Enantiopure trans- and cis-3-Aminoindan-1-ols: Preparation and application as novel basic resolving agents

Article abstract of DOI:10.1246/cl.2002.266

trans- and cis-3-Aminoindan-1-ols were prepared by moderately selective reductions of 3-aminoindan-1-one derivatives and separated into enantiopure forms. The enantiopure trans-isomer had a moderate resolving ability for 2-arylalkanoic acids having a naphthalene ring at the α-position. The X-ray crystallographic analysis showed that an infinite hydrogen-bond sheet was formed in the less-soluble salt, suggesting that the skeleton of these indanols would be favorable for the stabilization of the less-soluble salt by hydrogen-bonding interaction.

Full text of DOI:10.1246/cl.2002.266

266
Chemistry Letters 2002
Enantiopure trans- and cis-3-Aminoindan-1-ols:
Preparation and Application as Novel Basic Resolving Agents
Kazushi Kinbara, Yoshiyuki Katsumata, and Kazuhiko Saigoꢀ
Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo,
Hongo, Bunkyo-ku, Tokyo 113-8656
(Received November 8, 2001; CL-011123)
trans- and cis-3-Aminoindan-1-ols were prepared by mod-
erately selective reductions of 3-aminoindan-1-one derivatives
and separated into enantiopure forms. The enantiopure trans-
isomer had a moderate resolving ability for 2-arylalkanoic acids
having a naphthalene ring at the ꢀ-position. The X-ray crystal-
lographic analysis showed that an infinite hydrogen-bond sheet
was formed in the less-soluble salt, suggesting that the skeleton of
these indanols would be favorable for the stabilization of the less-
soluble salt by hydrogen-bonding interaction.
Scheme 1.
Amino alcohols are versatile compounds as chiral auxiliaries
in asymmetric syntheses, resolving agents, etc. We have been
focusing our attention on amino alcohols as resolving agents,
putting the final goal on the rational design of novel high-
performance basic resolving agents fit to target acidic racemates.
In the course of our studies on the diastereomeric resolution of
systematically-selected racemates by acidic resolving agents,1
we have found that the formation of a hydrogen-bond sheet in
less-soluble diastereomeric salts was important to achieve high
efficiency of resolution.2 On the basis of the results, it is expected
that the similar strategy would be applicable for the design of
basic resolving agents.3 After several systematic studies,3 we now
reached to an idea that an indane derivative, in which an amino
group and a hydroxy group exist apart from each other, would be
suitable for the formation of a stable hydrogen-bond sheet in the
less-soluble salts with acidic racemates. Thus, as a candidate
having the above-mentioned suitable skeleton, we chose 1,3-
amino alcohol, i.e. 3-aminoindan-1-ol in the present study. Here
we report the first preparation of enantiopure trans- and cis-1-
aminoindan-3-ols (1a and 1b) and discuss whether 1 are favorable
as resolving agents on the basis of the crystal structure of the less-
soluble diastereomeric salts with acidic racemates.
Scheme 2.
Scheme 3.
The selectivity could be switched by changing the order of
reduction and deprotection of 3 (Scheme 2). The reduction of 3 by
ꢁ
BH3 THF gave 3-acetamidoindan-1-ol (5) as a mixture of the
In contrast to the preparation of vicinal cyclic amino alcohols
reported so far, that of cyclic 1,3-amino alcohols is rather rare. As
a starting compound, which has a skeleton preferable for the
construction of a cyclic 1,3-amino alcohol, we selected a ꢁ-amino
acid derivative. As a result, the preparation of racemic 1-
aminoindan-3-ols could be accomplished (Schemes 1 and 2),
starting from N-acetyl-3-amino-3-phenylpropanoic acid (2)
which could be easily prepared by the acetylation of 3-amino-3-
phenylpropanoic acid.4 The Friedel-Crafts cyclization of 2
afforded 3-acetamidoindan-1-one (3), which was treated with
hydrochloric acid to give the amino ketone 4 in good yield. The
reduction of 4 by sodium borohydride afforded amino alcohols 1
as a 3 : 1 mixture of 1a and 1b. Pure racemic 1a could be obtained
by conversion of this mixture to the salt with naphthylacetic acid,
followed by recrystallization from dichloromethane. The total
yield of racemic 1a from 3 was 47%.
isomers (trans : cis ¼ 1 : 3). Recrystallization of this mixture
twice from ethyl acetate afforded pure cis-5, and the deprotection
of cis-5 with aqueous sodium hydroxide gave 1b in good yield.
The total yield of racemic 1b from 3 was 31%.
Enantiopure forms of 1a could be obtained by the
diastereomeric resolution using (À)-dibenzoyl-L-tartaric acid
((À)-6) as a resolving agent (Scheme 3). Thus, recrystallization of
the diastereomeric salt of 1a with (À)-6 three times from aqueous
ethanol afforded pure (1S, 3S)-1aꢁðÀÞ-6, which was hydrolized by
aqueous KOH to give pure (1S, 3S)-1a in 38% yield.5
(1R, 3R)-1a could be obtained in a similar manner to the
resolution of (1S, 3S)-1a by using (þ)-6 as a resolving agent:
From the mother liquor of the first crystallization, (1R, 3R)-1a-
enriched mixture could be recovered, which was treated with (þ)-
dibenzoyl-D-tatraric acid ((þ)-6) to afford enantiopure (1R, 3R)-
1a. The absolute stereochemistry of (1S, 3S)-1a was determined
Copyright Ó 2002 The Chemical Society of Japan

Chemistry Letters 2002
267
Table 1. Resolution of 2-arylalkanoic Acids by (1S, 3S)-1a
columnar hydrogen-bond network, as were found in less-soluble
diastereomeric salts of our previous studies (Figure 1a).1;2 The
þ
ꢁ
remarkable point is the role of the hydroxy group of 1a H in the
hydrogen-bond network. In this structure, the hydroxy group of
1aꢁHþ directly forms hydrogen-bonds with the carboxylate
oxygen, resulting in the formation of an infinite sheet of
hydrogen-bonds in the less-soluble salt (Figure 1b). This sheet
structure is reinforced by hydrogen-bonds with water molecules
incorporated in the less-soluble salt. As a result, a quite stable
hydrogen-bond sheet is realized in the less-soluble salt. This is the
first example of a less-soluble salt, in which the hydroxy group of
an amino alcohol directly interacts with a columnar structure,
made by ammonium hydrogens and carboxylate oxygens, to form
a hydrogen-bond sheet.
Although the resolution ability of this amino alcohol is not
high enough for practical use, the crystal structure of the less-
soluble salts shows that the geometrical relationship between the
hydroxy group and the amino group is very important for the
formation of a stable hydrogen-bond sheet. Thus, it is expected
that this structure would become a potential candidate for a novel
basic resolving agent; upon introducing a suitable substituent on
the aromatic group of 1a to realize close packing of less-soluble
diastereomeric salts, a morepowerful basic resolving agentwould
be achieved.
by the X-ray crystallographic analysis of (1S, 3S)-1aꢁðÀÞ-
ditoluoyltartrate.6
Concerning 1b, its enantiopure form was difficult to be
obtained by the diastereomeric resolution. Instead, chiral HPLC
was found to be effective for the separation of the enantiomers.7
The resolution of 2-arylalkanoic acids was performed using
enantiopure 1a as a resolving agent (Table 1). As a result, it was
found that the resulting diastereomeric salts had rather high
solubility in aqueous alcohol and that the efficiency of resolution
was quite low when the aryl group was a substituted phenyl group.
In contrast, moderate efficiency of resolution could be achieved in
the cases of 2-arylalkanoic acids having a naphthalene ring at the
ꢀ-position.
Dedicated to Prof. Teruaki Mukaiyama on occasion of his
75th birthday.
References and Notes
1
K. Kinbara, Y. Harada, and K. Saigo, J. Chem. Soc., Perkin Trans. 2,
2000, 1339; K. Kinbara, K. Oishi, Y. Harada, and K. Saigo,
Tetrahedron, 56, 6651 (2000).
K. Kinbara, K. Sakai, Y. Hashimoto, H. Nohira, and K. Saigo, J. Chem.
Soc., Perkin Trans. 2, 1996, 2615.
K. Kinbara, Y. Kobayashi, and K. Saigo, J. Chem. Soc., Perkin Trans. 2,
2000, 111; K. Kinbara, Y. Kobayashi, and K. Saigo, J. Chem. Soc.,
Perkin Trans. 2, 1998, 1767.
The crystal structure of the less-soluble salt of (1S, 3S)-
8
ꢁ
1a ðSÞ-naproxen (entry 2) is shown in Figure 1. This crystal has a
quite characteristic hydrogen-bonding pattern, compared with
otherþreported examples.1{3 At first, the ammonium hydrogen of
1aꢁH and the carboxylate oxygen of a naproxen anion form a
2
3
4
5
P. Kuehne, A. Linden, and M. Hesse, Helv. Chim. Acta, 79, 1085 (1996).
(1S, 3S)-1a: mp 113.5–114 ꢂC; 1H NMR (CDCl3) ꢂ ¼ 1:58 (br, s, 3H),
2.06(dt, 1H, J ¼ 6:3, 13.7 Hz), 2.46(ddd, J ¼ 3:0, 6.3, 13.7 Hz), 4.64(t,
1H, J ¼ 6:3 Hz), 5.34 (dd, 1H, J ¼ 3:0, 6.3 Hz), 7.31–7.43 ppm (m, 4H);
IR (KBr) 3350, 3300, 3125, 2925, 2700, 1650, 1320, 1300, 1040, 990,
17:2
770 cmÀ1; ½ꢀꢃ
¼ 38:1 (c ¼ 1:00, EtOH). (1R, 3R)-1a: mp 112–
D
17:2
113.5 ꢂC; ½ꢀꢃ
¼ À39:3 (c ¼ 1:00, EtOH); 1H NMR and IR spectra
D
were identical with (1S, 3S)-1a.
Crystal data for (1S, 2S)-1aꢁðÀÞ-ditoluoyl-L-tartrate: C29H29NO9,
6
7
ꢀ
M ¼ 535:55, Orthorhombic, space group P21212, a ¼ 14:994ð1Þ A,
ꢀ
ꢀ
ꢀ 3
b ¼ 24:595ð2Þ A, c ¼ 7:927ð2Þ A, V ¼ 2923:3ð3Þ A , Z ¼ 4, Dc ¼
1:217 Mg mÀ3, R ¼ 0:085, reflections used ¼ 3970. The details of the
refinement was submitted as supporting information.
Daicel CrownPak CRþ (eluent: pH1.9 HClO4Þ was used for the
separation of the enantiomers. A small amount of unknown compound
cotaminates (þ)-1b. The details for the separation and characterization
of (þ)- and (À)-1b will be reported elsewhere. (þ)-1b: The first
fraction; Colorless oil; 1H NMR (CDCl3) ꢂ ¼ 1:64 (dt, 1H, J ¼ 6:0,
13.2 Hz), 2.13 (br, s, 3H), 2.81 (dt, J ¼ 6:6, 14.1 Hz), 4.24 (t, 1H,
J ¼ 6:6 Hz), 5.05 (t, 1H, J ¼ 6:0 Hz), 7.30–7.44 ppm (m, 4H); IR (KBr)
3350, 2950, 1580, 1460, 1340, 1040, 770, 740 cmÀ1; CD (CHCl3,
7:2 ꢄ 10À4 M, 1.0 cm): ꢃðꢁ"Þ ¼ 280 (1.5). (À)-1b: The second
fraction; Colorless oil; CD (CHCl3, 7:2 ꢄ 10À4 M, 1.0 cm):
ꢃðꢁ"Þ ¼ 280 (0.23); 1H NMR and IR spectra were identical with
(þ)-1b.
8
Crystal data for (1S, 2S)-1aꢁðSÞ-naproxen: Space group, C2,
ꢀ
ꢀ
ꢀ
Figure 1. Crystal structure of less-soluble (1S, 3S)-1aꢁðSÞ-
naproxen. a) Schematic representation of the hydrogen-bond
column. b) Hydrogen-bond sheet viewed down the b-axis. The
dotted lines represent hydrogen bonds.
a ¼ 20:516ð5Þ (A), b ¼ 6:263ð1Þ (A), c ¼ 19:027ð4Þ (A), ꢁ ¼
119:73ð1Þ ( ), V ¼ 2123:0ð7Þ A , Z ¼ 2, Dc ¼ 1:272 Mg mÀ3, R ¼
0:052, reflections used ¼ 2735. The detail of the refinement was
submitted as supporting information.
ꢂ
ꢀ 3