Total synthesis of (±)-erythrocarine using dienyne metathesis

Article abstract of DOI:10.1016/j.jorganchem.2006.08.013

Total Synthesis of (±)-erythrocarine was achieved using ruthenium-catalyzed dienyne metathesis as a key step. A tetrahydroisoquinoline skeleton having tetrasubstituted carbon center was constructed using our method, that is, carbon dioxide and an alkyl group were introduced onto an alkyne having a heteroatom in a tether using the nickel complex to produce α,β-unsaturated carboxylic acid and then isoquinoline skeleton was constructed by Michael reaction of the tethered nitrogen to the resultant α,β-unsaturated ester.

Full text of DOI:10.1016/j.jorganchem.2006.08.013

Journal of Organometallic Chemistry 691 (2006) 5466–5475
www.elsevier.com/locate/jorganchem
Total synthesis of ( )-erythrocarine using dienyne metathesis
a
c
a
b,
*
Kazuya Shimizu , Masanori Takimoto , Yoshihiro Sato , Miwako Mori
a
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
b
Health Sciences University of Hokkaido, Ishikari-tobetsu, Hokkaido 061-0293, Japan
Organometallic Chemistry Laboratory, RIKEN, Hirosawa 2-1, Wako, Saitama 351-0198, Japan
c
Received 8 July 2006; received in revised form 28 July 2006; accepted 5 August 2006
Available online 17 August 2006
Abstract
Total Synthesis of ( )-erythrocarine was achieved using ruthenium-catalyzed dienyne metathesis as a key step. A tetrahydroisoquin-
oline skeleton having tetrasubstituted carbon center was constructed using our method, that is, carbon dioxide and an alkyl group were
introduced onto an alkyne having a heteroatom in a tether using the nickel complex to produce a,b-unsaturated carboxylic acid and then
isoquinoline skeleton was constructed by Michael reaction of the tethered nitrogen to the resultant a,b-unsaturated ester.
Ó 2006 Elsevier B.V. All rights reserved.
Keywords: Erythrocarine; Carboxylation; CO2; Dienyne metathesis; Enyne metathesis; Alkylative carboxylation
1. Introduction
bonds to form the new carbon-carbon bond. Recent
reports of nickel-mediated [4] and -catalyzed [5] carboxyla-
tion reactions to alkyne are very interesting because the
reaction proceeds under mild conditions. During the course
of our study of nickel-mediated or catalyzed carboxylation
to diene [6], allene [7], and alkyne [8], we developed the
novel synthetic method of heterocycles [8b] using this
method. Our procedure is shown in Scheme 1. If alkyne 1
having a hetero-atom in a tether is treated with an equimo-
lar amount of Ni(0) and DBU under an atmosphere of car-
bon dioxide, oxanickelacycle 4 is formed. Transmetalation
of an alkyl group of a zinc reagent to the nickel metal fol-
lowed by reductive elimination gives trisubstituted alkene
6, which was treated with CH2N2 after hydrolysis to give
a,b-unsaturated ester 2. Michael addition of a hetero-atom
in a tether of 2 to an a,b-unsaturated ester gives heterocycle
3. Using this method, we could synthesize various hetero-
cycles 3a-d in high yields, respectively.
Erythrina alkaloids [1], which are widely distributed
family, are structurally interesting and biologically active
natural products [2]. The structural features of these
alkaloids are that they possess a tetracyclic framework
containing tetrahydroisoquinoline skeleton and have tet-
rasubstituted carbon center at the benzylic position of tet-
rahydroisoquinoline ring. The typical erythrina alkaloids
are shown in Fig. 1. For the synthesis of erythrina alka-
loids, how to construct this tetracyclic framework con-
taining tetrasubstituted carbon center is important [3].
Carbon dioxide is a useful carbon 1-unit resource for
synthetic organic chemistry. The Grignard reaction using
carbon dioxide is an important method for conversion of
an aryl or alkyl halide into the corresponding carboxylic
acid. Transition metal-mediated or -catalyzed carboxyla-
tion is a promising reaction for utilization of carbon diox-
ide because the carbon–oxygen double bond of carbon
dioxide coordinates to the transition metal to produce oxa-
metalacyclopropane, which would react with the multiple
The remarkable feature of this procedure is that the
nitrogen or oxygen heterocycle having tetrasubstituted car-
bon center at the benzylic position can be synthesized.
Thus, we decided to synthesize erythrocarine, which is
one of the erythrina alkaloids and possesses the tetrasubsti-
tuted carbon center at the benzylic position. Erythrocarine
*
Corresponding author. Fax: +81 11 706 4982.
E-mail address: mori@pharm.hokudai.ac.jp (M. Mori).
0022-328X/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2006.08.013

K. Shimizu et al. / Journal of Organometallic Chemistry 691 (2006) 5466–5475
5467
R1O
O
O
MeO
C
5
N
N 9
B
N
R2O
MeO
A
MeO
RO
RO
R1=R2= Me: Dihydroerysotrine
R1=R1= -CH2-: Erythramine
R= H: Erythravine
R= Me: Erysotrine
R = H: Erythrocarine
R = Me: Erythraline
R1=OMe, R2= H: Dihydroerysovine
Fig. 1. Typical erythrina alkaloids.
R
1. Ni, CO2
then RZnX
R
CO2Me
YH
CO2Me
YH
n
Y
n
2. HCl aq.
3. CH2N2
n
2
3
1 Y=O, NR'
1. HCl
2. CH2N2
Ni(0), CO2
DBU
R
Ni
O
Ni
R
CO2ZnX
YH
CO2ZnX
YH
O
RZnX
YH
n
n
n
4
5
6
CO2Me
Me
CO2Me
Me
CO2Me
N Ph
CO2Me
Me
Me
O
O
N
Ph
3a
3b
3c
3d
Scheme 1. Novel synthesis of heterocycles using nickel-mediated alkylative carboxylation followed by Michael reaction.
O
O
O
C
5
N9
B
X
N
Ph
NR1
O
O
Ru
O
A
MeO2C
HO
RO
8
X=O
7a
erythrocarine
7b X=H2
O
O
1. CO2
Ni(0)-DBU
O
O
NHR1
NHR1
2.
TMS
3. CH2N2
ZnCl 10
CO2Me
11
9
CHO
Br
O
O
12
Scheme 2. Retrosynthetic analysis of erythrocarine.

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K. Shimizu et al. / Journal of Organometallic Chemistry 691 (2006) 5466–5475
TMS
1. CO2 (1 atm)
Ni(cod)2 (1 equiv)
DBU (2 equiv)
Boc
N
Ph
CO2Me
then 10 (3 equiv)
0 ˚C, 5 h
Boc
1e
Ph
N
2. 10% HCl aq.
3. CH2N2
slow add. 1 hr
2e 71%
TMS
TMS
CO2Me
Ph
TFA (10 equiv)
CO2Me
MeOH
reflux, 14 h
N
H
N
CH2Cl2
reflux, 5 h
Ph
13 89%
3e 96%
Scheme 3. Model study for construction of tetrasubstituted carbon center.
was isolated by Jackson in 1985 [9] and was not synthesized
yet. Our retrosynthetic analysis is shown in Scheme 2. A
framework of erythrocarine would be constructed from
compound 7 having a dienyne moiety on isoquinoline ring
using dienyne metathesis [10]. Compound 7 would be syn-
thesized from 8, whose tetrasubstituted carbon center
would be constructed from alkyne 11 using our nickel-med-
iated alkylative carboxylation followed by Michael reac-
tion. The starting alkyne 11 would be synthesized from
commercially available o-bromopiperonal (12).
the benzylic position in 62% yield based on 16 (see Scheme
4).
Since it is known that the nitrogen of an amino group
coordinates to the ruthenium catalyst and the catalytic
activity of the ruthenium catalyst decreases [11], metathesis
of dienyne 7a was examined. Compound 17 was converted
into 18 and olefin metathesis of 18 was first examined.
When a CH2Cl2 solution of compound 18 and the first gen-
eration ruthenium carbene complex i [12] was stirred at
room temperature under argon, none of the product was
obtained and starting material 18 was recovered unchanged
in 93% yield. However, the use of the second-generation
ruthenium catalyst ii [13] gave a good result and desired
compound 19 was obtained in 74% yield. Conversion of
19 into compound 20 having an alkene moiety was exam-
ined. The various attempts were made, for example, treat-
ment of 19 with DIBAL, LiAlH4, or vinyl lithium, or
hydrolysis of 19 with NaOH and then treatment with vinyl
lithium, but no desired compound was obtained. Presum-
ably, the pyrrolidone moiety in compound 19 would react
with these reagents (see Fig. 2; Scheme 5; Table 1).
Thus, dienyne metathesis of 7b having the tertiary amine
was examined. Treatment of 17 with allyl bromide gave 21,
which was reduced with LiAlH4 to afford alcohol 22. Swern
oxidation followed by treatment with vinyl magnesium
bromide gave a mixture of alcohol 7ba and 7bb, which
was acetylated to give a mixture of diastereomers 23a
and 23b (see Scheme 6).
Ruthenium catalyzed dienyne metathesis of 23 was car-
ried out. When a CH2Cl2 solution of a mixture of dienyne
23a and 23b and the first generation ruthenium catalyst i
was refluxed for 15 h, desired compound was not obtained
and starting material 23 was recovered in 69% yield. Use of
the second-generation ruthenium catalyst ii also did not
give desired product. Since dienyne 23 has a tertiary amino
group, it should coordinate to the ruthenium catalyst.
Therefore, a mixture of 23 was converted into 23 Æ HCl,
which was treated with ruthenium catalyst i at room tem-
perature in CH2Cl2 for 18 h [11]. We are pleased to find
Initially, it was examined using a model compound
whether a heterocycle having an alkynyl group at the ben-
zylic position can be synthesized. To a THF solution of an
equimolar amount of Ni(cod)2 and 2 equivalents of DBU
was added alkyne 1e slowly under an atmosphere of carbon
dioxide at 0 °C for 1 h. To this solution were added 3 equiv-
alents of zinc reagent 10 and the whole solution was stirred at
the same temperature for 5 h. The reaction mixture was
hydrolyzed and the crude product was treated with CH2N2
to give a,b-unsaturated ester 2e in 71% yield. Removal of
the protecting group on nitrogen afforded secondary amine
13 in 89% yield, and a MeOH solution of 13 was refluxed
for 14 h to give isoindoline 3e in 96% yield (see Scheme 3).
Since the result indicates that the alkynyl group could be
introduced at the benzylic position of isoindoline 3e, syn-
thesis of erythrocarine was started. Reaction of o-bromo-
piperonal with silylacetylene using PdCl2(PhCN)2 and
PPh3 smoothly proceeded to give 14 in quantitative yield.
Condensation of aldehyde 14 with CH3NO2 afforded nitro
compound 15 in 85% yield, which was reduced with
LiAlH4 followed by protection of the resultant primary
amine to give 1f in 61% yield. Introduction of a carboxyl
group and an alkynyl group on the alkyne of compound
1f was carried out in a similar manner for the synthesis
of 2e to give a,b-unsaturated ester 2f in 69% yield. Depro-
tection of 2f with TFA followed by Michael addition affor-
ded isoquinoline derivative 3f, whose silyl group was
removed with TBAF to afford desired tetrahydroisoquino-
line derivative 17 having tetrasubstituted carbon center at

K. Shimizu et al. / Journal of Organometallic Chemistry 691 (2006) 5466–5475
5469
PdCl2(PhCN)2 (3 mol %)
PPh3 (6 mol %)
CHO
Br
CHO
O
O
O
O
+
TMS
Et3N, reflux
30 min
(1.6 equiv)
TMS
14 quant.
1. LiAlH4
THF-Et2O
rt, 3 h
CH3NO2
O
O
NO2
O
O
NH4OAc
NHBoc
AcOH
100 ˚C, 7 h
2. (Boc)2O, Et3N
TMS
1f 61%
15 85%
1. CO2 (1 atm)
Ni(cod)2 (1.1 equiv)
DBU (3.3 equiv)
THF, 0 ˚C
NHBoc
O
O
NH2
TMS
O
O
TFA
TMS
1f
then 10 (3 equiv)
0 ˚C, 24 hr
2. 10% HCl aq.
3. CH2N2
CH2Cl2
reflux, 5 h
CO2Me
2f 69%
CO2Me
16
O
O
O
O
MeOH
TBAF
NH
NH
reflux
14 h
MeO2C
3f
MeO2C
17 76% from 16
TMS
Scheme 4. Synthesis of substrate.
Table 1
Olefin metathesis of 18
MesN
NMes
Cl
Cy3P
Ru
Cl
Entry
Catalyst
Conditions
Yield of 19
Ru
(%)
Cl
Ph
Cl
Ph
PCy3
PCy3
1
2
a
i (10 mol%)
ii (8 mol%)
CH2Cl2, rt, 1.5 h
Toluene, 80 °C, 1 h
0a
74
i
ii
18 was recovered in 93% yield.
Fig. 2. Ruthenium catalyst.
that a mixture of desired tetracyclic compounds 24a and
24b was obtained in a ratio of 1 to 1 in quantitative yield.
Compound 25 was not formed in this reaction. To deter-
mine the stereochemistry of them, they were separated
and each NOE experiment was carried out. An NOE of
compound 24a, which was found at the less polar position
ruthenium
O
O
COCl
catalyst
O
17
N
N
Py
O
O
O
CH2Cl2
-20 ˚C
MeO2C
MeO2C
18 81%
19
O
O
N
O
19
O
20
Scheme 5. Examination of olefin metathesis.

5470
K. Shimizu et al. / Journal of Organometallic Chemistry 691 (2006) 5466–5475
Br
O
O
O
O
K2CO3
LiAlH4
N
N
17
CH3CN
rt, 60 h
THF, 0 ˚C
2 h
MeO2C
HO
21
22
O
O
1. (COCl)2
DMSO, Et3N
N
Ac2O
N
O
O
Py, DMAP
2.
MgBr
HO
AcO
7ba, 7bb
23a, 23b 70% from 17
Scheme 6. Synthesis of isoquinoline having triene.
Table 2
Dienyene metathesis
O
O
Entry
Ru
Conditions
Product (%)
23
O
NOE
14
1
2
i
Reflux, 15 h
Reflux, 1.5 h
rt, 18 h
–
–
69
42
–
N
H
ii
i
O
3a
a
quant. (1:1)
H
N
14
3
3
AcO
23 Æ HCl was used as a substrate.
AcO
24a
Fig. 3. Determination of the stereochemistry.
and 24b were formed means that the ruthenium catalyst
would react at first with the alkene at the allylic position
of nitrogen to form ruthenium carbene complex 26. This
reacts with an alkyne part to produce complex 27. Ring
opening of ruthenacyclobutene of 27 gives ruthenium car-
bene 28, which reacts with an alkene to give ruthenacyclob-
utane 29. Ring opening of this gives desired tetracyclic
compound 24 Æ HCl.
A mixture of 7b was separated into two isomers 7ba
and 7bb. Compound 7ba was converted to 23a Æ HCl,
which was treated with ruthenium catalyst ii in CH2Cl2
at room temperature for 20 h to afford 24a in 62% yield
along with starting material 23a in 30% yield. To isomer-
ize the hydroxyl group of 7bb into 7ba [15], Mitsunobu
on TLC, was shown between the protons at the C3 position
and at the C14 position on an aromatic ring. It means that
an acetoxy group of 24a is placed at the a-position of the
cyclohexene ring and this is a same stereochemistry with
that of erythrocarine (see Fig. 3; Scheme 7; Table 2).
Compound 24a was treated with K2CO3 in MeOH to
give erythrocarine, whose spectral data agreed with those
reported in the literature [9]. The other isomer 24b was
treated in a similar manner to give 3-epierythrocarine.
Thus, the total synthesis of ( )-erythrocarine was achieved
[14] (see Scheme 8).
The possible reaction course for formation of 24 was
shown in Scheme 9. The fact that only compounds 24a
O
O
O
O
N
O
N
N
Ru catalyst
O
+
CH2Cl2,
AcO
AcO
24a
AcO
24b
23a, 23b
O
O
N
RO
25 0%
Scheme 7. Dienyne metathesis.

K. Shimizu et al. / Journal of Organometallic Chemistry 691 (2006) 5466–5475
5471
2. Experimental section
O
O
O
O
K2CO3
N
N
2.1. General information
MeOH
rt, 1 h
HO
erythrocarine
1H NMR and 13C NMR were recorded on a JEOL EX-
270 (270 MHz for 1H, 67.5 MHz for 13C), or JEOL AL-400
AcO
93%
24a
1
(400 MHz for H, 100 MHz, for 13C) instrument in CDCl3
with tetramethylsilane as an internal standard otherwise
mentioned. Data are reported as follows: chemical shift
in ppm (d), multiplicity (s = singlet, d = doublet, t =
triplet, q = quartet, m = multiplet, br = broad signal), cou-
pling constant (Hz), and integration of protons (H). Infra-
red spectra (IR) were obtained on a Perkin Elmer 1605
FTIR spectrometer. Mass spectra were obtained on a
JEOL JMS-FABmate (EI), a JEOL JMS-HX110 (FAB),
or a JEOL JMS-700TZ (ESI). For column chromatogra-
phy on silica gel, Merck Silica Gel 60 (70–230 or 230–400
mesh ATM) was used. For analytical or preparative
TLC, Merck Silica Gel 60 PF254 was used. All solvents
and reagents were purified when necessary using standard
procedures. Ni(cod)2 was prepared by a literature proce-
dure [16] and handled under an argon atmosphere. All
reactions were carried out under argon. Me2Zn was pur-
chased from Kanto Chemical Co. Inc.
O
O
O
K2CO3
N
N
O
MeOH
rt, 4 h
AcO
HO
53%
24b
3-epierythrocarine
Scheme 8. Synthesis of epierythrocarine.
reaction of 7bb was carried out using DIPAD (diisopro-
pylazodicarboxylate) and PPh3 in the presence of AcOH,
but starting material 7bb was recovered in 74% yield
along with acetylated compound 23b in 21% yield. The
reaction was carried out under various conditions but
only starting material was recovered. Although the reason
that conversion of 7bb into 7ba did not proceed is not
clear, a hydrogen bond between the hydroxyl group and
the amino nitrogen may prevent the reaction. Thus,
Swern oxidation of 7bb followed by treatment with
NaBH4 was carried out. As the result, compounds 7ba
and 7bb were obtained in 44% yield and in a ratio of 1
to 0.8. Although the yield was not good, conversion of
7bb to desired 7ba was achieved (see Scheme 10).
In conclusion, erythrocarine was synthesized using dien-
yne metathesis as a key step and an overall yield is 9% via
15 steps from commercially available o-bromopiperonal.
The tetrasubstituted carbon center at the benzylic position
of tetrahydroisoquinoline skeleton was constructed using
nickel mediated alkylative carboxylation followed by
Michael reaction developed by our group.
3. Preparation of zinc reagent 10
To a solution of (trimethylsilyl)acetylene (3.1 mL,
22.0 mmol) in THF (12.1 mL) was added BuLi (1.62 M
hexane solution, 15.4 mL, 22 mmol) at ꢀ78 °C and the
solution was stirred at ꢀ78 °C for 40 min. To a suspension
of ZnCl2 (2.3 g, 17.0 mmol), which was dried at 130 °C for
12 h under vacuum, in THF (11. 0 mL) was added an
above solution (THF solution, 0.74 M, 22.9 ml, 17.0 mmol)
at 0 °C and the solution was stirred at the same tempera-
ture for 3 h. The solution was filtered and the filtrate was
used as a zinc reagent of 10 (0.5 M THF/hexane solution).
O
O
O
O
O
-
H
-
H
Cl
H
Cl
N
+
N
+
Ph
-
N
+
Cl
O
Ru
Ru
AcO
AcO
AcO
Ru
27
23·HCl
26
O
O
O
O
O
H
H
+
+
-
-
N
N
Cl
H
Cl
+
-
N
Cl
O
AcO
AcO
AcO
Ru
Ru
Ru
24·HCl
28
29
Scheme 9. Possible reaction course.

5472
K. Shimizu et al. / Journal of Organometallic Chemistry 691 (2006) 5466–5475
O
O
separation
N
7b
N
O
O
HO
and
HO
7ba
7bb
1. Ac2O, Py
2. HCl
ii
7ba
7bb
23a·HCl
24a + 23a
62% 30%
CH2Cl2
rt, 20 h
O
O
O
DIPAD (1.5 equiv)
PPh3 (1.5 equiv)
N
N
O
AcOH, THF, 4 h
AcO
AcO
23a
23b
O
O
1.
(COCl)2 (10 equiv)
DMSO (15 equiv)
Et3N
N
CH2Cl2
7bb
2. NaBH4 (4 equiv)
CeCl3 (25 mol%)
HO
44%
7b (7ba : 7bb =1 : 0.8)
Scheme 10. Conversion of b-hydroxyl group to a-form.
4. Typical procedure for the synthesis of a,b-unsaturated
ester 2e
128.04, 128.37, 128.62, 128.84, 135.46, 136.09, 137.69,
155.86, 164.77; LR MS (EI) m/z 477 (M+), 404, 377, 318,
286; HR MS (EI) calcd for C28H35NO4Si 477.2335, found
477.2342.
To a stirred suspension of NiðcodÞ2 [16] (99 mg,
0.36 mmol) and DBU (0.11 ml, 0.72 mmol) in degassed
THF (2.9 mL) was slowly added 1e (115 mg, 0.36 mmol)
under an atmosphere of carbon dioxide at 0 °C for 1 h
and the solution was stirred at the same temperature for
2 h. To this solution was added alkynyl zinc reagent
(0.5 M THF/hexane solution, 2.2 mL, 1.1 mmol) at 0 °C
and the solution was stirred at 0 °C for 24 h. To this solu-
tion was added 10% HCl and the aqueous layer was
extracted with ethyl acetate. The combined organic layer
was washed with brine, dried over Na2SO4, and concen-
trated. The crude product was treated with CH2N2, whose
product was purified by column chromatography (hexane/
ethyl acetate, 10/1) on silica gel to give 3-{2-[(Benzyl-tert-
butoxycarbonyl-amino)-methyl]-phenyl}-5-(trimethyl-sil-
anyl)-pent-2-en-4-ynoic acid methyl ester (2e) (122 mg,
5. Typical procedure for synthesis of heterocycles using
michael addition
A solution of 2e (102 mg, 0.213 mmol) and TFA
(0.16 mL, 2.13 mmol) in CH2Cl2 (2.5 mL) was refluxed
for 5 h. To this solution was added sat. NaHCO3 solution
and the aqueous layer was extracted with ethyl acetate. The
combined organic layer was washed with brine, dried over
Na2SO4 and evaporated to give secondary amine 13. A
solution of crude product 13 (5 mg, 0.013 mmol) in MeOH
(3 mL) was refluxed for 14 h. Solvent was removed and the
residue was purified by column chromatography on silica
gel (hexane/ethyl acetate, 4/1) to give [2-Benzyl-1-(tri-
methyl-silanylethynyl)-2,3-dihydro-1H-isoindol-1-yl]-acetic
acid methyl ester (3e) (4.8 mg, 96%). IR (neat) 2952, 1928,
1734, 1456, 1248 cmꢀ1; 1H NMR (270 MHz, CDCl3) d 0.16
(s, 9H), 3.13 (s, 2H), 3.56 (s, 3H), 3.63 (d,J = 13.2Hz, 1H),
3.68 (d,J = 13.2 Hz, 1H), 3.90 (d,J = 13.2 Hz, 1H), 4.18
(d,J = 13.2 Hz, 1H), 6.98-7.43 (m, 9 H); LR MS (EI) m/z
362 (M-Me), 318, 244, 226; HR MS (EI) calcd for
C23H27NO2Si 377.1811, found 377.1819.
71%). IR (neat) 2966, 2147, 1732, 1699, 1602, 844 cmꢀ1
;
1H NMR (400 MHz, CDCl3) d 0.13 (s, 9H), 1.37 and
1,44 (s and s, 4H and 5H), 3.75 (s, 3H), 4.28 and 4.44 (s
and s, 0.9H, and 1.1H), 4.49 and 4.61(s and s, 1.1H and
0.9 H), 6.03 (s, 1H), 7.20-7.34 (m, 9 H);13C NMR (100
MHz, CDCl3) d ꢀ0.41, 28.37, 39.56, 47.34, 49.41, 51.58,
79.99, 101.19, 110.50, 126.40, 127.08, 127.27, 127.78,

K. Shimizu et al. / Journal of Organometallic Chemistry 691 (2006) 5466–5475
5473
6. (E)-trimethyl(2-(6-(2-nitrovinyl)benzo[d][1,3]dioxol-5-
yl)ethynyl)silane (15)
acetate, 5/1) to give ester 2f (111.2 mg, 69%). IR (film)
3445, 2977, 1710, 1595, 1167, 846, 739 cmꢀ1 1H NMR
;
(400 MHz, CDCl3) d 0.21 (s, 9 H), 1.40 (s, 9 H), 2.86 (t,
J = 7.2 Hz, 2H), 3.30 (br, 2H), 3.77 (s, 3H), 4.51 (br, 1
H), 5.93 (s, 2H), 6.09 (s, 1H), 6.66 (s, 1H), 6.70 (s, 1H);
13C NMR (100 MHz, CDCl3) d ꢀ0.33, 28.41, 33.00,
41.40, 51.53, 101.30, 101.81, 109.11, 109.68, 109.90,
128.28, 130.49, 131.79, 136.78, 146.07, 148.06, 155.62,
164.96; LR MS (EI) m/z 445 (M+), 389, 372, 344, 315;
HR MS (EI) calcd for C23H31NO6Si 445.1920, found
445.1922.
To a solution of 6-(trimethyl-silanylethynyl)-benzo[1,3]-
dioxole-5-carbaldehyde (14) [17] (246 mg, 1.0 mmol) and
NH4OAc (64 mg, 0.83 mmol) in AcOH (2.5 ml) was added
CH3NO2(0.27 ml, 5.0 mmol) and the solution was heated
at 100 °C for 7 h. The solvent was removed and the residue
was recrystalized from ether to give 15 (1.23 g, 85%). IR
1
(film) 3104, 2955, 2149, 1610, 1330, 1253, 1034 cmꢀ1; H
NMR (400 MHz, CDCl3) d 0.28 (s, 9 H), 6.05 (s, 2H),
6.94 (s, 1H), 6.96 (s, 1H), 7.57 (d, J = 13.6 Hz, 1H), 8.46
(d,J = 13.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) d
ꢀ0.21, 101.35, 101.40, 101.90, 105.95, 112.34, 120.84,
126.62, 136.50, 136.92, 148.63, 150.50; LR MS (EI) m/z
289 (M+), 243, 73; HR MS (EI) calcd for C14H15NO4Si
289.0770, found 289.0788; Anal. Calcd for C14H15NO4Si:
C, 58.11; H, 5.22; N, 4.84. Found: C, 58.06; H, 5.32; N,
4.82%.
9. Methyl 2-(5-ethynyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-
g]isoquinolin-5-yl)acetate (17)
A solution of 2f (933 mg, 3.1 mmol) and TFA (1.6 mL,
21 mmol, 10 equiv) in CH2Cl2 (8.4 mL) was stirred at room
temperature for 3 h. Solvent was removed and the residue
was dissolved in ethyl acetate. The organic layer was
washed with sat. NaHCO3 and brine, dried over Na2SO4
and evaporated. The residue was dissolved in THF (8 mL)
and TBAF (THF solution, 1.0 M, 1.1 equiv, 2.3 mL) was
added. The whole solution was stirred at 0 °C for 2 h. Water
was added and the aqueous layer was extracted with ethyl
acetate. The organic layer was washed with brine, dried
over Na2SO4, and concentrated. The residue was purified
by column chromatography on silica gel (ethyl acetate) to
give 17 (438 mg, 76% based on 16). IR (film) 3286, 2952,
7. [2-(6-Ethynyl-benzo[1,3]dioxol-5-yl)-ethyl]-carbamic acid
tert -butyl ester (1f)
To a suspension of LiAlH4 (885 mg, 23.3 mmol) in Et2O
(25 mL) was added 15 (2.25 g) in Et2O (25 mL) at ꢀ78 °C
and the solution was stirred at room temperature for 3 h.
To this solution was added 15% aq. NaOH solution
(0.9 mL) and the solution was stirred at room temperature
for 14 h. Undissolved material was filtered off and the
filtrate was concentrated. The residue was dissolved in
MeOH (26 mL) and to this solution was added
NEt3(1.6 mL, 11.66 mmol) and (Boc)2O (2.7 mL,
11.66 mmol) and the solution was stirred at room temper-
ature for 14 h. Solvent was removed and the residue was
purified by column chromatography on silica gel (hexane/
Et2O, 10/1) to give 1f (1.37 g, 61%). IR (neat) 3290, 2977,
1
1734 cmꢀ1; H NMR (400 MHz, CDCl3) d 1.26 (br, 1H),
2.46 (s, 1H), 2.62 (ddd, J = 16.0, 4.0, 3.2 Hz, 1H), 2.84
(ddd,J = 16.0, 10.4, 5.6 Hz, 1H), 2.89 (d, J = 16.0 Hz,
1H), 3.12 (ddd,J = 12.0, 5.6, 3.2 Hz, 1H), 3.13 (d, J =
16.0 Hz, 1H), 3.22 (ddd,J = 12.0, 10.4, 4.0 Hz, 1H), 3.70
(s, 3H), 5.90 (d, J = 1.2Hz, 1H), 5.92 (d, J = 1.2 Hz, 1H),
6.54 (s, 1H), 6.79 (s, 1H); 13C NMR (100 MHz, CDCl3) d
29.71, 39.57, 46.68, 51.77, 53.40, 71.61, 87.00, 100.89,
105.96, 108.84, 128.33, 130.29, 146.08, 146.55, 170.76; LR
MS (EI) m/z 273 (M+), 200, 185; HR MS (EI) calcd for
C15H15NO4 273.1001, found 273.1009.
1
2101, 1700, 1366, 1252, 1038 cmꢀ1; H NMR (400 MHz,
CDCl3) d 1.43 (s, 9H), 2.92 (t,J = 6.8 Hz, 2H), 3.17 (s,
1H), 3.37 (td,J = 6.8, 6.4 Hz, 2H), 4.57 (s, 1H), 5.96 (s,
2H), 6.68 (s, 1H), 6.91 (s, 1H); 13C NMR (100 MHz,
CDCl3) d 28.43, 34.60, 41.08, 79.11, 79.53, 82.10, 101.32,
109.55, 112.14, 114.39, 136.72, 145.78, 148.29, 155.71; LR
MS (EI) m/z 289 (M+), 233, 216, 188, 172, 159, 57; HR
MS (EI) calcd for C16H19NO4 289.1314, found 289.1315;
Anal. Calcd for C16H19NO4: C, 66.42; H, 6.62; N, 4.84.
Found: C, 66.23; H, 6.61; N, 4.74%.
10. 1-(6-Allyl-5-ethynyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-
g]isoquinolin-5-yl)but-3-en-2-ol (7ba,7bb)
To a solution of 17 (100 mg, 0.366 mmol) in CH3CN
(1.2 mL) was added K2CO3 (253 mg, 1.83 mmol) and allyl
bromide (0.12 mL, 1.46 mmol) at 0 °C and the solution was
stirred at room temperature for 60 h. Ethyl acetate was
added and the organic layer was washed with brine, dried
over Na2SO4 and evaporated. The residue 21 was dissolved
in THF (1 mL), and LiAlH4 (36 mg, 0.95 mmol) was added
at 0 °C. The suspension was stirred at 0 °C for 2 h.
Na2SO4 Æ 10H2O was added to the solution, and the solu-
tion was stirred at room temperature for 18 h. Undissolved
material was filtered off and the filtrate was concentrated
to give 2-(6-Allyl-5-ethynyl-5,6,7,8-tetrahydro-[1,3]diox-
olo[4,5-g]isoquinolin-5-yl)ethanol (22). To a solution of
oxalyl chloride (0.1 mL, 1.1 mmol) in CH2Cl2 (1.5 mL)
8. 3-[6-(2-tert-Butoxycarbonylamino-ethyl)-
benzo[1,3]dioxol-5-yl]-5-(trimethyl-silanyl)-
pent-2-en-4-ynoic acid methyl ester (2f)
The crude product which was prepared according to the
typical procedure for the synthesis of 2e from Ni(cod)2
(109 mg, 0.4 mmol) and DBU (0.18 mL, 1.2 mmol) in
THF (2. 9 mL), 1f(104 mg, 0.36 mmol) and 10 (2.2 mL,
1.1 mmol) in THF (5.8 mL) under carbon dioxide was puri-
fied by column chromatography on silica gel (hexane/ethyl

5474
K. Shimizu et al. / Journal of Organometallic Chemistry 691 (2006) 5466–5475
was added DMSO (0.16 mL, 2.2 mmol) at ꢀ78 °C and the
solution was stirred at the same temperature for 2 min. To
this solution was added the above crude product 22 in
CH2Cl2(1.5 mL) and the solution was stirred at ꢀ78 °C
for 30 min. NEt3(0.6 ml) was added to this solution at
the same temperature and the solution was stirred at 0 °C
for 30 min. Ethyl acetate was added and the organic layer
was washed with aq. K2CO3 solution and brine, dried over
Na2SO4 and concentrated. The residue was dissolved in
THF (2 mL), and to this solution was added vinyl magne-
sium bromide (THF solution, 1.0 M, 1.1 mL, 1.1 mmol) at
ꢀ78 °C and the solution was stirred at the same tempera-
ture for 2 h. Water was added and the aqueous layer was
extracted with ethyl acetate. The organic layer was washed
with brine, dried over Na2SO4 and evaporated to give 7,
which was purified by column chromatography on silica
to 1 ratio of 23a to 23b). 23a: IR (neat) 3287, 2900, 1738,
1642, 1487, 1235, 1039 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d 2.01 (s, 3H), 2.29 (dd,J = 15.4, 5.4 Hz, 1H), 2.46 (s, 1H),
2.46–2.51 (m, 2H), 2.65 (dd,J = 15.4, 5.4 Hz, 1H), 2.77–
2.97 (m, 3H), 3.64 (d,J = 14.0 Hz, 1H), 4.83 (d,J =
10.4 Hz, 1H), 4.92 (d,J = 16.8 Hz, 1H), 5.16 (d,J =
10.4 Hz, 1H), 5.23–5.27 (m, 2H), 5.39 (ddd,J = 17.2, 10.4,
6.2 Hz, 1H), 5.82–5.96 (m, 1H), 5.91 (d,J = 11.6 Hz, 2H),
6.49 (s, 1H), 6.82 (s, 1H); 13C NMR (100 MHz, CDCl3) d
21.51, 29.81, 43.96, 44.79, 53.91, 60.11, 71.47, 73.34,
84.44, 100.86, 107.28, 108.07, 114.93, 116.75, 129.81,
130.72, 136.40, 136.47, 146.11, 146.35, 169.61; LR MS
(EI) m/z 353 (M+), 328, 312, 294, 240; HR MS (EI) calcd
for C21H23NO4 353.1627, found 353.1622. 23b: IR (neat)
1
3282, 2900, 1736, 1642, 1484, 1236, 1038 cmꢀ1; H NMR
(400 MHz, CDCl3) d 1.57 (s, 3H), 2.35–2.57 (m, 3H),
2.46 (s, 1H), 2.53 (dd,J = 11.2, 11.2 Hz, 1H), 2.82–2.92
(m, 2H), 2.98 (d,J = 11.2 Hz, 1H), 3.51 (d,J = 14.8 Hz,
1H), 5.04 (d,J = 10.0 Hz, 1H), 5.08 (d,J = 15.6 Hz, 1H),
5.17 (d,J = 10.0 Hz, 1H), 5.32 (d,J = 16.8 Hz, 1H), 5.65
(d,J = 6.4 Hz, 1H), 5.73 (ddd,J = 16.8, 10.0, 5.6 Hz, 1H),
5.80–5.91 (m, 1H), 5.88 (s, 1H), 5.91 (s, 1H), 6.47 (s, 1
H) 6.91 (s, 1H); 13C NMR (100 MHz, CDCl3) d 20.46,
29.80, 44.51, 44.74, 54.03, 59.66, 70.00, 73.00, 84.84,
100.80, 107.91, 108.24, 114.92, 116.61, 129.08, 130.62,
136.14, 137.08, 145.74, 146.03, 169.35; LR MS (EI) m/z
353 (M+), 312, 294, 240; HR MS (EI) calcd for
C21H23NO4 353.1627, found 353.1601.
1
gel (ethyl acetate/hexane, 4:1). 7ba: H NMR (400 MHz,
CDCl3) d 2.05 (dd, J = 14.8, 2.0 Hz, 1H), 2.38 (dd,
J = 14.8 10.8 Hz, 1H), 2.46–2.55 (m, 2H), 2.53 (s, 1H),
2.91 (dd, J = 14.0, 8.8 Hz, 1H), 2.95–2.99 (m, 1H), 3.08
(ddd, J = 11.4, 5.2, 2.0 Hz, 1H), 3.74–3.80 (m,2 H), 5.00
(ddd, J = 10.4, 1.6, 1.6 Hz, 1H), 5.15 (ddd, J = 17.2, 1.6,
1.6 Hz, 1H), 5.23 (d, J = 10.4 H, 1H), 5.27 (d,
J = 16.8 Hz, 1H), 5.71 (ddd, J = 17.2, 10.4, 5.2 Hz, 1H),
5.85–5.95 (m, 1H), 5.91 (d, J = 1.6 Hz, 1H), 5.93 (d,
J = 1.6 Hz, 1H) 6.21 (br, 1H), 6.53 (s, 1H), 6.79 (s, 1H);
13C NMR (100 MHz, CDCl3) d 29.70, 44.37, 44.81,
54.61, 61.62, 69.39, 74.02, 74.09, 83.10, 100.95, 106.75,
108.04, 113.74, 118.62, 129.00, 129.41, 134,65, 140.09,
146.56.
12. (3R , 5R )-3-Acetoxy-15,16-methylenedioxyerythrina-
*
*
1
7bb: H NMR (400 MHz, CDCl3) d 2.02 (dd, J = 15.2,
1,6-diene (24a) and (3S , 5R )-3-Acetoxy-15,16-
* *
methylenedioxyerythrina-1,6-diene (24b)
2.8 Hz, 1H) 2.26 (dd, J = 15.2, 9.6 Hz, 1H), 2.48 (ddd,
J = 15.6, 4.8, 4.8 Hz, 1H), 2.67 (s, 1H), 2.78 (ddd,
J = 15.6, 10.0, 4.8 Hz, 1H), 2.95 (ddd, J = 14.0, 4.8,
4.8 Hz, 1H), 3.05 (dd, J = 13.6, 9.2 Hz, 1 H), 3.28 (ddd,
J = 14.0, 9.6, 4.8 Hz, 1H), 4.03 (brd, J = 13.6 Hz, 1H),
4.75 (brs, 1H), 4.97 (ddd, J = 10.0, 1.6, 1.6 Hz, 1H),
5.17–5.26 (m, 3H), 5.72 (ddd, J = 16.8, 10.8, 4.8 Hz, 1H),
5.83–5.93 (m, 2H), 5.90 (s, 1H), 5.91 (s, 1H) 6.50 (s, 1
H), 6.96 (s, 1H); 13C NMR (100 MHz, CDCl3) d 23.47,
40.65, 46.80, 52.70, 62.46, 70.92, 76.04, 84.10, 100.85,
107.66, 108.14, 113.20, 117.75, 126.67, 130.43, 135.68,
140.20, 146.17, 146.65.
To a solution of a mixture of 23 (8.2 mg, 0.023 mmol) in
Et2O (1 mL) was added HCl in Et2O solution (1.0 M,
0.05 mmol) at 0 °C and the solution was concentrated.
To the solution of 23 Æ HCl in degassed CH2Cl2 (0.5 mL)
was added the second-generation ruthenium catalyst ii
(2 mg, 0.002 mmol, 10 mol%) and the solution was stirred
at room temperature for 16 h under argon gas. To this
solution was added CH2Cl2 and aq. K2CO3 solution, and
the organic layer was washed with brine, dried over
Na2SO4 and concentrated. The residue was purified by col-
umn chromatography on silica gel (ethyl acetate/MeOH,
5:1) to give 24a (4.5 mg, 50%) and 24b (4.5 mg, 50%).
11. (R)-1-(6-allyl-5-ethynyl-5,6,7,8-tetrahydro-
[1,3]dioxolo[4,5-g]isoquinolin-5-yl)but-3-en-2-yl acetate
(23a) and (S)-1-(6-allyl-5-ethynyl-5,6,7,8-tetrahydro-
[1,3]dioxolo[4,5-g]isoquinolin-5-yl)but-3-en-2-yl acetate
(23b)
24a: IR (neat) 2931, 1734, 1684, 1484, 1237, 1038 cmꢀ1
;
1H NMR (400 MHz, CDCl3) d 1.92 (dd, J = 11.2,
11.2 Hz, 1H), 2.04 (s, 3H), 2.51 (dd, J = 11.2, 6.0 Hz,
1H), 2.60–2.67 (m, 1H), 2.82–2.91 (m, 2H), 3.42–3.51 (m,
2H), 3.73 (dd, J = 14.8, 2.8 Hz, 1H), 5.43 (ddd, J = 8.4,
6.0, 0.8 Hz, 1H), 5.77 (s, 1H), 5.82 (d, J = 10.0 Hz, 1H),
5.88 (s, 2 H), 6.59 (dd,J = 10.0, 2.8 Hz, 1H), 6.60 (s, 1H),
6.78 (s, 1H); 13C NMR (100 MHz, CDCl3) d 21.34,
25.11, 41.73, 44.46, 57.55, 67.08, 70.27, 100.64, 105.95,
108.65, 123.75, 126.17, 127.73, 129.58, 131.71, 141.42,
145.84, 146.09, 170.45; LR MS (EI) m/z 325 (M+), 282,
266, 236; HR MS (EI) calcd for C19H19NO4 325.1314,
The crude product of 7 was dissolved in pyridine (1 mL)
and Ac2O (0.5 mL, 5.3 mmol) and DMAP (5 mg) and the
solution was stirred at room temperature for 14 h. Ethyl
acetate was added and the organic layer was washed with
brine dried over Na2SO4 and evaporated. The residue
was purified by column chromatography on silica gel (hex-
ane/ethyl acetate, 4 : 1) to give 23 (90.2 mg, 5 steps 70%, 1

K. Shimizu et al. / Journal of Organometallic Chemistry 691 (2006) 5466–5475
5475
(b) R.K. Hill, in: R.H.F. Manske (Ed.), The Alkaloids, Vol. 9,
Academic Press, New York, 1967, p. 281;
(c) Y. Tsuda, T. Sano, in: G.A. Cordell (Ed.), The Alkaloids, Vol. 48,
Academic Press, New York, 1996, p. 249.
found 325.1313. 24b: IR (film) 2926, 1727, 1682, 1482,
1
1236, 1036 cmꢀ1; H NMR (400 MHz, CDCl3)d 1.70 (s,
3H), 2.39 (br, 1H), 2.55 (d, J = 14.4 Hz, 1H), 2.79–2.91
(m, 3H), 3.41 (d, J = 14.4 Hz, 1H), 3.62 (m, 1H), 3.86
(br, 1H), 5.38 (t, J = 5.6 Hz, 1H), 5.87 (s, 1H), 5.88 (s,
1H), 5.92 (s, 1H), 5.99–6.05 (m, 1H), 6.61 (s, 1H), 6.77
(d,J = 10.0 Hz, 1H), 6.88 (s, 1H); LR MS (EI) m/z 325
(M+), 282, 266, 236; HR MS (EI) calcd for C19H19NO4
325.1314, found 325.1289.
[2] K. Folkers, R.T. Major, J. Am. Chem. Soc. 59 (1937) 1580.
[3] Synthesis of erythotrine (a) A. Mondon, H.J. Nestler, Angew. Chem.
Int. Ed. 3 (1964) 588;
(b) Recent report for the synthesis of erythrina alkaloids and
references are therein: A. Padwa, H.I. Lee, P. Rashatasakhon, M.
Rose, J. Org. Chem. 69 (2004) 8209;
(c) S.M. Allin, G.B. Streetley, M. Slater, S.L. James, W.P. Martin,
Tetrahedron Lett. 45 (2004) 5493;
(d) H. Fukumoto, T. Esumi, J. Ishihara, S. Hatakeyama, Tetrahedron
Lett. 44 (2003) 8047.
13. Erythrocarine
[4] (a) G. Burkhart, H. Hoberg, Angew. Chem. Int. Ed. Engl. 21 (1982)
76;
A
solution of 24a (4.5 mg, 0.015 mmol) and
K2CO3(3.4 mg, 0.025 mmol) in MeOH (0.5 mL) was stirred
at room temperature for 1 h. Ethyl acetate was added and
the organic layer was washed with brine, dried over
Na2SO4 and concentrated. The residue was purified by col-
umn chromatography on silica gel (ethyl acetate/MeOH,
5:1) to give erythrocarine (3.7 mg, 93%). IR (neat) 2931,
(b) S. Saito, S. Nakagawa, T. Koizumi, K. Hirayama, Y. Yamamoto,
J. Org. Chem. 64 (1999) 3975.
[5] (a) E. Dunach, J. Pe´richon, J. Organomet. Chem. 352 (1988) 239;
˜
´
´
(b) E. Dunach, S. Derien, J. Perichon, J. Organomet. Chem. 364
˜
(1989) C33;
´
´
(c) S. Derien, E. Dunach, J. Perichon, J. Am. Chem. Soc. 113 (1991)
˜
8447.
1
3104, 2860, 1479, 1228, 1041 cmꢀ1; H NMR (400 MHz,
[6] (a) M. Takimoto, M. Mori, J. Am. Chem. Soc. 123 (2001) 2895;
(b) M. Takimoto, M. Mori, J. Am. Chem. Soc. 124 (2002) 10008;
(c) M. Takimoto, Y. Nakamura, K. Kimura, M. Mori, J. Am. Chem.
Soc. 126 (2004) 5956.
[7] (a) M. Takimoto, M. Kawamura, M. Mori, Org. Lett. 5 (2003)
2599;
CDCl3) d 1.13 (s, 1H), 1.83 (dd, J = 11.2, 11.2 Hz, 1H),
2.52 (dd, J = 11.2, 5.6 Hz, 1H), 2.71 (m, 1H), 2.83–2.91
(m, 2H), 3.51 (m, 2H), 3.79 (d, J = 15.2 Hz, 1H), 4.36
(m, 1H), 5.75 (br, 1H), 5.88 (s, 1H), 5.89 (s, 1H), 5.93 (d,
J = 9.6 Hz, 1H), 6.51 (dd, J = 9.6, 2.0 Hz, 1H), 6.62 (s,
1H), 6.75 (s, 1H);13C NMR (100 MHz, CDCl3) d 25.28,
44.65, 45.92, 57.71, 67.63, 67.69, 100.63, 106.01, 108.56,
122.95, 124.67, 127.82, 132.04, 134.12, 141.79, 145.74,
146.00; LR MS (EI) m/z 283 (M+), 266, 254; HR MS
(EI) calcd for C17H17NO3 283.1208, found 283.1220.
(b) M. Takimoto, M. Kawamura, M. Mori, Synthesis (2004) 791;
(c) M. Takimoto, M. Kawamura, M. Mori, Y. Sato, Synlett (2005)
2019.
[8] (a) M. Takimoto, K. Shimizu, M. Mori, Org. Lett. 3 (2001) 3345;
(b) K. Shimizu, M. Takimoto, M. Mori, Org. Lett. 5 (2003) 2323;
(c) M. Takimoto, T. Mizuno, Y. Sato, M. Mori, Tetrahedron Lett.
46 (2005) 5173.
[9] A.S. Chawla, F.M.J. Redha, A.H. Jackson, Phytochemistry 24 (1985)
1821.
[10] (a) S.-H. Kim, N. Bowden, R.H. Grubbs, J. Am. Chem. Soc. 116
(1994) 10801;
14. 3-Epierythrocarine
A solution of 24a (4.5 mg, 0.015 mmol) and K2CO3
(3.4 mg, 0.025 mmol) in MeOH (0.5 mL) was stirred at
room temperature for 4 h. Ethyl acetate was added and
the organic layer was washed with brine, dried over
Na2SO4 and concentrated. The residue was purified by col-
umn chromatography on silica gel (Ethyl acetate/MeOH,
5:1) to give erythrocarine (2.0 mg, 53%). 1H NMR
(400 MHz, CDCl3) d 2.55 (d, J = 13.4 Hz, 1H), 2.74
(ddd, J = 15.6, 4.8, 4.8 Hz, 1H), 2.93 (m, 1H), 3.21 (d,
J = 14.4 Hz, 1H), 3.64–3.72 (m, 3H), 3.86 (d, J =
13.4 Hz, 1 H), 4.23 (m, 1H), 5.35 (m, 1H), 5.86 (br, 1H),
5.89 (s, 1H), 5.90 (s, 1H), 6.05 (dd, J = 10.0, 5.2 Hz, 1H),
6.66 (d, J = 10.0 Hz, 1H), 6.70 (s, 1H), 6.80 (s, 1H).
(b) S.-H. Kim, W.J. Zuercher, N.B. Bowden, R.H. Grubbs, J. Org.
Chem. 61 (1996) 1073;
(c) T.-L. Choi, R.H. Grubbs, Chem. Commun. (2001) 2648;
(d) E.M. Codesido, L. Castedo, J.R. Granja, Org. Lett. 3 (2001)
1483;
(e) C.-J. Wu, R.J. Madhushaw, R.-S. Liu, J. Org. Chem. 68 (2003)
7889;
(f) F.-D. Boyer, I. Hanna, L. Ricard, Org. Lett. 3 (2001) 3095.
[11] G.C. Fu, S.T. Nguyen, R.H. Grubbs, J. Am. Chem. Soc. 115 (1993)
9856.
[12] P. Schwab, M.B. France, J.W. Ziller, R.H. Grubbs, Angew. Chem.
Int. Ed. Engl. 34 (1995) 2039.
[13] M. Scholl, S. Ding, C.W. Lee, R.H. Grubbs, Org. Lett. 1 (1999)
953.
[14] Recently, Hatakeyama succeeded in a total synthesis of erythravine
using dienyne metathesis. See Ref. [3d].
[15] Conversion of epierythrocarine to erythrocarine was carried out using
Mitsunobu reaction, but no product was obtained due to the steric
hindrance.
References
[1] (a) S.F. Dyke, S.N. Quessy, in: R.H.F. Manske (Ed.), The Alkaloids,
Vol. 18, Academic Press, New York, 1981, p. 1;
[16] R.A. Schunn, Inorg. Synth. 15 (1974) 5.
[17] D.B. Grotjahn, K.P.C. Vollhardt, Synthesis (1993) 579.