ble effect on the selectivity either (entries 1 and 8–10).
Scheme 2.
The steric influence of the bornane C-2 substituent on the
enantioselectivity of the epoxidation was evidenced from
the enhancement of ee with the size of the substituent
(phenyl to 4-biphenyl, Table 2, entries 2–7). It is notewor-
thy that, (2S,3S)-8a was obtained as the major product
when ligands 6 were constituents of the catalyst. On the
other hand, (2R,3R)-8a was the major product when
ligands 9 were employed. This reversal in enantioselectiv-
ity with variation of the ligand could not be rationalized
at this stage.
As significant selectivity could not be attained with chiral
hydroxamic acids 6, we modified the structure of these
chiral ligands by incorporating bulkier substituents at
C-2 of the bornane skeleton. This was a two-pronged
strategy—to study the effect of N-substituent on selectiv-
ity in a modified steric environment of the bornane
moiety and also to investigate the impact of the size of
the C-2 substituent of bornane on the selectivity. Chiral
hydroxamic acids 9 having the required structural fea-
tures were prepared starting from (+)-ketopinic acid 5
(Fig. 3).
Having attained good selectivity with substrate 7a, we
extended the asymmetric epoxidation to the allylic alco-
hols 7b–h to verify the scope of this methodology (Table
3).
Thus, epoxidation was performed by employing ligands
Interestingly, the presence of the C-2 phenyl group
appears to have a marked influence on the selectivity.
Thus, substrates 7a and 7e induced good selectivity
(entries 1 and 5), while in the case of ligands lacking a
C-2 phenyl group, only moderate selectivity was
observed (entries 4 and 8). The selectivity was only
moderate in the case of long chain allylic alcohols (entries
6 and 7) and for a highly substituted allylic alcohol (entry
3).
9a–f as the constituents of the vanadium catalyst in the
t
presence of BHP and the results are collected in Table
2. The observed selectivity with chiral hydroxamic acid
9a was indeed encouraging, especially when it was used
at a concentration of 0.84 M (Table 2, entry 2). Ligands
9a–e lacking an N-substituent imparted good selectivity
providing the epoxy alcohol (2R,3R)-8a in good yields,
but the selectivity decreased with increasing size of the
N-substituent, as observed before (Table 2, entry 8).
Table 1. Effect of the N-substituent of chiral hydroxamic acids 6, oxidant and temperature on the catalytic asymmetric
epoxidation of 7a to (2S,3S)-8a (Scheme 1)
Entry
Ligand
Temp. (°C)
Oxidant
Time (h)
Yield (%)
Eea (%)
1
2
3
4
5
6
7
8
9
6a
6b
6c
6d
6e
6a
6a
6a
6a
6a
0
0
0
0
0
tBHP
tBHP
tBHP
tBHP
tBHP
CHP
TrOOH
tBHP
tBHP
tBHP
4
6
7
6
4
4
9
1
32
72
90
87
80
89
88
85
52
89
89
80
44
19
10
5
0
0
0
35
39
41
44
43
rt
−10
−20
10
a See refs. 7 and 8.

H.-L. Wu, B.-J. Uang / Tetrahedron: Asymmetry 13 (2002) 2625–2628
2627
Table 2. The effect of the ligand and concentration in catalytic asymmetric epoxidation of 7a to (2R,3R)-8a (Scheme 2)
Entry
Ligand
Conc. (M)
Time (h)
Yield (%)
Eea (%)
1
2
3
4
5
6
7
8
9a
9a
9a
9b
9c
9d
9e
9f
0.42
0.84
1
0.84
0.84
0.84
0.84
0.84
8
6
5
5
3
9
12
6
60
85
90
89
86
88
89
85
60
70
65
70
75
73
89
25
a See refs. 7 and 8.
In conclusion, we have achieved moderate to high
enantioselectivities in the vanadium-catalyzed asymmet-
ric epoxidation of allylic alcohols employing readily
accessible new chiral hydroxamic acids with diverse
structural features as ligands for the vanadium catalyst.
The origin of the reversal in the sense of asymmetric
induction by ligands 6 and 9, which possess the same
chiral (+)-ketopinic acid unit is not clear at this stage.
Interestingly, the observed trend in enantioselectivity
with the variation in size of the N-substituent of the
ligand in the present catalytic asymmetric epoxidation
is opposite to that of Yamamoto’s findings, although
further investigation is required. Further studies of this
methodology involving the modification of the bornane
skeleton to provide better selectivity are under active
exploration.
Acknowledgements
We thank the National Science Council, Republic of
China for the financial support.
References
Table 3. Asymmetric epoxidation of allylic alcohols 7a–h
to 8a–h using 9e as liganda
1. (a) Behrens, C. H.; Sharpless, K. B. Aldrichim. Acta 1983,
16, 67; (b) Rao, A. S. In Comprehensive Organic Synthesis;
Trost, B. M.; Fleming, I., Eds.; Pergamon: Oxford, 1991;
Vol. 7, p. 357; (c) Jacobsen, E. N. In Catalytic Asymmetric
Synthesis; Ojima, I., Ed.; VCH: New York, 1993; p. 159;
(d) Katsuki, T. Coord. Chem. Rev. 1995, 140, 189; (e)
Katsuki, T. J. Mol. Catal. 1996, 113, 87; (f) Dalton, C. T.;
Ryan, K. M.; Wall, V. M.; Bousquet, C. D.; Gilheany, G.
Top. Catal. 1998, 5, 75; (g) Mun˜iz-Ferna´ndez, K.; Bolm,
C. In Transition Metals for Organic Synthesis; Beller, M.;
Bolm, C., Eds.; VCH-Wiley: Weinheim, 2000; Vol. 2, p.
271; (h) Katsuki, T. In Comprehensive Asymmetric Cataly-
sis; Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H., Eds.;
Springer: Berlin, 1999; Vol. 2, p. 621; (i) Ito, Y. N.;
Katsuki, T. Bull. Chem. Soc. Jpn. 1999, 72, 603.
2. (a) Michaelson, R. C.; Palermo, R. E.; Sharpless, K. B. J.
Am. Chem. Soc. 1977, 99, 1990; (b) Vanadium complex
bearing proline-based chiral hydroxamic acid provided
80% ee, see: Sharpless, K. B.; Verhoeven, T. R. Aldrichim.
Acta 1979, 12, 63.
3. Murase, N.; Hoshino, Y.; Oishi, M.; Yamamoto, H. J.
Org. Chem. 1999, 64, 338.
4. (a) Luong, T. K. K.; Harms, K.; Bolm, C. Chem Ber./Recl.
1997, 130, 887; (b) Ku¨hn, T.; Bolm, C. Synlett 2000, 6,
899; (c) More recently chiral hydroperoxides were used as
oxidant in asymmetric oxidations, see: Bolm, C.; Beck-
mann, O.; Ku¨hn, T.; Palazzi, C.; Adam, W.; Rao, P. B.;
Saha-Mo¨ller, C. R. Tetrahedron: Asymmetry 2001, 12,
2441.
5. Hoshino, Y.; Yamamoto, H. J. Am. Chem. Soc. 2000, 122,
10452.
6. (a) Hwang, D.-R.; Chu, C.-Y.; Wang, S.-K.; Uang, B.-J.
Synlett 1999, 1, 77; (b) Hwang, D.-R.; Chen, C.-P.; Uang,
B.-J. Chem. Commun. 1999, 1207; (c) Chu, C.-Y.; Hwang,

2628
H.-L. Wu, B.-J. Uang / Tetrahedron: Asymmetry 13 (2002) 2625–2628
D.-R.; Wang, S.-K.; Uang, B.-J. Chem. Commun. 2001,
980; (d) Hwang, D.-R.; Uang, B.-J. Org. Lett. 2002, 4,
ples.2a
9. The enantiomeric excess of 8a–e,h was determined as
mentioned in ref. 7. In the case of 8f and 8g, ee was
determined from the corresponding benzoate derivatives
(Chiralcel OD-H; n-hexanes:iPrOH=98:2; flow rate: 0.5
ml/min). Absolute configuration of all epoxy alcohols
except 8c was determined on the basis of the sign of the
specific rotation reported in the literature.2a
463.
7. The enantiomeric excess was determined by HPLC using a
chiral column (Chiralcel OD-H; n-hexanes:iPrOH=98:2;
flow rate: 1 ml/min).
8. The absolute configuration was determined by comparing
the sign of the specific rotation with that of known sam-