Pd-Catalyzed allylic alkylation of secondary nitroalkanes

Article abstract of DOI:10.1016/j.tet.2007.03.062

A Pd-catalyzed allylic alkylation of secondary nitroalkanes, using a catalytic amount of external base, was developed. Simple allyl carbonate and monosubstituted allyl carbonates were used as electrophiles, and bulky secondary nitroalkanes were used as nu

Full text of DOI:10.1016/j.tet.2007.03.062

Tetrahedron 63 (2007) 4250–4257
Pd-Catalyzed allylic alkylation of secondary nitroalkanes
*
Keisuke Maki, Motomu Kanai and Masakatsu Shibasaki
*
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Received 20 February 2007; revised 9 March 2007; accepted 12 March 2007
Available online 14 March 2007
Abstract—A Pd-catalyzed allylic alkylation of secondary nitroalkanes, using a catalytic amount of external base, was developed. Simple allyl
carbonate and monosubstituted allyl carbonates were used as electrophiles, and bulky secondary nitroalkanes were used as nucleophiles. This
is the first catalytic allylic alkylation of bulky secondary nitroalkanes, such as 2-nitroheptane. The use of the strong base DBU in the aprotic
polar solvent DMSO is a key in realizing the high reactivity. In an attempt to develop an asymmetric reaction, 2-aryloxazoline ligand PHOX
L1 gave excellent results for inducing chirality at the p-allyl moiety. As for asymmetric induction at the a-position of the NO2 functionality,
the free OH-group containing 2-aryloxazoline ligand L4 showed moderate selectivity.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
remains much room for improvement in a-asymmetric
induction.
Nitroalkanes are valuable prenucleophiles in synthetic or-
ganic chemistry, because the nitro group is easily trans-
formed into a wide variety of functional groups, such as
amines, carboxyl groups, hydroxylamines, imines, and ox-
imes.1–3 Nitroalkanes, however, are much less frequently
applied to Pd-catalyzed allylic alkylation,4 an effective syn-
thetic methodology for the formation of carbon–carbon
bonds, but are often used as prenucleophiles in 1,2- and
1,4-additions to carbonyl compounds.5 Although allylic al-
kylation of nitroalkanes has been reported,6,7 there are three
major problems in those reactions.
In this article, we report our effort to solve these problems.
2. Results and discussion
2.1. Solvent and external base effect
First, the solvent and external base effects were examined
using cinnamyl alcohol derivative 1a as an electrophile, 2-
nitroheptane (2a) as a nucleophile, and Pd-tol-BINAP com-
plex as a catalyst (Table 1). In entries 1–7, 10 mol % of
DABCO was used as a base, and various solvents were eval-
uated. The more polar the solvent, the higher the obtained
yield. In the case of DMSO, product 3aa was generated in
50% yield (entry 5). In protic solvents, the reaction hardly
proceeded (entries 6 and 7). Next, several catalytic bases
were screened using DMSO as the solvent (entries 8–13).
As the basicity increased, the yield improved. DBU was
the optimum base, and a maximum yield of 86% was ob-
tained (entry 13). In all entries, significant levels of enan-
tioinduction were not observed, although the chiral ligand
(S)-tol-BINAP was used (ee<5%).
(1) Applicable prenucleophiles are limited to nitromethane,
primary nitroalkanes, and 2-nitropropane because bulky
secondary nitroalkanes are hardly reactive; e.g., 2-nitro-
butane and 2-nitropentane are far less reactive than
2-nitropropane.6e
(2) A stoichiometric amount of external base is often uti-
lized. Although reactions without external base6b,h,7a
and with a catalytic base6e are reported, a large amount
of Pd catalyst and/or high temperature are usually re-
quired, perhaps because the reactivity is not satisfactory
in these reactions.
(3) Enantioinduction at the a-position of the NO2 group is
difficult. There is only one study in which this type of
enantioinduction was realized.7b Several primary nitro-
alkanes are applicable prenucleophiles in this reaction,
whereas 3-pentene-2-ol-derived methyl carbonate is
the only applicable p-allyl source. Therefore, there
2.2. Substrate generality
Substrate generality was investigated under the optimized
conditions described above. Based on examinations of the
Pd sources and ligands, Pd(PPh3)4 (catalyst A) was used
for electrophile 1e, and Pd2(dba)3$CHCl3 and rac-BINAP
(catalyst B) were used for other electrophiles. Yields
exceeded 70% in most cases (Table 2). 3-Penten-2-ol
* Corresponding authors. Fax: +81 3 5684 5206; e-mail: mshibasa@mol.f.
u-tokyo.ac.jp
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.03.062

K. Maki et al. / Tetrahedron 63 (2007) 4250–4257
4251
Table 1. Solvent and external base effect
2-nitroheptane (2a), and nitrocyclohexane (2c) showed
good reactivity.
Ph
OBoc
Pd2(dba)3-CHCl3
(2.5 mol %)
1a
NO2
+
Ph
(S)-tol-BINAP (7.5 mol %)
2.3. Mechanistic consideration
NO2
n-C5H11
2a (1.5 mol eq)
n-C5H11
base (10 mol %)
solvent, r.t., 48 h
3aa
The proposed catalytic cycle of Pd and DBU in this reaction
is depicted in Figure 1. p-Allyl–Pd complex III, generated
from Pd catalyst and starting allyl carbonate I via the forma-
tion of Pd–olefin complex II and subsequent decarboxyl-
ation, reacted with nitronate VII, which was produced from
starting nitroalkane VI and DBU, to give another Pd–olefin
complex, IV. Dissociation of product V from IV regenerated
the Pd catalyst. Protonated DBU in VII should be neutralized
by the tert-butoxide anion in p-allyl–Pd complex III. The
roles of DMSO and DBU are proposed to be as follows.
Entry
Base
Solvent
Yielda (%)
1
2
3
4
5
6
7
8
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
None
Toluene
CH2Cl2
THF
DMF
DMSO
t-BuOH
MeOH/CH2Cl2 (1:1)
DMSO
6
4
8
35
50
0
0
8
9
La (Oi-Pr)3
i-Pr2NEt
TMGb
DMSO/THF (1:1)
DMSO
DMSO
DMSO
DMSO
14
15
75
71
86
DMSO: Ionized states of p-allyl–Pd complex III and nitro-
nate VII should be stable due to the high polarity of DMSO.
As a result, the electrophilicity of the p-allyl–Pd cation and
the nucleophilicity of the nitronate would be enhanced.
These two factors should facilitate the nucleophilic attack
of nitronate VII to p-allyl–Pd species III, which is generally
thought to be the rate-determining step in catalytic allylic
alkylations.
10
11
12
13
TBDc
DBU
a
NMR analysis.
1,1,3,3-Tetramethylguanidine.
1,5,7-Triazabicyclo[4.4.0]dec-5-ene.
b
c
derivative 1f, however, was totally unreactive (entry 12), and
only 41% of the target molecule was obtained, even when
5 mol % of the Pd catalyst and a stoichiometric amount
of DBU were used (entry 13). Other acceptors, such as
simple allyl carbonate 1b, monosubstituted 1a, 1c, and
1d, and 1,3-diphenylprop-2-en-1-ol derivative 1e, gave
satisfactory results. As for the nucleophile, all those tested
reacted smoothly. In the case of 1-nitrohexane (2e), however,
diallylated product 4 was generated in 15% yield (entry
10). Secondary nitroalkanes, 2-nitropropane (2b), bulky
DBU: Nitroalkane is smoothly deprotonated by DBU. De-
protonation by tert-butoxide in III might be slow (Table 1,
entry 8), probably due to steric factors derived from both
nitroalkane and III. In the case of 2-nitropropane, the reac-
tion proceeded rapidly even in the absence of external base.8
This finding supports the assumption that the bulkiness of ni-
troalkane hinders the reactivity. A tert-butoxide III can be
considered as a bulky base, because it consists of tert-butyl
moiety and a sterically demanding counter cation, including
Table 2. Substrate generality
Pd2(dba)3-CHCl3 (0.5X mol %)
R3
R3
rac-BINAP (1.5X mol %) (A)
R4
NO2
or
R4 NO2
R1
OBoc
+
R1
Pd(PPh3)4 (X mol %) (B)
R2
1
R5
R2 R5
3
DBU (10 mol %)
DMSO, r.t., 48 h
2 (1.5 mol eq)
Entry
Electrophile
R3
Nucleophile
R5
Catalyst (A or B)
X
Temp (ꢀC)
Yielda (%)
R1
R2
R4
1
2
3
4
5
6
7
8
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph
Ph
H
Ph
Ph
H
Ph
Me
Me
1b
Me
Me
Me
Me
Me
Me
n-C5H11
n-C5H11
n-C5H11
n-C5H11
n-C5H11
Me
2a
2a
2a
2a
2a
2b
2c
2c
2d
2e
2e
2b
2b
A
A
A
A
B
B
A
B
B
A
B
A
A
1
2
2
1
2
1
1
2
1
1
2
2
5
rt
96
100
82
1c
1d
1a
1e
1e
1a
1e
1e
1a
1e
1f
50
50
50
rt
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
72
71b
100
79
rt
c-Hexyl
c-Hexyl
c-Pentyl
50
50
rt
50
50
50
50
82
9
100
51c
80b
Trace
41
10
11
12
13d
H
H
Me
Me
n-C5H11
n-C5H11
Me
Me
1f
a
NMR analysis.
dr¼1.1:1.
b
c
d
15% of diallylation product 4 was obtained.
100 mol % of DBU was used, X¼5.
Ph
NO2
Ph
4
C5H11

4252
K. Maki et al. / Tetrahedron 63 (2007) 4250–4257
t
O
O Bu
R
NO2
t
BuOH
I
O
R'
VI
N
Pd
t
O
O Bu
N
II
O
CO2
Pd
Pd0
t
O Bu
III
H
N
R
NO2
N
Pd
R'
O
N
R
IV
NO2
R
VII
O
R'
Figure 1. Catalytic cycle of Pd and DBU.
R'
V
a phosphine ligand and p-allyl moiety. A strong base such as
DBU is necessary to fully deprotonate the bulky nitroalkane.
A high concentration of nitronate should be crucial for pro-
moting this allylic substitution.
nitrocyclopentane (2d), the product was obtained quantita-
tively, but the enantioselectivity was very low (entry 3). In
entries 4 and 5, using ethyl 2-nitropropionate (2f) and 2-
nitro-1-phenylpropane (2g) as donors, the ees were high,
but the diastereomeric ratios were very low.
The low reactivity of the 3-penten-2-ol derivative 1f is attrib-
uted to the character of III, generated from 1f. Two methyl
substituents of this p-allyl moiety would make III less cat-
ionic and sterically more hindered.
The relative stereochemistry of 3ef was determined by NOE
analysis of 7, which was synthesized from 3ef in five steps
(Scheme 1).7d At first, the ester moiety and nitro group of
3ef (two diastereomers, 3efLP and 3efMP, separated by sil-
ica gel column chromatography; 3efLP and 3efMP stand for
the less polar and the more polar diastereomers of 3ef, re-
spectively) were reduced with LiAlH4 and Zn, respectively.
One-step reduction of these two functionalities using
2.4. Catalytic asymmetric reaction using 1e as an
electrophile
The asymmetric reaction was performed using 1e as an ac-
ceptor. In initial investigations of the reaction conditions,
PHOX ligand L19 showed high enantioselectivity. Using
this ligand, the generality of the nucleophile was examined
(Table 3). 2-Nitropropane (2b) gave the product 3eb in quan-
titative yield and 94% ee (entry 1). The absolute configura-
tion of 3eb was assigned as R by comparing the sign of its
optical rotation with data reported in the literature.10
Ph
Ph
1) LiAlH4, THF, -78 °C
NO2
NH2
OH
Ph
Ph
i
2) Zn, 1 N HCl aq., PrOH
CO2Et
3ef LP
5LP
3ef MP
5MP
t N
1) triphosgene, E
3
CH2Cl
2, -78 to -40 °C
The product derived from nitrocyclohexane (2c) was ob-
tained in 78% yield and 82% ee (entry 2). In the case of
2) allyl bromide, NaH
DMF, 0 °C to r.t.
Table 3. Nucleophile generality of catalytic asymmetric allylation using 1e
1st generation Grubbs'
catalyst (5 mol %)
CH2Cl2, reflux
Ph
Ph
Ph
OBoc
N
O
N
O
O
O
Ph
O
Ph
Ph
R1
NO2
PPh2
(6 mol %)
N
L1
1e
i
Ph
Pr
7LP (80%)
7MP(65%)
6LP (87% for 4 steps)
6MP(69% for 4 steps)
+
R1
R2
NO2
Pd2(dba)3-CHCl3 (2.5 mol %)
3
R2
2
DBU (10 mol %), DMSO, r.t., 24 h
Ph
H
Ph
H
Entry
R1
R2
Yielda (%)
dr
eeb (%)
N
O
O
N
O
O
1
2
3
4
5
Me
Me
c-Hexyl
c-Pentyl
2b
2c
2d
2f
100
78
100
83
—
—
—
1.6:1
1.1:1
94 (R)
82
5
93:94
93:94
8%
0%
7LP
7MP
Me
Me
CO2Et
Bn
LP = the less polar diastereomer
MP = the more polar diastereomer
2g
100
a
NMR analysis.
Chiral HPLC analysis.
b
Scheme 1. Conversion of 3ef and determination of stereochemistry.

K. Maki et al. / Tetrahedron 63 (2007) 4250–4257
4253
LiAlH4 was unsuccessful. The obtained aminoalcohol 5 was
converted to 6 via cyclic carbamate formation and N-allyl-
ation. The yields of 6LP and 6MP from 3ef were 87% and
69%, respectively. Ring-closing metathesis of 6 using first-
generation Grubbs’ catalyst gave 7 in good yield. NOE anal-
ysis of 7 demonstrated that 3efLP was a syn diastereomer
(minor), and 3efMP was an anti product (major).
9). A nearly quantitative yield of the target moleculewas pro-
duced when the amount of L4 was reduced to 1.3 mol %
(1.3 equiv of Pd; entry 10). When L1 was used, the same
ee values were obtained both in DMSO and toluene (entries
2 and 11). Therefore it is likely that the expected interaction
between the nitronate and the OH group of L4 did work
effectively. The ee was further improved to 49% by using
TBD as an external base (entry 12). Although enantioselec-
tivity was moderate, this is the first example of a catalytic
asymmetric allylic alkylation of secondary nitroalkane that
induces chirality at the a-position of an NO2 group.
2.5. Asymmetric induction at the a-position of NO2
group
Next, we attempted asymmetric induction at the a-position
of the NO2 group. The product should be a precursor of chi-
ral a-tertiary amines, which are not easily accessible using
the current catalytic methods.11 Results of the preliminary
investigation are listed in Table 4. Allyl carbonate 1b and
nitroalkane 2g were chosen as the substrates. Some chiral
ligands were first examined, but none of them gave satisfac-
tory results (entries 1–4), probably because the chiral ligand
exists very far from the prochiral donor nitroalkane 2g in the
enantioinduction step.
The absolute configuration of 3bg was determined as fol-
lows (Scheme 2). Cross metathesis between 3bg and 1-non-
ene in the presence of second-generation Grubbs’ catalyst,
hydrogenation of the product, and subsequent N-acetylation
gave known compound 814 in 53% yield in three steps. Com-
parison of the sign of its optical rotation with the reported
value indicated that the stereochemistry of 8 was S. When
molecular hydrogen was used instead of ammonium formate
in the hydrogenation of the cross metathesis product, the re-
action was sluggish, and the yield was only ca. 20%, even
under high pressure (ca. 50 atm). Adams’ catalyst and Pearl-
man’s catalyst gave the product in only trace amounts.
Therefore, L4 was used based on the assumption that the
nitronate derived from 2g could interact with L4 through
hydrogen bonding with its free OH functionality.12 This
interaction should position 2g closer to the chiral environ-
ment created by Pd and L4.13 In DMSO, however, almost
no chiral induction was observed (entry 5). Perhaps the polar
solvent weakened the expected interaction between the
ligand and the nitronate. To make the interaction more
effective, less polar solvents were tested (entries 6–9). As
expected, enantioselectivity was higher when a less polar sol-
vent was utilized, although the yield was lower. In toluene,
the yield and the ee were 56% and 42%, respectively (entry
1) 1-nonene, 2nd generation
Grubbs' catalyst (5 mol %)
CH2Cl2, 35 °C
NHAc
NO2
8
Bn
Bn
3bg (44% ee)
2) ammonium formate
Pd/C, MeOH, 50 °C
3) Ac2O, Et3N, DMAP, CH2Cl2
8 (53% for 3 steps)
[α]D21=+8.5
(c 0.5, acetone)
lit. [α]D29=+28.9 (c 0.5,
acetone) for S-enantiomer
Scheme 2. Conversion of 3bg and determination of its absolute configura-
tion.
Table 4. Attempts toward a-asymmetric induction
3. Conclusions
Pd2(dba)3-CHCl3 (0.5 mol %)
ligand (2 mol %)
OBoc
1b
NO2
+
NO2
We developed a Pd-catalyzed allylic alkylation of secondary
nitroalkanes using a catalytic amount of external base.
Monosubstituted allyl carbonates and bulky secondary nitro-
alkanes can be used as electrophiles and nucleophiles, re-
spectively. Bulky nitroalkanes such as 2-nitroheptane have
not before been used in the Pd-catalyzed allylic alkylation.
The strong base DBU and the aprotic polar solvent DMSO
have important roles in realizing the high reactivity. In the
asymmetric reaction using 1e as an electrophile, the 2-aryl-
oxazoline ligand PHOX L1 gave excellent results for induc-
ing chirality at the p-allyl moiety. As for asymmetric
induction at the a-position of the NO2 functionality, the
free OH group-containing 2-aryloxazoline ligand L4 pro-
duced moderate enantioselectivity. Chiral tertiary amines
can be synthesized by this method. Further investigation of
the effect of chiral ligands containing OH functionality
could improve the enantioselectivity.
DBU (10 mol %)
DMSO, r.t., 24 h
Bn
3bg
2g
Bn
Entry
Ligand
Solvent
Yielda (%)
eeb (%)
1
(S)-tol-BINAP
L1
Taniaphos (L2)
(R)-SEGPHOS (L3)
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
78
100
63
86
94
41
63
59
56
95
96
94
3
18
2
1
4
17
36
23
42
44
18
49
2c
3
4
5
6
7
8
9
L4
L4
L4
L4
L4
L4
L1
L4
THF
CH2Cl2
Toluene
Toluene
Toluene
Toluene
10c
11c
12c,d
a
NMR analysis.
Chiral HPLC analysis.
1.3 mol % of L1 (entries 2 and 12) or L4 (entries 10 and 11) was used.
TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene) was used as external base.
b
c
d
O
4. Experimental
4.1. General
Ph2P
O
O
O
PPh2
PPh2
Ph
Ph2P
Fe
N
PPh2
NMe2
CH2OH
O
Infrared (IR) spectra were recorded on a JASCO FTIR 410
Fourier transform infrared spectrophotometer. NMR spectra
(R)-SEGPHOS (L3)
Taniaphos (L2)
L4

4254
K. Maki et al. / Tetrahedron 63 (2007) 4250–4257
were recorded on a JEOL JNM-LA500, ECX500 or ECA500
spectrometer, operating at 500 MHz for 1H NMR and
125.65 MHz for 13C NMR. Chemical shifts were reported in
parts per million on the scale relative to residual CHCl3
(d¼7.24 for 1H NMR and d¼77.0 for 13C NMR) as an internal
reference. ESI mass spectra were measured on Waters-
ZQ4000. EI mass spectra were measured on a JEOL JMS-
BU20 GCmate or a JEOL JMS-700V. Optical rotations were
measured on a JASCO P-1010 polarimeter. Column chromato-
graphy was performed with silica gel Merck 60 (230–400 mesh
ASTM). The eewas determined by HPLC analysis. HPLC was
performedon JASCO HPLC systems consistingof the flowing:
pump, 880-PU or PU-980; detector, 875-UV or UV-970,
measured at 254 nm. Reactions were carried out in dry solvents
under an argon atmosphere, unless otherwise stated.
4.2.4. (1E)-4-Methyl-4-nitro-1-phenynon-1-ene (3aa). 1H
NMR (500 MHz, CDCl3) d: 0.81 (br t, J¼6.8 Hz, 3H),
1.10–1.31 (m, 6H), 1.69–1.78 (m, 1H), 1.90–1.99 (m, 1H),
2.60 (dd, J¼8.0, 14.3 Hz, 1H), 2.82 (dd, J¼7.5, 14.3 Hz,
1H), 5.95 (ddd, J¼7.5, 8.0, 16.1 Hz, 1H), 6.40 (d,
J¼16.1 Hz, 1H), 7.13–7.18 (m, 1H), 7.20–7.28 (m, 4H);
13C NMR (126 MHz, CDCl3) d: 13.9, 22.0, 22.3, 23.4,
31.6, 39.5, 43.1, 91.4, 122.4, 126.3, 127.7, 128.5, 135.1,
136.7; IR (neat, cmꢁ1): 969, 1091, 1389, 1537, 2955; MS
(EI) m/z 215 (M+ꢁNO2); HRMS (EI) calcd for C16H23
(M+ꢁNO2): 215.1800, found: 215.1802.
4.2.5. (1E)-4-Methyl-4-nitro-1,3-diphenylnon-1-ene (dia-
stereomixture) (3ea). 1H NMR (500 MHz, CDCl3) d: 0.76
(br t, J¼6.9 Hz, 3H for minor), 0.78 (br t, J¼6.9 Hz, 3H
for major), 0.93–1.08 (m, 1H), 1.08–1.30 (m, 5H), 1.32–
1.40 (m, 1H for minor), 1.48 (s, 3H for major), 1.51 (s, 3H
for minor), 1.64–1.73 (m, 1H for major), 2.07–2.18 (m,
1H), 3.97 (d, J¼9.2 Hz, 1H for minor), 4.05 (d, J¼9.8 Hz,
1H for major), 6.42–6.34 (m, 1H), 6.48 (dd, J¼9.2,
16.0 Hz, 1H for minor), 6.52 (d, J¼15.6 Hz, 1H for major),
7.10–7.33 (m, 10H); 13C NMR (126 MHz, CDCl3) d: 13.9,
13.9, 17.9, 18.0, 22.4, 22.4, 23.4, 23.5, 31.6, 31.7, 38.7,
38.9, 58.4, 58.6, 95.0, 95.6, 125.7, 126.4, 126.5, 127.6,
127.7, 127.7, 127.9, 128.5, 128.5, 128.6, 128.9, 129.3,
134.2, 134.6, 136.6, 136.7, 138.1, 138.3; IR (neat, cmꢁ1):
967, 1389, 1454, 1537, 2955; MS (EI) m/z 291
(M+ꢁNO2); HRMS (EI) calcd for C22H27 (M+ꢁNO2):
291.2113, found: 291.2108.
4.2. General procedure for Pd-catalyzed allylic
alkylation of secondary nitroalkane
To a stirred solution of Pd complex (Pd2(dba)3$CHCl3 and
phosphine ligand, or Pd(PPh3)4), and external base
(0.02 mmol) in the solvent indicated (200 mL), allyl carbon-
ate (0.2 mmol) and nitroalkane (0.3 mmol) were succes-
sively added at room temperature. After the time
indicated, the reaction mixture was passed through a plug
of silica gel (5 g) eluting with AcOEt (40 mL). After evapo-
1
ration of the solvent, yield and dr were determined by H
NMR using DMF as internal standard. ee was determined
by chiral HPLC analysis after PTLC purification.
4.2.1. 4-Methyl-4-nitronon-1-ene (3ba). 1H NMR
(500 MHz, CDCl3) d: 0.81 (br t, J¼6.1 Hz, 3H), 1.06–1.16
(m, 1H), 1.16–1.28 (m, 5H), 1.67–1.73 (m, 1H), 1.85–1.94
(m, 1H), 2.46 (dd, J¼7.4, 14.3 Hz, 1H), 2.66 (dd, J¼6.9,
14.3 Hz, 1H), 5.05–5.11 (m, 2H), 5.58 (dddd, J¼6.9, 7.4,
10.3, 17.2 Hz, 1H); 13C NMR (126 MHz, CDCl3) d: 13.9,
21.9, 22.3, 23.4, 31.6, 39.3, 43.8, 91.1, 120.3, 131.2; IR
(neat, cmꢁ1): 1092, 1539, 2957; MS (EI) m/z 139
(M+ꢁNO2); HRMS (EI) calcd for C10H19 (M+ꢁNO2):
139.1487, found: 139.1485.
4.2.6. (20E)-1-Nitro-1-(30-phenylprop-20-enyl)cyclohex-
ane (3ac). H NMR (500 MHz, CDCl3) d: 1.20–1.29 (m,
1
1H), 1.31–1.42 (m, 2H), 1.46–1.64 (m, 5H), 2.32–2.40 (m,
2H), 2.61 (br d, J¼7.5 Hz, 2H), 5.94 (dt, J¼7.5, 16.0 Hz,
1H), 6.34 (d, J¼16.0 Hz, 1H), 7.11–7.18 (m, 1H), 7.19–
7.27 (m, 4H); 13C NMR (126 MHz, CDCl3) d: 22.2, 24.7,
33.8, 43.9, 91.6, 121.8, 126.3, 126.3, 127.6, 128.5, 134.9,
136.6; IR (neat, cmꢁ1): 1074, 1343, 1448, 1525, 2936; MS
(EI) m/z 245 (M+); HRMS (EI) calcd for C15H19 NO2
(M+): 245.1416, found: 245.1421.
4.2.2. 2,4-Dimethyl-4-nitronon-1-ene (3ca). 1H NMR
(500 MHz, CDCl3) d: 0.81 (br t, J¼7.2 Hz, 3H), 1.02–1.12
(m, 1H), 1.16–1.32 (m, 5H), 1.45 (s, 3H), 1.61 (br s, 3H),
1.58–1.67 (m, 1H), 1.90–2.01 (m, 1H), 2.38 (d,
J¼14.3 Hz, 1H), 2.78 (d, J¼14.3 Hz, 1H), 4.65 (br s, 1H),
4.84 (br s, 1H); 13C NMR (126 MHz, CDCl3) d: 13.9,
21.3, 22.3, 23.4, 23.5, 31.6, 40.5, 47.8, 91.1, 116.5, 139.6;
IR (neat, cmꢁ1): 1092, 1539, 2957; MS (EI) m/z 153
(M+ꢁNO2); HRMS (EI) calcd for C11H21 (M+ꢁNO2):
153.1643, found: 153.1647.
4.2.7. (20E)-1-Nitro-1-(10,30-diphenylprop-20-enyl)cyclo-
hexane (3ec). H NMR (500 MHz, CDCl3) d: 1.09–1.10
1
(m, 1H), 1.13–1.31 (m, 2H), 1.41–1.50 (m, 1H), 1.50–1.64
(m, 4H), 2.41–2.53 (m, 2H), 3.71 (d, J¼9.8 Hz, 1H), 6.41
(d, J¼15.5 Hz, 1H), 6.48 (dd, J¼9.8, 15.5 Hz, 1H), 7.10–
7.13 (m, 2H), 7.13–7.21 (m, 2H), 7.21–7.27 (m, 4H),
7.27–7.31 (m, 2H); 13C NMR (126 MHz, CDCl3) d: 22.2,
24.5, 31.9, 32.4, 32.4, 59.1, 95.3, 125.7, 126.5, 127.7,
127.8, 128.5, 128.5, 128.9, 134.2, 136.7, 138.0; IR (neat,
cmꢁ1): 974, 1431, 1532, 2940; MS (EI) m/z 275
(M+ꢁNO2); HRMS (EI) calcd for C21H23 (M+ꢁNO2):
275.1800, found: 275.1801.; [a]2D1 ꢁ47.4 (c 1.27, CH2Cl2,
82% ee); HPLC (DAICEL CHIRALCEL OJ-H, 2-propa-
nol/hexane 1:99, flow 1.0 mL/min) tR 9.4 min (minor) and
16.3 min (major).
4.2.3. (2E)-5-Methyl-5-nitrodec-2-ene (3da). 1H NMR
(500 MHz, CDCl3) d: 0.86 (br t, J¼7.2 Hz, 3H), 1.10–1.19
(m, 1H), 1.21–1.33 (m, 5H), 1.47 (s, 3H), 1.64 (dd, J¼1.2,
6.9 Hz, 3H), 1.67–1.76 (m, 1H), 1.90–2.00 (m, 1H), 2.42
(dd, J¼8.0, 14.3 Hz, 1H), 2.62 (dd, J¼7.4, 14.3 Hz, 1H),
5.25 (qddd, J¼1.2, 7.4, 8.0, 16.2 Hz, 1H), 5.53 (qd, J¼6.9,
16.2 Hz, 1H); 13C NMR (126 MHz, CDCl3) d: 13.9, 18.0,
21.7, 22.3, 23.4, 31.7, 39.3, 42.9, 91.5, 123.5, 131.1; IR
(neat, cmꢁ1): 1092, 1539, 2928; MS (EI) m/z 153
(M+ꢁNO2); HRMS (EI) calcd for C11H21 (M+ꢁNO2):
153.1643, found: 153.1639.
4.2.8. (20E)-1-Nitro-1-(10,30-diphenylprop-20-enyl)cyclo-
pentane (3ed). H NMR (500 MHz, CDCl3) d: 1.48–1.65
1
(m, 4H), 1.81–1.91 (m, 1H), 1.93–2.03 (m, 1H), 2.46–2.55
(m, 2H), 4.13 (dd, J¼3.4, 5.2 Hz, 1H), 6.41–6.45 (m, 2H),
7.11–7.19 (m, 4H), 7.19–7.25 (m, 4H), 7.25–7.30 (m, 2H);
13C NMR (126 MHz, CDCl3) d: 23.1, 23.3, 34.1, 34.5,

K. Maki et al. / Tetrahedron 63 (2007) 4250–4257
4255
55.8, 104.5, 126.3, 126.4, 127.6, 127.8, 128.5, 128.6, 128.6,
134.1, 136.6, 138.6; IR (neat, cmꢁ1): 967, 1355, 1453, 1537,
2962; MS (EI) m/z 261 (M+ꢁNO2); HRMS (EI) calcd for
C20H21 (M+ꢁNO2): 261.1643, found: 261.1639; [a]2D0
ꢁ23.4 (c 4.92, CH2Cl2, 5% ee); HPLC (DAICEL CHIRAL-
CEL OD-H, 2-propanol/hexane 1:199, flow 1.0 mL/min) tR
9.9 min (major) and 11.5 min (minor).
(500 MHz, CDCl3) d: 1.12 (t, J¼7.1 Hz, 3H), 1.75 (s, 3H),
4.08 (q, J¼7.1 Hz, 2H), 4.56 (d, J¼8.6 Hz, 1H), 6.45 (d,
J¼16.0 Hz, 1H), 6.58 (dd, J¼8.6, 16.0 Hz, 1H), 7.12–7.30
(m, 10H); 13C NMR (126 MHz, CDCl3) d: 13.7, 20.3,
54.5, 62.9, 96.3, 125.7, 126.5, 127.8, 128.0, 128.5, 128.7,
129.5, 134.54, 136.6, 136.7, 166.6; IR (neat, cmꢁ1): 1104,
1254, 1550, 1745, 2923; MS (EI) m/z 293 (M+ꢁNO2);
HRMS (EI) calcd for C20H21O2 (M+ꢁNO2): 293.1542,
found: 293.1546; [a]D22 ꢁ70.2 (c 0.785, CH2Cl2, 93% ee);
HPLC (DAICEL CHIRALCEL OJ-H, methanol/hexane
1:19, flow 1.0 mL/min) tR 10.7 min (major) and 44.0 min
(minor).
4.2.9. (1E)-4-Nitro-1-phenylnon-1-ene (3ae). 1H NMR
(500 MHz, CDCl3) d: 0.81 (br t, J¼7.0 Hz, 3H), 1.14–1.35
(m, 6H), 1.64–1.73 (m, 1H), 1.89–1.98 (m, 1H), 2.57 (ddd,
J¼6.9, 8.0, 14.9 Hz, 1H), 2.75 (ddd, J¼7.5, 8.5, 14.9 Hz,
1H), 5.94–6.02 (m, 1H), 5.98 (ddd, J¼6.9, 7.5, 16.0 Hz,
1H), 6.40 (d, J¼16.0 Hz, 1H), 7.13–7.18 (m, 1H), 7.20–
7.27 (m, 4H); 13C NMR (126 MHz, CDCl3) d: 13.8, 22.3,
25.4, 31.1, 33.3, 37.3, 88.4, 122.7, 126.3, 126.3, 127.7,
128.5, 128.5, 134.3, 136.5; IR (neat, cmꢁ1): 966, 1074,
1377, 1550, 2928; MS (EI) m/z 201 (M+ꢁNO2); HRMS
(EI) calcd for C15H21 (M+ꢁNO2): 201.1643, found:
201.1644.
4.2.14. (1E)-4-Methyl-4-nitro-1,3,5-triphenylpent-1-ene
(diastereomixture) (3eg). H NMR (500 MHz, CDCl3) d:
1
1.38 (s, 3H for minor), 1.39 (s, 3H for major), 2.55 (d,
J¼14.3 Hz, 1H for major), 2.97 (d, J¼14.4 Hz, 1H for mi-
nor), 3.54–3.60 (m, 1H), 4.14 (d, J¼9.2 Hz, 1H for major),
4.25 (d, J¼10.3 Hz, 1H for minor), 6.42 (d, J¼16.1 Hz,
1H for major), 6.45–6.55 (m, 1H), 6.64 (d, J¼16.1 Hz, 1H
for minor), 6.85–6.92 (m, 1H), 6.94–7.00 (m, 1H), 7.10–
7.38 (m, 13H); 13C NMR (126 MHz, CDCl3) d: 17.1, 17.6,
44.8, 44.9, 58.4, 58.6, 95.4, 95.9, 125.4, 125.5, 126.5,
126.6, 127.4, 127.4, 127.8, 127.8, 127.9, 128.1, 128.5,
128.5, 128.6, 128.7, 128.8, 128.9, 129.5, 130.1, 130.2,
134.3, 134.5, 134.5, 135.3, 136.5, 136.6, 137.8, 138.1; IR
(neat, cmꢁ1): 909, 1495, 1539, 2250, 3029; MS (EI) m/z
311 (M+ꢁNO2); HRMS (EI) calcd for C24H23 (M+ꢁNO2):
311.1800, found: 311.1801; [a]2D3 ꢁ62.3 (c 1.86, CH2Cl2,
1.1:1 diastereomixture (93%–94% ee)); HPLC (DAICEL
CHIRALCEL OD-H, 2-propanol/hexane 1:99, flow
1.0 mL/min) tR 12.7 min (major A), 14.1 min (minor A),
19.6 min (major B), and 25.3 min (minor B).
4.2.10. (1E)-4-Nitro-1,3-diphenylnon-1-ene (less polar)
(3eeLP). 1H NMR (500 MHz, CDCl3) d: 0.75 (br t,
J¼7.5 Hz, 3H), 1.05–1.20 (m, 6H), 1.32–1.39 (m, 1H),
1.77–1.86 (m, 1H), 3.78 (dd, J¼9.2, 10.9 Hz, 1H), 4.75
(ddd, J¼2.9, 10.9, 10.9 Hz, 1H), 6.23 (dd, J¼9.2, 16.0 Hz,
1H), 6.37 (d, J¼16.0 Hz, 1H), 7.11–7.16 (m, 1H), 7.16–
7.25 (m, 7H), 7.25–7.32 (m, 2H); 13C NMR (126 MHz,
CDCl3) d: 13.8, 22.4, 25.5, 30.9, 31.9, 53.8, 93.2, 126.5,
127.2, 127.7, 127.8, 127.9, 128.4, 129.3, 133.0, 136.4,
138.7; IR (neat, cmꢁ1): 967, 1095, 1455, 1550, 2927; MS
(EI) m/z 277 (M+ꢁNO2); HRMS (EI) calcd for C21H25
(M+ꢁNO2): 277.1956, found: 277.1951.
4.2.11. (1E)-4-Nitro-1,3-diphenylnon-1-ene (more polar)
(3eeMP). 1H NMR (500 MHz, CDCl3) d: 0.84 (br t,
J¼6.9 Hz, 3H), 1.24–1.32 (m, 6H), 3.93 (dd, J¼9.7,
10.3 Hz, 1H), 4.85 (ddd, J¼3.4, 10.3, 10.9 Hz, 1H), 6.20
(dd, J¼9.7, 16.1 Hz, 1H), 6.54 (d, J¼16.1 Hz, 1H), 7.21–
7.25 (m, 4H), 7.27–7.34 (m, 6H); 13C NMR (126 MHz,
CDCl3) d: 13.9, 22.3, 25.6, 31.1, 32.4, 54.0, 92.5, 126.4,
126.8, 127.5, 127.6, 128.0, 128.6, 129.0, 133.6, 136.3,
139.0; IR (neat, cmꢁ1): 967, 1095, 1455, 1550, 2927; MS
(EI) m/z 277 (M+ꢁNO2); HRMS (EI) calcd for C21H25
(M+ꢁNO2): 277.1956, found: 277.1950.
4.2.15. (4E)-2-Methyl-2-nitro-1-phenylpent-4-ene (3bg).
1H NMR (500 MHz, CDCl3) d: 1.40 (s, 3H), 2.44 (dd,
J¼8.0, 14.3 Hz, 1H), 2.79 (dd, J¼7.4, 14.3 Hz, 1H), 2.98
(d, J¼13.8 Hz, 1H), 3.29 (d, J¼13.8 Hz, 1H), 5.08–5.15
(m, 2H), 5.63 (dddd, J¼7.4, 8.0, 9.7, 14.7 Hz, 1H), 7.00–
7.05 (m, 2H), 7.17–7.25 (m, 3H); 13C NMR (126 MHz,
CDCl3) d: 21.3, 43.8, 45.6, 91.5, 120.8, 127.5, 128.5,
130.1, 130.8, 134.6; IR (neat, cmꢁ1): 1092, 1388, 1540,
2926; MS (EI) m/z 159 (M+ꢁNO2); HRMS (EI) calcd for
C21H25 (M+ꢁNO2): 159.1174, found: 159.1178; [a]2D0
+17.0 (c 0.1, CH2Cl2, 49% ee); HPLC (DAICEL CHIRAL-
CEL OJ-H, 2-propanol/hexane 1:19, flow 1.0 mL/min) tR
9.8 min (minor) and 10.9 min (major).
4.2.12. Ethyl (4E)-2-methyl-2-nitro-3,5-diphenyl-4-pen-
tenoate (less polar diastereomer) (3efLP). 1H NMR
(500 MHz, CDCl3) d: 1.19 (t, J¼7.5 Hz, 3H), 1.75 (s, 3H),
4.18 (qd, J¼7.5, 7.5 Hz, 1H), 4.19 (qd, J¼7.5, 7.5 Hz,
1H), 4.54 (dd, J¼1.2, 6.9 Hz, 1H), 6.44–6.53 (m, 2H),
7.14–7.18 (m, 1H), 7.20–7.30 (m, 9H); 13C NMR
(126 MHz, CDCl3) d: 13.8, 20.2, 54.6, 62.9, 96.2, 125.5,
126.5, 127.9, 128.0, 128.5, 128.7, 129.5, 134.6, 136.6,
136.9, 166.6; IR (neat, cmꢁ1): 1095, 1246, 1553, 1747,
2928; MS (EI) m/z 293 (M+ꢁNO2); HRMS (EI) calcd for
C20H21O2 (M+ꢁNO2): 293.1542, found: 293.1546; [a]2D2
ꢁ52.7 (c 0.56, CH2Cl2, 94% ee); HPLC (DAICEL CHIR-
ALCEL OJ-H, methanol/hexane 1:19, flow 1.0 mL/min) tR
11.7 min (major) and 49.6 min (minor).
4.3. Conversion of 3ef and determination of its
stereochemistry
4.3.1. (100R,4R,200E)-4-(100,300-Diphenylprop-200-enyl)-3-
(20-propenyl)-4-methyl-oxazolidin-2-one (6LP). To a sus-
pension of LiAlH4 (10.5 mg, 0.28 mmol) in THF (0.5 mL),
a solution of 3efLP (62.7 mg, 0.185 mmol) in THF
(0.5 mL) was slowly added at ꢁ78 ꢀC. After 15 min, 1 N
aq HCl (1.0 mL) was slowly added to the mixture at 0 ꢀC.
The product was extracted with CH2Cl2. The combined or-
ganic layer was washed with brine and dried over Na2SO4.
After filtration and evaporation, the residue was dissolved
in 2-propanol (4.0 mL). To the solution, 1 N HCl (2.0 mL)
and Zn powder (0.240 g, 3.7 mmol) were added, and the
whole was stirred for 15 min at room temperature. To the
4.2.13. Ethyl (4E)-2-methyl-2-nitro-3,5-diphenyl-4-pen-
tenoate (more polar diastereomer) (3efMP). H NMR
1

4256
K. Maki et al. / Tetrahedron 63 (2007) 4250–4257
mixture, satd NaHCO3 was added, and the whole was stirred
for 30 min. After filtration, the product was extracted with
CH2Cl2, and the combined organic layer was dried over
Na2SO4. After filtration and evaporation, the residue was dis-
solved in CH2Cl2 (1.0 mL). To the solution, Et3N (69.7 mL,
0.50 mmol) and triphosgene (59.3 mg, 0.20 mmol) were
added at ꢁ78 ꢀC. The mixture was gradually warmed to
ꢁ40 ꢀC, and stirred for 15 min. 1 N HCl was slowly added
to the mixture, and the product was extracted with CH2Cl2.
The combined organic layer was washed with satd NaHCO3
and brine, and dried over Na2SO4. After filtration and evap-
oration, the residue was dissolved in DMF (1.0 mL). To the
solution, NaH (24 mg, 0.60 mmol) was added at 0 ꢀC, and
the whole was stirred for 15 min at the same temperature.
To the mixture, allyl bromide (51.7 mL, 0.60 mmol) was
added, and the whole was stirred for 2 h at room temperature.
After satd NH4Cl was added to the mixture, the product was
extracted with AcOEt. The combined organic layer was
washed with brine, and dried over Na2SO4. After filtration
and evaporation, the residue was purified through silica gel
column chromatography (AcOEt/hexane 2:8–3:7). The tar-
get molecule 6LP was obtained as colorless solid (53.6 mg,
(d, J¼7.9 Hz, 1H), 4.31 (br d, J¼18.9 Hz, 1H), 5.83–5.91
(m, 2H), 7.00–7.04 (m, 2H), 7.20–7.23 (m, 1H), 7.23–7.28
(m, 2H); 13C NMR (126 MHz, CDCl3) d: 25.4, 39.0, 49.4,
58.3, 71.6, 122.0, 127.2, 127.8, 128.8, 129.1, 138.2, 156.8;
IR (KBr, cmꢁ1) 1072, 1416, 1737, 2918, 3450; MS (EI)
m/z 229 (M+); HRMS calcd for C14H15NO2 (M+):
229.1098, found: 229.1096; [a]1D9 ꢁ730 (c 0.1, CHCl3).
The absolute configuration at C8 position is considered as
R by analogy with 3eb.
4.3.4. (8R,8aS)-8a-Methyl-8-phenyl-1,5,8,8a-tetrahydro-
oxazolo[3,4-a]pyridin-3-one (7MP). Following the proce-
dure for 7LP, 7MP was obtained as pale yellow oil in 65%
1
yield. H NMR (500 MHz, CDCl3) d: 1.05 (s, 3H), 3.69
(m, 1H), 3.64–3.71 (m, 1H), 3.83 (d, J¼8.9 Hz, 1H), 4.21–
4.29 (m, 1H), 4.40 (d, J¼8.9 Hz, 1H), 5.83–5.92 (m, 2H),
7.14–7.18 (m, 2H), 7.27–7.36 (m, 3H); 13C NMR
(126 MHz, CDCl3) d: 18.4, 39.1, 47.9, 58.5, 73.0, 123.8,
127.6, 128.3, 128.6, 129.0, 139.1, 157.0; IR (neat, cmꢁ1):
1066, 1409, 1757, 2920, 3400; MS (EI) m/z 229 (M+);
HRMS calcd for C14H15NO2 (M+): 229.1098, found:
229.1100; [a]1D9 +22 (c 0.15, CHCl3). The absolute configu-
ration at C8 position is considered as R by analogy with 3eb.
1
87%). H NMR (500 MHz, CDCl3) d: 1.22 (s, 3H), 3.42
(dd, J¼6.9, 16.6 Hz, 1H), 3.66 (d, J¼8.0 Hz, 1H), 3.76
(d, J¼8.8 Hz, 1H), 3.88 (dd, J¼5.7, 16.6 Hz, 1H), 4.57
(d, J¼8.8 Hz, 1H), 5.09 (d, J¼17.2 Hz, 1H), 5.15 (d,
J¼17.2 Hz, 1H), 5.80 (dddd, J¼5.7, 6.9, 10.3, 17.2 Hz,
1H), 6.36 (d, J¼16.0 Hz, 1H), 6.45 (dd, J¼8.0, 16.0 Hz,
1H), 7.15–7.31 (m, 10H); 13C NMR (126 MHz, CDCl3) d:
23.7, 43.8, 55.5, 64.1, 71.0, 117.2, 126.4, 126.5, 127.6,
127.8, 128.6, 128.8, 128.9, 129.0, 134.1, 134.6, 136.6,
139.0, 157.7; IR (KBr, cmꢁ1) 1054, 1400, 1743, 2922,
3470; MS (EI) m/z 140 (M+ꢁPhCHCHCHPh); HRMS calcd
for C7H10NO2 (M+ꢁPhCHCHCHPh): 140.0775, found:
140.0779; [a]1D9 +80.5 (c 0.19, CHCl3).
4.4. Conversion of 3bg and determination of its absolute
configuration
4.4.1. N-(1-Benzyl-1-methylundecyl)acetamide (8). To
a mixture of 3bg (101.7 mg, 0.496 mmol) and 1-nonene
(430 mL, 2.48 mmol) in CH2Cl2 (2.5 mL), second genera-
tion Grubbs’ catalyst (21.2 mg, 0.0248 mmol) was added.
The mixture was stirred at 35 ꢀC for 5 h. After cooling to
room temperature, the solvent was evaporated, and the resi-
due was passed through short pad silica gel (hexane only to
AcOEt/hexane 1:19) to remove the catalyst and 1-nonene de-
rivatives. After the solvent was evaporated, Pd/C (60.0 mg),
ammonium formate (1.89 g, 30.0 mmol), and MeOH
(5.0 mL) were added to the residue, and the mixture was
stirred at 50 ꢀC for 24 h. After filtration, the solventwas evap-
orated, and the residue was dissolved in CH2Cl2 (2.5 mL). To
this solution, DMAP (60.5 mg, 0.0496 mmol), Et3N
(280 mL, 0.992 mmol), and Ac2O (95.0 mL, 0.496 mmol)
were added. The mixture was stirred at room temperature
for 12 h. After the solvent was evaporated, the residue was
purified through silica gel column chromatography
(AcOEt/hexane 1:4). Product 8 was obtained in 53% yield
(72.3 mg, 0.263 mmol). [a]2D1 +8.5 (c 0.5, acetone).
4.3.2. (100R,4S,200E)-4-(100,300-Diphenylprop-200-enyl)-3-
(20-propenyl)-4-methyl-oxazolidin-2-one (6MP). Follow-
ing the procedure for 6LP, 6MP was obtained as colorless
1
oil in 69% yield. H NMR (500 MHz, CDCl3) d: 1.22 (s,
3H), 3.54 (dd, J¼6.9, 16.6 Hz, 1H), 3.59 (d, J¼8.0 Hz,
1H), 3.78 (d, J¼8.8 Hz, 1H), 3.95 (dd, J¼5.2, 16.6 Hz,
1H), 4.48 (d, J¼8.8 Hz, 1H), 5.08 (d, J¼10.3 Hz, 1H),
5.13 (d, J¼17.2 Hz, 1H), 5.68–5.79 (dddd, J¼5.2, 6.9,
10.3, 17.2 Hz, 1H), 6.41–6.50 (m, 2H), 7.15–7.31 (m,
10H); 13C NMR (126 MHz, CDCl3) d: 24.1, 44.3, 56.2,
63.9, 71.1, 117.0, 126.2, 126.3, 127.7, 127.9, 128.5, 128.7,
128.7, 134.0, 134.2, 136.5, 138.7, 157.5; IR (neat, cmꢁ1):
1056, 1402, 1746, 3027, 3469; MS (EI) m/z 140
(M+ꢁPhCHCHCHPh); HRMS calcd for C7H10NO2
(M+ꢁPhCHCHCHPh): 140.0775, found: 140.0774; [a]1D9
ꢁ60.9 (c 0.33, CHCl3).
Acknowledgements
Financial support was provided by a Grant-in-Aid for
Specially Promoted Research of MEXT.
4.3.3. (8R,8aR)-8a-Methyl-8-phenyl-1,5,8,8a-tetrahydro-
oxazolo[3,4-a]pyridin-3-one (7LP). To a solution of 6LP
(13.3 mg, 0.040 mmol) in CH2Cl2 (4.0 mL), first-generation
Grubbs’ catalyst (1.8 mg, 0.020 mmol) was added. The mix-
ture was refluxed for 1 h. After cooling to room temperature,
the solvent was evaporated, and the residue was chromato-
graphed on silica gel (AcOEt/hexane 2:8–3:7). The product
was obtained as pale yellow solid (7.3 mg, 80% yield). H
NMR (500 MHz, CDCl3) d: 1.46 (s, 3H), 3.20 (br s, 1H),
3.71 (br d, J¼18.9 Hz, 1H), 3.77 (d, J¼7.9 Hz, 1H), 3.79
References and notes
1. (a) Barrett, A. G. M.; Grabowski, G. G. Chem. Rev. 1986, 86,
751; (b) Ono, N. The Nitro Group in Organic Synthesis;
Wiley-VCH: Weinheim, NY, 2001; (c) Berner, O. M.;
Tedeschi, L.; Enders, D. Eur. J. Org. Chem. 2002, 1877.
2. (a) Seebach, D.; Colvin, E. W.; Lehr, F.; Weller, T. Helv. Chim.
Acta 1985, 68, 1592; (b) Brown, B. R. The Organic Chemistry
1

K. Maki et al. / Tetrahedron 63 (2007) 4250–4257
4257
of Aliphatic Nitrogen Compounds; Oxford University: Oxford,
1994; pp 443–469; (c) Seebach, D.; Colvin, E. W.; Lehr, F.;
Weller, T. Chimia 1979, 33, 1.
1986, 27, 4165; (h) Deardorff, D. R.; Savin, K. A.; Justman,
C. J.; Karanjawala, Z. E.; Sheppeck, J. E.; Harger, D. C.;
Aydin, N. J. Org. Chem. 1996, 61, 3616.
3. (a) The Chemistry of Amino, Nitro and Related Groups; Patai,
S., Ed.; John Wiley & Sons: Chichester, 1996; (b) Rosini, G.;
Ballini, R. Synthesis 1988, 833; (c) Coombes, R. G.
Comprehensive Organic Chemistry; Barton, D. H. R., Ollis,
W. D., Sutherland, I. O., Eds.; Pergamon: Oxford, 1979; Vol.
2, pp 303–382.
4. (a) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921;
(b) Acemoglu, L.; Williams, J. M. J. Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi,
E., Ed.; 2002; Vol. 2, p 1945; (c) Belda, O.; Moberg, C. Acc.
Chem. Res. 2004, 37, 2921; (d) Kazmaier, U. Curr. Org.
Chem. 2003, 7, 317; (e) Trost, B. M. Chem. Pharm. Bull.
2002, 50, 1.
5. Reviews of catalytic asymmetric reactions: (a) Palomo, C.;
Oiarbide, M.; Mielgo, A. Angew. Chem., Int. Ed. 2004, 43,
5442; (b) Shibasaki, M.; Sasai, H.; Arai, T. Angew. Chem.,
Int. Ed. 1997, 36, 1236; (c) Ballini, R.; Bosica, G.; Fiorini,
D.; Palmieri, A.; Petrini, M. Chem. Rev. 2005, 105, 933.
6. (a) Tsuji, J.; Yamakawa, T.; Mandai, T. Tetrahedron Lett. 1978,
19, 565; (b) Tsuji, J.; Shimizu, I.; Minami, I.; Ohashi, Y.;
Sugiura, T.; Takahashi, K. J. Org. Chem. 1985, 50, 1523; (c)
Aleksandrowicz, P.; Piotrowska, H.; Sas, W. Pol. J. Chem.
1981, 55, 1469; (d) Aleksandrowicz, P.; Piotrowska, H.; Sas,
W. Tetrahedron 1982, 38, 1321; (e) Aleksandrowicz, P.;
Piotrowska, H.; Sas, W. Monatsh. Chem. 1982, 113, 1221; (f)
Wade, P. A.; Morrow, S. D.; Hardinger, S. A. J. Org. Chem.
1982, 47, 365; (g) Ganet, J. P.; Grisoni, S. Tetrahedron Lett.
7. (a) Rieck, H.; Helmchen, G. Angew. Chem., Int. Ed. Engl. 1995,
34, 2687; (b) Trost, B. M.; Surivet, J.-P. J. Am. Chem. Soc.
2000, 122, 6291; (c) Trost, B. M.; Surivet, J.-P. Angew.
Chem., Int. Ed. 2000, 39, 3122; (d) Nemoto, T.; Jin, L.;
Nakamura, H.; Hamada, Y. Tetrahedron Lett. 2006, 47, 6577.
8. In the absence of external base, the reaction between 1e and
2-nitropropane (2b) using 2 mol % of Pd(PPh3)4 gave the prod-
uct 3eb in 87% yield.
9. (a) von Matt, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1993,
32, 566; (b) Sprinz, J.; Helmchen, G. Tetrahedron Lett. 1993,
34, 1769; (c) Dawson, G. J.; Frost, C. G.; Williams, J. M. J.
Tetrahedron Lett. 1993, 34, 3149.
10. Seebach, D.; Devaquet, E.; Ernst, A.; Hatakawa, M.; Kuehnle,
F. N. M.; Schweizer, W. B.; Weber, B. Helv. Chim. Acta 1995,
78, 1636.
11. (a) Wada, R.; Shibuguchi, T.; Makino, S.; Oisaki, K.; Kanai,
M.; Shibasaki, M. J. Am. Chem. Soc. 2006, 128, 7687; (b)
Suto, Y.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2007,
129, 500.
12. (a) Hayashi, T.; Yamamoto, A.; Ito, Y.; Nishioka, E.; Miura, H.;
Yanagi, K. J. Am. Chem. Soc. 1989, 111, 6301; (b) Hayashi, T.;
Kanehira, K.; Hagihara, T.; Kumada, M. J. Org. Chem. 1988,
53, 113.
13. (a) Lloyd-Jones, G. C.; Butts, C. P. Tetrahedron 1998, 54, 901;
(b) Froelander, A.; Lutsenko, S.; Privalov, T.; Moberg, C.
J. Org. Chem. 2005, 70, 9882.
14. Satoh, T.; Fukuda, Y. Tetrahedron 2003, 59, 9803.