Metal-controlled reversal of enantioselectivity in catalyzed asymmetric ring-opening reactions of meso-epoxides in water

Article abstract of DOI:10.1246/cl.2009.904

Reversal of enantioselectivity in Cu-chiral bipyridine catalyzed asymmetric ring-opening reactions of meso-epoxides with indole and aniline derivatives was observed compared to Sc-chiral bipyridine catalyzed reactions, where the same chiral ligand was use

Full text of DOI:10.1246/cl.2009.904

904
Chemistry Letters Vol.38, No.9 (2009)
Metal-controlled Reversal of Enantioselectivity in Catalyzed Asymmetric
Ring-opening Reactions of meso-Epoxides in Water
Masaya Kokubo, Takeshi Naito, and Shu¯ Kobayashiꢀ
Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033
The HFRE Division, ERATO, Japan Science and Technology Agency (JST), Hongo, Bunkyo-ku, Tokyo 113-0033
(Received June 29, 2009; CL-090607; E-mail: shu kobayashi@chem.s.u-tokyo.ac.jp)
Reversal of enantioselectivity in Cu–chiral bipyridine cata-
Table 1. Cu- and Sc-catalyzed asymmetric ring-opening reac-
tions of meso-epoxides with indoles
lyzed asymmetric ring-opening reactions of meso-epoxides with
indole and aniline derivatives was observed compared to Sc–
chiral bipyridine catalyzed reactions, where the same chiral li-
gand was used. It was revealed from X-ray crystal structural
analysis that a square pyramidal structure for the Cu(II) complex
and a pentagonal bipyramidal structure for the Sc(III) complex
were formed, which could explain the reversal of the enantiose-
lectivity.
R3
R3
Cu(O3SC11H23
or Sc(O3SC11H23
)
R1 OH
2
)
3
R1
R1
(10 mol%)
(S,S)-1 (12 mol%)
+
R1
O
R2
N
R2
N
H2O, rt, 22 h
H
H
2
3 (1.2 equiv)
4
Cu
Sc
Entry
R1
R2 R3
Yield/% ee/% Yield/% ee/%
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
H
H
H
H
Me
H
H
OMe
Me
Br
H
H
H
H
80
78
81
58
77
53
48
82
96a
92
92
90
92
85
87
92
69
80
72
59
58
57
46
65
ꢁ92b
ꢁ92
ꢁ95
ꢁ91
ꢁ85
ꢁ88
ꢁ84
ꢁ94
Organic reactions in water are currently of great interest.
Water is an inexpensive, clean, and non-toxic solvent, and plays
an important role in environmentally benign chemical synthe-
sis.1 In addition, unique reactivity and selectivity can often be
observed in water.2 Although there have been great advances
in asymmetric catalysis, it is still difficult to perform asymmetric
catalysis in water since most catalysts decompose rapidly in the
presence of water.3 To address this issue we have proposed a
new concept using Lewis acid/chiral multicoordinated ligand
combinations.4 For example, we developed Pb(II)–chiral crown
ether4a and Ln(III)–chiral crown ether4b complexes as catalysts
for asymmetric Mukaiyama aldol reactions in aqueous media.5
In these complexes, six heteroatoms coordinate to metals to sta-
bilize the complexes in the presence of water. Moreover, water
also coordinates to the metals assisting counter ion dissociation
thus increasing Lewis acidity of the complexes. It should be not-
ed that such complexes did not show any catalytic activity as
Lewis acids in organic solvents. It was reasoned that the six
heteroatoms worked as Lewis bases coordinating the metal thus
decreasing the Lewis acidity of the complexes significantly.
In the course of our investigation to expand this concept further
directed toward truly efficient asymmetric catalysis in water,
we envisioned that if metals were combined with multicoordi-
nated ligands, multiple coordination forms could be possible
depending on the metals employed, and unique reactivity and
stereochemical outcomes might be expected by judicious choice
of metals. In this paper, we show such examples in chiral metal-
catalyzed enantioselective ring-opening of meso-epoxides in
water.
2-Naphthyl
4-MeC6H4
4-BrC6H4
b
H
H
a1S,2S. 1R,2R.
We thought that if another metal salt that formed a pyramidal
structure where the bipyridines and one of the two hydroxy
groups of 1 coordinated to the metal in a tridentate manner
was used, the reaction course might be changed and different se-
lectivity might be obtained.
Several examples of Cu–(S,S)-1 catalyzed asymmetric ring-
opening reactions of meso-epoxides with indoles are shown in
Table 1. In most cases, the reactions proceeded well to afford
the desired optically active indole derivatives in high yields with
high enantiomeric excesses. Interestingly, reversal of enantiose-
lectivities was observed between Cu- and Sc-catalyzed reac-
tions.9 In addition, it is noted that much lower yields of the de-
sired compounds were obtained in organic solvents (CH2Cl2,
THF, toluene, etc.) using Cu(OTf)2– or Sc(OTf)3–(S,S)-1 as cat-
alyst, and that the use of water as a solvent is essential for this
reaction.10
We chose Cu(II) to investigate salts, when Cu(O3SC11-
H23)2–(S,S)-1 was used as a catalyst in the reaction of cis-stil-
bene oxide (2a) with indole (3a) in water, the desired alcohol re-
sulting from epoxide ring-opening was obtained in 80% yield
with 96% ee, and the absolute configuration of the product
was 1S,2S. On the other hand, Sc(O3SC11H23)3–(S,S)-1 cata-
lyzed the same reaction, where the same product was also ob-
tained in high enantiomeric excess (92% ee), but the absolute
configuration was reversed 1R,2R. Therefore, it is possible to ob-
tain both enantiomers of the same product in high enantiomeric
excess by selection of metal salts in combination with the same
ligand (S,S)-1 (Scheme 1).11
Catalytic enantioselective ring-opening of meso-epoxides
with indoles provides an efficient synthesis of optically active in-
dole derivatives. We have recently shown that chiral Sc-cata-
lyzed ring-opening of meso-epoxides with indole derivatives in
water.6 Sc(OSO3C12H25)3 (Sc(DS)3)7–chiral bipyridine ligand
18 was found to be an efficient catalyst; in the Sc–1 complex,
a pentagonal bipyramidal structure in which the bipyridine and
the hydroxy groups of 1 coordinate to Sc3þ in a tetradentate
manner was suggested by X-ray crystal structural analysis.5a
Copyright Ó 2009 The Chemical Society of Japan

Chemistry Letters Vol.38, No.9 (2009)
905
Ph
Ph
OH
Cu(O3SC11H23 2
(10 mol%)
)
H2O, 22 h
N
H
Ph
Ph
80% y, 96% ee
N
N
+
O
OH
HO
N
H
(S,S)-1 (12 mol%)
2a
3a (1.2 equiv)
Ph
OH
Sc(O3SC11H23 3
)
(10 mol%)
H2O, 22 h
Ph
.
Figure 1. X-raþy structure of [CuBr2 1] (left) and
. .
[ScBr2 H2O 1]
N
. . . .moiety in the X-ray structure of
H
58% y, 92% ee
[ScBr2 H2O 1] Br H2O.5a Hydrogen atoms are omitted for
clarity.
Scheme 1. Reversal of enantioselectivity in Cu- and Sc-cata-
lyzed ring-opening reactions of meso-epoxides.
unique catalysis as well as application of this concept to other
catalytic asymmetric reactions in water are now in progress.
Table 2. Cu- and Sc-catalyzed asymmetric ring-opening reac-
tions of meso-epoxides with anilines
This work was partially supported by a Grant-in-Aid for Sci-
ence Research from the Japan Society for the Promotion of Sci-
ence (JSPS) and Global COE Program (Chemistry Innovation
through Cooperation of Science and Engineering), The Univer-
sity of Tokyo, MEXT, Japan.
Cu(O3SC11H23 2
)
or Sc(O3SC11H23 3
)
R
R
R
R
OH
(10 mol%)
(S,S)-1 (12 mol%)
+
NHMePh
O
NMePh
H2O, rt, 22 h
2
5 (1.2 equiv)
6
Cu
Sc
References and Notes
Entry
R
1
a) Aqueous-Phase Organometallic Catalysis, 2nd ed., ed. by B. Cornils,
W. A. Herrmann, Wiley-VCH, Weinheim, 2004. b) S. Kobayashi, Pure
Appl. Chem. 2007, 79, 235.
Yield/% ee/% Yield/% ee/%
1
2
3
4
Ph
88
81
78
72
91
90
90
91
96
76
85
88
ꢁ97
ꢁ96
ꢁ96
ꢁ97
2-Naphthyl
4-MeC6H4
4-BrC6H4
2
a) Organic Reactions in Water, ed. by U. M. Lindstrom, Blackwell, Ox-
¨
ford, 2007. b) K. Manabe, S. Iimura, X.-M. Sun, S. Kobayashi, J. Am.
Chem. Soc. 2002, 124, 11971.
3
4
Catalytic Asymmetric Synthesis, 2nd ed., ed. by I. Ojima, Wiley-VCH,
Weinheim, 2000.
Furthermore, the reversal of enantioselectivity was also ob-
served in the meso-epoxide ring-opening reactions with anilines.
The Cu–(S,S)-1 complex catalyzed these reactions in water to af-
ford the corresponding ꢀ-amino alcohols in good to high yields
and enantioselectivity (Table 2). It is noted that the sense of
enantioselection in these reactions was again reversed compared
with that obtained using the Sc–(S,S)-1 complex as a catalyst.12
The reversal of enantioselectivity observed by switching
metal sources, Cu(II) and Sc(III), with the same chiral ligand
prompted us to further investigate the origin of the selectivity.
Single crystals suitable for X-ray structure analysis were ob-
tained from CuBr2–(S,S)-1 complex, the complex adopts a
square pyramidal structure where two nitrogens and only one
of the oxygens of 1 are attached to Cu(II) in a tridentate manner
(Figure 1). The structure is in remarkable contrast to that of the
ScBr3–(S,S)-1 analogue5a where two nitrogens and two oxygens
of 1 are bound to Sc(III) in a tetradentate manner. This difference
of the structure could explain the reversal of the enantioselectiv-
ity.13
In summary, we have observed reversal of enantioselectivity
in Cu–chiral bipyridine catalyzed asymmetric ring-opening reac-
tions of meso-epoxides with indole and aniline derivatives com-
pared to Sc–chiral bipyridine catalyzed reactions, where the
same chiral ligand was used. The key concept is use of multi-
coordinated ligands combined with appropriate metals in water.
X-ray crystal structural analysis of bromide analogues revealed a
square pyramidal structure for the Cu(II) complex and a pentag-
onal bipyramidal structure for the Sc(III) complex, which could
explain the reversal of the enantioselectivity. It is noted that the
reactions proceeded in water and that the use of water as a sol-
vent is essential. Investigation of the scope and limitation of this
a) S. Nagayama, S. Kobayashi, J. Am. Chem. Soc. 2000, 122, 11531. b) T.
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Lewis Acid Catalysis in Aqueous Media, in Asymmetric Synthesis—The
Essentials, ed. by M. Christmann, S. Brase, Wiley-VCH, Weinheim,
¨
2007, pp. 110–115.
5
Other examples, a) S. Ishikawa, T. Hamada, K. Manabe, S. Kobayashi,
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6
7
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8
9
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¨
10 Alkyl-substituted meso-epoxides did not react under the conditions.
11 Although we already reported Sc(DS)3–1 catalyzed reactions, we con-
ducted all experiments shown in Tables 1 and 2 using Sc(O3SC11H23
and (S,S)-1.
)
3
12 a) S. Azoulay, K. Manabe, S. Kobayashi, Org. Lett. 2005, 7, 4593. b) C.
Ogawa, S. Azoulay, S. Kobayashi, Heterocycles 2005, 66, 201.
13 See Supporting Information. Supporting Information is available elec-
tronically on the CSJ-Journal Web site, http://www.csj.jp/journals/
chem-lett/index.html.
Published on the web (Advance View) August 22, 2009; doi:10.1246/cl.2009.904