Catalytic asymmetric epoxidation of naphthoquinone derivatives under phase-transfer catalyzed conditions

Article abstract of DOI:10.1055/s-1998-1932

2-Alkyl-1,4-naphthoquinones were smoothly transformed to the corresponding epoxides in moderate to good yields with good enantioselectivities (up to 76% ee) under mild reaction conditions by use of a catalytic amount of chiral quaternary ammonium salts de

Full text of DOI:10.1055/s-1998-1932

November 1998
SYNLETT
1201
Catalytic Asymmetric Epoxidation of Naphthoquinone Derivatives Under Phase-Transfer
Catalyzed Conditions
Shigeru Arai,* Makoto Oku, Motoko Miura, and Takayuki Shioiri*
Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan
Fax:+81-52-834-4172. E-mail: shioiri@phar. nagoya-cu.ac.jp
Received 10 August 1998
Abstract: 2-Alkyl-1,4-naphthoquinones were smoothly transformed to
the corresponding epoxides in moderate to good yields with good
enantioselectivities (up to 76% ee) under mild reaction conditions by
use of a catalytic amount of chiral quaternary ammonium salts derived
from quinidine as a phase-transfer catalyst.
O
O
O
Me
O
Me
PTC (5 mol %)
aq. H2O2, LiOH
CHCl3
O
Recently, we have succeeded in the establishment of
a useful
1a
2a
methodology for the preparation of α,β-epoxyketones from (E)-enones
such as chalcone and its derivatives using chiral quaternary ammonium
salts as a phase-transfer catalyst (PTC).1 Known successful examples of
the PTC-catalyzed epoxidation of enones were limited in (E)-enones
such as chalcone and its derivatives as substrates.1a,2 On the other hand,
few results were reported by use of (Z)-enones in catalytic asymmetric
epoxidation. Wynberg3a-d and the others3e,f reported the PTC-catalyzed
asymmetric epoxidation of cycloalkenones or α-substituted
naphthoquinones with moderate enantiomeric excess. Recently, Taylor
and co-workers4 revealed that the epoxidation of a dienone proceeded
with good enantiomeric excess (89%) under PTC conditions. In this
paper, we report our own results on the catalytic asymmetric
epoxidation of naphthoquinone derivatives promoted by modified chiral
PTCs derived from cinchona alkaloids under mild reaction conditions.
PTC A : R = α-Naphthyl, X = Cl
PTC B : R = β-Naphthyl, X = Br
-
X
HO
N+
PTC C : R = 4-CF3-C6H4, X = Br
PTC D : R = 2,6-Cl2-C6H3, X = Br
PTC E : R = 2,4-Me2-C6H3, X = Br
MeO
R
N
Table 1. Asymmetric Epoxidation of 1a Under PTC Conditions
yield of
2a (%)
ee of
2a (%)
entry
PTC
temp & time
A
A
B
1
2
3
4
5
6
rt, 1 h
-10°C, 1 h
rt, 1 h
82
86
84
87
92
93
31
34
27
18
30
26
rt, 1 h
C
D
E
rt, 1 h
Our first target was vitamin K because the role of vitamin K and its
epoxide is interesting in its biological activity.5 Since many quinones
have been shown to possess antimicrobial and antitumor activity and,
since the corresponding epoxides seem to play an important role in
metabolic processes, development of the practical synthesis of quinone
epoxides as their optically active forms is an important goal. As a result,
commercially available naphthoquinone derivative 1a (vitamin K3) was
employed for initial studies and transformed to the corresponding
epoxide with a safety oxidant, H2O2, under a biphase-system in the
presence of a catalytic amount of quaternary ammonium salts derived
from quinidine as a chiral PTC. The reaction proceeded smoothly to
give the corresponding epoxide 2a in good yield but with low
enantioselectivities in a usual solvent system such as toluene or diethyl
ether. After screening of solvents, PTCs, bases, and reaction conditions,
we have found that the desired product 2a was obtained in the presence
of 5 mol % of PTC A with 30% H2O2 and a stoichiometric amount of
LiOH in chloroform at rt with 31% ee in good chemical yield (Table 1,
entry 1).6-8 On the other hand, treatment of 1a in the absence of PTC
afforded 2a with much lower chemical yield. The chiral PTC plays an
important role in not only asymmetric induction but acceleration of the
reaction rate in this reaction system. Since 2a has low values of optical
rotation in any solvent, its enantioselectivity was determined by HPLC
analysis. In order to obtain 2a with higher enantioselectivity, we turned
to use new PTCs derived from quinidine. As the result, PTCs including
an ortho-substituted benzyl moiety were found to give better results in
this asymmetric epoxidation. Particularly, the PTC involving the α-
naphthyl unit on the nitrogen atom of quinuclidine gave the best result
to afford 2a with 34% ee in chloroform at -10°C (Table 1, entry 2).
Encouraged by this result, we have paid attention to epoxidize other
easily prepared α-alkyl substituted 1,4-naphthoquinones under the same
reaction conditions. As shown in Table 2, by use of 5 mol % of PTC A,
N-(α-naphthylmethyl)quinidinium chloride,9 in the presence of aqueous
H2O2, the corresponding epoxides 2 were obtained with moderate to
rt, 1 h
O
O
R
O
R
PTC A (5 mol %)
aq. H2O2, LiOH (2.0 eq)
CHCl3, -10°C
O
O
1b-h
2b-h
Table 2. Substrate Effect on Asymmetric Epoxidation
yield of
2 (%)
ee of
2 (%)
entry
quinone
time (h)
: R = Et
1
2
3
4
5
6
7
1b
1c
1d
1e
1f
16
7
5
2b : 99
2c : 95
2d : 93
2e : 100
2f : 60
2g : 47
2h : 84
41
40
70
28
64
76
40
: R = n-Pr
: R = i-Pr
: R = i-Bu
: R = c-Hex
: R = Ph
30
23
23
21
1g
:
1h R =
C
CPh
good enantiomeric excess. In comparison with the case of 1a, substrates
involving more bulky alkyl groups at the α-position gave good
enantioselectivities (Table 2, entries 2-6). These results imply that the
PTC recognized two unequivalent carbonyl groups to afford the
corresponding epoxides with moderate ee. In particular, 2-isopropyl
(1d) and 2-phenyl-1,4-naphthoquinone (1g) were transformed to the
corresponding epoxides 2d and 2g with 70 and 76% ee, respectively.10
And also the α-alkynylated quinone was oxidized smoothly under the
same reaction conditions to afford the desired products with modest
enantioselectivities (Table 2, entry 7). According to our best knowledge,

1202
LETTERS
SYNLETT
2.
Quite recently, a successful result that utilized O-protected chiral
quaternary ammonium salt as PTC with NaOCl was reported, see
(a) Lygo, B.; Wainwright, G. P. Tetrahedron Lett. 1998, 39, 1599.
R1
R2
R1
R2
O
PTC A (5 mol %)
aq. H2O2, LiOH (2.0 eq)
CHCl3, -10°C
A
review for PTC catalyzed asymmetric epoxidation was
O
O
published, see (b) Ebrahim, S.; Wills, M.; Tetrahedron Asymmetry
1997, 8, 3163. Recently, successful results of asymmetric
epoxidation promoted by metal reagents were reported, see (c)
Enders, D.; Zhu, J.; Raabe, G. Angew. Chem., Int. Ed. Eng. 1996,
35, 1725. (d) Bougauchi, M.; Watanabe, S.; Arai, T.; Sasai, H.;
Shibasaki, M. J. Am. Chem. Soc. 1997, 119, 2329. (e) Elston, C.
L.; Jackson, R. F. W.; MacDonald, S. J. F.; Murray, P. J. Angew.
Chem., Int. Ed. Eng. 1997, 36, 410.
3
4
Table 3
entry
1
yield of ee of
4 (%) 4 (%)
(config.)
enone
time (h)
3a:R1 = H, R2 = Ph
3b:R1 = H, R2 = i-Pr
44
14
4a :85
4b :97
4c :34a
4d :88b
4d :61b
17 (αS,βR)
35 (αS,βR)
26 (αS,βR)
21 (αS,βR)
29 (αR,βS)
2
3
4
5
:R1 = H, R2 = c-Hex
:R1 = H, R2 = Et
:R1 = Et, R2 = H
3c
3d
3e
48
44
44
3.
(a) Helder, R.; Hummelen, J. C.; Laane, R. W. P. M.; Wiering, J.
S.; Wynberg, H. Tetrahedron Lett. 1976, 21, 1831. (b) Wynberg,
H.; Marsman, B. J. Org. Chem. 1980, 45, 158. (c) Pluim, H.;
Wynberg, H. J. Org. Chem. 1980, 45, 2498. (d) Snatzke, G.;
Wynberg, H.; Feringa, B.; Marsman, B. G.; Greydanus, B.; Pluim,
H. J. Org. Chem. 1980, 45, 4094. (e) Harigaya, Y.; Yamaguchi, H.;
Onda, M. Heterocycles 1981, 15, 183. (f) Baba, N.; Oda, J.
Kawaguchi, M. Agric. Biol. Chem. 1986, 50, 3113.
a) Conversion yield. b) Twenty mol % of PTC A was used.
these results are the first establishment of the generality on catalytic
asymmetric epoxidation of 2-substituted-1,4-naphthoquinone
derivatives to obtain the corresponding epoxides with moderate to good
enantioselectivities.
4.
5.
6.
7.
8.
9.
(a) Alcaraz, L.; Macdonald, G.; Ragot, J. P.; Lewis, N.; Taylor, R.
J. K. J. Org. Chem. 1998, 63, 3526. (b) Macdonald, G.; Alcaraz,
L.; Lewis, N. J.; Taylor, R. J. K. Tetrahedron Lett. 1998, 39, 5433.
Next, we attempted to examine the application of PTC A to the (E)-
enone system. As shown in Table 3, the substrates which involve the
same partial moiety relative to α-alkylnaphthoquinones 3a-d were
easily oxidized to the corresponding trans epoxides 4a-d under similar
reaction conditions, respectively. These enantiomeric excesses were
found to be much lower. Indeed, the (Z)-enone 3e was also transformed
to the corresponding epoxide 4d in 61% yield with 29% ee, and its
absolute configuration was found to be (αR,βS). These results represent
that PTC A seems to act as a quite effective phase-transfer catalyst in the
naphthoquinone system.
(a) Willingham, A. K.; Matchiner, J. T. Biochem. J. 1974, 140,
435. (b) Suttie, J. W.; Lawson, A. E.; Canfield, L. M.; Carlisle, T.
L. Fed. Proc. Fed. Am. Soc. Exp. Biol. 1978, 37, 2605.
Wynberg et al. reported that 2a was obtained via asymmetric
epoxidation with 5% ee in 60-70% yield under phase-transfer
catalyzed conditions, see ref. 3c,d.
The absolute configuration of epoxides was determined by [α]D
and CD spectral data by comparison with the literature results, see
ref. 3c,d.
In conclusion, we have realized the catalytic asymmetric epoxidation of
α-substituted naphthoquinones under phase-transfer catalyzed
conditions with the achievement of
enantioselectivities in comparison to the known results. N-(α-
Naphthylmethyl)quinidinium salt appears to act as a quite effective PTC
in this reaction system. This methodology can be a practical synthesis
for the preparation of optically active quinone epoxides. Although it is
not clear that stereo and electronic effects between PTC and substrates
determine the asymmetric induction in this reaction system at present,
these results described here will lead to further progress.
Enantiomeric excess of the epoxide 2a (34% ee) can be easily
increased to 98% ee (as white needles) after recrystallization from
hexane-Et2O.3d
a dramatic increase in
All PTCs used in this reaction system were easily prepared from
quinidine and commercially available arylmethyl halide
derivatives. PTCs having alkyl groups on the phenyl ring afforded
2 with better ee than PTCs having other electron-withdrawing or
donating groups.
10. A typical procedure for the catalytic asymmetric epoxidation
under phase-transfer catalyzed conditions: Synthesis of 2d (Table
2, entry 3). PTC A (29.6 mg, 0.05 mmol) and LiOH (47.9 mg, 2.0
mmol) were added to a solution of naphthoquinone 1d (201 mg,
1.0 mmol) in chloroform (3.0 mL) and 30% aqueous H2O2 (1.0
mL) at -10°C. After being stirred for 5 h at -10°C, the reaction
mixture was quenched with 1N HCl and extracted with diethyl
ether (15 mL x 3). The combined organic layer was dried over
Na2SO4. Removal of the solvent followed by flash column
chromatography (silica gel, hexane:Et2O = 3:1) gave the desired
product 2d (201.8 mg, 93%, 70% ee) as a colorless oil. Ee was
determined by HPLC analysis (DAICEL CHIRALCEL OD,
hexane:i-PrOH = 50:1, flow rate = 0.5 mL/min, retention time;
12.5 min (minor) and 13.0 min (major)).
Acknowledgments: One of the authors (S. A.) is grateful to Ciba-Geigy
Foundation (Japan) for the promotion of Science for their financial
support. This work was also supported by a Grant-in-Aid from the
Ministry of Education, Science, Sports and Culture of Japan, and Ohara
Award in Synthetic Organic Chemistry, Japan (to S. A.).
References and Notes
1.
(a) Arai, S.; Tsuge, H.; Shioiri, T. Tetrahedron Lett. in press. Quite
recently, we have published some successful results for PTC-
catalyzed asymmetric reactions, see (b) Arai, S.; Shioiri, T.
Tetrahedron Lett. 1998, 39, 2145. (c) Arai, S.; Hamaguchi, S.;
Shioiri, T. Tetrahedron Lett. 1998, 39, 2997.