Stereoselective synthesis of O,O-dimethylkorupensamine A via palladium(o)-mediated cross-coupling of a planar chiral (arene)Cr(CO)3 complex with naphthylboronic acid

Article abstract of DOI:10.1039/a800075a

O,O-Dimethylkorupensamine A was stereoselectively synthesized by using the palladium(o)-mediated cross-coupling of the enantiomerically pure tricarbonylchromium complex of 3,5-dimethoxy-2-bromobenzene having a functional group at C-l position with naphthy

Full text of DOI:10.1039/a800075a

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Stereoselective synthesis of O,O-dimethylkorupensamine A via
palladium(0)-mediated cross-coupling of a planar chiral (arene)Cr(CO)3
complex with naphthylboronic acid
Takashi Watanabe and Motokazu Uemura*†
Department of Chemistry, Faculty of Integrated Arts and Sciences, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan
OR
O,O-Dimethylkorupensamine A was stereoselectively syn-
thesized by using the palladium(0)-mediated cross-coupling
MeO
Me
MeO
Me
OR
i
of the enantiomerically pure tricarbonylchromium complex
of 3,5-dimethoxy-2-bromobenzene having
a functional
group at C-1 position with naphthylboronic acid as a key
step.
OMe
2
OMe
3 R = H
4 R,R = CMe2
ii
iii
Korupensamines and michellamines have been isolated from
the tropical liana Ancistrocladus korupensis in Cameroon and
some of these alkaloids possess significant pharmacological
activities such as antimalarial properties,1 and remarkable
antiviral activity against human immunodeficiency virus strains
HIV-1 and HIV-2.2 Structurally, the korupensamines have a
naphthyltetrahydroisoquinoline skeleton with an axial chirality
between the naphthalene and tetrahydroisoquinoline rings, and
the michellamines are atropisomerically dimeric alkaloids of
the korupensamines. These alkaloids have been previously
synthesized via construction of the axial bond between the
naphthalene and tetrahydroisoquinoline rings as a key step.3,4
However, the palladium(0)-catalyzed cross-coupling3 of two
arene rings or nucleophilic addition4 of aryl Grignards to the
o-methoxyaryl oxazoline compounds for the central bond
formation of the naphthalene and tetrahydroisoquinoline rings
gave unfortunately various ratios of the atropisomeric mixture
in the previous reports. In continuation of our studies on
development of the planar chiral (arene)chromium complexes
in the asymmetric reactions, we have recently reported5,6 that
both enantiomers of the axial biaryls could be stereoselectively
prepared from a single planar chiral (arene) chromium complex
by the palladium(0)-mediated cross-coupling of (2,6-disub-
stituted 1-bromobenzene)chromium complexes with aryl-
boronic acids and following axial isomerization of the cross-
coupling products under thermal conditions. This paper
describes the asymmetric synthesis of (2)-O,O-dimethyl-
korupensamine A (1, R = Me) utilizing the stereoselective
palladium(0)-catalyzed cross-coupling of the planar chiral
(arylhalide)Cr(CO)3 with napthylboronic acid as the key step.
Ha
O
Br
O
O
Me
O
MeO
R
MeO
R
v
Me
Cr(CO)3
Hb
Cr(CO)3
OMe
OMe
7 R = SiMe3
8 R = H
5 R = H
6 R = SiMe3
iv
vi
Scheme 1 Reagents and conditions: i, AD-mix-a, CH3SO2NH2, ButOH,
H2O, 99%, > 98% ee; ii, Me2C(OMe)2, TsOH, 97%; iii, Cr(CO)6, dibutyl
ether, THF, reflux, 20 h, 89%, > 99% ee; iv, BunLi, THF, TMEDA,
278 °C, then Me3SiCl, THF, 278 °C, 97%; v, BunLi, THF, TMEDA,
278 °C, then BrCF2CF2Br, THF, 278 °C, 98%; vi, Bun4NF, THF, AcOH,
97%
a,7 and the resulting diol was subsequently protected with
acetone dimethylacetal to give the acetonide 4 ([a]2D7 +23.8)‡ in
96% yield with > 98% ee. Tricarbonylchromium complexation
of 4 with Cr(CO)6 in dibutyl ether and THF (10: 1) at reflux
gave the corresponding (arene)chromium complex 5 ([a]D26
24.0) in 89% yield. In order to introduce the bromine atom at
either ortho-position of the C-1 side-chain group regio-
selectively, the C-4 position was initially protected by the
introduction of the easily removable Me3Si group. Thus, the
lithiation of 5 with BunLi followed by treatment with trime-
thylsilylchloride afforded the trimethylsilylated complex 6
([a]2D7 236.0) in 97% yield. Subsequent lithiation§ of 6
followed by quenching with 1,2-dibromo-1,1,2,2-tetrafluoro-
ethane gave the bromination complex 8 ([a]2D6 293.0) at the Ha-
position without the regioisomeric complex after detrimethylsi-
lylation in 95% overall yield. The planar chirality of 8 was
determined by X-ray crystallography.¶
OH
OMe
The palladium(0)-catalyzed cross-coupling of the planar
chiral (arene)Cr(CO)3 complex 8 with 4-benzyloxy-5-methoxy-
6-methylnaphthylboronic acid 98 in the presence of sodium
carbonate in aqueous MeOH at reflux for 30 min produced a
single atropisomeric coupling product 10 ([a]2D8 2142.9) in
90% yield without any formation of the atropisomers (Scheme
2). The axial stereochemistry of the coupling product 10 was
Me
Me
S
RO
R
NH
R
OR
Me
1
1
assigned to be the (S)-configuration by H NMR spectra, in
R = H; Korupensamine A
R = Me; O,O-Dimethylkorupensamine A
which the peri-proton of the naphthalene ring appeared at lower
field (d 8.62) due to the anisotropic effect of the syn-Cr(CO)3
fragment.5 An oxidative demetallation of 10 and subsequent
treatment with dilute HCl afforded the dihydroxyl compound 12
([a]2D7 +3.5). Selective protection of the hydroxyl at the
homobenzylic position of 12 with tert-butyltrimethylsilyl
chloride gave the monosilylated compound 13 ([a]2D5 +35.8) in
The planar chiral tricarbonylchromium complex of 3,5-dime-
thoxyphenylbromide having a functional group at C-1 position
as a coupling partner was initially prepared as follows (Scheme
1).
An
asymmetric
catalytic
dihydroxylation
of
(E)-(3,5-dimethoxyphenyl)propene 2 was treated with AD-mix-
Chem. Commun., 1998
871

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OBn OMe
([a]2D3 220.6) along with a small amount of the corresponding
cis-isomer (ratio, 93: 7) in 70% overall yield. Finally, debenzyl-
ation with Pd-black in a solution of 8.8% formic acid in MeOH
gave O,O-dimethylkorupensamine A 22 (R = H) ([a]2D2 229.1)
in 91% yield.
In conclusion, we have demonstrated the asymmetric synthe-
sis of O,O-dimethylkorupensamine A via a stereoselective Pd0-
mediated cross-coupling method for the construction of the
highly hindered biaryl bond as the key bond forming reaction.
This procedure should have broad utility for the stereoselective
synthesis of structural analogs of the atropisomeric naphthyl-
tetrahydroisoquinoline alkaloids.
OBn OMe
Me
O
i
Me
O
B(OH)2
MeO
Me
9
(CO)3Cr
OMe
10
OBn OMe
ii
Partial financial support for this work was provided by a
Grant-in-Aid for Scientific Research from the Ministry of
Education, Science, Sports and Culture of Japan. We acknowl-
edge the financial support by the Ciba-Geigy Foundation (for
Japan) and The Asahi Glass Foundation.
Me
Me
OR1
MeO
11: R1, R2 = CMe2
iii
12: R1 = H, R2 = H
OR2
iv
Notes and References
13: R1 = H, R2 = TBDMS
14: R1 = C(=S)imid, R2 = TBDMS
v
† E-mail: uemura@ms.cias.osakafu-u.ac.jp
OMe
‡ All optical rotation values were measured in CHCl3 solution.
§ The corresponding di-MOM ether chromium complex analog instead of
the dimethoxy ether complex 6 resulted in a regioisomeric mixture of the
bromination compounds in a 85 :15 ratio by the ortho-lithiation with BunLi
followed by bromination.
vi
OBn OMe
OBn OMe
¶ Crystal data for 10: C17H19BrCrO7, M = 467.23, yellow prismatic,
¯
triclinic, space group P1, a = 9.829(2), b = 13.393(3), c = 7.996(2) Å, a
= 98.27(2), b = 110.31(2), g = 94.38(2)°, U = 967.7(4) Å3, Z = 2, Dc
=
Me
Me
Me
ix
1.603 g cm23, F(000) = 472.00, m = 26.96 cm21, R(Rw) = 0.039 (0.053).
A total of 4729 data were collected using w scans with 22.35 < 2q <
24.98°. Of these 4467 were unique (Rint = 0.085). CCDC 182/795.
Me
MeO
MeO
R2
R1
NHR
1 Y. F. Hallock, K. P. Manfredi, J. W. Blunt, J. H. Cardellina II, M.
Scha¨ffer, K.-P. Gulden, G. Bringmann, A. Y. Lee, J. Clardy, G. François
and M. R. Boyd, J. Org. Chem., 1994, 59, 6349.
OMe
OMe
15: R1 = OTBDMS, R2 = H
16: R1 = OH, R2 = H
17: R1 = H, R2 = N3
18: R = H
19: R = Ac
vii
x
2 K. P. Manfredi, J. W. Blunt, J. H. Cardellina II, J. B. McMahon, L. L.
Pannell, G. M. Cragg and M. R. Boyd, J. Med. Chem., 1991, 34, 3402;
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C. Lackman-Smith, Y. F. Hallock and M. R. Boyd, Antimicrob. Agents
Chemother., 1995, 39, 484.
3 T. R. Hoye, M. Chen, L. Mi and O. P. Priest, Tetrahedron Lett., 1994,
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Hoye and M. Chen, Tetrahedron Lett., 1996, 37, 3099; T. R. Hoye and
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Keller, R. Walter, P. Henschel, M. Scha¨ffer, M. Sta¨blein, T. R. Kelly
and M. R. Boyd, Heterocycles, 1994, 39, 503; P. D. Hobbs, V. Upender,
J. Liu, D. J. Pollart, D. W. Thomas and M. I. Dawson, Chem. Commun.,
1996, 923; P. D. Hobbs, V. Upender and M. I. Dawson, Synlett, 1997.
965.
4 M. A. Rizzacasa and M. V. Sargent, J. Chem. Soc., Chem. Commun.,
1990, 894; B. N. Leighton and M. A. Rizzacasa, J. Org. Chem., 1995,
60, 5702.
5 K. Kamikawa, T. Watanabe and M. Uemura, J. Org. Chem., 1996, 61,
1375.
6 K. Kamikawa, T. Watanabe and M. Uemura, Synlett, 1996, 1040.
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viii
OR
OBn OMe
OMe
xi
Me
Me
Me
Me
MeO
xii
MeO
NH
N
Me
OMe
Me
OMe
20
21: R = Bn
22: R = H
xiii
Scheme 2 Reagents and conditions: i, 8, Pd(PPh3)4 (0.05 mol equiv.), aq.
Na2CO3, MeOH, 75 °C, 30 min, 90%; ii, hn, O2, diethyl ether, 92%; iii, 1 m
aq. HCl, THF, 50 °C, 96%; iv, ButMe2SiCl, imidazole, DMF, 84%;
v, (imid)2CNS, THF; vi, Bun3SnH, AIBN, toluene, 62% from 13; vii,
Bun4NF, THF, 96%; viii, (PhO)2PON3, DEAD, PPh3, THF; ix, SnCl2,
MeOH; x, Ac2O, py, 66%, from 16; xi, POCl3, MeCN; xii, LiAlH4, Me3Al,
THF, 278 to 0 °C, 70% from 19; xiii, Pd-black, HCO2H, MeOH, 45 °C,
91%
84% yield. The benzylic hydroxyl of 13 was removed by the
Barton method9 to give the deoxygenation compound 15 ([a]2D6
+11.9) in 62% yield. The substitution of the hydroxyl to
nitrogen atom with stereochemical inversion was achieved
under Mitsunobu conditions.10 Thus, deprotection of the silyl
ether 15 and subsequent treatment with (PhO)2PON3 in the
presence of DEAD and PPh3 produced the azide compound 17
which was reduced with SnCl2 followed by acetylation to give
the amide compound 19 ([a]2D6 +8.1) in 66% overall yield.
Bischler–Napieralski cyclization of 19 with POCl3 in acetoni-
trile gave the naphthyldihydroisoquinoline compound 20.
Reduction11 of the imine double bond of 20 with LiAlH4 in the
presence of Me3Al afforded trans-dimethyl compound 21
8 Compound 11 was prepared by a modified procedure of the following
reference; M. Watanabe, S. Hisamatsu, H. Hotokezaka and S.
Furukawa, Chem. Pharm. Bull., 1986, 34, 2810.
9 D. H. R. Barton and S. W. McCombie, J. Chem. Soc., Perkin Trans. 1,
1975, 1574.
10 O. Mitsunobu, Synthesis, 1981, 1.
11 G. Bringmann, J. R. Jansen and H.-P. Rink, Angew. Chem., Int. Ed.
Engl., 1986, 25, 913; G. Bringmann, R. Weirich, H. Reuscher, J. R.
Jansen, L. Kinzinger and T. Ortmann, Liebigs. Ann. Chem., 1993, 877;
R. Jansen and H.-P. Rink, Angew. Chem., Int. Ed. Engl., 1986, 25, 913;
K. Maruoka and H. Yamamoto, Angew. Chem., Int. Ed. Engl., 1985, 24,
668.
Received in Cambridge, UK, 2nd January 1998; 8/00075A
872
Chem. Commun., 1998