Lanthanide-catalyzed asymmetric 1,3-dipolar cycloaddition of nitrones to alkenes using 3,3′-bis(2-oxazolyl)-1,1′-bi-2-naphthol (BINOL-Box) ligands

Article abstract of DOI:10.1016/S0022-328X(00)00024-3

New BINOL-derived ligands, 3,3′-bis(2-oxazolyl)-1,1′-bi-2-naphthols (BINOL-Box), bearing chiral bis-oxazoline at the 3,3′-carbons, were synthesized from commercially available 1,1′-bi-2-naphthol (BINOL). With the new ligands obtained, we found that asymmetric 1,3-dipolar cycloaddition reaction of N-benzylidenebenzylamine N-oxide (2) to 3-((E)-2-butenoyl)-1,3-oxazolidin-2-one (1) was catalyzed by BINOL-Box-scandium complexes to give isoxazolidine 3 in high yield with high diastereo- and enantioselectivity. For example, the reaction of 1 with 2 catalyzed by a 6 mol% (S,R)-7d and 5 mol% Sc(OTf)₃ complex proceeded to give the endo-3 as the major diastereomer with an endo:exo ratio of 97:3 and 87% ee of the endo-product in the presence of 4 ? molecular sieves. Interestingly, the absolute configuration of the major product was changed according to the kind of additive used.

Full text of DOI:10.1016/S0022-328X(00)00024-3

www.elsevier.nl/locate/jorganchem
Journal of Organometallic Chemistry 603 (2000) 6–12
Lanthanide-catalyzed asymmetric 1,3-dipolar cycloaddition of
nitrones to alkenes using 3,3%-bis(2-oxazolyl)-1,1%-bi-2-naphthol
(BINOL-Box) ligands
Hidehiko Kodama, Junji Ito, Kazushige Hori, Tetsuo Ohta *, Isao Furukawa
Department of Molecular Science and Technology, Faculty of Engineering, Doshisha Uni6ersity, Kyotanabe, Kyoto 610-0394, Japan
Received 18 November 1999; received in revised form 12 January 2000
Abstract
New BINOL-derived ligands, 3,3%-bis(2-oxazolyl)-1,1%-bi-2-naphthols (BINOL-Box), bearing chiral bis-oxazoline at the 3,3%-car-
bons, were synthesized from commercially available 1,1%-bi-2-naphthol (BINOL). With the new ligands obtained, we found that
asymmetric 1,3-dipolar cycloaddition reaction of N-benzylidenebenzylamine N-oxide (2) to 3-((E)-2-butenoyl)-1,3-oxazolidin-2-
one (1) was catalyzed by BINOL-Box–scandium complexes to give isoxazolidine 3 in high yield with high diastereo- and
enantioselectivity. For example, the reaction of 1 with 2 catalyzed by a 6 mol% (S,R)-7d and 5 mol% Sc(OTf)3 complex proceeded
to give the endo-3 as the major diastereomer with an endo:exo ratio of 97:3 and 87% ee of the endo-product in the presence of
,
4 A molecular sieves. Interestingly, the absolute configuration of the major product was changed according to the kind of additive
used. © 2000 Elsevier Science S.A. All rights reserved.
Keywords: 1,3-Dipolar; Lanthanide catalysis; Isoxazolidine; 3,3%-bis(2-oxazolyl)-1,1%-bi-2-naphthols
1. Introduction
bis[(R)-1-(1-naphthyl)ethyl]amine, was quite effective in
catalytic enantioselective 1,3-dipolar cycloaddition of
nitrones [2c]. The reaction proceeded smoothly at room
temperature (r.t.) in the presence of 20 mol% ytterbium
triflate. In this reaction, the axial chirality of BINOL
has been considered to be transmitted to the reaction
site through the bulky amine, which binds to BINOL
by a hydrogen bond, so in as much as the BINOL alone
could not induce asymmetry in the product effectively.
However, there was a problem, it was difficult to sepa-
rate them from this reaction system including (S)-1,1%-
bi-2-naphthol. In addition, recently, oxazoline ligands,
which are at present widely used for various kinds of
transition metal-catalyzed enantioselective reactions,
have been reported [6].
Considering these results, we designed 3,3%-bis(2-oxa-
zolyl)-1,1%-bi-2-naphthols (BINOL-Box) as chiral lig-
ands. The BINOL-Box ligands have chiral bis-oxazo-
line at the 3,3%-carbons of 1,1%-bi-2-naphthol through
the s-bond. Thus, a rigid asymmetric environment can
be formed around the two hydroxyl moieties, which
would work as coordinating groups to the metal center.
Furthermore, the chiral oxazoline parts are eas-
The 1,3-dipolar cycloaddition of nitrones to alkenes
is a useful and convenient method for the preparation
of isoxazolidine derivatives, which are converted into
amino alcohols [1], precursors to biologically important
alkaloids, b-lactams, etc. [2]. In 1994, catalytic enan-
tioselective 1,3-dipolar cycloaddition reactions by chiral
catalysts were reported by Seerden or Jørgensen et al.
In these reactions, the catalysts [3,4], which were Lewis
acids with chiral ligands, were quite sensitive to a small
amount of water. Previously, we reported that 1,3-dipo-
lar cycloaddition reaction of nitrones with alkenes was
catalyzed by phosphine–palladium complexes [5],
which can be used in the presence of water. But this
reaction needs to be stirred in chloroform under reflux
to obtain the product in good yield. Moreover,
Kobayashi et al. recently reported that a heterochiral
ytterbium complex, which was prepared from
Yb(OTf)3, (S)-1,1%-bi-2-naphthol, and N-methyl-
* Corresponding author. Fax: +81-774-656789.
E-mail address: tota@mail.doshisha.ac.jp (T. Ohta)
0022-328X/00/$ - see front matter © 2000 Elsevier Science S.A. All rights reserved.
PII: S0022-328X(00)00024-3

H. Kodama et al. / Journal of Organometallic Chemistry 603 (2000) 6–12
7
ily modified by changing the amino alcohol reagents in
2. Results and discussion
synthesis, which are conveniently obtained from natural
a-amino acids. The effect of axial chirality of 1,1%-bi-2-
naphthol and chirality at the carbon center of oxazoli-
nes is also easily examined for obtaining good
selectivities. We found that the scandium-catalyzed
asymmetric 1,3-dipolar cycloaddition of N-benzyl-
idenebenzylamine N-oxide (2) to 3-((E)-2-butenoyl)-1,3-
oxazolidin-2-one (1) [7] using these ligands proceeded in
high yield with high diastereo- and enantioselectivity.
2.1. Synthesis of 3,3%-bis(2-oxazolyl)-1,1%-bi-2-
naphthols (BINOL-Box)
Synthesis of the BINOL-Box ((S,S)-7a–c, (S,R)-7d–
f) was started from commercially available (S)-1,1%-bi-2-
naphthol ((S)-BINOL: (S)-4), as shown in Scheme 1.
The hydroxy groups of (S)-4 were protected as
methoxymethyl ethers, and the resulting compound was
subjected to ortholithiation [8], followed by carboxyla-
tion to give the corresponding 3,3%-dicarboxylic acid,
which was hydrolyzed by treatment with hydrogen
chloride in isopropyl alcohol–tetrahydrofuran to give
(S)-5 [9]. Then, the compound (S)-5 was exposed to
thionyl chloride, and the resulting acid chloride was
treated with chiral amino alcohols to give the corre-
sponding amides (6a–f). Moreover, amides 6a–f were
halogenated by the reaction with thionyl chloride, and
Scheme 1.

8
H. Kodama et al. / Journal of Organometallic Chemistry 603 (2000) 6–12
Table 1
Effect of Ln(OTf)3 in 1,3-dipolar cycloaddition reaction a
c
Entry
Ln(OTf)3
Yield (%) b
endo:exo
Ee (%) d
Configuration d,e
1
2
3
4
5
6
Sc(OTf)3
Y(OTf)3
La(OTf)3
Pr(OTf)3
Yb(OTf)3
Lu(OTf)3
86
86
77
81
88
87
92:8
97:3
95:5
96:4
94:6
95:5
83
7
9
10
5
7
R,S,R
S,R,S
S,R,S
S,R,S
S,R,S
S,R,S
a Reaction conditions: the catalyst Ln(OTf)3 (0.10 mmol) and (S,R)-7d (0.10 mmol) were stirred with powdered 4 A molecular sieves (125 mg)
,
in CH2Cl2 (1.5 ml) for 0.5 h, and the nitrone (0.50 mmol) and alkene (0.50 mmol) were added, and then the mixture was stirred for 20 h at room
temperature.
b Based on 3-((E)-2-butenoyl)-1,3-oxazolidin-2-one.
c Determined by 1H-NMR spectroscopy.
d Ee of the endo-product determined by HPLC analysis using a DAICEL CHIRALCEL OD-H column (eluent, 30:70 2–propanol-hexane; flow
rate, 0.3 ml min−1; detection, UV 220 nm).
e The order of 3,4,5-positions of isoxazolidine ring.
Table 2
Sc(OTf)3-catalyzed 1,3-dipolar cycloaddition reaction a
c
Entry
Ligand
Solvent
Yield (%) b
endo:exo
Ee (%) d
Configuration d,e
1
2
3
4
5
6
7
8
9
None
(S)-4
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
PhCH3
THF
86
81
80
86
82
89
86
75
43
99:1
98:2
97:3
92:8
97:3
97:3
93:7
99:1
84:16
30
31
83
67
8
6
7
72
S,R,S
R,S,R
R,S,R
R,S,R
S,R,S
S,R,S
S,R,S
S,R,S
(S,S)-7a
(S,R)-7d
(S,R)-7d
(S,R)-7d
(S,R)-7d
(S,R)-7e
(S,R)-7f
CH2Cl2
CH2Cl2
a Reaction conditions: the catalyst Sc(OTf)3 (0.10 mmol) and ligand (0.10 mmol) were stirred with powdered 4 A molecular sieves (125 mg) in
,
solvent (1.5 ml) for 0.5 h, and the nitrone (0.50 mmol) and alkene (0.50 mmol) were added, and then the mixture was stirred for 20 h at room
temperature.
b Based on 3-((E)-2-butenoyl)-1,3-oxazolidin-2-one.
c Determined by 1H-NMR spectroscopy.
d Ee of the endo-product determined by HPLC analysis using a DAICEL CHIRALCEL OD-H column (eluent, 30:70 2-propanol–hexane; flow
rate, 0.3 ml min−1; detection, UV 220 nm).
e The order of 3,4,5-positions of isoxazolidine ring.
the resulting compounds were cyclized in the presence
of potassium carbonate to give the BINOL-Box 7a–f in
good yields (38–65% from (S)-5).
(OTf)3)) was examined. As shown in Table 1, lanthanide
elements strongly influenced the enantioselectivities.
The reaction of 1 with 2 catalyzed by 20 mol% (S,R)-
7d–Sc(OTf)3 complexes proceeded to give the endo-3 as
the major diastereomer with an endo:exo ratio of 92:8
and 83% ee of the endo-product (Table 1, Entry 1). On
the other hand, when other lanthanide triflates were
used, the enantioselectivities diminished largely (Table
1, Entries 2–6). Probably, the results were dependent on
the enlargement of the ionic radii. Furthermore, the
absolute configuration of the major product in the
presence of Sc(OTf)3 was 3R,4S,5R, while an adduct
with absolute configuration of 3S,4R,5S was obtained
in the presence of other lanthanide triflates.
The structures of 7a–f were confirmed by elemental
and spectral analyses. Interestingly, signals of the phe-
1
nolic protons appeared at around 12 ppm in H-NMR.
This shows that these phenolic protons have a hydrogen
bond to the nitrogen atom, which is more basic than the
oxygen atom, and these hydrogen bonds could make a
rigid array of the oxazoline moieties.
2.2. Asymmetric Ln(OTf)3-catalyzed 1,3-dipolar
cycloaddition reaction by using BINOL-Box ligands
First, the effect of lanthanide triflates (scandium tri-
flate (Sc(OTf)3), yttrium triflate (Y(OTf)3), lanthanum
triflate (La(OTf)3), praseodymium triflate (Pr(OTf)3),
ytterbium triflate (Yb(OTf)3), and lutetium triflate (Lu-
Therefore, as models, we chose 3-((E)-2-butenoyl)-
1,3-oxazolidin-2-one (1), N-benzylidenebenzylamine N-
oxide (2) and scandium triflate Sc(OTf)3 as a metal
triflate. The reaction of 1 with 2 in the absence of a

H. Kodama et al. / Journal of Organometallic Chemistry 603 (2000) 6–12
9
ligand, only Sc(OTf)3, proceeded to give the endo-3 as
the major diastereomer with an endo:exo ratio of 99:1
in 86% yield (Table 2, Entry 1). The product 3 was
obtained from the reaction with a (S)-4–Sc(OTf)3 com-
plex in 81% yield with 30% ee of the endo isomer
(endo:exo=98:2) (Table 2, Entry 2). The application of
(S,S)-7a, which has same axial chirality as (S)-4, led to
similar yield, diastereoselectivity, and enantiomeric ex-
cess, but with the opposite configuration of the product
3 compared with the case of (S)-4. The use of (S,R)-7d,
which is the diastereomeric isomer of (S,S)-7a, resulted
in much higher enantioselectivity. From this result, it
was apparent that (S,R)-configurated ligands give bet-
ter results than (S,S)-configurated ligands. So, the ef-
fect of substituents on the oxazoline rings was
examined by use of (S,R)-configurated ligands, such as
(S,R)-7d, derived from (R)-phenylglicinol (phenyl),
(S,R)-7e, derived from (R)-valinol (isopropyl), and
(S,R)-7f, derived from (R)-phenylalaninol (benzyl)
(Table 2, Entries 4, 8, and 9). The reaction using
phenyl-substituted (S,R)-7d gave the best enantioselec-
tivity, while the products from the reaction with iso-
propyl- or benzyl-substituted (S,R)-7 had lower
enantiomeric excesses and the opposite configuration.
These results show that the chirality on the oxazoline
ring affects both the enantiomeric excesses and absolute
configuration of endo-3. The effect of solvents was
examined for the reaction with (S,R)-7d. The reaction
proceeded faster in dichloromethane or chloroform as a
solvent, and enantioselectivities were much higher than
that in toluene or tetrahydrofuran (Table 2, Entries
4–7), while in toluene or tetrahydrofuran enatioselec-
tivities were lower (Table 2, Entries 6 and 7).
Jørgensen et al. reported [10,11] that both conversion
and endo/exo selectivity of the Yb(OTf)3 and Sc(OTf)3
catalyzed reactions proved to be dependent on the
amount of molecular sieves added and, on the other
hand, in the Mg(II)-bisoxazoline catalyzed reaction, the
absolute stereochemistry of the endo-product was
,
changed in the presence and absence of 4 A molecular
,
sieves. So, the effects of 4 A molecular sieves, magne-
sium sulfate, kinds of alcohols, and water as an additive
,
were examined. In the absence of 4 A molecular sieves,
the reaction of 1 with 2 proceeded to give the endo-3 as
the major diastereomer with an endo:exo ratio of 72:23
and 38% ee of the endo-product, and the absolute
stereochemistry of endo-3 was assigned to be
(3S,4R,5S) (Table 3, Entry 1). Addition of 10 mg of 4
,
A molecular sieves to the reaction mixture leads to an
increase in the enantioselectivity (Table 3, Entry 2).
,
Moreover, addition of 50 mg or 125 mg of 4 A molec-
ular sieves causes increase in ee compared with the use
of 10 mg (Table 3, Entries 3 and 4), while the reaction
,
did not proceed in the presence of 250 mg of 4 A
molecular sieves because of the sluggish mixture. But
addition of magnesium sulfate leads to a decrease in ee
,
(Table 3, Entry 5). Interestingly, in the presence of 4 A
molecular sieves or magnesium sulfate, the absolute
stereochemistry of endo-3 changed to (3R,4S,5R) in
comparison with that from the reaction without an
additive.
The above results show that a small amount of water
in the reaction system may influence the selectivities of
the reaction. So the reaction was performed by adding
water (Table 3, Entries 6 and 7). Addition of a larger
amount of water resulted in better enantioselectivities
Table 3
Effect of additives in Sc(OTf)3-catalyzed 1,3-dipolar cycloaddition reaction a
c
Entry
Additive
None
Yield (%) b
endo:exo
Ee (%) d
Configuration d,e
1
2
3
4
5
6
7
8
9
60
95
86
86
83
56
20
50
72
79
84
64
77:23
89:11
94:6
38
55
66
83
37
58
88
58
6
S,R,S
R,S,R
R,S,R
R,S,R
R,S,R
S,R,S
S,R,S
S,R,S
R,S,R
R,S,R
R,S,R
S,R,S
,
4 A molecular sieves 10 mg
,
4 A molecular sieves 50 mg
,
4 A molecular sieves 125 mg
92:8
MgSO4 250 mg
H2O 20 mol%
87:13
78:22
80:20
79:21
87:13
86:14
91:9
H2O 40 mol%
MeOH 40 mol%
EtOH 40 mol%
i-PrOH 40 mol%
t-BuOH 40 mol%
HO(CH2)2OH 40 mol%
10
11
12
20
58
34
90:10
a Reaction conditions: the catalyst Sc(OTf)3 (0.10 mmol) and (S,R)-7d (0.10 mmol) were stirred with additive in CH2Cl2 (1.5 ml) for 0.5 h, and
the nitrone (0.50 mmol) and the alkene (0.50 mmol) were added, and then the mixture was stirred for 20 h at room temperature.
b Based on 3-((E)-2-butenoyl)-1,3-oxazolidin-2-one.
c Determined by 1H-NMR spectroscopy.
d Ee of the endo-product determined by HPLC analysis using a DAICEL CHIRALCEL OD-H column (eluent, 30:70 2-propanol–hexane; flow
rate, 0.3 ml min−1; detection, UV 220 nm).
e The order of 3,4,5-positions of isoxazolidine ring.

10
H. Kodama et al. / Journal of Organometallic Chemistry 603 (2000) 6–12
up to 88% ee less than 40 mol% of water as an additive,
while the use of more water made the reaction mixture
heterogeneous. Moreover, the effect of several alcohols,
as an additive, was examined. In the presence of
methanol, the reaction of 1 with 2 proceeded to give the
endo-3 as the major diastereomer with an endo:exo ratio
of 79:21 and 58% ee of the endo-product (Table 3, Entry
8). When bulkier alcohols, for example, ethanol, iso-
propyl alcohol, tert-butyl alcohol and ethylene glycol,
were used as an additive, the enantiomeric excesses and
the absolute configuration were changed according to
the bulkiness of the alcohol (Table 3, Entries 9–12).
That is, the use of the smallest protic additive, i.e. water,
resulted in endo-3 with 88% ee of the (3S,4R,5S)-isomer,
while the reaction with a bulkier additive gave endo-3
with a higher ratio of the (3R,4S,5R)-isomer. The reac-
tion with the bulkiest tert-BuOH yielded (3R,4S,5R)-3
with 58% ee. These results suggested that addition of
alcohols did not affect the catalytic activity, but caused
some change in the coordination sphere of the scan-
dium. According to Jørgensen et al. [11], in the octahe-
dral lanthanide intermediate, including bidentate ligand
and bidentate substrate, there are two free coordination
sites, and additives, nitrones, or solvents coordinate to
them. For the difference in coordinates to the two free
coordination sites, coordination modes in the lan-
thanide intermediate may be different and, therefore,
the absolute stereochemistry changed. So we thought
that in the case of the large ligand preferring a trans
coordination, the absolute stereochemistry of the endo-3
was 3R,4S,5R, and in the case of the small ligand
preferring a cis coordination, the absolute stereochem-
istry of the endo-3 was 3S,4R,5S.
4. Experimental
All experiments were carried out under an argon
atmosphere. Commercial reagents were used as received
without further purification. All solvents were dried
1
using standard procedures. The H-NMR (400 MHz)
spectra were recorded on a Jeol JNM A-400 spectrome-
ter with TMS as an internal standard. Optical rotations
were recorded with a Horiba SEPA-200 polarimeter.
High-performance liquid chromatography (HPLC) was
measured on a Hitachi L-7100. Chiral HPLC analysis
was performed on the same apparatus with a chiral
column, as described below. Preparation of (S)-2,2%-di-
hydroxy-1,1%-binaphthyl-3,3%-dicarboxylic acid ((S)-5)
was carried out according to the reported method [9].
4.1. Preparation of 3,3%-bis(2-oxazolyl)-1,1%-bi-2-
naphthols (BINOL-Box)
4.1.1. (S,S)-3,3%-Bis(4-phenyloxazol-2-yl)-1,1%-bi-2-
naphthol ((S,S)-7a)
A solution of (S)-2,2%-dihydroxy-1,1%-binaphthyl-3,3%-
dicarboxylic acid (S)-5 (1.87 g, 5.00 mmol) in thionyl
chloride (15 ml) was refluxed for 4.5 h. After removal of
the remaining thionyl chloride, the resulting acid chlo-
ride was dissolved in dichloromethane (20 ml). The
mixture was added to a solution of (S)-phenylglicinol
(1.51 g, 11.0 mmol) and triethylamine (0.81 g, 8.00
mmol) in dichloromethane (20 ml) at 0°C, and stirred
for 24 h at r.t. Then, the reaction mixture was cooled to
0°C. Thionyl chloride (4.4 ml) in dichloromethane (13
ml) was added to this mixture, and the resulting solution
was stirred for 24 h at r.t. Water was added to the
reaction mixture, the separated organic layer was
washed three times with water, and the aqueous layer
was extracted with dichloromethane. The combined
organic layers were dried over anhydrous sodium sul-
fate, and then concentrated under reduced pressure. To
the crude residue in acetonitrile (50 ml) were added the
distilled water (13 ml) and potassium carbonate (3.75 g,
27 mmol), and this mixture was refluxed for 24 h. After
removal of the solvent, the residue was partitioned
between dichloromethane and water. The organic layer
was washed with 1.0 M hydrochloric acid. The water
layer was extracted with dichloromethane. The com-
bined organic layers were dried over anhydrous sodium
sulfate and concentrated. The residue was chro-
matographed on silica gel (5:1 hexane–ethyl acetate) to
give (S,S)-3,3%-bis(4-phenyloxazol-2-yl)-1,1%-bi-2-naph-
thol ((S,S)-7a) as a yellow solid (1.30 g, 45% from
(S)-5): m.p. 173–175°C; MS m/z 576 (M+). [h]D23 +144
Moreover, the effect of the amount of catalyst was
also examined. The catalyst Sc(OTf)3 5 mol% and
,
(S,R)-7d 6 mol% was stirred with powdered 4 A molec-
ular sieves (125 mg) in CH2Cl2 (1.5 ml) for 0.5 h, and the
nitrone 2 (0.50 mmol) and the alkene 1 (0.50 mmol)
were added. After stirring for 48 h, the reaction pro-
ceeded to give the endo-3 as the major diastereomer with
an endo:exo ratio of 97:3 and 87% ee of the endo-
product.
3. Conclusions
In conclusion, asymmetric 1,3-dipolar cycloaddition
reaction of N-benzylidenebenzylamine N-oxide (2) to
3-((E)-2-butenoyl)-1,3-oxazolidin-2-one (1) catalyzed by
new BINOL-Box–scandium complexes has been devel-
oped. The reaction of 1 with 2 catalyzed by 6 mol%
1
,
(S,R)-7d and 5 mol% Sc(OTf)3 in the presence of 4 A
(c 1, CHCl3); H-NMR (CDCl3): l 4.34 (t, J=8.8 Hz,
molecular sieves proceeded to give 3 in 94% yield with
an endo:exo ratio of 97:3 and 87% ee of the endo-
product. We found that the choice of the additive and
the ligand was very important in this reaction.
2H), 4.90 (dd, J=8.8 and 9.6 Hz, 2H), 5.52 (dd, J=9.6
and 8.8 Hz, 2H), 7.20–7.34 (m, 16H), 7.90–7.92 (m,
2H), 8.50 (s, 2H), 12.22 (s, 2H, OH); IR (KBr): 3000,
1600, 1490, 1440, 1250, 1190, 1150, 1130, 1050, 930, 900,

H. Kodama et al. / Journal of Organometallic Chemistry 603 (2000) 6–12
11
700 cm−1; HRMS Found: m/z 576.2024 (M+). Anal.
4.1.6. (S,R)-3,3%-Bis(4-benzyloxazol-2-yl)-1,1%-bi-2-
naphthol ((S,R)-7f)
Calc. for C38H28N2O4: M+, 576.2049.
Yield 44% (from 5); m.p. 143–145°C; MS m/z 604
In a similar manner, compounds 7b–7f were pre-
pared from (S)-2,2%-dihydroxy-1,1%-binaphthyl-3,3%-di-
carboxylic acid (S)-5 and the corresponding amino
alcohols.
1
(M+). [h]2D3 −121 (c 1, CHCl3); H-NMR (CDCl3): l
2.76–2.81 (m, 2H, ArCH2), 3.06–3.12 (m, 2H, ArCH2),
4.17 (t, J=8.8 Hz, 2H), 4.47 (t, J=8.8 Hz, 2H),
4.61–4.69 (m, 2H), 7.17–7.30 (m, 16H), 7.86–7.88 (m,
2H), 8.41 (s, 2H), 12.13 (s, 2H, OH); IR (KBr): 2900,
1600, 1500, 1430, 1350, 1300, 1260, 1220, 1200, 1150,
1030, 950, 900, 800, 750, 700 cm−1; Found: C, 79.39;
H, 5.38; N, 4.34%. Anal. Calc. for C40H32N2O4: C,
79.45; H, 5.33; N, 4.63%.
4.1.2. (S,R)-3,3%-Bis(4-phenyloxazol-2-yl)-1,1%-bi-2-
naphthol ((S,R)-7d)
Yield 55% (from 5); m.p. 156–158°C; MS m/z 576
1
(M+). [h]2D3 −189 (c 1, CHCl3); H-NMR (CDCl3): l
4.33 (t, J=9.2 Hz, 2H), 4.87 (t, J=9.2 Hz, 2H), 5.49
(t, J=9.2 Hz, 2H), 7.23–7.33 (m, 16H), 7.89–7.91 (m,
2H), 8.50 (s, 2H), 12.16 (s, 2H, OH); IR (KBr): 2800,
1600, 1500, 1450, 1330, 1250, 1200, 1150, 1130, 950,
900, 800, 750, 700 cm−1; HRMS Found: m/z 576.2054
(M+). Anal. Calc. for C38H28N2O4: M+, 576.2049.
4.2. A typical procedure for lanthanide-catalyzed
asymmetric 1,3-dipolar cycloaddition reaction
The catalyst Sc(OTf)3 (0.10 mmol) and (S,S)-7d (0.10
,
mmol) were stirred with powdered 4 A molecular sieves
(125 mg) in solvent (1.5 ml) for 0.5 h. Compounds 1
(0.50 mmol) and 2 (0.50 mmol) were added, and then
the mixture was stirred for 20 h. Distilled water was
then added to quench the reaction, and insoluble mate-
rials were filtered. The reaction mixture was extracted
with dichloromethane, and dried on anhydrous sodium
sulfate. The organic layer was evaporated to dryness
and the residue was analyzed. The reaction yield and
4.1.3. (S,S)-3,3%-Bis(4-isopropyloxazol-2-yl)-1,1%-bi-2-
naphthol ((S,S)-7b)
Yield 38% (from 5); m.p. 210–212°C; MS m/z 508
1
(M+). [h]2D3 +66 (c 1, CHCl3); H-NMR (CDCl3): l
0.93 (d, J=6.8 Hz, 6H), 0.99 (d, J=6.8 Hz, 6H),
1.74–1.83 (m, 2H, CH3CHCH3), 4.41–4.17 (m, 4H),
4.54 (t, J=8.0 Hz, 2H), 7.14–7.32 (m, 6H), 7.88–7.90
(m, 2H), 8.42 (s, 2H), 12.43 (s, 2H, OH); IR (KBr):
3000, 1600, 1500, 1440, 1370, 1300, 1250, 1200, 1150,
1135, 1060, 950, 900, 750, 700 cm−1; HRMS Found:
m/z 508.2377 (M+). Anal. Calc. for C32H32N2O4: M+,
508.2362.
1
endo:exo ratio were determined by H-NMR analysis,
and the enantiomeric excess of the endo adduct was
determined by HPLC analysis (DAICEL CHIRALCEL
OD-H column (eluent, 30:70 2-propanol–hexane; flow
rate, 0.3 ml min−1; detection, UV 220 nm)). The abso-
lute configuration was assigned by comparison of the
optical rotation with that of the literature [3a].
4.1.4. (S,R)-3,3%-Bis(4-isopropyloxazol-2-yl)-1,1%-bi-2-
naphthol ((S,R)-7e)
Yield 55% (from 5); m.p. 254–256°C; MS m/z 508
(M+). [h]2D3 −153 (c 1, CHCl3); H-NMR (CDCl3): l
1
Acknowledgements
0.93 (d, J=6.8 Hz, 6H), 0.99 (d, J=6.8 Hz, 6H),
1.70–1.82 (m, 2H, CH3CHCH3), 4.09–4.19 (m, 4H),
4.53 (t, J=8.0 Hz, 2H), 7.19–7.31 (m, 6H), 7.87–7.90
(m, 2H), 8.42 (s, 2H), 12.35 (s, 2H, OH); IR (KBr):
3000, 1630, 1500, 1440, 1340, 1300, 1260, 1220, 1200,
1150, 1135, 1060, 950, 900, 800, 750, 700 cm−1; HRMS
Found: m/z 508.2368 (M+). Anal. Calc. for
C32H32N2O4: M+, 508.2362.
We thank Dr Takayuki Yamashita for helpful discus-
sions during the course of this work. We also thank
undergraduate project students Takashi Okamoto and
Yukiko Ogura. This work was partially supported by
Doshisha University’s Research Promotion Fund and a
grant to RCAST at Doshisha University from the
Ministry of Education, Japan.
4.1.5. (S,S)-3,3%-Bis(4-benzyloxazol-2-yl)-1,1%-bi-2-
naphthol ((S,S)-7c)
References
Yield 65% (from 5); m.p. 108–110°C; MS m/z 604
1
(M+). [h]2D3 +70 (c 1, CHCl3); H-NMR (CDCl3): l
[1] (a) J.J. Tufariello, in: A. Padwa, (Ed.), 1,3-Dipolar Cycloaddi-
tion Chemistry, vol. 2, Wiley, New York, 1984, p. 83. (b) K.B.G.
Torssell, Nitrile Oxides, Nitrones and Nitronates in Organic
Synthesis, VCH, New York, 1988. (c) K.V. Gothelf, K.A.
Jørgensen, Chem. Rev. 98 (1998) 863.
[2] (a) S. Kobayashi, H. Ishitani, J. Am. Chem. Soc. 116 (1994)
4083. (b) S. Kobayashi, H. Ishitani, I. Hachiya, M. Araki,
Tetrahedron 50 (1994) 11623. (c) S. Kobayashi, M. Kawamura,
J. Am. Chem. Soc. 120 (1998) 5840.
2.67–2.72 (m, 2H, ArCH2), 2.94–2.99 (m, 2H, ArCH2),
4.04 (t, J=8.4 Hz, 2H), 4.33 (t, J=8.4 Hz, 2H),
4.49–4.57 (m, 2H), 7.07–7.21 (m, 16H), 7.76–7.79 (m,
2H), 8.31 (s, 2H), 12.08 (s, 2H, OH); IR (KBr): 2900,
1630, 1490, 1440, 1350, 1200, 1050, 950, 790, 750, 700
cm−1; Found: C, 79.17; H, 5.24; N, 4.33%. Anal. Calc.
for C40H32N2O4: C, 79.45; H, 5.33; N, 4.63%.

12
H. Kodama et al. / Journal of Organometallic Chemistry 603 (2000) 6–12
[3] (a) K.V. Gothelf, K.A. Jørgensen, J. Org. Chem. 59 (1994) 5687.
Zhang, T. Kida, Y. Nakatsuji, I. Ikeda, Tetrahedron Lett. 39
(1998) 4343. (d) R. Pretot, A. Pfaltz, Angew. Chem. Int. Ed.
Engl. 37 (1998) 323 and refs. therein.
(b) K.V. Gothelf, I. Thomsen, K.A. Jfrgensen, J. Am. Chem.
Soc. 118 (1996) 59. (c) K.V. Gothelf, R.G. Hazell, K.A.
Jørgensen, J. Org. Chem. 61 (1996) 346.
[7] D.A. Evans, K.T. Chapman, J. Bisaha, J. Am. Chem. Soc. 110
(1988).
[8] P.J. Cox, W. Wang, V. Snieckus, Tetrahedron Lett. 33 (1992)
2253.
[9] H. Kitajima, K. Ito, Y. Aoki, T. Katsuki, Bull. Chem. Soc. Jpn.
70 (1997) 207.
[10] A.I. Sanchez-Blanco, K.V. Gothelf, K.A. Jørgensen, Tetrahe-
dron Lett. 38 (1997) 7923.
[4] (a) J.-P.G. Seerden, A.W.A. Scholte op Reimer, H.W. Scheeren,
Tetrahedron Lett. 35 (1994) 4419. (b) J.-P.G. Seerden, M.M.M.
Kuypers, H.W. Scheeren, Tetrahedron: Asymmetry 6 (1995)
1441.
[5] K. Hori, H. Kodama, T. Ohta, I. Furukawa, Tetrahedron Lett.
37 (1996) 5947.
[6] (a) K. Nordstro¨m, E. Macedo, C. Moberg, J. Org. Chem. 62
(1997) 1604. (b) H. Steinhagen, M. Reggelin, G. Helmchen,
Angew. Chem. Int. Ed. Engl. 36 (1997) 2108. (c) Y. Imai, W.
[11] K.V. Gothelf, R.G. Hazell, K.A. Jørgensen, J. Org. Chem. 63
(1998) 5483.
.
.