Copper-catalyzed intermolecular generation of ammonium ylides with subsequent [2,3]sigmatropic rearrangement. Efficient synthesis of bifunctional homoallylamines

Article abstract of DOI:10.1246/bcsj.81.142

The [2,3]sigmatropie rearrangement of allylic ammonium ylides generated by the reaction of N,N-dimethyl-l- alkyl-2-methylallylamines derived from terpene alcohols with diazo compounds in the presence of copper catalysts gave trisubstituted E-olefins in one-pot. In addition, a cyano substituent at the 2-position of N,N-dimethylallylamine increased the occurrence of the catalytic [2,3]sigmatropic rearrangement to give the corresponding bifunctional homoallylamines. 2008 The Chemical Society of Japan.

Full text of DOI:10.1246/bcsj.81.142

142 Bull. Chem. Soc. Jpn. Vol. 81, No. 1, 142–147 (2008)
Ó 2008 The Chemical Society of Japan
Copper-Catalyzed Intermolecular Generation of Ammonium
Ylides with Subsequent [2,3]Sigmatropic Rearrangement.
Efficient Synthesis of Bifunctional Homoallylamines#
ꢀ1
Kiyoshi Honda, Hiromasa Shibuya,1 Hiroto Yasui,1 Yujiro Hoshino,2 and Seiichi Inoue2
1Graduate School of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501
2Graduate School of Environment and Information Scieneces, Yokohama National University,
79-7 Tokiwadai, Hodogaya-ku, Yokohama 240-8501
Received July 13, 2007; E-mail: k-honda@ynu.ac.jp
The [2,3]sigmatropic rearrangement of allylic ammonium ylides generated by the reaction of N,N-dimethyl-1-
alkyl-2-methylallylamines derived from terpene alcohols with diazo compounds in the presence of copper catalysts gave
trisubstituted E-olefins in one-pot. In addition, a cyano substituent at the 2-position of N,N-dimethylallylamine increased
the occurrence of the catalytic [2,3]sigmatropic rearrangement to give the corresponding bifunctional homoallylamines.
[2,3]Sigmatropic rearrangement is used widely in the regio-
and stereocontrolled synthesis of carbon frameworks in natural
products.1,2 In general, the treatment of a quaternary ammoni-
um salt with a base can cause the formation of an ammonium
R2C NR'3
MLn
R2CN2
ylide species, followed by a spontaneous [2,3]sigmatropic re-
arrangement to give 3-butenylamines (hereafter named homo-
allylamines).3 We have reported the [2,3]sigmatropic rear-
LnM CR2 NR'3
rangement of ammonium methylides4a and ethoxycarbonyl-
substituted ammonium ylides4b–4d to give Z- and E-olefins with
high stereoselectivity, respectively. Some quaternary ammoni-
um salts are highly hygroscopic and difficult to handle, and un-
desirable side reactions, including Hofmann elimination and
[1,2]rearrangement, may occur when strong bases are used to
generate ammonium ylides.5
N2
LnM CR2
NR'3
Scheme 1.
The catalyzed decomposition of diazo compounds to form
ammonium ylide is a useful alternative to the widely employed
base-promoted methodology (Scheme 1).6,7 Because of their
basicity, amines or imines are good ligands for catalytically
active transition-metal compounds, and reaction temperatures
required for diazo decomposition in the presence of amines
or imines are higher than for reactions in the presence of sub-
strates that possess other heteroatoms. Rhodium carboxylates
and homogenous copper complexes have emerged as highly
efficient catalysts for the generation of metal-stabilized oxoni-
um ylides. The use of rhodium carboxylates for diazo decom-
position made possible the generation of metal carbenes at
more moderate temperatures than were previously possible
with most copper catalysts.8 Doyle and co-workers have re-
ported several examples of intermolecular ammonium ylide
generation from ethyl diazoacetate (EDA) in the presence of
[Rh6(CO)16] or [Rh2(OAc)4]. These intermediates undergo
[2,3]sigmatropic rearrangement to produce homoallylamine7a
and alleneamine.7b Hata and Watanabe have reported the
treatment of 1-benzylazetidine with EDA in the presence of
[Cu(acac)2] underwent ring expansion to give pyrrolidine via
Stevens rearrangement.9 In contrast, Burger and co-workers
have claimed that the reaction of 1-benzylazetidine with
methyl 3,3,3-trifluoro-2-diazopropanoate, instead of EDA, in
the presence of rhodium(II) acetate does not undergo ring en-
largement and results in a [1,2]-benzyl migration to give ꢀ-
(trifluorophenyl)alanine derivative.6 West and co-workers
have carried out an investigation on the intermolecular gener-
ation of ammonium ylides, followed by [1,2]-benzyl migration
in the presence of Cu metal extensively.10 The copper-cata-
lyzed intermolecular [2,3]sigmatropic rearrangement of dihy-
dropyridinium ylides has been reported to be a ring-contractive
method.11 The intramolecular version of allylamine possessing
diazo moiety has been explored by several groups12 to provide
a general method for the preparation of cyclic amines.
However, there has been few reports on the stereocontrolled
synthesis of trisubstituted olefins through [2,3]sigmatropic re-
arrangement of ammonium ylides induced by allylamines and
reactive electrophilic metal carbene intermediates. Intermolec-
ular ylide formation with subsequent [2,3]sigmatropic rear-
rangement offers a potentially versatile method for the stereo-
selective synthesis of quaternary centers flanked by useful
functional groups. Since the reaction proceeds under non-basic
mild conditions, a catalytic protocol can be adopted for elabo-
ration to highly functionalized complex compounds. Herein,
Published on the web January 10, 2008; doi:10.1246/bcsj.81.142

K. Honda et al.
Bull. Chem. Soc. Jpn. Vol. 81, No. 1 (2008)
143
we report the efficient stereoselective synthesis of E-trisubsti-
tuted olefins via copper-catalyzed generation of ammonium
ylides. In addition, we report the substituent effect at the 2-
position of N,N-dimethylallylamine derivatives on the catalytic
[2,3]sigmatropic rearrangement.
arrangement product 3a and a cyclopropane compound were
obtained in 11% and 12% yields, respectively (Entry 2). Thus,
it is suggested that [Cu(OTf)2] interacted with a double bond
as well as an amino group in an allylamine due to the strong
Lewis acidity of [Cu(OTf)2]. The effectiveness of the ylide
formation of the carbenoid intermediate can be determined
by the competition between [2,3]sigmatropic rearrangement
of the generated ylide and the cyclopropanation of the carbon–
carbon double bond.13 However, the use of [Cu(hfacac)2] or
[Cu(acac)2] gave the single product without cyclopropane de-
rivative (Entries 4 and 5). As has been previously observed
with the use of the rhodium catalysts,7a increasing the initial
concentration of the allylamine relative to that of the diazo
compound resulted in higher yields of the ylide rearrangement
products. Thus, the potential drawbacks of this approach in-
clude the requirement of a large excess of the amine.
Results and Discussion
Copper-Catalyzed Intermolecular Formation of Ammo-
nium Ylides and Subsequent [2,3]Sigmatropic Rearrange-
ment. The copper-catalyzed intermolecular generation of
ammonium ylides, followed by [2,3]sigmatropic rearrange-
ment, was carried out using EDA 1a and N,N-dimethylallyl-
amine (2a) (Table 1). When [Cu(OTf)2] was used, both the re-
Table 1. Catalytic [2,3]Sigmatropic Rearrangement Using
Copper Saltsa)
Copper-Catalyzed Intermolecular Formation of Ammo-
nium Ylides and Subsequent Stereoselective [2,3]Sigma-
tropic Rearrangement of N,N-Dimethyl-1-alkyl-2-methyl-
allylamines. The copper-catalyzed intermolecular generation
of ammonium ylides, followed by [2,3]sigmatropic rearrange-
ment, was applied to the stereoselective synthesis of trisubsti-
tuted olefin. The use of N,N-dimethylallylamine derivatives in-
duced from terpene alcohols afforded the corresponding trisub-
stituted olefins in one-pot.
At first, we examined the reaction of N,N-dimethyl-2-meth-
ylallylamine (2b) with 1a in the presence of copper catalyst
(Table 2). When the reaction was carried out at 60 ꢁC in ben-
zene in the presence of [Cu(hfacac)2], the rearrangement prod-
uct 3b was obtained in 23% yield along with the cyclopropane
derivative in 19% yield. When [Cu(acac)2] was used at 60 ꢁC
in benzene, product 3b was obtained in 22% yield without
N2
10% of Cat.
H
NMe2
CO2Et
+
NMe2
Benzene, 60 °C
H
CO2Et
1a
2a
3a
Entry
Cu-cat.
[CuBr]
[Cu(OTf)2]
[Cu2(OAc)4]
[Cu(hfacac)2]
[Cu(acac)2]
Time/h
Yield/%b)
1
2
3
4
5
13
6
20
20
22
16
11c)
23
31
35
a) The reaction was carried out by using 5.0 molar equivalent
of allylamine 2a unless otherwise noting. b) Yield was calcu-
lated on the basis of the amount of the diazo compound.
c) The cyclopropane derivative was obtained concomitantly.
Table 2. Reaction of Diazo Compounds 1a–1d with Allylamines 2b–2da)
R2
NMe2
CO2Et
3b-h
N2
R2
NMe2
10% of [Cu(acac)2]
+
R1
R1
CO2Et
Toluene
reflux, 3 h
2b: R2 = H
1a-d
2c: R2 = CH2OBn
2d: R2 =
OBn
Entry
Diazo
compound
R1
Amine
Product
Yield/%b)
Ratio of
E/Zc)
1d)
2
3
4
1a
1a
1b
1b
1c
1d
1d
1d
H
H
Ph
Ph
Ac
CO2Et
CO2Et
CO2Et
2b
2c
2c
2d
2c
2c
2d
2d
3b
3c
3d
3e
3f
3g
3h
3h
50
20
45
67
23
64
65
32
—
91/9
71/29
64/36
94/6
93/7
90/10
94/6
5
6e)
7f)
8d)
a) The reaction was carried out by using 3.0 molar equivalent of allylamines
2b–2d unless otherwise noting. b) Yield was calculated on the basis of the
amount of the diazo compounds. c) Determined by 1H NMR spectroscopy.
d) Reaction was carried out in benzene at reflux for 3 h. e) The reaction
was carried out by using 1.0 molar equivalent of allylamines. f) Reaction
was carried out in the presence of MS4A.

144 Bull. Chem. Soc. Jpn. Vol. 81, No. 1 (2008)
Copper-Catalyzed [2,3]Sigmatropic Rearrangement
a cyclopropane compound, and in refluxing benzene, it was
obtained in 50% yield (Entry 1).
dominatly.15
The Substituent Effect at 2-Position of N,N-Dimethyl-
allylamine Derivatives. The reaction was carried out by
using diazo compounds 1a–1d, N,N-dimethylallylamine deriv-
atives 2e–2g and [Cu(acac)2] in order to investigate the sub-
stituent effect of the functional group R3 at the 2-position
(Table 3). Treatment of allylamines bearing an electron-with-
drawing group (R3 = Cl and CO2Et) with 1a gave rearrange-
ment products 3i and 3j in moderate yields (Entries 1 and 2).
When allylamine 2g possessing the cyano group at the 2-posi-
tion was used (Entry 4), we found that [2,3]sigmatropic rear-
rangement occurred more readily. Next, we investigated the
reaction using allylamine 2g under milder conditions. Among
the possible solvents (e.g. benzene, toluene, THF, chloroform,
dichloromethane, dichloroethane, and chlorobenzene) for the
reaction at low temperature, we found dichloromethane to be
Notably, the reaction of N,N-dimethyl-1-alkyl-2-methyl-
allylamines, induced from terpene alcohols, with diazo com-
pounds in the presence of [Cu(acac)2] underwent the catalytic
[2,3]sigmatropic rearrangement to give the desired E-trisubsti-
tuted olefins (Entries 2–8). Whereas the treatment of 2c with
1a at reflux in benzene gave a trace amount of the product,
E-olefin 3c was obtained in refluxing toluene in 20% yield
with E/Z = 91:9 (Entry 2). The reaction of 2c and 2d with di-
azo compounds possessing two electron-withdrawing groups,
1c (R1 = Ac) or 1d (R1 = CO2Et), afforded bifunctional E-
olefins 3f–3h (Entries 5–8). It should be noted that the reaction
did not need a large amount of amine. Thus, the reaction
was performed by using 1 molar equivalent of amine 2c to give
product 3g in 64% yield (Entry 6).
The reaction of 2d with 1d afforded product 3h in good
yield (65%) with E/Z = 90:10 (Entry 7). In refluxing benzene
instead of toluene, product 3h was obtained with high E-
stereoselectivity (Entry 8). Treatment of allylamine 2c to a
catalytic amount of [Rh2(OAc)4] in benzene at reflux did not
produce product 3c.
H
EtO2C
Me
H
Me
C
N
EtO2C
H
Me
H
H
Me
H C H
R4
CH2R4
R1
C
N
Me
R1
H
Me
A stable ylide may undergo [2,3]sigmatropic rearrangement
to give E-olefins via a concerted transition state involving a
double suprafacial mode, in which R4CH2 on the allyl moiety
takes a pseudoequatorial conformation to avoid synclinal re-
pulsion with the methyl substituent and 1,3-diaxial interaction
with a hydrogen atom14 (Fig. 1). As the phenyl group may pre-
fer a pseudoaxial alignment in the transition state to some de-
gree, the corresponding rearrangement afforded an E/Z mix-
ture of products 3d and 3e (Entries 3 and 4). It has been report-
ed that [2,3]sigmatropic rearrangement of allylic sulfoxides
possessing a phenyl group at the 1-position gives Z-olefins pre-
EtO2C
Me2N
Me2N
EtO2C R1
R4
R4
R1
E
Z
R4 = OBn
R4 =
OBn
Fig. 1. Concerted transition state of E-selective [2,3]sigma-
tropic rearrangement.
Table 3. Reaction of Diazo Compounds 1a–1d with Allylamine 2e–2ga)
R3
R3
N2
10% of [Cu(acac)2]
+
R1
CO2Et
Solvent
Temp.
R1
NMe2
NMe2
CO2Et
1a-d
2e-g
Amine R3
3i-n
Entry
Diazo
compound
R1
Solvent Time
Temp Product Yield
/ꢁC
/%b)
1
2
3
4c)
5
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
H
H
H
H
H
H
H
H
2e
2f
Cl
CO2Et Benzene 1 h
Benzene 20 min Reflux
Reflux
3i
3j
56
45
76
84
49
37
43
53
88
63
87
2g
2g
2g
2g
2g
2g
2g
2g
2g
CN
CN
CN
CN
CN
CN
CN
CN
CN
Benzene 20 min Reflux
Benzene 20 min Reflux
Benzene 12 h
3k
3k
3k
3k
3k
3k
3l
60
60
rt
Reflux
Reflux
Reflux
Reflux
6
THF
DCM
DCM
23 h
5 h
18 h
7d)
8
9
10
11
Ph
Ac
CO2Et
Toluene 2 h
Toluene 2 h
Benzene 4 h
3m
3n
a) The reaction was carried out by using 3.0 molar equivalent of allylamines 2e–2g unless
otherwise noting. b) Yield was calculated on the basis of the amount of the diazo compound.
c) Six molar equivalent of 2g was used. d) The reaction was carried out at room temperature
using 1.2 molar equivalent of 2g in the presence of CuI species induced from Cu(dpm)2 with
phenylhydrazine.

K. Honda et al.
Bull. Chem. Soc. Jpn. Vol. 81, No. 1 (2008)
145
million downfield from tetramethylsilane, and 13C NMR spectra
are reference to the internal solvent standard. Coupling constants
(J) are quoted in hertz. Thin-layer chromatography (TLC) was
performed on precoated Merck TLC plates with silica gel 60
F-254. Column chromatography was carried out with Cica-Merck
Silica gel 60 (Kanto Chemical Industries). All reagents were
obtained from commercial suppliers and were used as received
unless otherwise indicated. The diazo compounds (1b–1d) were
prepared by diazo-transfer reaction.18 Amines 2b,19a 2c and
2d,4,19b,19c and 2e19d were prepared by using previously reported
methods. Amines 2f and 2g were prepared from paraformaldehyde
and dimethylamine hydrochloride with cyanoacetic acid or ethyl
malonate under Mannich reaction conditions, respectively.19e
General Procedure for the Reaction of EDA with N,N-
Dimethylallylamine in the Presence of Copper-Catalyst
(Table 1). Catalyst (0.1 mmol) was added to a stirred solution
of N,N-dimethylallylamine (5 mmol) in benzene (10 mL) under
an atmosphere of argon. The reaction mixture was heated to
60 ꢁC, a solution of EDA (1 mmol) in benzene (2 mL) was added
using a syringe pump. After the addition of EDA, the reaction
mixture was stirred for 6–22 h. When the reaction mixture was
cooled, diethyl ether was added, and the suspension was filtered.
The solvent was then removed in vacuo, and the residue was
purified by column chromatography on silica gel with hexane/
EtOAc (3:1) to give homoallylamines as pale yellow oil. The yield
was calculated on the basis of the amount of the diazo compound.
General Procedure for the Copper-Catalyzed [2,3]Sigma-
a
Br
OBn
+
2d
EtO2C
CO2Et
EtO2C
NMe2
Br
CO2Et
Scheme 2. Reagents and conditions: (a) MeCN, rt, 2 d or
ether, rt, 2 d or CHCl3, reflux, 6 h.
the best (Entries 5–8). By controlling the concentration of
amine, we found that the reaction proceeded in dichloro-
methane at ambient temperature. When using 1.2 molar equiv-
alent of 2g, product was obtained in 34% yield. When the re-
action was carried out in the presence of a more active cop-
per(I) species16 generated from [Cu(dpm)2] and phenylhydra-
zine,17 the product was obtained in 43% yield in a short time
(Entry 7). When the process was carried out in dichloro-
methane at room temperature with [Rh2(OAc)4], the desired
product was obtained in 18% yield. In addition, the use of
2g with diazo compounds 1b–1d afforded bifunctional homo-
allylic amines 3l–3n efficiently (Entries 9–11).
Though we tried to prepare the bifunctional homoallyl-
amines 3f–3h, 3m, and 3n from allylic tert-amines and alkyl-
halides having two electron-withdrawing groups, the corre-
sponding ammonium salts were not obtained owing to the de-
composition of alkylhalides by allylic tert-amines themselves
(Scheme 2). It should be noted that bifunctional homoallyl-
amines 3f–3h, 3m, and 3n, which could not be obtained by
the general base-promoted methodology, could be obtained
effectively by using the copper-catalyzed carbenoid protocol.
tropic Rearrangements (Table 2).
Unless otherwise noted,
the reaction was performed with Cu(acac)2 (0.1 mmol), allylamine
(3 mmol) in toluene (7 mL), and diazo compound (1 mmol) in
toluene (2 mL) under an atmosphere of argon. After the addition
of the diazo compound using a syringe pump, the reaction mixture
was stirred for 3 h at reflux. When the reaction mixture was
cooled, diethyl ether was added, and the suspension was filtered.
The solvent was then removed in vacuo, and the residue was pu-
rified by column chromatography on silica gel with hexane/
EtOAc (3:1) to give E/Z mixture of homoallylamines as pale
yellow oil. The yield was calculated on the basis of the amount
of the diazo compounds except for the Entry 6. In Entry 6, the
yield was based on the recovery of the starting material (allyl-
Conclusion
We demonstrated the reaction of N,N-dimethylallylamine
derivatives with diazo compounds in the presence of bisacetyl-
acetonatocopper(II), which may undergo the generation of am-
monium ylides species, followed by the spontaneous [2,3]-
sigmatropic rearrangement, to give rearrangement products in
one-pot. The reaction of N,N-dimethyl-1-alkyl-2-methylallyl-
amines, derived from terpene alcohols, with diazo compounds
afforded the trisubstituted E-homoallylamines. A cyano sub-
stituent at the 2-position of N,N-dimethylallylamine derivatives
caused the [2,3]sigmatropic rearrangement to occur more
readily. Bifunctional homoallylamines, which could not be
obtained by using the general base-promoted [2,3]rearrange-
ment, were obtained efficiently using our catalytic carbenoid
protocol.
With substituted allylamines and diazoketones in the pres-
ence of Cu catalyst, generation of the ammonium ylides occur-
red almost exclusively, and the subsequent [2,3]sigmatropic
rearrangement products were afforded with a high degree of
stereocontrol, favoring the E-isomer. These results can be ex-
plained by steric and/or electronic influences in the transition
states for the [2,3]sigmatropic rearrangement.
1
amine 2c). The E stereochemistry was confirmed by the H NMR
spectrum.
Ethyl 2-(Dimethylamino)-4-methyl-4-pentenoate (3b): IR
(neat): 2979, 2938, 2871, 2832, 2789, 1731, 1650, 1455, 1371,
1
1262, 1173, 1098, 1029, 891 cmꢂ1. H NMR (400 MHz, CDCl3):
ꢁ 1.28 (t, J ¼ 7:3 Hz, 3H), 1.76 (s, 3H), 2.30–2.53 (m, 2H), 2.36
(s, 6H), 3.36 (dd, J ¼ 6:4, 8.9 Hz, 1H), 4.17 (q, J ¼ 7:3 Hz, 2H),
4.75 (d, J ¼ 1:0 Hz, 1H), 4.80 (s, 1H). 13C NMR (100 MHz,
CDCl3): ꢁ 12.4, 22.2, 37.9, 41.7, 60.3, 65.9, 112.9, 141.8, 171.7.
Anal. Calcd for C10H19NO2: C, 64.83; H, 10.34; N, 7.56%. Found:
C, 65.01; H, 10.35; N, 7.34%.
Ethyl 6-Benzyloxy-2-(dimethylamino)-4-methyl-4-hexenoate
(E-3c): IR (neat): 2979, 2936, 2863, 2787, 1730, 1453, 1173,
1091, 1070, 1028, 739, 699 cmꢂ1. 1H NMR (400 MHz, CDCl3): ꢁ
1.25 (t, J ¼ 7:1 Hz, 3H), 1.67 (s, 3H), 2.32–2.52 (m, 2H), 2.35 (s,
6H), 3.33 (dd, J ¼ 6:1, 9.1 Hz, 1H), 4.01 (dd, J ¼ 2:8, 6.6 Hz,
2H), 4.14 (dq, J ¼ 1:2, 7.1 Hz, 2H), 4.47 (s, 2H), 5.45 (t, J ¼
6:83 Hz, 1H), 7.26–7.34 (m, 5H). 13C NMR (100 MHz, CDCl3):
ꢁ 14.5, 16.4, 40.0, 41.8, 60.1, 66.2, 66.3, 71.8, 123.8, 127.4, 127.7,
128.2, 136.3, 138.4, 171.5. Anal. Calcd for C18H27NO3: C, 70.79;
H, 8.91; N, 4.59%. Found: C, 70.76; H, 9.01; N, 4.47%.
Ethyl 6-Benzyloxy-2-(dimethylamino)-2-phenyl-4-methyl-4-
Experimental
General. IR spectra were recorded on a Perkin-Elmer Paragon
1000 Fourier transform IR spectrometer. 1H and 13C NMR spectra
were recorded on a JEOL JNM-ALS 400 (400 MHz) spectrometer.
Unless otherwise stated, deuterated chloroform was used as the
solvent, and tetramethylsilane was used as the internal standard.
Chemical shifts in 1H NMR spectra are reported in parts per

146 Bull. Chem. Soc. Jpn. Vol. 81, No. 1 (2008)
Copper-Catalyzed [2,3]Sigmatropic Rearrangement
hexenoate (3d): Each of rearrangement products were separated
carefully from E/Z mixture to give 13% of Z-3d and 32% of E-3d.
E-3d: IR (neat): 2980, 2932, 2865, 2834, 2790, 1718, 1494, 1447,
1384, 1365, 1204, 1092, 1068, 1028, 739, 701. 1H NMR (400
MHz, CDCl3): ꢁ 1.21 (s, 3H), 1.33 (t, J ¼ 7:1 Hz, 3H), 2.30 (s,
6H), 2.49 (d, J ¼ 13:2 Hz, 1H), 3.07 (d, J ¼ 13:2 Hz, 1H), 3.81 (d,
J ¼ 6:3 Hz, 2H), 4.27–4.32 (m, 4H), 5.12 (t, J ¼ 6:3 Hz, 1H),
7.08–7.36 (m, 10H). 13C NMR (100 MHz, CDCl3): ꢁ 14.8, 17.8,
40.4, 47.4, 60.2, 66.4, 71.5, 74.3, 126.3, 126.7, 127.1, 127.3,
127.6, 128.0, 128.2, 128.3, 129.6, 136.0, 138.5, 169.7. Anal. Calcd
for C24H31NO3: C, 75.56; H, 8.19; N, 3.67%. Found: C, 75.54; H,
8.28; N, 3.38%.
syringe pump, the reaction mixture was stirred for 20 min–18 h
listed in the table. When the reaction mixture was cooled, diethyl
ether was added, and the suspension was filtered. The solvent
was then removed in vacuo, and the residue was purified by
column chromatography on silica gel with hexane/EtOAc (3:1)
to give corresponding homoallylamines as pale yellow oil. The
yield was calculated on the basis of the amount of the diazo
compounds.
Ethyl 4-Chloro-2-(dimethylamino)-4-pentenoate (3i):
(neat): 2980, 2940, 2871, 2834, 2789, 1731, 1637, 1455, 1371,
1246, 1228, 1175, 1098, 1035, 886, 637 cmꢂ1 1H NMR (400
IR
.
MHz, CDCl3): ꢁ 1.29 (t, J ¼ 7:1 Hz, 3H), 2.37 (s, 6H), 2.65 (ddd,
J ¼ 0:7, 6.8, 14.4 Hz, 1H), 2.78 (ddd, J ¼ 0:7, 7.8, 14.4 Hz, 1H),
3.59 (dd, J ¼ 6:8, 7.8 Hz, 1H), 4.19 (dq, J ¼ 2:4, 7.1 Hz, 2H),
5.22 (d, J ¼ 1:2 Hz, 1H), 5.24 (d, J ¼ 1:2 Hz, 1H). 13C NMR
(100 MHz, CDCl3): ꢁ 14.4, 39.0, 41.5, 60.3, 64.8, 114.7, 139.0,
170.7. Anal. Calcd for C9H16ClNO2: C, 52.56; H, 7.84; N, 6.81%.
Found: C, 52.48; H, 7.80; N, 6.62%.
Ethyl 10-Benzyloxy-4,8-dimethyl-2-(dimethylamino)-2-phen-
yl-4,8-decadienoate (E-3e): IR (neat): 2978, 2937, 2866, 2790,
.
1719, 1446, 1120, 1094, 1067, 1027, 737, 701 cmꢂ1 1H NMR
(400 MHz, CDCl3): ꢁ 1.18 (s, 3H), 1.32 (t, J ¼ 6:9 Hz, 3H), 1.57
(s, 3H), 1.80–1.89 (m, 4H), 2.29 (s, 6H), 2.36 (d, J ¼ 13:2 Hz,
1H), 3.02 (d, J ¼ 13:2 Hz, 1H), 4.00 (d, J ¼ 6:6 Hz, 2H), 4.28
(q, J ¼ 6:9 Hz, 2H), 4.49 (s, 2H), 4.80 (t, J ¼ 6:6 Hz, 1H), 5.31
(t, J ¼ 6:6 Hz, 1H), 7.12–7.35 (m, 10H). 13C NMR (100 MHz,
CDCl3): ꢁ 14.9, 16.6, 17.4, 26.4, 39.1, 40.5, 47.5, 60.1, 66.6, 72.0,
74.4, 120.4, 126.5, 126.9, 127.3, 127.7, 128.2, 128.3, 129.0, 131.1,
138.3, 139.6, 140.2, 169.6. Anal. Calcd for C29H39NO3: C, 77.47;
H, 8.74; N, 3.12%. Found: C, 77.30; H, 8.87; N, 2.91%.
Diethyl 2-Dimethylamino-4-methyleneglutarate (3j):
(neat): 2980, 2938, 2871, 2833, 2788, 1728, 1632, 1448, 1370,
1298, 1266, 1243, 1185, 1097, 1033, 937, 817 cmꢂ1 1H NMR
IR
.
(400 MHz, CDCl3): ꢁ 1.27 (t, J ¼ 7:1 Hz, 3H), 1.31 (t, J ¼ 7:1 Hz,
3H), 2.35 (s, 6H), 2.64–2.74 (m, 2H), 3.45 (dd, J ¼ 6:7, 8.5 Hz,
1H), 4.15 (dq, J ¼ 2:1, 7.1 Hz, 2H), 4.22 (q, J ¼ 7:1 Hz, 2H), 5.61
(d, J ¼ 1:3 Hz, 1H), 6.20 (d, J ¼ 1:3 Hz, 1H). 13C NMR (100
MHz, CDCl3): ꢁ 14.2, 14.4, 31.9, 41.7, 60.2, 60.7, 66.3, 127.1,
137.1, 166.7, 171.4. Anal. Calcd for C12H21NO4: C, 59.24; H,
8.70; N, 5.76%. Found: C, 59.04; H, 8.73; N, 5.71%.
Ethyl 4-Cyano-2-(dimethylamino)-4-pentenoate (3k): IR
(neat): 2981, 2941, 2871, 2836, 2790, 2224, 1729, 1624, 1454,
1370, 1236, 1178, 1097, 1034 cmꢂ1. 1H NMR (400 MHz, CDCl3):
ꢁ 1.30 (t, J ¼ 7:1 Hz, 3H), 2.36 (s, 6H), 2.55–2.68 (m, 2H), 3.49
(dd, J ¼ 7:3, 8.3 Hz, 1H), 4.14–4.26 (m, 2H), 5.80 (d, J ¼ 0:5 Hz,
1H), 5.92 (d, J ¼ 0:5 Hz, 1H). 13C NMR (100 MHz, CDCl3): ꢁ
14.5, 34.3, 41.4, 60.5, 65.2, 118.1, 119.9, 132.3, 170.2. Anal.
Calcd for C10H16N2O2: C, 61.20; H, 8.22; N, 14.27%. Found:
C, 60.97; H, 8.29; N, 14.02%.
Ethyl 4-Cyano-2-(dimethylamino)-2-phenyl-4-pentenoate
(3l): IR (neat): 2983, 2940, 2836, 2793, 2223, 1721, 1493, 1447,
1297, 1227, 1192, 1068, 1027, 946, 705 cmꢂ1 1H NMR (400
.
MHz, CDCl3): ꢁ 1.35 (t, J ¼ 7:1 Hz, 3H), 2.38 (s, 6H), 2.91 (dabq,
J ¼ 1:0, 14.0, 28.0 Hz, 2H), 4.34 (q, J ¼ 7:1 Hz, 2H), 5.10 (d,
J ¼ 1:0 Hz, 1H), 5.68 (d, J ¼ 1:0 Hz, 1H), 7.24–7.32 (m, 5H).
13C NMR (100 MHz, CDCl3): ꢁ 14.8, 40.7, 42.9, 60.8, 74.1, 118.4,
118.6, 127.5, 127.6, 128.1, 135.4, 138.5, 159.5. Anal. Calcd for
C16H20N2O2: C, 70.56; H, 7.40; N, 10.29%. Found: C, 70.33;
H, 7.51; N, 10.00%.
Ethyl 2-Acetyl-6-benzyloxy-2-(dimethylamino)-4-methyl-4-
hexenoate (E-3f): IR (neat): 2930, 2856, 2792, 1717, 1454,
.
1352, 1206, 1072, 1027, 740, 699 cmꢂ1 1H NMR (400 MHz,
CDCl3): ꢁ 1.30 (t, J ¼ 7:1 Hz, 3H), 1.61 (s, 3H), 2.18 (s, 3H), 2.33
(s, 6H), 2.76 (abq, J ¼ 13:9, 76.1 Hz, 2H), 3.97 (d, J ¼ 6:6 Hz,
2H), 4.24 (q, J ¼ 7:1 Hz, 2H), 4.46 (s, 2H), 5.46 (dt, J ¼ 1:0,
6.6 Hz, 1H), 7.25–7.35 (m, 5H). 13C NMR (100 MHz, CDCl3): ꢁ
14.5, 17.0, 28.0, 40.8, 43.1, 60.8, 66.2, 72.0, 79.7, 126.2, 127.4,
127.7, 128.2, 135.6, 138.3, 168.2, 204.1. Anal. Calcd for C20H29-
NO4: C, 69.14; H, 8.41; N, 4.03%. Found: C, 69.12; H, 8.47; N,
3.82%.
Diethyl 2-(4-Benzyloxy-2-methyl-2-butenyl)-2-(dimethyl-
amino)malonate (E-3g): IR (neat): 2981, 2956, 2905, 2871,
2792, 1754, 1726, 1454, 1227, 1072, 1027, 741, 699 cmꢂ1
.
1H NMR (400 MHz, CDCl3): ꢁ 1.27 (t, J ¼ 7:1 Hz, 6H), 1.68 (s,
3H), 2.38 (s, 6H), 2.82 (s, 2H), 4.00 (d, J ¼ 6:6 Hz, 2H), 4.21 (q,
J ¼ 7:1 Hz, 4H), 4.46 (s, 2H), 5.52 (t, J ¼ 6:6 Hz, 1H), 7.27–7.35
(m, 5H). 13C NMR (100 MHz, CDCl3): ꢁ 14.4, 17.3, 40.8, 43.7,
61.0, 66.3, 71.9, 75.5, 125.6, 127.3, 127.6, 128.1, 135.5, 138.3,
167.9. Anal. Calcd for C21H31NO5: C, 66.82; H, 8.28; N, 3.71%.
Found: C, 66.90; H, 8.34; N, 3.57%.
Diethyl 2-(8-Benzyloxy-2,6-dimethyl-2,6-octadienyl)-2-(di-
methylamino)malonate (E-3h): IR (neat): 2980, 2936, 2857,
2790, 1755, 1726, 1454, 1226, 1098, 1068, 1029, 740, 699 cmꢂ1
.
Ethyl
(3m): IR (neat): 2985, 2843, 2796, 2224, 1718, 1617, 1462,
2-Acetyl-4-cyano-2-(dimethylamino)-4-pentenoate
1H NMR (400 MHz, CDCl3): ꢁ 1.23 (t, J ¼ 7:1 Hz, 6H), 1.63 (s,
6H), 1.99–2.11 (m, 4H), 2.36 (s, 6H), 2.75 (s, 2H), 4.02 (d, J ¼
6:7 Hz, 2H), 4.20 (q, J ¼ 7:1 Hz, 4H), 4.50 (s, 2H), 5.25 (t, J ¼
6:7 Hz, 1H), 5.39 (dt, J ¼ 1:0, 6.7 Hz, 1H), 7.25–7.37 (m, 5H).
13C NMR (100 MHz, CDCl3): ꢁ 14.5, 16.6, 16.8, 26.5, 39.4,
40.8, 43.9, 60.8, 66.6, 72.0, 75.7, 120.8, 127.3, 127.6, 128.2,
128.5, 131.0, 138.4, 139.9, 168.0. Anal. Calcd for C26H39NO5:
C, 70.08; H, 8.82; N, 3.14%. Found: C, 69.90; H, 8.87; N, 3.02%.
General Procedure for the Copper-Catalyzed [2,3]Sigma-
tropic Rearrangements (Table 3). Unless otherwise noted, the
reaction was performed with Cu(acac)2 (0.1 mmol) and allylamine
(3 mmol) in the solvents (7 mL) listed in the table and diazo com-
pound (1 mmol) in the appropriate solvent (2 mL) under an atmo-
sphere of argon. After the addition of the diazo compound using a
1
1356, 1233, 1168, 1050, 952 cmꢂ1. H NMR (400 MHz, CDCl3):
ꢁ 1.33 (t, J ¼ 7:1 Hz, 3H), 2.24 (s, 3H), 2.41 (s, 6H), 2.90 (dabq,
J ¼ 1:1, 14.9, 24.4 Hz, 2H), 4.29 (dq, J ¼ 1:2, 7.1 Hz, 2H), 5.85
(s, 1H), 5.99 (s, 1H). 13C NMR (100 MHz, CDCl3): ꢁ 14.3, 27.9,
36.4, 40.8, 61.6, 79.4, 117.9, 118.2, 135.5, 167.9, 203.3. Anal.
Calcd for C12H18N2O3: C, 60.49; H, 7.61; N, 11.76%. Found: C,
60.38; H, 7.65; N, 11.54%.
Diethyl 2-(2-Cyanoallyl)-2-dimethylaminomalonate (3n):
IR (neat): 2984, 2906, 2839, 2795, 2224, 1756, 1728, 1620, 1465,
1448, 1391, 1367, 1303, 1235, 1209, 1094, 1064, 1041, 953, 859
cmꢂ1
.
1H NMR (400 MHz, CDCl3): ꢁ 1.31 (t, J ¼ 7:1 Hz, 6H),
2.43 (s, 6H), 2.97 (d, J ¼ 1:2 Hz, 2H), 4.27 (q, J ¼ 7:1 Hz, 4H),
5.90 (d, J ¼ 0:7 Hz, 1H), 6.00 (s, 1H). 13C NMR (100 MHz,

K. Honda et al.
Bull. Chem. Soc. Jpn. Vol. 81, No. 1 (2008)
147
CDCl3): ꢁ 14.1, 37.8, 40.6, 61.5, 74.7, 117.8, 118.2, 135.0, 167.5.
Anal. Calcd for C13H20N2O4: C, 58.19; H, 7.51; N, 10.44%.
Found: C, 58.01; H, 7.52; N, 10.34%.
12 a) F. G. West, B. N. Naidu, J. Am. Chem. Soc. 1993, 115,
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Hodgson, M. D. Goldsmith, L. J. Street, J. Chem. Soc., Perkin
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