Nickel-catalyzed highly stereoselective ring opening of 7-oxa- and azanorbornenes with organic halides

Article abstract of DOI:10.1021/jo982312e

Nickel-catalyzed ring-opening reactions of 7-heteroatom norbornadienes and norbornenes with various organic halides to give products with multiple stereocenters are described. Treatment of 7-oxabenzonorbornadiene (1a) and 7- carbomethoxy-7-azabenzonorbornadiene (1b) with aryl iodides (ArI) in the presence of NiCI₂(PPh₃)₂ and Zn powder gave the corresponding ring- opening addition products cis-1,2-dihydro-2-aryl-1-naphthol (2a-m) and methyl N-[cis-1,2-dihydro-2-aryl-1-naphthyl]carbamate (3a-e) completely stereoselectively in 40-99% yields. The nickel system also catalyzes the reaction of highly substituted oxabicyclic [2.2.1] compounds (1c-e) with organic halides (PhI, PhCH₂Br, PhCHCHBr, and PhCBrCH₂) to give the corresponding ring-opening products (4a-d, 5, 6a,b) that consist of four fixed stereocenters. Studies on the effect of solvent on the reaction of 1a with PhI show that CH₃CN gives the highest yield of product 2a; no product 2a is observed when toluene, dichloromethane, methanol, DMF, or DMSO is used as solvent. Addition of extra PPh₃ to the reaction mixture reduced the yield of 2a. A mechanism is proposed to account for the formation of these nickel- catalyzed ring-opening addition products.

Full text of DOI:10.1021/jo982312e

3538
J . Org. Chem. 1999, 64, 3538-3543
Nick el-Ca ta lyzed High ly Ster eoselective Rin g Op en in g of 7-Oxa -
a n d Aza n or bor n en es w ith Or ga n ic Ha lid es
Chiou-Chii Feng, Malay Nandi, Thota Sambaiah, and Chien-Hong Cheng*
Department of Chemistry, National Tsing Hua University, Hsinchu 30043, Taiwan
Received November 24, 1998
Nickel-catalyzed ring-opening reactions of 7-heteroatom norbornadienes and norbornenes with
various organic halides to give products with multiple stereocenters are described. Treatment of
7-oxabenzonorbornadiene (1a ) and 7-carbomethoxy-7-azabenzonorbornadiene (1b) with aryl iodides
(ArI) in the presence of NiCl2(PPh3)2 and Zn powder gave the corresponding ring-opening addition
products cis-1,2-dihydro-2-aryl-1-naphthol (2a -m ) and methyl N-[cis-1,2-dihydro-2-aryl-1-naphthyl]-
carbamate (3a -e) completely stereoselectively in 40-99% yields. The nickel system also catalyzes
the reaction of highly substituted oxabicyclic [2.2.1] compounds (1c-e) with organic halides (PhI,
PhCH2Br, PhCHCHBr, and PhCBrCH2) to give the corresponding ring-opening products (4a -d , 5,
6a ,b) that consist of four fixed stereocenters. Studies on the effect of solvent on the reaction of 1a
with PhI show that CH3CN gives the highest yield of product 2a ; no product 2a is observed when
toluene, dichloromethane, methanol, DMF, or DMSO is used as solvent. Addition of extra PPh3 to
the reaction mixture reduced the yield of 2a . A mechanism is proposed to account for the formation
of these nickel-catalyzed ring-opening addition products.
In tr od u ction
powder, and zinc chloride in the ring opening of 7-het-
eroatom-norbornene derivatives.6 Interesting observa-
tions by Lautens et al. regarding the nucleophilic ring
opening of oxabicyclic alkenes catalyzed by nickel com-
plexes and the success of the palladium-catalyzed ring
opening of 7-heteroatom-norbornadiene derivatives with
organic halides prompted us to investigate the catalytic
activity of Ni systems in the addition of organic halides
to various oxa- and azabicyclic alkenes. The results show
that nickel phosphine complexes are more reactive than
palladium complexes in these ring-opening addition
reactions. Nickel complexes catalyze the ring-opening
addition of various organic halides to not only 7-hetero-
atom-benzonorbornadiene but also highly substituted
7-oxanorbornenes to yield products with multiple stereo-
centers (eq 1-3). Moreover, the mechanism for this
nickel-catalyzed reaction appears different from that for
nickel-catalyzed nucleophilic ring opening of oxabicyclic
alkenes reported by Lautens.5 Here, we report the scope
and mechanism of this facile one-pot transformation.
Ring opening of oxabicyclic and azabicyclic compounds
is an exceedingly important method in the synthesis of
cyclic and acyclic compounds with multiple stereo-
centers.1,2 A general strategy is to construct highly
substituted rings with the required stereocenters, which
are then cleaved to give chemically complex acyclic
molecules. Nucleophilic ring opening of oxabicyclic alk-
enes using nucleophiles such as organocuprates, organo-
lithium reagents, organomagnesium compounds, diphen-
ylphosphide, and Lewis acidic anhydrides has been
extensively studied.3,4 Recently, Lautens et al. have
reported nickel-catalyzed regio- and enantioselective
nucleophilic ring opening of oxabicyclic alkenes with
DIBAL-H and Grignard reagents.5
Previously, we successfully applied electrophilic re-
agents such as aryl halides, alkenyl halides, and alkyl
halides in the presence of a palladium complex, zinc
(1) (a) Masamune, S.; Kim, C. U.; Wilson, K. E.; Spessard, G. O.;
Georghiou, P. E.; Bates, G. S. J . Am. Chem. Soc. 1975, 97, 3512. (b)
Nakano, A.; Takimoto, S.; Inanaga, J .; Katsuki, T.; Ouchida, S.; Inoue,
K.; Aiga, M.; Okukado, N.; Yamaguchi, M. Chem. Lett. 1979, 1019,
1021. (c) Grieco, P. A.; Ohfune, Y.; Yokoyama, Y.; Owens, W. J . Am.
Chem. Soc. 1979, 101, 4749. (d) White, J . D.; Fukuyama, Y. J . Am.
Chem. Soc. 1979, 101, 226. (e) For an interesting discussion of this
approach, see: White, J . D. Strategies and Tactics in Organic Synthesis;
Lindberg, T., Ed.; Academic Press: New York, 1984; Chapter 13.
(2) Oxabicyclic compounds as valuable intermediates, selected
reviews, see: (a) Lipshutz, B. H. Chem. Rev. 1986, 86, 795. (b) Vogel,
P.; Fattori, D.; Gasparini, F.; Le Drian, C. Synlett 1990, 173. (c)
Lautens, M. Synlett 1993, 177. For leading ref, see: (d) Arjona, O.; Dios
de, A.; Fernandez de la Pradilla, R.; Plumet, J .; Viso, A. J . Org. Chem.
1994, 59, 3906 and references therein. Oxanorbornenic derivative used
for the synthesis of macrocyclic ring systems, see: (e) Ashton, P. R.;
Brown, G. R.; Isaacs, N. S.; Giuffrida, D.; Kohnke, F. H.; Mathias, J .
P.; Slawin, A. M. Z.; Smith, D. R.; Stoddart, J . F.; Williams, D. J . J .
Am. Chem. Soc. 1992, 114, 6330. (f) Ashton, P. R.; Girreser, U.;
Giuffrida, D.; Kohnke, F. H.; Mathias, J . P.; Raymo, F. M.; Slawin, A.
M. Z.; Stoddart, J . F.; Williams, D. J . J . Am. Chem. Soc. 1993, 115,
5422.
(3) (a) Woo, S.; Keay, B. A. Synthesis 1996, 669. (b) Lautens, M.
Synlett 1993, 177. (c) Lautens, M. Pure Appl. Chem. 1992, 64, 1873.
(d) Vogel, P. Bull. Soc. Chim. Belg. 1990, 99, 395. (e) Lautens, M.; Ma,
S. Tetrahedron Lett. 1996, 37, 1727. (f) Arjona, O.; Conde, S.; Plumet,
J .; Viso, A. Tetrahedron Lett. 1995, 36, 6157. (g) Arjona, O.; Fernandez
de la Pradilla, R.; Garcia, E.; Martin-Domenech, A.; Plumet, J .
Tetrahedron Lett. 1989, 30, 6437. (h) Lautens, M.; Abd-El-Aziz, A. S.;
Lough, A. J . Org. Chem. 1990, 55, 5305. (i) Arjona, O.; Fernandez de
la Pradilla, R.; Mallo, A.; Plumet, J .; Viso, A. Tetrahedron Lett. 1990,
31, 1475. (j) Lautens, M.; Fillion, E.; Sampat, M. J . Org. Chem. 1997,
62, 7080.
(4) (a) Gillespie, D. G.; Walker, B. J .; Stevens, D.; McAuliffe, C. A.
J . Chem. Soc., Perkin Trans. 1 1983, 1697. (b) Cuny, G. D.; Buchwald,
S. L. Organometallics 1991, 10, 363.
(5) (a) Lautens, M.; Chiu, P.; Ma, S.; Rovis, T. J . Am. Chem. Soc.
1995, 117, 532. (b) Lautens, M.; Ma, S. J . Org. Chem. 1996, 61, 7246.
(c) Lautens, M.; Rovis, T. J . Org. Chem. 1997, 62, 5246. (d) Lautens,
M.; Rovis, T. Tetrahedron 1998, 54, 1107.
(6) (a) Duan, J .-P.; Cheng, C.-H. Tetrahedron Lett. 1993, 34, 4019.
(b) Duan, J .-P.; Cheng, C.-H. Organometallics 1995, 14, 1608.
10.1021/jo982312e CCC: $18.00 © 1999 American Chemical Society
Published on Web 04/27/1999

Ni-Catalyzed Stereoselective Ring Opening
J . Org. Chem., Vol. 64, No. 10, 1999 3539
Similarly to substrate 1a , 7-carbomethoxy-7-azabenzo-
norbornadiene (1b) reacted with various organic iodides
in the presence of NiCl2(PPh3)2 and zinc in acetonitrile
to afford ring-opening products 2-substituted methyl
N-[cis-1,2-dihydro-1-naphthyl]carbamates (3) in good to
excellent yields (Table 1, entries 19-24). These catalytic
reactions also yield completely stereoselective products.
1
Products 3 were characterized by H and 13C NMR, IR,
and mass spectral data. Most of these reactions show
trends similar to those with 1a as substrate. The reaction
of 4-iodoacetophenone with 1b (Table 1, entry 24) yields
no expected product similar to 2j; for comparison, the
reaction of 4-iodoacetophenone with 1a (entry 10) af-
forded product 2j in 55% yield.
The catalytic reaction is successfully extended to highly
substituted 7-oxanorbornenes (1c-e) as bicyclic alkenes.
The addition reaction between iodobenzene and com-
pound 1c (Table 2, entry 1) in acetonitrile in the presence
8
of Ni(PPh3)2Cl2 (5 mol %) and zinc (3 equiv) occurs at
70 °C, affording completely stereoselective ring-opening
product 4a . Compound 4a is fully characterized by
spectral methods. Benzyl bromide and R- and â-bromo-
styrenes also give ring-opening products in good yields
(Table 2, entries 2-4). The styryl group in compound 4c
was found to be trans, although a mixture of both cis and
trans â-bromo styrene was used for the addition reaction.
3-Iodopentenone and methallyl bromide (Table 2, entries
5 and 6) failed to give the corresponding ring-opening
product. Compound 1d with two methyl groups attached
to bridgehead carbons of the 7-oxanorbornene moiety also
undergoes electrophilic ring opening to give stereoselec-
tive product 5 (Table 2, entry 7) in moderate yield. For
the unsymmetrical 7-oxanorbornene 1e, the addition
reaction in acetonitrile gave two regioisomers 6a and 6b
in a 2:1 ratio in 72% total yield. The major product 6a
was from addition of the phenyl group to the olefin carbon
distal to the bridgehead methyl group. For this nickel-
catalyzed ring opening of bicyclic alkenes 1c-e, four fixed
stereocenters are readily constructed. It is interesting to
note that in the nickel-catalyzed nucleophilic ring open-
ing of bicyclic alkenes involving organomagnesium
reagents,5b the products observed also possess four ste-
reocenters, but the stereochemistry is different from that
observed in eqs 2 and 3.
We showed previously that PdCl2(PPh3)2 catalyzed the
ring opening of 1a and 1b.6 Because the reaction condi-
tions for nickel and palladium systems are substantially
different, it is difficult to compare their catalytic activi-
ties. In general, the palladium-catalyzed ring-opening
reactions were carried out in THF at 60 °C in the
presence of Zn, ZnCl2, and Et3N, whereas the nickel-
catalyzed reactions were performed in acetonitrile in the
presence of Zn at 70 °C. The time required for completion
of reaction is ca. 2-3 times shorter for the nickel system
than for the palladium system. A major difference
between these two metal catalysts is that the palladium
system does not effectively catalyze ring opening of
norbornene derivatives 1c-e with aryl iodides.
Resu lts a n d Discu ssion
Treatment of 7-oxabenzonorbornadiene (1a ) with an
aryl iodide in the presence of NiCl2(PPh3)2 (5 mol %) and
zinc (10 equiv) in acetonitrile at 70 °C afforded the
corresponding ring-opening product 2-substituted cis-1,2-
dihydro-1-naphthol 2 (eq 1 and Table 1). The net result
of this nickel-promoted reaction may be considered to be
an exo 1,4-C-H addition of an arene to compound 1a .
1
There was no trans isomer detected by H NMR spectra
or GC analysis, indicating that the reactions were
completely stereoselective. A large number of aryl iodides
were found to undergo this ring opening, and the results
are shown in Table 1. However, aryl iodides with COCH3,
NO2, OH, and NH2 substituents decreased the catalytic
activities and yields (Table 1, entries 10-13). No addi-
tion product was detected from the reaction of chloroben-
zene with 1a (entry 17), and a poor yield (entry 16) of
the ring-opening product was obtained for bromobenzene.
The use of KI along with bromobenzene failed to improve
the yield (entry 16).7 Alkyl iodides such as ethyl iodide
and n-propyl iodide did not react with 1a under the
reaction conditions for addition of aryl iodide to 1a , but
methyl iodide added to 1a slowly gave the corresponding
2-substituted cis-1,2-dihydro-1-naphthol 2m in 40% yield.
Products 2 were fully characterized by spectral meth-
ods. For example, in the 1H NMR spectrum of 2a , signals
for the olefinic protons appear at 6.12 (H-3) and 6.69 (H-
4) ppm, whereas the protons (H-1 and H-2) bonded to
the carbons at which hydroxyl and phenyl groups are
attached show signals at 4.92 and 3.86 ppm, respectively.
The cis stereochemistry of the hydroxyl and aryl groups
was established on the basis of the 1H NMR coupling
constant (J H1-H2 ) 6 Hz) and earlier precedents.6 13C
NMR spectral and mass data are also consistent with the
proposed structure.
(8) Ni-catalyzed Felkin-type coupling, see: (a) Felkin, H.; Swierczew-
ski, G. Tetrahedron 1975, 31, 2735. (b) Consiglio, G.; Morandini, F.;
Piccolo, O. Helv. Chim. Acta 1980, 63, 987. (c) Consiglio, G.; Waymouth,
R. M. Chem. Rev. 1989, 89, 257. (d) Wenkert, E.; Fernandes, J . B.;
Michelotti, E. L.; Swindell, C. S. Synthesis 1983, 701. (e) Didiuk, M.
T.; Morken, J . P.; Hoveyda, A. H. J . Am. Chem. Soc. 1995, 117, 7273.
(f) Consiglio, G.; Morandini, F.; Piccolo, O. J . Am. Chem. Soc. 1981,
103, 1846. (g) Felkin, H.; J oly-Goudket, M.; Davies, S. G. Tetrahedron
Lett. 1981, 22, 1157.
(7) (a) Chao, C. S.; Cheng, C.-H.; Chang, C. T. J . Org. Chem. 1983,
48, 4904. (b) Yang, S. H.; Li, C. S.; Cheng, C.-H. J . Org. Chem. 1987,
52, 691.

3540 J . Org. Chem., Vol. 64, No. 10, 1999
Ta ble 1. Ad d ition Rea ction of Or ga n ic Iod id es w ith 1a a n d 1b in th e P r esen ce of NiCl2(P P h 3)2/Zn
Feng et al.
a
b
Starting material was recovered. Reaction was carried out with 4 equiv of KI. c Reactions were carried out at 70 °C in CH3CN, and
yields were obtained from NMR spectra using an internal standard (1,3,5-trimethylbenzene); isolated yields are shown in parentheses.
Ta ble 2. Ad d ition Rea ction of RX w ith 1c-e in th e
In most cases, addition reaction of aryl iodides to 1a
P r esen ce of NiCl2(P P h 3)2/Zn
and 1b in the presence of NiCl2(PPh3)2/Zn produces small
amounts of 1-naphthol 7 and 1,2-dihydro-1-naphthol 89,10
(combined yields are less than 10%). Compound 8 became
a major product when the catalyst was changed from
NiCl2(PPh3)2 to NiCl2(dppe) (eq 4). Addition of water (0.5
a
A mixture of cis and trans isomers were used for the reaction.
Isolated yields. c Starting material (15%) was recovered.
b
room temperature in 24 h. In THF the reaction produced
2a in 10% yield at 60 °C in 24 h. In other solvents such
as toluene, dichloromethane, methanol, DMF, and DMSO,
the reaction yielded no 2a . The lack of catalytic activity
in toluene and dichloromethane is likely due to ready
decomposition of the Ni(0) catalyst in these essentially
noncoordinating solvents. This is evidenced by the ob-
servation that in these two cases, the dissolved catalyst
lost color rapidly to give a clear solution and precipitate
of nickel metal. The absence of product 2a in MeOH
results from the fact that the Ni(0) catalyst is protonated
by methanol to yield side product 8. In strongly coordi-
nating solvents such as DMF and DMSO, 1a competes
ineffectively with solvent molecules for coordination to
the nickel center, precluding the addition reaction. It is
interesting to note that for the same addition reaction
catalyzed by PdCl2(PPh3)2 and zinc metal, THF was the
best solvent.6
equiv) increased the yield of 1,2-dihydro-1-naphthol to
44% yield (8:2a ) 7:1). If MeOH was employed as solvent,
product 8 was isolated in 81% yield.
Effect of Rea ction Con d ition s on Rin g Op en in g
of 1a w ith Iod oben zen e. To understand the effect of
reaction conditions on the present catalytic reactions, we
carried out the reaction of iodobenzene with 1a in the
presence of NiCl2(PPh3)2 and Zn metal in various solvents
at different temperatures. To our surprise, of the several
tested solvents including toluene, dichloromethane, metha-
nol, DMF, DMSO, and THF, only acetonitrile appears
effective for the catalytic reaction, giving 83% yield of
addition product 2a in 1.2 h at 70 °C and 14% yield at
(9) Brown, H. C.; Prasad, J . V. N. V. J . Org. Chem. 1985, 50, 3002.
(10) (a) J effrey, A. M.; J erina, D. M. J . Am. Chem. Soc. 1972, 94,
4048. (b) Agarwal, R.; Boyd, D. R.; McMordie, R. A. S.; O’Kane, G. A.;
Porter, P.; Sharma, N. D.; Dalton, H.; Gray, D. J . J . Chem. Soc., Chem.
Commun. 1990, 1711 and references therein.

Ni-Catalyzed Stereoselective Ring Opening
J . Org. Chem., Vol. 64, No. 10, 1999 3541
Sch em e 1
Excess PPh3 in the reaction inhibits the catalytic
activity. For example, on addition of 2, 8, and 16 equivs
of PPh3 to the reaction of 1a with iodobenzene, yields of
2a decreased to 75%, 67%, and 64%, respectively. Ap-
parently, PPh3 competes effectively with 1a for coordina-
tion to the nickel center and hence inhibits the product
formation.
benzene with Ni(PPh3)4 failed because this complex is
thermally unstable. Treatment of NiPh(PPh3)2Br with 1a
at 60 °C in acetonitrile for 1 h afforded 2a in essentially
quantitative yield. These observations firmly suggest that
NiR(PPh3)2X is an important intermediate for the cata-
lytic ring-opening reaction. The proposed exo addition of
an organic group in NiR(PPh3)2X to 1a to yield 9 gains
strong support from the observed cis stereochemistry of
products 2 and the observation that reaction of Pd(PPh3)2-
ArI with norbornadiene or its derivatives yielded Pd
complexes 10 in which the aryl group and the Pd center
Rea ction Mech a n ism . On the basis of the known
chemistry of oxidative addition of aryl halides to Ni(0)
complexes and insertion of norbornadiene and its deriva-
tives into metal-carbon bonds, a mechanism shown in
Scheme 1 is proposed to account for the present nickel-
catalyzed reactions. The first step of the reaction involves
the reduction of Ni(II) to Ni(0) by zinc.11 This is followed
by oxidative addition of RX to Ni(0) species to form Ni-
(PPh3)2RI.12 Exo addition of Ni-R in Ni(PPh3)2RI to
substrate 1 affords intermediate 9. â-Heteroatom elimi-
nation of 9 followed by reduction with zinc metal gives a
zinc salt of 2 and regenerates the nickel(0) catalyst, which
then reacts with RI to continue the catalytic cycle.
Hydrolysis of the zinc salt affords the final product 2.
To show that Ni(PPh3)2ArX is an intermediate in the
catalytic ring opening, we synthesized NiPh(PPh3)2Br
from the reaction of PhBr with Ni(PPh3)4.13 It is note-
worthy that the attempt to prepare the corresponding
iodide complex NiPh(PPh3)2I from the reaction of iodo-
are all at an exo position.14
Both Pd(PPh3)2ArI and 10
are active catalytic intermediates in addition reactions
of aryl halides to 1a to give 2 in the presence of the PdCl2-
(PPh3)2/ZnCl2/Zn/NEt3 system.
The observed retardation of the reaction rate by excess
PPh3 indicates that dissociation of PPh315 from Ni(PPh3)2-
ArI to create a vacant coordination site so as to accom-
modate the incoming substrate 7-heteroatom norborna-
diene in the proposed catalytic cycle (Scheme 1) is a rate-
limiting step. Further evidence for dissociation of PPh3
from Ni(PPh3)2ArI16 arises from the observation that
replacement of Ni(PPh3)2Cl2 by Ni(dppe)Cl2 as the cata-
(11) (a) Kende, A. S.; Liebeskind, L. S.; Braitsch, D. M. Tetrahedron
Lett. 1975, 3375. (b) Zembayashi, M.; Tamao, K.; Yoshida, J .; Kumada,
M. Tetrahedron Lett. 1977, 4089. (c) Takagi, K.; Hayama, N. Chem.
Lett. 1983, 637. (d) Takagi, K.; Hayama, N.; Inokawa, S. Bull. Chem.
Soc. J pn. 1980, 53, 3691.
(12) (a) Amatore, C.; J utand, A. Organometallics 1988, 7, 2203. (b)
Morrell, D. G.; Kochi, J . K. J . Am. Chem. Soc. 1975, 97, 7262.
(13) Hidai, M.; Kashiwagi, T.; Ikeuchi, T.; Uchida, Y. J . Organomet.
Chem. 1971, 30, 279.
(14) Duan, J . P.; Cheng, C.-H. J . Chin. Chem. Soc. 1994, 41, 749.
(15) (a) Brumbaugh, J . S.; Whittle, R. R.; Parvez, M.; Sen, A.
Organometallics 1990, 9, 1735. (b) Samsel, E. G.; Norton, J . R. J . Am.
Chem. Soc. 1984, 106, 5505.

3542 J . Org. Chem., Vol. 64, No. 10, 1999
Feng et al.
Sch em e 2
lyst for addition of iodobenzene with 1a sharply decreased
the yield of 2a . The bidentate dppe ligand is expected to
be much less favored for dissociation. The solvent de-
pendence of the present addition may be understood on
the basis of the dissociation of PPh3 from Ni(PPh3)2ArI
and competition of substrate 1a with solvent molecules
for the vacant site. In the strongly coordinating solvents
dimethylformamide and dimethyl sulfoxide, the vacant
site generated is completely occupied by a solvent mol-
ecule, leading to complete deactivation of the catalyst.
Another possible mechanism for the present nickel-
catalyzed ring-opening reaction involves a nickel π-allyl
complex as suggested by Lautens et al.5b Oxidative addi-
tion of compound 1 to Ni(0) forms a π-allyl complex.
Reaction of the latter with RZnX generated from the
reaction of organic halide (RX) with zinc metal followed
by hydrolysis gives compound 2. To explore the possibility
of this mechanism, several experiments were carried out,
leading to the following observations. First, the reaction
of PhZnCl and 1a in the presence of Ni(PPh3)2Cl2 in ace-
tonitrile at 70 °C yields no 2a , but produces the biphenyl
in 78% yield. Second, a control reaction indicates that
there is no reaction of iodobenzene with the zinc metal
powder we used in THF or acetonitrile at 60-70 °C.
Third, for all reactions shown in eq 1, there are no ring-
opening products 11 and 12, which were observed for the
ring-opening reaction involving a nickel π-allyl complex
as catalyst intermediate. On the basis of the above
observations, a nickel π-allyl mechanism is unlikely.
An acid-catalyzed aromatization of 1a likely accounts
for formation of side product 7.6 This is evidenced by the
observation that heating 1a in the presence of zinc halide,
which is produced in the catalytic reaction, in acetonitrile
leads to formation of 7 in quantitative yield. For the
formation of product 8 (Scheme 2), the reaction pathway
likely involves a Ni(II) hydride, generated in situ by
reducing NiL2Cl2 with zinc metal followed by oxidative
addition of a water or alcohol molecule. Subsequent
insertion of 1a into the Ni(II)-hydride bond and â-het-
eroatom elimination followed by reduction with zinc
metal gives a zinc metal salt and regenerates the nickel-
(0) catalyst. Hydrolysis of the zinc salt affords product
8. Pentacoordinated Ni(II) hydride17 is probably a reac-
tive intermediate as Ni(dppe)Cl2 showed greater selectiv-
ity for product 8 than did Ni(PPh3)2Cl2.
Con clu sion
We have developed a nickel-catalyzed stereoselective
ring opening of oxa- and azabicyclic alkenes with various
organic halides. This methodology is successfully ex-
tended to highly substituted 7-oxanorbornenes to give
products with multiple stereocenters. The nickel catalyst
is more active than the previously reported palladium
analogue; the latter is unable to promote ring opening of
oxabicyclic [2.2.1] compounds. The mechanism for the
present catalytic reaction, involving oxidative addition
of an organic halide to a nickel(0) species as a key step,
(16) Ozawa, F.; Kubo, A.; Hayashi, T. J . Am. Chem. Soc. 1991, 113,
1417.
(17) Rajanbabu, T. V.; Casalnuovo, A. L. J . Am. Chem. Soc. 1996,
118, 6325.

Ni-Catalyzed Stereoselective Ring Opening
J . Org. Chem., Vol. 64, No. 10, 1999 3543
Meth yl N-[cis-1,2-Dih yd r o-2-(2-m eth ylp h en yl)-1-n a p h -
th yl]ca r ba m a te (3b): H NMR (300 MHz, CDCl3) δ 2.39 (s,
differs completely from that proposed by Lautens et al.
for nucleophilic ring openings of oxabicyclic compounds
catalyzed by nickel complexes.
1
CH3, 3H), 3.52 (s, OCH3, 3H), 4.20 (br s, 1H), 4.79 (br d, J )
9.58 Hz, NH, 1H), 5.26 (br t, J ) 8.17 Hz, 1H), 6.05 (dd, J )
9.65 Hz, J ) 4.22 Hz, 1H), 6.68 (dd, J ) 9.58 Hz, J ) 2.06 Hz,
1H), 7.03-7.31 (m, 8H); 13C{1H} NMR (75 MHz, CDCl3) δ
19.61, 40.53, 51.57, 52.07, 126.08, 126.29, 126.45, 127.12,
128.00, 128.13, 128.25, 128.52, 130.51, 130.66, 132.82, 134.46,
Exp er im en ta l Section
All reactions were conducted under a nitrogen atmosphere
on a dual-manifold Schlenk line using purified deoxygenated
solvents and standard inert atmosphere techniques, unless
otherwise stated. Reaction chemicals were used as purchased
without further purification. The catalysts NiCl2(PPh3)2,18 and
NiCl2(dppe),18 3-iodocyclopentenone, and N-carbomethoxy-7-
azabenzonorbornadiene19 were synthesized according to re-
ported procedures.
136.40, 136.58, 156.44; IR (neat) 3367, 3038, 2944, 1714 cm-1
HRMS calcd for C19H19NO2 293.1416, found 293.1417.
;
Meth yl N-[cis-1,2-Dih yd r o-2-(3-ch lor op h en yl)-1-n a p h -
1
th yl]ca r ba m a te (3d ): H NMR (300 MHz, CDCl3) δ 3.64 (s,
OCH3, 3H), 3.84 (br t, J ) 5.22, 1H), 4.74 (br d, J ) 9.99 Hz,
NH, 1H), 5.32 (br t, J ) 8.46 Hz, 1H), 6.09 (dd, J ) 9.69 Hz,
J ) 4.86 Hz, 1H), 6.72 (dd, J ) 9.63 Hz, J ) 1.65 Hz, 1H),
6.99-7.31 (m, 8H); 13C{1H} NMR (75 MHz, CDCl3) δ 44.65,
52.26, 52.71, 125.55, 126.61, 127.15, 127.56, 128.05, 128.36,
128.84, 129.07, 129.29, 129.70, 132.85, 134.12, 134.25, 139.75,
Gen er a l Rea ction P r oced u r e for th e Rea ction of
Or ga n ic Iod id es w ith 7-Oxa -, 7-Aza n or bor n a d ien es or
7-Oxa n or bor n en es (1a -e). A round-bottom sidearm flask
(50 mL) was charged with NiCl2(PPh3)2 (0.016 g, 0.025 mmol),
zinc powder (0.315 g, 5 mmol), a 7-heteroatom norbornene
derivative (0.500 mmol), and a magnetic stirring bar. After
the flask was sealed with a rubber septum, the system was
evacuated and purged with nitrogen gas three times. A
mixture of freshly distilled acetonitrile (3.0 mL) and organic
halide (1.00 mmol) was added via a syringe through the rubber
septum into the flask. The mixture was heated with stirring
at 70 °C until the 7-heteroatom norbornene derivative was
consumed as indicated by TLC analysis of the solution. During
the reaction, the color of the mixture gradually changed from
green to yellow-green and remained the same color for the rest
of reaction period. The reaction mixture was then cooled and
stirred under air for 20 min at room temperature. After
filtration through Celite, the solution was concentrated on a
rotary evaporator and separated on a silica gel column using
a mixture of ethyl acetate/hexane as eluent to give the pure
addition product.
Products 2a -m , 3a -e, 4a -d , and 5 were obtained with this
procedure. Compounds 2a -d , 2f-g, 2i-l, 3a ,c, and 4a ,b were
characterized by comparing their spectral data with those
reported earlier. Important spectral data for products 2e,h ,m ,
3b,e, 4c,d , and 5 follow.
cis-1,2-Dih yd r o-2-(2-m eth oxyp h en yl)-1-n a p h th ol (2e):
1H NMR (300 MHz, CDCl3) δ 2.02 (d, J ) 5.31 Hz, OH, 1H),
3.86 (s, OCH3, 3H), 4.42 (ddd, J ) 5.55 Hz, J ) 2.85 Hz, J )
2.84 Hz, 1H), 4.91 (t, J ) 5.28 Hz, 1H), 6.05 (dd, J ) 9.67 Hz,
J ) 3.50 Hz, 1H), 6.72 (dd, J ) 9.66 Hz, J ) 2.46 Hz, 1H),
6.94 (m, 2 H), 7.12-7.37 (m, 6H); 13C{1H} NMR (75 MHz,
CDCl3) δ 40.29, 55.44, 69.94, 110.48, 120.82, 126.32, 126.82,
127.46, 127.72, 128.01, 128.21, 128.26, 129.77, 130.07, 132.35,
135.72, 157.23; IR (neat) 3526, 3456, 3034, 2930 cm-1; HRMS
calcd for C17H16O2 252.1150, found 252.1140.
156.51; IR (neat) 3419, 3319, 3039, 2953, 2843, 1713 cm-1
HRMS calcd for C18H16N2OCl 313.0870, found 313.0856.
;
Meth yl N-(cis-1,2-Dih yd r o-2-n a p h th yl-1-n a p h th yl)ca r -
ba m a te (3e): 1H NMR (300 MHz, CDCl3) δ 3.44 (s, OCH3, 3H),
4.77 (br d, J ) 9.21 Hz, NH, 1H), 4.88 (br t, J ) 9.99 Hz; 1H),
5.45 (br t, J ) 8.37 Hz, 1H), 6.20 (dd, J ) 9.65 Hz, J ) 4.28
Hz, 1H), 6.77 (dd, J ) 9.63 Hz, J ) 1.95 Hz, 1H), 7.17-7.55
(m, 8H), 7.74 (t, J ) 4.68 Hz, 1H), 7.86 (d, J ) 7.83 Hz, 1H),
8.16 (d, J ) 8.25 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ
39.30, 51.96, 52.58, 123.04, 125.32, 125.58, 126.09, 126.32,
126.59, 127.73, 127.94, 128.08, 128.20, 128.35, 128.77, 129.04,
130.67, 132.30, 132.95, 133.82, 133.94, 134.46, 156.50; IR
(neat) 3416, 3320, 3046, 2953, 1712 cm-1; HRMS calcd for
C
22H19NO2 329.1418, found 329.1416.
(1R*,2R*,5R*,6R*)-5,6-Bis(m eth oxym eth yl)-2-(â-styr yl)-
1
cycloh ex-3-en -1-ol (4c): H NMR (400 MHz, CDCl3) δ 2.41
(ddd, J ) 8 Hz, J ) 7 Hz, J ) 2 Hz, 1H), 2.57 (m, 1H), 3.1 (m,
1H), 3.38 (s, 3H), 3.4 (s, 3H), 3.46 (d, J ) 10 Hz, 2H), 3.55 (d,
J ) 8 Hz, 2H), 3.86 (dd, J ) 10 Hz, J ) 2 Hz, 1H), 4.16 (d, J
) 10 Hz, 1H), 5.63 (dd, J ) 10 Hz, J ) 1 Hz, 1H), 5.71 (dd, J
) 10 Hz, J ) 3 Hz, 1H), 6.43 (dd, J ) 16 Hz, J ) 7 Hz, 2H),
7.16 (d, J ) 7 Hz, 1H), 7.24 (d, J ) 8 Hz, 2H), 7.36 (d, J ) 8
Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 36.14, 41.18, 45.88,
58.84, 67.78, 71.33, 72.74, 126.18, 126.97, 128.35, 128.82,
130.67, 131.31, 137.63; IR (neat) 3384, 3024, 2885, 2242 cm-1
HRMS calcd for C18H24O3 288.1725, found 288.1719.
;
(1R*,2R*,5R*,6R*)-5,6-Bis(m eth oxym eth yl)-2-(r-styr yl)-
1
cycloh ex-3-en -1-ol (4d ): H NMR (400 MHz, CDCl3) δ 2.36
(q, J ) 8 Hz, 6 Hz, 1H), 2.57 (m, 1H), 3.29 (s, 3H), 3.34 (s, 3H)
3.46 (m, 4H), 3.54 (dd, J ) 10 Hz, J ) 2 Hz, 1H), 3.75 (d, J )
9 Hz, 1H), 5.11 (s, 1H), 5.38 (s, 1H), 5.82 (m, 1H), 7.28 (m,
5H); 13C{1H} NMR (75 MHz, CDCl3) δ 36.13, 41.46, 46.87,
58.74, 58.8, 64.07, 71.48, 73.04, 114.65, 126.74, 127.3, 128.17,
cis-1,2-Dih yd r o-2-(2-ch lor op h en yl)-1-n a p h th ol (2h ): 1H
NMR (300 MHz, CDCl3) δ 1.56 (d, J ) 6.21 Hz, OH, 1H), 4.49
(m, 1H), 4.89 (t, J ) 5.43 Hz, 1H), 6.04 (dd, J ) 9.50 Hz, J )
2.84 Hz, 1H), 6.74 (dd, J ) 6.74 Hz, J ) 2.78 Hz, 1H), 7.19-
7.48 (m, 8H); 13C{1H} NMR (75 MHz, CDCl3) δ 43.98, 69.17,
126.68, 126.93, 127.95, 128.05, 128.28, 128.40, 128.77, 128.99,
129.52, 130.95, 132.06, 134.13, 136.85; IR (neat) 3389, 3048,
2913 cm-1; HRMS calcd for C16H13OCl 256.0655, found
256.0641.
128.26, 129.06, 142.02, 149.13; IR (neat) 3408, 2894 cm-1
HRMS calcd for C18H24O3 288.1725, found 288.1716.
;
(1R*,2R*,5R*,6R*)-5,6-Bis(m eth oxym eth yl)-4-m eth yl-2-
1
p h en yl-cycloh ex-3-en -1-ol (5): H NMR (400 MHz, CDCl3)
δ 1.05 (s, 3H), 1.70 (s, 3H), 2.34 (m, 1H), 2.48 (m, 1H), 3.34 (s,
3H), 3.39 (s, 3H), 3.48 (d, J ) 10 Hz, 1H), 3.59 (d, J ) 10 Hz,
1H), 3.71 (dd, J ) 15 Hz, J ) 6 Hz, 2H), 3.78 (dd, J ) 15 Hz,
J ) 6 Hz, 2H), 4.69 (s, 1H), 5.37 (s, 1H), 7.23 (m, 5H); 13C{1H}
NMR (75 MHz, CDCl3) δ 21.76, 24.94, 40.39, 46.32, 54.29,
58.70, 58.89, 67.79, 68.50, 70.47, 126.20, 126.86, 127.36,
130.68, 132.97, 141.78; IR (neat) 3424, 2905 cm-1; HRMS calcd
for C18H24O2 (M+ - O) 272.1776, found 272.1760.
cis-1,2-Dih yd r o-2-m eth yl-1-n a p h th ol (2m ): 1H NMR (300
MHz, CDCl3) δ 1.25 (d, J ) 7.60 Hz, CH3, 3H), 1.55 (s, OH,
1H), 2.61-2.69 (m, 1H), 4.58 (d, J ) 4.40 Hz, 1H), 5.80 (dd, J
) 9.50 Hz, J ) 3.00 Hz, 1H), 6.51 (dd, J ) 9.50 Hz, J ) 2.40
Hz, 1H), 7.11 (dd, J ) 6.80 Hz, J ) 1.60 Hz, 1H), 7.22-7.30
(m, 2H), 7.36 (dd, J ) 6.80 Hz, J ) 1.2 Hz, 1H); 13C{1H} NMR
(75 MHz, CDCl3) δ 13.86, 35.10, 71.43, 126.26, 126.41, 127.12,
127.47, 128.22, 132.26, 132.41, 136.55; IR (neat) 3262, 2965
cm-1; HRMS calcd for C11H12O 160.0888, found 160.0889.
Ack n ow led gm en t. We thank the National Science
Council of the Republic of China for financial support
(Grant NSC85-2113-M-007-004) of this work, and M.N.
and T.S. thank NSC for postdoctoral fellowships.
(18) (a) Colquhoun, H. M.; Thompson, D. J .; Twigg, M. V. Carbo-
nylation; Plenum Press: New York, 1991. (b) Colquhoun, H. M.; Holton,
J .; Thompson, D. J .; Twigg, M. V. New Pathways For Organic
Synthesis-Practical Applications of Transition Metals; Plenum
Press: New York, 1988.
(19) Cragg, G. M. L.; Giles, R. G. F.; Roos, G. H. P. J . Chem. Soc.,
Perkin Trans. 1 1975, 1339.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for 2e,h , 3b,d -e, 4c-d , and 5 are provided. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O982312E