Catalytic asymmetric ring opening of meso-epoxides with aromatic amines in water

Article abstract of DOI:10.1021/ol051546z

(Chemical Equation Presented) An operationally simple and environmentally benign protocol for the catalytic asymmetric ring opening of meso-epoxides with aromatic amines has been developed. The reactions proceeded smoothly in the presence of 1 mol % of Sc

Full text of DOI:10.1021/ol051546z

ORGANIC
LETTERS
2005
Vol. 7, No. 21
4593-4595
Catalytic Asymmetric Ring Opening of
meso-Epoxides with Aromatic Amines in
Water
Ste´phane Azoulay, Kei Manabe, and Shu¯ Kobayashi*
Graduate School of Pharmaceutical Sciences, The UniVersity of Tokyo,
The HFRE DiVision, ERATO, Japan Science and Technology Agency (JST),
Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
skobayas@mol.f.u-tokyo.ac.jp
Received June 30, 2005
ABSTRACT
An operationally simple and environmentally benign protocol for the catalytic asymmetric ring opening of meso-epoxides with aromatic amines
has been developed. The reactions proceeded smoothly in the presence of 1 mol % of Sc(OSO3C12H25 and 1.2 mol % of a chiral bipyridine
)
3
ligand in water to afford
â-amino alcohols in high yields with excellent enantioselectivities.
Organic reactions in water are now of great interest. Water
is a cheap, safe, and clean solvent.1 Indeed, industry prefers
to use water as a solvent rather than toxic organic solvents.2
In general, however, water-soluble materials are preferred,
whereas most organic compounds are not soluble in water.
To achieve truly environmentally benign chemical syntheses,
it is an important task to treat water-insoluble organic
materials in water as well as to treat water-unstable materials
in water. In this report, we focused on epoxides, which are
important intermediates and building blocks in organic
synthesis,3 while they are readily decomposed under acidic
conditions in water. We now report that optically active
amino alcohols can be readily synthesized using Sc-catalyzed
asymmetric ring-opening reactions of meso-epoxides with
amines in water.
Chiral â-amino alcohol units are found in many biologi-
cally active compounds and chiral auxiliaries/ligands used
in asymmetric reactions.4 Catalytic enantioselective synthesis
of these chiral building blocks mainly relies on asymmetric
ring opening of meso-epoxides. Indeed, several examples
using a chiral catalyst (typically a chiral Lewis acid) are
reported in the literature;5 however, all of these reactions
proceeded in organic solvents. As a part of our ongoing
program to develop new asymmetric reactions in aqueous
media, we recently reported that a combination of scandium
triflate (Sc(OTf)3) and chiral bipyridine 16 was effective to
provide high enantioselectivities in catalytic asymmetric
(4) For reviews on the asymmetric synthesis and use of vicinal amino
alcohols, see: (a) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. Rev. 1996,
96, 835. (b) Bergmeier, S. C. Tetrahedron 2000, 56, 2561. (c) Yamashita,
M.; Yamada, K.; Tomioka, K. Org. Lett. 2005, 7, 2369. (d) Kolb, H. C.;
Sharpless, K. B. In Transition Metals for Organic Synthesis; Beller, M.,
Bolm, C., Eds.; Wiley-VCH: Weinheim, Germany, 1998; p 243.
(5) (a) Hou, X. L.; Wu, J.; Dai, L. X.; Xia, L. J.; Tang, M. H.
Tetrahedron: Asymmetry 1998, 9, 1747. (b) Sagawa, S.; Abe, H.; Hase,
Y.; Inaba, T. J. Org. Chem. 1999, 64, 4962. (c) Sekine, A.; Ohshima, T.;
Shibasaki, M. Tetrahedron 2002, 58, 75. (d) Schneider, C.; Sreekanth, A.
R.; Mai, E. Angew. Chem., Int. Ed. 2004, 43, 5691. (e) Carre´e, F.; Gil, R.;
Collin, J. Org. Lett. 2005, 7, 1023.
(1) (a) Li, C.-J.; Chan, T.-H. Organic Reactions in Aqueous Media; John
Wiley & Sons: New York, 1997. (b) Organic Synthesis in Water; Grieco,
P. A., Ed.; Blackie Academic and Professional: London, 1998.
(2) Aqueous-Phase Organometallic Catalysis, 2nd ed.; Cornils, B.,
Herrmann, W. A., Eds.; Wiley-VCH: Weinheim, Germany, 2004.
(3) For examples, see: (a) Jacobsen, E. N. Acc. Chem. Res. 2000, 33,
421. (b) Lauret, C. Tetrahedron: Asymmetry 2001, 12, 2359. (c) Lauret,
C.; Roberts, S. M. Aldrichimica Acta 2002, 35, 47.
10.1021/ol051546z CCC: $30.25
© 2005 American Chemical Society
Published on Web 09/14/2005

hydroxymethylation of silicon enolates.7 To extend the use
of this novel chiral scandium complex to other reactions in
water, we decided to investigate the asymmetric ring opening
of cis-stilbene oxide with aniline in water. Quite recently,
Schneider et al. reported the same ring-opening reaction using
Sc(OTf)3 and 1 in dichloromethane.5d Independently, we were
pleased to find that the reaction proceeded smoothly in high
yield with high enantioselectivity using 10 mol % of
scandium tris(dodecyl sulfate) (Sc(DS)3) as a Lewis acid-
surfactant combined catalyst, a concept previously introduced
by our group,8 and 20 mol % of 1 in water (Table 1, entry
Table 2. Asymmetric Ring Opening of meso-Epoxidesa
Table 1. Optimization of the Reaction Conditions
entry catalyst
X
Y
solvent
H2O
H2O
H2O
H2O
yielda (%) eeb (%)
1
Sc(DS)3 10
20
10
6
91
79
76
90
89
32
14
15
<5
85
94
94
94
94
91
91
2
3
4c
5c
6
7
8
9
10
Sc(DS)3
Sc(DS)3
Sc(DS)3
Sc(DS)3
Sc(DS)3
Sc(DS)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
5
3
1
1
0.25
1
1
1
1
2
1.2 H2O
0.3 H2O
0
1.2 H2O
1.2 THF/H2Od
1.2 CH2Cl2
H2O
85
71
74
a Isolated yield after silica gel chromatography. b Enantioselectivity was
determined by chiral HPLC analysis. c Reaction time was 30 h. d THF/H2O
) 9/1.
1). It is noted that the ring-opening reaction proceeded
smoothly in water, and that no diol formation was observed.
Reducing the catalyst loading (entries 2-4) led to a decrease
in conversion, which could be overcome by a longer reaction
time (entry 4). The enantioselectivity was not affected neither
by reducing the ratio of the ligand to the metal from 2 to
1.2 (entry 5) nor by the catalyst loading; indeed, the
enantioselectivity was maintained even with only 0.25 mol
% of the catalyst (entry 6). Hydrophobic interactions upon
increasing the concentration of organic reactants may play
a crucial role in these results.9 Interestingly, the reaction
proceeded sluggishly without ligand 1 (entry 7). Moreover,
the use of Sc(OTf)3 instead of Sc(DS)3 in water (entry 8) or
water/THF (entry 9) gave the desired ring-opening product
in only poor yield. Finally, it has been demonstrated that
(6) (a) Bolm, C.; Zehnder, M.; Bur, D. Angew. Chem., Int. Ed. 1990,
29, 191. (b) Bolm, C.; Ewald, M.; Zehnder, M.; Neuburger, M. A. Chem.
Ber. 1992, 125, 453.
(7) Ishikawa, S.; Hamada, T.; Manabe, K.; Kobayashi, S. J. Am. Chem.
Soc. 2004, 126, 12236.
(8) Manabe, K.; Mori, Y.; Wakabayashi, T.; Nagayama, W.; Kobayashi,
S. J. Am. Chem. Soc. 2000, 122, 7202.
a The reaction conditions of entry 5 (Table 1), except time, were
employed. b Isolated yield after silica gel chromatography. c Enantioselec-
tivity was determined by chiral HPLC analysis.
4594
Org. Lett., Vol. 7, No. 21, 2005

Sc(DS)3 and 1 in water gave higher yield and enantioselec-
tivity than Sc(OTf)3 and 1 in dichloromethane (entry 10).
Conducting the reaction at lower temperature (5 °C) had no
effect on the enantioselectivity, while the conversion was
significantly slowed. On the other hand, higher temperature
(40 °C) increased the reaction rate but had a detrimental
effect on the enantioselectivity (not shown in the table).
Thus, the asymmetric ring-opening reaction of cis-stilbene
oxide with aniline was carried out with only 1 mol % of
Sc(DS)3 and 1.2 mol % of 1 in water as the sole solvent,
affording the desired â-amino alcohol in 89% yield and 91%
ee. In general, even a trace amount of water exerts a
detrimental effect on yield and enantioselectivity, and only
few examples of enantioselective Lewis acid-catalyzed
reactions in pure water have been reported.10 To the best of
our knowledge, this is, to date, the first example of an
asymmetric epoxide ring opening in pure water.11
Under the optimized conditions, we next examined other
substrates (Table 2). Sterically hindered anilines, such as
N-methylaniline, maintained high yields and led to a further
increase in enantioselectivity to 96% ee (Table 2, entry 2).
The ring opening with an electron-rich amine, such as
o-anisidine, proceeded with slightly improved enantioselec-
tivity and yielded product 3c, which may be easily converted
into the free 1,2-amino alcohol (entry 3). R-Naphthylamine
also reacted smoothly to provide the amino alcohol 3d in
high yield with high enantioselectivity. Similarly, R-naph-
thylamine bearing a functional group, such as 1-amino-4-
bromo naphthalene, gave the desired product 3e, which could
be further transformed to introduce other functional groups
(entry 5). On the other hand, benzylamine and other aliphatic
amines did not yield the desired products. Aromatic cis-
epoxides, cis-4,4′-dimethylstilbene oxide 2b and cis-1,2-
dinaphthylethylene oxide 2c, reacted with aniline in good
yields with high enantioselectivity to furnish 1,2-amino
alcohol 3f and 3g, respectively (entries 6 and 7). Aliphatic
epoxides, cis-1,6-diphenyl-3-hexene oxide (2c) and cis-5-
decene oxide (2d), reacted with aniline under otherwise
identical reaction conditions to afford the desired products
3g and 3h, respectively, in good to high yields with good
enantioselectivity (entries 8 and 9).
In conclusion, we have established the first catalytic,
enantioselective addition of amines to meso-epoxides em-
ploying a scandium-bipyridine complex in pure water.
Chiral â-amino alcohols were prepared in mostly high yields
with excellent enantioselectivities. It is noted that the use of
water as a solvent gave a higher yield and enantioselectivity
than that of dichloromethane. Current research efforts are
directed toward further improvement of the scope of this
process by ligand optimization and studying others nucleo-
philes.
Acknowledgment. This work was partially supported by
a Grant-in-Aid for Scientific Research from the Japan Society
of the Promotion of Science (JSPS).
(9) (a) Otto, S.; Engberts, J. B. F. N. Org. Biomol. Chem. 2003, 1, 2809.
(b) Engberts, J. B. F. N.; Blandamer, M. J. Chem. Commun. 2001, 1701.
(10) (a) Otto, S.; Engberts, J. B. F. N. J. Am. Chem. Soc. 1999, 121,
6798. (b) Manabe, K.; Kobayashi, S. Chem.sEur. J. 2002, 8, 4094. (c)
Sinou, D.; Rabeyrin, C.; Nguefack, C. AdV. Synth. Catal. 2003, 345, 357.
(d) Hamada, T.; Manabe, K.; Kobayashi, S. J. Am. Chem. Soc. 2004, 126,
7768.
(11) For examples of nonenantioselective ring opening of meso-epoxides
in water, see: (a) Iranpoor, N.; Firouzabadi, H.; Shekarize, M. Org. Biomol.
Chem. 2003, 1, 724. (b) Fan, R. H.; Hou, X. L. J. Org. Chem. 2003, 68,
726. (c) Ollevier, T.; Lavie-Compain, G. Tetrahedron Lett. 2004, 45, 49.
Supporting Information Available: Experimental pro-
1
cedures, analytical data, and H and 13C NMR spectra of
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL051546Z
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