Synthesis of 3,3′-(4H,4′H)-spirobi(2H-naphtho[1,2-b]pyran)-6, 6′-dicarboxylic acid and its optical resolution

Article abstract of DOI:10.1246/cl.2008.930

The synthesis and optical resolution of 3,3′-(4H,4′H)- spirobi(2H-naphtho[1,2-b]pyran)-6,6′-dicarboxylic acid were successfully accomplished. The formation of the spiro skeleton and the bromination of the aromatic ring were easily achieved in the presence of bromine. Optical resolution was achieved by amidation with L-valinol (2-amino-3-methyl-1-butanol) . Copyright

Full text of DOI:10.1246/cl.2008.930

930
Chemistry Letters Vol.37, No.9 (2008)
Synthesis of 3,30-(4H,40H)-spirobi(2H-naphtho[1,2-b]pyran)-6,60-dicarboxylic Acid
and Its Optical Resolution
Kenta Tojo, Tatsuya Arisawa, Mikio Yasutake, Yoshio Aoki, and Daiyo Terunumaꢀ
Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakura-ku, Saitama 338-8570
(Received June 11, 2008; CL-080582; E-mail: s06ds006@mail.saitama-u.ac.jp)
The synthesis and optical resolution of 3,30-(4H,40H)-spiro-
LAH to give 6. The diol 6 was treated with bromine to facilitate
intramolecular cyclization and concurrent bromination of the
aromatic ring, giving 7. This reaction proceeded under mild
conditions, and was quickly completed after addition of the
bromine solution. The mechanism of this reaction probably
proceeded as follows (Figure 2). First, a bromination of the
naphthalene ring occurred, and hydrogen bromide was generat-
ed. Second, the oxygen atom of the hydroxy group was protonat-
ed by the hydrogen bromide. Third, intramolecular cyclization
occurred with elimination of water. Fourth, the bromide ion at-
tacked the methyl carbon. As a result, (ꢁ)-7 and bromomethane
were generated. This reaction is useful for obtaining 6-bromo-
2H-benzo[1,2-b]pyran derivatives from 3-(2-methoxy-1-phe-
nyl)propan-1-ol derivatives. The bromide (ꢁ)-7 was converted
into the cyanide (ꢁ)-8 using copper cyanide. Owing to the diffi-
culty of hydrolyzing (ꢁ)-8 with sodium hydroxide, (ꢁ)-8 was
converted into (ꢁ)-9 using n-butanol and p-toluenesulphonic
acid. Finally, (ꢁ)-9 was easily hydrolyzed to (ꢁ)-1 using sodium
hydroxide.
bi(2H-naphtho[1,2-b]pyran)-6,60-dicarboxylic acid were suc-
cessfully accomplished. The formation of the spiro skeleton
and the bromination of the aromatic ring were easily achieved
in the presence of bromine. Optical resolution was achieved by
amidation with L-valinol (2-amino-3-methyl-1-butanol).
Optically active compounds are used industrially as pharma-
ceutical products, perfume ingredients, and liquid crystalline
materials. The majority of these chiral compounds contain asym-
metric carbons, however, some axial asymmetric chiral com-
pounds have been reported to be effective chiral ligands for
asymmetric synthesis1 and as chiral dopants with large helical
twisting power for nematic liquid crystals.2,3 Many axial asym-
metric chiral compounds have a biaryl structure. Optically active
spiro compounds having a rigid asymmetric structure can poten-
tially be used as new chiral materials, but few have been report-
ed.4–7 For example, spiro phosphoramide ligands derived from
optically active 1,10-spirobiindane-7,70-diol performed as chiral
ligands in the asymmetric rhodium-catalyzed hydrogenation of
functionalized olefins4a and the rhodium-catalyzed asymmetric
addition of arylboronic acids to aldehydes or ꢀ-ketoesters.4b,4c
Also, 2,20-spirobiindane-5,50-diheptyloxy-1,10-dione was report-
ed as a chiral dopant for smectic liquid crystalline mixtures.7
Here, we report the synthesis and optical resolution of the
novel spiro compound, 3,30-(4H,40H)-spirobi(2H-naphtho[1,2-
b]pyran)-6,60-dicarboxylic acid (1, Figure 1). The two naphtha-
lene rings of 1 are fixed by the spiro structure. In order to facil-
itate the optical resolution and synthesis of 1 derivatives, two
carboxyl groups are introduced. The new optically active car-
boxylic acid 1 and its derivatives may have the ability to resolve
racemic amines, chiral ligands for asymmetric synthesis, and
chiral liquid crystalline materials.
Next, we attempted the optical resolution of (ꢁ)-1 via its
diastereomeric salts and diastereomeric esters. The solubility
of the diastereomeric salts prepared from (ꢁ)-1 and (S)-(ꢂ)-1-
HO
O
MeO
O
MeO
a
b
OH
OMe
X
2 (Yield 92.4%)
3, X = OH (Yield 99.3%)
4, X = Br (yield 87.8%)
c
EtO
MeO
d
O
O
O
e
EtO
OEt
O
OMe
OEt
5 (Yield 80.6%)
X
HO
MeO
f
h
O
X
O
The synthetic route for (ꢁ)-1 is shown in Scheme 1.8 The
starting material, 1-hydroxy-2-naphthoic acid was methylated
using iodomethane and sodium hydride. After the methylation,
2 was reduced with lithium aluminum hydride (LAH) to give
3, which was then successfully brominated using phosphorus
tribromide to give 4. Diethyl malonate was alkylated by using
4 and potassium t-butoxide to afford 5, which was reduced with
OMe
OH
( )-7, X = Br (Yield 88.4%)
( )-8, X = CN (Yield 81.0%)
6 (Yield 92.4%)
g
O
OBu
i
O
O
( )-1 (Yield 98.6%)
O
OH
O
OBu
O
O
( )-9 (Yield 73.3%)
Scheme 1. Synthetic route of (ꢁ)-1: (a) CH3I, NaH, dry
DMF. (b) LiAlH4, dry THF, 50 ꢃC. (c) PBr3, dry toluene. (d) 1:
t-BuOK, THF, 2: 4. (e) LiAlH4, dry THF. (f) Br2, CH2Cl2. (g)
CuCN, N-methylpyrroridone, 200 ꢃC. (h) n-BuOH, PTSA. H2O,
reflux. (i) NaOHaq., EtOH, THF, reflux.
O
OH
1
Figure 1. Structure of 1.
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.9 (2008)
931
CH3
CH3
H
H
O
O
H
O
O
N
O
Br
H
Br
O
O
Br Br
CH3
H
Br
O
H
O
CH3
O
N
O
O
H
Br
H
Br
Figure 3. X-ray analysis of (S)-11 derived from 10 having
higher Rf .
Br
Br
CH3
Br CH3
Because of the steric hindrance between the carbonyl group
and the isopropyl group, it was difficult to hydrolyze (S)-10
using sodium hydroxide. Therefore, (S)-10 was converted into
the oxazoline ((S)-11) using thionyl chloride (Scheme 2).9,10
The oxazoline ring was opened with trifluoroacetic acid and
water, and the liberated amino group was acetylated.9,10 Finally,
the ester (S)-12 was hydrolyzed into (S)-(ꢂ)-1 using potassium
t-butoxide and water.9,10 The optically active (S)-(ꢂ)-1 was
converted into (S)-9 using n-butanol and phosphoryl chloride
for determination of enantiomeric excess (ee). The ee of (S)-9
was determined by chiral HPLC analysis [Daicel Chiralpak
AD-H column, n-hexane/2-propanol = 9:1 as eluent, flow
rate = 0.50 mL/min, tR ¼ 25:6 min for (S)-9 and 31.1 min
for (R)-9]. The absolute configuration of (ꢂ)-1 was determined
to be the S configuration by single crystal X-ray diffraction
of 11 derived from 10 having higher Rf (Figure 3).11
O
O
Br
Br
Figure 2. A plausible mechanism of the spiro structure formation.
OH
O
NH
(S)-10
(Yield 39%)
j
k
( )-1
O
O
(R)-10
(Yield 34%)
O NH
OH
In conclusion, the synthesis and the optical resolution
of the new spiro compound 1 were achieved. The absolute
configuration of (ꢂ)-1 was determined by single crystal X-ray
diffraction of the diastereomeric oxazoline 11. The applications
of 1 and the synthesis of its derivatives as novel chiral materials
are in progress.
10
AcNH
O
O
N
O
m
l
O
O
O
O
References and Notes
1
2
3
4
R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley, New
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O
O
O
N
NHAc
(S)-11 (Yield 70.9%)
(S)-12 (Yield 87.5%)
n

(S)-( )-1 (Yield 83%)
Scheme 2. Synthetic route of (S)-(ꢂ)-1: (j): 1) SOCl2, dry
toluene, reflux, 2) L-valinol, Et3N, dry CH2Cl2. (k) Column chro-
matography (Silicagel 60 N, spherical neutral; eluent: 2-prop-
anol:CH2Cl2 = 1:9), (l) SOCl2, dry CH2Cl2. (m): 1) TFA, THF,
H2O, 2) AcCl, pyridine, dry CH2Cl2. (n) t-BuOK, H2O, THF.
5
6
H. Zhou, W.-H. Wang, Y. Fu, J.-H. Xie, W.-J. Shi, L.-X. Wang, Q.-L.
Zhou, J. Org. Chem. 2003, 68, 1582.
T. Takahashi, H. Tsutsui, M. Tamura, S. Kitagaki, M. Nakajima,
S. Hashimoto, Chem. Commun. 2001, 1604; M. A. Arai, M. Kurihashi,
T. Arai, H. Sasai, J. Am. Chem. Soc. 2001, 123, 2907; M. L. Patil,
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644.
phenylethylamine or (1S,2R)-(ꢂ)-2-(benzylaminocyclohexyl)-
methanol were very low in most solvents, causing separation
of the salts to fail. The diastereomeric esters derived from (ꢁ)-
1 and (R)-(ꢂ)-2-butanol, (ꢂ)-borneol, or L-menthol could not
be separated by silica gel chromatography. Finally, it was found
that the optical resolution of (ꢁ)-1 was successfully achieved via
the diastereomeric amide 10 derived from (ꢁ)-1 and L-valinol
(2-amino-3-methyl-1-butanol) (Scheme 2). The diastereomeric
amide was separated by silica gel chromatography (Silica gel
60 N, Spherical, neutral, Kanto, Rf ¼ 0:6 and 0.7) using 2-prop-
anol and dichloromethane (1:9) as the eluent. Here, the diaster-
eomeric amide of Rf ¼ 0:6 is (S)-10, and the diastereomeric
amide of Rf ¼ 0:7 is (R)-10.
7
8
9
Supporting Information is available electronically on the CSJ-Journal
Web site, http://www.csj.jp/journals/chem-lett/index.html.
´
´
G. Solladie, P. Hugele, R. Bartsch, A. Skouious, Angew. Chem., Int.
Ed. Engl. 1996, 35, 1533.
´
´
10 G. Solladie, P. Hugele, R. Bartsch, J. Org. Chem. 1998, 63, 3895.
11 CCDC 685376 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12,
Union Road, Cambridge, CB2 1EZ, UK; fax: +44 1223 336033;
e-mail: deposit@ccdc.cam.ac.uk).
Published on the web (Advance View) July 26, 2008; doi:10.1246/cl.2008.930