Investigation on amino-heck cyclization of 1-(2-vinylcyclohexyl)ketone diethyl phosphinyloximes

Article abstract of DOI:10.3987/COM-11-12396

Upon the treatment with Pd(PPh₃)₄ and Et₃N in DMF at 80 °C, a range of trans-1-(2-vinylcyclohexyl)-substituted ketone diethylphosphinyloximes underwent the cyclization in a 6-endo pathway to afford 1-substituted tetrahydroisoquinolines in varying yields. Among which, the reactions of the substrates bearing the saturated alkyl groups were severely competed by hydrolysis and/or Beckmann rearrangement, while these undesired side reactions could be suppressed by introducing a β-aryl moiety possibly due to the stabilizing π-π stacking interactions between the phosphoryl and/or vinyl group and the aryl.

Full text of DOI:10.3987/COM-11-12396

HETEROCYCLES, Vol. 85, No. 2, 2012
383
HETEROCYCLES, Vol. 85, No. 2, 2012, pp. 383 - 401. © 2012 The Japan Institute of Heterocyclic Chemistry
Received, 21st November, 2011, Accepted, 26th December, 2011, Published online, 29th December, 2011
DOI: 10.3987/COM-11-12396
INVESTIGATION
ON
AMINO-HECK
CYCLIZATION
OF
1-(2-VINYLCYCLOHEXYL)KETONE DIETHYL PHOSPHINYLOXIMES
Sheng-Wei Tsao and Jia-Liang Zhu*
Department of Chemistry, National Dong-Hwa University, Hualien 974, Taiwan,
R.O.C.
E-mail: jlzhu@mail.ndhu.edu.tw
Abstract – Upon the treatment with Pd(PPh3)4 and Et3N in DMF at 80 oC, a range
of trans-1-(2-vinylcyclohexyl)-substituted ketone diethylphosphinyloximes
underwent the cyclization in a 6-endo pathway to afford 1-substituted
tetrahydroisoquinolines in varying yields. Among which, the reactions of the
substrates bearing the saturated alkyl groups were severely competed by
hydrolysis and/or Beckmann rearrangement, while these undesired side reactions
could be suppressed by introducing a β-aryl moiety possibly due to the stabilizing
π-π stacking interactions between the phosphoryl and/or vinyl group and the aryl
rings.
INTRODUCTION
The palladium-catalyzed intramolecular cyclization of unsaturated acyloxime derivatives (amino-Heck
reaction) has emerged as a powerful means for preparing aza-heterocyclic compounds.1,2 The
well-accepted mechanism for this process involves the oxidative insertion of Pd(0) to N-O bond, followed
by the reaction of the resulting aminopalladium(II) complex with an internal olefin to form a cyclic
product. To ensure an efficient annulation, the selection of the leaving groups on the oxime nitrogen has
proven to be an important issue. First, this group should possess enough stability to minimize the
competitive side reactions, mostly as Beckmann rearrangement and hydrolysis. On the other hand, it
should also be sufficiently reactive towards the initial oxidative addition by Pd(0) catalyst. In term of
achieving a subtle balance between the two demands, pioneering work by Narasaka and co-workers has
established that O-pentafluorobenzoyl oximes are more useful in practice than many other types of
oximes,2a and from which, the preparation of a large range of valuable heterocycles such as pyrroles,4
pyridines,6 imidazoles7 and pyrrolines8 have been realized.

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HETEROCYCLES, Vol. 85, No. 2, 2012
Recently we reported the application of O-diethylphosphinyloximes as the new precursors into
amino-Heck reaction.10 Under the catalysis of Pd(PPh3)4, the cyclization of a range of acyclic γ,δ-, or
δ,ε-unsaturated phosphinyloximes occurred smoothly to provide the substituted pyrroles or pyridines in
moderate to excellent yields. More interestingly, it was observed that the regioselectivity of the
cyclization (5-exo versus 6-endo) of the γ,δ-unsaturated substrates could be controlled by the adjustment
of catalytic conditions, to thus allow the selective generation of pyrroles10a or pyridines10b with the same
precursors. Following this investigation, we have further extended the reaction to the
2-vinylcyclohexyl-substituted phosphinyloxime derivatives. To our knowledge, it is the first time that the
amino-Heck reaction has been applied to the oximes bearing such structural motif. In addition to
documenting the utility of the protocol in the construction of azabicyclic molecules, our research program
is also aimed at investigating the substituting and steric factors playing on the cyclization. Herein we wish
to disclose our preliminary experimental results.
RESULTS AND DISCUSSION
To access the 2-vinylcyclohexyl-substituted precursors, we first carried out the 1,4-addition reaction of
1-acetylcyclohexene with vinylmagnesium bromide in the established protocol11 to produce the known
ketone 2a11 along with its trans-isomer 2b (2a/2b = 81:19) (Scheme 1). The mixture was then allowed to
react with hydroxylamine hydrochloride (NH2OH·HCl) in the presence of sodium acetate (NaOAc)10a to
yield four oxime intermediates (cis-E/cis-Z/trans-E/trans-Z = 72:8.7:13.8:5.5). After chromatographic
separation, the major cis-E-isomer12 was treated with diethyl chlorophosphate [(EtO)2POCl] and sodium
hydride (NaH) in THF to give the cis-substrate 3a (E/Z = 100:0) (Scheme 1). Moreover, compound 2a
was further transformed into 2b through the base-promoted isomerization,13 which was similarly
converted into the trans-substrate 3b as a mixture of two isomers (E/Z = 56:44).14
With 3a and 3b in hand, we submitted them to the amino-Heck reaction. We first examined the
cyclization of 3a under the catalysis of Pd(PPh3)4 (0.2 equiv) in N,N-dimethylformamide (DMF) with the
different
bases10
including
triethylamine,
1,8-diazabicycloundec-7-ene
(DBU),
N,N-diisopropylethylamine (DIPEA), and K2CO3 (Table 1). At 80 ºC,15 the cyclization reactions with
triethylamine, DBU, and DIPEA all proceeded in a 6-endo pathway and were followed by the in situ
oxidative
dehydrogenation
mediated
by
palladium
species10b
to
provide
1-methyl-5,6,7,8-tetrahydroisoquinoline (4a)16 in 12-38% yields, and the best conversion was obtained
with triethylamine (entry 3). Besides, large amounts of recovered 2a (10-40%) were isolated from these
reactions (Table 1, entries 1-3). On the other hand, the use of K2CO3 did not afford any cyclization
product but rather gave 2a solely (entry 4). By using triethylamine as a base, we further screened the
catalytic conditions of Pd(OAc)2/PPh3/DMF/80 ºC and Pd(PPh3)4/CH3CN/reflux, but did not receive any

HETEROCYCLES, Vol. 85, No. 2, 2012
385
improvement on the yield (entries 5 and 6). The application of the catalytic conditions in entry 3 to 3b led
to the formation of 4a in a slightly higher yield (40%, entry 7). Moreover, the time for the cyclization of
3b (30 min) was found to be much shorter than that of 3a (3 h), suggesting that trans-oxime precursors
should be more suited for the cyclization than the cis-isomers due to the favorable proximity of the
equatorial-equatorial steric relationship (Figure 1). As such, we utilized the trans-oximes throughout the
following investigations.
OPO(OEt)2
1) NH2OH·HCl (1.5 eq)
NaOAc (1.5 eq), MeOH
20 oC, 3.5 h
O
N
O
(1.2 eq), Me SCuBr (0.1 eq)
MgBr
2
THF, -55 oC to -30 oC, 2 h, 67%
2) ClPO(OEt)2 (8 eq)
NaH (3.6 eq), THF, rt
2a (2a/2b = 81:19) 24 h, 35% over two steps
3a (E/Z = 100:0)
NaOMe (1.34 eq)
MeOH, reflux, 24 h
94%
OPO(OEt)2
O
N
57% over two steps
3b (E/Z = 56:44)
2b
Scheme 1. Preparation of 3a and 3b
Table 1. Optimization of reaction conditions for Pd(PPh3)4–catalyzed cyclization of 3a and 3b
N
cat. Pd (0.2 eq), base (5eq)
solvent, 80 oC or reflux
3a or 3b
4a
time
(h)
3
entrya substrate
catalytic conditions
yield (%)b
1
2
3
4
5
6
7
3a
3a
3a
3a
3a
3a
3b
Pd(PPh3)4/DBU/DMF/80 ºC
Pd(PPh3)4/DIPEA/DMF/80 ºC
Pd(PPh3)4/Et3N/DMF/80 ºC
Pd(PPh3)4/K2CO3/DMF/80 ºC
12
15
38
-
21
3
3
Pd(OAc)2 /PPh3 (0.4 eq)/ Et3N/DMF/80 ºC
Pd(PPh3)4/Et3N/MeCN/reflux
23
3
21
18
40
Pd(PPh3)4/Et3N/DMF/80 ºC
0.5
a ) All reactions were performed using 0.02 M of substrates. b) Isolated yields.

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HETEROCYCLES, Vol. 85, No. 2, 2012
H
H
N
N
Pd(II)
L
H
Pd(II)
L
H
Disfavored
Favored
Figure 1. Effect of cis- and trans-steric relationships on cyclization
After the optimization of the catalytic conditions, we subsequently carried out the alkylation on 2b with
iodomethane, iodoethane and benzyl bromide, respectively, to prepare ketones 2c-e (Scheme 2).17 Their
oximination afforded the hydroxyloxime intermediates uniformly as the separable E- and Z-isomers.
During the phosphinylation, it was observed that partial phosphinyloximes derived from 2c and 2d (3c
and 3d) underwent the in situ rearrangement to yield amides 5a/5b (from E-isomers) and 6a/6b (from
Z-isomers), which could be attributed to the increased steric hindrance as compared with 3b. Interestingly,
no rearrangement was seen for the phosphinylation of 3e18 bearing an even larger 2-phenylethyl group.
The Pd(PPh3)4-catalyzed cyclization of 3c and 3d afforded isoquinolines 4b and 4c only in 14-34% yields
(Table 2, entries 1-4), and the reactions were all severely competed by the rearrangement or the
hydrolysis to give the corresponding amides or ketone. Markedly different from this, the cyclization of 3e
in E-form took place efficiently to furnish 4d in 70% yield without giving any detectable by-products
(entry 5). Besides, a synthetically useful yield of 4d (53%) was also obtained from the Z-isomer (entry 6).
For 3c-e, it was noticed that the E-oximes (entries 1, 3 and 5) are more favored for the cyclization than
the corresponding Z-isomers (entries 2, 4 and 6). Furthermore, we envision that the relatively high yields
of 4d should be due to a stabilizing π-π interaction between the vinyl and the β-phenyl groups of 3e to
suppress the competitive side reactions. In addition, the reaction of the E-isomer may further benefit from
an additional orbital interaction between the P=O bond and the benzene ring (Figure 2).
OPO(OEt)2
1) NH2OH·HCl (1.5 eq)
NaOAc (1.5 eq), MeOH
20 oC, 3.5 h
O
O
N
H
N
R
R
CH2R
N
R
RX, LDA, THF
-78 oC to rt, 2 d
H
O
or
2b
+
2) ClPO(OEt)2 (2-8 eq), NaH
(1.2-4.8 eq), THF, rt, 24 h
2c R = Me (65%)
2d R = Et (40%)
2e R = Bn (30%)
6a (R = Me, 9%
3c (R
=
Me, E-form: 23%
5a (R = Me, 18%
over 2 steps)
over 2 steps)
Z-form: 17%, over 2 steps)
6b (R = Et, 5%
3d (R
=
Et, E-form: 20%
5b (R = Et, 17%
over 2 steps)
over 2 steps)
Z-form: 9.4%, over 2 steps)
_
3e (R
=
Bn, E-form: 29%
_
Z-form: 23%, over 2 steps)
Scheme 2. Preparation of 3c-e

HETEROCYCLES, Vol. 85, No. 2, 2012
387
Table 2. Pd(PPh3)4-catalyzed cyclization of 3c-e
CH R
2
Pd(PPh ) (0.2 eq), Et N (5eq), DMF
N
3 4
3
3c, 3d or 3e
o
80 C
4b-d
entrya
substrate
time (min)
product(s) & yield (%)b
1
2
3
4
5
6
3c (E-form)
3c (Z-form)
3d (E-form)
3d (Z-form)
3e (E-form)
3e (Z-form)
11
12
12
13
15
15
4b (R = Me, 34%); 2c (15%)
4b (R = Me, 17%); 2c (30%)
4c (R = Et, 22%); 5b (20%)
4c (R = Et, 14%); 6b (25%)
4d (R = Bn, 70%)
4d (R = Bn, 53%)
a ) All reactions were performed using 0.02 M of substrates. b) Isolated yields.
(EtO) OPO
2
H
Pd(II)
N
H
N
Pd (II)
O
H
O
H
P
OEt
EtO
Z-form
E-form
Figure 2. Possible stablizing π-π interactions of aminopalladium(II) intermediates of 3e
To verify the effect of the π-π interactions, we further synthesized the aromatic precursors 3f and 3g
through the alkylation of 2b with α-bromo-p-xylene and 2-(bromomethyl)naphthalene, followed by the
oximination and phosphinylation (Scheme 3, 2b → 2f/2g→ 3f/3g). In the sequence, the formation of
trace amounts of amides 5c and 5d were also observed. Under the standard catalytic conditions, the
cyclization of both substrates proceeded smoothly to provide 4e and 4f in good to acceptable yields
without accompanying by hydrolysis and rearrangement, thus again confirming the positive role that the
aryl moieties played on the cyclization.

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HETEROCYCLES, Vol. 85, No. 2, 2012
OPO(OEt)
2
1) NH OH·HCl (1.5 eq)
N
O
2
H
N
NaOAc (1.5 eq), MeOH
R
R
o
CH R
20 C, 3.5 h
2
RX, LDA, THF
+
O
2b
o
2) ClPO(OEt) (8 eq), NaH
2
(4.8 eq), THF, rt, 24 h
-78 C to rt, 2 d
2f (R = p-tolylmethyl, 41%)
5c (R = p-tolylmethyl, trace)
3f (R = p-tolylmethyl, E-form: 35%)
3g (R = 2-naphthalenylmethyl, E-form: 37%)
2g (R = 2-naphthalenylmethyl, 14%)
5d (R = 2-naphthalenylmethyl, trace)
Pd(PPh ) (0.2 eq), Et N (5eq)
3 4
o
3
DMF, 80 C, 15 or 8 min
CH R
2
N
4e (R = p-tolylmethyl, 65%)
4f (R = 2-naphthalenylmethyl, 50%)
Scheme 3. Preparation and Pd(PPh3)4–catalyzed cyclization of 3f and 3g
In addition to the ketone oximes, we also attempted the protocol on a phosphinylaldoxime. As outlined in
Scheme 4, the synthesis of the precursor began with the 1,4-addition of 1-cyclohexene-1-carboxaldehyde
followed by the isomerization19 to afford aldehyde 2h, which was subsequently transformed into 3h as the
sole E-isomer.20 Herein, we used CH2Cl2 as the solvent instead of previously employed CH3OH in the
oximination step to avoid the formation of the acetal. Based on the previous experience,21 we predicted
that the cyclization of 3h would be inevitably competed by the cyanation under the basic reaction
conditions, and consequently utilized a duplicated catalytic loading (0.4 equiv) to minimize this. Under
the catalysis, the reaction afforded 34% of isoquinoline (4g)10b,22 together with 30% of cyanide 7 as the
side product. Therefore the utility of the strategy has been further underscored by the generation of 4g
possessing the significant biological23 and synthetic values.
OPO(OEt)
2
N
O
1) NH OH·HCl (3 eq), NaOAc
2
O
1) vinylmagnesium bromide (3 eq), Me S·CuBr (0.27 eq)
2
(3 eq), CH Cl , rt, 4 h
2
2
o
TMSCl (2 eq), HMPA (3 eq),THF, -55 C, 2 h
H
H
H
2) ClPO(OEt) (1.2 eq), NaH
2
(0.9 eq), THF, rt, 10 h
2) DBU (1.03 eq), CH Cl , rt, 2 d
2
2
3h (22%)
2h (61% over 2 steps)
Pd(PPh ) (0.4 eq)
3 4
Et N (5eq), DMF
3
o
80 C, 8 min
CN
N
+
4g (34%)
7 (30%)
Scheme 4. Preparation and Pd(PPh3)4–catalyzed cyclization of 3h

HETEROCYCLES, Vol. 85, No. 2, 2012
389
In summary, we have disclosed that a range of 2-vinylcyclohexyl O-diethylphosphinyloximes underwent
a 6-endo cyclization under the catalysis of Pd(PPh3)4 to furnish tetrahydroisoquinoline derivatives in
varying yields. As we know, it is the first time that this type of compounds has been prepared through the
amino-Heck approach.24 More importantly, we discovered that the undesired side reactions competing
with the cyclization could be suppressed by introducing a β-aryl moiety, and the π-π stacking interactions
between the phosphoryl and/or vinyl group and aryl ring are proposed to account for this. Therefore, this
method should be of particular use for preparing the tetrahydroisoquinolines bearing an 2-arylethyl
appendage.
EXPERIMENTAL
All of starting materials were obtained from commercial suppliers and used without further purification.
Tetrahydrofurane was distilled from sodium and benzophenone, N,N-dimethylformamide, triethylamine,
diisopropylamine and dichloromethane were distilled from calcium hydride before use. TLC analysis and
preparation were carried out on Merck 25 DC-Alufolien Kieselgel 60F254 glass-backed plates visualised
by using UV light, or by means of ethanolic solution of vanillin (5%) with sulphuric acid (5%), iodine or
aqueous KMnO4 solution (10%). The flash chromatographic purifications were performed on Merck
Art.9385 Kiesegel 60 silica gel (230–400 mesh) or Brockmann I basic aluminum oxide (~150 mesh).
13
NMR spectra (1H, C-NMR, DEPT, 2D-NOESY) were recorded on a Bruker 400 or Varian 600 MHz
spectrometer using deuteriochloroform (CDCl3) as solvent. Chemical shifts measurements are reported in
delta (δ) units. Splitting patterns are described as singlet (s), doublet (d), triplet (t), quartet (q) or multiplet
(m). Coupling constants (J) are reported in Hertz (Hz). Infrared (IR) spectra were recorded on an IR-FT
JASCO 410 spectrophotometer (neat) and resonances are reported in wave numbers (cm-1). High
resolution mass spectra (HRMS) were determined by a Finnigan/Thermo Quest MAT 95XL spectrometer
in electron impact (EI) or electrospray ionization (ESI) modes.
Typical Procedure for the Preparation of o–Diethylphosphinyloximes from Ketones; cis-(E)-Diethyl
1-(2-vinylcyclohexyl)ethylideneaminooxyphosphonate
(3a):
To
a
stirred
solution
of
1-(2-vinylcyclohexyl)ethanone (2a) (cis/trans = 81:19, 354 mg, 2.33 mmol) in MeOH (6.4 mL), sodium
acetate (289 mg, 3.50 mmol) and NH2OH·HCl (253 mg, 3.50 mmol) were successively added. The
resulting suspension was stirred at 20 ºC for 3.5 h, then diluted with CH2Cl2 (200 mL) and washed with
water (40 mL x 2) and brine (40 mL). After concentration, the crude residue was purified by flash
chromatography on silica gel (hexane-EtOAc 30:1, 5:1) to give the cis-E-oxime (213 mg) as the major
isomer followed by the mixture of cis-Z- and the trans-E, Z-oximes (82.6 mg, cis-Z/trans-E/trans-Z =
1
31:49:20). cis-E-oxime: H NMR (400 MHz, CDCl3) δ 8.10 (broad s, 1H), 5.97 (m, 1H), 5.03 (dm, J =
10.8 Hz, 1H), 5.02 (dm, J = 16.3 Hz, 1H), 2.67 (ddd, J = 8.2, 7.8, 3.3 Hz, 1H), 2.34 (ddd, J = 11.3, 3.9,

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HETEROCYCLES, Vol. 85, No. 2, 2012
3.9 Hz, 1H), 1.85–1.77 (m, 2H), 1.83 (s, 3H), 1.73–1.55 (m, 3H), 1.51–1.43 (m, 2H), 1.33–1.23 (m, 1H).
1
cis-Z-oxime: H NMR (400 MHz, CDCl3) δ 6.12 (ddd, J = 17.2, 10.2, 9.5 Hz, 1H), 5.08–4.86 (m, 2H),
3.30 (ddd, J = 12.8, 3.9, 3.8 Hz, 1H), 2.87 (ddd, J = 9.1, 8.2, 3.4 Hz, 1H), 1.74 (s, 3H), 1.72–1.67 (m, 2H),
1.52 (m, 4H), 1.42-1.26 (m, 2H). Under a nitrogen atmosphere, NaH (60%, 183 mg, 4.58 mmol) and
diethyl chlorophosphate (95%, 1.55 mL, 10.2 mmol) were successively added to a stirred solution of
cis-E-oxime (213 mg, 1.27 mmol) in dry THF (7.7 mL) pre-cooled at 0 ºC. The reaction mixture was
continued to stir for 24 h at room temperature, then cooled at 0 ºC and carefully quenched with saturated
aqueous NH4Cl solution (20 mL). The resulting mixture was diluted with EtOAc (100 mL), washed with
water (20 mL x 2) and brine (20 mL), and concentrated under vacuo. The crude mixture was subjected to
chromatographic purification on silica gel (hexane-EtOAc 15:1, 5:1, 3:1, 1:1) to afford 3a as a pale
yellow oil (248 mg, 35% over two steps).
1
IR (neat) 3050, 2982, 2932, 1637, 1448, 1276, 1033, 978, 916 cm-1; H NMR (400 MHz, CDCl3) δ 5.95
(ddd, J = 17.0, 9.2, 8.8 Hz, 1H), 4.98 (br d, J = 17.6 Hz, 1H), 4.97 (br d, J = 9.2 Hz, 1H), 4.23–4.10 (m,
4H), 2.61 (ddd, J = 8.4, 8.2, 3.8 Hz, 1H), 2.47–2.43 (m, 1H), 1.86 (s, 3H), 1.81–1.71 (m, 2H), 1.70–1.57
(m, 3H), 1.48–1.41 (m, 2H), 1.31 (t, J = 7.0, 3H), 1.30 (t, J = 7.1, 3H), 1.27–1.19 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 168.9 (d, J = 12.4 Hz), 137.7, 115.8, 64.4 (d, J = 5.9 Hz), 64.2 (d, J = 5.8 Hz), 47.4, 41.5,
32.1, 25.4, 24.1, 21.3, 16.2 (d, J = 6.5 Hz), 14.8; HRMS-EI: m/z [M]+ calcd. for C14H26NO4P: 303.1599;
found: 303.1594.
trans-(E,Z)-Diethyl 1-(2-vinylcyclohexyl)ethylideneaminooxyphosphonate (3b): The typical procedure
for the preparation of 3a was followed; 2b (211 mg, 1.39 mmol) was used as the starting material. Flash
chromatography on silica gel (hexane-EtOAc 8:1, 5:1, 3:1, 2:1) gave 3b as a mixture of two isomers (E/Z
= 56:44) in 57% (236 mg) yield over two steps.
1
The E- and Z-oxime intermediates were isolated as a inseperable mixture (hexane-EtOAc 30:1, 5:1): H
NMR (400 MHz, CDCl3) E-isomer: δ 8.19 (br s, 1H), 5.61 (ddd, J = 17.2, 10.2, 7.8 Hz, 1H), 4.95 (dd, J =
17.3, 1.8 Hz, 1H), 4.90 (dd, J = 10.3, 1.8 Hz, 1H), 2.11–2.06 (m, 2H), 1.82–1.73 (m, 3H), 1.78 (s, 3H),
1.70 (m, 1H), 1.42–1.15 (m, 4H); Z-isomer: δ 8.36 (br s, 1H), 5.70–5.56 (m, 1H), 5.03–4.88 (m, 2H),
2.14–2.02 (m, 2H), 1.82–1.73 (m, 3H), 1.77 (s, 3H), 1.70 (m, 1H), 1.42–1.15 (m, 4H).
3b: IR (neat) 3050, 2982, 2928, 1639, 1278, 1033, 973, 916 cm-1; 1H NMR (400 MHz, CDCl3): E-isomer
δ 5.64–5.52 (m, 1H), 5.00–4.84 (m, 2H), 4.25-4.10 (m, 4H), 2.29 (ddd, J = 11.3, 11.3, 3.2 Hz, 1H),
2.12–1.98 (m, 1H), 1.85 (s, 3H), 1.82-1.67 (m, 5H), 1.37–1.27 (m, 8H), 1.24–1.15 (m, 1H); Z-isomer: δ
5.64–5.52 (m, 1H), 5.00–4.84 (m, 2H), 4.25–4.10 (m, 4H), 3.18 (m, 1H), 2.12-1.98 (m, 1H), 1.86 (s, 3H),
1.82–1.67 (m, 5H), 1.37–1.27 (m, 8H), 1.24–1.15 (m, 1H); 13C NMR (100 MHz, CDCl3): E-isomer δ
169.8 (d, J = 12.3 Hz), 141.5, 114.3, 64.3 (d, J = 5.8 Hz), 64.1 (d, J = 5.5 Hz), 48.4, 44.5, 32.7, 29.8, 25.5,
25.3, 16.1 (d, J = 6.4 Hz), 11.9; Z-isomer: δ 169.9 (d, J = 13.2 Hz), 141.2, 114.3, 64.3 (d, J = 5.2 Hz),

HETEROCYCLES, Vol. 85, No. 2, 2012
391
64.2 (d, J = 6.6 Hz), 43.7, 32.6, 28.6, 25.6, 25.2, 16.1 (d, J = 6.4 Hz); HRMS-EI m/z [M]+ cacld. for
C14H26NPO4 303.1599; found 303.1608.
Typical Procedure for Amino-Heck Cyclization of trans-2-Vinylcyclohexyl-substituted
Phosphinyloximes; 1-Methyl-5,6,7,8-tetrahydroisoquinoline (4a): To a solution of 3b (186 mg, 0.61
mmol) in dry DMF (30.7 mL, 0.02 M) was added Pd(PPh3)4 (143 mg, 0.12 mmol) under N2. The mixture
was stirred at room temperature for 5 min before the addition of Et3N (0.43 mL, 3.07 mmol). The reaction
mixture was heated at 80 ºC for 30 min, cooled to rt and diluted with water (30 mL). The solution was
extracted with Et2O (100 mL x 2). The combined organic layers were washed with water (40 mL x 2) and
brine (40 mL). After concentration, the crude residue was subjected to chromatographic purification on
aluminum oxide (hexane-EtOAc 50:1, 20:1, 10:1) to afford recovered 2b (9.3 mg, 10%) followed by the
known 4a16 (36 mg, 40%).
1
4a: IR (neat) 3051, 2929, 1643, 1567, 1589, 835, 808 cm-1; H NMR (400 MHz, CDCl3) δ 8.15 (d, J = 5.0
Hz, 1H), 6.82 (d, J = 5.0 Hz, 1H), 2.71 (t, J = 6.2 Hz, 2H), 2.61 (d, J = 6.2 Hz, 2H), 2.42 (s, 3H),
1.88–1.80 (m, 2H), 1.79–1.72 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 156.9, 146.0, 145.1, 130.9, 122.1,
29.4, 25.9, 23.0, 22.1; HRMS-EI m/z [M]+ cacld. for C10H13N 147.1048; found 147.1042.
Typical Procedure for Alkylation of 2b; trans-1-(2-vinylcyclohexyl)propan-1-one (2c): Under a N2
atmosphere, a solution of n-BuLi (2.25 mL, 1.6 M in hexane, 3.60 mmol) was slowly added to a stirred
solution of diisopropylamine (0.5 mL, 3.60 mmol) in dry THF (4.7 mL) pre-cooled to 0 ºC via a syringe
in 5 min. The resulting pale-yellow solution was then cooled at -78 ºC and stirred for 30 min. After this, a
solution of 2b (498 mg, 3.27 mmol) in dry THF (3.7 mL) was added dropwise to the mixture via a
syringe within 18 min, and stirring was continued for an additional 30 min at -78 ºC before the quick
addition of iodomethane (0.19 mL, 2.94 mmol). The mixture was allowed to stir at room temperature for
42 h, then diluted with saturated aqueous NH4Cl solution (15 mL) and extracted with Et2O (100 mL). The
organic layer was separated and washed with water (40 mL x 2) and brine (40 mL). The combined
aqueous layers were re-extracted with another portion of Et2O (100 mL) and the organic layer was
washed with water and brine. The combined organic layers were concentrated under reduced pressure,
and the crude reside was purified by flash chromatography on silica gel (hexane-EtOAc 300:1, 150:1) to
give 2c in 65% yield (355.4 mg,) along with recovered 2b (54 mg).
2c: IR (neat) 3078, 2974, 2931, 1711, 1640, 917, 622 cm-1; 1H NMR (400 MHz, CDCl3) δ 5.65 (ddd, J =
17.2, 10.2, 7.6 Hz, 1H), 4.94 (dm, J = 17.1 Hz, 1H), 4.89 (dd, J = 10.3, 1.8 Hz, 1H), 2.51–2.26 (m, 4H),
13
1.80–1.71 (m, 4H), 1.38–1.15 (m, 4H), 0.99 (t, J = 7.2 Hz, 3H); C NMR (100 MHz, CDCl3) δ 214.6,
141.6, 114.4, 55.8, 43.7, 35.9, 31.9, 29.1, 25.4, 25.4, 7.4; HRMS-EI: m/z [M]+ calcd. for C11H18O:
166.1358; found: 166.1365.

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trans-1-(2-Vinylcyclohexyl)butan-1-one (2d): 2d was similarly prepared as 2c from 2b (200 mg, 1.31
mmol) by using 1.5 equiv of iodoethane (0.16 mL, 1.97 mmol) and 1.16 equiv of LDA (n-BuLi: 1.6 M in
hexane, 1.15 mL, 1.84 mmol; diisopropylamine: 0.21 mL, 1.52 mmol). After chromatographic
purification on silica gel (hexane-EtOAc 400:1, 300:1, 200:1, 100:1), 73.5 mg of 2d was obtained (40%
yield based on recovered 2b).
IR (neat) 3077, 2955, 1727, 1601, 1462, 1122, 723, 700 cm-1; 1H NMR (400 MHz, CDCl3) δ 5.61 (ddd, J
= 17.3, 10.2, 7.5 Hz, 1H), 4.95 (dm, J = 17.0 Hz, 1H), 4.89 (dd, J = 10.3, 1.6 Hz, 1H), 2.44–2.24 (m, 4H),
1.82–1.71 (m, 4H), 1.59–1.49 (m, 2H), 1.38–1.10 (m, 4H), 0.88 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 214.0, 141.6, 114.4, 55.9, 44.6, 43.5, 31.9, 29.1, 25.4, 25.4, 16.7, 13.8; HRMS-EI: m/z [M]+
calcd. for C12H20O: 180.1514; found: 180.1506.
trans-3-Phenyl-1-(2-vinylcyclohexyl)propan-1-one (2e): 2e was similarly prepared as 2c from 2b
(278.3 mg, 1.83 mmol) by using 2 equiv of benzyl bromide (0.45 mL, 3.66 mmol) and 1.16 equiv of LDA
(n-BuLi: 1.6 M in hexane, 1.6 mL, 2.56 mmol; diisopropylamine: 0.30 mL, 2.12 mmol). After
chromatographic purification on silica gel (hexane-EtOAc 100:0, 200:1), 98.7 mg of 2e was obtained
(30% yield based on recovered 2b).
1
IR (neat) 3097, 3064, 2928, 2855, 1710, 1639, 1604, 916, 748, 700 cm-1; H NMR (400 MHz, CDCl3) δ
7.31–7.24 (m, 2H), 7.21–7.15 (m, 3H), 5.59 (ddd, J = 17.2, 10.2, 7.5 Hz, 1H), 4.94 (dm, J = 17.5 Hz, 1H),
4.89 (dm, J = 10.3, Hz, 1H), 2.85 (t, J = 7.2 Hz, 2H), 2.77–2.61 (m, 2H), 2.34–2.21 (m, 2H), 1.80 (m, 4H),
1.34–1.27 (m, 2H), 1.23–1.09 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 213.0, 141.5, 141.4, 128.4, 128.3,
126.0, 114.5, 56.1, 44.3, 43.7, 31.9, 29.3, 28.9, 25.3; HRMS-EI m/z [M]+ cacld. for C17H22O 242.1671;
found 242.1664.
trans-3-p-Tolyl-1-(2-vinylcyclohexyl)propan-1-one (2f): 2f was similarly prepared as 2c from 2b (493.3
mg, 3.24 mmol) by using 0.9 equiv of α-bromo-p-xylene (551 mg, 2.92 mmol, dissolved in 2.0 mL of
THF before the addition) and 1.1 equiv of LDA (n-BuLi: 1.6 M in hexane, 2.2 mL, 3.56 mmol;
diisopropylamine: 0.5 mL, 3.56 mmol). After chromatographic purification on silica gel (hexane-EtOAc
100:0, 200:1), 211.8 mg of 2f was obtained (41% yield based on recovered 2b).
IR (neat) 3088, 3030, 2927, 1711, 1639, 1516, 992, 809 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.08 (d, J =
8.3 Hz, 2H), 7.05 (d, J = 8.3 Hz, 2H), 5.59 (ddd, J = 17.2, 10.2, 7.4 Hz, 1H), 4.94 (dm, J = 17.0 Hz, 1H),
4.89 (dm, J = 10.3, 1H), 2.81 (br d, J = 7.0 Hz, 2H), 2.77 (dd, J = 9.4, 4.2 Hz, 1H), 2.74–2.58 (m, 2H),
13
2.34–2.24 (m, 2H), 2.31 (s, 3H), 1.80–1.70 (m, 4H), 1.37–1.29 (m, 2H), 1.23–1.12 (m, 2H); C NMR
(100 MHz, CDCl3) δ 213.0, 141.5, 138.3, 135.4, 129.1, 128.2, 114.5, 56.1, 44.4, 43.7, 31.9, 28.9, 28.8,
25.4, 21.0; HRMS-EI m/z [M]+ cacld. for C18H24O 256.1827; found 256.1823.
trans-3-Naphthalen-2-yl-1-(2-vinylcyclohexyl)propan-1-one (2g): 2g was similarly prepared as 2c from
2b (502.9 mg, 3.30 mmol) by using 0.9 equiv of 2-(bromomethyl)naphthalene (685 mg, 2.97 mmol,

HETEROCYCLES, Vol. 85, No. 2, 2012
393
dissolved in 2.0 mL of THF before the addition) and 1.2 equiv of LDA (n-BuLi: 1.6 M in hexane, 2.48
mL, 3.96 mmol; diisopropylamine: 0.56 mL, 3.96 mmol). After chromatographic purification on silica gel
(hexane-EtOAc 400:1, 200:1, 100:1, 60:1), 138.5 mg of 2g (14%) was obtained mixed with the
dialkylated byproduct.
1
IR (neat) 3054, 2927, 2855, 1707, 1640, 1509, 917, 854, 817 cm-1; H NMR (400 MHz, CDCl3) δ
7.86–7.70 (m, 3H), 7.61 (s, 1H), 7.50–7.38 (m, 3H), 5.61 (ddd, J = 17.1, 10.2, 7.6 Hz, 1H), 4.95 (dm, J =
17.1 Hz, 1H), 4.89 (dm, J = 10.4, 1H), 3.02 (t, J = 7.9 Hz, 2H), 2.90–2.64 (m, 2H), 2.37–2.23 (m, 2H),
1.81–1.71 (m, 4H), 1.40–1.07 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 212.8, 141.5, 138.9, 133.6, 132.0,
128.0, 127.6, 127.4, 127.2, 126.4, 126.0, 125.2, 114.5, 56.2, 44.2, 43.7, 32.0, 29.4, 29.0, 25.4; HRMS-EI:
m/z [M]+ calcd. for C21H24O: 292.1827; found: 292.1835.
trans-(E)-
and
(Z)-Diethyl
1-(2-vinylcyclohexy)lpropylideneaminooxyphosphonate
(3c),
trans-N-(2-vinylcyclohexyl)propionamide (5a) and trans-N-ethyl-2-vinylcyclohexanecarboxamide
(6a): 3c was similarly prepared as 3a by using 2c as the starting material. Oximination of 2c (328.4 mg,
1.98 mmol) with NH2OH·HCl and NaOAc gave 181 mg of E-oxime and 98 mg of Z-oxime after the
chromatographic purification on silica gel (hexane-EtOAc 80:1, 40: 1 and 10:1). E-oxime: 1H NMR (400
MHz, CDCl3) δ 8.84 (broad s, 1H), 5.64 (ddd, J = 17.2, 10.1, 7.6 Hz, 1H), 4.94 (dm, J = 17.2 Hz, 1H),
4.90 (dm, J =10.0 Hz, 1H), 2.37 (dq, J = 15.0, 7.6 Hz, 1H), 2.14 (dq, J = 15.0, 7.6 Hz, 1H), 2.20-2.11 (m,
1H), 2.05 (ddd, J = 11.3, 11.1, 3.0 Hz, 1H), 1.82-1.72 (m, 4H), 1.44-1.14 (m, 4H), 1.11 (t, J = 7.5 Hz, 3H);
Z-oxime: 1H NMR (400 MHz, CDCl3) δ 9.66 (br s, 1H), 5.64 (ddd, J = 17.2, 10.2, 7.8 Hz, 1H), 4.96 (dm,
J = 17.2 Hz, 1H), 4.89 (dm, J = 10.5 Hz, 1H), 3.10 (m, 1H), 2.20 (q, J = 7.3 Hz, 2H), 2.16-2.03 (m, 1H),
1.81-1.66 (m, 4H), 1.43-1.13 (m, 4H), 1.06 (t, J = 7.3 Hz, 3H).
The phosphinylation of E-oxime (61.4 mg, 0.34 mmol) was carried out with (EtO)2POCl (95%, 0.10 mL,
0.68 mmol) and NaH (60%, 16 mg, 0.41 mmol) in THF. Chromatographic purification on silica gel
(hexane-EtOAc 10:1, 5:1, 3:1, 1:1) gave 3c (E-form, 49.7 mg, 23% over two steps) and 5a (22.3 mg, 18%,
over two steps) as an inseparable mixture.
1
3c (E-form): H NMR (400 MHz, CDCl3): δ 5.73–5.54 (m, 1H), 5.03–4.84 (m, 2H), 4.27–4.12 (m, 4H),
2.42 (dq, J = 12.7, 7.6 Hz, 1H), 2.25 (ddd, J = 11.4, 11.3, 2.6 Hz, 1H), 2.20–2.12 (m, 2H), 1.86–1.66 (m,
13
4H), 1.47–1.14 (m, 4H), 1.34 (td, J = 7.1, 0.9 Hz, 6H),1.11 (t, J = 7.6 Hz, 3H); C NMR (100 MHz,
CDCl3) major: δ 173.5 (J = 12.2 Hz), 141.8, 114.3, 64.2 (J = 5.6 Hz), 64.1 (J = 5.6 Hz), 48.6, 44.4, 32.7,
30.4, 25.5, 25.4, 21.1, 16.1 (d, J = 6.7 Hz).
1
5a: IR (neat) 3307, 3074, 2975, 2933, 1642, 1543, 994, 912 cm-1; H NMR (400 MHz, CDCl3) δ 5.66
(ddd, J = 17.1, 10.1, 8.6 Hz, 1H), 5.23 (br s, 1H), 4.99 (dm, J = 17.2 Hz, 1H), 4.95 (dm, J = 10.3 Hz, 1H),
3.60 (dtd, J = 15.0, 6.8, 4.0, 1H), 2.14 (q, J = 7.6 Hz, 2H), 2.05 (dm, J = 12.6 Hz, 1H), 1.85–1.65 (m, 4H),
13
1.42–1.28 (m, 2H), 1.27–1.18 (m, 2H), 1.11 (t, J = 7.6 Hz, 3H); C NMR (100 MHz, CDCl3) δ 173.1,

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HETEROCYCLES, Vol. 85, No. 2, 2012
141.3, 115.0, 51.5, 49.4, 33.2, 32.5, 30.0, 25.3, 25.1, 10.0; HRMS-EI m/z [M]+ cacld. for C11H19NO
181.1467; found 181.1459.
The phosphinylation of Z-oxime (85.3 mg, 0.47 mmol) was carried out with (EtO)2POCl (95%, 0.29 mL,
1.88 mmol) and NaH (60%, 45 mg, 1.13 mmol) in THF. Chromatographic purification on silica gel
(hexane-EtOAc 10:1, 5:1, 2:1) gave 3c (Z-form, 94.0 mg, 17% over two steps) and 6a (28 mg, 9%, over
two steps) as an inseparable mixture.
1
3c (Z-form): H NMR (400 MHz, CDCl3) δ 5.69–5.52 (m, 1H), 5.04–4.85 (m, 2H), 4.26–4.10 (m, 4H),
3.14–2.91 (m, 1H), 2.25 (q, J = 7.2 Hz, 2H), 2.18–2.05 (m, 1H), 1.84–1.71 (m, 4H), 1.33 (t, J = 7.0 Hz, 6
H), 1.30–1.11 (m, 4H), 1.07 (t, J = 7.1Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 172.2 (J = 12.1 Hz), 141.5,
114.2, 64.4 (J = 5.9 Hz), 64.3 (J = 6.0 Hz), 43.6, 32.8, 28.8, 25.6, 25.4, 16.2 (d, J = 6.4 Hz), 10.3.
6a: IR (neat) 3295, 3081, 2975, 1639, 1556, 995, 911 cm-1; 1H NMR (400 MHz, CDCl3) δ 5.64 (ddd, J =
17.2, 10.2, 7.7 Hz, 1H), 5.52 (br s, 1H), 5.00 (dm, J = 17.2 Hz, 1H), 4.90 (dm, J = 10.2 Hz, 1H),
3.32–3.15 (m, 2H), 2.29–2.18 (m, 1H), 1.84–1.68 (m, 5H), 1.53 (ddm, J = 19.4, 12.9 Hz, 1H), 1.34-1.10
13
(m, 3H), 1.08 (t, J = 7.2 Hz, 3H); C NMR (100 MHz, CDCl3) δ 174.9, 141.5, 114.2, 51.6, 43.8, 34.4,
31.8, 29.8, 25.4, 25.4, 14.9; HRMS-EI: m/z [M]+ calcd. for C11H19NO: 181.1467; found: 181.1470.
trans-(E) and (Z)- Diethyl 1-(2-vinylcyclohexyl)butylideneaminooxyphosphonate (3d),
trans-N-(2-vinylcyclohexyl)butyramide (5b) and trans-N-propyl-2-vinylcyclohexanecarboxamide
(6b): 3d was similarly prepared as 3a by using 2d as the starting material. Oximination of 2d (164.6 mg,
0.91 mmol) with NH2OH·HCl and NaOAc gave 99 mg of E-oxime and 41.6 mg of Z-oxime after the
1
chromatographic purification on silica gel (hexane-EtOAc 60:1, 40:1, 10:1). E-oxime: H NMR (400
MHz, CDCl3) δ 8.42 (br s, 1H), 5.64 (ddd, J = 17.2, 10.2, 7.8 Hz, 1H), 4.94 (dm, J = 17.3 Hz, 1H), 4.90
(dm, J = 10.4 Hz, 1H), 2.30 (ddd, J = 12.5, 11.0, 5.5 Hz, 1H), 2.18–1.98 (m, 3H), 1.82–1.72 (m, 4H),
1
1.68–1.57 (m, 1H), 1.54–1.43 (m, 1H), 1.39–1.16 (m, 4H), 0.96 (t, J = 7.4 Hz, 3H); Z-oxime: H NMR
(400 MHz, CDCl3) δ 9.23 (br s, 1H), 5.65 (ddd, J = 17.3, 10.2, 7.8 Hz, 1H), 4.96 (dm, J = 17.2 Hz, 1H),
4.90 (dm, J = 10.5 Hz, 1H), 3.10 (m, 1H), 2.11 (td, J = 7.8, 2.7 Hz, 2H), 2.13–2.09 (m, 1H), 1.81–1.66 (m,
4H), 1.61–1.46 (m, 2H), 1.45–1.12 (m, 4H), 0.92 (t, J = 7.3 Hz, 3H).
The phosphinylation of E-oxime (98 mg, 0.50 mmol) was carried out with (EtO)2POCl (95%, 0.31 mL,
2.00 mmol) and NaH (60%, 48 mg, 1.20 mmol) in THF. Chromatographic purification on silica gel
(hexane-EtOAc 10:1, 5:1, 2:1) gave 3d (E-form, 60 mg, 20% over two steps) mixed with 5b (31.4 mg,
17.8%, over two steps).
3d (E-form): 1H NMR (400 MHz, CDCl3) major: δ 5.73–5.56 (m, 1H), 5.04–4.86 (m, 2H), 4.27–4.09 (m,
4H), 2.35 (ddd, J = 12.2, 11.1, 5.5 Hz, 1H), 2.26–2.14 (m, 2H), 2.14–2.03 (m, 1H), 1.86–1.67 (m, 4H),
1.55–1.43 (m, 2H), 1.43–1.14 (m, 4H), 1.34 (t, J = 7.0 Hz, 6H), 0.91 (t, J = 7.2 Hz, 3H); 13C NMR (100

HETEROCYCLES, Vol. 85, No. 2, 2012
395
MHz, CDCl3) major: δ 172.3 (d, J = 12.1 Hz), 141.7, 114.2, 64.2 (d, J = 5.8 Hz), 64.1 (d, J = 5.8 Hz),
48.6, 44.5, 32.7, 30.6, 30.2, 25.5, 25.4, 19.6, 16.1 (d, J = 6.4 Hz), 14.6.
5b: IR (neat) 3289, 3075, 2959, 1640, 1550, 989, 909 cm-1; 1H NMR (400 MHz, CDCl3) δ 5.66 (ddd, J =
17.3, 10.0, 8.6 Hz, 1H), 5.23 (br s, 1H), 4.99 (dm, J = 17.3 Hz, 1H), 4.95 (dm, J = 10.0 Hz, 1H), 3.61 (dtd,
J = 13.1, 8.7, 4.3 Hz, 1H), 2.15–2.02 (m, 3H), 1.85–1.70 (m, 4H), 1.61 (tq, J = 7.4, 7.4 Hz, 2H),
1.42–1.14 (m, 3H), 1.12–1.01 (m, 1H), 0.91 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 172.3,
141.3, 115.0, 51.6, 49.3, 39.0, 33.3, 32.5, 25.3, 25.1, 19.3, 13.8; HRMS-EI: m/z [M]+ calcd. for
C12H21NO: 195.1623; found: 195.1615.
The phosphinylation of Z-oxime (23.3 mg, 0.12 mmol) was carried out with (EtO)2POCl (95%, 0.07 mL,
0.48 mmol) and NaH (60%, 11 mg, 0.29 mmol) in THF. Chromatographic purification on silica gel
eluting with hexane and EtOAc (15:1, 6:1, 3:1) gave 6b (5.1 mg, 5% over two steps) followed by 3d
(Z-form, 15.9 mg, 9.4% over two steps).
3d (Z-form): IR (neat) 3083, 2964, 1640, 1448, 1276, 1035, 967, 914 cm-1; 1H NMR (400 MHz, CDCl3) δ
5.59 (ddd, J = 17.2, 10.0, 8.0 Hz, 1H), 4.95 (br d, J = 17.2 Hz, 1H), 4.89 (dm, J = 9.9 Hz, 1H), 4.26–4.12
(m, 4H), 3.22–2.92 (m, 1H), 2.23–2.07 (m, 3H), 1.81–1.71 (m, 3H), 1.67 (br d, J = 13.1 Hz, 1H),
1.63–1.53 (m, 2H), 1.37-1.11 (m, 4H), 1.34 (t, J = 7.0 Hz, 3H), 1.33 (t, J = 7.1 Hz, 3H), 0.91 (t, J = 7.3
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 171.1 (d, J = 12.6 Hz), 141.5, 114.2, 64.3 (d, J = 5.9 Hz), 64.2 (d,
J = 5.8 Hz), 46.5, 32.8, 28.7, 25.6, 25.4, 19.1, 16.2 (d, J = 6.5 Hz), 14.0; HRMS-EI: m/z [M]+ calcd. for
C16H30NO4P: 331.1912; found: 331.1903.
6b: IR (neat) 3300, 3081, 2960, 1638, 1556, 995, 911cm-1; 1H NMR (400 MHz, CDCl3) δ 5.66 (ddd, J =
17.3, 10.2, 7.7 Hz, 1H), 5.37 (br s, 1H), 5.02 (dm, J = 17.2 Hz, 1H), 4.93 (dm, 10.3 Hz, 1H), 3.27–3.09
(m, 2H), 2.30–2.20 (m, 1H), 1.87-1.69 (m, 5H), 1.62–1.52 (m, 1H), 1.48 (qt, J = 7.3, 7.3 Hz, 2H),
1.39-1.09 (m, 3H), 0.90 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 175.0, 114.5, 114.3, 51.8, 43.8,
40.9, 31.8, 29.9, 25.4, 25.3, 22.9, 11.4; HRMS-EI: m/z [M]+ calcd. for C12H21NO: 195.1623; found:
195.1616.
trans-(E) and (Z)-Diethyl 3-phenyl-1-(2-vinylcyclohexyl)propylideneaminooxyphosphonate (3e): 3e
was similarly prepared as 3a by using 2e as the starting material. Oximination of 2e (98.7 mg, 0.43 mmol)
with NH2OH·HCl and NaOAc gave 53.4 mg of E-oxime and 35.4 mg of Z-oxime after the
chromatographic purification on silica gel (hexane-EtOAc 50:1, 20:1, 10:1).
The phosphinylation of E-oxime (53.4 mg, 0.21 mmol) was carried out with (EtO)2POCl (95%, 0.25 mL,
1.66 mmol) and NaH (60%, 40 mg, 1.00 mmol) in THF. Chromatographic purification on silica gel
(hexane-EtOAc 10:1, 5:1, 2:1) gave 3e (E-form,18 50 mg, 29% over two steps).
1
IR (neat) 3027, 2982, 1640, 1604, 1276, 1033, 979, 924 cm-1; H NMR (400 MHz, CDCl3) δ 7.32–7.28
(m, 2H), 7.21 (m, 1H), 7.22 (br d, J = 7.2 Hz, 2H), 5.61 (ddd, J = 17.1, 10.2, 8.2 Hz, 1H), 4.94 (dm, J =

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HETEROCYCLES, Vol. 85, No. 2, 2012
17.1 Hz, 1H), 4.90 (dm, J = 10.2 Hz, 1H), 4.27–4.14 (m, 4H), 2.93 (ddd, J = 11.8, 11.6, 5.0 Hz, 1H), 2.75
(ddd, J = 11.6, 11.6, 4.5 Hz, 1H), 2.66 (ddd, J = 11.6, 11.6, 4.5 Hz, 1H), 2.41 (ddd, J = 11.8, 11.5, 5.1 Hz,
1H), 2.27 (ddd, J = 11.3, 11.3, 3.1 Hz, 1H), 2.20–2.11 (m, 1H), 1.81–1.72 (m, 4H), 1.46–1.18 (m, 4H),
1.36 (t, J = 7.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 171.7 (d, J = 12.3 Hz), 141.8, 141.1, 128.6, 128.2,
126.4, 114.5, 64.4 (d, J = 5.9 Hz), 64.2 (d, J = 5.7 Hz), 48.8, 44.7, 32.8, 32.0, 30.3, 30.2, 25.5, 25.4,
16.2(d, J = 6.5 Hz); HRMS-EI m/z [M]+ cacld. for C21H32NPO4 393.2069; found 393.2075.
The phosphinylation of Z-oxime (34 mg, 0.13 mmol) was carried out with (EtO)2POCl (95%, 0.08 mL,
0.53 mmol) and NaH (60%, 13 mg, 0.32 mmol) in THF. Chromatographic purification on silica gel
(hexane-EtOAc 8:1, 2:1) gave 3e (Z-form, 37 mg, 23% over two steps).
1
IR (neat) 3055, 2921, 1639, 1452, 1266, 1034, 965, 916 cm-1; H NMR (400 MHz, CDCl3) δ 7.34–7.26
(m, 2H), 7.23–7.16 (m, 3H), 5.60 (ddd, J = 17.2, 10.3, 8.1 Hz, 1H), 4.95 (dm, J = 17.2 Hz, 1H), 4.90 (dm,
J = 10.3 Hz, 1H), 4.28–4.14 (m, 4H), 3.32–3.03 (m, 1H), 2.93–2.83 (m, 2H), 2.60–2.49 (m, 2H),
2.19–2.06 (m, 1H), 1.86–1.63 (m, 4H), 1.36 (t, J = 7.1 Hz, 6H), 1.33–1.13 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ 170.7 (d, J = 12.4 Hz), 141.5, 141.4, 128.4, 128.4, 126.1, 114.4, 64.4 (d, J = 6.0 Hz), 64.3 (d, J
= 5.9 Hz), 43.7, 32.7, 31.5, 28.7, 25.6, 25.3, 16.2 (d, J = 6.4 Hz); HRMS-EI m/z [M]+ cacld. C21H32NPO4
393.2069; found 393.2078.
1-Ethyl-5,6,7,8-tetrahydroisoquinoline (4b): The typical procedure for the preparation of 4a was
followed; 3c (E-form) (49.3 mg, 0.16 mmol, mixed with 22.1 mg of 5a) was used as the starting material.
The reaction time was 11 min. Flash chromatography on silica gel (hexane-EtOAc 30:1, 5:1, 2:1) gave 4b
(8.4 mg, 34%) plus non-reacted 5a (20 mg) and 2c (3.9 mg, 15%). 4b was also prepared from the Z-form
of 3c (73.3 mg, 0.23 mmol, mixed with 21.6 mg of 6a). Chromatographic purification on silica gel
(hexane-EtOAc 30:1, 8:1, 1:1) gave 4b (6.6 mg, 17.7%) plus non-reacted 6a (19 mg) and 2c (11.5 mg,
30%).
1
4b: IR (neat) 3066, 2925, 1773, 1674, 1591, 1578, 1457, 841, 736 cm-1; H NMR (400 MHz, CDCl3) δ
8.22 (d, J = 5.1 Hz, 1H), 6.82 (d, J = 5.1 Hz, 1H), 2.79–2.66 (m, 6H), 1.87-1.81 (m, 2H), 1.81–1.73 (m,
2H), 1.26 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 161.3, 146.1, 145.4, 130.2, 122.0, 29.5, 27.9,
25.3, 23.0, 22.1, 12.7; HRMS-EI: m/z [M]+ calcd. for C11H15N: 161.1204; found: 161.1197.
1-Propyl-5,6,7,8-tetrahydroisoquinoline (4c): The typical procedure for the preparation of 4a was
followed; 3d (E-form) (59.6 mg, 0.18 mmol, mixed with 31.1 mg of 5b) was used as the starting material.
The reaction time was 12 min. Flash chromatography on silica gel (hexane-EtOAc 20:1, 10:1, 2:1) gave
4c (6.8 mg, 22%) plus 5b (38.1 mg, 20% based on the total amount). 4c was also prepared from the
Z-form of 3d (14.7 mg, 0.044 mmol). Chromatographic purification on silica gel (hexane-EtOAc 20:1,
8:1, 2:1) gave 4c (1.1 mg, 14%) plus 6b (2.2 mg, 25%).

HETEROCYCLES, Vol. 85, No. 2, 2012
397
IR (neat) 3049, 2926, 1650, 1587, 1564, 1460, 836, 812 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J =
5.0 Hz, 1H), 6.82 (d, J = 4.9 Hz, 1H), 2.75–2.67 (m, 6H), 1.88–1.65 (m, 6H), 1.00 (t, J = 7.4 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 160.4, 146.2, 145.3, 130.4, 122.0, 36.9, 29.7, 25.4, 23.1, 22.1, 22.0, 14.3;
HRMS-EI: m/z [M]+ calcd. for C12H17N: 175.1361; found: 175.1366.
1-Phenethyl-5,6,7,8-tetrahydroisoquinoline (4d): The typical procedure for the preparation of 4a was
followed; 3e (E-form) (39.6 mg, 0.10 mmol) was used as the starting material. The reaction time was 15
min. Flash chromatography on silica gel (hexane-EtOAc 30:1, 8:1, 4:1) provided 4d (17 mg, 70%). 4d
was also prepared from the Z-form of 3e (35.9 mg, 0.09 mmol). Chromatographic purification on silica
gel (hexane-EtOAc 30:1, 8:1) gave 4d (11.5 mg, 53%).
IR (neat) 3057, 3026, 2928, 1643, 1588, 1563, 840, 812 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.26 (d, J =
5.0 Hz, 1H), 7.31–7.26 (m, 2H), 7.25-7.17 (m, 3H), 6.86 (d, J = 5.0 Hz, 1H), 3.01 (s, 4H), 2.74 (dd, J =
6.2, 6.2 Hz, 2H), 2.62 (dd, J = 5.9, 5.9 Hz, 2H), 1.84–1.71 (m, 4H) ; 13C NMR (100 MHz, CDCl3) δ 159.4,
146.3, 145.5, 142.2, 130.6, 128.5, 128.4, 125.9, 122.3, 36.9, 35.0, 29.5, 25.4, 23.0, 22.0; HRMS-EI m/z
[M]+ cacld. for C17H19N 237.1517; found 237.1510.
trans-(E)-Diethyl
3-p-tolyl-1-(2-vinylcyclohexyl)propylideneaminooxyphosphonate
(3f)
and
trans-3-p-tolyl-N-(2-vinylcyclohexyl)propionamide (5c): 3f was similarly prepared as 3a by using 2f as
the starting material. Oximination of 2f (176.2 mg, 0.69 mmol) with NH2OH·HCl and NaOAc gave 113
mg of E-oxime, which was then subjected to phosphinylation with (EtO)2POCl (0.51 mL, 3.32 mmol) and
NaH (60%, 80 mg, 1.99 mmol) in THF. Flash chromatography on silica gel (hexane-EtOAc 8:1, 2:1)
gave 97 mg of 3f (35%, over 2 steps) as a viscous oil and a trace amount of 5c.
3f: IR (neat) 3080, 1638, 1516, 1100, 1066, 980, 922 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.11 (br s, 4H),
5.61 (ddd, J = 17.2, 10.3, 8.2 Hz, 1H), 4.94 (dm, J = 17.2 Hz, 1H), 4.89 (dm, J = 10.3 Hz, 1H), 4.27–4.14
(m, 4H), 2.89 (ddd, J = 12.2, 11.0, 4.8 Hz, 1H), 2.70 (ddd, J = 12.3, 11.6, 4.8 Hz, 1H), 2.63 (ddd, J = 11.8,
11.6, 4.8 Hz, 1H), 2.39 (ddd, J = 11.6, 10.9, 4.8 Hz, 1H), 2.32 (s, 3H), 2.27 (ddd, J = 11.2, 11.4, 3.1 Hz,
1H), 2.21–2.11 (m, 1H), 1.82–1.73 (m, 4H), 1.36 (t, J = 7.0 Hz, 6H), 1.31–1.22 (m, 4H); 13C NMR (100
MHz, CDCl3) δ 171.7 (d, J = 12.3 Hz), 141.8, 138.0, 135.9, 129.2, 128.1, 114.4, 64.3 (d, J = 5.8 Hz), 64.2
(d, J = 5.8 Hz), 48.8, 44.7, 32.8, 31.6, 30.5, 30.3, 25.5, 25.4, 21.0, 16.2 (d, J = 6.6 Hz); HRMS-EI: m/z
[M]+ calcd. for C22H34NPO4: 407.2225; found: 407.2229.
1
5c: H NMR (400 MHz, CDCl3) δ 7.08 (s, 4H), 5.60 (ddd, J = 17.1, 10.1, 8.3 Hz, 1H), 5.10 (br s, 1H),
4.94 (dm, J = 17.2 Hz, 1H), 4.91 (dm, J = 10.1 Hz, 1H), 3.58 (dtd, J = 13.4, 8.4, 4.3 Hz, 1H), 2.89 (t, J =
7.6 Hz, 2H), 2.44–2.36 (m, 2H), 2.31 (s, 3H), 2.03 (dm, J = 12.8 Hz, 1H), 1.80-1.66 (m, 4H), 1.41–1.16
(m, 3H), 1.06–0.94 (m, 1H); HRMS-EI: m/z [M]+ calcd. for C18H25NO: 271.1936; found: 271.1927.
trans-(E)-Diethyl 3-(naphthalen-2-yl)-1-(2-vinylcyclohexyl)propylideneaminooxyphosphonate (3g)
and 3-naphthalen-2-yl-N-(2-vinylcyclohexyl)propionamide (5d): 3g was similarly prepared as 3a by

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HETEROCYCLES, Vol. 85, No. 2, 2012
using 2g as the starting material. Oximination of 2g (117.7 mg, 0.40 mmol) with NH2OH·HCl and
NaOAc gave 91.4 mg of E-oxime, which was then subjected to phosphinylation with (EtO)2POCl (0.35
mL, 2.32 mmol) and NaH (60%, 56 mg, 1.39 mmol) in THF. Flash chromatography on silica gel
(hexane-EtOAc 5:1, 2:1) afforded 64mg of 3g (37%, over 2 steps) and a trace amount of 5d.
3g: IR (neat) 3056, 1636, 1508, 1281, 1034, 973, 920 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.86–7.76 (m,
3H), 7.65 (s, 1H), 7.45 (m, 2H), 7.37 (dd, J = 8.4, 1.5 Hz, 1H), 5.63 (ddd, J = 17.2, 10.2, 8.1 Hz, 1H),
4.96 (dm, J = 17.2 Hz, 1H), 4.91 (dm, J = 10.3 Hz, 1H), 4.29–4.15 (m, 4H), 3.09 (ddd, J = 12.1, 13.5, 5.3
Hz, 1H), 2.92 (ddd, J = 12.6, 11.0, 5.3Hz, 1H), 2.76 (ddd, J = 12.0, 12.4, 5.3Hz, 1H), 2.51 (ddd, J = 12.0,
12.0, 5.2 Hz, 1H), 2.30 (ddd, J = 11.2, 11.4, 2.7 Hz, 1H), 2.26–2.14 (m, 1H), 1.85–1.74 (m, 4H),
1.51–1.42 (m, 1H), 1.37 (t, J = 7.0 Hz, 3H), 1.36 (t, J = 7.0 Hz, 3H), 1.32–1.17 (m, 3H); 13C NMR (100
MHz, CDCl3) δ 171.6 (d, J = 11.8 Hz), 141.8, 138.5, 133.6, 132.2, 128.2, 127.6, 127.4, 126.9, 126.4,
126.1, 125.4, 114.5, 64.4 (d, J = 6.0 Hz), 64.2 (d, J = 5.7 Hz), 48.9, 44.7, 32.8, 32.2, 30.4, 30.3, 25.5, 25.4,
16.2 (d, J = 6.5 Hz); HRMS-EI: m/z [M]+ calcd. for C25H34NO4P: 443.2225; found: 443.2216.
5d: 1H NMR (400 MHz, CDCl3) δ 7.83–7.72 (m, 3H), 7.62 (s, 1H), 7.42-7.39 (m, 2H), 7.32 (dd, J = 8.5,
1.3 Hz, 1H), 5.53 (ddd, J = 17.1, 10.0, 8.4 Hz, 1H), 5.22 (br s, 1H), 4.89 (dm, J = 17.1 Hz, 1H), 4.77 (dm,
J = 10.2, 1.6 Hz, 1H), 3.58 (dtd, J = 14.0, 8.1, 3.9 Hz, 1H), 3.10 (t, J = 7.6 Hz, 2H), 2.50 (t, J = 7.9 Hz,
2H), 2.01 (dm, J = 12.6 Hz, 1H), 1.79–1.62 (m, 4H), 1.40–1.23 (m, 2H), 1.20–1.10 (m, 1H), 1.03-0.90 (m,
1H); HRMS-EI: m/z [M]+ calcd. for C21H25NO: 307.1936; found: 307.1945.
1-(2-p-Tolyl-ethyl)-5,6,7,8-tetrahydroisoquinoline (4e): The typical procedure for the preparation of 4a
was followed; 3f (54 mg, 0.13 mmol) was used as the starting material. The reaction time was 15 min.
Flash chromatography on silica gel (hexane-EtOAc 30:1, 15:1, 4;1) provided 4e (22 mg, 65%) as a brown
oil.
IR (neat) 3046, 3008, 1645, 1586, 1514, 839, 809 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 5.0 Hz,
1H), 7.14 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 5.0 Hz, 1H), 2.98 (s, 4H), 2.74 (t, J =
13
6.3 Hz, 2H), 2.64 (t, J = 6.4 Hz, 2H), 2.33 (s, 3H), 1.85-1.73 (m, 4H); C NMR (100 MHz, CDCl3) δ
159.5, 146.2, 145.5, 139.2, 135.3, 130.6, 129.0, 128.3, 122.2, 37.0, 34.5, 29.5, 25.4, 23.0, 22.1, 21.0;
HRMS-EI: m/z [M]+ calcd. for C18H21N: 251.1674; found: 251.1680.
1-(2-Naphthalen-2-yl-ethyl)-5,6,7,8-tetrahydroisoquinoline (4f): The typical procedure for the
preparation of 4a was followed; 3g (31.4 mg, 0.071 mmol) was used as the starting material. The reaction
time was 8 min. Flash chromatography on silica gel (hexane-EtOAc 10:1) provided 4f (10.3 mg, 50%) as
a brown oil.
IR (neat) 3050, 1635, 1589, 1508, 959, 890, 853, 816, 746 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.28 (d, J
= 5.0 Hz, 1H), 7.86–7.74 (m, 3H), 7.66 (s, 1H), 7.47–7.37 (m, 3H), 6.87 (d, J = 5.0 Hz, 1H), 3.22–3.15 (m,
2H), 3.15–3.06 (m, 2H), 2.74 (t, J = 6.0 Hz, 2H), 2.65 (t, J = 6.0 Hz, 2H), 1.81–1.72 (m, 4H); 13C NMR

HETEROCYCLES, Vol. 85, No. 2, 2012
399
(100 MHz, CDCl3) δ 159.3, 146.3, 145.5, 139.8, 133.7, 132.0, 130.6, 127.9, 127.6, 127.5, 127.4, 126.4,
125.9, 125.1, 122.3, 36.7, 35.1, 29.5, 25.5, 23.0, 22.0; HRMS-EI: m/z [M]+ calcd. for C21H21N: 287.1674;
found: 287.1678.
trans-(E)-Diethyl (2-vinylcyclohexyl)methyleneaminooxyphosphonate (3h): Vinylmagnesium bromide
(0.7 M in THF, 57.4 mL, 40.17 mmol) and hexamethylphosphoramide (7.06 mL, 40.17 mmol) were
successively added to a solution of Me2S·CuBr (762 mg, 3.67 mmol) in THF (20 mL) pre-cooled to -55
ºC. The resulting dark orange solution was continued to stir for 30 min and added dropwise with a
mixture of 1-cyclohexene-1-carboxaldehyde (1.56 mL, 13.39 mmol) and chlorotrimethylsilane (3.4 mL,
26.78 mmol) in dry THF (10 mL) via a syringe. At -55 ºC, the reaction mixture was stirred for an
additional 2 hours, then diluted with Et2O (350 mL), and successively washed with aqueous 10% HCl
solution (70 mL), water (70 mL x 2) and brine (70 mL). After concentration, the crude residue was
subjected to chromatographic purification on silica gel (hexane-EtOAc 200:1) to afford 1.07 g of
vinyl-aldehyde as a mixture of two isomers (cis: trans = 60:40). The freshly prepared vinylaldehyde (1.07
g) was dissolved in dry CH2Cl2 (36 mL) and added with 1,8-diazabicyclo[5.4.0]undec-7-ene (1.22 mL,
7.98 mmol). The mixture was stirred at room temperature for 2 days and concentrated under reduced
pressure.
Chromatography
on
silica
gel
(hexane-EtOAc
200:1)
gave
1
trans-2-vinylcyclohexanecarbaldehyde (2h) (870 mg, 61%). H NMR (400 MHz, CDCl3) δ 9.56 (d, J =
3.2 Hz, 1H), 5.72 (ddd, J = 17.2, 10.1, 7.8 Hz, 1H), 5.02 (dm, J = 17.2 Hz, 1H), 5.00 (dm, J = 10.0 Hz,
1H), 2.31–2.20 (m, 1H), 2.18–2.08 (m, 1H), 1.87–1.72 (m, 4H), 1.68–1.54 (m, 1H), 1.40–1.14 (m, 3H).
To a stirred solution of 2h (411.6 mg, 2.98 mmol) in CH2Cl2 (12 mL), NaOAc (737 mg, 8.93 mmol) and
NH2OH·HCl (647 mg, 8.93 mmol) were successively added. The resulting suspension was stirred at room
temperature for 4 h, then diluted with CH2Cl2 (200 mL) and washed with water (50 mL x 2) and brine (30
mL). After concentration, the crude residue was purified by flash chromatography on silica gel
(hexane-EtOAc 20:1, 10:1) to give the oxime intermediate as a single isomer (398 mg). Under a nitrogen
atmosphere, NaH (60%, 25 mg, 0.63 mmol) and diethyl chlorophosphate (95%, 0.13 mL, 0.84 mmol)
were successively added to a stirred solution of the oxime (107 mg, 0.70 mmol) in dry THF (3 mL)
pre-cooled at 0 ºC. The reaction mixture was continued to stir for 24 h at room temperature, then cooled
at 0 ºC and carefully quenched with saturated aqueous NH4Cl solution (2 mL). The resulting mixture was
diluted with EtOAc (20 mL), washed with water (5 mL x 2) and brine (5 mL), and concentrated under
vacuo. The crude mixture was subjected to chromatographic purification on silica gel (hexane-EtOAc
12:1, 1:1) to afford 3h20 as a yellow oil (43.2 mg, 22% over two steps, base on the recovered starting
oxime) plus 16.7 mg of recovered oxime.
IR (neat) 3057, 1737, 1642, 1037, 982, 910, 738 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 7.8 Hz,
1H), 5.61 (ddd, J = 17.2, 10.0, 8.4 Hz, 1H), 5.04–4.92 (m, 2H), 4.25–4.14 (m, 4H), 2.28–2.18 (m, 1H),

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HETEROCYCLES, Vol. 85, No. 2, 2012
2.02–1.92 (m, 1H), 1.88–1.73 (m, 4H), 1.33 (t, J = 7.1 Hz, 6H), 1.31–1.22 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ 163.6 (J = 13.9 Hz), 141.4, 115.1, 64.4 (J = 5.9 Hz), 64.3 (J = 5.6 Hz), 45.4, 42.9, 32.4, 29.8,
25.2, 24.9, 16.1 (d, J = 6.6 Hz); HRMS-ESI m/z [M]+ cacld. for C13H24O4NP: 289.1443; found: 289.1043.
Isoquinoline (4g) and trans-2-vinylcyclohexanecarbonitrile (7): To a solution of 3h (41.2 mg, 0.14
mmol) in dry DMF (7.1 mL, 0.02 M) was added Pd(PPh3)4 (66 mg, 0.057 mmol) under N2. The mixture
was stirred at room temperature for 5 minutes before the addition of Et3N (0.1 mL, 0.71 mmol). The
reaction mixture was heated at 80 ºC for 8 min, cooled to rt and diluted with water (7 mL). The solution
was extracted with Et2O (70 mL x 2). The combined organic layers were washed with water (20 mL x 2)
and brine (20 mL). After concentration, the cure residue was subjected to TLC preparation (eluting
solvent: hexane-EtOAc 2:1) to afford 4g22 (6.3 mg, 34%) and 7 (5.8 mg, 30%).
4g: 1H NMR (400 MHz, CDCl3) δ 9.26 (s, 1H), 8.53 (d, J = 5.8 Hz, 1H), 7.98 (d, J = 8.2 Hz, 1H), 7.83 (d,
J = 8.2 Hz, 1H), 7.7 (td, J = 6.9, 0.8 Hz, 1H), 7.66 (d, J = 5.8 Hz, 1H), 7.61 (td, J = 7.5, 0.8 Hz, 1H) ; 13C
NMR (100 MHz, CDCl3) δ 152.6, 143.0, 135.8, 130.3, 128.7, 127.6, 127.3, 126.5, 120.5.
1
7: IR (neat) 3081, 2936, 2238, 1642, 995, 922 cm-1; H NMR (400 MHz, CDCl3) δ 5.76 (ddd, J = 17.2,
10.3, 7.2 Hz, 1H), 5.19 (dm, J = 17.2 Hz, 1H), 5.15 (dm, J = 10.3 Hz, 1H), 2.25 (ddd, J = 11.0, 10.9, 3.6
Hz, 1H), 2.21–2.10 (m, 2H), 1.90–1.84 (m, 1H), 1.83–1.73 (m, 2H), 1.65–1.56 (m, 1H), 1.38–1.12 (m,
3H); 13C NMR (100 MHz, CDCl3) δ 139.4, 121.8, 116.3, 44.3, 34.3, 31.2, 29.7, 24.7, 24.6.
ACKNOWLEDGEMENTS
We are grateful to the National Science Council of Taiwan (R.O.C.) for financial support.
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