Indium-bipyridine catalyzed, enantioselective aminolysis of meso-epoxides

Article abstract of DOI:10.1055/s-2007-984902

The enantioselective aminolysis of meso-epoxides is efficiently catalyzed by an indium(III)-bipyridine catalyst to furnish highly enantiomerically enriched 1,2-amino alcohols in good yields and up to 98% ee. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-984902

2136
LETTER
Indium–Bipyridine Catalyzed, Enantioselective Aminolysis of meso-Epoxides
Enantioselective
n
Aminolysis
z
of
m
eso-E
o
s
Mai, Christoph Schneider*
Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig, Germany
Fax +49(341)9736599; E-mail: schneider@chemie.uni-leipzig.de
Received 11 April 2007
Table 1 Indium–Bipyridine 2a Catalyzed Aminolysis of cis-Stil-
bene Oxide (1a) with Aniline
Abstract: The enantioselective aminolysis of meso-epoxides is ef-
ficiently catalyzed by an indium(III)–bipyridine catalyst to furnish
highly enantiomerically enriched 1,2-amino alcohols in good yields
and up to 98% ee.
10 mol%
Key words: amine, asymmetric catalysis, bipyridine, epoxides,
indium
N
N
2a
OH
HO
Ph
Ph
Ph
Ph
OH
InX3
O
The catalytic asymmetric ring opening of meso-epoxides
has proven to be a valuable tool for the straightforward
synthesis of enantiomerically highly enriched 1,2-difunc-
tionalized fine chemicals.1 In particular, chiral 1,2-azido
alcohols,2 1,2-diol derivatives,3 1,2-cyano alcohols,4 1,2-
mercapto alcohols,5 and 1,2-halohydrins6 have become
available in partly excellent optical purity using this
strategy. The direct nucleophilic addition of amines to
meso-epoxides is complicated by compatibility problems
between the Lewis basic amine and the typically Lewis
acidic chiral catalyst. Therefore the azidolysis of meso-
epoxides has been used extensively as a solution to this
problem. There are, however, some protocols for the di-
rect aminolysis of meso-epoxides giving rise to 1,2-amino
alcohols in varying enantioselectivities and typically
rather limited substrate scope.7
aniline, CH2Cl2, r.t., 48 h
NHPh
1a
3a
Entry
InX3
InCl3
InBr3
Concn (M)a
0.25
Yield (%)b ee (%)c
1
2
3
4
34
50
47
69
82
85
91
87
0.25
In(OTf)3
In(OTf)3
0.25
0.50
a With respect to the epoxide.
b Isolated yield after chromatography.
c Determined by chiral HPLC analysis.
We have developed a highly enantioselective scandium–
bipyridine-catalyzed process for the addition of alcohols
and amines to meso-epoxides furnishing 1,2-diol mono-
ethers and 1,2-amino alcohols in up to 97% ee.8 In
addition, we have recently shown that a highly enantiose-
lective thiol addition to aromatic meso-epoxides takes
place when the corresponding indium(III)–bipyridine
complex was employed as chiral catalyst and 1,2-mer-
capto alcohols were obtained in excellent yields and
enantioselectivities.9
close to 50% yield and up to 91% ee (entries 2 and 3).
When the latter reaction was run in more concentrated
solution (0.50 M in CH2Cl2), the conversion was further
improved and the product 3a was obtained in 69% yield
thereby slightly compromising the ee to 87% (entry 4).
Interestingly, in the absence of the ligand or when bipyri-
dine bis-O-methylether 2b (Figure 1) was employed as
chiral ligand a completely unreactive indium(III) catalyst
was formed documenting the assistance of the hydroxyl
protons in the catalytic cycle possibly by hydrogen bond-
ing to the amine.13
We now report that a chiral indium(III)–bipyridine cata-
lyst may also be employed for the highly enantioselective
aminolysis of meso-epoxides.10,11 In the model reaction of
cis-stilbene oxide (1a) and aniline in CH2Cl2 various indi-
um(III) salts were tested in combination with the bipyri-
dine ligand 2a (Table 1).12 Whereas the InCl3–bipyridine
2a complex (10 mol% each) displayed only moderate
catalytic activity (entry 1), the corresponding InBr3–bi-
pyridine and In(OTf)3–bipyridine complexes were more
reactive and furnished 1,2-amino alcohol 3a in yields
N
N
OMe
MeO
2b
Figure 1
Under the optimized reaction conditions14 a variety of
aromatic amines was reacted with cis-stilbene oxide (1)
and furnished 1,2-amino alcohols 3a–k in typically good
yields and enantioselectivities approaching and in many
SYNLETT 2007, No. 13, pp 2136–2138
Advanced online publication: 17.07.2007
DOI: 10.1055/s-2007-984902; Art ID: G09707ST
© Georg Thieme Verlag Stuttgart · New York
1
3
.0
8
.2
0
0
7

LETTER
Enantioselective Aminolysis of meso-Epoxides
2137
Table 2 Indium–Bipyridine 2a Catalyzed Aminolysis of meso-
Epoxides 1 (continued)
cases exceeding 90% (Table 2, entries 1–10). In particu-
lar, electron-deficient and sterically hindered anilines
gave rise to very high enantioselectivities of up to 98% ee
thereby maintaining the yields at a good level (entries 5–
10). Other aromatic meso-epoxides were ring-opened
with aniline in good yields and up to 95% ee (entries 11–
13). Just as in the scandium–bipyridine-catalyzed process
alkyl-substituted epoxides were ring-opened with only
moderate enantioselectivities (entries 14 and 15).8
10 mol%
N
N
2a
In(OTf)3
OH
HO
R1
R1
R1
R1
OH
O
R2NH2, CH2Cl2, r.t., 48 h
NHR2
Table 2 Indium–Bipyridine 2a Catalyzed Aminolysis of meso-
Epoxides 1
1
3
Entry
8
Producta
Yield (%)b
ee (%)c
98
10 mol%
Ph
Ph
OH
N
N
80
NH-4-MeO2C-Ph
2a
In(OTf)3
3h
OH
HO
R1
R1
R1
R1
OH
O
Ph
OH
R2NH2, CH2Cl2, r.t., 48 h
NHR2
9
10
11
84
82
83
95
97
94
1
3
Ph
NH-2-t-BuC6H4
3i
Entry
1
Producta
Yield (%)b
ee (%)c
87
Ph
OH
Ph
Ph
OH
Ph
NH-2,6-Me2C6H3
69
83
89
NHPh
3k
3a
4-ClC6H4
OH
Ph
OH
2
3
4
5
6
7
72
88
88
90
92
97
4-ClC6H4
NHPh
Ph
NHPMP
3l
3b
3-MeC6H4
OH
Ph
Ph
OH
12
13
14
15
91
90
82
91
90
95
36
31
3-MeC6H4
NHPh
NH-4-MeC6H4
3m
3c
2-Naphthyl
OH
Ph
OH
86
95
80
80
2-Naphthyl
NHPh
Ph
NH-4-FC6H4
3n
3d
OH
Ph
Ph
OH
NHPh
NH-4-ClC6H4
3o
3e
OH
Ph
OH
NHPh
Ph
NMePh
3p
3f
a The absolute configuration of the products was determined by com-
parison of the rotation values with literature values or by analogy.
b Isolated yield after chromatography.
Ph
Ph
OH
c Determined by chiral HPLC analysis.
NH-4-CNC6H4
3g
A crystal structure9 of the related InBr3–bipyridine 2a cat-
alyst revealed a pentagonal-bipyramidal coordination ge-
ometry around the metal center with the hydroxyl protons
still attached to the complex which very closely resembles
Synlett 2007, No. 13, 2136–2138 © Thieme Stuttgart · New York

2138
E. Mai, C. Schneider
LETTER
the related scandium–bipyridine complex.15 Consequent-
ly, the sense of asymmetric induction is identical in both
processes furnishing the products with the same absolute
configuration.
(7) (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) Azoulay, S.; Manabe, K.; Kobayashi, S.
Org. Lett. 2005, 7, 4593. (e) Ogawa, C.; Azoulay, S.;
Kobayashi, S. Heterocycles 2005, 66, 201. (f) Carree, F.;
Gil, R.; Collin, J. Org. Lett. 2005, 7, 1023. (g) Kureshy, R.
I.; Singh, S.; Khan, N. H.; Abdi, S. H. R.; Suresh, E.; Jasra,
R. V. Eur. J. Org. Chem. 2006, 1303. (h) Arai, K.; Salter,
M. M.; Yamashita, Y.; Kobayashi, S. Angew. Chem. Int. Ed.
2007, 46, 955; Angew. Chem. 2007, 119, 973.
(8) (a) Schneider, C.; Sreekanth, A. R.; Mai, E. Angew. Chem.
Int. Ed. 2004, 43, 5691; Angew. Chem. 2004, 116, 5809.
(b) Mai, E.; Schneider, C. Chem. Eur. J. 2007, 13, 2729.
(c) Tschöp, A.; Marx, A.; Sreekanth, A. R.; Schneider, C.
Eur. J. Org. Chem. 2007, 2318.
In conclusion, we have devised a novel chiral indium(III)-
based catalyst for the aminolysis of meso-epoxides fur-
nishing 1,2-amino alcohols in generally good yields and
up to 98% ee at ambient temperature. Aromatic meso-
epoxides were ring-opened with good to excellent enan-
tioselectivity whereas alkyl-substituted epoxides under-
went the aminolysis with only moderate selectivity. Work
is currently being continued to further improve the effi-
ciency and enantioselectivity of the process.
(9) Nandakumar, M. V.; Tschöp, A.; Krautscheid, H.;
Schneider, C. Chem. Commun. 2007, 2756.
Acknowledgment
This work was generously supported by the Deutsche Forschungs-
gemeinschaft (Schn 441/3-2). We thank BASF and Wacker for the
generous donation of chemicals.
(10) For previous reports on non-enantioselective indium(III)-
catalyzed aminolyses of epoxides, see: (a) Rajender Reddy,
R.; Arjun Reddy, M.; Bhanumathi, N.; Rama Rao, K. New J.
Chem. 2001, 25, 221. (b) Rodriguez, J. R.; Navarro, A.
Tetrahedron Lett. 2004, 45, 7495.
(11) For selected recent reports on enantioselective, indium-
catalyzed transformations, see: (a) Harada, S.; Takita, R.;
Ohshima, T.; Matsunaga, S.; Shibasaki, M. Chem. Commun.
2007, 948. (b) Takita, R.; Yakura, K.; Ohshima, T.;
Shibasaki, M. J. Am. Chem. Soc. 2005, 127, 13760. (c)Teo,
Y.-C.; Tan, K.-T.; Loh, T.-P. Chem. Commun. 2005, 1318.
(d) Teo, Y.-C.; Loh, T.-P. Org. Lett. 2005, 7, 2539.
(e) Harada, S.; Handa, S.; Matsunaga, S.; Shibasaki, M.
Angew. Chem. Int. Ed. 2005, 44, 4365. For reviews, see:
(f) Loh, T.-P.; Chua, G.-C. Chem. Commun. 2006, 2739.
(g) Podlech, J.; Maier, T. C. Synthesis 2003, 633. (h) Ranu,
B. C. Eur. J. Org. Chem. 2002, 2347.
(12) For the first synthesis and application of ligand 2a in
asymmetric catalysis, see: Bolm, C.; Zehnder, M.; Bur, D.
Angew. Chem., Int. Ed. Engl. 1990, 29, 191; Angew. Chem.
1990, 102, 206.
(13) We have made the same observation in the related
indium(III)–bipyridine 2a catalyzed thiolysis of meso-
epoxides (ref. 9).
References and Notes
(1) (a) Reviews: Schneider, C. Synthesis 2006, 3919.
(b) Pastor, I. M.; Yus, M. Curr. Org. Chem. 2005, 9, 1.
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(14) Typical Experimental Procedure
In an oven-dried flask and under inert atmosphere In(OTf)3
(28 mg, 0.05 mmol) and bipyridine 2a (20 mg, 0.05 mmol)
were dissolved in CH2Cl2 (1 mL) and treated with epoxide
(0.50 mmol) and amine (1.00 mmol) at r.t. The reaction
mixture was stirred for 48 h at r.t. whereupon it was
concentrated in vacuo and purified by silica gel
chromatography. For analytical and spectroscopic details of
the products, see ref. 8b.
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Chem. Soc. 2004, 126, 12236.
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