Asymmetric cycloaddition reactions of diazoesters with 2-alkenoic acid derivatives catalyzed by binaphthyldiimine-Ni(II) complexes

Article abstract of DOI:10.1021/jo201061f

The catalytic activity of chiral binaphthyldiimine (BINIM)-Ni(II) complexes for asymmetric enantioselective diazoalkane cycloadditions of ethyl diazoacetate with 3-acryloyl-2-oxazolidinone and 2-(2-alkenoyl)-3-pyrazolidinone derivatives was evaluated. The

Full text of DOI:10.1021/jo201061f

ARTICLE
pubs.acs.org/joc
Asymmetric Cycloaddition Reactions of Diazoesters with 2-Alkenoic
Acid Derivatives Catalyzed by BinaphthyldiimineꢀNi(II) complexes
Hiroyuki Suga,*,† Yasuhisa Furihata,† Atsushi Sakamoto,† Kennosuke Itoh,† Yukihisa Okumura,†
Teruko Tsuchida,† Akikazu Kakehi,† and Toshihide Baba‡
†Department of Chemistry and Material Engineering, Faculty of Engineering, Shinshu University, Wakasato, Nagano 380-8553, Japan
‡Department of Environmental Chemistry & Engineering, Interdisciplinary Graduate School of Science & Engineering,
Tokyo Institute of Technology, G1-14, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan
S Supporting Information
b
ABSTRACT: The catalytic activity of chiral binaphthyldiimine
(BINIM)ꢀNi(II) complexes for asymmetric enantioselective dia-
zoalkane cycloadditions of ethyl diazoacetate with 3-acryloyl-
2-oxazolidinone and 2-(2-alkenoyl)-3-pyrazolidinone derivatives was
evaluated. The cycloadditions of 3-acryloyl-2-oxazolidinone and its
5,5-dimethyl derivative, in the presence of the BINIMꢀNi(II)
complex (10 mol %; prepared from (R)-BINIM-4Ph-2QN (ligand
C) and Ni(ClO4)2 6H2O) afforded 2-pyrazolines having a methine
3
carbon substituted with an oxazolidinonyl group in moderate ratios
(70:30 to 72:28), along with high enantioselectivities (90ꢀ92% ee) via 1,3-proton migration. On the basis of the investigations on
the counteranions of the Ni(II) complex, the N-substituent of pyrazolidinone, and reaction temperatures, the optimal
enantioselectivity (97% ee) and ratio (85:15) of 2-pyrazoline were obtained for the reaction of 2-acryloyl-1-benzyl-5,5-dimethyl-
3-pyrazolidinone in the presence of (R)-BINIM-4Ph-2QNꢀNi(II) ((R)-C/Ni(II)) complex prepared using Ni(BF4)2 6H2O. In
3
the cases of 1-benzyl-2-crotonoyl-5,5-dimethyl-3-pyrazolidinone, 1-benzyl-2-(2-butenoyl)-5,5-dimethyl-3-pyrazolidinone, and
1-benzyl-5,5-dimethyl-2-(3-ethoxycarbonyl)propenoyl-3-pyrazolidinone, the use of the (R)-BINIM-2QNꢀNi(II) ((R)-A/Ni(II))
complex gave good to high enantioselectivities (85ꢀ93% ee) with the sole formation of the 2-pyrazoline having a methine carbon
substituted with a pyrazolidinonyl group. Relatively good enantioselectivity (77% ee) was observed for the reaction between
2-acryloyl-5,5-dimethyl-1-naphthylmethyl-3-pyrazolidinone and an R-substituted diazo ester, ethyl 2-diazo-3-phenylpropanoate,
which has yet to be employed as a diazo substrate in asymmetric cycloaddition reactions catalyzed by a chiral Lewis acid.
’ INTRODUCTION
The 1,3-dipolar cycloaddition reactions between diazoalkanes
and alkenes form relatively unstable 1-pyrazolines as the initial
cycloadducts that either spontaneously release nitrogen to give
the corresponding cyclopropanes, or undergo a 1,3-proton migra-
tion to give the thermodynamically more stable 2-pyrazoline deriv-
atives. Diazo substrates such as trimethylsilyldiazomethane and
diazoacetates undergo enantioselective diazoalkane cycloadditions
in the presence of a chiral Lewis acid to give the 2-pyrazolines with
high levels of asymmetric induction. In the case of trimethylsilyldia-
zomethane, Kanemasa reported the first successful examples of the
enantioselective cycloaddition reactions using 3-(2-alkenoyl)-2-ox-
azolidinones and R,R-DBFOX/Phꢀtransition metal aqua com-
plexes as the chiral Lewis acids.5 For the diazoacetates, Maruoka
reported on the highly enantioselective 1,3-dipolar cycloadditions
using monodentate R-substituted acroleins and a chiral titanium
BINOLate.6a Furthermore, Sibi described the highly enantioselec-
tive synthesis of 2-pyrazolines via Mg(II)-catalyzed cycloadditions
of diazoesters in the formation of β-substituted, R-substituted, and
R,β-disubstituted R,β-unsaturated pyrazolidinone imides.6b
Catalytic asymmetric 1,3-dipolar cycloadditions have been re-
cognized as one of the most efficient reactions for the construction
of five-membered heterocyclic compounds containing several
stereogenic centers.1 Accordingly, during the past two decades,
numerous enantioselective 1,3-dipolar cycloadditions catalyzed by
chiral Lewis acids have been developed, which include successful
examples of isolable 1,3-dipoles such as nitrones,1cꢀe,2ꢀ4 trimethyl-
silyldiazomethane,5 diazoacetates,6 and azomethine imines,7,8 and
also unstable 1,3-dipoles such as nitrile oxides,9 nitrile imines,10 and
carbonyl ylides.11 Organocatalytic asymmetric cycloadditions have
also been reported for isolable 1,3-dipoles such as nitrones12 and
azomethine imines.13 Although numerous chiral Lewis acids have
been developed as efficient catalysts in the enantioselective 1,
3-dipolar cycloadditions, a chiral Lewis acid for the cycloaddition
of 1,3-dipoles possessing strong basic or unstable properties has
remained elusive. Recently, we have reported on the use of chiral
Ni(II) complexes of binaphthyldiimine (BINIM) as highly
effective catalysts in providing high levels of asymmetric induc-
tion for the cycloadditions of nitrones,3i azomethine imines,7a
nitrile oxides,9e and carbonyl ylides.11d,e
Received: May 26, 2011
Published: July 28, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/jo201061f J. Org. Chem. 2011, 76, 7377–7387
|

The Journal of Organic Chemistry
ARTICLE
Figure 1. Reaction of ethyl diazoacetate (1a) with 3-acryloyl-2-oxazolidinone (2a) in CDCl3.
out between ethyl diazoacetate (1a) and 3-acryloyl-2-oxazolidi-
none (2a) in the absence of any Lewis acids. The reaction was
carried out in CDCl3 at rt for 36 h in a NMR tube. As shown in
Figure 1b, the 1H NMR spectrum of the mixture exhibited two
sets of methine protons (5.52 (ddd), 6.79 (ddd), and 5.19 (dt),
6.37 (dt) ppm) in a ratio of 70:30, which presumably correspond
to those of trans- and cis-1-pyrazolines. Treatment of the mixture
by silica gel chromatography facilitated the smooth 1,3-proton
migration to give 2-pyrazolines that exhibit NH protons (6.87
Figure 2. (R)-BINIM-4X-2QN ligands.
1
and 6.09 ppm) by H NMR in a ratio of 75:25, as shown in
In this paper, we describe our investigations to evaluate the effec-
tiveness and scope of BINIMꢀNi(II) as chiral Lewis acid catalysts for
the enantioselective diazoalkane cycloaddition reactions of diazoace-
tates and R-substituted diazo ester with 3-(2-alkenoyl)-2-oxazolidi-
nones and/or 2-(2-alkenoyl)-3-pyrazolidinone derivatives. Several
Ni(II)-complexes of chiral N,N0-bis(2-quinolylmethylene)-1,10-
binaphthyl-2,20-diamine (BINIM-2QN) derivatives (Figure 2,
ligands AꢀE) were employed for the asymmetric cycloadditions
of ethyl diazoacetate with 3-alkenoyl-2-oxazolidinone and several
2-(2-alkenoyl)-3-pyrazolidinone derivatives to give the products
with good to high enantioselectivities (up to 97% ee). Our
investigations revealed that, depending on the diopolarophile,
the enantioselectivities are affected by the counteranion of the
Ni(II)-complex and by the 4-substituent of the quinoline ring on
BINIM-2QN. Relatively good enantioselectivities (up to 77% ee)
were obtained for the chiral BINIMꢀNi(II) catalyzed reactions
between 2-acryloyl-3-pyrazolidinone derivatives and an R-sub-
stituted diazo ester, ethyl 2-diazo-3-phenylpropanoate, which has
yet to be employed as a diazo substrate for asymmetric cycload-
dition reactions catalyzed by a chiral Lewis acid.
Figure 1c. The reaction in CH2Cl2 under similar conditions also
gave the 2-pyrazolines in a ratio of 76:24 with a purified yield
of 98%. The major product was determined to be 2-pyrazoline
3aa, possessing a methine carbon substituted with an oxazolidi-
nonyl group that causes the chemical shift of the methine protons
(5.25 vs 4.39ꢀ4.56 ppm).
The chiral (R)-BINIM-2QNꢀNi(II) ((R)-A/Ni(II)) complex
was prepared by mixing (R)-BINIM-2QN (Figure 2, ligand A) and
Ni(ClO4)2 6H2O in CH2Cl2 at rt for 6 h. A mixture of 1a with
3
2a, in the presence of the (R)-A/Ni(II) complex (10 mol %), was
stirred in CH2Cl2 at rt for 24 h to give the cycloaddition products
after purification by silica gel chromatography (Scheme 1). Similar
to that of the uncatalyzed reaction, 2-pyrazoline 3aa was obtained as
the major product along with 2-pyrazoline 4aa (3aa/4aa = 63:37) in
80% total yield (Table 1, entry 1); the enantiomeric excesses were
determined to be 70% ee for 3aa and 37% ee for 4aa using HPLC
analysis (Daicel Chiralpak AD-H). To improve the 3aa/4aa ratio of
the 2-pyrazolines and the enantioselectivities, the reactions were
carried out using different solvents (Table 1, entries 3ꢀ8), and a
different substituent at the 4-position at a quinoline ring of the
BINIM-4X-2QN ligands (ligands BꢀE, Table 1, entries 2, 3, 9, and
10). The 3aa/4aa ratio was improved using solvents such as
chlorobenzene and acetonitrile, whereas the best enantioselectivity
was obtained using CH2Cl2 as the solvent (entry 3). Substitution at
the 4-position resulted in slightly higher 3aa/4aa ratios, in which
’ RESULTS AND DISCUSSION
Cycloaddition Reactions of Ethyl Diazoacetate with Ac-
rylic Acid Derivatives. Initially, the cycloaddition was carried
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The Journal of Organic Chemistry
Scheme 1. Reaction of Ethyl Diazoacetate (1a) with 3-Acryloyl-2-oxazolidinone (2a) Catalyzed by BINIMꢀNi(II) Complexes
ARTICLE
Table 1. Reaction of Ethyl Diazoacetate (1a) with 3-Acryloyl-
2-oxazolidinone (2a) Catalyzed by BINIMꢀNi(II)
Complexesa
substituent with a methyl group resulted in a significantly lower
enantioselectivity of the major 2-pyrazoline (entry 3). In the case
of 1-naphthylmethyl 5b (R = 1-naphthyl, entry 2), the enantios-
electivity (95% ee) of the major 2-pyrazoline was slightly higher,
whereas the 2-pyrazoline ratio was similar to that of phenyl-
substituted 5a. Furthermore, the effect of temperature was in-
vestigated using pyrazolidinone 5a and pyrazolidinone 5b as the
dipolarophiles (entries 1, 2, and 4ꢀ7). For pyrazolidinone 5a,
higher enantioselectivities of the major 2-pyrazoline were obtained
at low reaction temperatures (entries 1 and 4ꢀ6); 97% ee was
achieved using a reaction temperature of ꢀ45 °C (entry 6). In
contrast, for pyrazolidinone 5b, lower enantioselectivity was obtained
at ꢀ45 °C (entry 7), albeit at a slightly higher ratio of 2-pyrazoline.
Cycloaddition Reactions between Ethyl Diazoacetate and
Other 2-(2-Alkenoyl)-3-pyrazolidinoneDerivatives. To further
investigate the applicability of our methodology, the cycloaddition
reactions were carried out using other 2-(2-alkenoyl)-3-pyrazoli-
dinone derivatives under various conditions (Scheme 4, Table 4).
First, to investigate the effect of substitution at the 4-position,
different BIMINꢀNi(II) complexes (10 mol %) were prepared
with a series of (R)-BINIM-4X-2QN ligands (ligands AꢀC) with
X
time yield
% eec
(%) 3aa:4aab 3aa 4aa
entry
solvent
(ligand)
(h)
1
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
benzene
C6H5Cl
THF
H (A)
24
24
24
25
51
44
46
51
80
86
93
68
73
41
55
66
77
80
63:37
80:20
72:28
65:35
84:16
92:8
70 37
69 25
90 47
44 23
12 10
18 11
2
Me (B)
Ph (C)
Ph (C)
Ph (C)
Ph (C)
Ph (C)
Ph (C)
3
4
5
6
7
70:30
90:10
71:29
78:22
30
11
4
1
8
MeCN
CH2Cl2
CH2Cl2
9
3,5-xylyl (D) 24
70 45
58 28
10
3,5-(CF3)2-
24
C6H3 (E)
a Reactions were carried out on a 0.5-mmol scale (1a/2a = 1.5:1) at rt in
the presence of the Ni(II) complex (10 mol %), which was prepared by
mixing the corresponding BINIM ligand, Ni(ClO4)2 6H2O, and MS
3
4 Å for 6 h at rt. b Determined by 1H NMR analysis. c Determined by HPLC
analysis (Daicel Chiralpak AD-H).
Ni(BF4)2 6H2O. Using these catalysts, cycloaddition reactions
3
between ethyl diazoacetate (1a) and 1-benzyl-2-crotonoyl-5,
5-dimethyl-3-pyrazolidinone (8a) were carried out in CH2Cl2 at
rt to yield only 2-pyrazoline 9aa bearing an ethoxycarbonyl group
at the 3-position in high yield and enantioselectivity (entries 1ꢀ3).
Among the three ligands (ligands AꢀC), the one without any
substituents at the 4-position on the quinoline ring (ligand A, entry3)
exhibited enantioselectivity (93% ee) slightly higher than those of
the 4-Me or 4-Ph derivatives.
The reaction of 1-benzyl-5,5-dimethyl-2-(2-pentenoyl)-3-pyr-
azolidinone (10a) under similar conditions gave 2-pyrazoline
11aa in a high yield with good enantioselectivity (entry 4).
For the reactions of 1-benzyl-5,5-dimethyl-2-(3-ethoxycarbonyl)-
propenoyl-3-pyrazolidinone (12a), slightly higher enantioselec-
tivity was obtained using the Ni complex of (R)-BINIM-4Ph-
a phenyl substituent (X = Ph, ligand C) exhibited the highest
enantioselectivity (90% ee) of 3aa (entry 3).
Next, dimethyl-substituted oxazolidinone and pyrazolidinone
derivatives as dipolarophiles were employed to investigate their
effects on the 2-pyrazoline ratio and enantioselectivity (Scheme 2
and Table 2). In the case of 4,4-dimethyloxazolidione 2b, the
cycloaddition under similar conditions resulted in a high 2-pyr-
azoline 3ab/4ab ratio of 85:15 but with a significantly lower
enantioselectivity of 3ab (entry 2). In contrast, the reaction of 5,
5-dimethyl-substituted 2c showed slightly higher enantioselectivity of
3ac with a comparable ratio of the 2-pyrazolines to that of 2a
(entry 3). The cycloaddition of pyrazolidinone 5a resulted in
both higher enantioselectivity and higher ratio of the 2-pyrazo-
lines (entry 4). It is interesting to note that a shorter reaction time
was required when pyrazolidinone 5a was used as a dipolarophile.
Among the several counteranions for the Ni(II) complex (entries
2QN (X = Ph, ligand C) prepared from Ni(ClO4)2 6H2O (entry
3
6) compared to that from Ni(BF4)2 6H2O (entry 5). For the
3
reactions of 12a catalyzed by Ni complexes prepared from Ni-
(ClO4)2 6H2O, the ligand without any substituents on the 4-posi-
3
ꢀ
4, 6, and 7), the use of BF4 exhibited the highest 2-pyrazoline
tion(X=H, ligandA) showed an enantioselectivity (85% ee, entry 8)
higher than those with the 4-Ph and 4-Me substituents (entries 6 and
7, respectively). These studies show that our asymmetric BINIMꢀ
Ni(II)-catalyzed cycloaddition reactions of ethyl diazoacetate can be
successfully applied to other 2-(2-alkenoyl)-3-pyrazolidinone deriva-
tives with good to excellent enantioselectivities (85ꢀ93% ee).
ratio (85:15), and with a high enantioselectivity (93% ee) of 6aa.
Next, the influence on enantioselectivity was investigated using
pyrazolidinone with various substitutents (CH2R) on the 1-posi-
tion (Scheme 3 and Table 3) as the dipolarophiles. In accordance
to the chiral relay concept,3h,9a,14 replacement of the phenyl
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ARTICLE
Scheme 2. Reactions ofEthyl Diazoacetate (1a) withAcryloyloxazolidinones2aꢀc and Pyrazolidinone5aCatalyzed by(R)-BINIM-
4Ph-2QNꢀNi(II) ((R)-C/Ni(II)) Complex
Table 2. Reactions of Ethyl Diazoacetate (1a) with Acryloyloxazolidinones 2aꢀc and Pyrazolidinone 5a Catalyzed by ( R)-C/Ni(II)
Complexa
% eec
entry
dipolarophile
Ni salt
time (h)
products
yield (%)
3:4 (6:7)b
3 (6)
4 (7)
1
2
3
4
5e
6
7
2a
2b
2c
5a
5a
5a
5a
Ni(ClO4)2
Ni(ClO4)2
Ni(ClO4)2
Ni(ClO4)2
Ni(ClO4)2
Ni(OTf)2
Ni(BF4)2
24
54
24
5
3aa, 4aa
3ab, 4ab
3ac, 4ac
6aa, 7aa
6aa, 7aa
6aa, 7aa
6aa, 7aa
93
91
77
84
80
80
83
72:28
85:15
70:30
83:17
73:27
82:18
85:15
90
25
92
93
90
63
93
47
28
70
NDd
NDd
NDd
NDd
5
7
5
a Reactions were carried out on a 0.5-mmol scale (1a/2aꢀc, or 5a = 1.5:1) at rt in CH2Cl2 in the presence of the Ni(II) complex (10 mol %), which was
prepared by mixing the corresponding (R)-BINIM-4Ph-2QN (ligand C), Nisalt 6H2O, and MS 4 Å in CH2Cl2 for 6 h at rt. b Determined by 1H NMR analysis.
3
c Determined by HPLC analysis (Daicel Chiralpak AD-H). Although the absolute configuration of 2-pyrazoline 6aa could only be assigned to be 5Sbased on the
optical rotation previously reported,6b the other major products probably have the same configurations. d Not determined. e Chloroform was used as the solvent.
Scheme 3. Reactions of Ethyl Diazoacetate (1a) with 2-Acryloyl-3-pyrazolidinones 5a, 5b, and 5c Catalyzed by (R)-C/Ni(II)
Complex
Cycloaddition Reactions of r-Substituted Diazo Esters
with 2-Acryloyl-3-pyrazolidinone. To examine the applicability
of our methodology toward other diazo esters, we carried out the
(R)-BINIMꢀNi(II)-catalyzed cycloaddition reactions of 2-acry-
loyl-3-pyrazolidinone 5a using various R-substituted diazo esters,
which have yet to be reported as diazo substrates for asymmetric
cycloaddition reactions catalyzed by chiral Lewis acids. Initially,
reactions were carried out in CH2Cl2 using ethyl diazophenylace-
tate (1b) as the diazo substrate, and catalyzed by (R)-C/Ni(II)
14 (33% yield) and olefin 15 (38% yield). In contrast, the
Ni(BF4)2 6H2O-derived complex afforded 2-pyrazoline 7ba in a
3
higher yield (40% yield) but with much lower enantioselectivity
(13% ee), along with cyclopropane 14 (40% yield) and olefin
15 (11% yield). Attempts to improve the yield of 2-pyrazoline 7ba,
which included different reaction temperatures (rt, ꢀ20 °C,
or ꢀ40 °C) and quenching the reaction with silica gel,
were unsuccessful. It is important to note that, for these reac-
tions, the ratio among products 7ba/14/15 was somewhat
irreproducible.
complexes that were prepared using either Ni(ClO4)2 6H2O or
3
Ni(BF4)2 6H2O as the Ni(II) salts (Scheme 5). Using the
The formation of cyclopropane 14 and alkene 15 can be
attributed to the biradical generated via elimination of nitro-
gen from the 1-pyrazoline. In the case of diazo substrate 1b
3
complex derived from Ni(ClO4)2 6H2O, the cycloaddition at
0 °C afforded 7ba (15% yield, 70% ee), along with cyclopropane
3
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The Journal of Organic Chemistry
ARTICLE
Table 3. Reactions of Ethyl Diazoacetate (1a) with 2-Acryloyl-3-pyrazolidinones 5a, 5b, and 5c Catalyzed by (R)-C/Ni(II)
Complexa
entry
pyrazolidinone (R)
temp (°C)
time (h)
product
yield (%)
6a:7ab
%eec (6a)
1
2
3
4
5
6
7
5a (Ph)
rt
5
6aa, 7aa
6ab, 7ab
6ac, 7ac
6aa, 7aa
6aa, 7aa
6aa, 7aa
6ab, 7ab
83
85
68
89
89
87
78
85:15
84:16
79:21
88:12
87:13
85:15
89:11
93
95
8
5b (1-naphthyl)
5c (Me)
rt
1
rt
48
5
5a (Ph)
0
95
94
97
81
5a (Ph)
ꢀ20
ꢀ45
ꢀ45
12
24
18
5a (Ph)
5b (1-naphthyl)
a Reactions were carried out on a 0.5-mmol scale (1a/2aꢀ2c, or 5a = 1.5:1) in CH2Cl2 in the presence of the Ni(II) complex (10 mol %), which was
prepared by mixing the corresponding (R)-BINIM-4Ph-2QN (ligand C), Ni(BF4)2 6H2O, and MS 4 Å in CH2Cl2 for 6 h at rt. b Determined by 1H
3
c
NMR analysis. Determined by HPLC analysis (Daicel Chiralpak AD-H). Although the absolute configuration of 2-pyrazoline 6aa could only be
assigned to be 5S based on the optical rotation previously reported,6b the other major products were also assigned similar to 6aa.
Scheme 4. Reactions of Ethyl Diazoacetate (1a) with 2-(2-Alkenoyl)-3-pyrazolidinones 8a, 10a, and 12a Catalyzed by (R)-
BINIMꢀNi(II) Complexes
reaction temperature to ꢀ40 °C (entry 2, 75% ee). Varying the
Table 4. Reactions of Ethyl Diazoacetate (1a) with
X-substituents of the (R)-BINIM-4X-2QN ligands (ligands BꢀD)
2-(2-Alkenoyl)-3-pyrazolidinones 8a, 10a, and 12a Catalyzed
by (R)-BINIMꢀNi(II) Complexesa
or the counteranion of the Ni(II) catalyst did not improve the
enantioselectivity (entries 3ꢀ5). Although a bulky ester substituent
entry
R
counter anion X (ligand) time (h) yield (%) %eeb
on the diazo substrate (R = t-Bu, 17c) decreased both yield and
enantioselectivity (entry 8), a bulky 1-naphthylmethyl substituent
on the pyrazolidinone dipolarophiles slightly improved the enan-
tioselectivity to 77% ee (entries 6 and 7).
ꢀ
1
2
3
4
5
6
7
8
Me
BF4ꢀ
BF4ꢀ
BF4ꢀ
BF4ꢀ
BF4
Ph (C)
Me (B)
H (A)
86
96
96
96
36
36
48
36
87
97
94
88
91
92
94
92
91
92
93
86
77
79
82
85
Me
Me
Selective Conversion of 2-Pyrazoline 9aa to the Corre-
sponding Alcohol. For some demonstration of how the final
products can be processed, selective conversion of the pyrazolidi-
none moiety of 2-pyrazoline 9aa to the corresponding alcohol was
investigated. 2-Pyrazoline 9aa was treated with NaBH4 (4 equiv)
in THF at ꢀ40 °C for 24 h to give the desired alcohol 20 in 69%
yield without reduction of an ethyl ester moiety. The enantiomeric
excess (96% ee) of 9aa could be also maintained to be 96% ee by
this reduction process (Scheme 7).
Proposed Mechanism for Asymmetric Induction. The high
enantioselectvity of the cycloaddition reactions can be ex-
plained as the Si-face approach of the diazo esters toward the
hexa-coordinated Ni(II) complex, which has been suggested
for BINIMꢀNi(II)-catalyzed azomethine imine7a and nitrile
oxide9e cycloaddition reactions, by means of molecular modeling
program using PM3 calculations (Figure 3).15 In the proposed
mechanism, during the transition state, the 4-phenylquinoline
moiety of the Ni(II) complex and N-benzyl group of the
pyrazolidinone dipolarophile efficiently shield the Re-face of
the dipolarophile. In contrast, the Si-face is located in a rela-
tively open space. This Si-face approach can reasonably explain
the selective formation of (5S)-2-pyrazoline 6aa and (4S,5S)-
2-pyrazoline 9aa, their absolute configurations being reported
by Sibi.6b
Et
H (A)
CO2Et
CO2Et
CO2Et
CO2Et
Ph (C)
Ph (C)
Me (B)
H (A)
ꢀ
ClO4ꢀ
ClO4ꢀ
ClO4
a Reactions were carried out on a 0.5-mmol scale (1a/2a = 1.5:1) at
rt in CH2Cl2 in the presence of the Ni(II) complex (10 mol %),
which was prepared by mixing the corresponding BINIM ligand
(ligands AꢀC), Ni(ClO4)2 6H2O or Ni(BF4)2 6H2O, and MS 4 Å
3
3
for 6 h at rt. b Determined by HPLC analysis (Daicel Chiralpak
AD-H). Although the absolute configuration of 2-pyrazolines
9aa and 11aa could only be assigned based on the optical rotation
previously reported,6b 2-pyrazoline 13aa was also assigned similar
to 9aa and 11aa.
(Scheme 5), the R-phenyl substituent presumably facilitates such
transformation. In contrast, the R-benzyl substituent of ethyl
2-diazo-3-phenylpropanoate (1c) discourages such transforma-
tion. As shown in Scheme 6, the reaction between 2-acryloyl-3-
pyrazolidinone 5a and 1c in the presence of (R)-C/Ni(II)
complex proceeded smoothly at 0 °C for 1 h to give only 2-pyrazo-
line 7ca in high yield (83%, 63% ee) without any formation of
the corresponding cyclopropane and alkene (Table 5, entry 1). The
moderate enantioselectivity (63% ee) was improved by lowering the
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Scheme 5. Reactions of Ethyl Diazophenylacetate (1b) with 3-Pyrazolidinone 5a Catalyzed by (R)-C/Ni(II) Complex
Scheme 6. Reactions of 2-Diazo-3-phenylpropanoic Acid Esters 1c, 16c, and 17c with 3-Pyrazolidinones 5a and 5b Catalyzed by
(R)-BINIMꢀNi(II) Complexes
Table 5. Reactions of 2-Diazo-3-phenylpropanoic Acid Esters 1c, 16c, and 17c with 3-Pyrazolidinones 5a and 5b Catalyzed by (R)-
BINIMꢀNi(II) Complexesa
entry
R
Ar
counter anion
X (ligand)
temp (°C)
time (h)
product
yield (%)
%eeb
ꢀ
1
2
3
4
5
6
7
8
Et
Ph
ClO4ꢀ
Ph (C)
0
1
7ca
82
73
53
61
79
86
83
41
63
75
27
71
59
77
77
44
Et
Ph
ClO4ꢀ
ClO4ꢀ
ClO4
Ph (C)
ꢀ40
ꢀ40
ꢀ40
ꢀ40
ꢀ40
ꢀ40
ꢀ40
15
20
15
56
15
10
4
7ca
Et
Ph
Me (B)
3,5-Xylyl (D)
Ph (C)
7ca
Et
Ph
7ca
ꢀ
Et
Ph
BF4
7ca
Et
1-naphc
1-naphc
Ph
ClO4ꢀ
Ph (C)
7cb
18cb
19ca
ꢀ
Me
t-Bu
ClO4ꢀ
ClO4
Ph (C)
Ph (C)
a Reactions werecarried out ona 0.5-mmolscale (diazocompound/dipolarophile=1.5:1) atrt inCH2Cl2 in the presence of theNi(II) complex (10mol %),
which was prepared by mixing the corresponding BINIM ligand (ligands BꢀD), Ni(ClO4)2 6H2O, or Ni(BF4)2 6H O, and MS 4 Å for 6 h at rt.
2
3
3
b Determined by HPLC analysis (Daicel Chiralpak OZ-3). The absolute configuration was not determined. c 1-Naphthyl.
Scheme 7. Reductionof2-Pyrazoline9aatotheCorresponding
Alcohol 20
formation of 2-pyrazolines having a methine carbon substituted
to the coordination auxiliary groups. The enantioselectivity was
found to be affected by both the counteranion of the Ni(II)-
complex and the 4-substituent of the quinoline ring on the
BINIM-2QN ligand. Relatively good enantioselectivity (up to
77% ee) was also observed in the reactions of an R-substituted
diazo ester 1c with 2-acryloyl-3-pyrazolidinone derivatives in the
presence of the BINIMꢀNi(II) catalysts.
’ EXPERIMENTAL SECTION
General. Melting points were determined on a melting point apparatus
’ CONCLUSION
and are uncorrected. IR spectra were taken with a FT/IR spectrophot-
1
Our studies have shown that the BINIMꢀNi(II) catalysts are
extremely effective in affording high levels of asymmetric induc-
tion (up to 97% ee) for 1,3-dipolar cycloaddition reactions
between ethyl diazoacetate and 3-acryloyl-2-oxazolidinones or
2-(2-alkenoyl)-3-pyrazolidinone derivatives in the selective
ometer. H NMR spectra were recorded on a 400 MHz spectrometer.
Chemical shifts are expressed in parts per million downfield from tetra-
methylsilane as an internal standard. 13C NMR spectra were recorded on a
100 MHz spectrometer using broadband proton decoupling. Chemical
shifts are expressed in parts per million using the middle resonance of
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Figure 3. Proposed mechanism for (R)-C/Ni(II)-catalayzed reaction.
CDCl3 (77.0 ppm) as an internal standard. Hydrogen multiplicity (C, CH,
CH2, CH3) information was obtained from the carbon DEPT spectrum.
For preparative column chromatography, Wakogel C-300HG was em-
ployed. All reactions were carried out under an argon atmosphere in dried
glassware.
(1H ꢁ 72/100, dd, J = 8.1, 18.1, Hz, 3aa), 4.04ꢀ4.08 (2H ꢁ 72/100, m,
3aa), 4.31 (2H ꢁ 72/100, q, J = 7.1 Hz, 3aa), 4.50ꢀ4.55 (2H ꢁ 72/100,
m, 3aa), 5.25 (1H ꢁ 72/100, ddd, J = 2.7, 8.1, 12.4 Hz, 3aa), 6.87 (1H ꢁ
72/100, bs, 3aa), 1.30 (3H ꢁ 28/100, t, J = 7.1 Hz, 4aa), 3.29 (1H ꢁ 28/
100, m, 4aa), 3.41 (1H ꢁ 28/100, m, 4aa), 4.03ꢀ4.21 (2H ꢁ 28/100,
m, 4aa), 4.24 (2H ꢁ 28/100, q, J = 7.1 Hz, 4aa), 4.39ꢀ4.56 (3H ꢁ 28/
100, m, 4aa), 6.77 (1H ꢁ 28/100, bs, 4aa); 13C NMR (CDCl3) δ 14.2
(CH3, 3aa), 34.6 (CH2, 3aa), 42.6 (CH2, 3aa), 61.1 (CH2, 3aa), 62.6
(CH, 3aa), 62.9 (CH2, 3aa), 142.8 (C, 3aa), 153.2 (C, 3aa), 161.6 (C,
3aa), 169.7 (C, 3aa); MS (EI) m/z 255 (M+), 149, 87, 69, 55, 38, 26, 15;
HRMS (EI) Calcd for C10H13N3O5 (M+): 255.0854. Found: 255.0853.
A 85:15 mixture of 5-[(4,4-dimethyl-2-oxo-3-oxazolidinyl)carbonyl]-
3-(2-pyrazoline)carboxylic acid ethyl ester (3ab) and 3-[(4,4-dimethyl-
2-oxo-3-oxazolidinyl)carbonyl]-5-(2-pyrazoline)carboxylic acid ethyl
ester (4ab): Yellow viscous oil, [R]25D = +3.2 (c 1.0, CHCl3, 3ab:4ab =
85:15, 28% ee (3ab)); IR (KBr) 3378, 2977, 2938, 1778, 1704, 1550,
Materials. Known chiral binaphthyldiimine (BINIM) ligands were
prepared by the procedure reported previously.9e,16 3-Acryloyl-2-oxa-
zolidinone (2a),17,18 3-acryloyl-4,4-dimethyl-2-oxazozolidinone (2b),22
2-acryloyl-1-benzyl-5,5-dimethyl-3-pyrazolidinone (5a),6b 2-acryloyl-5,
5-dimethyl-1-(1-naphthylmethyl)-3-pyrazolidinone (5b),14a 2-acryloyl-
5,5-dimethyl-1-ethyl-3-pyrazolidinone (5c),e 1-benzyl-2-[(E)-crotonoyl]-5,
5-dimethyl-3-pyrazolidinone (8a),6b 1-benzyl-5,5-dimethyl-2-[(E)-2-pen-
tenoyl]-3-pyrazolidinone (10a),6b and 1-benzyl-5,5-dimethyl-2-[(E)-3-(eth-
oxycarbonyl)propenoyl]-3-pyrazolidinone (12a)9a were prepared by the
procedure reported in the literature. Ethyl diazoacetate (1a),19 ethyl diazo-
phenylacetate (1b),20 and 2-diazo-3-phenylpropanoic acid esters 1c,21 16c,21
and 17c21 were prepared by the procedure reported in the literature.
Powdered 4 Å molecular sieves (MS 4 Å) is commercially available
1
1380, 1311, 1234, 1184, 1095, 1029, 968 cmꢀ1; H NMR (CDCl3)
δ 1.35 (3H ꢁ 85/100, t, J = 7.1 Hz, 3ab), 1.59 (6H ꢁ 85/100, s, 3ab),
3.21 - 3.40 (2H ꢁ 85/100, m, 3ab), 4.05 - 4.13 (2H ꢁ 85/100, m, 3ab),
4.31 (2H ꢁ 85/100, q, J = 7.1 Hz, 3ab), 5.23 (1H ꢁ 85/100, ddd, J = 2.7,
8.3, 12.4 Hz, 3ab), 6.85 (1H ꢁ 85/100, bs, 3ab), 1.30 (3H 15/100, t,
J = 7.1 Hz, 4ab), 1.60 (6H 15/100, s, 4ab), 3.20ꢀ3.39 (2H ꢁ 15/100, m,
4ab), 4.07 (2H ꢁ 15/100, s, 4ab), 4.24 (2H ꢁ 15/100, q, J = 7.1 Hz,
4ab), 4.44 (1H ꢁ 15/100, dd, J = 5.4, 11.9 Hz, 4ab), 6.68 (1H ꢁ 15/100,
bs, 4ab); 13C NMR (CDCl3) δ 14.3 (CH3, 3ab), 24.5 (CH3, 3ab), 24.53
(CH3, 3ab), 35.8 (CH2, 3ab), 60.2 (C, 3ab), 60.7 (CH2, 3ab), 63.5
(CH2, 3ab), 66.7 (CH, 3ab), 135.6 (C, 3ab), 153.2 (C, 3ab), 161.6
(C, 3ab), 170.1 (C, 3ab); MS (EI) m/z 283 (M+), 264, 238, 210, 195,
170, 141, 116, 95, 69, 54, 39; HRMS (EI) Calcd for C12H17N3O5 (M+):
283.1167. Found: 283.1158. The enantiomeric excesses were deter-
mined by HPLC analysis (Daicel Chiralpak AD-H, i-PrOH:hexane = 1:9,
detector: UV 254 nm, flow rate =1.0 mL/min, 35 °C). 3ab: tmajor = 57.9 min,
tminor = 104.7 min. 4ab: tmajor = 30.7 min, tminor = 42.8 min.
(Aldrich) anddriedinvacuoat200°Cfor12hbeforeuse.Ni(ClO4)2 6H2O
3
and Ni(BF4)2 6H2O are commercially available and used without further
3
purification. CH2Cl2 was purified by distillation first from CaCl2 and then
CaH2 under argon before use.
General Procedure for the (R)-BINIMꢀNi (II)-Catalyzed
Reaction Was Exemplified in the Reaction of Ethyl Diazoa-
cetate (1a) with 3-Acryloyl-2-oxazolidinone (2a). A suspension
of (R)-BINIM-4Ph-2QN (37.5 mg, 0.05 mmol), powdered MS 4 Å (127 mg),
and Ni(ClO4)2 6H2O (18.3 mg, 0.05 mmol) in CH2Cl2 (2.5 mL) was
3
stirred for 6 h at room temperature. 3-Acryloyl-2-oxazolidinone (2a)
(70.6 mg, 0.50 mmol) in CH2Cl2 (1.0 mL) and ethyl diazoacetate (1a)
(85.6 mg, 0.75 mmol) in CH2Cl2 (1.0 mL) were successively added to
the catalyst suspension. After being stirred at room temperature for 24 h,
the mixture was filtered through Celiteꢀsilica gel using AcOEt (50 mL)
as an eluent. The solvent was evaporated in vacuo, and then the residue
was chromatographed on silica gel (15 g) with hexaneꢀethyl acetate
(7:3 v/v) as an eluent to give cycloadduct 3aa and 4aa (118 mg, 93%).
5-[(5,5-Dimethyl-2-oxo-3-oxazolidinyl)carbonyl]-3-(2-
pyrazoline)carboxylic Acid Ethyl Ester (3ac). Colorless plates,
1
The 3aa/4aa ratio was determined to be 72:28 by H NMR analysis
mp 114ꢀ116 °C (CH2Cl2ꢀhexane); [R]25 = +33.1 (c 0.2, CHCl3,
D
(400 Mz). The enantiomeric excesses of 3aa and 4aa were determined
by HPLC analysis (Daicel Chiralpak AD-H, i-PrOHꢀhexane (1:2 vol/vol),
detector: UV 254 nm, flow rate =0.5 mL/min, 35 °C). 3aa: tmajor = 39.8 min,
tminor = 61.7 min. 4aa: tmajor = 31.2 min, tminor = 43.7 min.
90% ee); IR (KBr) 3370, 2958, 2341, 1762, 1724, 1693, 1380, 1334,
1292, 1214, 1172, 1110, 1029 cmꢀ1; 1H NMR (CDCl3) δ 1.35 (3H, t,
J = 7.1 Hz), 1.54 (3H, s), 1.55 (3H, s), 3.28 (1H, dd, J = 12.4, 18.0 Hz),
3.41 (1H, dd, J = 8.1, 18.0, Hz), 3.77 (2H, s), 4.31 (2H, q, J = 7.1 Hz),
5.25 (1H, ddd, J = 2.7, 8.1, 12.4 Hz), 6.09 (1H, bs); 13C NMR (CDCl3)
δ 14.3 (CH3), 27.3 (CH3), 27.4 (CH3), 34.6 (CH2), 54.4 (CH2), 61.3
(CH2), 62.9 (CH), 80.1 (C), 143.2 (C), 152.4 (C), 161.7 (C) 169.9
(C); MS (EI) m/z 283 (M+), 237, 167, 141, 116, 95, 69, 56, 35, 26, 16.
Anal. Calcd for C12H17N3O5: C, 50.88; H, 6.05; N, 14.83%. Found: C,
50.99; H, 6.29; N, 14.48%. The enantiomeric excess was determined
by HPLC analysis (Daicel Chiralpak AD-H, i-PrOH:hexane = 1:9,
A 72:28 mixture of 5-[(2-oxo-3-oxazolidinyl)carbonyl]-3-(2-pyrazo-
line)carboxylic acid ethyl ester (3aa) and 3-[(2-oxo-3-oxazolidinyl)-
carbonyl]-5-(2-pyrazoline)carboxylic acid ethyl ester (4aa): Yellow
viscous oil, [R]25 = +12.9 (c 0.3, CHCl3, 3aa:4aa = 72:28, 90% ee
D
(3aa)); IR (CHCl3) 3382, 3000, 2927, 2341, 1758, 1712, 1473, 1384,
1276, 1234, 1195, 1118 cmꢀ1; 1H NMR (CDCl3) δ 1.35 (3H ꢁ 72/100,
t, J = 7.1 Hz, 3aa), 3.29 (1H ꢁ 72/100, dd, J = 12.4, 18.1 Hz, 3aa), 3.41
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detector: UV 254 nm, flow rate = 0.5 mL/min, 35 °C). tmajor = 53.8 min,
tminor = 80.3 min.
1508, 1423, 1384, 1338, 1307, 1234, 1153, 1118, 1025, 744 cmꢀ1; 1H NMR
(CDCl3) δ 1.34 (3H, t, J = 7.1 Hz), 1.34 (3H, s), 1.40 (3H, s), 2.75 (1H, d,
J=17.3Hz),2.84(1H,d,J=17.3Hz),3.01(2H,m),4.28(2H,m),4.39(1H,d,
J = 12.9 Hz), 4.51 (1H, d, J = 12.9 Hz), 4.74 (1H, bs), 6.41 (1H, bs), 7.34 (1H,
m), 7.47ꢀ7.58(3H, m), 7.75(1H, m), 7.84(1H, m), 8.22(1H, m);13CNMR
(CDCl3) δ 14.4 (CH3), 25.9 (CH3), 26.3 (CH3), 35.1 (CH2), 42.9 (CH2),
55.0(CH2), 61.2 (CH2), 61.7 (C), 63.1 (CH), 123.2 (CH), 124.9 (CH), 125.7
(CH), 126.2 (CH), 127.9 (CH), 128.5 (CH), 128.6 (CH), 131.7 (C), 131.8
(C), 133.4 (C), 142.7 (C), 161.8 (C), 167.3 (C), 174.6 (C); MS (EI) m/z422
(M+), 393, 376, 348, 281, 266, 253, 238, 210, 197, 182, 167, 154, 142, 127, 115,
95, 83, 69, 56, 35, 24, 13. Anal. Calcd for C23H26N4O4: C, 65.39; H, 6.20;
N, 13.26%. Found: C, 65.35; H, 6.23; N, 13.27%. The enantiomeric excess was
determined by HPLC analysis (Daicel Chiralpak OD-H, i-PrOH:hexane = 1:7,
A 70:30 mixture of 5-[(5,5-dimethyl-2-oxo-3-oxazolidinyl)carbonyl]-
3-(2-pyrazoline)carboxylic acid ethyl ester (3ac) and 3-[(5,5-dimethyl-
2-oxo-3-oxazolidinyl)carbonyl]-5-(2-pyrazoline)carboxylic acid ethyl
ester (4ac): Although 4ac could not be separated by chromatography
from a mixture with major 3ac, it could be characterized by 1H NMR.
[R]25D = +28.9 (c 1.0, CHCl3, 3ac:4ac = 70:30, 92% ee (3ac)); 1H NMR
(CDCl3) δ 1.35 (3H ꢁ 70/100, t, J = 7.1 Hz, 3ac), 1.54 (3H ꢁ 70/100,
s, 3ac), 1.55 (3H ꢁ 70/100, s, 3ac), 3.28 (1H ꢁ 70/100, dd, J = 12.4,
18.0 Hz, 3ac), 3.41 (1H ꢁ 70/100, dd, J = 8.1, 18.0, Hz, 3ac), 3.77
(2H ꢁ 70/100, s, 3ac), 4.31 (2H ꢁ 70/100, q, J = 7.1 Hz, 3ac), 5.25 (1H
ꢁ 70/100, ddd, J = 2.7, 8.1, 12.4 Hz, 3ac), 6.09 (1H ꢁ 70/100, bs, 3ac),
1.30 (3H ꢁ 30/100, t, J = 7.1 Hz, 4ac), 1.51 (6H ꢁ 30/100, s, 4ac),
3.23ꢀ3.51 (2H ꢁ 30/100, m, 4ac), 3.89 (2H ꢁ 30/100, s, 4ac), 4.23
(2H ꢁ 30/100, q, J = 7.1 Hz, 4ac), 4.43 (1H ꢁ 30/100, m, 4ac), 6.75
(1H ꢁ 30/100, bs, 4ac). The enantiomeric excesses were determined by
HPLC analysis (Daicel Chiralpak AD-H, i-PrOH:hexane = 1:9, detector:
detector: UV 254 nm, flow rate = 0.5 mL/min, 35 °C). tminor = 119.7, tmajor
=
132.1 min. The absolute configuration of 2-pyrazoline 6ab was assigned similar
to 6aa.
A 84:16 mixture of 5-[(5,5-dimethyl-1-(1-naphthylmethyl)-3-oxo-2-
pyrazolidinyl)carbonyl]-3-(2-pyrazoline)carboxylic acid ethyl ester
(6ab) and 3-[(5,5-dimethyl-1-(1-naphthylmethyl)-3-oxo-2-pyrazolidinyl)car-
bonyl]-5-(2-pyrazoline)carboxylic acid ethyl ester (7ab): Although 7ab
UV 254 nm, flow rate = 0.5 mL/min, 35 °C). 3ac: tmajor = 53.8 min, tminor
80.3 min. 4ac: tmajor = 75.0 min, tminor = 120.1 min.
(5S)-5-[(1-Benzyl-5,5-dimethyl-3-oxo-2-pyrazolidinyl)-
=
could not be separated by chromatography from a mixture with major
carbonyl]-3-(2-pyrazoline)carboxylic Acid Ethyl Ester (6aa):6b
1
6ab, it could be characterized by H NMR. [R]25 = +147.1 (c 1.0,
D
Colorless plates; mp 42ꢀ43 °C (CH2Cl2ꢀhexane); [R]25 = +106.7
1
CHCl3, 6ab:7ab = 84:16, 95% ee (6ab)); H NMR (CDCl3) δ 1.34
D
(c 0.5, CHCl3, 92% ee); IR (KBr) 3356, 3062, 2982, 2937, 1756, 1716,
1576, 1351, 1060, 737 cmꢀ1; 1H NMR (CDCl3) δ 1.29 (3H, s), 1.31 (3H,
s), 1.36 (3H, t, J = 7.0 Hz), 2.58 (1H, d, J = 17.3 Hz), 2.65 (1H, d, J = 17.3
Hz), 3.20 (2H, d, J = 10.2 Hz), 4.03 (1H, d, J = 13.5 Hz), 4.10 (1H, d,
J = 13.5 Hz), 4.30 (2H, q, J = 7.0 Hz), 5.01 (1H, bt, J = 10.2 Hz), 6.71 (1H,
bs), 7.22ꢀ7.32 (3H, m), 7.36ꢀ7.41 (2H, m); MS (EI) m/z 372 (M+),
358, 327, 318, 308, 294, 279, 268, 250, 231, 216, 204, 190, 187, 174, 162,
152, 121, 109, 99, 81, 51, 23, 12; HRMS (EI) Calcd for C19H24N4O4
(M+): 372.1796. Found: 372.1812. The enantiomeric excess was deter-
mined byHPLCanalysis (DaicelChiralpak AD-H, i-PrOH:hexane = 1:19,
detector: UV 254 nm, flow rate = 1.0 mL/min, 35 °C). tmajor = 103.9 min,
tminor = 125.6 min. The absolute configuration of 2-pyrazoline 6aa was
assigned based on the optical rotation previously reported.6b
A 85:15 mixture of 5-[(1-Benzyl-5,5-dimethyl-3-oxo-2-pyrazolidinyl)-
carbonyl]-3-(2-pyrazoline)carboxylic acid ethyl ester (6aa) and 3-
[(1-Benzyl-5,5-dimethyl-3-oxo-2-pyrazolidinyl)carbonyl]-5-(2-pyrazoline)
carboxylic acid ethyl ester (7aa): Although 7aa could not be separated by
chromatography from a mixture with major 6aa, it could be character-
ized by 1H NMR. [R]25D = +114.9 (c 1.0, CHCl3, 6aa:7aa = 85:15, 97%
ee (6aa)); 1H NMR (CDCl3) δ 1.29 (3H ꢁ 85/100, s, 6aa), 1.31 (3H ꢁ
85/100, s, 6aa), 1.36 (3H ꢁ 85/100, t, J = 7.0 Hz, 6aa), 2.58 (1H ꢁ 85/
100, d, J = 17.3 Hz, 6aa), 2.65 (1H ꢁ 85/100, d, J = 17.3 Hz, 6aa), 3.20
(2H ꢁ 85/100, d, J = 10.2 Hz, 6aa), 4.03 (1H ꢁ 85/100, d, J = 13.5 Hz,
6aa), 4.10 (1H ꢁ 85/100, d, J = 13.5 Hz, 6aa), 4.30 (2H ꢁ 85/100, q,
J = 7.0Hz, 6aa), 5.01 (1Hꢁ 85/100, bt, J = 10.2 Hz, 6aa), 6.71 (1Hꢁ 85/
100, bs, 6aa), 7.22ꢀ7.32 (3H ꢁ 85/100, m, 6aa), 7.36ꢀ7.41 (2H ꢁ 85/
100, m, 6aa), 1.29 (3H ꢁ 15/100, t, J = 7.1 Hz, 7aa), 1.32 (3H ꢁ 15/
100, s, 7aa), 1.36 (3H ꢁ 15/100, s, 7aa), 2.54 (2H ꢁ 15/100, s, 7aa),
2.97 (1H ꢁ 15/100, dd, J = 12.2, 17.1 Hz, 7aa), 3.14 (1H ꢁ 15/100, d,
J = 4.88, 17.1 Hz, 7aa), 4.01 (1H ꢁ 15/100, d, J = 12.9 Hz, 7aa), 4.11
(1H ꢁ 15/100, d, J = 12.9 Hz, 7aa), 4.23 (2H ꢁ 15/100, q, J = 7.1 Hz,
7aa), 4.32 (1H ꢁ 15/100, dd, J = 4.88, 12.2 Hz, 7aa), 6.62 (1H ꢁ 15/
100, bs, 7aa), 7.21ꢀ7.39 (5H ꢁ 15/100, m, 7aa). The enantiomeric
excesses were determined by HPLC analysis (Daicel Chiralpak AD-H,
i-PrOH:hexane = 1:19, detector: UV 254 nm, flow rate = 0.5 mL/min,
35 °C). 6aa: tmajor = 103.9 min, tminor = 125.6 min. 7aa: tmajor = 131.5
min, tminor = 135.8 min (partly overlap).
(3H ꢁ 84/100, t, J = 7.1 Hz, 6ab), 1.34 (3H ꢁ 84/100, s, 6ab), 1.40
(3H ꢁ 84/100, s, 6ab), 2.75 (1H ꢁ 84/100, d, J = 17.3 Hz, 6ab), 2.84
(1H ꢁ 84/100, d, J = 17.3 Hz, 6ab), 3.01 (2H ꢁ 84/100, m, 6ab), 4.28
(2H ꢁ 84/100, m, 6ab), 4.39 (1H ꢁ 84/100, d, J = 12.9 Hz, 6ab), 4.51
(1H ꢁ 84/100, d, J = 12.9 Hz, 6ab), 4.74 (1H ꢁ 84/100, bs, 6ab), 6.41
(1H ꢁ 84/100, bs, 6ab), 7.34 (1H ꢁ 84/100, m, 6ab), 7.47ꢀ7.58
(3H ꢁ 84/100, m, 6ab), 7.75 (1H ꢁ 84/100, m, 6ab), 7.84 (1H ꢁ 84/
100, m, 6ab), 8.22 (1H ꢁ 84/100, m, 6ab), 1.23 (3H ꢁ 16/100, t, J =
7.1 Hz, 7ab), 1.44 (6H ꢁ 16/100, s, 7ab), 2.59ꢀ2.89 (4H ꢁ 16/100, m,
7ab), 3.70 (1H ꢁ 16/100, dd, J = 6.3, 12.2 Hz, 7ab), 4.26 (2H ꢁ
16/100, m, 7ab), 4.35 (1H ꢁ 16/100, d, J = 12.9 Hz, 7ab), 4.54 (1H ꢁ
16/100, d, J = 12.9 Hz, 7ab), 6.20 (1H ꢁ 16/100, bs, 7ab), 7.32ꢀ7.58
(7H ꢁ 16/100, m, 7ab). The enantiomeric excesses were determined by
HPLC analysis (Daicel Chiralpak OD-H, i-PrOH:hexane = 1:7, detector:
UV 254 nm, flow rate = 0.5 mL/min, 35 °C). 7ab: tmajor = 100.0 min,
tminor = 106.9 min (partly overlap). 6ab: tmajor = 117.1 min, tminor
=
133.9 min.
A 79:21 mixture of 5-[(5,5-dimethyl-1-ethyl-3-oxo-2-pyrazolidinyl)-
carbonyl]-3-(2-pyrazoline)carboxylic acid ethyl ester (6ac) and3-[(5,5-dimeth-
yl-1-ethyl-3-oxo-2-pyrazolidinyl)carbonyl]-5-(2-pyrazoline)carboxylic
acid ethyl ester (7ac): Yellow viscous oil; [R]25D = +8.5 (c 1.0, CHCl3,
6ac:7ac = 79:21, 8% ee (6ac), 3% ee (7ac)); IR (KBr) 3262, 3058, 2981,
1689, 1596, 1442, 1373, 1330, 1241, 1160, 1114, 1029, 744 cmꢀ1; 1H
NMR (CDCl3) δ 1.05 (3H ꢁ 79/100, t, J = 7.3 Hz, 6ac), 1.33 (3H ꢁ
79/100, s, 6ac), 1.34 (3H ꢁ 79/100, s, 6ac), 1.35 (3H ꢁ 79/100, t,
J = 7.1 Hz, 6ac), 2.61 (1H ꢁ 79/100, d, J = 17.3 Hz, 6ac), 2.66 (1H ꢁ
79/100, d, J = 17.3 Hz, 6ac), 3.02 (2H ꢁ 79/100, m, 6ac), 3.29 (1H ꢁ
79/100, dd, J = 12.5, 18.3 Hz, 6ac), 3.39 (1H ꢁ 79/100, dd, J = 8.0, 18.3
Hz, 6ac), 4.31 (2H ꢁ 79/100, q, J = 7.1 Hz, 6ac), 5.16 (1H ꢁ 79/100,
ddd, J = 2.4, 8.0, 12.5 Hz, 6ac), 6.89 (1H ꢁ 79/100, bs, 6ac), 1.10 (3H ꢁ
21/100, t, J = 7.1 Hz, 7ac), 1.31 (3H ꢁ 21/100, t, J = 7.1 Hz, 7ac), 1.33
(3H ꢁ 21/100, s, 7ac), 1.35 (3H ꢁ 21/100, s, 7ac), 2.65 (2H ꢁ 21/100,
s, 7ac), 2.96ꢀ3.02 (2H ꢁ 21/100, m, 7ac), 3.23ꢀ3.43 (2H ꢁ 21/100,
m, 7ac), 4.23 (2H ꢁ 21/100, q, J = 7.1 Hz, 7ac), 4.44 (2H ꢁ 21/100, dd,
J = 5.4, 12.2 Hz, 7ac), 6.71 (1H ꢁ 21/100, bs, 7ac); 13C NMR (CDCl3)
δ 12.9 (CH3, 6ac), 14.3 (CH3, 6ac), 25.2 (CH3, 6ac), 25.5 (CH3, 6ac),
34.7 (CH2, 6ac), 42.7 (CH2, 6ac), 43.7 (CH2, 6ac), 46.9 (CH2, 6ac),
61.2 (CH, 6ac), 63.1 (C, 6ac), 149.3 (C, 6ac), 161.8 (C, 6ac), 169.7 (C,
6ac), 174.8 (C, 6ac); MS (EI) m/z 310 (M+), 288, 279, 264, 255, 236,
226, 212, 199, 186, 173, 166, 152, 126, 114, 98, 84, 72, 60, 51, 23, 14;
Anal. Calcd for C14H22N4O4: C, 54.18; H, 7.15; N, 18.05%. Found: C,
(5S)-5-[(5,5-Dimethyl-1-(1-naphthylmethyl)-3-oxo-2-pyra-
zolidinyl)carbonyl]-3-(2-pyrazoline)carboxylic Acid Ethyl Ester
(6ab).Colorless plates; mp 167ꢀ168 °C(CH2Cl2ꢀhexane); [R]25D = +166.8
(c 0.5, CHCl3, 95% ee); IR (KBr) 3359, 2981, 2931, 2854, 1712, 1577,
7384
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ARTICLE
54.10; H, 7.44; N, 17.84%. The enantiomeric excesses were determined
by HPLC analysis (Daicel Chiralpak AD-H, i-PrOH:hexane = 1:9,
(c 0.10, CHCl3, 43%ee); IR (KBr) 3459, 3278, 3058, 2973, 2931, 1739,
1673, 1569, 1434, 1376, 1299, 1245, 1141, 1087, 1041, 998, 848, 821,
767, 690, 501, 466 cmꢀ1; 1H NMR (CDCl3) δ 1.25 (3H, t, J = 7.3 Hz),
1.34 (3H, s), 1.35 (3H, s), 2.57 (1H, d, J = 16.8 Hz), 2.63 (1H, d, J = 16.8
Hz), 2.94 (1H, d, J = 17.1 Hz), 3.82 (1H, d, J = 17.1 Hz), 4.04 (1H, d,
J = 12.9 Hz), 4.09 (1H, d, J = 12.9 Hz), 4.22 (2H, q, J = 7.3 Hz), 7.16 (1H,
bs), 7.18ꢀ7.25 (3H, m), 7.28ꢀ7.43 (7H, m); 13C NMR (100 MHz)
δ 14.0 (CH3), 26.0 (CH3), 26.2 (CH3), 42.8 (CH2), 43.1 (CH2), 57.7
(CH2), 61.8 (C), 62.4 (CH2), 75.1 (C), 125.5 (CH), 127.4 (CH), 127.9
(CH), 128.0 (CH), 128.5 (CH), 129.7 (CH), 136.1 (C), 139.4 (C),
144.2 (C), 160.5 (C), 172.3 (C), 173.4 (C); MS (EI) m/z 448 (M+),
419, 374, 332, 316, 283, 260, 245, 232, 217, 203, 188, 172, 159, 144, 127,
106, 90, 76, 63, 47, 23, 10. Anal. Calcd for C25H28N4O4: C, 66.95; H,
6.29; N, 12.49%. Found: C, 66.92; H, 6.32; N, 12.49%. The enantiomeric
excess was determined by HPLC analysis (Daicel Chiralpak AD-H,
i-PrOH:hexane = 1:6, detector: UV 254 nm, flow rate = 0.5 mL/min,
35 °C). tminor = 97.1, tmajor = 129.4 min.
detector: UV 254 nm, flow rate = 1.0 mL/min, 35 °C). 6ac: tmajor
30.2, tminor = 42.1 min. 7ac: tmajor = 33.9, tminor = 37.7 min.
=
(4S,5S)-5-[(1-Benzyl-5,5-dimethyl-3-oxo-2-pyrazolidinyl)-
carbonyl]-4-methyl-3-(2-pyrazoline)carboxylic Acid Ethyl
Ester (9aa):6b Colorless plates; mp 117ꢀ119 °C (CH2Cl2ꢀhexane);
[R]25D = +171.2 (c 1.0, CHCl3, 93% ee); IR (KBr) 3349, 2979, 2933,
1748, 1700, 1588, 1453, 1369, 1327, 1093, 771 cmꢀ1 1H NMR
;
(CDCl3) δ 1.28 (3H, s), 1.32 (3H, s), 1.36 (3H, t, J = 7.1 Hz), 1.36
(3H, d, J = 7.1 Hz), 2.58 (1H, d, J = 17.3 Hz,), 2.68 (1H, d, J = 17.3 Hz),
3.41 (1H, dq, J = 4.6, 7.1 Hz), 3.99 (1H, d, J = 13.4 Hz), 4.09 (1H, d,
J = 13.4 Hz), 4.24ꢀ4.36 (2H, m), 4.57 (1H, bd, J = 4.6 Hz), 6.61 (1H,
bs), 7.22ꢀ7.32 (3H, m), 7.36ꢀ7.41 (2H, m); 13C NMR (CDCl3) δ 14.4
(CH3), 17.1 (CH3), 26.1 (CH3), 26.3 (CH3), 43.2 (CH2), 43.3 (CH),
56.9 (CH2), 61.0 (CH2), 61.6 (C), 70.9 (CH), 127.5 (CH), 128.2 (CH),
129.1 (CH), 136.4 (C), 146.6 (C), 161.5 (C), 167.3 (C), 174.8 (C); MS
(EI) m/z 386 (M+), 358, 276, 203,190, 155, 114, 90, 78, 51, 24, 14. Anal.
Calcd for C20H26N4O4: C, 62.16; H, 6.78; N, 14.50%. Found: C, 62.17;
H, 7.06; N, 14.29%. The enantiomeric excess was determined by HPLC
analysis (Daicel Chiralpak AD-H, i-PrOH:hexane = 1:9, detector: UV
254 nm, flow rate = 1.0 mL/min, 35 °C). tmajor = 38.8, tminor = 51.2 min.
The absolute configuration of 2-pyrazoline 9aa was assigned based on
the optical rotation previously reported.6b
Although cyclopropane 14 and alkene 15 could not be separated
1
completely by chromatography, these could be characterized by H
NMR or 13C NMR. A 78:22 mixture of 2-[(1-benzyl-5,5-dimethyl-
3-oxo-2-pyrazolidinyl)carbonyl]-1-phenyl-1-cyclopropane carboxylic acid
ethyl ester (14) and 4-[(1-benzyl-5,5-dimethyl-3-oxo-2-pyrazolidinyl)-
carbonyl]-2-phenyl-2-butenoic acid ethyl ester (15): 1H NMR (CDCl3)
δ 1.01 (3H ꢁ 78/100, s, 14), 1.21 (3H ꢁ 78/100, t, J = 7.1 Hz, 14), 1.25
(3H ꢁ 78/100, s, 14), 1.84 (1H ꢁ 78/100, dd, J = 4.6, 8.1 Hz, 14), 2.26
(1H ꢁ 78/100, dd, J = 4.6, 6.8 Hz, 14), 2.60 (2H ꢁ 78/100, s, 14), 3.60
(1H ꢁ 78/100, dd, J = 6.8, 8.1 Hz, 14), 3.70 (1H 78/100, d, J = 13.9 Hz,
14), 3.78 (1H ꢁ 78/100, d, J = 13.9 Hz, 14), 4.12ꢀ4.25 (2H ꢁ 78/100,
m, 14), 7.14ꢀ7.26 (8H ꢁ 78/100, m, 14) 7.32ꢀ7.34 (2H ꢁ 78/100, m,
14), 1.22 (6H ꢁ 22/100, s, 15), 1.27 (3H ꢁ 22/100, t, J = 7.1 Hz, 15),
2.52 (2H ꢁ 22/100, s, 15), 3.42 (2H ꢁ 22/100, brd, J = 7.1 Hz, 15), 3.99
(2H ꢁ 22/100, s, 15), 4.21 (2H ꢁ 22/100, q, J = 7.1 Hz, 15), 7.08
(1H ꢁ 22/100, t, J = 7.1 Hz, 15), 7.12ꢀ7.17 (2H ꢁ 22/100, m, 15),
7.19ꢀ7.39 (8H ꢁ 22/100, m, 15); 13C NMR (CDCl3) δ 14.3 (CH3,
15), 18.0 (CH2, 15), 26.2 (CH3, 15), 26.3 (CH3, 15), 32.7 (CH, 15),
43.6 (CH2, 15), 56.5 (CH2, 15), 60.7 (CH2, 15), 61.7 (CH2, 15), 127.1
(CH, 15), 127.4 (CH, 15), 127.8 (CH, 15), 128.1 (CH, 15), 128.6 (CH,
15), 130.5 (CH, 15), 133.7 (C, 15), 137.6 (C, 15), 164.1 (C, 15), 171.8
(C, 15), 174.0 (C, 15).
(4S,5S)-5-[(1-Benzyl-5,5-dimethyl-3-oxo-2-pyrazolidinyl)-
carbonyl]-4-ethyl-3-(2-pyrazoline)carboxylic Acid Ethyl Ester
(11aa):6b Colorless plates; mp 41ꢀ42 °C (CH2Cl2ꢀhexane); [R]25
=
D
+194.9 (c 1.0, CHCl3, 86% ee); IR (KBr) 3356, 2972, 2934, 1750, 1701,
1568, 1349, 1233, 1103, 733 cmꢀ1; 1H NMR (CDCl3) δ 0.85 (3H, t, J =
7.6 Hz), 1.29 (3H, s), 1.30 (3H, s), 1.32ꢀ1.36 (3H, m), 1.74 (1H, m), 1.90
(1H, m), 2.60 (1H, d, J = 17.3 Hz), 2.67 (1H, d, J = 17.3 Hz), 3.57 (1H, m),
4.03 (1H, d, J = 13.4 Hz), 4.08 (1H, d, J = 13.4 Hz), 4.24ꢀ4.33 (2H, m),
4.68 (1H, bs), 6.69 (1H, bs), 7.17ꢀ7.44 (5H, m); 13C NMR (CDCl3)
δ 10.1 (CH3), 14.2 (CH3), 24.1 (CH2), 26.0 (CH3), 26.3 (CH3), 43.2
(CH2), 48.3 (CH), 56.7 (CH2), 60.8 (CH2), 61.4 (C), 68.1 (CH), 127.4
(CH), 128.1 (CH), 129.0 (CH), 136.4 (C), 144.8 (C), 161.7 (C), 166.9
(C), 174.7 (C); MS (EI) m/z 400 (M+), 355, 189, 123, 92, 65, 39, 15. Anal.
Calcd for C21H28N4O4: C, 62.98; H, 7.05; N, 13.99%. Found: C, 62.95; H,
7.08; N, 13.76%. The enantiomeric excess was determined by HPLC
analysis (Daicel Chiralpak AD-H, i-PrOH:hexane = 1:9, detector: UV
254 nm, flow rate = 1.0 mL/min, 35 °C). tmajor = 41.1, tminor = 46.9 min. The
absolute configuration of 2-pyrazoline 11aa was assigned based on the
optical rotation previously reported.6b
5-Benzyl-3-[(1-benzyl-5,5-dimethyl-3-oxo-2-pyrazolidinyl)-
carbonyl]-5-(2-pyrazoline)carboxylic Acid Ethyl Ester (7ca).
Colorless amorphous; [R]25 = ꢀ106.4 (c 0.40, CHCl3, 75% ee); IR
D
(KBr) 3357, 2979, 1735, 1681, 1496, 1455, 1373, 1302, 1232, 1033,
702 cmꢀ1; 1H NMR (CDCl3) δ 1.19 (3H, t, J = 7.1 Hz), 1.32 (3H, s),
1.34 (3H, s), 2.55 (1H, d, J = 16.8 Hz), 2.63 (1H, d, J = 16.8 Hz),
2.78 (1H, d, J = 17.1 Hz), 3.04 (1H, d, J = 13.4 Hz), 3.19 (1H, d, J = 13.4
Hz), 3.24 (1H, d, J = 17.1 Hz), 4.00 (1H, d, J = 12.7 Hz), 4.07 (1H, d,
J = 12.7 Hz), 4.12 (2H, q, J = 7.1 Hz), 6.60 (1H, bs), 7.10ꢀ7.38 (10H,
m); 13C NMR (CDCl3) 14.0 (CH3), 25.9 (CH3), 26.3 (CH3), 41.0
(CH2), 42.9 (CH2), 43.4 (CH2), 57.7 (CH2), 61.79 (C), 61.82 (CH2),
73.5 (C), 127.1 (CH), 127.4 (CH), 128.0 (CH), 128.3 (CH), 129.5
(CH), 129.8 (CH), 134.9 (C), 136.1 (C), 144.2 (C), 160.7 (C), 172.6 (C),
173.6 (C); MS (EI) m/z 462 (M+), 231, 204, 189, 157, 129, 113,
91, 69, 55, 41, 28, 3. Anal. Calcd for C26H30N4O4: C, 67.51; H, 6.54; N,
12.11%. Found: C, 67.62; H, 6.49; N, 12.05%. The enantiomeric excess
was determined by HPLC analysis (Daicel Chiralpak OZ-3, i-PrOH:
hexane = 50:50, detector: UV 254 nm, flow rate = 0.5 mL/min, 35 °C).
tmajor =20.3, tminor = 27.6 min.
(4S,5S)-5-[(1-Benzyl-5,5-dimethyl-3-oxo-2-pyrazolidinyl)-
carbonyl]-4-ethoxycarbonyl-3-(2-pyrazoline)carboxylic Acid
Ethyl Ester (13aa). Colorless plates; mp 38ꢀ40 °C (CH2Cl2ꢀhexane);
[R]25D = +226.7 (c 1.0, CHCl3, 85% ee); IR (KBr) 3351, 2981, 1735, 1565,
1376, 1230, 1118, 732 cmꢀ1; 1H NMR (CDCl3) δ 1.29 (3H, t, J = 7.1 Hz),
1.30 (3H, s), 1.31 (3H, s), 1.34 (3H, t, J = 7.1 Hz), 2.62 (2H, s), 4.04 (1H, d,
J = 13.7 Hz), 4.09 (1H, d, J = 13.7 Hz), 4.13ꢀ4.36 (4H, m), 4.49 (1H, d, J =
8.1 Hz), 5.25 (1H, bs), 6.84 (1H, bs), 7.22ꢀ7.32 (3H, m), 7.36ꢀ7.41 (2H,
m); 13C NMR (CDCl3) δ 14.2 (CH3), 14.4 (CH3), 26.0 (CH3), 26.6
(CH3) 43.3 (CH2), 51.9 (CH), 56.8 (CH2), 61.4 (CH2), 61.6 (C), 61.9
(CH2), 68.5 (CH), 127.6 (CH), 128.4 (CH), 129.2 (CH), 136.3 (C), 140.0
(C), 160.9 (C), 164.5 (C), 169.3 (C), 175.0 (C); MS (EI) m/z 444 (M+),
398, 370, 294, 258, 204, 188, 166, 140, 127, 84, 66, 52, 34, 10. Anal. Calcd for
C22H28N4O6: C, 59.45; H,6.35; N, 12.60%. Found: C, 59.42; H, 6.31;
N, 12.46%. The enantiomeric excess was determined by HPLC analysis
(Daicel Chiralpak AD-H, i-PrOH:hexane = 1:12, detector: UV 254 nm, flow
rate = 1.0 mL/min, 35 °C). tmajor = 104.0, tminor = 116.1 min. The absolute
configuration of 2-pyrazoline 13aa was assigned similar to 11aa.
3-[(1-Benzyl-5,5-dimethyl-3-oxo-2-pyrazolidinyl)carbonyl]-
5-naphthylmethyl-5-(2-pyrazoline)carboxylic Acid Ethyl Ester
(7cb). Colorless amorphous; [R]25D = ꢀ142.3 (c 0.40, CHCl3, 77% ee);
IR (KBr) 3340, 2978, 2360, 1735, 1373, 1303, 1227, 1032, 797, 776, 702,
418 cmꢀ1; 1H NMR (CDCl3) δ 1.10 (3H, t, J = 7.1 Hz), 1.47 (3H, s),
1.50 (3H, s), 2.04 (1H, d, J = 17.1 Hz), 2.52 (1H, d, J = 13.4 Hz), 2.68 (1H,
3-[(1-Benzyl-5,5-dimethyl-3-oxo-2-pyrazolidinyl)carbonyl]-
5-phenyl-5-(2-pyrazoline)carboxylic Acid Ethyl Ester (7ba).
Colorless plates; mp 159ꢀ160 °C (CH2Cl2ꢀhexane); [R]25D = ꢀ50.9
7385
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ARTICLE
d, J = 16.8 Hz), 2.80 (1H, d, J = 16.8 Hz), 2.86 (1H, d, J = 17.1 Hz), 2.87
(1H, d, J = 13.4 Hz), 3.96ꢀ4.04 (2H, m), 4.38 (1H, d, J = 12.2 Hz), 4.52
(1H, d, J = 12.2 Hz), 6.24 (1H, bs), 6.96ꢀ8.27 (12H, m); 13C NMR
(CDCl3) 13.7 (CH3), 25.5 (CH3), 26.3 (CH3), 40.4 (CH2), 42.2 (CH2),
42.9 (CH2), 55.6 (CH2), 61.3 (CH2), 61.6 (C), 72.9 (C), 123.7 (CH),
124.8 (CH), 125.2 (CH), 125.9 (CH), 126.7 (CH), 127.9 (CH), 128.1
(CH), 128.5 (CH), 128.9 (CH), 129.6 (CH), 130.7 (C), 131.7 (C), 133.2
(C), 134.8 (C), 143.3 (C), 160.0 (C), 172.1 (C), 173.1 (C); MS (EI) m/z
512 (M+), 282, 254, 231, 211, 185, 157, 141, 115, 91, 77, 55, 28, 3; HRMS
(EI) Calcd for C30H32N4O4 (M+): 512.2422. Found: 512.2449. The
enantiomeric excess was determined by HPLC analysis (Daicel Chiralpak
OZ-3, i-PrOH:hexane = 65:35, detector: UV 254 nm, flow rate = 0.5 mL/
min, 35 °C). tminor = 22.1, tmajor = 33.8 min.
i-PrOHꢀhexane 1:9, detector: UV 254 nm, flow rate = 1 mL/min,
35 °C), tmajor = 10.1, tminor = 11.3 min.
(4S,5S)-4,5-Dihydro-3-ethoxycarbonyl-5-hydroxymethyl-
4-methyl-1H-pyrazole. Colorless oil; [R]25D = +25.9 (c 0.17, CHCl3,
96% ee), IR (neat) 3358, 2929, 1708, 1555, 1453, 1377, 1241, 1101 cmꢀ1
;
1H NMR (CDCl3) δ 1.28 (3H, d, J = 6.8 Hz), 1.35 (3H, t, J = 7.2 Hz), 2.35
(1H, bs), 3.04 (1H, quint, J = 6.8 Hz), 3.61ꢀ3.68 (3H, m), 4.23ꢀ4.35 (2H,
m); 13C NMR (CDCl3) 14.4 (CH3), 16.9 (CH3), 40.5 (CH), 61.0 (CH2),
63.2 (CH2), 70.2 (CH), 146.1 (C), 162.3 (C); MS (EI) m/z 186 (M+),
155, 141, 109, 91, 83, 71, 65, 55, 39, 29, 15; HRMS (EI) Calcd for
C8H14N2O3 (M+): 186.1004. Found: 186.1032.
Preparation of (R)-BINIM-4(3,5-TFXylyl)-2QN by the Reac-
tion of (R)-1,10-Binaphthyl-2,20-diamine with 4-[3,5-Bis-
(trifluoromethyl)phenyl]-2-quinolinecarbaldehyde. A suspension
of (R)-1,10-binaphthyl-2,20-diamine (0.427 g, 1.5 mmol), 4-[3,5-bis(trifluoro-
methyl)phenyl]-2-quinolinecarbaldehyde (1.10 g, 3.0 mmol), and MS 4 Å
(9.0 g) in benzene (25 mL) was heated under reflux for 6 h. After removal of
MS 4 Å by filtration, the solvent was evaporated in vacuo. The residual solid
was recrystallized from diethyl ether to give the corresponding (R)-BINIM-
4(3,5-CF3Ph)-2QN (0.829 g, 56%).
3-[(1-Benzyl-5,5-dimethyl-3-oxo-2-pyrazolidinyl)carbonyl]-
5-naphthylmethyl-5-(2-pyrazoline)carboxylic Acid Methyl
Ester (18cb). Colorless amorphous; [R]25D = ꢀ114.2 (c 0.40, CHCl3,
77% ee); IR (KBr) 3341, 2972, 2359, 1739, 1439, 1303, 1228, 797,
703 cmꢀ1; 1H NMR (CDCl3) δ 1.47 (3H, s), 1.50 (3H, s), 2.06 (1H, d,
J = 17.0 Hz), 2.51 (1H, d, J = 13.4 Hz), 2.67 (1H, d, J = 16.8 Hz), 2.80
(1H, d, J = 16.8 Hz), 2.84 (1H, d, J = 17.0 Hz), 2.87 (1H, d, J = 13.4 Hz),
3.56 (3H, s), 4.37 (1H, d, J = 12.2 Hz), 4.51 (1H, d, J = 12.2 Hz), 6.21
(1H, s), 6.91ꢀ8.27 (12H, m); 13C NMR (CDCl3) 25.6 (CH3), 26.3
(CH3), 40.4 (CH2), 42.2 (CH2), 42.9 (CH2), 52.2 (CH3), 55.7 (CH2),
61.7 (C), 73.1 (C), 123.7 (CH), 124.9 (CH), 125.3 (CH), 125.9 (CH),
126.9 (CH), 128.0 (CH), 128.2 (CH), 128.6 (CH), 128.9 (CH), 129.7
(CH), 130.7 (C), 131.7 (C), 133.2 (C), 134.7 (C), 143.4 (C), 159.9
(C), 172.6 (C), 173.3 (C); MS (EI) m/z 498 (M+), 254, 217, 185, 157,
141, 115, 91, 77, 55, 28, 3; HRMS (EI) Calcd for C29H30N4O4 (M+):
498.2265. Found: 498.2267. The enantiomeric excess was determined
by HPLC analysis (Daicel Chiralpak OZ-3, i-PrOH:hexane = 65:35,
detector: UV 254 nm, flow rate = 0.5 mL/min, 35 °C). tminor = 23.2,
(R)-N,N0-Bis{4-[3,5-bis(trifluoromethyl)phenyl]-2-quinolyl-
methylene}-1,10-binaphthyl-2,20-diamine. Yellow powder; mp
142ꢀ145 °C (diethyl ether); [R]25 = ꢀ135.7 (c 1.0, CHCl3); IR
D
(KBr) 1335, 1281, 1182, 1138 cmꢀ1; 1H NMR (CDCl3) δ 7.23ꢀ7.27
(4H, m), 7.32ꢀ7.36 (2H, m), 7.43 (2H, bd, J = 8.3 Hz), 7.52ꢀ7.58 (4H,
m), 7.63ꢀ7.65 (2H, m), 7.69ꢀ7.73 (6H, m), 7.84 (2H, bd, J = 8.0 Hz),
7.97ꢀ8.04 (6H, m), 8.69 (2H, s); 13C NMR (CDCl3) δ 116.7 (CH),
118.5 (CH), 122.0 (CH, m), 122.9 (C, q, JCꢀF = 272.2 Hz), 124.2 (CH),
125.2 (CH), 125.9 (C), 126.3 (CH), 126.9 (CH), 127.5 (CH), 128.1
(CH), 129.1 (CH), 129.2 (CH, d, JCꢀF = 3.1 Hz), 129.5 (C), 129.7
(CH), 130.0 (CH), 131.7 (C, q, JCꢀF = 33.6 Hz), 132.1 (C), 133.2 (C),
139.6 (C), 144.6 (C), 145.4 (C), 147.8 (C), 154.2 (C), 158.5 (CH).
Anal. Calcd for C56H30F12N4: C, 68.16; H, 3.06; N, 5.68%. Found: C,
68.32; H, 3.06; N, 5.52%.
t
major = 37.1 min.
3-[(1-Benzyl-5,5-dimethyl-3-oxo-2-pyrazolidinyl)carbonyl]-
5-naphthylmethyl-5-(2-pyrazoline)carboxylic Acid tert-Bu-
3-Acryloyl-5,5-dimethyl-2-oxazozolidinone (2c)9e was prepared accord-
tyl Ester (19ca). Colorless amorphous; [R]25 = ꢀ69.6 (c 0.40,
ing to the procedure reported by Evans.17
D
CHCl3, 44% ee); IR (KBr) 3327, 2977, 1756, 1728, 1689, 1496, 1424,
1370, 1306, 1254, 1153, 843, 772, 700 cmꢀ1; 1H NMR (CDCl3) δ 1.32
(3H, s), 1.35 (3H, s), 1.38 (9H, s), 2.55 (1H, d, J = 16.9 Hz), 2.64 (1H, d,
J = 16.9 Hz), 2.74 (1H, d, J = 17.1 Hz), 3.03 (1H, d, J = 13.4 Hz), 3.16
(1H, d, J = 13.4 Hz), 3.24 (1H, d, J = 17.1 Hz), 4.03 (1H, d, J = 12.8 Hz),
4.10 (1H, d, J = 12.8 Hz), 6.57 (1H, s), 7.18ꢀ7.42 (11H, m); 13C NMR
(CDCl3) δ 25.9 (CH3), 26.4 (CH3), 27.9 (CH3), 41.1 (CH2), 42.9
(CH2), 43.4 (CH2), 57.7 (CH2), 61.8 (C), 73.6 (C), 82.7 (C), 127.0
(CH), 127.4 (CH), 128.0 (CH), 128.2 (CH), 129.8 (CH), 129.8 (CH),
135.1 (C), 136.2 (C), 144.0 (C), 160.9 (C), 171.6 (C), 173.5 (C); MS
(EI) m/z 490 (M+), 231, 204, 189, 157, 129, 113, 91, 71, 57, 41, 28, 2;
HRMS (EI) Calcd for C28H34N4O4 (M+): 490.2578. Found: 490.2569.
Anal. Calcd for C28H34N4O4: C, 68.55; H, 6.99; N, 11.42%. Found: C,
68.30; H, 6.93; N, 11.72%. The enantiomeric excess was determined by
HPLC analysis (Daicel Chiralpak OZ-3, i-PrOH:hexane = 1:1, detector:
UV 254 nm, flow rate = 0.5 mL/min, 35 °C). tminor =13.9, tmajor = 20.8 min.
Reductive Conversion of 2-Pyrazoline 9aa to Alcohol 20
by NaBH4. Sodium borohydride (19.7 mg, 0.52 mmol) was added to a
solution of 9aa (50.0 mg, 0.13 mmol) in THF (1.6 mL) at ꢀ40 °C and
stirred for 24 h. After completion, a saturated solution of ammonium
chloride (2 mL) and water (2 mL) was added to the reaction mixture at
ꢀ40 °C and then allowed to warm to room temperature with vigorous
stirring. The mixture was extracted with ethyl acetate (4 mL ꢁ 5). The
combined extracts were washed with brine, dried over magnesium
sulfate, and evaporated in vacuo, and then the residue was chromato-
graphed on silica gel (5 g) with hexaneꢀethyl acetate (1:1 v/v) as an
eluent to give the alcohol (16.8 mg, 69%). The enantiomeric excess of
alcohol 20 was determined by HPLC analysis (Daicel Chiralpak AD-H,
3-Acryloyl-5,5-dimethyl-2-oxazozolidinone (2c). Colorless
prisms; mp 83ꢀ85 °C (diethyl etherꢀhexane); IR (KBr) 1767, 1678 cmꢀ1
;
1H NMR (CDCl3) δ 1.53 (6H, s), 3.81 (2H, s), 5.90 (1H, dd, J = 1.9,
10.5 Hz), 6.55 (1H, dd, J = 1.9, 17.1 Hz), 7.52 (1H, dd, J = 10.5, 17.1
Hz); 13C NMR (CDCl3) δ 27.3 (CH3), 54.4 (CH2), 78.7 (C), 127.1
(CH), 131.4 (CH2), 152.3 (C), 165.0 (C); MS (EI) m/z 169 (M+), 125,
97, 82, 67, 55, 43, 27, 18, 15. Anal. Calcd for C8H11NO3: C, 56.80; H,
6.55; N, 8.28%. Found: C, 56.75; H, 6.85; N, 8.21%.
’ ASSOCIATED CONTENT
S
Supporting Information. Spectroscopic data of the pro-
ducts. This material is available free of charge via the Internet at
http://pubs.acs.org.
b
’ AUTHOR INFORMATION
Corresponding Author
*Phone: +81-26-269-5392. Fax: +81-26-269-5424. E-mail:
sugahio@shinshu-u.ac.jp.
’ ACKNOWLEDGMENT
This work was supported in part by a Grant-in-Aid for Scientific
Research (nos. 17550097, 20550094, and 20200052) from the
Ministry of Education, Science and Culture, Japan.
7386
dx.doi.org/10.1021/jo201061f |J. Org. Chem. 2011, 76, 7377–7387

The Journal of Organic Chemistry
ARTICLE
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