Novel chiral dibenzo[a,c]cycloheptadiene bis(oxazoline) and catalytic enantioselective cyclopropanation of styrene

Article abstract of DOI:10.1016/S0040-4020(03)00144-3

A series of chiral C₂-symmetric bis(oxazoline) ligands containing dibenzo[a,c]cycloheptadiene units were synthesized. The copper complexes, prepared in situ from copper (I)-triflate and the new enantiopure oxazoline ligands, were assessed as chiral catalysts in the enantioselective cyclopropanation of styrene with diazoacetate. Enantioselectivities up to 82 and 62%, respectively, for trans- and cis-2-phenylcyclopropanecarboxylate were observed.

Full text of DOI:10.1016/S0040-4020(03)00144-3

Tetrahedron 59 (2003) 1933–1938
Novel chiral dibenzo[a,c]cycloheptadiene bis(oxazoline)
and catalytic enantioselective cyclopropanation of styrene
*
Da-Ming Du, Bin Fu and Wen-Ting Hua
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education,
College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, People’s Republic of China
Received 29 October 2002; revised 2 January 2003; accepted 23 January 2003
Abstract—A series of chiral C2-symmetric bis(oxazoline) ligands containing dibenzo[a,c]cycloheptadiene units were synthesized. The
copper complexes, prepared in situ from copper (I)-triflate and the new enantiopure oxazoline ligands, were assessed as chiral catalysts in the
enantioselective cyclopropanation of styrene with diazoacetate. Enantioselectivities up to 82 and 62%, respectively, for trans- and cis-2-
phenylcyclopropanecarboxylate were observed. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
Continuing on our ongoing project on the synthesis,
structure and catalytic enantioselective cyclopropanation
of styrene by novel chiral bis(oxazoline) ligands containing
2,5-diaryl-1,3,4-oxadizole units and other reactions using
heterocyclic ligands,12 in this paper, we report the synthesis
and the catalytic enantioselective cyclopropanation of
styrene by copper (I) complex of a series of new
bis(oxazoline) ligands 5 containing axial biaryl of dibenzo-
[a,c]cycloheptadiene and chiral center of bis(oxazoline).
We expect the combination of dibenzo[a,c]cycloheptadiene
unit and chiral oxazoline unit in new ligands may result in
unique characteristics for catalytic reaction.
The transition metal catalyzed cyclopropanation of alkenes
with diazoacetates is the effective method developed for the
synthesis of enantioenriched cyclopropanes.1 Over the last
decade, C2-symmetric chiral oxazoline metal complexes
have been recognized as an effective class of chiral catalyst
in a variety of transition metal catalyzed asymmetric
reactions.2 High catalytic activities and enantiomeric
excesses have been obtained for example in hydrosilylation
of ketone,3 allylic alkylation,4 Michael addition,5 Diels–
Alder cycloaddition,6 and cyclopropanation7 mainly using
C2-symmetric chiral ligands in conjunction with suitable
transition metal ion. Thus, the design and synthesis of new
chiral oxazoline ligands has inspired many scientists to
work with great efforts.
This type of ligands most studied were the ligand 1 with a
one carbon spacer and 2 with a two carbon spacer between
the bis(oxazoline) rings.8,9 In their molecular structure, only
the central chirality element in the oxazoline moiety and the
asymmetric induction was controlled only by the central
chirality element in the oxazoline moiety. Later, Ikeda,10
Hayashi11 and their co-workers developed bis(oxazoline)
ligands 3 and 4 which include an axially flexible and
rigid chiral biaryl skeleton and high enantioselectivity for
cyclopropanation of olefin were obtained. However, in their
studies chiral biaryl bis(oxazoline) need separation of the
two diastereomers of the ligand, and only one of the two
diastereomers shows high enantioselectivity.11
2. Results and discussion
The usual method for preparation of chiral bis(oxazoline) is
the reaction of diacid derivatives with chiral b-amino
alcohol. The cyclic diethyl carboxylate 6 was0 synthesized
according to literature procedure from 2,2 -bis(bromo-
methyl)biphenyl.13 The cyclic diethyl carboxylate 6 was
transformed into dihydroxy diamide 7 by the following
Keywords: bis(oxazoline); synthesis; dibenzo[a,c]cycloheptadiene;
enantioselective cyclopropanation; styrene.
*
Corresponding author. Tel.: þ86-10-6275-6568; fax: þ86-10-6275-1708;
e-mail: dudm@pku.edu.cn
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00144-3

1934
D.-M. Du et al. / Tetrahedron 59 (2003) 1933–1938
Scheme 1. Synthesis of new bis(oxazoline) 5a–e.
reaction sequence. Hydrolysis of diethyl carboxylate 6 in an
alcohol solution of NaOH gave the corresponding dicarb-
oxylate, which was refluxed with thionyl chloride to afford
the diacyl chloride. The diacyl chloride was treated with
b-amino alcohols and triethylamine to afford the corre-
sponding chiral intermediate dihydroxy diamides 7 as solids
in 65–73% yields. In the present work, the procedure
developed by Denmark14 was selected to synthesize the
desired ligands 5a–e. The dihydroxy diamides were treated
with methanesulfonyl chloride (MsCl) (2.2 equiv.) and Et3N
(4.4 equiv.) in dichloromethane to afford the corresponding
bismesylates, which were treated with an aqueous metha-
nolic solution of NaOH (8 equiv.) to furnish the bis(oxazo-
line) 5 in good yields (70–82%) (Scheme 1). In all cases, the
intermediate bismesylates were too unstable to tolerate
chromatographic purification, thus the intermediate bisme-
sylates were not isolated and directly cyclized in situ. The
Although compounds 5 possess an axial chirality, they
cannot be isolated in enantiomerically pure state of chiral
configuration, because fast interconversion between (R) and
(S) enantiomers of biphenyl occurs at room temperature
owing to the low rotation barrier energy along the 1,10 bond
of biphenyl moiety.15 Then, the chirality of 5 only came
from chiral oxazoline, this reduce the difficulty in separating
the diastereoisomers resulting from the double chirality of
biphenyl skeleton and oxazoline.
These ligands were then examined for the copper-catalyzed
cyclopropanation of styrene with diazoacetate which is the
model reaction most often investigated with chiral oxazo-
line ligands.16 The asymmetric cyclopropanation was
carried out in dichloromethane in the presence of 1% mol
of copper (I) catalyst generated by mixing Cu(OTf).1/2C6H6
and the bis(oxazoline) ligands 5 to give 2-phenyl-cyclo-
propanecarboxylate as a mixture of trans and cis isomers
(Scheme 2). The ratio of trans and cis isomer were
1
structures of new ligands were characterized by H NMR,
MS, IR and elemental analysis.
Scheme 2. Cyclopropanation reaction of styrene and diazoacetate.
Table 1. Asymmetric cyclopropanation of styrene with diazoacetates catalyzed by copper (I)-bis(oxazoline)
Entry
Ligands
Diazoacetate
Temp. (8C)
Yieldsa (%)
trans/cisb
ee%c (trans)
Config.d
ee%c (cis)
Config.d
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5a
5a
5a
8a
8a
8a
8a
8a
8a
8b
8c
20
20
20
20
20
0
72
76
68
70
71
74
72
75
61:39
64:36
56:44
62:38
60:40
62:38
66:34
68:32
63
42
41
61
60
68
76
82
1R, 2R
1R, 2R
1R, 2R
1R, 2R
1S, 2S
1R, 2R
1R, 2R
1R, 2R
54
28
32
41
38
55
61
64
1R, 2S
1R, 2S
1R, 2S
1R, 2S
1S, 2R
1R, 2S
1R, 2S
1R, 2S
0
0
a
Isolated yield of a mixture of trans and cis by chromatographic purification.
1
The ratio of trans and cis was determined by H NMR.
ee values were determined by HPLC (Chiracel Daicel OD and OJ Column, elution with hexane–isopropanol 90:10, 0.5 ml/min).
Based on the sign of optical rotation.
b
c
d

D.-M. Du et al. / Tetrahedron 59 (2003) 1933–1938
1935
Figure 1. Perspective view of compound 5c, showing 30% probability ellipsoids for the non-hydrogen atoms and the numbering scheme of the atoms in the
molecule.
determined by 1H NMR analysis, and the enantiomeric
excesses were determined by HPLC analysis using a chiral
column (Chiracel OD and OJ). The representative results
are summarized in Table 1.
107.128. From the crystal structure of 5c, it turns out that the
twist conformation of biphenyl may has effect on the chiral
environment of two oxazoline units in corresponding copper
(I) complex. The conformation of biphenyl unit may be
affected by temperature and thus the dibenzo[a,c]cyclohep-
tadiene bis(oxazoline) copper (I) complex will result in
different enantioselectivity on different temperatures.
Among the bis(oxazoline) ligands, 5a containing isobutyl
substitutent on its oxazolines gave the highest enantiomeric
excess for trans 9 in 63% ee and cis 10 in 52% ee (entry 1),
the ligands 5b and 5c containing isopropyl and benzyl group
afforded comparably lower enantioselectivity (trans 42 and
41% ee, respectively, entry 2, 3). Also, the ligands 5d and 5e
with phenyl substituent present good enantioselectivity for
cyclopropanation in 61 and 60% ee (entry 4, 5).
In conclusion, we have synthesized a series of new chiral
dibenzo[a,c]cycloheptadiene bis(oxazoline) ligands. Pre-
liminary results in asymmetric cyclopropanation of styrene
with diazoacetate have been obtained. The C2-symmetric
bis(oxazoline) 5 derived from dibenzo[a,c]cycloheptadiene
showed different reactivity in the asymmetric copper-
catalyzed cyclopropanation. The highest enantioselectivity
has been obtained with isobutyl substituted bis(oxazoline)
5a. Although the trans/cis stereoselectivity and enantio-
selectivity are moderate to good, the preliminary results at
least suggest that these novel dibenzo[a,c]cycloheptadiene
bis(oxazoline) ligands have much potential as new catalyst
system for asymmetric reaction. Further studies on other
asymmetric reactions are undergoing in our research group.
Meanwhile we examined the effect of temperature and
different diazoacetate for cyclopropanation of the ligand 5a
as shown in Table 1. The reactions were carried out under
the same condition as above, except addition of diazoacetate
for 5 h and reaction proceeding for 16 h at 08C, the ee value
of copper (I)-catalyzed cyclopropanation rise to 68% (entry
6). As expected, the enantioselectivity was improved by
use of steric bulkier diazoacetate ester. The reaction of
L-menthyl diazoacetate with styrene in the presence of
Cu(I)-ligand 5a catalyst gave trans menthyl cyclopropane-
carboxylates up to 82% ee and cis isomer in 64% ee (entry
8). The best advantage is that our new ligand can give good
enantioselectivity using the very cheap ligand derivated
from L-leucinol. In contrast, very expensive ligands
derivated from L-t-leucinol were usually used in litera-
ture.8,9
3. Experimental
3.1. General
Melting points were measured on an XT-4 melting point
apparatus and were uncorrected. 1H NMR spectra were
recorded on a Mercury 200 spectrometer with tetramethyl-
silane serving as internal standard. Infrared spectra were
obtained on a Bruker Vector 22 spectrometer. Mass spectra
were obtained on a VG-ZAB-HS mass spectrometer.
Optical rotations were measured on a Perkin–Elmer 341
LC spectrometer. Elemental analyses were carried out on an
Elementar Vario EL instrument. The optical purities of
trans- and cis-cyclopropanes were determined by HPLC
analysis using a chiral column (Daicel Chiralcel OD and OJ;
eluent, hexane–isopropyl alcohol 90:10; flow rate,
0.5 mL/min; UV detector, 220 nm). The absolute configu-
ration of the major enantiomer was assigned according to
In order to obtain a direct understanding of the structure of
new dibenzo[a,c]cycloheptadiene bis(oxazoline) ligands,
the stereostructure of ligand 5c was determined by X-ray
crystal diffraction analysis.17 Compound 5c was obtained as
air-stable, colorless crystal upon slow evaporation of a
solution of 5c in ethyl acetate–petroleum ether (v/v 1:3). A
perspective view of compound 5c was shown in Figure 1.
The dibenzo[a,c]cycloheptadiene is twist conformation in
compound 5c. The C1–C2–C3–C4–C5–C6 benzene ring
has a dihedral angle with C21–C22–C23–C24–C25–C26
benzene ring of 44.28. The w angle of bis(oxazoline) is

1936
D.-M. Du et al. / Tetrahedron 59 (2003) 1933–1938
the sign of the specific rotation.18 Solvents used were
purified and dried by standard procedures.
127.9, 127.4, 127.2, 126.6, 65.4, 63.4, 58.2, 36.6. MS
(FAB): 549 (Mþ1). Anal. for C35H36O4N2 Calcd (%) C,
76.64; H, 6.56; N, 5.11. Found (%): C, 76.72; H, 6.66; N,
5.20.
3.1.1. 6,6-Bis[N-(10S)-(10-isobutylhydroxyethyl)amido]-
dibenzo[a,c]-1,3-cycloheptadiene (7a). General procedure
I. To a solution of diethyl dibenzo[a,c]-1,3-cyclohepta-
diene-6,6-dicarboxylate 6 (1.0 g, 2.96 mmol) in CH3OH
(10 mL) was added NaOH solution (10 mL, 2N). The
mixture was refluxed for 8 h, then the methanol was
removed in vacuo. The residue was cooled to 08C and
acidified with aqueous HCl (6N). The acidified mixture was
extracted with ether (10 mL£3), the organic layer was dried
with anhydrous Na2SO4 and evaporated. The obtained white
solid was directly refluxed with SOCl2 (5 mL) for 2 h, the
excess SOCl2 was removed in vacuo. Benzene (10 mL) was
added and the solvent was removed again to dryness to
remove the trace of SOCl2 and afford the diacyl dichloride.
The diacyl dichloride in CH2Cl2 (20 mL) was added
dropwise to a solution of L-leucinol (0.75 g, 6.4 mmol)
and Et3N (4 mL, 28.9 mmol) in CH2Cl2 (20 mL) at 08C and
stirred at room temperature for 4 h. The reaction mixture
was washed with water (5 mL£2). The organic layer was
dried over anhydrous Na2SO4 and concentrated to give
crude solid. Purification by silica gel column chroma-
tography (40% ethyl acetate in petroleum ether) afforded the
dihydroxy diamide 7a 0.96 g (67.6%). Mp 162–163.58C.
[a]2D0¼26.8 (c¼0.8, CHCl3). IR (KBr): n 3406, 2958, 1639,
1534, 1451, 1262 cm21. 1H NMR (CDCl3): d 7.39–7.20 (m,
8H), 6.20 (br s, 2H), 4.02–4.18 (m, 2H), 3.73 (t, J¼6.4 Hz,
2H), 3.41–3.25 (m, 6H), 2.80 (br s, 2H), 1.55–1.25 (m, 6H),
0.86 (d, J¼7.0 Hz, 12H). 13C (50 MHz, CDCl3): d 172.0,
140.6, 135.6, 127.8, 127.3, 65.3, 58.1, 49.8, 36.9, 24.8, 22.7,
21.7, 18.2. MS (FAB): 481 (Mþ1). Anal. for C29H40O4N2
Calcd (%) C, 72.50; H, 8.33; N, 5.83. Found (%): C, 72.44;
H, 8.20; N, 5.68.
3.1.4. 6,6-Bis[N-(10S)-(10-phenylhydroxyethyl)amido]-
dibenzo[a,c]-1,3-cycloheptadiene (7d). Following general
procedure I, diethyl dibenzo[a,c]-1,3-cycloheptadiene-6,6-
dicarboxylate 6 (1.0 g, 2.96 mmol), L-phenylglycinol (0.88 g,
6.4 mmol) and Et3N (4 mL, 28.9 mmol) to afford the
dihydroxy diamide 7d 1.08 g (70.1%). Mp 181–1838C.
[a]2D0¼250.0 (c¼0.44, CHCl3). IR (KBr): n 3406, 2936,
1
1641, 1539, 1453, 1262 cm21. H NMR (CDCl3): d 7.37–
7.16 (m, 18H), 6.90 (br s, 2H), 5.16–5.09 (m, 2H), 3.91–
3.80 (m, 4H), 3.50–2.80 (m, 6H). 13C (CDCl3): d 171.8,
140.4, 135.3, 129.8, 127.9, 127.8, 127.6, 127.5, 126.6, 65.9,
65.6, 55.9, 37.5. MS (FAB): 521 (Mþ1). Anal. for
C33H32O4N2 Calcd (%) C, 76.15; H, 6.15; N, 5.38. Found
(%): C, 76.34; H, 6.20; N, 5.14.
3.1.5. 6,6-Bis[N-(10R)-(10-phenylhydroxyethyl)amido]-
dibenzo[a,c]-1,3-cycloheptadiene (7e). Following general
procedure I, diethyl dibenzo[a,c]-1,3-cycloheptadiene-6,6-
dicarboxylate
6 (1.0 g, 2.96 mmol), D-phenylglycinol
(0.88 g, 6.4 mmol) and Et3N (4 mL, 28.9 mmol) to afford
the dihydroxy diamide 7e 1.12 g (72.7%). Mp 175–1778C.
[a]2D0¼þ69.6 (c¼0.56, CHCl3). IR (KBr): n 3406, 2936,
1
1640, 1536, 1456, 1262 cm21. H NMR (CDCl3): d 7.38–
7.16 (m, 18H), 6.91 (br s, 2H), 5.18–5.09 (m, 2H), 3.91–
3.80 (m, 4H), 3.40–2.80 (m, 6H). 13C (CDCl3): d 171.7,
140.3, 135.2, 129.9, 127.8, 127.7, 127.6, 127.5, 126.5, 65.7,
65.5, 55.8, 37.2. MS (FAB): 521 (Mþ1). Anal. for
C33H32O4N2 Calcd (%) C, 76.15; H, 6.15; N, 5.38. Found
(%): C, 76.38; H, 6.28; N, 5.19.
3.1.6. 6,6-Bis[(40S)-40-isobutyloxazolin-20-yl]-dibenzo-
[a,c]-1,3-cycloheptadiene (5a). General procedure II. To
an ice cold solution of the dihydroxy diamide 7a (1.20 g,
2.5 mmol) and Et3N (2 mL, 14 mmol) in CH2Cl2 (20 mL)
was added MsCl (0.60 g, 5.2 mmol) slowly. The mixture
was allowed to warm to room temperature and was stirred
for 1 h. The mixture was washed with water (5 ml). The
organic layer was dried over anhydrous Na2SO4 and
concentrated to dryness in vacuo to give the crude
bismesylate as a yellow oil. The crude bismesylate was
dissolved in CH3OH (20 mL) and was treated with NaOH
solution (4 mL, 1N) at room temperature for 12 h. The
methanol was removed in vacuo and 30 mL CH2Cl2 was
added to it. The solution was washed with water (5 mL£2).
The organic layer was dried over anhydrous Na2SO4 and
concentrated in vacuo to give a pale yellow oil. Purification
by silica gel column chromatography (petroleum ether–
ethyl acetate 5:1) to afford colorless viscous oil 5a 0.91 g
(81.9% yield). [a]2D0¼228.9 (c¼0.95, CHCl3). IR (KBr): n
3.1.2. 6,6-Bis[N-(10S)-(10-isopropylhydroxyethyl)amido]-
dibenzo[a,c]-1,3-cycloheptadiene (7b). Following general
procedure I, from diethyl dibenzo[a,c]-1,3-cyclohepta-
diene-6,6-dicarboxylate 6 (1.0 g, 2.96 mmol), L-valinol
(0.66 g, 6.4 mmol) and Et3N (4 mL, 28.9 mmol) to afford
the dihydroxy diamide 7b 0.88 g (65.7%). Mp 170–1728C.
[a]2D0¼214.6 (c¼0.24, CHCl3). IR (KBr): n 3406, 2960,
1
1637, 1539, 1451, 1262 cm21. H NMR (CDCl3): d 7.42–
7.25 (m, 8H), 6.24 (br s, 2H), 3.83–3.70 (m, 4H), 3.60–3.25
(m, 4H), 3.05–2.70 (m, 4H), 1.82–1.73 (m, 2H), 0.92 (d,
J¼7.0 Hz, 6H), 0.88 (d, J¼8.8 Hz, 6H). 13C (CDCl3): d
172.5, 140.3, 135.5, 130.4, 128.0, 127.6, 65.9, 63.8, 57.4,
37.2, 28.9, 19.6, 19.0. MS (FAB): 453 (Mþ1). Anal. for
C27H36O4N2 Calcd (%) C, 71.68; H, 7.96; N, 6.19. Found
(%): C, 71.73; H, 7.82; N, 6.06.
3.1.3. 6,6-Bis[N-(10S)-(10-benzylhydroxyethyl)amido]-
dibenzo[a,c]-1,3-cycloheptadiene (7c). Following general
procedure I, from diethyl dibenzo[a,c]-1,3-cyclohepta-
diene-6,6-dicarboxylate 6 (1.0 g, 2.96 mmol), L-phenyl-
alaninol (0.97 g, 6.4 mmol) and Et3N (4 mL, 28.9 mmol) to
afford the dihydroxy diamide 7c 1.15 g (70.8%). Mp 196–
1988C. [a]2D0¼þ74.2 (c¼0.48, CHCl3). IR (KBr): n 3406,
1
3010, 2966, 1654, 1508, 1482 cm21. H NMR (CDCl3):
d 7.25–7.44 (m, 8H), 4.36 (t, J¼8.4 Hz, 2H), 4.22–4.07
(m, 2H), 3.89 (s, 2H), 3.26–2.90 (m, 4H), 1.86–1.42
(m, 4H), 1.36–1.19 (m, 2H), 0.88 (d, J¼3.8 Hz, 12H). 13C
NMR (50 MHz, CDCl3): d 166.1, 140.9, 138.1, 127.9,
127.4, 127.1, 73.5, 65.8, 64.6, 45.6, 37.6, 25.3, 22.8. MS
(EI): 444 (Mþ, 100), 429 (7), 387 (20), 318 (45), 304 (32).
HRMS (EI): calcd for C29H36O2N2 444.2777, found:
444.2777.
1
2932, 1640, 1539, 1453, 1262 cm21. H NMR (CDCl3):
d 7.34–7.12 (m, 18H), 6.31 (br s, 2H), 4.38–4.20 (m,
2H), 3.85–3.70 (m, 2H), 3.50–3.44 (m, 2H), 2.90–2.56 (m,
8H). 13C (CDCl3): d 171.9, 140.2, 137.2, 135.3, 128.5,

D.-M. Du et al. / Tetrahedron 59 (2003) 1933–1938
1937
3.1.7. 6,6-Bis[(40S)-40-isopropyloxazolin-20-yl]-dibenzo-
[a,c]-1,3-cycloheptadiene (5b). Following general pro-
cedure II, from dihydroxy diamide 7b (0.91 g, 2.0 mmol),
MsCl (0.50 g, 4.4 mmol) and Et3N (2 mL, 14 mmol) to
afford the crude bismesylate. The crude bismesylate was
treated with a NaOH/MeOH–H2O solution as the above to
afford 5b (0.64 g, 76.4%) as a colorless viscous oil after
purification by column chromatography on silica gel (ethyl
acetate–petroleum ether 1:6). [a]2D0¼217.5 (c¼0.80,
1H NMR (CDCl3): d 7.46–7.06 (m, 18H), 5.26 (dd, J¼9.6,
8.2 Hz, 2H), 4.72 (dd, J¼8.0, 9.6 Hz, 2H), 4.18 (dd, J¼8.2,
8.0 Hz, 2H), 3.28–2.90 (m, 4H). 13C NMR (CDCl3): d
168.0, 140.9, 135.7, 130.2, 128.6, 128.2, 127.6, 127.5,
127.3, 126.7, 75.5, 69.6, 53.7, 37.8. MS (EI): 484 (Mþ, 74),
380 (14), 306 (100). HRMS (EI): calcd for C33H28O2N2
484.2150. Found: 484.2151.
3.2. General procedure for the asymmetric
cyclopropanation
1
CHCl3). IR (KBr): n 2966, 1654, 1508, 1482 cm21. H
NMR (CDCl3): 7.41–7.23 (m, 8H), 4.26 (t, J¼8.2 Hz, 2H),
4.13–3.90 (m, 4H), 3.42–2.80 (m, 4H), 1.78–1.68 (m, 2H),
0.87 (t, J¼4.0 Hz, 12H). 13C NMR (CDCl3): d 166.1, 140.7,
135.8, 130.4, 127.7, 127.1, 126.9, 126.8, 71.7, 70.8, 53.2,
37.4, 32.2, 18.4, 17.7. MS (EI): 416 (Mþ, 8), 304 (58), 191
(38), 127 (100). HRMS (EI) calcd for C27H32O2N2
416.2464. Found: 416.2463.
A mixture of CuOTf-1/2C6H5 (6.0 mg, 0.024 mmol) and
ligand 5a (12.0 mg, 0.027 mmol) was stirred in dry CH2Cl2
(2 mL) under nitrogen for 30 min Styrene (1.60 g,
15.4 mmol) was added at room temperature or 08C.
Followed by slow addition of a CH2Cl2 solution (2 mL) of
ethyl (or t-butyl, L-menthyl) diazoacetate (310 mg,
2.72 mmol) over 5 h by syringe. The reaction mixture was
stirred for an addition 16 h at room temperature or 08C. The
solution was diluted with Et2O (20 mL). The solution was
then washed with water (5 mL) and brine (5 mL), dried over
anhydrous Na2SO4. The solvent was removed under
reduced pressure, the residue was purified by column
chromatography on silica gel (petroleum ether–ethyl
acetate 50:1) to afford the mixture of trans- and cis-2-
phenyl-cyclopropane-1-carboxylates as colorless oil. The
3.1.8. 6,6-Bis[(40S)-40-benzyloxazolin-20-yl]-dibenzo[a,c]-
1,3-cycloheptadiene (5c). Following general procedure II,
from dihydroxy diamide 7c (1.60 g, 2.92 mmol), MsCl
(0.70 g, 6.1 mmol) and Et3N (2 mL, 14 mmol) to afford the
crude bismesylate. The crude bismesylate was treated with a
NaOH/MeOH–H2O solution as the above to afford 5c
(1.06 g, 70.8%) as a colorless solid after purification by
column chromatography on silica gel (ethyl acetate–
petroleum ether 1:3). Mp 82–83.58C. [a]2D0¼219.0 (c¼
0.35, CHCl3). IR (KBr): n 3010, 1656, 1452 cm21. 1H NMR
(CDCl3): d 7.46–7.14 (m, 18H), 4.42–4.30 (m, 2H), 4.23 (t,
J¼7.8 Hz, 2H), 4.15–3.98 (m, 2H), 3.25–3.02 (m, 4H),
3.00–2.48 (m, 4H). 13C NMR (CDCl3): d 166.1, 140.8,
137.7, 135.8, 129.3, 127.9, 127.3, 127.2, 126.3, 72.2, 67.1,
53.2, 37.5. MS (EI): 512 (Mþ, 90), 421 (100), 334 (46).
Anal. for C35H32O2N2 Calcd (%): C. 82.10; H. 6.48; N,
5.46. Found (%): C, 82.31; H, 6.52; N, 5.40.
1
trans/cis ratio of this mixture was determined by H NMR
(200 MHz) in CDCl3. The enantiomeric excess was
determined by HPLC with a chiral column (Daicel Chiralcel
OD and OJ; eluent, hexane–isopropyl alcohol 90:10; flow
rate 0.5 mL/min).
3.3. X-Ray crystallographic analysis
A colorless crystal was selected and mounted on a fine-focus
sealed tube and used for data collection. Cell constants and
an orientation matrix for data collection were obtained by
least-squares refinement of the diffraction data from 25
reflections in the 2u range from 1.50 to 28.05 degree in a
Rigaku AFC6S diffractometer equipped with a graphite
crystal incident beam monochromator. Data were collected
3.1.9. 6,6-Bis[(40S)-40-phenyloxazolin-20-yl]-dibenzo[a,c]-
1,3-cycloheptadiene (5d). Following general procedure II,
from dihydroxy diamide 7d (0.84 g, 1.62 mmol), MsCl
(0.40 g, 3.5 mmol) and Et3N (2 mL, 14 mmol) to afford the
crude bismesylate. The crude bismesylate was treated with a
NaOH/MeOH–H2O solution as the above to afford 5d
(0.78 g, 78.2%) as a colorless viscous oil after purification
by column chromatography on silica gel (ethyl acetate–
petroleum ether 1:6). [a]2D0¼219.0 (c¼1.80, CHCl3). IR
(KBr): n 3010, 2964, 1656, 1482 cm21. 1H NMR (CDCl3):
d 7.46–7.17 (m, 18H), 5.30 (dd, J¼8.2, 8.2 Hz, 2H), 4.72
(dd, J¼8.2, 8.4 Hz, 2H), 4.17 (t, J¼8.4 Hz, 2H), 3.41–3.12
(m, 4H). 13C NMR (CDCl3): d 168.0, 140.9, 135.7, 130.2,
128.5, 128.1, 127.5, 127.4, 127.3, 126.7, 75.5, 69.5, 53.7,
37.8. MS (EI): 484 (Mþ, 64), 380 (12), 306 (100). HRMS
(EI): C33H28O2N2 Calcd 484.2139. Found: 484.2150.
˚
at 293 K using Mo Ka radiation (l¼0.71073 A) and the
v–2u variable-scan mode. The intensity data obtained were
corrected for Lorentz and polarization effects. An empirical
absorption correction based on c-scan data was applied. The
crystal structure was resolved by the direct method using
SHELXS97, and full-matrix least-squares refinement on F2
was performed with SHELXL97 program. All the non-
hydrogen atoms were deduced from an E-map and refined
anisotropically. The positions of hydrogen atoms were
generated geometrically and included in structure factor
calculations with assigned isotropic thermal parameters.
All computations were performed on a FOUNDER FPþ
5-166 586 personal computer.
3.1.10. 6,6-Bis[(40R)-40-phenyloxazolin-20-yl]-dibenzo-
[a,c]-1,3-cycloheptadiene (5e). Following general pro-
cedure II, from dihydroxy diamide 7e (0.92 g, 2.5 mmol),
MsCl (0.45 g, 3.94 mmol) and Et3N (2 mL, 14 mmol) to
afford the crude bismesylate. The crude bismesylate was
treated with a NaOH/MeOH–H2O solution as the above to
afford 5e (0.70 g, 81.7%) as a colorless viscous oil after
purification by column chromatography on silica gel
(ethyl acetate–petroleum ether 1:6). [a]2D0¼þ41.1 (c¼
5c: C35H32N2O2, FW¼512.63, monoclinic, space group
˚
P(2)1, a¼9.9894 (2), b¼10.2532 (4), c¼13.7784 (7) A; a¼
3
˚
908, b¼99.981 (2)8, g¼908, V¼1389.8 (5) A , Z¼2,
F(000)¼544, Dc¼1.225 Mg/m3, m¼0.076 mm21. Crystal
size 0.60£0.50£0.25 mm; Index ranges 212#h#12,
213#k#13, 217#l#17; Reflections collected/unique,
1272/3367 (fint¼0.0485); Data/restraints/parameters,
3367/1/353; Goodness-of-fit on F 2 0.833; Final R indices
0.45, CHCl3). IR (KBr): n 3010, 2966, 1650, 1508 cm21
.

1938
D.-M. Du et al. / Tetrahedron 59 (2003) 1933–1938
Int. Ed. Engl. 1992, 31, 430. (b) Gant, T. G.; Noe, M. C.;
Corey, E. J. Tetrahedron Lett. 1995, 36, 8745. (c) Kim, S. G.;
Cho, C. W.; Ahn, K. H. Tetrahedron: Asymmetry 1997, 8(7),
1023. (d) Bedekar, A. V.; Koroleva, E. B.; Andersson, P. G.
J. Org. Chem. 1997, 62, 2518.
[I.2s(I)]: R1¼0.0352, wR2¼0.0624; Extinction coefficient
0.0293 (17); Largest diff. peak and hole, 0.134 and
.
23
˚
20.171 e A
8. Evans, D. A.; Wocrpel, K. A.; Hinman, M. M. J. Am. chem.
Soc. 1991, 113, 726–728.
Acknowledgements
9. (a) Bedekar, A. V.; Andersson, P. G. Terahedron Lett. 1996,
37, 4073–4076. (b) Bedekar, A. V.; Koroleva, E. B.;
Andersson, P. G. J. Org. Chem. 1997, 62, 2518–2526.
10. Imai, Y.; Zhang, W. B.; Kida, T.; Nakatsuji, Y. L.; Iketa, I.
J. Org. Chem. 2000, 65, 3326–3333.
This work was supported by the National Natural Science
Foundation of China (Grant No. 20172001).
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