Synthesis of novel C2-symmetric and enantiomerically pure bisbenzoxazoles and bisbenzothiazoles derived from L- and D-tartaric acids

Article abstract of DOI:10.1016/S0957-4166(01)00547-X

Five pairs of novel C₂-symmetric and enantiomerically pure bisbenzoxazoles and a pair of bisbenzothiazoles derived from L- and D-tartaric acids have been synthesized from L- and D-2,3-O-isopropylidenetartaric dichlorides and o-aminophenol derivatives or o-aminothiophenol, respectively, in two- or one-step reactions. The mechanism for the formation of bisbenzoxazoles and bisbenzothiazoles was suggested. The UV and ¹H NMR spectra showed that no coordination between the bisbenzoheterazoles and Cu(I) or Ni(II) cations occurred due to the lack of a sufficiently basic nitrogen donor atom in the benzoheterazole moiety.

Full text of DOI:10.1016/S0957-4166(01)00547-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 3081–3088
Synthesis of novel C2-symmetric and enantiomerically pure
bisbenzoxazoles and bisbenzothiazoles derived from - and
-tartaric acids
L
D
Peng Jiao,a Jiaxi Xu,a,* Qihan Zhang,a Michael C. K. Choib and Albert S. C. Chanb
aCollege of Chemistry and Molecular Engineering, Peking University, Beijing 100871, PR China
bOpen Laboratory of Chirotechnology and Department of Applied Biology and Chemical Technology,
The Hong Kong Polytechnic University, Hong Kong, PR China
Received 18 June 2001; accepted 20 November 2001
Abstract—Five pairs of novel C2-symmetric and enantiomerically pure bisbenzoxazoles and a pair of bisbenzothiazoles derived
from L- and D-tartaric acids have been synthesized from L- and D-2,3-O-isopropylidenetartaric dichlorides and o-aminophenol
derivatives or o-aminothiophenol, respectively, in two- or one-step reactions. The mechanism for the formation of bisbenzoxazoles
and bisbenzothiazoles was suggested. The UV and 1H NMR spectra showed that no coordination between the bisbenzoheterazoles
and Cu(I) or Ni(II) cations occurred due to the lack of a sufficiently basic nitrogen donor atom in the benzoheterazole moiety.
© 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
and Andrus recently reported a set of biaryl-linked
bisoxazoline ligands with different substituents in the
oxazoline ring.10c,15 Herein we report the preparation of
a new kind of C2-symmetric chiral bisbenzoxazoles 1a–e
and 2a–e, and a pair of new C2-symmetric chiral bis-
benzothiazoles 1f and 2f (Scheme 1).
The C2-symmetrical chiral bisoxazoline derivatives have
recently been employed as ligands in a wide variety of
metal-catalyzed asymmetric reactions,1 including the
cyclopropanation of olefins,2 aziridination of olefins,3
Diels–Alder and hetero-Diels–Alder reactions,4 1,3-
dipolar cycloadditions,5 allylic displacement,6 addition
of dialkylzinc to aldehydes,7 organolithium addition to
imines,8 hydrosilylative reduction,9 allylic oxidation of
olefins,10 hydrosilylation of ketones,11 Friedel–Crafts
reaction,12 diene cyclization/hydrosilylation,13 glyoxyl-
ate-ene reaction,14 and so on. Over the last decade a
wide range of C2-symmetric chiral bisoxazoline ligands
have been synthesized from readily available diacid
derivatives and amino alcohols.1 The Lewis basicity of
the nitrogen donor atoms and the conformationally
rigid framework of the chelate represent important
structural features of this type of ligand. The influence
of substitution at the oxazoline ring and the C2-sym-
metric arrangement of the stereogenic centers in close
proximity to the coordination site on the course of
reactions mediated by bisoxazoline-ligated metal species
has been studied.2b While the vast majority of bisoxazo-
line ligands are methylene, benzo and pyridyl linked
with different substituents in the oxazoline ring, Corey
2. Results and discussion
Our design for these new ligands is such that it is
possible for them to possess an obvious different struc-
tural feature to previously reported bisoxazoline lig-
ands. In our ligands two stereogenic centers come from
L
- or
D
-tartaric acid 3 or 4, and the rigid benzoxazole
rings with different substituents on the benzene rings.
The designed ligands may give a chiral environment
with large specific rotation values. It may also produce
an effective asymmetric environment in the course of
reactions and induce good enantioselectivity in some
asymmetric reactions.
Although there are several methods reported for the
preparation of benzoxazoles from acids and o-
aminophenol derivatives,16 most of them require acidic
and high temperature conditions, for example, reactions
catalyzed by PPA or PPE,17 POCl3,18 and SOCl2.19 In
the case of preparing ligands such as 1a–f and 2a–f,
* Corresponding author.
0957-4166/01/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00547-X

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P. Jiao et al. / Tetrahedron: Asymmetry 12 (2001) 3081–3088
i) EtOH/H+
O
O
O
O
HO
OH
NaOH
(COCl)2
91%
Cl
Cl
EtO
OEt
79%
or i) LiOH
ii) TMSCl
HOOC
COOH ii) HC(OEt)3
Me2CO, H+
>99%
O
O
O
O
3
5
7
NH2
O
O
R
XH
O
O
O
X
X
R'
Ph3P, DEAD
N
N
9a-f
HN
NH
O
R'
R'
R
XH HX
R
R
R
1a-f
R'
R'
10a-f
i) EtOH/H+
91%
O
O
O
O
HO
HOOC
OH
NaOH
(COCl)2
Cl
Cl
EtO
OEt
79%
or i) LiOH
ii) TMSCl
COOH ii) HC(OEt)3
Me2CO, H+
>99%
O
O
O
O
4
8
6
NH2
O
O
R
XH
O
O
O
X
X
R'
Ph3P, DEAD
N
N
9a-f
HN
NH
O
R
XH HX
R
R'
R'
R
R
R'
R'
2a-f
11a-f
a X = O, R = R' = H,
b X = O, R = Me, R' = H,
c X = O, R = Cl, R' = H,
d X = O, R = NO2, R' = H,
e X = O, R = Cl, R' = NO2,
f X = S, R = R' = H
Scheme 1. Synthesis of enantiomerically pure 4,5-bis(benzoheterazol-2-yl)-2,2-dimethyl-1,3-dioxolanes.
method for the preparation of 2,2-dimethyl-1,3-diox-
olane-4,5-dicarboxamides from amines and 2,2-
however, these methods cannot be adopted because of
the presence of acid-sensitive 1,3-dioxolane groups in
the compounds. Instead, another approach using the
Mitsunobu reaction for the preparation of oxazoline
derivatives and benzoxazoles, under mild and neutral
conditions, as investigated by Roush20 and Wang,21
respectively, was found to be successful in this
synthesis.
dimethyl-1,3-dioxolane-4,5-dicarboxylic
dichloride,
which was prepared from dimethyl 2,2-dimethyl-1,3-
dioxolane-4,5-dicarboxylate through base-catalyzed
hydrolysis in methanolic aqueous lithium hydroxide,
conversion into di(trimethylsilyl) diester using 18-
crown-6 as a phase transfer catalyst, followed by treat-
ment with oxalyl chloride and a catalytic amount of
DMF. We felt that it would be a useful method for us
to synthesize diamides 10 and 11. However, when we
used this method to synthesize a pair of dihydroxy-
The diamides 10 and 11 are very important intermedi-
ates for the preparation of bisbenzoheterazoles 1 and 2
using the Mitsunobu reaction. Choi et al.22 reported a

P. Jiao et al. / Tetrahedron: Asymmetry 12 (2001) 3081–3088
3083
dichlorides 7 and 8 and o-aminothiophenol 9f using this
one-pot method. This showed that in the synthesis of
bisbenzoxazoles through the Mitsunobu reaction, the
oxygen atoms in the benzoxazole ring originate in the
hydroxyl group of the o-aminophenols 9a–e and not
the amide group.
phenyl diamides 10a and 11a from 2-aminophenol and
diethyl - and -tartrates 5 and 6, we found that
racemization occurred. Based on the structures of
and -2,3-O-isopropylidenetartaric dichlorides 7 and 8,
it should be unfavorable for them to racemize because
they would convert into the less favored meso-2,3-O-
isopropylidenetartaric dichloride bearing a dioxolane
ring with cis-acyl chloride groups in the 4- and 5-posi-
L
D
L
-
D
A suggested mechanism for the Mitsunobu reaction is
as follows: triphenylphosphine attacks DEAD to form
the zwitterionic adduct A, which abstracts an acidic
hydrogen from the hydroxyl (or mercapto) group of the
phenol (or thiophenol) to yield an azaphosphonium
phenolate B. The amide in B then tautomerizes into a
hydroxy imine form C, the hydroxyl group of which
attacks the phosphonium ion to form an activated
oxyphosphonium ion intermediate D, which then
undergoes an addition–elimination process to produce
the benzoxazole (or benzothiazole) ring and
triphenylphosphine oxide (Scheme 2).
tions, from an
L- or D-2,3-O-isopropylidenetartaric
dichloride bearing a dioxolane ring with trans-car-
boxylic chloride groups in the 4- and 5-positions. We
rationalized that high temperature would be a major
reason for the observed racemization. When we pre-
pared dichlorides 7 and 8 at low temperature, followed
by removal of solvent and excess oxalyl chloride, and
reacted them directly with the aromatic amines 9a–e,
we successfully obtained the corresponding enantiomer-
ically pure N,N%-bis(2-hydroxyphenyl)-2,2-dimethyl-1,3-
dioxolane-4,5-dicarboxamides 10a–e and 11a–e in good
yields. We also found another available method
reported by Picard et al.23 for the preparation of enan-
tiomerically pure diacid chlorides 7 and 8 in high yields
The efficiency of bisbenzoxazoles and bisbenzothiazoles
1 and 2 as ligands in asymmetric aziridination catalyzed
by [Cu(MeCN)4]PF6 was evaluated.28 Unfortunately,
almost no enantiomeric excess has been obtained
(Scheme 3). The asymmetric cyclopropanation of sty-
rene with ethyl diazoacetate2a using 1 and 2 also gave a
racemic mixture.
directly from
L- and D-2,3-O-isopropylidenetartaric
acid disodium salts, respectively, with an excess of
oxalyl chloride in anhydrous benzene. Attempts to con-
vert the L- and D-tartrates 5 and 6 into the correspond-
ing dicarboxamides 10a and 11a directly under neutral
conditions,9c,24 under fluoride-25 or cyanide-catalyzed
neutral conditions,26 or under basic conditions in the
presence of sodium hydride27 were unsuccessful due to
the poor nucleophilicity of 2-aminophenol 9a.
Ts
TsN=IPh, [Cu(MeCN)4]PF6
N
Ligand 1a-f or 2a,f
MeCN
40-88%, ee% 0-4.6
The enantiomerically pure dicarboxamides 10a–e and
11a–e were cyclized successfully into chiral bisbenzoxa-
zole derivatives via Mitsunobu reaction using
triphenylphosphine and diethyl azodicarboxylate
(DEAD).20,21 We found that the crude dihydroxyaryl
diamides could be used directly to synthesize bisbenzox-
azole derivatives in satisfactory yields without further
purification. A pair of enantiomerically pure bisben-
zothiazoles 1f and 2f were also synthesized from the
Scheme 3. Asymmetric aziridination of styrene using bisbenzo-
heterazoles.
Most of the ligands derived from chiral tartaric acid
showed moderate to excellent enantiomeric excesses in
asymmetric reactions.2b,9c,29–35 To understand why the
bisbenzoheterazoles 1 and 2 did not induce enantiose-
NH
O
X
NH
R
O
-X
N
H
EtO2CN NCO2Et
EtO2C
N-
R
H O
R'
N
CO2Et
-X
R
Ph3P:
+PPh3
EtO2C
+PPh3
N
EtO2C
+PPh3
R'
N
R'
A
NHCO2Et
NHCO2Et
B
C
N
R
R
- EtO2CNHNHCO2Et
Ph3P+
N
X
N-
O
-X
R
Ph3P+
O
X
R'
R'
R'
X = O, S
1 and 2
D
Scheme 2. Suggested mechanism for the formation of bisbenzoheterazoles.

3084
P. Jiao et al. / Tetrahedron: Asymmetry 12 (2001) 3081–3088
lectivity in these reactions, it is necessary to check the
validity of the coordination of the azoles with
[Cu(MeCN)4]PF6. The UV spectra of bisbenzoxazole
1a, the Cu catalyst, and bisbenzoxazole 1a with the
catalyst in molar ratios of 1:0.5 and 1:1 were deter-
mined in acetonitrile (Fig. 1). The results showed that
no coordination occurred, as additive spectra were
obtained for the samples of bisbenzoxazole 1a with the
Cu catalyst. To confirm the results, the 1H NMR
spectra of bisbenzoxazole 1a and bisbenzoxazole 1a
with equimolar non-paramagnetic NiCl2 were also
determined in DMSO-d6 solution (Fig. 2). There was no
significant change in the chemical shifts in the spectra.
Thus, we can conclude that no coordination between
the bisbenzoxazole 1a and Cu(I) or Ni(II) cations
occurred, which explains why bisbenzoxazoles and bis-
benzothiazoles 1 and 2 did not give asymmetric induc-
tion in the asymmetric aziridination and cyclopro-
panation reactions.
Bisbenzoxazole 1a showed no coordination with the
transition metals Cu(I) and Ni(II). The reason was
Figure 1. UV spectra of bisbenzoxazole 1a, [Cu(MeCN)4]PF6, and bisbenzoxazole 1a with [Cu(MeCN)4]PF6.
Figure 2. 1H NMR spectra of bisbenzoxazole 1a and bisbenzoxazole 1a with NiCl2 in DMSO-d6.

P. Jiao et al. / Tetrahedron: Asymmetry 12 (2001) 3081–3088
3085
rationalized that C2-symmetrically chiral bisoxazolines
are important and effective ligands in asymmetric cata-
lytic reactions due to the suitable Lewis basic property
of the nitrogen donor atoms in the oxazoline rings.
However, the Lewis basicity of the nitrogen donor
atoms in the bisbenzoheterazoles 1 and 2, in which the
oxazoline and thiazoline rings are fused with a benzene
ring to become aromatic oxazoles and thiazoles, is
weaker than that in bisoxazolines because of the lack of
a sufficiently basic nitrogen donor atom in the azole
moiety.
THF (30 mL) was added dropwise a solution of DEAD
(3.83 mL, 22 mmol) in dry THF (10 mL) under stirring
and nitrogen atmosphere in an ice bath. The resulting
mixture was stirred at room temperature for 8 h. After
removal of the solvent, diethyl ether (60 mL) was added
and the resulting mixture was stirred for 1 h. The
insoluble solid was filtered off. The filtrate was concen-
trated and the residue was purified on a silica gel
column with a mixture of petroleum ether (60–90°C)
and ethyl acetate (10:1, v/v) as the eluent to give a solid
product. If necessary, further crystallization could be
carried out from a mixture of petroleum ether (60–
90°C) and ethyl acetate to give pure crystals of product.
3. Conclusion
4.2.1.
(4R,5R)-4,5-Bis(benzoxazol-2-yl)-2,2-dimethyl-
In conclusion, novel C2-symmetric and enantiomerically
pure bisbenzoxazoles and bisbenzothiazoles derived
1,3-dioxolane 1a. Colorless needles; mp: 109–110°C;
1
yield: 75%; [h]2D0=−224 (c 1.15, CHCl3). H NMR (200
from
from
L
- and
D
-tartaric acids have been synthesized
D-2,3-O-isopropylidenetartaric dichlorides
MHz, CDCl3/TMS) l (ppm): 7.74–7.78 (m, 2H, ArH),
7.55–7.60 (m, 2H, ArH), 7.35–7.43 (m, 4H, ArH), 5.92
(s, 2H, 2CH), 1.66 (s, 6H, 2CH3). IR (KBr pellet, cm−1):
1616 (CꢀN). MS (EI) m/z (rel. intensity): 336 (1.82,
M+), 321 (5.96, M−CH3), 278 (68.51, M−CH3COCH3),
251 (21.53), 189 (100.00), 172 (31.68), 160 (91.45), 148
(52.04), 132 (40.02), 120 (19.55), 119 (19.02), 103 (9.37),
77 (8.05). Anal. calcd for C19H16N2O4: C, 67.85; H,
4.79; N, 8.33. Found: C, 67.86; H, 4.71; N, 8.08%
L
- and
and o-aminophenol derivatives or o-aminothiophenol,
respectively, in two- or one-step reactions. The mecha-
nism for the formation of bisbenzoxazoles and bisben-
zothiazoles was suggested. The absence of coordination
with Cu and Ni ions was rationalized as being the result
of the poor Lewis basicity of the nitrogen donor atom
in the benzoheterazole moiety.
4.2.2.
(4R,5R)-4,5-Bis(5-methylbenzoxazol-2-yl)-2,2-
4. Experimental
4.1. General method
dimethyl-1,3-dioxolane 1b. Colorless crystals; mp: 48–
49°C; yield: 92%; [h]2D0=−235 (c 2.07, CHCl3). 1H
NMR (200 MHz, CDCl3/TMS) l (ppm): 7.17–7.52 (m,
6H, ArH), 5.88 (s, 2H, 2CH), 2.46 (s, 6H, 2CH3), 1.65
(s, 6H, 2CH3). IR (KBr pellet, cm−1): 1614 (CꢀN). MS
(EI) m/z (rel. intensity): 364 (1.31, M+), 349 (2.63,
M−H2O), 306 (45.43, M−CH3COCH3), 279 (14.23), 203
(63.18), 186 (23.00), 174 (100.00), 162 (41.32), 146
(38.86), 133 (15.66), 116 (6.56), 78 (17.34). Anal. calcd
for C21H20N2O4: C, 69.22; H, 5.53; N, 7.69. Found: C,
69.29; H, 5.40; N, 7.62%.
Melting points were measured on a Yanaco MP-500
melting point apparatus and are uncorrected. H NMR
1
spectra were recorded on a Varian Mercury 200 (200
MHz) spectrometer in CDCl3 with TMS as an internal
standard or in DMSO-d6. Mass spectra were obtained
on a VG-ZAB-HS mass spectrometer. CHN analyses
were recorded on an Elementar Vario EL analyzer.
Optical rotations were measured on a Perkin Elmer
341LC polarimeter with a thermally jacketed 10 cm cell
(concentration c given as g/100 mL). IR spectra were
taken on a Brucker Vector 22 FT-IR spectrophotome-
ter in KBr pellet.
4.2.3. (4S,5S)-4,5-Bis(benzoxazol-2-yl)-2,2-dimethyl-1,3-
dioxolane 2a. Colorless needles; mp: 110–111°C; yield:
1
78%; [h]2D0=+220 (c 0.98, CHCl3). H NMR (200 MHz,
CDCl3/TMS) l (ppm): 7.74–7.78 (m, 2H, ArH), 7.56–
7.60 (m, 2H, ArH), 7.35–7.40 (m, 4H, ArH), 5.92 (s,
2H, 2CH), 1.66 (s, 6H, 2CH3). IR (KBr pellet, cm−1):
1613 (CꢀN). MS (EI) m/z (rel. intensity): 336 (1.61,
M+), 321 (10.15, M−CH3), 278 (100.00, M−
CH3COCH3), 251 (39.93), 189 (100.00), 172 (47.23), 160
(99.17), 148 (80.20), 132 (70.18), 120 (31.49), 119
(30.11), 103 (18.11), 77 (15.23). Anal. calcd for
C19H16N2O4: C, 67.85; H, 4.79; N, 8.33. Found: C,
67.72; H, 4.70; N, 8.22%.
L
- and D-2,3-O-isopropylidenetartaric dichlorides 7 and
8 were synthesized according to a known method23 and
our modified method. All remaining chemicals were
purchased from Beijing Chemical Co., Tokyo Kasei
Kogyo Co., Ltd. or Acros Chemical Co., Inc. Benzene
and THF were heated under reflux over sodium and
distilled prior to use. Dichloromethane was heated
under reflux over calcium hydride and distilled prior to
use. Triethylamine and pyridine were heated under
reflux over sodium hydroxide and distilled prior to use.
4.2.4.
(4S,5S)-4,5-Bis(5-methylbenzoxazol-2-yl)-2,2-
dimethyl-1,3-dioxolane 2b. Colorless crystals; mp: 49–
1
4.2. General procedure for the synthesis of 4,5-bis(ben-
zoxazol-2-yl)-2,2-dimethyl-1,3-dioxolanes 1a–b and
2a–b
50°C yield: 99%; [h]D20=+235 (c 1.06, CHCl3). H NMR
(200 MHz, CDCl3/TMS) l (ppm): 7.16–7.52 (m, 6H,
ArH), 5.88 (s, 2H, 2CH), 2.46 (s, 6H, 2CH3), 1.65 (s,
6H, 2CH3). IR (KBr pellet, cm−1): 1614 (CꢀN). MS (EI)
m/z (rel. intensity): 364 (3.59, M+), 349 (6.11, M−H2O),
306 (93.59, M−CH3COCH3), 279 (26.41), 203 (100.00),
186 (37.23), 174 (99.18), 162 (66.54), 146 (58.18), 133
To a solution of N,N%-bis(2-hydroxyaryl)-2,2-dimethyl-
1,3-dioxolane-4,5-dicarboxamide 10a–b or 11a–b (10
mmol) and triphenylphosphine (5.76 g, 22 mmol) in dry

3086
P. Jiao et al. / Tetrahedron: Asymmetry 12 (2001) 3081–3088
(23.25), 116 (9.15), 78 (21.62). Anal. calcd for
C21H20N2O4: C, 69.22; H, 5.53; N, 7.69. Found: C,
69.15; H, 5.71; N, 7.54%.
MS (EI) m/z (rel. intensity): 479 (5.01, M−CH3), 436
(9.84, M−CH3COCH3), 268 (100.00), 239 (41.83), 227
(20.59), 211 (12.21), 198 (13.84). Anal. calcd for
C19H12Cl2N4O8: C, 46.08; H, 2.44; N, 11.31. Found: C,
46.00; H, 2.54; N, 11.61%.
4.3. General procedure for the one-pot synthesis of 4,5-
bis(benzoxazol-2-yl)-2,2-dimethyl-1,3-dioxolanes 1c–e
and 2c–e, and 4,5-bis(benzothiazol-2-yl)-2,2-dimethyl-
1,3-dioxolanes 1f and 2f
4.3.4.
(4S,5S)-4,5-Bis(5-chlorobenzoxazol-2-yl)-2,2-
dimethyl-1,3-dioxolane 2c. Colorless oil; yield: 75%;
[h]2D0=+216 (c 0.81, CHCl3). 1H NMR (200 MHz,
CDCl3/TMS) l (ppm): 7.34–7.74 (m, 6H, ArH), 5.87 (s,
2H, 2CH), 1.64 (s, 6H, 2CH3). IR (KBr pellet, cm−1):
1630 (CꢀN). MS (EI) m/z (rel. intensity): 404 (0.76,
M+), 389 (3.67, M−CH3), 346 (31.92, M−CH3COCH3),
319 (9.64), 223 (100.00), 206 (16.01), 194 (70.74), 182
(48.48), 166 (51.80), 153 (16.51), 138 (10.57). Anal.
calcd for C19H14Cl2N2O4: C, 56.31; H, 3.48; N, 6.91.
Found: C, 56.51; H, 3.37; N, 6.99%.
To a solution of
L
- or
D
-dichloride 7 or 8 (2.03 g, 10
mmol) in anhydrous THF (10 mL) in an ice bath was
added dropwise a solution of one of the aromatic
amines 9c–f (30 mmol) in anhydrous THF (50 mL).
The resulting mixture was stirred at room temperature
for 1 h, and then the solid amine salt was filtered off.
The filtrate was concentrated to give a solid product.
The above product and triphenylphosphine (5.76 g, 22
mmol) was dissolved in dry THF (30 mL). A solution
of DEAD (3.83 mL, 22 mmol) in dry THF (10 mL) was
added dropwise under stirring and a nitrogen atmo-
sphere in an ice bath. The resulting mixture was stirred
at room temperature for 8 h. After removal of the
solvent, diethyl ether (60 mL) was added and the
resulting mixture was stirred for 1 h. The insoluble solid
was filtered off. The filtrate was concentrated and the
residue was purified on a silica gel column with a
mixture of petroleum ether (60–90°C) and ethyl acetate
(10:1, v/v) as an eluent to give a solid product except
products 1c and 2c. If necessary, further crystallization
could be carried out from a mixture of petroleum ether
(60–90°C) and ethyl acetate to give pure crystal.
4.3.5.
(4S,5S)-4,5-Bis(5-nitrobenzoxazol-2-yl)-2,2-
dimethyl-1,3-dioxolane 2d. Yellowish crystal; mp: 102–
103°C; yield: 62%; [h]2D0=+238 (c 1.04, CHCl3). 1H
NMR (200 MHz, CDCl3/TMS) l (ppm): 7.71–8.67 (m,
6H, ArH), 5.96 (s, 2H, 2CH), 1.67 (s, 6H, 2CH3). IR
(KBr pellet, cm−1): 1618 (CꢀN), 1531 (NO2). MS (EI)
m/z (rel. intensity): 426 (0.31, M+), 411 (28.97, M−
CH3), 368 (60.07, M−CH3COCH3), 341 (15.96), 234
(100.00), 217 (39.11), 205 (88.38). Anal. calcd for
C19H14N4O8: C, 53.53; H, 3.31; N, 13.14. Found: C,
53.71; H, 2.97; N, 12.90%.
4.3.6. (4S,5S)-4,5-Bis(5-chloro-6-nitrobenzoxazol-2-yl)-
2,2-dimethyl-1,3-dioxolane 2e. Yellowish crystal; mp:
1
153–155°C; yield: 52%; [h]2D0=+215 (c 1.33, CHCl3). H
4.3.1.
(4R,5R)-4,5-Bis(5-chlorobenzoxazol-2-yl)-2,2-
NMR (200 MHz, CDCl3/TMS) l (ppm): 8.16 (s, 2H,
ArH), 7.94 (s, 2H, ArH), 5.90 (s, 2H, 2CH), 1.64 (s, 6H,
2CH3). IR (KBr pellet, cm−1): 1621 (CꢀN), 1529 (NO2).
MS (EI) m/z (rel. intensity): 479 (8.50, M−CH3), 436
(14.47, M−CH3COCH3), 409 (3.93), 268 (100.00), 239
(58.12), 227 (27.25), 211 (15.71), 199 (13.00). Anal.
calcd for C19H12Cl2N4O8: C, 46.08; H, 2.44; N, 11.31.
Found: C, 46.37; H, 2.39; N, 11.48%.
dimethyl-1,3-dioxolane 1c. Colorless oil; yield: 79%;
[h]2D0=−214 (c 0.74, CHCl3). 1H NMR (200 MHz,
CDCl3/TMS) l (ppm): 7.34–7.74 (m, 6H, ArH), 5.87 (s,
2H, 2CH), 1.64 (s, 6H, 2CH3). IR (KBr pellet, cm−1):
1638 (CꢀN). MS (EI) m/z (rel. intensity): 404 (0.99,
M+), 389 (5.38, M−CH3), 346 (45.20, M−CH3COCH3),
319 (14.01), 223 (100.00), 206 (18.58), 194 (86.98), 182
(36.43), 166 (41.73), 154 (14.62), 138 (8.98). Anal. calcd
for C19H14Cl2N2O4: C, 56.31; H, 3.48; N, 6.91. Found:
C, 56.28; H, 3.57; N, 6.81%.
4.3.7. (4R,5R)-4,5-Bis(benzothiazol-2-yl)-2,2-dimethyl-
1,3-dioxolane 1f. Colorless crystals; mp: 114–115°C;
1
yield: 35%; [h]2D0=−249 (c 0.68, CHCl3). H NMR (200
4.3.2.
(4R,5R)-4,5-Bis(5-nitrobenzoxazol-2-yl)-2,2-
MHz, CDCl3/TMS) l (ppm): 7.90–8.06 (m, 4H, ArH),
7.40–7.49 (m, 4H, ArH), 5.80 (s, 2H, 2CH), 1.68 (s, 6H,
2CH3). IR (KBr pellet, cm−1): 1639 (CꢀN). MS (EI) m/z
(rel. intensity): 368 (4.39, M+), 353 (1.99, M−CH3), 310
(100.00, M−CH3COCH3), 282 (41.42), 205 (56.12), 190
(46.76), 176 (64.89), 164 (52.38), 148 (29.18), 135
(69.22), 108 (14.14). Anal. calcd for C19H16N2O2S2: C,
61.93; H, 4.38; N, 7.60. Found: C, 61.79; H, 4.21; N,
7.43%.
dimethyl-1,3-dioxolane 1d. Yellowish crystal; mp: 101–
102°C; yield: 67%; [h]2D0=−243 (c 1.03, CHCl3). 1H
NMR (200 MHz, CDCl3/TMS) l (ppm): 7.71–8.68 (m,
6H, ArH), 5.96 (s, 2H, 2CH), 1.67 (s, 6H, 2CH3). IR
(KBr pellet, cm−1): 1621 (CꢀN), 1533 (NO2). MS (EI)
m/z (rel. intensity): 426 (0.20, M+), 411 (27.43, M−
CH3), 368 (56.56, M−CH3COCH3), 341 (15.80), 234
(100.00), 217 (36.73), 205 (93.24), 193 (48.32). Anal.
calcd for C19H14N4O8: C, 53.53; H, 3.31; N, 13.14.
Found: C, 53.67; H, 2.96; N, 13.02%.
4.3.8.
(4S,5S)-4,5-Bis(benzothiazol-2-yl)-2,2-dimethyl-
1,3-dioxolane 2f. Colorless crystals; mp: 115–116°C;
1
4.3.3. (4R,5R)-4,5-Bis(5-chloro-6-nitrobenzoxazol-2-yl)-
2,2-dimethyl-1,3-dioxolane 1e. Yellowish crystal; mp:
yield: 34%; [h]2D0=+249 (c 0.96, CHCl3). H NMR (200
MHz, CDCl3/TMS) l (ppm): 7.90–8.06 (m, 4H, ArH),
7.37–7.53 (m, 4H, ArH), 5.81 (s, 2H, 2CH), 1.68 (s, 6H,
2CH3). IR (KBr pellet, cm−1): 1629 (CꢀN). MS (EI) m/z
(rel. intensity): 368 (9.80, M+), 353 (3.14, M−CH3), 310
(100.00, M−CH3COCH3), 282 (45.47), 205 (74.95), 190
1
154–156°C; yield: 51%; [h]2D0=−213 (c 1.23, CHCl3). H
NMR (200 MHz, CDCl3/TMS) l (ppm): 8.16 (s, 2H,
ArH), 7.94 (s, 2H, ArH), 5.91 (s, 2H, 2CH), 1.64 (s, 6H,
2CH3). IR (KBr pellet, cm−1): 1622 (CꢀN), 1530 (NO2).

P. Jiao et al. / Tetrahedron: Asymmetry 12 (2001) 3081–3088
3087
(51.00), 176 (71.67), 164 (59.88), 148 (30.36), 135
(99.38), 108 (27.86). Anal. calcd for C19H16N2O2S2: C,
61.93; H, 4.38; N, 7.60. Found: C, 61.76; H, 4.50; N,
7.57%.
acetone). 1H NMR (200 MHz, DMSO-d6) l (ppm):
9.86 (s, 2H, 2OH), 9.12 (s, 2H, 2CONH), 7.89 (s, 2H,
ArH), 6.76 (s, 4H, ArH), 4.93 (s, 2H, 2CH), 2.20 (s, 6H,
2CH3Ar), 1.50 (s, 6H, 2CH3). IR (KBr pellet, cm−1):
3354 (O–H), 1665 (CꢀO). MS (EI) m/z (rel. intensity):
400 (17.45, M+), 382 (19.30, M−H2O), 250 (6.74), 202
(11.32), 176 (74.36), 149 (19.41), 123 (100.00), 122
(40.05, HNPh(Me)OH). Anal. calcd for C21H24N2O6: C,
62.99; H, 6.04; N, 7.00. Found: C, 62.93; H, 5.83; N,
6.72%.
4.4. General procedure for the synthesis of N,N%-bis(2-
hydroxyaryl)-2,2-dimethyl-1,3-dioxolane-4,5-dicarbox-
amides 10a–b and 11a–b
To a solution of
L- or D-2,3-O-isopropylidenetartaric
dichloride 7 or 8 (2.03 g, 10 mmol) in anhydrous THF
(10 mL) in an ice bath was added dropwise a solution
of 2-aminophenol 9a or 9b (30 mmol) in anhydrous
THF (50 mL). The resulting mixture was stirred at
room temperature for 1 h, and the solid amine salt was
filtered off. The filtrate was concentrated to give a solid
product. After washing with diethyl ether, the crude
product was crystallized from acetonitrile to give crys-
tals of pure product.
Acknowledgements
We thank Professor Pang Zhang for his kind help. We
also thank the National Natural Science Foundation of
China and The Hong Kong Polytechnic University
ASD fund for financial support.
4.4.1. (4R,5R)-N,N%-Bis(2-hydroxyphenyl)-2,2-dimethyl-
1,3-dioxolane-4,5-dicarboxamide 10a. Colorless crystals;
mp: 205–207°C; yield 88%; [h]2D0=−105 (c 0.96, acet-
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(s, 2H, 2OH), 9.18 (s, 2H, 2CONH), 8.04 (d, J=8.0 Hz,
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2CH3Ar), 1.50 (s, 6H, 2CH3). IR (KBr pellet, cm−1):
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