Preparation and application of bisoxazoline ligands with a chiral spirobiindane skeleton for asymmetric cyclopropanation and allylic oxidation

Article abstract of DOI:10.1016/j.tetasy.2006.02.010

A new type of bisoxazoline ligand 4 (abbreviated as SpiroBOX) containing a chiral spirobiindane scaffold were easily prepared in high yields from enantiomerically pure 1,1′-spirobiindane-7,7′-diol (SPINOL) with 1,1′-spirobiindane-7,7′-dicarboxylic acid as

Full text of DOI:10.1016/j.tetasy.2006.02.010

Tetrahedron: Asymmetry 17 (2006) 634–641
Preparation and application of bisoxazoline ligands with a chiral
spirobiindane skeleton for asymmetric cyclopropanation
and allylic oxidation
Bin Liu, Shou-Fei Zhu, Li-Xin Wang and Qi-Lin Zhou*
State Key Laboratory and Institute of Elemento-organic Chemistry, Nankai University, Tianjin 300071, China
Received 21 November 2005; revised 9 February 2006; accepted 10 February 2006
Available online 20 March 2006
Dedicated to Professor Jack Halpern on the occasion of his 80th birthday
Abstract—A new type of bisoxazoline ligand 4 (abbreviated as SpiroBOX) containing a chiral spirobiindane scaffold were easily
prepared in high yields from enantiomerically pure 1,10-spirobiindane-7,70-diol (SPINOL) with 1,10-spirobiindane-7,70-dicarboxylic
acid as the key intermediate. Ligands 4 were applied to the Cu-catalyzed asymmetric cyclopropanation of styrenes with menthyl
diazoacetate and allylic oxidation of cyclic alkenes with tert-butyl perbenzoates. The copper complexes of ligands 4 showed high
activities and moderate to good enantioselectivities.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
bones, such as ligands 2 and 3, were also synthesized.7
As the chiralities on the oxazoline ring and backbone
match each other, the enantioselectivities of the ligands
are normally enhanced. For instance, in the Pd-cata-
lyzed Wacker-type cyclization of 2,3-dimethyl-2-bute-
nylphenol, ligand (S,S)-3 afforded dihydrobenzofuran
product in 97% ee, while ligand 1 gave the same product
in only 35% ee.8 Over the last few years, we have devel-
oped a new series of chiral phosphorous ligands based
on the spirobiindane scaffold and demonstrated that
they are highly efficient for asymmetric hydrogenation9
and C–C bond forming reactions.10 Herein, we report
the synthesis of the bisoxazoline ligands bearing a chiral
spirobiindane scaffold, 7,70-bis[(S)-4-alkyl-oxazolin-
2-yl]-1,10-spirobiindane 4 (abbreviated as SpiroBOX)
(Scheme 1) and their applications in Cu-catalyzed asym-
metric cyclopropanation of styrenes with menthyl
diazoacetate and allylic oxidation of cyclic olefins with
tert-butyl perbenzoates.
The synthesis of new chiral ligands is a focus of research
in transition metal-catalyzed asymmetric reactions. A
large number of chiral ligands have been developed over
the last few decades, some of which have been success-
fully applied in the production of chiral compounds in
industry.1 There are many features that have to be con-
sidered in the design of new chiral ligands. Among them,
an appropriate scaffold is a fundamental element for an
efficient ligand. One of the excellent examples is that the
axially chiral 1,10-binaphthyl structure has been proven
to be an ideal skeleton for many types of ligands.2
C2-Symmetric bisoxazolines are the most popular chiral
nitrogen ligands because of their convenient synthesis,
modular nature, and more importantly wide applicabi-
lity in metal-catalyzed transformations. Since Masamune
and co-workers,3 Pfaltz and co-workers,4 and Evans
et al.5 reported the first bisoxazoline ligands 1 with a
methylene bridge independently in the early 1990s, a
variety of chiral bisoxazolines with different bridges
and substituents have been developed.6 The bisoxazo-
lines with a chiral biphenyl, binaphthyl, and other back-
2. Results and discussion
2.1. Preparation of SpiroBOX ligands
Enantiomerically
pure
1,10-spirobiindane-7,70-diol
*
(SPINOL)11 is a suitable starting compound for the prep-
aration of chiral spiro ligands. SPINOL was firstly
Corresponding author. Tel.: +86 22 2350 0011; fax: +86 22 2350
6177; e-mail: qlzhou@nankai.edu.cn
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.02.010

B. Liu et al. / Tetrahedron: Asymmetry 17 (2006) 634–641
635
O
O
O
R1
N
R1
N
R
R
R
R
R
R
O
N
N
N
N
O
N
N
O
R
R
O
O
1
4
2
3
Scheme 1.
converted into bis(triflate) 5 in quantitative yield by
treatment with trifluoromethane–sulfonic anhydride with
the aid of pyridine. The reaction of compound 5 with
Zn(CN)2 catalyzed by Pd(PPh3)4 afford dicarbonitrile
6. The utilization of Zn(CN)2 as a cynation agent is
crucial for this transformation. When KCN or NaCN,
instead of Zn(CN)2 was used, there was no target
compound formed, even under harsh reaction condition.
It was reported that the aromatic cyanides could react
with amino alcohols in the presence of ZnCl2 or other
Lewis acid catalysts to construct oxazoline rings.12
However, in our attempt, the dicarbonitrile 6 was found
to be inert in the reaction with amino alcohols in virtue
of the steric hindrance of the siprobiindane backbone. A
step-wise strategy was finally taken to prepare dioxazo-
lines. Dicarbonitrile 6 was hydrolyzed to the dicarbox-
ylic acid 7 with dilute H2SO4, followed by treatment
with optically active amino alcohols in the presence of
dicyclohexyl-carbodiimide (DCC) and benzotriazol-1-
ol (HOBt) to give amides 8 in almost quantitative yields.
Amides 8 were subjected to oxazoline ring formation by
the reaction with triphenylphosphine, carbon tetrachlo-
ride, and triethylamine to afford SpiroBOX ligands 4 in
73–97% yield.13 As there are two stereogenic factors,
one on the spirobiindane skeleton and the other on
oxazoline rings, the SpiroBOX ligands 4 should have a
pair of diastereomers. By using different enantiomers
of SPINOL, both diastereomers of SpiroBOX ligands,
(Ra,S,S)-4 and (Sa,S,S)-4, were prepared in high yields
(Scheme 2).
uation of efficiency of nitrogen ligands.14 To test the
activity and enantioselectivity of SpiroBOX ligands 4,
we first investigated the asymmetric cyclopropanation
of styrene with (1S,2R,5S)-menthyl diazoacetate cata-
lyzed by the copper complexes of SpiroBOX ligands.
The reaction was carried out in dichloromethane with
(CuOTf)2C6H6 as a precatalyst at refluxing temperature.
Comparison of the two diastereomers of SpiroBOX
ligands clearly revealed that the ligand (Ra,S,S)-4 has
a matched combination of chiralities (Table 1, entries
1 and 2). Ligand (Ra,S,S)-4c gave the highest yield
(93%), diastereoselectivity (cis/trans = 11:89) and ee
value (70% ee for trans-isomer). When using chloroform
as solvent, the reaction became sluggish and the yield
decreased to 53% (Table 1, entry 5). The other copper
salts, such as CuPF6(MeCN)4, CuClO4(MeCN)4, and
CuCl, were also tried, with (CuOTf)2C6H6 being the best
choice of precatalyst.
Various para-substituted styrenes were examined in the
cyclopropanation reaction. The results illustrated in
Table 2 showed that the electron-withdrawing substitu-
ents on the styrene benefit enantioselectivity. The high-
est enantioselectivity (82% ee) was achieved by using
4-trifluoromethylstyrene substrate (Table 2, entry 1).
In all cases, the trans/cis ratios were more than 80:20
and the electronic character of the substrate only had
a slight influence on the diastereoselectivity.
2.3. Asymmetric allylic oxidation of cycloalkenes
2.2. Asymmetric cyclopropanation of styrenes
The copper-catalyzed asymmetric allylic oxidation of
olefins with peresters provided an efficient route to pre-
pare chiral allylic alcohols and their derivates, which are
useful building blocks in organic synthesis. Since Pfaltz
Copper-catalyzed asymmetric cyclopropanation of sty-
renes with diazoacetates is a model reaction for the eval-
H2SO4, H2O, HAc
100%
Pd(PPh3)4, Zn(CN)2
Tf2O, Pyridine
100%
OH
OH
CO2H
CO2H
OTf
OTf
CN
CN
99%
7
SPINOL
5
6
H2N
R
OH
O
R
O
PPh3/CCl4/NEt3
MeCN
R
OH
a: R = Ph
N
N
NH
HN
HO
b: R = Bn
O
R
c: R = iPr
HOBt, DCC
R
O
8a-c
4a-c
73-97% from 7
Scheme 2.

636
B. Liu et al. / Tetrahedron: Asymmetry 17 (2006) 634–641
Table 1. Asymmetric cyclopropanation of styrene with (1S,2R,5S)-menthyl diazoacetate: optimizing reaction conditionsa
O
CO
N2HC
O
[Cu]/L*, 5 mol%
CH2Cl2, reflux
+
O
Entry
Ligand
[Cu]
Time
Yieldb (%)
cis/transc
eec (%)
1
2
3
4
5d
6
7
8
(Ra,S,S)-4a
(Sa,S,S)-4a
(Ra,S,S)-4b
(Ra,S,S)-4c
(Ra,S,S)-4c
(Ra,S,S)-4c
(Ra,S,S)-4c
(Ra,S,S)-4c
(CuOTf)2C6H6
(CuOTf)2C6H6
(CuOTf)2C6H6
(CuOTf)2C6H6
(CuOTf)2C6H6
CuPF6(MeCN)4
CuClO4(MeCN)4
CuCl
5 d
6 d
6 h
3 h
3 d
3 h
24 h
24 h
62
71
53
93
53
86
30
37
24:76
25:75
30:70
11:89
21:79
12:88
20:80
25:75
40/49
11/13
23/21
62/70
77/68
65/69
47/31
9/31
a Reaction conditions: 5 mol % [Cu], 6 mol % ligands, 0.5 mmol menthyl diazoacetate, and 4 mmol styrene in dichloromethane at refluxing
temperature.
b Isolated yield based on the menthyl diazoacetate.
c Determined by GC on HP-5 column.
d Chloroform as solvent at refluxing temperature.
Table 2. Asymmetric cyclopropanation of para-substituted styrene with (1S,2R,5S)-menthyl diazoacetatea
O
(CuOTf)2C6H6, 2.5 mol%
CO
(R,S,S)-4c, 6 mol%
N2HC
O
+
CH2Cl2, reflux
O
R
R
Entry
R
Yield (%)
cis/trans
ee (%)b
1
2
3
4
5
6
4-CF3
4-Cl
4-Br
H
4-Me
4-OMe
56
54
61
93
67
55
14:86
14:84
17:83
11:89
18:82
15:85
82
82
72
70
55
53
a For reaction conditions and analyses, see Table 1 and Experimental section.
b Ee of trans-isomer.
and co-workers15 and Andrus et al.16 first introduced the
chiral bisoxazolines into this reaction, it has drawn
much attention to use bisoxazoline ligands for improv-
ing the activity and enantioselectivity of copper cata-
lysts. Although great efforts have been made, only
limited successful results have been achieved.17 The
major unsolved problems in asymmetric allylic oxida-
tion include: (1) the activities of catalysts are too low,
in most cases the reaction needs one or two weeks for
completion and (2) the enantioselectivities of reactions
are not high. Therefore, the search for new catalysts
with high activity and enantioselectivity still remains
to be a focus in the study of this important asymmetric
transformation. To extend the scope of application of
SpiroBOX ligands 4 in transition metal-catalyzed asym-
metric reactions, we investigated the Cu-catalyzed allylic
oxidation of cyclic olefins with perbenzoates, producing
the corresponding allyl benzoate in moderate to good
enantioselectivities.
dant in acetone at room temperature in the presence of
5 mol % of copper (I) catalyst generated in situ from
copper(I) salts and the ligands 4. Comparison of ligands
showed that the (Ra,S,S) ligands have matched chirali-
ties for the asymmetric allylic oxidation (Table 3, entries
1 and 2), which is similar to that in the asymmetric
cyclopropanation reaction. Ligand (Ra,S,S)-4b, which
contained benzyl groups on the oxazoline rings, gave
the highest enantioselectivity. Different copper salts,
such as CuPF6(MeCN)4, (CuOTf)2C6H6, and Cu(OTf)2
could be used as a resource of catalyst. Further studies
revealed that the reaction temperature has almost no
influence on the ee value of product, but strongly im-
pacted on the reactivity of the reaction. When the reac-
tion temperature was increased to 40 ꢁC, the reaction
finished within 6 h without loss of yield or enantioselec-
tivity (entry 7). This result represents one of the highest
activities of Cu/bisoxazoline catalysts in the asymmetric
allylic oxidation reaction. In addition to acetone, aceto-
nitrile can also be used as a solvent to give a comparable
activity, while the enantioselectivity became lower (entry
9).
A model reaction was established with cyclohexene as
the standard substrate and tert-butyl perbenzoate as oxi-

B. Liu et al. / Tetrahedron: Asymmetry 17 (2006) 634–641
637
Table 3. Asymmetric allylic oxidation of cyclohexene with tert-butyl perbenzoate: optimizing reaction conditionsa
O
O
[Cu], 5 mol%
Ligand, 6 mol%
O
O
O
+
Entry
Ligand
[Cu]
Solvent
T (ꢁC)
Time
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
10
(Ra,S,S)-4a
(Sa,S,S)-4a
(Ra,S,S)-4b
(Ra,S,S)-4c
(Ra,S,S)-4b
(Ra,S,S)-4b
(Ra,S,S)-4b
(Ra,S,S)-4b
(Ra,S,S)-4b
(Ra,S,S)-4b
CuPF6(MeCN)4
CuPF6(MeCN)4
CuPF6(MeCN)4
CuPF6(MeCN)4
(CuOTf)2C6H6
Cu(OTf)2
CuPF6(MeCN)4
CuPF6(MeCN)4
CuPF6(MeCN)4
CuPF6(MeCN)4
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetonitrile
Benzene
rt
rt
rt
rt
rt
rt
40
0
15 h
20 h
2 d
25 h
2 d
2 d
6 h
12 d
2 d
2 d
60
65
58
59
45
43
57
45
69
57
38
ꢀ15
70
2
70
68
70
69
58
rt
rt
14
a Reaction conditions: 5 mol % [Cu], 6 mol % ligands, 0.2 mmol tert-butyl perbenzoate, and 3 mmol cyclohexene.
b Isolated yield based on tert-butyl perbenzoate.
c Determined by HPLC on Chiralcel OD-H column.
Under the optimized conditions, cyclohexene and cyclo-
pentene were oxidized with different perbenzoates and
the results are illustrated in Table 4. The ring size of
the cycloalkenes and the electronic characters of substi-
tuents at the para-position of tert-butyl perbenzoates
only have a slight influence on the ee value of products.
The properties of the substituent on the peresters have a
great impact on the yield of oxidation products. For
example, the introduction of a strong electron-with-
drawing NO2 group at the para-position of tert-butyl
perbenzoate enhanced the yield of the allylic oxidation
product to 80% (entry 5). However, a ortho-NO2 group
in the perester dramatically lowered the yield of oxida-
tion product to 16%, indicating the steric hindrance of
substituent has a negative impact to the reactivity of
tert-butyl perbenzoate oxidant (entry 6).
metric cyclopropanation of styrenes with menthyl di-
azoacetate, and high diastereoselectivities with moderate
to good enantioselectivities were obtained. Ligands 4
were also proven to be efficient in the Cu-catalyzed asym-
metric allylic oxidation of cyclic alkenes with tert-butyl
perbenzoates, providing cycloalkenyl benzoates in mod-
erate enantioselectivities.
4. Experimental
4.1. General methods
All reactions and manipulations were performed using
standard Schlenk techniques. Acetone was distilled from
˚
4 A molecular sieves. Benzene was distilled from sodium
benzophenone ketyl. Acetonitrile was distilled from cal-
cium hydride. The cyclic olefins were distilled before use.
The perbenzoates were prepared according to the previ-
ous method.18 CuOTf, HOBt, and DCC were purchased
from Aldrich and used directly. CuPF6 was recrystal-
lized from acetonitrile before use. NMR spectra were
recorded with a Bruker or Varian spectrometer at 400
or 300 (1H NMR), 100 or 75 (13C NMR) MHz. Chemical
shifts were reported in ppm down field from internal
3. Conclusion
A series of C2-symmetric chiral bisoxazoline ligands 4
with a spirobiindane scaffold were prepared from enantio-
merically pure 1,10-spirobiindane-7,70-diol and 2-amino
alcohols, in five steps, in high yields. These new types
of bisoxazolines were evaluated in Cu-catalyzed asym-
Table 4. Asymmetric allylic oxidation of cyclic olefins with tert-butyl benzoatesa
O
CuPF6(MeCN)4, 5 mol%
(R,S,S)-4b, 6 mol%
O
O
O
O
+
R
R
acetone, rt, 2 d
n
n
Entry
R
n
Yield (%)
ee (%)
1
2
3
4
5
6
H
H
4-OMe
4-Me
4-NO2
2-NO2
1
2
2
2
2
2
58
58
67
65
80
16
70
70
67
66
67
59
a For the reaction conditions and analyses, see Table 1 and Experimental section.

638
B. Liu et al. / Tetrahedron: Asymmetry 17 (2006) 634–641
Me4Si. Optical rotations were determined using a Perkin
Elmer Model 341 polarimeter. Elemental analyses were
performed on Yanaca CDRDER MT-3 instrument.
Mass spectra were recorded on a LCQ Advantage spec-
trometer with ESI resource. GC analyses were per-
formed using a Hewlett Packard Model HP 6890
Series. HPLC analyses were performed using a Hewlett
Packard Model HP 1100 Series chromatography.
over anhydrous MgSO4, and concentrated in reduced
pressure. The residue was purified by flash chroma-
tography (ethyl acetate/petroleum ether = 1:1) to give
(R)-7 (4.0 g, 100%). Further purification by recrys-
tallization from toluene afforded a white solid; mp
20
230–231 ꢁC; ½aꢁD ¼ þ303 (c 0.5, CH2Cl2); 1H NMR
(300 MHz, CDCl3) d 2.22–2.28 (m, 2H), 2.36–2.50 (m,
2H), 3.02–3.10 (m, 4H), 7.12 (t, J = 7.5 Hz, 2H), 7.39
(d, J = 7.2 Hz, 2H), 7.63 (d, J = 7.5 Hz, 2H), 9.8 (s,
2H); 13C NMR (75 MHz, CDCl3) d 30.9 (CH2), 38.2
(CH2), 63.2 (C), 125.2 (CH), 126.5 (CH), 128.8 (C),
129.5 (CH), 145.5 (C), 151.5 (C), 172.1 (COOH); MS
(EI) m/z (relative intensity) 308 (M+, 6), 290 (100). Anal.
Calcd for C19H16O4: C 74.01, H 5.23. Found: C 74.06, H
5.40.
4.2. (R)-7,70-Bis(trifluoromethanesulfonyloxy)-1,10-
spirobiindane (R)-5
To a solution of (R)-1,10-spirobiindane-7,70-diol (5.0 g,
19.8 mmol) and pyridine (7.0 mL, 86.7 mmol) in
100 mL of CH2Cl2, trfluoromethanesulfonic anhydride
(8.2 mL, 43.7 mmol) was added slowly at 0 ꢁC. The mix-
ture was stirred at room temperature overnight. After
removal of the solvent, the residue was diluted with
CH2Cl2 (200 mL) and washed with 5% aqueous HCl,
saturated NaHCO3, and brine. The organic layer was
dried over anhydrous sodium sulfate and concentrated
under reduced pressure. The residue was purified by
flash chromatography (ethyl acetate/petroleum ether =
1:20) to afford (R)-5 (10.2 g, 100%) as a white solid;
4.5. (Ra,S,S)-N,N0-Bis(2-hydroxy-1-phenylethyl)-1,10-
spirobiindane-7,70-diamide [(Ra,S,S)-8a]
A solution of (R)-7 (308 mg, 1.0 mmol), dicyclohexyl-
carbodiimide (870 mg, 4.2 mmol), benzotriazol-1-ol
(300 mg, 2.2 mmol), and (S)-2-amino-2-phenyl-ethanol
(300 mg, 2.2 mmol) in dry THF was stirred at ꢀ5 ꢁC
for an hour and then at room temperature overnight.
The resulting mixture was concentrated under reduced
pressure, and purified by silica gel column chromato-
graphy (petroleum ester/ethyl acetate = 1:1) to give
20
1
mp 62–64 ꢁC; ½aꢁD ¼ þ143 (c 0.5, CH2Cl2); H NMR
(300 MHz, CDCl3) d 2.35 (m, 4H), 3.10 (m, 4H), 7.15
(dd, 2H, J = 1.8 and 6.6 Hz), 7.26–7.30 (m, 4H); 13C
NMR (75 MHz, CDCl3) d 31.1 (CH2), 38.6 (CH2), 59.4
(CH), 115.9 (C), 118.5 (CF3), 120.1 (CH), 124.4 (CH),
129.4 (CH), 138.2 (C), 145.8 (C), 147.7 (C); MS (EI)
m/z (relative intensity) 516 (M+, 100). Anal. Calcd for
C19H14F6O6S2: C 44.19, H 2.73. Found: C 43.97, H 2.83.
(Ra,S,S)-8a (550 mg, 1.0 mmol, 99%) as
a white
20
1
solid; mp 262–264 ꢁC; ½aꢁD ¼ þ102 (c 0.5, CHCl3); H
NMR (300 MHz, CDCl3): d 1.83 (m, 2H), 2.28 (m,
2H), 3.09 (m, 6H), 3.46 (m, 2H), 3.59 (m, 2H), 4.99
(m, 2H, J = 3.0 Hz), 7.28 (m, 16H), 8.10 (d, 2H,
J = 9.3 Hz); 13C NMR (100 MHz, CDCl3): d 31.1
(CH2), 39.6 (CH2), 54.5 (CH), 62.6 (C), 66.2 (CH2),
126.4 (CH), 126.5 (CH), 126.8 (CH), 127.7 (CH), 129.0
(CH), 132.1 (C), 139.0 (C), 146.8 (C), 148.5 (C), 169.9
(C@O); MS (ESI): 547 (M+1). Anal. Calcd for
C35H34N2O4: C 76.90, H 6.27, N 5.12. Found: C
77.07, H 6.29, N 5.25.
4.3. (R)-1,10-Spirobiindane-7,70-dicarbonitrile (R)-6
A mixture of bis(triflate) (R)-5 (6.7 g, 13 mmol),
Zn(CN)2 (3.6 g, 30.1 mmol), and Pd(PPh3)4 (1.6 g,
1.38 mmol) in DMF (13 mL) was stirred at 140 ꢁC for
24 h. The resulting mixture was diluted with ethyl ace-
tate, washed sequentially with aqueous Na2CO3 and
brine and dried over anhydrous MgSO4. The dried
organic layers were filtrated and concentrated under
reduced pressure. The residue was purified by flash
chromatography (ethyl acetate/petroleum ether = 1:7)
4.6. (Sa,S,S)-N,N0-Bis(2-hydroxy-1-phenylethyl)-1,10-
spirobiindane-7,70-diamide (Sa,S,S)-8a
Compound (Sa,S,S)-8a was prepared by the same proce-
dure for the preparation of (Ra,S,S)-8a from (S)-1,10-
to afford (R)-6 (3.5 g, 99%) as white crystals; mp
20
194–195 ꢁC; ½aꢁD ¼ þ144 (c 0.5, CH2Cl2); 1H NMR
spirobiindanyl-7,70-dicarboxylic acid (S)-7. Yield
20
(300 MHz, CDCl3) d 2.33–2.50 (m, 4H), 3.09–3.16 (m,
4H), 7.34 (t, J = 7.8 Hz, 2H), 7.47–7.54 (m, 4H);
13C NMR (75 MHz, CDCl3) d 31.1 (CH2), 39.6 (CH2),
61.8 (C), 108.3 (CH), 116.7 (CN), 128.5 (CH), 129.6
(CH), 132.0 (C), 146.0 (C), 151.1 (C); MS (EI) m/z
(relative intensity) 270 (M+, 100). Anal. Calcd for
C19H14N2: C 84.42, H 5.22, N 10.36. Found: C 84.42,
H 5.36, N 10.56.
(87%), as a white solid, mp 103–107 ꢁC; ½aꢁD ¼ ꢀ103
1
(c 0.5, CHCl3); H NMR (400 MHz, CDCl3): d 1.25
(m, 2H), 2.26 (m, 2H), 2.48 (m, 2H), 2.86 (s, 2H), 3.00
(m, 4H), 3.56 (m, 4H), 4.45 (m, 2H), 6.97 (m, 6H),
7.14 (t, 2H J = 7.6 Hz), 7.26 (m, 8H); 13C NMR
(100 MHz, CDCl3): d 30.8 (CH2), 40.3 (CH2), 57.1
(CH), 62.11 (C), 66.8 (CH2), 126.4 (CH), 127.2 (CH),
127.4 (CH), 128.0 (CH), 128.9 (CH), 133.4 (C), 138.5
(C), 145.4 (C), 145.5 (C), 165.63 (C@O); MS (ESI):
547 (M+1). Anal. Calcd for C35H34N2O4: C 76.90, H
6.27, N 5.12. Found: C 77.05, H 6.31, N 5.27.
4.4. (R)-1,10-Spirobiindanyl-7,70-dicarboxylic acid (R)-7
Dinitrile (R)-6 (3.5 g, 13.0 mmol) was added to a mix-
ture of H2O (90 mL), HOAc (30 mL), and H2SO4
(60 mL), and the mixture stirred at 145 ꢁC for 48 h.
The resulting mixture was diluted with water
(600 mL), and extracted with ethyl acetate (3 · 100
mL). The organic layer was washed with brine, dried
4.7. (Ra,S,S)-N,N0-Bis(1-benzyl-2-hydroxyethyl)-1,10-
spirobiindane-7,70-diamide (Ra,S,S)-8b
Compound (Ra,S,S)-8b was prepared by the same proce-
dure for the preparation of (Ra,S,S)-8a from (S)-2-

B. Liu et al. / Tetrahedron: Asymmetry 17 (2006) 634–641
639
amino-3-phenylpropan-1-ol. Yield (99%), as a white
8a. Yield (93%), white solid, mp 167–169 ꢁC;
20
20
1
solid, mp 213–215 ꢁC; ½aꢁD ¼ þ90 (c 0.5, CHCl3); H
NMR (300 MHz, CDCl3): d 1.62 (m, 2H), 2.24 (m,
2H), 2.77 (m, 4H), 3.03 (m, 8H), 3.28 (m, 2H), 4.04
(m, 2H), 6.87 (m, 2H), 7.06 (t, 2H, J = 7.5 Hz), 7.24
(m, 14H), 7.54 (d, 2H J = 9.3 Hz); 13C NMR
(75 MHz, CDCl3): d 30.8 (CH2), 36.8 (CH2), 39.3
(CH2), 51.1 (CH2), 62.2 (C), 63.5 (CH), 125.9 (CH),
126.1 (CH), 126.3 (CH), 126.6 (CH), 128.5 (CH), 129.1
(CH), 132.0 (C), 137.9 (C), 146.4 (C), 148.0 (C), 169.7
(C@O); MS (ESI): 575 (M+1). Anal. Calcd for
C37H38N2O4: C 77.33, H 6.66, N 4.87. Found: C
77.17, H 6.60, N 4.93.
½aꢁD ¼ ꢀ322 (c 0.5, CH2Cl2); 1H NMR (300 MHz,
CDCl3): d 2.31 (dd, 2H, J = 4.8 and 7.2 Hz), 2.60 (m,
2H, J = 10.8 Hz), 3.05 (m, 4H), 3.37 (m, 2H), 3.72 (t,
2H, J = 7.2 Hz), 4.98 (dd, 2H, J = 3.0 and 6.9 Hz),
7.07 (m, 4H), 7.23 (m, 8H), 7.36 (d, 2H J = 6.9 Hz),
7.81 (d, 2H, J = 7.5 Hz); 13C NMR (75 MHz, CDCl3):
d 30.9 (CH2), 38.9 (CH2), 63.5 (C), 69.1 (CH), 74.5
(CH2), 126.3 (CH), 126.8 (CH), 127.3 (CH), 127.4
(CH), 128.7 (CH), 128.9 (CH), 142.8 (C), 145.4 (C),
149.1 (C), 165.6 (C@N); MS (ESI): 511 (M+1). Anal.
Calcd for C35H30N2O2: C 82.33, H 5.92, N 5.49. Found:
C 82.17, H 6.12, N, 5.52.
4.8. (Ra,S,S)-N,N0-Bis(1-hydroxymethyl-2-methyl-
propyl)-1,10-spirobiindane-7,70-diamide (Ra,S,S)-8c
4.11. (Ra,S,S)-7,70-Bis(4-benzyloxazolin-2-yl)-1,10-
spirobiindane (Ra,S,S)-4b
Compound (Ra,S,S)-8c was prepared by the same proce-
dure for the preparation of (Ra,S,S)-8a from (S)-2-
amino-3-methylbutan-1-ol. Yield (99%), as a white solid,
Compound (Ra,S,S)-4b was prepared by the same proce-
dure for the preparation of (Ra,S,S)-4a from (Ra,S,S)-
20
8b. Yield (97%), colorless sticky oil; ½aꢁD ¼ þ111
20
1
1
mp 195–197 ꢁC, ½aꢁD ¼ þ84 (c 0.5, CHCl3); H NMR
(400 MHz, CDCl3): d 0.88 (m, 6H), 0.93 (m, 6H), 1.57
(m, 2H), 1.74 (m, 2H), 2.25 (m, 2H), 3.13 (m, 8H),
3.41 (m, 4H), 7.13 (m, 4H), 7.32 (d, 2H, J = 6.8 Hz),
7.69 (d, 2H, J = 7.2 Hz). 13C NMR (100 MHz, CDCl3):
d 19.4 (CH3), 29.2 (CH2), 31.0 (CH), 34.2 (CH2), 39.3
(C), 56.1 (CH), 63.0 (CH2), 126.1 (CH), 126.3 (CH),
126.7 (CH), 132.2 (C), 146.7 (C), 148.5 (C), 170.4
(C@O); MS (ESI): 479 (M+1). Anal. Calcd for
C29H38N2O4: C 72.77, H 8.00, N 5.85. Found: C
72.56, H 7.97, N 6.01.
(c 0.5, CH2Cl2); H NMR (300 MHz, CDCl3): d 2.24
(dd, 2H, J = 3.6 and 8.1 Hz), 2.43 (dd, 2H, J = 4.5
8.7 Hz), 2.66 (m, 2H), 2.89 (m, 4H, J = 6.6 Hz), 3.01
(m, 4H), 3.93 (m, 4H), 7.08 (d, 4H, J = 6.9 Hz), 7.26
(m, 12H), 7.64 (d, 2H, J = 7.5 Hz); 13C NMR
(75 MHz, CDCl3): d 30.70 (CH2), 38.6 (CH2), 41.4
(CH2), 63.1 (C), 68.0 (CH2), 71.6 (CH), 124.0 (CH),
125.8 (CH), 126.7 (CH), 128.1 (CH), 128.3 (CH), 129.1
(CH), 138.9 (C), 145.5 (C), 149.1 (C), 163.6 (C@N);
MS (ESI): 539 (M+1). Anal. Calcd for C37H34N2O2: C
82.50, H 6.36, N 5.20. Found: C 82.31, H 6.30, N 5.29.
4.9. (Ra,S,S)-7,70-Bis(4-phenyloxazolin-2-yl)-1,10-
spirobiindane (Ra,S,S)-4a
4.12. (Ra,S,S)-7,70-Bis(4-isopropyloxazolin-2-yl)-1,10-
spirobiindane (Ra,S,S)-4c
A solution of (Ra,S,S)-8a (234 mg, 0.42 mmol), tri-
phenylphosphane (384 mg, 0.90 mmol), triethylamine
(200 lL, 0.88 mmol), and tetrachloromethane (138 lL,
0.88 mmol) in dry acetonitrile was stirred overnight.
After being concentrated in vacuum, the residue was
dissolved with CH2Cl2, washed with water, dried over
anhydrous magnesium sulfate, and then concentrated
in vacuum. The residue was purified by silica gel column
chromatography with petroleum/ethyl acetate (3:1) to
Compound (Ra,S,S)-4c was prepared by the same proce-
dure for the preparation of (Ra,S,S)-4a from (Ra,S,S)-
20
8c. Yield (91%), as a colorless sticky oil. ½aꢁD ¼ þ155
1
(c 0.5, CH2Cl2); H NMR (300 MHz, CDCl3): d 0.66
(d, 6H, J = 6.6 Hz), 0.85 (d, 6H, J = 6.6 Hz), 1.41 (m,
2H), 2.23 (m, 2H), 2.74 (m, 2H, J = 11.1 Hz), 3.00 (m,
6H), 3.21 (m, 2H), 3.91 (m, 2H), 7.13 (t, 2H, J =
7.5 Hz), 7.31 (d, 2H, J = 7.2 Hz), 7.52 (d, 2H,
J = 7.5 Hz); 13C NMR (100 MHz, CDCl3): d 18.9
(CH3), 19.7 (CH3), 30.8 (CH2), 32.7 (CH2), 38.5 (CH),
63.2 (C), 70.0 (CH2), 73.3 (CH), 124.1 (CH), 125.6
(CH), 126.4 (CH), 128.0 (C), 145.3 (C), 149.2 (C),
162.6 (C@N); MS (ESI): 443 (M+1). Anal. Calcd for
C29H34N2O2: C 78.7, H 7.74, N 6.33. Found: C 78.80,
H 7.57, N 6.47.
give (Ra,S,S)-4a (204 mg, 95%) as a white solid; mp
20
130–132 ꢁC; ½aꢁD ¼ þ93 (c 0.5, CH2Cl2); 1H NMR
(300 MHz, CDCl3): d 2.31 (dd, 2H, J = 5.1 and
6.9 Hz), 2.87 (m, 2H), 3.07 (m, 6H), 4.26 (dd, 2H,
J = 1.8 and 8.4 Hz), 4.70 (t, 2H, J = 10.5 Hz), 7.09 (t,
2H, J = 7.2 Hz), 7.28 (m, 12H), 7.67 (d, 2H,
J = 7.5 Hz); 13C NMR (75 MHz, CDCl3): d 30.9
(CH2), 39.0 (CH2), 63.2 (C), 70.1 (CH2), 74.0 (CH),
123.6 (CH), 126.0 (CH), 126.8 (CH), 127.1 (CH), 128.4
(CH), 128.5 (CH), 141.9 (C), 145.7 (C), 149.7 (C),
164.6 (C@N); MS (ESI): 511 (M+1). Anal. Calcd for
C35H30N2O2: C 82.33, H 5.92, N 5.49. Found: C
82.22, H 6.07, N 5.59.
4.13. Typical procedure for copper(I) catalyzed
asymmetric cyclopropanation of styrene
A mixture of [(Cu(I)OTf)2C6H6] (2.5 mg, 0.01 mmol)
and ligand 4 (0.012 mmol) in dichloromethane (2.0
mL) was stirred at room temperature for 1 h under an
argon atmosphere. After the addition of a styrene sub-
strate (4 mmol), a solution of menthyl diazoacetate
(112 mg, 0.5 mmol) in dichloromethane (2.0 mL) was
added, and the reaction solution stirred at 40 ꢁC for
1.5 h. The reaction mixture was filtered through a short
silica pad. The filtrate was concentrated in vacuum to
4.10. (Sa,S,S)-7,70-Bis(4-phenyloxazolin-2-yl)-1,10-
spirobiindane (Sa,S,S)-4a
Compound (Sa,S,S)-4a was prepared by the same proce-
dure for the preparation of (Ra,S,S)-4a from (Sa,S,S)-

640
B. Liu et al. / Tetrahedron: Asymmetry 17 (2006) 634–641
give a crude product, which was chromatographed on a
silica gel column with petroleum ether/ethyl acetate
(20:1) to afford the product. The analyses were illus-
trated as follows.
give a crude product. The crude product was purified
by column chromatography with petroleum ester/ethyl
acetate (40:1) to give benzoic acid cyclohex-2-enyl ester
as a colorless oil. The analyses were illustrated as
follows.
4.13.1. (+)-Menthyl 2-phenylcyclopropanecarboxylate.
Yield (93%), 62% ee for cis-isomer and 70% ee for
trans-isomer [GC: HP-5 column (30 m); carrier gas, N2
(0.7 mL/min); injection temp, 230 ꢁC; initial column
temperature, 150 ꢁC; rate, 4 ꢁC/min; final column
temperature, 220 ꢁC; cis-isomer: tR = 14.42 min, tR =
4.14.1. Cyclopent-2-enyl benzoate. Yield (58%), 70% ee
[HPLC: chiralpak OD-H column (25 cm · 0.46 cm ID),
n-hexane/i-PrOH = 10,000:3, 0.8 mL/min, tR = 17.47
min (S), tR = 21.41 min (R)].
14.54 min;
15.74 min].
trans-isomer:
tR = 15.38 min,
tR =
4.14.2. Cyclohex-2-enyl benzoate. Yield (58%), 70% ee
[HPLC: chiralpak OD-H column (25 cm · 0.46 cm
ID), n-hexane/i-PrOH = 10,000:5, 0.8 mL/min, tR =
15.72 min (S), tR = 16.51 min (R)].
4.13.2. (+)-Menthyl 2-p-tolylcyclopropanecarboxylate.
Yield (67%), 55% ee for trans-isomer [GC: HP-5 column
(30 m); carrier gas, N2 (0.7 mL/min); injection temp,
230 ꢁC; initial column temperature, 40 ꢁC; rate, 1 ꢁC/
min; final column temperature, 220 ꢁC; trans-isomer:
tR = 17.51 min, tR = 17.89 min].
4.14.3. Cyclohex-2-enyl 4-methoxybenzoate. Yield
(67%), 67% ee [HPLC: chiralpak OB column (25 cm ·
0.46 cm ID), n-hexane/i-PrOH = 99:1, 0.8 mL/min,
tR = 11.54 min (S), tR = 13.44 min (R)].
4.13.3. (+)-Menthyl 2-(4-chlorophenyl)cyclopropanecarb-
oxylate. Yield (54%), 82% ee for trans-isomer [GC:
HP-5 column (30 m), carrier gas, N2 (0.7 mL/min);
injection temp, 230 ꢁC; initial column temperature,
150 ꢁC; rate, 4 ꢁC/min; final column temperature,
220 ꢁC; trans-isomer: tR = 19.68 min, tR = 20.22 min].
4.14.4. Cyclohex-2-enyl 4-methylbenzoate. Yield (65%),
66% ee [HPLC: chiralpak OD-H column (25 cm ·
0.46 cm ID), n-hexane/i-PrOH = 10,000:5, 1 mL/min,
tR = 16.91 min (S), tR = 17.70 min (R)].
4.14.5. Cyclohex-2-enyl 4-nitrobenzoate. Yield (80%),
67% ee [HPLC: chiralpak OB column (25 cm · 0.46 cm
ID), n-hexane, 0.9 mL/min, tR = 33.38 min (S), tR =
33.96 min (R)].
4.13.4. (+)-Menthyl 2-(4-bromophenyl)cyclopropanecarb-
oxylate. Yield (61%), 72% ee for trans-isomer [GC:
HP-5 column (30 m), carrier gas, N2 (0.7 mL/min);
injection temp, 230 ꢁC; initial column temperature,
150 ꢁC; rate, 4 ꢁC/min; final column temperature,
220 ꢁC; trans-isomer: tR = 22.72 min, tR = 23.39 min].
4.14.6. Cyclohex-2-enyl 2-nitrobenzoate. Yield (16%),
59% ee [HPLC: chiralpak OB column (25 cm · 0.46 cm
ID), n-hexane, 0.8 mL/min, tR = 51.6 min (S), tR =
67.0 min (R)].
4.13.5. (+)-Menthyl 2-(4-methoxyphenyl)cyclopropane-
carboxylate. yield (55%), 53% ee for trans-isomer
[GC: HP-5 column (30 m), carrier gas, N2 (0.7 mL/
min); injection temp, 230 ꢁC; initial column tempera-
ture, 150 ꢁC; rate, 4 ꢁC/min; final column temperature,
220 ꢁC; trans-isomer: tR = 21.42 min, tR = 22.00 min].
Acknowledgments
We thank the National Natural Science Foundation of
China, the Major Basic Research Development Program
(Grant No. G2000077506), the Ministry of Education of
China and the Committee of Science and Technology of
Tianjin City for financial support.
4.13.6. (+)-Menthyl 2-(4-trifluoromethylphenyl)cyclopro-
panecarboxylate. Yield (56%), 82% ee for trans-isomer
[GC: HP-5 column (30 m), carrier gas, N2 (0.7 mL/min);
injection temp, 230 ꢁC; initial column temperature,
150 ꢁC; rate, 5 ꢁC/min; final column temperature,
220 ꢁC; trans-isomer: tR = 14.93 min, tR = 15.38 min].
References
4.14. General procedure for the copper/SpiroBOX cata-
lyzed asymmetric allylic oxidation of cyclic alkenes
1. (a) For reviews, see: Comprehensive Asymmetric Catalysis;
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer: Berlin, 2004; Vols. I–III including supplement
1 and supplement 2; (b) Catalytic Asymmetric Synthesis,
2nd ed.; Ojima, I., Ed.; Wiley: New York, 2000; (c)
Lin, G.-Q.; Li, Y.-M.; Chan, A. S. C. Principles and
Applications of Asymmetric Synthesis; Wiley: New York,
2001.
2. For reviews, see: (a) McCarthy, M.; Guiry, P. J. Tetra-
hedron 2001, 57, 3809; (b) Brunel, J. M. Chem. Rev. 2005,
105, 857.
3. Lowenthal, R. E.; Abiko, A.; Masamune, S. Tetrahedron
Lett. 1990, 31, 6005.
A solution of CuPF6(MeCN)4 (3.7 mg, 0.01 mmol) and
(Ra,S,S)-4b (6.4 mg, 0.012 mmol) in anhydrous acetone
(2 mL) was stirred at room temperature for 1 h. Then
0.2 mL (3 mmol) of cyclohexene was added. After being
stirred for 2 min, tert-butyl benzoate (38 lL, 0.2 mmol)
was added. The reaction solution was then stirred at
room temperature for two days, after which the reaction
was quenched by addition of 1 mL water and extracted
with ethyl acetate (10 mL, twice). The extract was
washed by saturated NaHCO3, water, and saturated
brine, dried over MgSO4, filtered, and concentrated to
4. Muller, D.; Umbricht, G.; Weber, B.; Pfaltz, A. Helv.
Chim. Acta 1991, 74, 232.

B. Liu et al. / Tetrahedron: Asymmetry 17 (2006) 634–641
641
5. Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M.
M. J. Am. Chem. Soc. 1991, 113, 726.
L.-X.; Shi, W.-J.; Zhou, Q.-L. J. Org. Chem. 2005, 70,
3734; (d) Zhu, S.-F.; Yang, Y.; Wang, L.-X.; Liu, B.;
Zhou, Q.-L. Org. Lett. 2005, 7, 2333.
6. For reviews on bisoxazoline ligands, see: (a) Ghosh, A. K.;
Mathivanan, P.; Cappiello, J. Tetrahedron: Asymmetry
1998, 9, 1; (b) Fache, F.; Schulz, E.; Tommasino, L.;
Lemaire, M. Chem. Rev. 2000, 100, 2159; (c) McManus,
H. A.; Guiry, P. J. Chem. Rev. 2004, 104, 4151.
7. (a) Gant, T. G.; Noe, M. C.; Corey, E. J. Tetrahedron Lett.
1995, 36, 8745; (b) Uozumi, Y.; Kyota, H.; Kishi, E.;
Kitayama, K.; Hayashi, T. Tetrahedron: Asymmetry 1996,
7, 1603; (c) Chelucci, G. Tetrahedron: Asymmetry 1997, 8,
2667; (d) Rippert, A. J. Helv. Chim. Acta 1998, 81, 676; (e)
Meyers, A. I.; Price, A. J. Org. Chem. 1998, 63, 412; (f)
Benaglia, M.; Benincori, T.; Mussini, P.; Pilati, T.; Rizzo,
S.; Sannicolo, F. J. Org. Chem. 2005, 70, 7488.
11. (a) Birman, V. B.; Rheingold, A. L.; Lam, K.-C. Tetra-
hedron: Asymmetry 1999, 10, 125; (b) Zhang, J.-H.; Liao,
J.; Cui, X.; Yu, K.-B.; Deng, J.-G.; Zhu, S.-F.; Wang,
L.-X.; Zhou, Q.-L.; Chung, L.-W.; Ye, T. Tetrahedron:
Asymmetry 2002, 13, 1363.
12. Witte, H.; Seeliger, W. Liebigs Ann. Chem. 1974, 996.
13. Appel, R. Angew. Chem., Int. Ed. Engl. 1975, 14, 801.
14. For reviews on asymmetric cyclopropanation, see: (a)
Doyle, M. P.; Forbes, D. C. Chem. Rev. 1998, 98, 911; (b)
Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B.
Chem. Rev. 2003, 103, 977.
15. Gokhale, A. S.; Minidis, A. B. E.; Pfaltz, A. Tetrahedron
Lett. 1995, 36, 1831.
16. Andrus, M. B.; Argade, A. B.; Chen, X.; Pamment, M. G.
Tetrahedron Lett. 1995, 36, 2945.
8. Uozumi, Y.; Kato, K.; Hayashi, T. J. Am. Chem. Soc.
1997, 119, 5063.
9. (a) Fu, Y.; Xie, J.-H.; Hu, A.-G.; Zhou, H.; Wang, L.-X.;
Zhou, Q.-L. Chem. Commun. 2002, 480; (b) Hu, A.-G.;
Fu, Y.; Xie, J.-H.; Zhou, H.; Wang, L.-X.; Zhou, Q.-L.
Angew. Chem., Int. Ed. 2002, 41, 2348; (c) Fu, Y.; Hou,
G.-H.; Xie, J.-H.; Xing, L.; Wang, L.-X.; Zhou, Q.-L. J.
Org. Chem. 2004, 69, 8157; (d) Xie, J.-H.; Wang, L.-X.;
Fu, Y.; Zhu, S.-F.; Fan, B.-M.; Duan, H.-F.; Zhou, Q.-L.
J. Am. Chem. Soc. 2003, 125, 4404.
10. (a) Zhou, H.; Wang, W.-H.; Fu, Y.; Xie, J.-H.; Shi, W.-J.;
Wang, L.-X.; Zhou, Q.-L. J. Org. Chem. 2003, 68, 1582;
(b) Fan, B.-M.; Xie, J.-H.; Li, S.; Tu, Y.-Q.; Zhou, Q.-L.
Adv. Synth. Catal. 2005, 347, 759; (c) Zhang, W.; Wang,
17. For selective examples of the application of bisoxazoline
ligands in asymmetric allylic oxidation, see: (a) Datta-
Gupta, A.; Singh, V. K. Tetrahedron Lett. 1996, 37,
2633; (b) Andrus, M. B.; Asgari, D.; Sclafani, J. A. J. Org.
Chem. 1997, 62, 9365; (c) Sekar, G.; DattaGupta, A.;
Singh, V. K. J. Org. Chem. 1998, 63, 2961; (d) Andrus, M.
B.; Asgari, D. Tetrahedron 2000, 56, 5775; (e) Andrus, M.
B.; Zhou, Z. J. Am. Chem. Soc. 2002, 124, 8806; (f)
Bayardon, J.; Sinou, D.; Guala, M.; Desimoni, G.
Tetrahedron: Asymmetry 2004, 15, 3195.
18. Kawasaki, K.; Katsuki, T. Tetrahedron 1997, 53, 6337.