Palladium-catalyzed enantioselective ring opening of oxabicyclic alkenes with organozinc halides

Article abstract of DOI:10.1021/ol048816i

Palladium-catalyzed asymmetric ring opening of oxabenzonorbornadienes with readily available organozinc halides under mild conditions in the presence of (S)-Prⁱ-PHOX produces the corresponding 1,2-dihydronaphth-1-ols in good yield and high enan

Full text of DOI:10.1021/ol048816i

ORGANIC
LETTERS
2004
Vol. 6, No. 16
2833-2835
Palladium-Catalyzed Enantioselective
Ring Opening of Oxabicyclic Alkenes
with Organozinc Halides
Ming Li,† Xiao-Xia Yan,† Wei Hong,‡ Xia-Zhen Zhu,† Bo-Xun Cao,† Jie Sun,† and
,†,‡
Xue-Long Hou*
State Key Laboratory of Organometallic Chemistry and Shanghai-Hong Kong Joint
Laboratory in Chemical Synthesis, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China
xlhou@mail.sioc.ac.cn
Received June 21, 2004
ABSTRACT
Palladium-catalyzed asymmetric ring opening of oxabenzonorbornadienes with readily available organozinc halides under mild conditions in
the presence of (S)-Pri-PHOX produces the corresponding 1,2-dihydronaphth-1-ols in good yield and high enantioselectivity.
Catalytic asymmetric reactions using organozinc reagents
have been well documented.1 However, the most widely used
reagents are dialkylzinc, and less attention has been paid to
the use of alkylzinc halides, although they are more readily
available.2 On the other hand, ring opening of oxabicyclic
compounds with a variety of nucleophiles, first reported by
Caple and co-workers and developed by Luatens,3,4 has
emerged as an attractive strategy for the preparation of cyclic
and acyclic compounds with multiple stereocenters.4 Re-
cently, Lautens reported a palladium- or copper-catalyzed
addition of dialkylzinc to oxabicyclic alkenes, and excellent
results were obtained.5 However the reagents were limited
to dialkylzinc. To date, there is no report on the enantiose-
lective ring opening of oxabicyclic alkenes with organozinc
† State Key Laboratory of Organometallic Chemistry.
‡ Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis.
(1) For reviews, see: (a) Noyori, R.; Kitamura, M. Angew. Chem., Int.
Ed. Engl. 1991, 30, 49. (b) Soai, K.; Niwa, S. Chem. ReV. 1992, 92, 833.
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Bromm, L. O.; Lotz, M.; Knochel, P. Angew. Chem., Int. Ed. 2000, 39,
4415. (e) Pu, L.; Yu, H.-B. Chem. ReV. 2001, 101, 837.
(3) Caple, R.; Chen, G. M.-S.; Nelson, J. D. J. Org. Chem. 1971, 36,
2874.
(2) (a) Hayashi, T.; Hagihara, T.; Katsuro, Y.; Kumada, M. Bull. Chem.
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1746. Catalytic asymmetric Reformatsky reactions: (e) Braun, M.; Vonder-
hagen, A.; Waldmu¨ller, D. Liebigs Ann. 1995, 1447. (f) Andre´s, J. M.;
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Pini, D.; Mastantunono, A.; Salvadori, P. Tetrahedron: Asymmetry 1994,
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J. M.; Martin, Y.; Pedrosa, R.; Pe´rez-Encabo, A. Tetrahedron 1997, 53,
3787.
(4) For reviews, see: (a) Chiu, P.; Lautens, M. Top. Curr. Chem. 1997,
190, 1. (b) Lautens, M. Synlett 1993, 177. (c) Lautens, M.; Fagnou, K.;
Hiebert, S. Acc. Chem. Res. 2003, 36, 48 and reference therein. For a recent
paper: (d) Rayabarapu, D. K.; Chiou, C.-F.; Cheng, C.-H. Org. Lett. 2002,
4, 1679. (e) Murakami, M.; Igawa, H. Chem. Commun. 2002, 390. (f)
Lautens, M.; Dockendorff, C. Org. Lett. 2003, 5, 3695. (g) Li, L.-P.;
Rayabarapu, D. K.; Nandi, M.; Cheng, C.-H. Org. Lett. 2003, 5, 1621. (h)
Feng, C.-C.; Nandi, M.; Sambaiah, T.; Cheng, C.-H. J. Org. Chem. 1999,
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Lett. 2003, 5, 1373. (j) Millward, D. B.; Sammis, G.; Waymouth, R. M. J.
Org. Chem. 2000, 65, 3902. (k) Arraya´s, R. G.; Cabrera, S.; Carretero, J.
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10.1021/ol048816i CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/08/2004

halides, although they are more versatile and more easily
available.6 We now report here the palladium-catalyzed ring
opening of 7-oxabenzonorborna-diene and its derivatives with
alkylzinc halides to furnish 2-alkyl-1,2-dihydro-1-naphthol
in high enantiomeric excess.
Table 1. Effect of Reaction Conditions on the
Enantioselectivity of Ring Opening of 1a with Benzylzinc
Bromidea
entry
ligand
yield (%)b
ee (%)c
In our initial experiment, 7-oxabenzonorbornadiene (1a)
was treated with benzylzinc bromide7 in the presence of 5
mol % of Pd(dppb)Cl2 in dichloromethane under reflux for
8 h to provide 2-benzyl-1,2-dihydro-1-naphthol 3aa in 78%
yield (Scheme 1). A control experiment indicated that no
reaction occurred in the absence of Pd-catalyst.
1
2
3
4
5
6
7d
8e
4
5
6
7
8
9
6
6
46
66
64
70
80
85
13
98
47
66
90
66
6
2
84
78
a All reactions run at 10 °C with ratio of 1a/BnZnBr/Pd(CH3CN)2Cl2/
ligand ) 1:1.5:0.05:0.05. b Isolated yield based on oxabicyclic alkene.
c Determined by HPLC. d The reaction runs at -20 °C. e The reaction runs
at reflux.
Scheme 1
although the chemical yield was higher (entries 5 and 6).
Temperature effect was also significant, with a lower
enantioselectivity being given at temperatures either lower
or higher than 10 °C. However, the yield was higher if the
reaction proceeded at higher temperature (entries 7 and 8).
To extend the scope of substrate, other substituted ben-
zylzinc bromides were investigated. In almost all cases,
substituted benzylzinc bromides reacted with 1a smoothly
to provide corresponding 2-benzyl-1,2-dihydro-1-naphthol
with high ee values (Table 2, entries 1-4 and 6-10), while
Encouraged by this result, we carried out an asymmetric
version of the same reaction using different kinds of chiral
ligands commercially available or developed by us (Scheme
2), and the results are shown in Table 1.
Scheme 2
Table 2. Enantioselective Ring Opening of Oxabicyclic
Alkenes with Benzylzinc Bromidea
entry
R1, R2, R3
R4, R5, R6
yield (%)b
ee (%)c,d
1
2
3
4
5
6
7
8
H, H, H
H, H, H
H, H, H
H, H, H
H, H, H
H, H, H
H, H, H
H, H, H
H, H, H
H, H, H
Me, H, H
H, Me, H
H, Br, H
H, H, Me
H, H, H
Br, H, H
F, H, H
3a a
3a b
3a c
3a d
3a e
3a f
3a g
3a h
3a i
64
70
57
65
44
53
35
76
49
20
76
72
52
52
90
96
90
87
76
89
95
93
94
88
95
90
81
64
From Table 1, it can be seen that N,P-ligands are effective,
although diphosphine ligands are most often used in this ring-
opening reaction.4,5 Among them, (S)-Pri-PHOX 68 gave the
highest ee value with acceptable chemical yield at 10 °C
(Table 1, entry 3). (R)-BINAP 4, (S)-But-PHOX 5,8 and fer-
rocene 79 gave moderate enantioselectivity (entries 1, 2, and
4), and ferrocene 810 and 911 gave low enantioselectivity,
Me, H, H
H, OMe, H
Cl, Cl, H
H, Br, H
H, H, Br
H, H, OMe
H, H, Me
Br, H, H
Br, H, H
Br, H, H
Br, H, H
9
10
11
12
13
14
3a j
3bb
3cb
3d b
3eb
(5) (a) Lautens, M.; Renaud, J.-L.; Hiebert, S. J. Am. Chem. Soc. 2000,
122, 1804. (b) Bertozzi, F.; Pineschi, M.; Macchia, F.; Arnold, L. A.;
Minnaard, A. J.; Feringa, B. L. Org. Lett. 2002, 4, 2703-2705. (c) Priego,
J.; Manchenˇo, O. G.; Cabrera, S.; Arraya´s, R. G.; LIamas, T.; Carretero, J.
C. Chem. Commun. 2002, 2512-2513.
(6) Duan, J.-P.; Cheng, C.-H. Tetrahedron lett. 1993, 34, 4019
(7) (a) Organozinc Reagents; Knochel, P., Jones, P., Eds.; Oxford
University Press: New York, 1998. (b) Berk. S. C.; Yeh, M. C. P.; Jeong,
N.; Knochel, P. Orgnometallics 1990, 9, 3053. (c) Knochel, P.; Yeh, M. C.
P.; Berk, S. C.; Talbert, J. J. Org. Chem. 1988, 53, 2390.
a All reactions run at 10 °C with ratio of 1a/BnZnBr/Pd(CH3CN)2Cl2/
ligand ) 1:1.5:0.05:0.05. b Isolated yield based on oxabicyclic alkenes.
c Determined by HPLC. d Rotation sign is (+) for all products.
(8) (a) Williams, J. M. J. Synlett 1996, 705 and references therein. (b)
Spinz, J.; Helmchen, G. Tetrahedron Lett. 1993, 34, 1769. (c) Von Matt,
P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1993, 32, 566. For reviews,
see: (d) Ghosh, A. K.; Mathivanan, P.; Cappiello, J. Tetrahedron:
Asymmetry 1998, 9, 1. (e) Pfaltz, A. Synlett 1999, 835.
the yield varied from 20% (entry 10) to 76% (entry 8) despite
the position of substituents. When 4-bromobenzylzinc bro-
mide was used, product 3ab was given with 70% yield and
2834
Org. Lett., Vol. 6, No. 16, 2004

96% ee (Table 2, entry 2), which increased to 99% after
one single recrystallization from diethyl ether. Ring opening
of oxabenzonorbornadienes bearing substituents at various
positions with 4-bromobenzylzinc bromide also provided the
corresponding products in high enantioselectivity (entries
11-13), except that derived from dimethylfuran, which gave
the product containing quaternary chiral carbon 3eb in 64%
ee (entry 14). Addition of 4-bromobenzyl-zinc bromide to
5,8-dimethyl derivative 1b delivered the corresponding
adduct 3bb with 95% ee (entry 11).
The relative and absolute configuration of adduct 3ab was
unequivocally demonstrated by single-crystal X-ray analysis
(see Supporting Information). Configuration of it was as-
signed as (S,S), and the hydroxyl group and benzyl group
are in a syn-substituted pattern.
Not only benzylzinc bromide but also methyl- and eth-
ylzinc iodide are suitable reagents in this ring-opening
reaction. 1,2-Dihydro-2-methyl-1-naphthol 10 was obtained
with 80% yield and 80% ee with 5 mol % of (S)-Pri-PHOX
6, and in the presence of 5 mol % of (R)-BINAP 4, 1,2-
dihydro-2-ethyl-1-naphthol 11 was obtained with 81% yield
and 92% ee (Scheme 3).
the reaction is expected to involve transmetalation of the
palladium catalyst with benzylzinc bromide to generate
palladium alkyl species.13 Coordination of the carbon-carbon
double bond of the alkene substrate and subsequent â-oxygen
elimination and then protonation of the latter species afford
the ring-opening product and a Pd(II) species.
In conclusion, we have developed a Pd-catalyzed nucleo-
philic ring-opening reaction of oxabicylic alkenes with
readily available organozinc halides, and high ee is provided.
It is complementary to metal-catalyzed ring opening with
dialkylzinc developed by Lautens3,4 and thus widens the
scope of the reaction. Further applications of organozinc
halides in asymmetric synthesis are in progress.
Acknowledgment. Financially supported by the National
Natural Science Foundation of China, the Major Basic
Research Development Program (Grant G2000077506), the
National Outstanding Youth Fund, the Chinese Academy of
Sciences, and the Shanghai Committee of Science and
Technology. This paper is dedicated to Professor Li Xin Dai
on the occasion of his 80th Birthday.
Supporting Information Available: Experimental details
describing the synthesis, spectral data, and HPLC analysis
for all new compounds and CIF file for compound 3ab. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Scheme 3
OL048816I
(9) (a) Richards, C. J.; Locke, A. J. Tetrahedron: Asymmetry 1998, 9,
2377. (b) Nishibayashi, Y.; Uemura, S. Synlett 1995, 79. (c) Richards, C.
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123, 6834.
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palladium, see: Negishi, E. Acc. Chem. Res. 1982, 15, 340.
Although the detailed pathway is not clear, on the basis
of the syn-stereochemistry of products and the known
chemistry of ring opening of oxabicylic alkene with dialkyl-
zinc in the presence of Pd catalyst,12, 6 the mechanism for
Org. Lett., Vol. 6, No. 16, 2004
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