The enantioselective total synthesis of alkaloid (-)-galipeine

Article abstract of DOI:10.1016/j.tetasy.2004.02.012

The first total synthesis of (-)-galipeine was accomplished in seven steps with 54% overall yield from isovanillin based on Ir-catalyzed asymmetric hydrogenation of a quinoline derivative as a key step, with its absolute stereochemistry being established.

Full text of DOI:10.1016/j.tetasy.2004.02.012

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 1145–1149
The enantioselective total synthesis of alkaloid ())-galipeine
Peng-Yu Yang and Yong-Gui Zhou*
Dalian Institute of Chemical Physics, The Chinese Academy of Sciences, Dalian 116023, PR China
Received 16 January 2004; accepted 13 February 2004
Abstract—The first total synthesis of ())-galipeine was accomplished in seven steps with 54% overall yield from isovanillin based on
Ir-catalyzed asymmetric hydrogenation of a quinoline derivative as a key step, with its absolute stereochemistry being established.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
1999. The isolated yield was low with only 14 mg of
())-galipeine being obtained from 1 kg of the dried bark.
Its structure was determined by extensive NMR spec-
troscopy studies, but the absolute configuration of the
natural product was not assigned. To study this fasci-
nating novel molecule and its biological activity, finding
an appropriately efficient and economic way to synthe-
size ())-galipeine is required.
Galipea officinalis Hancock (Rutaceae) is a Venezuelan
shrubby tree that is acclaimed in folk medicine as a tonic
and stimulant and can be used against fevers.1 Galipea
species are known to contain 2-substituted tetrahydro-
quinoline alkaloids (Fig. 1), whose structures have been
known for some time.2 The biological activity of an
ethanolic extract of Galipea officinalis bark against
Mycobacterium tuberculosis was initially tested by
HoughtonÕs group,3 with some differences in the bio-
activities of 2-substituted tetrahydroquinolines (angus-
tureine, galipinine, cuspareine, and galipeine) being
reported.1
4
€
Very recently, Brase et al. introduced a general meth-
odology for the syntheses of much simpler 2-alkyl
tetrahydroquinolines via intramolecular aza-xylylene
Diels–Alder reactions, but the long synthetic route was a
major problem. Moreover, the methodology could not
be used for the enantioselective syntheses of naturally
occurring 2-alkyl tetrahydroquinoline alkaloids.
O
In continuing efforts directed toward the development of
catalytic asymmetric hydrogenation of aromatic and
heteroaromatic compounds,5a;b we reported the first
catalytic asymmetric hydrogenation of quinolines using
[Ir(COD)Cl]2/MeO-Biphep/I2 as the catalyst with high
enantioselectivities.5c As an application of our devel-
oped method, the first total synthesis of ())-galipeine is
reported herein, featuring Ir-catalyzed asymmetric
hydrogenation of quinoline derivatives as a key step.
Furthermore, the synthesis serves to define the absolute
configuration of ())-galipeine.
N
Me
N
Me
O
(-)-Angustrureine
(-)-Galipinine
OMe
OMe
OH
N
Me
N
Me
OMe
(-)-Cuspareine
(-)-Galipeine
Figure 1. Structures of some quinoline alkaloids isolated from Galipea
officinalis.
())-Galipeine was first isolated from the bark of Galipea
officinalis Hancock by Jacquemond-Collet et al.2a in
2. Result and discussions
A retrosynthetic analysis for ())-galipeine 1 is shown in
Scheme 1. Target molecule 1 can be synthesized via
asymmetric hydrogenation of the corresponding
hydroxy-protected quinoline derivative 6, followed by
* Corresponding author. Tel.: +86-411-4379220; fax: +86-411-46847-
46; e-mail: ygzhou@dicp.ac.cn
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.02.012

1146
P.-Y. Yang, Y.-G. Zhou / Tetrahedron: Asymmetry 15 (2004) 1145–1149
OH
OBn
OMe
N
N
Me
Me
OMe
7
(-)-Galipeine
Key Step
HO
CHO
BnO
MeO
Br
MeO
2
5
OBn
OMe
N
+
Isovanillin
6
Quinaldine
N
Scheme 1. Retrosynthetic analysis.
N-methylation and deprotection of the O-benzyl.
Compound 6 can be constructed by alkylation of the
quinaldine with the bromide 5, which can be synthesized
in three steps through the protection of the free hydroxy,
the reduction of the aldehyde, and bromination from
commercially available isovanillin 2. Among the above
synthetic steps, the asymmetric hydrogenation of quin-
oline derivative 6 and protection of the free hydroxy of
isovanillin 2 are the key steps. Asymmetric hydrogen-
ation can be solved via our previous work on asym-
metric hydrogenation of heteroaromatic compounds.5c
Due to potential problems in carrying a free hydroxy
group through several steps of the synthesis, we decided
to protect the hydroxy functional group by benzylation
of the starting material 2.
cially available aldehyde 2. Treatment of 2 with benzyl
chloride and sodium bicarbonate gave the benzyl group
protected compound 3 in 89% yield via an adaptation of
MendelsonÕs method.6 Compound 3 was reduced with
sodium borohydride to afford the corresponding alcohol
4 in 96% yield, followed by bromination with phos-
phorus tribromide in the presence of pyridine to give
compound 5 in 85% yield, which was directly employed
in the next alkylation without further purification. A
carbanion was generated from the quinaldine in Et2O b y
treatment with n-butyllithium; it was then alkylated with
the bromide 5 to give the key intermediate 6.
Asymmetric hydrogenation of the quinoline derivative 6
was the key step. Firstly we used the previous standard
conditions to screen several commercially available bis-
phosphine ligands with the results shown in Table 1.
Axial chirality ligands BINAP and MeO-Biphep gave
The synthetic route to ())-galipeine is outlined in
Scheme 2. The synthesis of 1 starts from the commer-
BnO
BnO
MeO
CHO
HO
CHO
OH
b
a
c
MeO
MeO
2
4
3
BnO
MeO
e
d
Br
OBn
OMe
OBn
OMe
N
N
H
6
5
7
f
g
OH
OMe
OBn
OMe
N
Me
(-)-Galipeine
N
Me
8
1
Scheme 2. Enantioselective total synthesis of ())-galipeine. Reagents and conditions: (a) BnCl, NaHCO3/KI, CH3CN, 89%; (b) NaBH4, CH3OH,
96%; (c) PBr3, Et2O/pyridine, 85%; (d) Quinaldine, n-BuLi/Et2O, 86%; (e) [Ir(COD)Cl]2/(S)-MeO-Biphep, I2, toluene, H2 (500 psi), 94%; (f) HCHO/
HOAc, NaBH3CN, CH3CN, 96%; (g) 5% Pd/C, EtOAc/HOAc, 95%.

P.-Y. Yang, Y.-G. Zhou / Tetrahedron: Asymmetry 15 (2004) 1145–1149
Table 1. Iridium-catalyzed asymmetric hydrogenation of 6a
1147
[Ir(COD)Cl]2 /Ligands*
I2, toluene, H2 (500 psi)
OBn
OMe
OBn
OMe
N
N
H
6
7
MeO
MeO
PPh2
PPh2
(S)-MeO-Biphep
Entry
Ligands
Yieldb (%)
Eec (%)
Config.d
1
2
3
(S,S)-Me-DuPhos
(S)-BINAP
(S)-MeO-Biphep
65
84
94
18
82
96
R
S
S
a Reaction conditions: 1.0 mmol 2-(30-benzyloxy-40-methoxy-phenethyl)quinoline, [Ir(COD)Cl]2 (0.5%), chiral ligand (1.1%), I2 (10%), 5 mL toluene.
b Isolated yield based on compound 6.
c Determined by HPLC analysis with Chiralpak AS-H column.
d The absolute configuration of the product was assigned by analogy with the previous paper5c on the asymmetric sense of the product.
higher eeÕs and conversions (entries 2 and 3). Me-Du-
Phos, which is generally a good ligand for asymmetric
hydrogenation of functionalized olefins,8 proved not to
be effective herein. As a result we choose MeO-Biphep as
the ligand, with 96% ee being obtained.
3. Conclusion
In conclusion, the first total synthesis of ())-galipeine
was achieved in seven steps with 54% overall yield from
commercially available isovanillin, using the asymmetric
hydrogenation of the quinoline derivative as a key step
with the absolute configuration estimated to be (S).
Further studies on the biology of this and other mem-
bers of this class of natural products are currently
underway in our laboratory and will be reported in due
course.
N-Methylation of 7 using HCHO/NaBH3CN gave 8 in
96% yield by BorchÕs method.7 The final step was the
removal of the benzyl protective group of 8. This pro-
cess was sluggish with Pd on carbon (200 psi H2) in
EtOH, but could be accomplished with EtOH/AcOH
(10:1) to give the tetrahydroquinoline alkaloid ())-gal-
15
{½aŠ ¼ À26:1, (c ¼ 0:44, CHCl3), lit.2a
ipeine
25
1
D
½aŠ ¼ À13:6} in 95% yield. The spectral data (1H
4. Experimental section
4.1. General
D
NMR, 13C NMR) were identical to that reported for the
natural product. The specific rotation of ())-galipeine
synthesized by us is higher than the naturally occurring
())-galipeine isolated from the bark of Galipea officinalis
Hancock by Jacquemond-Collet et al.,2a who stated that
the hexane and chloroform extracts from the bark of
Galipea officinalis Hancock, tetrahydroquinoline alka-
loids were obtained as a racemic mixture in the latter
paper on testing the bioactivities of 2-substituted tetra-
hydroquinolines (angustureine, galipinine, cuspareine,
and galipeine).1 The ())-galipeine was perhaps race-
mized partially over the course of extraction and so the
authors did not determine the ee values. To verify this,
we synthesized the racemic galipeine using a similar
route. The enantiomeric purity of the ())-galipeine
synthesized by us was 96% by HPLC analysis,9 which is
the same with the hydrogenation product 7. This sug-
gested that N-methylation and hydrogenolysis of the
O-benzyl group afforded the corresponding compounds
8 and 1 without deterioration of the enantiomeric
purity. In our previous paper on asymmetric hydro-
genation of quinoline derivatives,5c the asymmetric sense
of the product was (S) when (S)-MeO-Biphep was
used. As a result, the absolute configuration of the
naturally occurring ())-galipeine can be assumed to
b e S( ).
Melting points were determined on a Metter FP5 cap-
illary melting point apparatus and are uncorrected. Ee
values were determined by chiral HPLC with Chiralpak
AS-H and Chiralcel OD-H columns. Optical rotations
1
were measured with a JASCO P-1010 polarimeter. H
NMR and 13C NMR spectra were measured in CDCl3 at
400 Hz. Chemical shifts are given in parts per million
relative to TMS as an internal standard. All reactions
were performed under a nitrogen atmosphere using
oven-dried glassware. High-resolution mass spectra
(HRMS, EI/DP) were obtained at 70 ev.
4.2. Materials
Commercially available reagents and solvents were used
throughout without further purification other than
those detailed below. Solvents were treated prior to use
according to the standard methods. Flash column
chromatography was performed on silica gel (200–300
mesh). Sodium bicarbonate was grounded to a fine
powder and dried under vacuum at 120 ꢁC for 24 h.
3-Hydroxy-4-methoxy-benzaldehyde 2 was purchased

1148
P.-Y. Yang, Y.-G. Zhou / Tetrahedron: Asymmetry 15 (2004) 1145–1149
from Aldrich and quinaldine from Fluka. n-Butyl-
lithium (1.6 M solution in hexane) was purchased from
Acros. Sodium borohydride and sodium cyanoboro-
hydride were purchased from Rohm and Hass. (S)-BI-
NAP, (S,S)-Me-DuPhos and (S)-MeO-Biphep were
purchased from Strem.
rate maintaining reflux. After heating and stirring for an
additional 2 h under a nitrogen atmosphere, TLC anal-
ysis indicated all the starting materials had been con-
sumed. The mixture was cooled and poured into 20 mL
of water and extracted with ethyl acetate (3 · 20 mL).
The combined organic layers were washed successively
with a saturated Na2CO3 solution, water, and brine,
then dried over anhydrous Na2SO4. The solvent was
removed under vacuum to give compound 5 (2.35 g, 85%
yield): mp 94.5 ꢁC (lit.10 mp 94–95 ꢁC). 1H NMR
(CDCl3, 400 MHz) d 7.40–7.20 (m, 5H), 7.00–6.65 (m,
3H), 5.10 (s, 2H), 4.40 (s, 2H), 3.83 (s, 3H). This material
was used in the next step without further purification.
4.3. Experimental procedures
4.3.1. 3-Benzyloxy-4-methoxybenzaldehyde 3. A mixture
of isovanillin 2 (3.04 g, 20 mmol, 1.00 equiv), anhydrous
NaHCO3 (1.92 g, 22.8 mmol, 1.14 equiv) and KI
(332 mg, 2.0 mmol, 0.10 equiv) in dry acetonitrile
(50 mL) was stirred and heated. When the temperature
reached 60 ꢁC, benzyl chloride (3.3 g, 26 mmol,
1.30 equiv) was added in a single portion with a small
volume of acetonitrile as rinse. The resulting mixture
was refluxed for about 10 h under nitrogen, at which
point TLC analysis indicated all the starting materials
had been consumed. After removal of acetonitrile under
reduced pressure, the reaction mixture was poured into
30 mL of water, hydrochloric acid (3 M, 10 mL) and
extracted with ethyl acetate (3 · 50 mL). The combined
organic layers were washed successively with 3% aque-
ous K2CO3, water, and brine, then dried over anhydrous
Na2SO4. The solvent was removed under vacuum, and
the residue purified by flash column chromatography
(silica gel, petroleum ether/ethyl acetate ¼ 10:1) to afford
compound 3 as a white solid (4.3 g, 89% yield): mp
4.3.4. 2-(30-Benzyloxy-40-methoxy-phenethyl)quinoline 6.
To a stirred solution of quinaldine (1.29 g, 9.08 mmol) in
dry ether (50 mL) was added a hexane solution of
n-butyllithium (1.6 M solution, 9.08 mmol) at 0 ꢁC. After
the mixture was stirred for 30 min, compound 5 (2.3 g,
7.5 mmol) in dry ether (20 mL) was added dropwise at
room temperature under nitrogen atmosphere. The
reaction was monitored by TLC. The reaction was
worked up with a saturated Na2CO3 solution (10 mL),
the mixture extracted with ethyl acetate (3 · 20 mL), and
the combined organic layer washed sequentially with a
saturated NH4Cl solution, water, and brine, then dried
over anhydrous Na2SO4. The solvent was removed
under vacuum and the residue purified by flash column
chromatography (silica gel, petroleum ether/ethyl ace-
tate ¼ 10:1) to afford compound 6 as a white solid
(2.40 g, 86% yield): mp 84.3 ꢁC; 1H NMR (CDCl3,
400 MHz) d 3.05–3.09 (m, 2H), 3.21–3.25 (m, 2H), 3.87
(s, 3H), 5.06 (s, 2H), 6.78–6.81 (m, 3H), 7.16 (d,
J ¼ 8:44 Hz 1H) 7.27–7.31 (m, 1H), 7.34–7.42 (m, 4H),
7.51 (d, J ¼ 7:52 Hz, 1H), 7.72 (m, 1H), 7.78 (d,
J ¼ 8:12 Hz, 1H), 8.02 (d, J ¼ 8:4 Hz, 1H), 8.08 (d,
J ¼ 8:44 Hz, 1H); 13C NMR (400 MHz, CDCl3) 35.4,
41.0, 56.0, 71.0, 111.8, 114.7, 121.0, 121.6, 125.8, 126.7,
127.2, 127.5, 127.7, 128.4, 128.8, 129.4, 134.0, 136.1,
137.2, 148.0, 161.9; HRMS Calcd for C25H23NO2 (M+1)
370.1802, found 370.1791.
1
63.4 ꢁC (lit.10 mp 63.5 ꢁC); H NMR (CDCl3, 400 MHz)
d 9.83 (s, 1H), 7.49–7.47 (m, 4H), 7.41–7.33 (m, 3H),
7.01 (d, J ¼ 7:92 Hz, 1H), 5.20 (s, 2H), 3.98 (s, 3H).
4.3.2. 3-Benzyloxy-4-methoxybenzyl alcohol 4. Com-
pound 3 (2.42 g, 10 mmol) was dissolved in methanol
(20 mL) in a round-bottomed flask and the solution
cooled in an ice-bath to produce a fine suspension.
NaBH4 (0.5 g, 12 mmol) was carefully added and
allowed to stand for 15 min; the solution was allowed to
warm up to room temperature and stirred for 2 h. TLC
analysis indicated when the reaction was complete. After
removal of methanol under reduced pressure, the reac-
tion mixture was poured into 20 mL of water, and
extracted with ethyl acetate (3 · 20 mL). The combined
organic layers were washed successively with a saturated
NH4Cl solution, water, and brine, then dried over
anhydrous Na2SO4. The solvent was removed under
vacuum and the residue purified by flash column chro-
matography (silica gel, petroleum ether/ethyl ace-
tate ¼ 10:1) to afford compound 4 as a white solid
4.3.5.
1,2,3,4-tetrahydroquinoline 7. In
())-(S)-2-(30-Benzyloxy-40-methoxy-phenethyl)-
glovebox, the
a
Ir–phosphine complex was made in situ by mixing
[Ir(COD)Cl]2 (3.4 mg, 0.005 mmol) and (S)-MeO-Bip-
hep (6.4 mg, 0.011 mmol) in toluene (3 mL). After the
mixture was stirred at room temperature for 30 min, the
solution was transferred by a syringe to a stainless steel
autoclave, in which I2 (12.7 mg, 0.05 mmol) and 2-(30-
benzyloxy-40-methoxy-phenethyl)quinoline 6 (370.0 mg,
1.0 mmol) were placed beforehand in a toluene solution
(2 mL). The hydrogenation was performed at room
temperature under H2 (500 psi) for 12–15 h. After care-
fully releasing the hydrogen, the reaction mixture was
diluted with dichloromethane (20 mL), saturated
Na2CO3 solution (5 mL) was added, then stirred for
15 min, the aqueous layer was extracted with dichloro-
methane (3 · 15 mL), and the combined organic layers
washed sequentially with water and brine and dried over
anhydrous Na2SO4. The solvent was removed under
1
(2.35 g, 96% yield): mp 71.5 ꢁC (lit.10 mp 71–72 ꢁC); H
NMR (CDCl3, 400 MHz) d 7.46 (d, J ¼ 7:36 Hz, 2H),
7.39–7.35 (m, 2H), 7.32 (d, J ¼ 7:2 Hz, 1H), 6.96 (d,
J ¼ 1:44 Hz, 1H), 6.93–6.87 (m, 2H), 5.16 (s, 2H), 4.58
(s, 2H), 3.89 (s, 3H).
4.3.3. 3-Benzyloxy-4-methoxybenzyl bromide 5. To a
solution of compound 4 (2.20 g, 9 mmol) and ca. 0.3 mL
of pyridine in dry ether (30 mL) was added phosphorous
tribromide (975 mg, 3.6 mmol) in dry ether (20 mL) at a

P.-Y. Yang, Y.-G. Zhou / Tetrahedron: Asymmetry 15 (2004) 1145–1149
1149
vacuum, and the residue purified by flash column
chromatography (silica gel, petroleum ether/ethyl ace-
tate ¼ 10:1) to afford pure 2-(30-benzyloxy-40-methoxy-
to separate the catalyst. The filtrate was concentrated to
give crude 1 as colorless oil. Purification was performed
by a silica gel column eluted with petroleum ether/
EtOAc to give pure 2-(30-hydroxy-40-methoxy-phen-
phenethyl)-1,2,3,4-tetrahydroquinoline 7 354 mg with
20
94% yield. Ee: 96%, ½aŠ ¼ À38:6 (c 1.0, CHCl3), HPLC
ethyl)-2,3,4-tetrahydro-1-methylquinoline 282 mg with
D
20
D
(AS-H, elute: Hexanes/i-PrOH ¼ 97:3, detector: 254 nm,
flow rate: 0.5 mL/min), (R) t1 ¼ 31:7 min, (S)
t2 ¼ 34:3 min. The absolute configuration was assigned
95% yield. Ee: 96%, ½aŠ ¼ À26:1 (c 0.44, CHCl3),
HPLC (OD-H, elute: Hexanes/i-PrOH ¼ 70:30, detector:
254 nm, flow rate: 1.0 mL/min), (R) t1 ¼ 8:2 min, (S)
t2 ¼ 9:2 min. The absolute configuration was estimated
1
as S by analogue. H NMR (CDCl3, 400 MHz) d 1.67
1
(m, 1H), 1.77 (m, 2H), 1.96 (m, 1H), 2.65 (m, 2H), 2.77
(m, 2H), 3.23 (m, 1H), 3.70 (br-s, 1H), 3.89 (s, 3H), 5.17
(s, 2H), 6.46 (d, J ¼ 7:8 Hz, 1H), 6.62 (m, 1H), 6.78 (m,
2H), 6.85 (d, J ¼ 8:68 Hz, 1H), 6.98 (m, 2H), 7.30 (m,
1H), 7.37 (m, 2H), 7.46 (m, 2H); 13C NMR (400 MHz,
CDCl3) 26.1, 27.9, 31.5, 38.2, 50.9, 56.1, 71.0, 112.0,
114.1, 114.6, 117.0, 120.8, 121.3, 126.7, 127.3, 127.8,
128.5, 129.2, 134.3, 137.2, 144.4, 148.0; HRMS Calcd
for C25H27NO2 (M+1) 374.2115, found 374.2110.
to be S. H NMR (CDCl3, 400 MHz) d 1.73 (m, 2H),
1.92 (m, 2H), 1.96 (s, 2H), 2.52 (m, 1H), 2.66 (m, 1H),
2.86 (m, 1H), 2.92 (s, 3H), 3.29 (m, 1H), 3.88(s, 3H),
5.60 (m, 1H), 6.54 (d, J ¼ 8:12 Hz, 1H), 6.61 (m, 1H),
6.68 (d, J ¼ 8:08 Hz, 1H), 6.78 (m, 2H), 7.0 (d,
J ¼ 7:16 Hz, 1H), 7.10 (m, 1H); 13C NMR (400 MHz,
CDCl3) 23.5, 24.3, 31.6, 32.9, 38.0, 56.0, 58.2, 110.6,
114.5, 115.3, 119.5, 121.7, 127.1, 128.6, 135.3, 144.7,
145.3, 145.5.
4.3.6. ())-(S)-2-(30-Benzyloxy-40-methoxy-phenethyl)- 2,3,4-
tetrahydro-1-methylquinoline 8. To a stirred solution of
2-(30-benzyloxy-40-methoxy-phenethyl)-1,2,3,4-tetrahydro-
quinoline 7 (373 mg, 1.0 mmol) and 0.8 mL (10 mmol) of
37% aqueous formaldehyde in 5 mL of acetonitrile was
added 200 mg of sodium cyanoborohydride. Glacial
acetic acid (200 lL) was added and the reaction stirred
at room temperature for 30 min. An additional 200 lL
of glacial acid was added and stirring continued for
30 min more. The reaction mixture was poured into
30 mL of ether and then washed with three 10 mL por-
tions of 1 M KOH and one portion of brine. The ether
solution was dried over potassium carbonate and
evaporated in vacuo to give the crude product as yellow
oil. Purification was performed by a silica gel column
eluted with petroleum ether/EtOAc to give pure 2-(30-
Acknowledgements
We are grateful for the financial support from National
Science Foundation of China (20302005) and Talent
Scientist Program, The Chinese Academy of Sciences.
References and notes
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20
D
methylquinoline 8 372 mg with 96% yield. ½aŠ ¼ À16:1
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as S. 1H NMR (CDCl3, 400 MHz) 1.68 (m, 1H), 1.90 (m,
3H), 2.50 (m, 1H), 2.65 (m, 2H), 2.83 (m, 1H), 2.86 (s,
3H), 3.21 (m, 1H), 3.89 (s, 3H), 5.16 (s, 2H), 6.53 (d,
J ¼ 8:20 Hz, 1H), 6.61 (m, 1H), 6.75 (m, 2H), 6.83 (d,
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J ¼ 7:92 Hz, 1H), 7.30 (m, 1H), 7.37 (m, 2H), 7.45 (m,
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J. Am. Chem. Soc. 1993, 115, 10125.
9. ())-Galipeine: HPLC (Chiralcel OD-H, elute: Hexanes/
i-PrOH ¼ 70:30, detector: 254 nm, flow rate: 1.0 mL/min),
(R) t1 ¼ 8:2 min, (S) t2 ¼ 9:2 min. Ee: 96%. The absolute
configuration was assigned as S.
10. Robin, J. P.; Landais, Y. Tetrahedron 1992, 48, 819–
830.
4.3.7. ())-Galipeine or ())-(S)-2-(30-hydroxy-40-methoxy-
phenethyl)-2,3,4-tetrahydro-1-methylquinoline 1. To a
solution of 387 mg (1 mmol) of 8 in 8 mL of mixing
solvent system of EtOAc/AcOH (10:1) was added 88 mg
of 5% Pd/C, and the mixture stirred under 10 atm of
hydrogen at room temperature for 10 h. After carefully
releasing the hydrogen, the mixture was filtered through
a pad of celite topped with a layer of anhydrous Na2SO4