Tandem suzuki coupling-norbornadiene insertion reactions. A convenient route to 5,6-diarylnorbornene compounds

Article abstract of DOI:10.1021/jo016212b

This paper presents optimization studies on a palladium-catalyzed tandem norbornadiene insertion-Suzuki coupling reaction, which provides a one-pot procedure for the formation of diarylnorbornene derivatives. This procedure allows for the synthesis of the

Full text of DOI:10.1021/jo016212b

unsubstituted phenyl ring. Afterward, Kosugi performed
an analogous tandem Stille coupling-norbornadiene
insertion reaction (eq 2).11,12 This allowed for the syn-
Ta n d em Su zu k i Cou p lin g-Nor bor n a d ien e
In ser tion Rea ction s. A Con ven ien t Rou te to
5,6-Dia r yln or bor n en e Com p ou n d s
Katie M. Shaulis, Bradley L. Hoskin,
J ohn R. Townsend, and Felix E. Goodson*
Department of Chemistry, West Chester University of
Pennsylvania, West Chester, Pennsylvania 19383
thesis of various derivatives; however, for aryl groups
other than phenyl, the tin reagents would still have to
be synthesized. Also, the formation of toxic tin byprod-
ucts, from which the product would have to be purified,
was another drawback for this protocol. Novak was able
to synthesize a di(p-bromophenyl) derivative by perform-
ing a tandem Suzuki coupling-norbornadiene insertion
reaction (eq 3, Ar and Ar′ ) 4-bromophenyl, X ) I).1 This,
Christopher D. Incarvito and Arnold L. Rheingold
Department of Chemistry and Biochemistry, University of
Delaware, Newark, Delaware 19716
fgoodson@wcupa.edu
Received October 17, 2001
Abstr a ct: This paper presents optimization studies on a
palladium-catalyzed tandem norbornadiene insertion-
Suzuki coupling reaction, which provides a one-pot proce-
dure for the formation of diarylnorbornene derivatives. This
procedure allows for the synthesis of these compounds from
readily available aryl halides, arylboronic acids, and sub-
stituted norbornadienes.
Reactions that form multiple carbon-carbon single
bonds are valuable synthetic tools in that they can be
used to form complicated molecular structures in a single
step. Our research group has been interested in finding
a simple, general route to 5,6-diarylnorbornene diester
compounds (1), since certain examples can be used as
monomers in soluble precursor polymerization routes to
conjugated polymers.1 Chiusoli,2-4 Larock,5,6 Torii,7 Kang,8
and Kosugi9-12 have all been active in developing pal-
ladium-catalyzed ternary coupling reactions between
bicyclic olefins, aryl or vinyl halides, and various nucleo-
philes. Of these researchers, Chiusoli was the first to
develop a route to a 5,6-diarylnorbornene compound by
performing a ternary coupling reaction between 4-bromo-
toluene, norbornadiene, and sodium tetraphenylborate
(eq 1).4 Unfortunately, this route was not general enough
in theory, could provide the generality we were looking
for, since numerous aryl halides and aryl boronic acid
compounds are commercially available. However, the
yield for this reaction (which was not optimized) was
limited to 25%. In this paper, we present optimization
studies in which we have been able to improve consider-
ably the yield of the title reaction by varying reaction
parameters. We also present the synthesis and charac-
terization of several derivatives to show the scope and
utility of the reaction.
A possible mechanism, analogous to that proposed for
Chiusoli’s similar ternary coupling reaction,4 is presented
in Scheme 1. First, oxidative addition of the aryl halide
onto a Pd(0) species forms an arylpalladium(II) halide
complex (2). Then a ligand exchange occurs in which the
norbornadiene substitutes for a phosphine to form com-
plex 3. Alkene insertion results in species 4, and trans-
metalation, by which the palladium obtains the other aryl
group from the boron, produces complex 5. Finally, a
reductive elimination reaction delivers the product and
regenerates the Pd(0) catalyst.
for our purposes since one of the aryl groups (provided
by the tetraphenylborate ion) was restricted to be an
During this cycle, there are a number of side reactions
that can occur, resulting in the formation of unwanted
byproducts. First of all, a Suzuki coupling reaction can
occur without the insertion, resulting in the formation
of a biphenyl derivative. Second, arylpalladium(II) halide
bisphosphine compounds (e.g., 2) are known to undergo
an aryl-aryl exchange reaction, by which the Pd-bound
(1) Goodson, F. E.; Novak, B. M. Macromolecules 1997, 30, 6047.
(2) Catellani, M.; Chiusoli, G. P. J . Organomet. Chem. 1983, 250,
509 and references therein.
(3) Catellani, M.; Chiusoli, G. P.; Mari, A. J . Organomet. Chem.
1984, 275, 129.
(4) Catellani, M.; Chiusoli, G. P.; Concari, S. Tetrahedron 1989, 45,
5263.
(5) Larock, R. C.; Hershberger, S. S.; Takagi, K.; Mitchell, M. A. J .
Org. Chem. 1986, 51, 2450 and references therein.
(6) Larock, R. C.; J ohnson, P. L. J . Chem. Soc., Chem. Commun.
1989, 1368.
(7) Torii, S.; Okumoto, H.; Ozaki, H.; Nakayasu, S.; Kotani, T.
Tetrahedron Lett. 1990, 31, 5319.
(9) Kosugi, M.; Tamura, H.; Sano, H.; Migita, T. Chem. Lett. 1987,
193.
(10) Kosugi, M.; Tamura, H.; Sano, H.; Migita, T. Tetrahedron 1989,
45, 961.
(11) Kosugi, M.; Kumura, T.; Oda, H.; Migita, T. Bull. Chem. Soc.
J pn. 1993, 66, 3522.
(8) Kang, S.-K.; Kim, J .-S.; Choi, S.-C.; Lim, K.-H. Synthesis 1998,
1249.
(12) Oda, H.; Ito, K.; Kosugi, M.; Migita, T. Chem. Lett. 1994, 1443.
10.1021/jo016212b CCC: $22.00 © 2002 American Chemical Society
Published on Web 07/09/2002
5860
J . Org. Chem. 2002, 67, 5860-5863

TABLE 1. Micr osca le Op tim iza tion Stu d ies
SCHEME 1
entry [ArB(OR)2]/[ArI]a [NBD]/[ArI]b phosphine % Pd % yieldc
1
2
3
4
5
6
7
8
1.1
1.1
1.1
1.1
1.1
1.1
0.8
1.1
2.0
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
2.0
1.1
4
PPh3
P(o-Tol)3
P(Cy)3
P(t-Bu)3
DTBPBf
none
PPh3
PPh3
4
4
4
4
4
4
4
4
76
66
58
23
69
57
75g
80
54
84
70
d
e
9
10
11
PPh3
PPh3
PPh3
4
4
0.1
1.1
a
Ratio of initial equivalents of phenylboronic ester to iodoben-
b
zene. Ratio of initial equivalents of norbornadiene diester to
iodobenzene. c Yield determined by HPLC using 1,4-dimethoxy-
benzene as an internal standard. Tri(o-tolyl)phosphine. e Tricy-
d
clohexylphosphine. f 2-[Di(tert-butyl)phosphino]biphenyl. Yield
g
based on limiting phenylboronic ester.
aryl group switches places with a phosphine-bound aryl
ring.13 This would result in the phosphine-derived aryl
group being incorporated into the product in lieu of the
intended aryl group from the halide. The third is a
competing reduction reaction in which species 4 acquires
a hydride from the reaction medium, and subsequent
reductive elimination would then produce a monoaryl-
norbornene byproduct.6 Also, the bicyclic alkene can react
with multiple equivalents of aryl halide in a palladium-
catalyzed domino reaction to give polyarylated prod-
ucts.2,14,15 Many of these side reactions have been noted
in other palladium-catalyzed coupling reactions, and
various phosphine cocatalysts have been developed and
used in order to combat them.12,16-22
To determine which of these cocatalysts would be most
effective for optimizing the yields of our tandem insertion
and coupling reactions, we performed several microscale
experiments and monitored the results by HPLC (eq 3,
Pd ) Pd(OAc)2, X ) I, Ar′ ) Ph, Table 1). Surprisingly,
the best phosphine cocatalyst appears to be simple
triphenylphosphine, which produced marginally better
results than tri(o-tolyl)phosphine and di(tert-butyl)phos-
phinobiphenyl and significantly better yields than the
other ligands. We also investigated the role of stoichi-
ometry on the reaction with the thought that excess
boronic acid (formed in situ by hydrolysis of the 1,3-
propanediol ester) and/or norbornadiene diester could
improve product yield at the expense of competing
reduction and simple biphenyl formation. Excess phe-
nylboronic ester (entry 9) lowered the yield, while excess
norbornadiene (entries 8 and 10) improved it marginally.
It is noteworthy that satisfactory yields are obtained with
only a slight excess of both reagents or even when the
boronic acid is limiting (entry 7). This is important
because the boron reagent is usually the most expensive
component of the reaction, and the norbornadiene diester
needs to be synthesized (though the procedure is quite
simple) with the amount used in excess being separated
from the product at the end. Also, although most of these
trials were set up with a large amount of catalyst (4%),
successful yields were obtained with catalyst loadings as
low as 0.1% (entry 11). A control experiment with no
palladium showed no product formation, verifying that
a catalyst of some sort is required.
The fact that a significant amount of product was
formed without the addition of a cocatalyst (entry 6)
raises the question as to whether the phosphine is
actually involved in the catalytic cycle. The parent Suzuki
coupling reactions are known to proceed readily without
phosphine present,23 and Kang has found palladium-
mediated ternary couplings of iodonium salts to occur
with ligandless catalyst systems.8 The kinetics for the
reactions with and without the addition of triphenylphos-
phine were measured side-by-side at 50 °C by removing
aliquots at various time intervals and monitoring the
appearance of product via HPLC. The observed pseudo-
first-order rate constant for the reaction without the
phosphine was found to be an order of magnitude faster
than that for the reaction with the added cocatalyst (7.0
× 10-2 vs 6.6 × 10-3 s-1). Hence, it appears that the role
of the phosphine is to tone down the reactivity of the
palladium center and thereby to improve its selectivity
for the desired product.
To investigate the scope of the reaction, we performed
different ternary couplings using various aryl halide and
aryl boronic acid substrates (eq 3, 1 equiv of aryl halide,
1.1 equiv of boronic acid, 1.1 equiv of norbornadiene
diester, 4% Pd(OAc)2/PPh3). For successful trials, we also
scaled up the reactions and isolated the products. The
results of these experiments are presented in Table 2.
From the first three entries, it is apparent that the halide
must be iodide in order for the reaction to be successful.
As can be seen from the other entries, the reaction is very
general for different aryl iodides and different aryl
(13) Kong, K.-C.; Cheng, C.-H. J . Am. Chem. Soc. 1991, 113, 6313.
(14) Reiser, O.; Weber, M.; de Meijere, A. Angew. Chem., Int. Ed.
Engl. 1989, 28, 1037.
(15) Albrecht, K.; Reiser, O.; Weber, M.; Knieriem, B.; de Meijere,
A. Tetrahedron 1994, 50, 383.
(16) Goodson, F. E.; Wallow, T. I.; Novak, B. M. J . Am. Chem. Soc.
1997, 119, 12441.
(17) Yamamoto, T.; Nishiyama, M.; Koie, Y. Tetrahedron Lett. 1998,
39, 2367.
(18) Old, D. W.; Wolfe, J . P.; Buchwald, S. L. J . Am. Chem. Soc.
1998, 120, 9722.
(19) Hartwig, J . F.; Kawatsura, M.; Hauck, S. I.; Shaughnessy, K.
H.; Alkazar-Roman, L. M. J . Org. Chem. 1999, 64, 5575.
(20) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1998, 37, 3387.
(21) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1999, 38, 2411.
(22) Littke, A. F.; Fu, G. C. J . Org. Chem. 1999, 64, 10.
(23) Wallow, T. I.; Novak, B. M. J . Org. Chem. 1994, 59, 5034 and
references therein.
J . Org. Chem, Vol. 67, No. 16, 2002 5861

TABLE 2. Sca le-Up a n d Scop e
to promote the reaction (entry 6) is somewhat surprising.
While other failed trials (entries 2 and 5) resulted
primarily in the unhindered formation of biphenyl, the
presence of 6f appeared to prevent completely all coupling
reaction. This could be due to a partial retro-Diels-Alder
reaction of this component to yield diethyl acetylenedi-
carboxylate, which we have found to be a potent catalyst
poison in these reactions. However, a 13C NMR spectrum
of the crude reaction (upon removal of solvent) showed
no evidence for the presence of this compound.
Finally, in terms of the stereochemistry of the products,
other researchers have found analogous ternary reactions
with norbornene (mono olefin) to proceed in a cis, exo
fashion.10 However, certain reactions involving palladium
and norbornadiene (bis olefin) have been found to result
in endo insertion,24 while others yield products that have
isomerized to a nortricyclyl skeleton.25 For our products,
NMR chemical shifts appear to be consistent with a cis,
exo arrangement of the phenyl rings (based on assign-
ments made on similar compounds in the literature4).
This stereochemical assignment was unambiguously
confirmed with an X-ray crystallographic analysis on
compound 1a (Supporting Information).
In summary, we have successfully developed a one-step
procedure for the synthesis of 5,6-diarylnorbornene di-
ester derivatives. The reaction is very general, producing
viable isolated yields (as high as 78%) of several products
starting from a variety of aryl iodide and aryl boronic
acid substrates. We found that simple triphenylphos-
phine was the best cocatalyst for the reaction, that
satisfactory results were obtained with as little as 0.1%
catalyst, and that only slight excess amounts of norbor-
nadiene diester and boronic acid were required. Finally,
from X-ray crystallography, we have unambiguously
determined that the product is formed in a cis and exo
stereochemical fashion.
entry
ArX
Ar′
product % yielda
1
2
3
4
chlorobenzene
bromobenzene
phenyltriflate
iodobenzene
phenyl
phenyl
phenyl
phenyl
1a
1a
1a
1a
1b
1c
1d
1e
1f
1g
1h
1c
1h
<5
12
<5
76 (63)
(43)
74 (66)
(70)
(46)
(53)
(40)
(78)
(76)
(72)
5
6
7
4-iodonitrobenzene phenyl
4-iodoanisole phenyl
1-iodonaphthalene phenyl
8
9
10
11
12
13
4-iodoaniline
iodobenzene
4-iodoaniline
2-iodoanisole
iodobenzene
iodobenzene
phenyl
4-formylphenyl
4-aminophenylb
phenyl
4-methoxyphenyl
2-methoxyphenyl
a
Determined by HPLC. Isolated yields are in parentheses.
From the pinacol cyclic boronic ester
b
TABLE 3. Va r ia tion of Dien e Com p on en t
isolated
diene product yield
entry
X
Y
Z
R
1
2
3
4
5
6
H
CH2
H
COOEt
6a
6b
6c
6d
6e
6f
1a
63
a
CH3 CH(CH3)
CH3 COOEt
H
H
H
H
CH2
H
H
H
H
H
H
1i
1j
28
9b
c
CH(Ot-Bu)
CH2CH2
O
COOEt
COOEt
d
a
Only biphenyl and residual diene were observed by TLC and
b
GC-MS. Only one isomer could be separated and purified from
oligomeric impurities. c A trace amount of a possible product was
observed in a crude NMR spectrum of the reaction mixture.
However, it was not enough (<10%) to purify and characterize.
d
Only starting materials were recovered from the reaction mix-
ture.
Exp er im en ta l Section
boronic acids, with the products being isolated pure in
moderate to good yields. Electron-donating groups in the
aryl iodide (entries 6, 8, 10, and 11) and aryl boronic acids
(entries 10, 12, and 13) do not appear to adversely affect
the reaction. For the 4-iodoanisole entry, the HPLC
chromatogram revealed evidence for only minor contami-
nation (ca. 6%) by the unsubstituted phenyl product,
suggesting that aryl-aryl exchange is not a significant
concern under these reaction conditions. This is note-
worthy because this side reaction is known to be en-
hanced by the presence of electron-donating groups.13,16
Steric hindrance on either the aryl iodide (entries 7 and
11) or the aryl boronic acid (entry 13) also did not appear
to have an adverse effect on the reaction.
While the reaction works for a variety of aryl iodide
and aryl boronic acid substrates, the choice for the diene
component is critical (Table 3). Increased sterics at the
active alkene site (entry 2) completely prevent the
insertion. However, hindrance of some sort is required
at the second olefin to prevent unwanted reactions from
occurring there. Both norbornadiene (entry 3) and 7-tert-
butoxynorbornadiene (entry 4) yielded a sizable amount
of oligomeric byproducts, from which it was difficult to
purify the desired product. Increasing the bridge size by
one carbon (entry 5) similarly resulted in little or no
ternary reaction. The failure of the 7-oxo derivative (6f)
Gen er a l. Diethyl norbornadiene-2,3-dicarboxylate (6a ),26 di-
ethyl bicyclo[2.2.2]octa-2,5-diene-2,3-dicarboxylate (6e),27 and
diethyl 7-oxonorbornadiene-2,3-dicarboxylate (6f)28 were syn-
thesized via literature procedures and purified by careful
Kugelrohr distillation under
a dynamic vacuum at 65 °C.
Similarly, 2-phenyl-1,3,2-dioxaborinane29 was synthesized as
described in the literature. The synthesis of diethyl 1,4,5,6,7-
pentamethylbicyclo[2.2.2]hepta-2,5-diene-2,3-dicarboxylate (6b)
is outlined in Supporting Information. Iodobenzene was vacuum
distilled from CaH2 and stored in the dark in a drybox. All other
chemicals and solvents were used as received from chemical
suppliers. 1H and 13C NMR spectra were obtained at 300 and
75 MHz, respectively, using CDCl3 as a solvent and tetramethyl-
silane as an internal reference. Analytical data were obtained
by Robertson Microlit Laboratories, Inc. HPLC chromatograms
were obtained using an instrument equipped with a Whatman
silica column and a UV-visible detector. Yields were calculated
(24) Segnitz, A.; Kelly, E.; Taylor, S. H.; Maitlis, P. M. J . Organomet.
Chem. 1977, 124, 113.
(25) Larock, R. C.; Leach, D. R.; Bjorge, S. M. Tetrahedron Lett.
1982, 23, 715.
(26) Kobayashi, Y.; Mizojiri, R.; Ikeda, E. J . Org. Chem. 1996, 61,
5391.
(27) Cossu, S.; Cuomo, G.; De Lucchi, O.; Maggini, M.; Valle, G. J .
Org. Chem. 1996, 61, 153.
(28) McCulloch, A. W.; Stanovnik, B.; Smith, D. G.; McInnes, A. G.
Can. J . Chem. 1969, 47, 4319.
(29) Delaude, L.; Demonceau, A.; Noels, A. F. Macromolecules 1999,
32, 2091.
5862 J . Org. Chem., Vol. 67, No. 16, 2002

on the basis of integrations of the product relative to an internal
standard of 1,4-dimethoxybenzene.
J d ) 9.3 Hz, 1H), 1.28-1.34 (overlapping triplets, J ) 7.2 Hz,
6H); 13C NMR (75 MHz, CDCl3) δ 164.7, 164.7, 147.3, 146.7,
144.2, 141.6, 131.2, 129.6, 128.9, 127.6, 125.6, 114.8, 60.8, 51.3,
50.7, 48.8, 48.5, 45.1, 14.1. Anal. Calcd for C25H27NO4: C, 74.05;
H, 6.71; N, 3.45. Found: C, 73.78; H, 6.45; N, 3.41.
Gen er a l P r oced u r e for P r od u ct Isola tion . A 50-mL
Schlenk flask was charged with aryl halide (2.5 mmol), aryl
boronic acid (2.75 mmol), diene (6) (2.75 mmol), triphenylphos-
phine (16 mg, 0.062 mmol), K2CO3 (0.912 g, 6.6 mmol), THF (5
mL), water (5 mL), and a stirbar. The mixture was then degassed
via three freeze-pump-thaw cycles, and Pd(OAc)2 (6 mg in 250
µL of degassed THF) was added via syringe under a nitrogen
backflow. The reaction was degassed once more and placed in a
60 °C oil bath overnight. The two phases were separated, and
the aqueous phase was extracted with 2 × 15 mL of CH2Cl2.
The organic layers were combined, extracted with 5% NaCN (1
× 25 mL) to remove colored palladium impurities, and dried over
Na2SO4. Afterward, the solvent was removed with a rotary
evaporator, and the residue was heated at 60 °C under a
dynamic vacuum in a Kugelrohr oven to distill off biphenyl and
excess norbornadiene diester. The resulting resin left in the pot
was purified by column chromatography (silica gel) and/or
recrystallization.
Dieth yl 5-(4-F or m ylp h en yl)-6-p h en ylbicyclo[2.2.1]h ep t-
2-en e-2,3-d ica r boxyla te (1f). Isolated as a yellow resin after
chromatography (10% EtOAc in hexanes): 1H NMR (300 MHz,
CDCl3) δ 9.83 (s, 1H), 7.53, 7.06 (second-order AA′BB′ pattern,
J ) 8.1 Hz, 4H), 6.85-7.05 (m, 5H), 4.28 (q, J ) 7.1 Hz, 4H),
3.55-3.57 (m, 4H), 2.43 (dm, J d ) 9.8 Hz, 1H), 2.13 (dm, J d
)
9.8 Hz, 1H), 1.33 (t, J ) 7.1 Hz, 6H); 13C NMR (75 MHz, CDCl3)
δ 191.5, 164.5, 164.4, 148.7, 147.4, 146.4, 140.4, 134.4, 129.4,
129.0, 128.6, 127.9, 126.1, 61.1, 50.8, 50.4, 49.5, 45.2, 14.2. Anal.
Calcd for C26H26O5: C, 74.62; H, 6.26. Found: C, 74.49; H, 6.29.
Dieth yl 5,6-Di(4-a m in op h en yl)bicyclo[2.2.1]h ep t-2-en e-
2,3-d ica r boxyla te (1g). Isolated as tan crystals after chroma-
tography (2% EtOH in CHCl3) and recrystallization from
methanol: mp 172.5-174.0 °C (MeOH); 1H NMR (300 MHz,
CDCl3) δ 6.66, 6.38 (second-order AA′BB′ pattern, J ) 8.4 Hz,
8H), 4.25 (q, J ) 7.2 Hz, 4H), 3.32-3.45 (multiple broad
resonances, 8H), 2.32 (br d, J d ) 9.6 Hz, 1H), 1.98 (dm, J d ) 9.3
Hz, 1H), 1.30 (t, J ) 7.2 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ
164.8, 146.9, 143.9, 131.4, 129.5, 114.7, 60.8, 50.8, 47.6, 45.1,
14.1. Anal. Calcd for C25H28N2O4: C, 71.41; H, 6.71; N, 6.66.
Found: C, 71.17; H, 6.83; N, 6.46.
Dieth yl 5,6-Dip h en ylbicyclo[2.2.1]h ep t-2-en e-2,3-d ica r -
boxyla te (1a ). Isolated as
a white crystalline solid after
chromatography (10% EtOAc in hexanes) and recrystallization
from methanol: mp 82.0-84.5 °C (MeOH); 1H NMR (300 MHz,
CDCl3) δ 6.85-7.05 (m, 10H), 4.26 (q, J ) 7.0 Hz, 4H), 3.51-
3.53 (m, 4H), 2.43 (dm, J d ) 9.6 Hz, 1H), 2.07 (dm, J d ) 9.6 Hz,
1H), 1.31 (t, J ) 7.0 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 164.6,
147.1, 141.2, 128.8, 127.7, 125.7, 60.9, 50.8, 49.2, 45.2, 14.2. Anal.
Calcd for C25H26O4: C, 76.90; H, 6.71. Found: C, 76.76; H, 6.45.
Dieth yl 5-(4-Nitr op h en yl)-6-p h en ylbicyclo[2.2.1]h ep t-2-
en e-2,3-d ica r boxyla te (1b). Isolated as a yellow resin after
chromatography (10% EtOAc in hexanes): 1H NMR (300 MHz,
CDCl3) δ 7.87 (app d, 2H) 6.85-7.05 (m, 7H), 4.28 (q, J ) 7.2
Hz, 4H), 3.53-3.60 (m, 4H), 2.41 (dm, J d ) 9.9 Hz, 1H), 2.14
(dm, J d ) 9.9 Hz, 1H), 1.33 (t, J ) 7.2 Hz, 6H); 13C NMR (75
MHz, CDCl3) δ 164.5, 164.4, 149.3, 147.6, 146.4, 146.1, 140.2,
129.5, 128.6, 128.2, 126.5, 122.8, 61.2, 51.0, 50.5, 49.7, 49.4, 45.1,
14.2. Anal. Calcd for C25H25NO6: C, 68.95; H, 5.79; N, 3.22.
Found: C, 68.66; H, 5.54; N, 3.08.
Dieth yl 5-(2-Meth oxyph en yl)-6-ph en ylbicyclo[2.2.1]h ept-
2-en e-2,3-d ica r boxyla te (1h ). Isolated as a clear resin after
chromatography (10% EtOAc in hexanes): 1H NMR (300 MHz,
CDCl3) δ 6.76-7.11 (m, 9H), 6.41 (app d, J app ) 8.1 Hz, 1H),
4.21-4.31 (overlapping quartets, J ) 6.9 Hz, 4H), 3.68 (br d, J
) 9.9 Hz, 1H), 3.59 (br d, J ) 1.2 Hz, 1H), 3.49 (br d, J ) 9.9
Hz, 1H), 3.46 (s, 3H), 3.31 (br d, J ) 1.2 Hz, 1H), 2.44 (dm, J d
) 9.3 Hz, 1H), 2.03 (dm, J d ) 9.3 Hz, 1H), 1.28-1.35 (overlap-
ping triplets, J ) 6.6 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 164.9,
164.3, 157.1, 148.0, 146.2, 141.5, 130.2, 128.5, 127.0, 126.9, 125.9,
125.5, 119.9, 109.4, 60.9, 54.4, 52.3, 49.2, 48.3, 45.2, 42.2, 14.1.
Anal. Calcd for C26H28O5: C, 74.26; H, 6.71. Found: C, 74.19;
H, 6.75.
Dieth yl 5-(4-Meth oxyph en yl)-6-ph en ylbicyclo[2.2.1]h ept-
2-en e-2,3-d ica r boxyla te (1c). Isolated as a white crystalline
solid after chromatography (10% EtOAc in hexanes) and recrys-
tallization from hexanes/CH2Cl2: mp 115.0-116.5 °C (hexanes/
CH2Cl2); 1H NMR (300 MHz, CDCl3) δ 6.94-7.06 (m, 3H), 6.86-
6.91 (m, 2H), 6.78, 6.56 (second-order AA′BB′ pattern, J ) 8.7
Hz, 4H), 4.22-4.30 (overlapping quartets, J ) 7.2 Hz, 4H), 3.65
5,6-Dip h en ylbicyclo[2.2.1]h ep t-2-en e (1i). Isolated as a
white crystalline solid after chromatography (petroleum ether)
and recrystallization from ligroin: mp 86.5-88.5 °C (ligroin);
1H NMR (300 MHz, CDCl3) δ 6.89-7.25 (m, 10H), 6.43 (s, 2H),
3.19 (s, 2H), 3.11 (s, 2H), 2.31 (dm, J d ) 8.4 Hz, 1H), 1.77 (dm,
J d ) 8.7 Hz, 1H) [lit.8 (400 MHz, CDCl3) δ 6.89-7.26 (m, 10H),
6.44 (d, J ) 1.8 Hz, 2H), 3.21 (d, J ) 1.8 Hz, 2H), 3.11 (m, 2H),
2.32 (d, J ) 8.8 Hz, 1H), 1.78 (m, 1H)].
(s, 3H), 3.52-3.54 (br, 1H), 3.42-3.47 (m, 3H), 2.39 (dm, J d
)
9.5 Hz, 1H), 2.06 (dm, J d ) 9.5 Hz, 1H), 1.29-1.34 (overlapping
triplets, J ) 7.2 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 164.6,
157.9, 147.1, 146.8, 141.4, 133.3, 129.6, 128.8, 127.7, 125.6, 113.4,
60.8, 55.2, 51.2, 50.7, 48.9, 48.4, 45.0, 14.1. Anal. Calcd for
C26H28O5: C, 74.26; H, 6.71. Found: C, 74.39; H, 6.56.
Dieth yl 5-(1-Naph th yl)-6-ph en ylbicyclo[2.2.1]h ept-2-en e-
2,3-d ica r boxyla te (1d ). Isolated as a yellow resin after chro-
matography (10% EtOAc in hexanes): 1H NMR (300 MHz,
CDCl3) δ 7.92 (app d, 1H), 7.58 (app d, 1H), 7.50 (app d, 1H),
7.24-7.34 (m, 5H), 6.78-6.81 (m, 2H), 6.69-6.71 (m, 2H), 4.22-
4.34 (m, 4H), 4.16 (br. d, J ) 9.6 Hz, 1H), 3.76 (d, J ) 1.2 Hz,
1H), 3.70 (br. d, J ) 9.6 Hz, 1H), 2.64 (br. d, J ) 9.6 Hz, 1H),
2.12 (br. d, J ) 9.6 Hz, 1H), 1.34 (t, J ) 7.2 Hz, 3H), 1.29 (t, J
) 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 164.8, 164.6, 147.7,
147.0, 140.8, 138.1, 133.5, 132.9, 128.6, 128.4, 127.1, 126.8, 125.8,
125.3, 125.2, 124.9, 124.8, 123.2, 61.0, 53.0, 50.2, 50.1, 45.3, 44.6,
14.2, 14.2. Anal. Calcd for C29H28O4: C, 79.04; H, 6.41. Found:
C, 78.74; H, 6.55.
7-ter t-Bu toxy-5,6-d ip h en ylbicyclo[2.2.1]h ep t-2-en e (1j).
Isolated as a white crystalline solid after chromatography
1
(petroleum ether): mp 85.0-88.0 (not recrystallized); H NMR
(300 MHz, CDCl3) δ 7.18-7.20 (m, 4H), 6.98-7.00 (m, 6H), 6.30
(s, 2H), 3.74 (s, 1H), 3.42, (s, 2H), 3.00 (s, 2H), 1.19 (s, 9H); 13
C
NMR (75 MHz, CDCl3) δ 142.0, 136.5, 131.5, 126.5, 124.8, 85.1,
74.4, 51.5, 49.9, 27.9. Anal. Calcd for C23H26O: C, 86.75; H, 8.23.
Found: C, 86.52; H, 8.20.
Ack n ow led gm en t. We are grateful to the Camille
and Henry Dreyfus Foundation (Faculty Start-up Grant
Program for Undergraduate Institutions) and West
Chester University (College of Arts and Sciences Faculty
Development Award) for funding this work. We would
also like to thank Dr. Gustave Mbuy for use of HPLC
instrumentation.
Dieth yl 5-(4-Am in op h en yl)-6-p h en ylbicyclo[2.2.1]h ep t-
2-en e-2,3-d ica r b oxyla t e (1e). Isolated as yellow crystals
(MeOH): mp 151.0-152.5 °C (MeOH); 1H NMR (300 MHz,
CDCl3) δ 6.95-7.07 (m, 3H), 6.86-6.91 (m, 2H), 6.64, 6.35
(second-order AA′BB′ pattern, J ) 8.4 Hz, 4H), 4.22-4.29
(overlapping quartets, J ) 7.2 Hz, 4H), 3.35-3.51 (multiple
broad resonances, 6H), 2.37 (br d, J d ) 9.3 Hz, 1H), 2.02 (dm,
Su p p or tin g In for m a tion Ava ila ble: X-ray crystallo-
graphic characterization data for 1a . Synthesis and charac-
terization data for 6b, and experimental procedures for
microscale and kinetics experiments. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O016212B
J . Org. Chem, Vol. 67, No. 16, 2002 5863