Facial Selectivity in the Diels-Alder Reactions of 5-Chloro-, 5-Bromo-, and 5-Iodo-l,3-cyclopentadiene and Derivatives

Article abstract of DOI:10.1021/jo961710j

A variety of dienophiles was used to assess the facial selectivity of Diels-Alder reactions in a series of 1,3-cyclopentadiene derivatives (1-3, 6-10) in which chlorine, bromine, and iodine were planenonsymmetric atoms pitted against hydrogen or methyl at C-5. The results were rationalized in terms of the major factor controlling the facial selectivity being related to steric hindrance between the diene and the dienophile. Selectivity did not correlate with reactivity. Facial selectivity in the reactions with 4-phenyl-l,2,4-triazoline-3,5-dione as the dienophile was also influenced by a second significant factor, postulated to be filled-orbital repulsion with the halogen substituent.

Full text of DOI:10.1021/jo961710j

J . Org. Chem. 1997, 62, 939-946
939
F a cia l Selectivity in th e Diels-Ald er Rea ction s of 5-Ch lor o-,
5-Br om o-, a n d 5-Iod o-1,3-cyclop en ta d ien e a n d Der iva tives
Mark A. Wellman, Lori C. Burry, J ohnathon E. Letourneau, J ohn N. Bridson,†
David O. Miller, and D. J ean Burnell*
Department of Chemistry, Memorial University of Newfoundland, St. J ohn’s,
Newfoundland A1B 3X7, Canada
Received September 5, 1996X
A variety of dienophiles was used to assess the facial selectivity of Diels-Alder reactions in a series
of 1,3-cyclopentadiene derivatives (1-3, 6-10) in which chlorine, bromine, and iodine were plane-
nonsymmetric atoms pitted against hydrogen or methyl at C-5. The results were rationalized in
terms of the major factor controlling the facial selectivity being related to steric hindrance between
the diene and the dienophile. Selectivity did not correlate with reactivity. Facial selectivity in
the reactions with 4-phenyl-1,2,4-triazoline-3,5-dione as the dienophile was also influenced by a
second significant factor, postulated to be filled-orbital repulsion with the halogen substituent.
In tr od u ction
in the energy required to deform the two addends into
their transition-state geometries that is the major con-
tributor to facial selectivity in the reactions of all the
simpler cyclopentadienes. Computational work requires
reliable, experimental selectivity data for comparison,
and further efforts on the computational side are now
hampered by inconsistencies and shortcomings in the
experimental data for the simplest dienes. Chlorine-
substituted dienes are of particular interest because in
the ab initio work the reaction of the simple 5-substituted
chloro diene 1 was the only instance in which deformation
of the dienophile (ethylene) was a major factor in the
determining facial selectivity, which was calculated to
be 73% syn to the chlorine.8 The facial selectivity in
Diels-Alder reactions involving 1 have been reported
twice. Breslow and co-workers9 indicated that with
4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) the product
was a mixture, and it was implied that the anti-addition
product was the major adduct. On the other hand,
Franck-Neumann and Sedrati10 reported that 1 showed
a modest preference (ratio 1.5:1) for syn-addition with
dimethyl acetylenedicarboxylate. The pentachloro diene
2 offers the same facial alternative as 1, but 2 is obviously
electronically quite different. Williamson and co-work-
ers11 claimed that maleic anhydride reacted with 2 91%
syn to the chlorine, and this reaction became almost
facially specific when catalyzed by AlCl3. Furthermore,
they reported a range of facial selectivities when 2
reacted with different dienophiles,11 as Ishida et al.7d have
recently done with a sulfur-substituted cyclopentadiene.
The pentamethyl derivative 3 added maleic anhydride
exclusively syn to the chlorine,4 but this facial selectivity
is helped by the fact that, with many dienophiles, 4
directs addition mainly anti to the C-5 methyl group.12
In contrast to Williamson’s and Ishida’s results, we
recently reported that facial selectivity with 5 showed
There are many examples of facial selectivity in Diels-
Alder reactions involving plane-nonsymmetric cyclopen-
tadienes.1 The published precedent indicates that cyclo-
pentadienes substituted at C-5 with fluorine,2 oxygen,3
or nitrogen4 all add dienophiles very predominantly syn
to the heteroatom. Indeed, even when the C-5 substitu-
ent is an sp3-hybridized carbon, there are instances in
which a preference for addition syn to carbon have been
reported,5 and a number of more complex carbon-
substituted examples have also been studied.6 Substitu-
tion with sulfur leads to Diels-Alder reactions with little
facial selectivity, and larger substituents give anti-
addition products predominantly.4,7
We have proposed, on the basis of an ab initio compu-
tational study,8 that it is the syn-versus-anti difference
† Author to whom correspondence regarding X-ray crystal structures
should be addressed.
X Abstract published in Advance ACS Abstracts, J anuary 15, 1997.
(1) Review: Fallis, A. G.; Lu, Y.-F. In Advances in Cycloaddition;
Curran, D. P., Ed.; J AI Press, Inc.: Greenwich, CT, 1993; Vol. 3, pp
1-66.
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Am. Chem. Soc. 1955, 77, 4183-4184. (b) Mironov, V. A.; Dolgaya, M.
E.; Lukyanov, V. T.; Yankovskii, S. A. Zh. Org. Khim. 1976, 12, 1436-
1442. (c) J ones, D. W. J . Chem. Soc., Chem. Commun. 1980, 739-740.
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Commun. 1995, 839-840. (j) Cossu, S.; Cuomo, G.; De Lucchi, O.;
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1973, 3723-3726.
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1391-1394.
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112, 8980-8982. (c) Ishida, M.; Aoyama, T.; Beniya, Y.; Yamabe, S.;
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Am. Chem. Soc. 1969, 91, 6129-6138. (b) Williamson, K. L.; Hsu, Y.-
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S0022-3263(96)01710-0 CCC: $14.00 © 1997 American Chemical Society

940 J . Org. Chem., Vol. 62, No. 4, 1997
Wellman et al.
no dependence on the nature of the dienophile: addition
was exclusively anti to chlorine.13
1,2,3,4,5-Pentachloro-1,3-cyclopentadiene (2) was pre-
pared by a procedure based on that of McBee and
Smith.18 Deprotonation of 2 with n-butyllithium followed
by addition of CH3I gave the methyl analog 6. Diene 2
would also dimerize on standing, but this was less of a
problem than with 1. In order to compare our results
fairly with those of Williamson and co-workers,11 maleic
anhydride (MA) and styrene were also used as dieno-
philes with the polychlorinated dienes 2 and 6. Produc-
tion of the pentamethyl dienes 3, 9, and 10 was by
trapping the pentamethylcyclopentadienyl anion with the
appropriate electrophile: NCS, NBS, or I2. It should be
noted that chlorination of 4 was not an efficient process,
and diene 3 was always contaminated with 4, which was
inseparable without considerable losses. Therefore, reac-
tions involving 3 were always carried out with a mixture
of 3 and 4, but, as we had spectra for the adducts derived
from 4 in hand,12 the analysis of the adduct mixtures was
still straightforward. Dienes 3, 9, and 10 were reacted
with the same three dienophiles as were used with 1, 7,
and 8.
Systematic experimental results with chlorine-substi-
tuted dienes are clearly required. In this paper, the
reactions of chloro diene 1 are reported with different
dienophiles, and we reevaluate some of the previously
reported11 reactions of 2. We also extend the data for 3
to other dienophiles, and, to complement this work with
a diene electronically related to 2, we assess for the first
time the facial selectivity of reactions involving the
pentachloro methyl diene 6.
Cyclopentadienes substituted with bromine and iodine
have received little attention and need to be examined
more thoroughly. It had been implied that anti addition
was the exclusive mode of cycloaddition with dienes 7
and 8, in spite of yields of less than 40% for the
adducts.9,10,14 However, our calculations suggested that
some syn-addition products should be found with 7,
although we agree that the facial selectivity of 8 should
be extremely high.8 Thus, we have also measured facial
selectivities for dienes 7 and 8 as well as the pentamethyl
dienes 9 and 10, which might be expected to have a better
chance of providing mixtures of syn and anti adducts of
measurable proportions.
After an appropriate reaction time, the solvents were
evaporated from the reaction mixtures. Adduct ratios
1
were determined by careful integration of the H NMR
spectra of these crude mixtures, but, in most instances,
it was also evident from the simplicity of these spectra
that the very predominant process was the Diels-Alder
reaction; i.e., the degree of chemical transformation was
very high. Also, every adduct (11-31, 33, 35-54)
Resu lts a n d Discu ssion
The simple 5-chloro-, 5-bromo-, and 5-iodo-1,3-cyclo-
pentadienes (1, 7, and 8) are known compounds, which
were prepared from cyclopentadienylthallium and the
corresponding N-halosuccinimide.9,14 Because of possible
complications arising from dimerization or isomerization
of the dienes to plane-symmetric 1- and 2-halo-1,3-
cyclopentadienes by a 1,5-sigmatropic mechanism,9 solu-
tions of the dienes were added directly to cool solutions
of dienophiles. Three dienophiles of very different char-
acteristics were employed. N-Phenylmaleimide (NPM)
is a relatively reactive ethylene derivative, which was
likely to best mimic the simple dienophile (ethylene itself)
used in our initial computational work.8 4-Phenyl-1,2,4-
triazoline-3,5-dione (PTAD)15 is a reactive, heteroatomic
dienophile that resembles NPM in its nonreacting por-
tion. It has been implicated in nonconcerted Diels-Alder
reactions.16 Tetracyanoethylene (TCNE) is the most
reactive dienophile,17 but also more sterically demanding
than either NPM or PTAD in the exo-region of its Diels-
Alder transition state.
(13) Burry, L. C.; Bridson, J . N.; Burnell, D. J . J . Org. Chem. 1995,
60, 5931-5934.
(14) Breslow, R.; Hoffman, J . M., J r. J . Am. Chem. Soc. 1972, 94,
derived from dienes 1-3 and 6-10 arose by reaction with
the intended diene, not a plane-symmetric isomer result-
ing from a 1,5-sigmatropic rearrangement. There were
two exceptions. The NMR spectra of the crude products
2110-2111.
(15) Cookson, R. C.; Gupte, S. S.; Stevens, I. D. R.; Watts, C. T.
Organic Syntheses; Wiley: New York, 1988; Collect. Vol. VI, pp 936-
940.
(16) J ensen, F.; Foote, C. S. J . Am. Chem. Soc. 1987, 109, 6376-
6385.
(17) Sauer, J .; Wuest, H.; Mielert, A. Chem. Ber. 1964, 97, 3183-
3207.
(18) McBee, E. T.; Smith, D. K. J . Am. Chem. Soc. 1955, 77, 389-
391.

Facial Selectivity in Diels-Alder Reactions
J . Org. Chem., Vol. 62, No. 4, 1997 941
Ta ble 1. Rela tive Am ou n ts (%) of th e An ti-Ad d u cts fr om
th e Rea ction s of Ch lor in e-Su bstitu ted Dien es w ith
Va r iou s Dien op h iles
Calculations predicted that ethylene should add to
diene 1, via CS-constrained transition states, preferen-
tially to the face syn to the chlorine, i.e., only 27% anti-
addition.8 Our experiments with the ethylenic dieno-
philes NPM and NQ gave exellent agreement with this
calculated selectivity (Table 1). If the reason for the
facial selectivity was largely steric, then the pentachloro
diene 2 should react with selectivity similar to that of 1.
The selectivity that Williamson11 reported for the reaction
of 2 with MA was 9% anti (21), which was significantly
more selective than the reaction of 1. However, in our
hands, 2 with MA and also with NPM showed selectivity
more like that of 1 (Table 1). Our results were in fact
similar to the selectivity Williamson gave for 2 with
another ethylenic dienophile, 1,4-benzoquinone (40%
anti-adduct), and we conjecture that the slight attenua-
tion of selectivity of 2 relative to 1 was due to the
necessity of reacting 2 at higher temperatures or the fact
that in the transition state for syn-addition with 2 the
C-5 chlorine must become coplanar with four other
chlorines, whereas in 1 the C-5 chlorine becomes coplanar
with hydrogens. We noticed that 21 and 22 were
sparingly soluble in CDCl3. Hence, the ratio reported
previously may have been colored by the relative solubili-
ties of the adducts.
dienophile
diene
NPM
MA
NQ
styrene
PTAD
TCNE
70
1
2
3
6
21
42
0
28
40a
0
58
78
100
81
37
0b
0
67
25
0
0
a
b
The result is for 1,4-benzoquinone, ref 11a. Reference 4.
Ta ble 2. Rela tive Am ou n ts (%) of th e An ti-Ad d u cts fr om
th e Rea ction s of Br om in e- a n d Iod in e-Su bstitu ted Dien es
w ith Th r ee Dien op h iles
dienophile
diene
NPM
PTAD
TCNE
7
9
8
85
50
100
100
96
100
100
100
100
95
100
100
10
of the reactions of 6 with NPM and with MA showed two
sets of adduct signals, but the minor adducts proved to
be unsymmetrical (tentatively 32 and 34). Facial selec-
tivities with the chlorine-substituted dienes are sum-
marized in Table 1, and selectivities with the bromine-
and iodine-substituted dienes are found in Table 2. Some
effort was made to obtain a sample of each adduct in a
form that was homogeneous by NMR; therefore, almost
every adduct mixture was subjected to chromatography.
This was successful in most instances in which an adduct
was produced in a reasonable proportion. For many
adducts, the relative stereochemistry was determined by
measurement of NOE’s in the 1H NMR spectra of the
homogeneous adducts. Nevertheless, single-crystal X-ray
structure determinations19 were performed on 13 adducts
for which NOE’s were either ambiguous or impossible.
For some of the less stable adducts we had to rely on an
analysis of trends in the NMR spectra in order to infer
the stereochemistry.
An effort was also made to verify that adduct ratios
were the result of kinetically controlled processes. Iso-
lated adducts were heated for long periods at or above
the temperatures used for their formation, sometimes in
the presence of a surrogate dienophile. In no instance
was there a hint of the development of symmetrical or
unsymmetrical isomeric adducts, or of dimers of the
diene, or of products derived from surrogate dienophiles.
In the Diels-Alder reactions of the 1,3-cyclopentadiene
derivatives under study, there must be a steric interac-
tion between the incoming dienophile and the syn-
substituent at C-5 of the diene, but our computational
work suggested that the facial selectivity comes from the
energy required to deform the addends into their transi-
tion-state geometries.8 It seems that at the transition
state the steric hindrance has been translated largely into
this deformation because the calculations indicated very
little interaction energy (between the dienophile and the
diene) at the transition state. Thus, we propose that,
with 5-substituted 1,3-cyclopentadienes, facial selectivity
can be traced back mainly to the difference in the
magnitudes of the dienophile-diene steric interactions,
syn versus anti.
With TCNE, two CN groups extend into the exo region
of the Diels-Alder transition state, and these would be
expected to interact unfavorably with a syn-chlorine on
1. Indeed, with TCNE the major adduct 18 (70%) was
the result of anti-addition. PTAD was expected to
present less steric hindrance toward a syn-chlorine, but
its reactions with both 1 and 2 suggested otherwise
because their major adducts 16 and 26 were the results
of anti-addition. The reason for this behavior became
apparent from the reactions with dienes 3 and 6, in which
a C-5 chlorine was pitted against a methyl group. Diene
4 adds dienophiles mainly to its sterically less hindered
face, anti to its C-5 methyl.12 This, in concert with the
tendency seen with 1 and 2 to add ethylenic dienophiles
syn to the chlorine, resulted in additions of NPM, MA,
and NQ exclusively syn to the chlorine with 3 and 6.
Whereas the selectivities of TCNE and PTAD were
similar with 1, these dienophiles showed dramatically
opposite selectivities with 3. TCNE, like the ethylenic
dienophiles, added exclusively syn to the chlorine (30).
PTAD added exclusively anti (29) to the chlorine of 3 and
81% anti (38) to the chlorine of 6. From these results it
was inferred that the reactions of PTAD were also
(19) Atomic coordinates for the X-ray structures of 16, 18, 26, 27,
29, 30, 38, 42, 43, 48, 49, 50, and 51 have been deposited with the
Cambridge Crystallographic Data Centre. The coordinates can be
obtained, on request, from the Director, Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK.

942 J . Org. Chem., Vol. 62, No. 4, 1997
Wellman et al.
affected by a second phenomenon, which was not steric
hindrance. The possibility of an attractive interaction
between the C-5 hydrogen of 1 or 2 and a nitrogen lone-
pair from PTAD, which might have enhanced anti-
addition, was ruled out because in 3 and 6 the C-5
hydrogen had been replaced by a methyl group. What
was consistent with these observations was either a
destabilizing electrostatic interaction in the syn transi-
tion state, as might have been expected with a more ionic,
less concerted mechanism,16 or a filled-orbital repulsion
of the type postulated by Coxon et al.20
The behavior of 2 and of 6 with styrene suggested that
the filled-orbital explanation was more plausible. In
contrast with the symmetrical dienophiles, styrene,
which must react via an unsymmetrical transition state
that also is likely to be asynchronous, reacted with 2 (via
an endo transition state) mainly by anti-addition (24).
Nevertheless, styrene gave only 25% anti-adduct (36)
with 6, completely in accord with an increase in the steric
hindrance on the anti face. The same trend might have
been expected if the selectivity with PTAD were the
result of an asynchronous process.
syn to sulfur, a lone-pair-bearing group, just as we
suggest occurred with the halogenated dienes.
Any rationalization based on steric hindrance must
take into account two issues. The first is the “size” of
the substituents, and the other is geometry. For these
Diels-Alder reactions, using A values as a measure of
steric hindrance would lead to no correlation with facial
selectivity, because the geometry8 of these Diels-Alder
reactions is very different to that of axial substituents
on cyclohexane. Simple van der Waals radii of the
substituents do correlate with facial selectivity, with the
exception of hydrogen. Hydrogen seems to exert a steric
presence larger than its van der Waals radius would
suggest, but the steric hindrance provided by a C-H
bond, which uniquely involves an sp3-to-s linkage, may
be more than a match for carbon bonds to the atoms that
give syn-adducts, viz. C-F,2 C-O,3 C-N,4 and, as we
have shown, C-Cl. Prompted by the results reported
here, we are using high-level ab initio methods to
investigate the steric influences of these bonds in the
Diels-Alder reaction as well as to clarify the source of
PTAD’s anti-directing factor.
As seen in Table 2, the Diels-Alder reaction of the
bromine-substituted diene 7 with NPM was not ste-
reospecific, 15% of the syn-adduct 39 was detected, but,
with the more sterically demanding dienophile TCNE,
all the product (43) was derived by anti-addition. PTAD
again showed an aversion for addition syn to a lone-pair-
bearing halogen in its reaction of 7. The pentamethyl
diene 9 displayed no facial selectivity whatsoever with
NPM, indicating a fortuitous balance in the steric factors.
Anti-adducts (46 or 48) predominated in the reactions of
9 with PTAD and TCNE. The results of additions with
the iodine-substituted dienes 8 and 10 were not unex-
pected on the basis of the computational data.8 Addition
of every dienophile was exclusively anti, which showed
that sterically even a methyl group was completely
subjugated by iodine.
Recently, Inagaki and co-workers7d proposed that Di-
els-Alder reactions are members of a class of reactions
in which reactivity enhances selectivity. To illustrate
this phenomenon, they reported the facial selectivities
of 5-(phenylthio)-1,3-cyclopentadiene (55) with MA, NPM,
PTAD, and TCNE. Reactivity increased in that order,
and so did the facial selectivity, from 55% anti-addition
with MA up to 100% anti-addition with TCNE. The data
in Table 1 do not correlate with reactivity, but it might
be argued that rigorous rate data in these systems are
not available. Thus, we decided to probe the reactivity-
selectivity parameter in a different way. Two reactions
were accelerated by catalysis. The reaction of 1 with
NPM was carried out in the presence of 0.3 molar equiv
of SnCl4. The reaction was over very quickly, but the
proportion of syn-adduct 11 increased very marginally,
from 79% to only 81%. The SnCl4-catalyzed reaction of
7 with NPM showed no significant change in the propor-
tion of the anti-adduct 40, which remained at 85%.
Obviously, enhancement of selectivity by reactivity is
either tiny or negligible in these reactions. In light of
our work, Inagaki’s data can be rationalized as follows:
NPM and MA are similar in shape and similar in facial
selectivity. TCNE is more sterically demanding than is
NPM in the exo region, so syn-addition is discouraged,
and the nitrogen lone-pairs of PTAD may resist addition
Exp er im en ta l Section
Gen er a l Meth od s. N-Phenylmaleimide (NPM), 1,4-naph-
thoquinone (NQ), and 4-phenyl-1,2,4-triazoline-3,5-dione
(PTAD)15 were purified by sublimation under vacuum. All
reactions were performed under nitrogen. Adducts were
usually purified by flash chromatography on silica gel with
elution with hexane containing an increasing proportion of
EtOAc and then recrystallization. IR spectra (cm-1) were
recorded as casts. Absorption intensities: s, strong; m,
medium; w, weak. 1H NMR spectra were obtained at 300 MHz
in CDCl3 solution unless otherwise noted; chemical shifts are
relative to internal TMS; apparent multiplicities are reported
here because in many instances the signals are second order;
standard abbreviations are used for multiplicities (nar )
narrow). NOE measurements were made with difference
spectra, using previously described parameters.21 NOE data
take this form: saturated signal (enhanced signal, enhance-
ment). 13C NMR spectra are at 75 MHz in CDCl3 unless
otherwise noted; chemical shifts are relative to a solvent
resonance. MS data are m/ z (% of largest peak).
1,2,3,4,5-P en ta ch lor o-1,3-cyclop en ta d ien e (2). A solu-
tion of hexachlorocyclopentadiene (20.4 g, 74.9 mmol) in
acetone (8.0 mL) was cooled in an ice bath as a solution of
SnCl2‚H2O (17.2 g, 76.7 mmol) in acetone (30 mL) was added
at a rate such as to maintain the temperature of the diene
solution in the 30-35 °C range. After addition was complete
(approximately 10 min), the brown solution was stirred at rt
for 1 h. The acetone was removed under vacuum, and the
residue was taken up in CCl4. This solution was washed with
H2O and brine and then dried over CaCl2. Vacuum distillation
(73-76 °C/4 Torr) provided 2 as a yellow liquid (12.1 g, 68%).
IR: 2938 (m), 1603 (s). 1H NMR: δ 4.75 (s). 13C NMR: δ
129.6, 129.0, 60.2. MS: 244 (0.3), 242 (5), 240 (14), 238 (22)
and 236 (14) all M+, 207 (11), 205 (49), 203 (100), 201 (79),
171 (2), 169 (7), 167 (8), 135 (2), 133 (9), 131 (13), 98 (6), 96
(20), 61 (22), 60 (11).
1,2,3,4,5-P en ta ch lor o-5-m eth yl-1,3-cyclopen ta d ien e (6).
A 2.5 M solution of n-butyllithium (2.21 mL, 5.53 mmol) in
hexanes was added dropwise to a solution of 2 (1.01 g, 4.25
mmol) in dry THF (40 mL) at -78 °C. Iodomethane (0.35 mL,
5.5 mmol) was added, and the mixture was allowed to warm
slowly to rt. The solution was concentrated under vacuum,
and the brown residue was redissolved in CH2Cl2. The
solution was washed with water and brine and then dried over
anhydrous MgSO4. Flash chromatography with hexane as the
(20) Coxon, J . M.; Fong, S. T.; McDonald, D. Q.; Steel, P. J .
Tetrahedron Lett. 1993, 34, 163-166.
(21) Gillard, J . R.; Newlands, M. J .; Bridson, J . N.; Burnell, D. J .
Can. J . Chem. 1991, 69, 1337-1343.

Facial Selectivity in Diels-Alder Reactions
J . Org. Chem., Vol. 62, No. 4, 1997 943
eluent gave 6 (0.719 g, 67%) as an orange oil. IR: 2983, 2929,
2859, 1601, 1569, 1437, 1374. 1H NMR: δ 1.69 (s). 13C
NMR: δ 134.3, 127.4, 69.7, 23.8. MS: 258 (1), 256 (7), 254
(24), 252 (34) and 250 (22) all M+, 239 (3), 237 (5), 235 (3),
223 (0.5), 221 (10), 219 (48), 217 (100), 215 (75), 186 (3), 184
(24), 182 (76), 180 (79), 149 (0.7), 147 (5), 145 (16), 143 (10),
109 (23), 108 (17), 74 (26).
(7r )- (17) a n d (7s)-7-Ch lor obicyclo[2.2.1]h ep t-5-en e-
2,2,3,3-tetr a n itr ile (18). The same procedure as for 11/12
was followed except that TCNE was used as the dienophile.
1
Syn-adduct 17 (white solid). Mp: 200-201 °C. IR: 2254. H
NMR: δ 6.79 (2H, t, J ) 2.2 Hz), 4.35 (1H, t, J ) 1.5 Hz), 4.04
(2H, nar m). NOE data: 6.79 (4.35, 0.5%; 4.04, 2%), 4.35 (6.79,
0.5%). 13C NMR (CD3COCD3): δ 140.0, 113.0, 111.8, 66.2,
59.6, 46.3. MS: no M+, 201 (1), 193 (3), 166 (7), 139 (4), 129
(2), 128 (3), 102 (31), 100 (100), 76 (9), 65 (23). HRMS calcd
for C11H5N4 (M+ - Cl): 193.0514, found 193.0506.
(3ar,4r,7a,7ar,8r )- (11) an d (3ar,4r,7r,7ar,8s)-8-Ch lor o-
3a ,4,7,7a -tetr a h yd r o-2-p h en yl-4,7-m eth a n o-1H-isoin d ole-
1,3(2H)-d ion e (12). A solution of cyclopentadienylthallium
(0.576 g, 2.14 mmol) and N-chlorosuccinimide (0.293 g, 2.14
mmol) in ether (20 mL) under N2 was stirred in an ice bath
for 1 h. While still cool, the resulting suspension was filtered
quickly through a plug of glass wool into a solution of NPM in
C6H6 (10 mL). The stirred solution was returned to the ice
bath for 12 h before being allowed to warm to rt. The solution
was concentrated under vacuum to provide a cream-colored
solid. Flash chromatography provided a sample of each
adduct, 0.216 g (37%) of 11 and 0.074 g (13%) of 12, for
spectroscopic analysis. Syn-adduct 11 (colorless solid from
EtOAc/hexane). Mp: 166-167.5 °C. IR: 1711. 1H NMR: δ
7.44-7.37 (3H, m), 7.14 (2H, br d, J ) 8.2 Hz), 6.32 (2H, t, J
) 2.2 Hz), 4.07 (1H, br t, J ) 1.6 Hz), 3.81 (2H, dd, J ) 1.6,
3.0 Hz), 3.48 (2H, m). NOE data: 6.32 (7.14, 0.5%; 4.07, 1.3%;
3.48, 3%), 4.07 (6.32, 0.7%; 3.48, 3%), 3.81 (3.48, 4%), 3.48
(6.32, 3%; 4.07, 7%; 3.81, 4%). 13C NMR: δ 176.1, 134.7, 131.7,
129.1, 128.7, 126.5, 70.8, 50.3, 43.7. MS (GC-MS): 275 (7) and
273 (21) both M+, 238 (1), 210 (1), 174 (12), 173 (100), 145 (4),
129 (17), 126 (4), 119 (27), 103 (8), 100 (6), 91 (43), 77 (10), 65
(23), 54 (12). HRMS calcd for C15H1235ClNO2: 273.0556, found
273.0547.
Anti-adduct 18 (colorless crystals from hexane/CH2Cl2).
Mp: 206-207.5 °C. IR: 2255. 1H NMR: δ 6.69 (2H, nar m),
4.52 (1H, nar m), 4.09 (2H, q, J ≈ 1.8 Hz). 13C NMR (CD3-
COCD3): δ 136.2, 112.7, 111.9, 68.1, 60.8, 46.0. MS: no M+,
201 (1), 193 (5), 166 (10), 139 (4), 129 (2), 128 (4), 102 (38),
100 (100), 76 (11), 65 (30). HRMS calcd for C11H5N4 (M+
-
Cl): 193.0514, found 193.0514. The structure of 18 was
determined by X-ray crystallography.19
(3a r,4â,7â,7a r,8s)- (19) a n d (3a r,4â,7â,7a r,8r )-4,5,6,7,8-
P en ta ch lor o-3a ,4,7,7a -tetr a h yd r o-2-p h en yl-4,7-m eth a n o-
1H-isoin d ole-1,3-d ion e (20). Diene 2 (3 equiv) and NPM in
C6H6 were refluxed for 12 h. Sparingly soluble syn-adduct 19
(colorless crystals from acetone). Mp: 286-287 °C. IR: 1715.
1H NMR: δ 7.48-7.44 (3H, m), 7.16 (2H, m), 4.33 (1H, s), 4.00
(2H, s). 13C NMR: δ 169.7, 131.7, 130.7, 129.3, 129.2, 126.4,
80.2, 78.4, 52.6. MS: 417 (1), 415 (6), 413 (17), 411 (27), 409
(17) all M+, 242 (2), 240 (6), 238 (10), 236 (6), 233 (1), 231 (7),
229 (14), 227 (11), 205 (4), 203 (8), 201 (6), 173 (100), 119 (23),
91 (17), 54 (17). HRMS calcd for C15H837Cl35Cl4NO2: 410.8968,
found 410.8949. Anal. Calcd for C15H8Cl5NO2: C, 43.78; H,
1.96; N, 3.40. Found: C, 43.29; H, 1.89; N, 3.39.
Anti-adduct 12 (colorless solid). Mp: 169.5-171 °C. IR:
1719. 1H NMR: δ 7.47-7.38 (3H, m), 7.13 (2H, br d, J ) 6.9
Hz), 6.26 (2H, nar m), 4.06 (1H, nar m), 3.64 (2H, nar m), 3.45
(2H, dd, J ) 1.6, 3.0 Hz). NOE data: 6.26 (7.13, 0.6%; 3.64,
3%), 4.06 (3.64, 3%; 3.45, 4%), 3.64 (6.26, 3%; 4.06, 4%; 3.45,
1.3%), 3.45 (7.13, 0.5%; 4.06, 10%; 3.64, 4%). 13C NMR: δ
174.9, 131.6, 129.2, 128.8, 126.5, 72.5, 51.5, 42.8. MS (GC-
MS): 275 (8) and 273 (25) both M+, 238 (1), 210 (1), 174 (23),
173 (100), 145 (4), 129 (19), 126 (14), 119 (27), 103 (9), 100
Anti-adduct 20 (colorless crystals from hexane/MeOH). Mp:
221-223 °C. IR: 1722. 1H NMR: δ 7.51-742 (3H, m), 7.16
(2H, m), 4.47 (1H, s), 3.78 (2H, s). NOE data: 4.47 (3.78, 6%),
3.78 (4.47, 14%). 13C NMR: δ 169.1, 130.7, 130.0, 129.5, 126.4,
81.4, 74.6, 51.9. MS: 415 (2), 413 (6), 411 (8), 409 (5) all M+,
242 (1), 240 (4), 238 (7), 236 (4), 231 (4), 229 (9), 227 (7), 205
(3), 203 (6), 201 (5), 173 (100), 119 (15), 91 (13), 54 (15). Anal.
Calcd for C15H8Cl5NO2: C, 43.78; H, 1.96; N, 3.40. Found: C,
43.20; H, 2.02; N, 3.36.
(3a r,4â,7â,7a r,8s)- (21) a n d (3a r,4â,7â,7a r,8r )-4,5,6,7,8-
P en ta ch lor o-3a ,4,7,7a -tetr a h yd r o-4,7-m eth a n oisoben zo-
fu r a n -1,3-d ion e (22). Diene 2 and MA (1.5 equiv) in toluene
was refluxed for 6 h and then at 70 °C for 2 days. Syn-adduct
21 (colorless solid from EtOAc/hexane). Mp: 211-212 °C.
IR: 1864, 1788, 1588. 1H NMR: δ 4.33 (1H, s), 4.14 (2H, s).
[1H NMR for corresponding diacid: δ 4.14 (1H, s), 4.01 (2H,
s).] 13C NMR: δ 164.5, 132.3, 80.3, 73.4, 54.1. MS: 340 (2),
338 (7), 336 (11), 334 (6) all M+, 303 (2), 301 (4), 299 (3), 261
(2), 259 (6), 257 (14), 255 (10), 244 (4), 242 (21), 240 (71), 238
(100), 236 (68), 233 (5), 231 (21), 229 (45), 227 (36), 207 (4),
205 (17), 203 (34), 201 (26), 259 (13), 157 (20), 96 (19). HRMS
calcd for C9H335Cl437ClO3: 335.8495, found 335.8466. Anal.
Calcd for C9H3Cl5O3: C, 32.14; H, 0.90. Found: C, 31.92; H,
0.95.
Anti-adduct 22 (from mixture containing 21 and MA). 1H
NMR: δ 4.45 (1H, s), 4.00 (2H, s). [1H NMR of corresponding
diacid: δ 4.32 (1H, s), 3.80 (2H, s). NOE data: 4.32 (3.80,
12%).]
(1R*,4S*,5S*,7R*)- (23) a n d (1R*,4S*,5S*,7S*)-1,2,3,4,7-
P en ta ch lor o-5-p h en ylbicyclo[2.2.1]h ep t-2-en e (24). Di-
ene 2 and styrene (1.1 equiv) in p-xylene were refluxed at 100
°C for 12 h. Syn-adduct 23 (from mixture containing a small
amount of a dimer of 2). 1H NMR: δ 7.35-7.29 (3H, m), 7.10
(2H, m), 4.18 (1H, d, J ) 1.7 Hz), 3.96 (1H, dd, J ) 4.4, 9.5
Hz), 2.90 (1H, dd, J ) 9.5, 12.8 Hz), 2.40 (1H, ddd, J ) 1.7,
4.4, 12.8 Hz). NOE data: 3.96 (7.10, 3%; 2.90, 4%). 13C
NMR: δ 134.4, 132.1, 131.9, 128.8, 128.4, 128.1, 77.9, 77.5,
72.7, 52.2, 40.8.
(14), 91 (47), 77 (12), 65 (28), 54 (14). HRMS calcd for C15H12
-
35ClNO2: 273.0556, found 273.0549.
(1r,4r,4a r,9a r,11r )- (13) a n d (1r,4r,4a r,9a r,11s)-11-
Ch lor o-1,4,4a ,9a -tetr a h yd r o-1,4-m eth a n oa n th r a cen e-9,-
10-d ion e (14). The same procedure as for 11/12 was followed
except that NQ was used as the dienophile. The adducts
1
decomposed rapidly; thus, the H NMR data are nonaromatic
signals from crude adduct mixtures. Syn-adduct 13. 1H
NMR: δ 6.13 (2H, t, J ) 2.1 Hz), 3.81 (1H, t, J ) 1.8 Hz), 3.63
(2H, dd, J ) 1.6, 2.4 Hz), 3.50 (2H, nar m). Anti-adduct 14.
1H NMR: δ 6.09 (2H, nar m), tentatively 3.81 (1H, nar m,
probably coincident with the corresponding signal for 13), 3.66
(2H, nar m), 3.35 (2H, nar m).
(10s)- (15) a n d (10r )-10-Ch lor o-5,8-d ih yd r o-2-p h en yl-
5,8-m eth a n o-1H-[1,2,4]tr ia zolo[1,2-a ]p yr id a zin e-1,3(2H)-
d ion e (16). The same procedure as for 11/12 was followed
except that PTAD was used as the dienophile. Syn-adduct 15
(colorless solid). Mp: 175.5-176 °C. IR: 1725. 1H NMR: δ
7.47-7.38 (5H, m), 6.56 (2H, t, J ) 2.1 Hz), 5.05 (2H, nar m),
4.23 (1H, t, J ) 1.3 Hz). NOE data: 6.56 (5.05, 3%; 4.23, 1.4%),
4.23 (6.56, 0.5%; 5.05, 3%). 13C NMR: δ 158.0, 132.8, 129.2,
128.6, 125.6, 67.8, 65.6. MS: 277 (12) and 275 (36) both M+,
240 (100), 214 (2), 156 (4), 121 (32), 119 (63), 102 (17), 100
(56), 91 (23), 78 (28), 65 (41), 64 (17). HRMS calcd for C13H10
-
35ClN3O2: 275.0461, found 275.0453.
Anti-adduct 16 (colorless crystals from EtOAc/hexane). Mp:
166.5-167.5 °C. IR: 1719. 1H NMR: δ 7.47-7.34 (5H, m),
6.47 (2H, dt, J ) 0.6, 1.8 Hz), 5.11 (2H, q, J ) 1.8 Hz), 4.56
(1H, nar m). 13C NMR: δ 157.9, 129.2, 129.0, 128.7, 125.5,
78.5, 66.4. MS: 277 (14) and 275 (41) both M+, 240 (42), 214
(2), 158 (8), 156 (24), 121 (52), 119 (93), 102 (31), 100 (100), 91
(27), 78 (22), 65 (58), 64 (20). HRMS calcd for C13H1035ClN3-
O2: 275.0461, found 275.0453. Anal. Calcd for C13H10ClN3-
O2: C, 56.72; H, 3.63; N, 15.27, found C, 56.66; H, 3.69; N,
15.36. The structure of 16 was confirmed by X-ray crystal-
lography.19
Anti-adduct 24. Orange oil. IR: 3033 (m), 2924 (m), 1748
(m), 1599 (s), 1278 (s). 1H NMR: δ 7.34 (3H, nar m), 7.10 (2H,
nar m), 4.49 (1H, s), 3.72 (1H, dd, J ) 4.9, 9.5 Hz), 2.74 (1H,
dd, J ) 9.5, 12.9 Hz), 2.58 (1H, dd, J ) 4.9, 12.9 Hz). NOE
data: 4.49 (3.72, 6%; 2.74, 2%), 3.72 (7.10, 4%; 4.49, 10%; 2.74,
4%). 13C NMR: δ 134.8, 130.2, 129.8, 128.6, 128.4, 128.3, 81.2,

944 J . Org. Chem., Vol. 62, No. 4, 1997
Wellman et al.
79.8, 74.1, 52.7, 41.7. MS: 342 (0.3, M+), 240 (2), 238 (3), 236
(2), 205 (2), 203 (3), 201 (3), 125 (11), 104 (100), 103 (7), 78
(8), 77 (6).
(1.90, 0.3%; 1.64, 0.7%). 13C NMR: δ 141.0, 111.3, 109.8, 83.0,
68.6, 50.9, 21.4, 12.4, 9.6. MS: no M+, 263 (2), 170 (100), 135
(84), 119 (51). The structure of 30 was determined by X-ray
crystallography.19
(5R,8S,10s)- (25) an d (5R,8S,10r )-5,6,7,8,10-P en tach lor o-
5,8-d ih yd r o-2-p h en yl-5,8-m eth a n o-1H-[1,2,4]tr ia zolo[1,2-
a ]p yr id a zin e-1,3(2H)-d ion e (26). Diene 2 and PTAD in
C6H6 were warmed from rt to 70 °C. Syn-adduct 25 (beige
crystals from petroleum ether/ether/MeOH). Mp: 160-165 °C
dec. IR: 1805 (m), 1742 (s). 1H NMR: δ 7.51-7.39 (3H, m),
7.32-7.25 (2H, m), 4.33 (1H, s). 13C NMR: δ 155.4, 129.8,
129.5, 129.4, 125.5, 87.4, 74.7. MS: 415 (0.2), 413 (0.7), and
411 (0.2) all M+, 244 (4), 242 (21), 240 (66), 238 (100), 236 (64),
207 (14), 205 (64), 203 (88), 202 (43), 201 (69), 119 (91), 91
(53), 64 (31). Anal. Calcd for C13H6Cl5N3O2: C, 37.76; H, 1.46;
N, 10.16. Found: C, 37.82; H, 1.49; N, 10.23.
Anti-adduct 26 (beige crystals from petroleum ether/ether/
MeOH). Mp: 144-145, 148 °C dec. IR: 1806 (m), 1750 (s).
1H NMR: δ 7.49-7.44 (3H, m), 7.32-7.27 (2H, m), 4.70 (1H,
s). 13C NMR: δ 155.2, 129.5 (many resonances), 128.0, 125.5,
89.2, 75.8. MS: 415 (2), 413 (3), and 411 (2) all M+, 244 (1),
242 (7), 240 (21), 238 (33), 236 (21), 207 (5), 205 (24), 203 (48),
202 (3), 201 (36), 119 (100), 91 (80), 64 (43). Anal. Calcd for
C13H6Cl5N3O2: C, 37.76; H, 1.46; N, 10.16. Found: C, 37.53;
H, 1.53; N, 10.14. The structure of 26 was determined by
X-ray crystallography.19
(3a r,4â,7â,7a r,8s)-4,5,6,7,8-P en t a ch lor o-3a ,4,7,7a -t et -
r a h yd r o-8-m et h yl-2-p h en yl-4,7-m et h a n o-1H -isoin d ole-
1,3-d ion e (31). Diene 6 and NPM (1.6 equiv) in C6H6 were
refluxed for 6 days and then refluxed in toluene for 24 h. In
the 1H NMR spectrum, signals were present for a minor
amount of an unsymmetrical adduct, likely 32. Chromatog-
raphy provided 75 mg (53%) of an off-white solid, still contain-
ing the unsymmetrical adduct, and recrystallization from
CH2Cl2/hexane gave 31 as colorless needles (mp 207-209 °C)
that were still contaminated with the second adduct, so
spectral data are for these needles. IR: 1782 (m), 1721 (s).
1H NMR: δ 7.48-7.37 (3H, m), 7.15-7.10 (2H, m), 4.06 (2H,
s), 1.65 (3H, s). 13C NMR: δ 170.1, 130.8, 130.5, 129.3, 129.2,
126.4, 91.6, 77.7, 53.6. MS: 431 (1), 429 (9), 427 (25), 425 (38),
423 (24) all M+, 394 (0.9), 392 (5), 390 (10), 388 (8), 256 (2),
254 (8), 252 (12), 250 (7), 247 (3), 245 (14), 243 (29), 241 (22),
173 (100), 119 (98). HRMS calcd for C16H1035Cl5NO2: 422.9153,
found 422.9170. Anal. Calcd for C16H10Cl5NO2: C, 45.16; H,
2.37; N, 3.29. Found: C, 44.97; H, 2.41; N, 3.27. Readily
discerned signals for putative 32. 1H NMR: δ 3.88 (1H, d, J
) 7.5 Hz), 3.60 (1H, d, J ) 7.5 Hz), 1.73 (3H, s). 13C NMR: δ
51.4, 49.7, 11.7.
(3ar,4r,7r,7ar,8s)-8-Ch lor o-3a,4,7,7a-tetr ah ydr o-2-ph en -
yl-4,7-m eth a n o-1H-isoin d ole-1,3-d ion e (27). A stirred so-
lution of 4 (250 mg, 1.83 mmol) in THF (25 mL) was cooled in
an ice bath as n-butyllithium (1.7 mL, 2.5 M in hexane) was
added. The resulting slurry was stirred for 15 min before
N-chlorosuccinimide (250 mg, 1.87 mmol) was added in one
portion. After being stirred for 2 h at 0 °C, the mixture was
diluted to two to three times the initial volume with ether,
and this solution was washed with saturated aqueous Na2S2O3
and H2O. The organic solution was dried over MgSO4, and
the solvent was removed under vacuum. The residue was
taken up in ether (15 mL), and NPM (260 mg, 150 mmol) was
added. The solution was stirred at rt for 24 h. The solvent
(3a r,4â,7â,7a r,8s)-4,5,6,7,8-P en t a ch lor o-3a ,4,7,7a -t et -
r a h yd r o-8-m et h yl-4,7-m et h a n oisoben zofu r a n -1,3-d ion e
(33). Diene 6 and MA (4 equiv) in toluene were refluxed for
1
8 days. In the H NMR spectrum, signals were present for a
minor amount of an unsymmetrical adduct, likely 34. Syn-
adduct 33 (from mixture containing small amount of 34).
Mp: 135 °C (sub). IR: 1852, 1783, 1594. 1H NMR: δ 4.22
(2H, s), 1.63 (3H, s). 13C NMR: δ 164.8, 131.0, 91.8, 77.6, 55.0,
18.7. MS (GC-MS): 352 (5), 350 (6), 348 (2) all M+, 322 (4),
317 (8), 315 (23), 313 (17), 256 (10), 252 (26), 252 (49), 250
(28), 247 (9), 245 (51), 243 (100), 241 (89), 219 (13), 217 (26),
216 (17), 215 (25), 209 (29), 207 (70), 205 (56), 172 (25), 171
(20), 170 (40), 86 (35), 85 (56). Signals for putative 34. 1H
NMR: δ 4.06 (1H, d, J ≈ 7.5 Hz), 3.79 (1H, d, J ≈ 7.5 Hz),
1.72 (3H, s).
1
was removed under vacuum, and H NMR analysis of the solid
residue showed signals for only one adduct derived from 3 as
well as signals for the adducts derived from 4. Flash chro-
matography gave a homogeneous sample of syn-adduct 27
(colorless crystals). Mp: 184-185 °C. IR: 1713. 1H NMR: δ
7.37 (3H, m), 7.06 (2H, d, J ) 7.1 Hz), 3.42 (2H, s), 1.64 (6H,
s), 1.43 (6H, s), 1.30 (3H, s). 13C NMR: δ 176.3, 135.5, 131.9,
129.2, 128.5, 126.6, 92.6, 61.3, 51.5, 18.6, 11.6, 11.4. MS: 343
(9, M+), 308 (3), 173 (8), 170 (100), 135 (43). HRMS calcd for
C20H2235ClNO2: 343.1338, found 343.1339. The structure of
27 was determined by X-ray crystallography.19
(1r,4r,4a r,9a r,11s)-11-Ch lor o-1,4,4a ,9a -tetr a h yd r o-1,-
2,3,4,11-p e n t a m e t h yl-1,4-m e t h a n oa n t h r a ce n e -9,10-d i-
on e (28). The same procedure as for 27 was followed except
that NQ was used as the dienophile. Syn-adduct 28 (colorless
solid). Mp: 194-200 °C dec. IR: 1672. 1H NMR (C6D6): δ
7.92 (2H, m), 7.08 (2H, m), 3.38 (2H, s), 1.39 (6H, s), 1.05 (3H,
s), 0.95 (6H, s). 13C NMR (C6D6): δ 195.9, 136.1, 135.3, 133.1,
125.8, 88.9, 64.0, 54.8, 17.7, 11.0, 10.7. MS: no M+, 267 (3),
157 (15), 152 (100), 137 (49).
(10r )-10-Ch lor o-5,8-d ih yd r o-5,6,7,8,10-p en ta m eth yl-2-
p h en yl-5,8-m eth a n o-1H-[1,2,4]tr ia zolo[1,2-a ]p yr id a zin e-
1,3(2H)-d ion e (29). The same procedure as for 27 was
followed except that PTAD was used as the dienophile. Anti-
adduct 29 (colorless crystals after preparative TLC). Mp: 127-
127.5 °C. IR: 1726. 1H NMR: δ 7.37 (5H, m), 1.79 (6H, s),
1.77 (6H, s), 1.59 (3H, s). 13C NMR: δ 158.9, 133.1, 131.1,
129.1, 128.4, 125.4, 84.7, 81.1, 19.8, 11.3, 10.4. MS: 347 (1)
and 345 (4) both M+, 330 (3), 256 (5), 170 (100), 135 (32, 119
(16). HRMS calcd for C18H2035ClN3O2: 345.1243, found
345.1242. The structure of 29 was determined by X-ray
crystallography.19
(7r )-7-Ch lor o-2,2,3,3-tetr a cya n o-1,4,5,6,7-p en ta m eth yl-
bicyclo[2.2.1]h ep t-5-en e (30). The same procedure as for
27 was followed except that TCNE was used as the dienophile.
Syn-adduct 30 (colorless solid). Mp: 135 °C dec. IR: 2245.
1H NMR: δ 1.90 (6H, s), 1.64 (6H, s), 1.39 (3H, s). NOE data:
1.90 (1.64, 0.9%; 1.39, 0.5%), 1.64 (1.90, 1.7%, 1.39, 2%), 1.39
(1R*,4S*,5S*,7R*)- (35) a n d (1R*,4S*,5S*,7S*)-1,2,3,4,7-
P en ta ch lor o-7-m eth yl-5-p h en ylbicyclo[2.2.1]h ep t-2-en e
(36). Diene 6 and styrene (3 equiv) in toluene were refluxed
for 9 days. Syn-adduct 35 (colorless solid). Mp: 53-54 °C.
1
IR: 3065, 3033, 2995, 2941, 2870, 1600, 1497, 1458, 1381. H
NMR: δ 7.36-7.28 (3H, m), 7.11 (2H, m), 4.07 (1H, dd, J )
4.2, 9.2 Hz), 2.97 (1H, dd, J ) 9.2, 12.7 Hz), 2.41 (1H, dd, J )
4.2, 9.2 Hz), 1.63 (3H, s). NOE data: 4.07 (7.11, 2%; 2.97,
4%), 2.97 (4.07, 4%; 2.41, 11%), 2.41 (7.11, 2%; 2.97, 11%).
MS: 358 (1), 356 (2), 354 (1) all M+, 258 (2), 256 (14), 254 (44),
252 (59), 250 (44), 237 (1), 235 (5), 233 (19), 231 (34), 229 (25),
221 (4), 219 (16), 217 (33), 215 (26), 198 (21), 196 (52), 194
(55), 186 (4), 184 (9), 182 (27), 180 (23), 127 (19), 125 (71), 104
(100).
Anti-adduct 36 (colorless crystals from hexane/ether). Mp:
94-96 °C. IR: 3064, 3032, 2999, 2944, 2869, 1603, 1512, 1454,
1383. 1H NMR: δ 7.36-7.31 (3H, m), 7.10 (2H, m), 3.65 (1H,
dd, J ) 4.6, 9.1 Hz), 2.66 (1H, dd, J ) 9.1, 13.2 Hz), 2.51 (1H,
dd, J ) 4.6, 13.2 Hz), 1.81 (3H, s). NOE data: 3.65 (2.66, 5%;
1.81, 1.6%), 2.66 (3.65, 2%; 2.51, 7%; 1.81, 0.7%), 2.51 (2.66,
9%), 1.81 (3.65, 8%; 2.66, 3%). MS: 358 (0.3), 356 (0.6), 354
(0.3) all M+, 256 (2), 254 (7), 252 (12), 250 (8), 219 (2), 217 (4),
215 (3), 196 (2), 194 (2), 182 (3), 180 (3), 125 (21), 104 (100).
(5R,8S,10s)- (37) an d (5R,8S,10r )-5,6,7,8,10-P en tach lor o-
5,8-d ih yd r o-10-m eth yl-2-p h en yl-5,8-m eth a n o-1H-[1,2,4]-
tr iazolo[1,2-a ]pyr idazin e-1,3(2H)-dion e (38). Diene 6 (0.167
g, and PTAD in C6H6 were refluxed for 12 h. Syn-adduct 37
(colorless crystals). Mp: 163-166 °C but first turning pink at
147 °C. IR: 1802 (m), 1749 (s). 1H NMR: δ 7.50-7.42 (3H,
m), 7.33-7.26 (2H, m), 1.63 (3H, s). 13C NMR: δ 155.4, 129.8,
129.4, 128.1, 125.5, 91.4, 84.5, 19.4. MS: 429 (0.1), 427 (0.6),
and 425 (0.1) all M+, 394 (0.8), 392 (2), 390 (1), 275 (1), 273
(3), 271 (2), 258 (3), 256 (20), 254 (64), 252 (100), 250 (62), 223
(0.5), 221 (6), 219 (29), 217 (60), 215 (47), 186 (1), 184 (12),
182 (36), 180 (38), 119 (54), 91 (29), 64 (18). Anal. Calcd for

Facial Selectivity in Diels-Alder Reactions
J . Org. Chem., Vol. 62, No. 4, 1997 945
C14H8Cl5N3O2: C, 39.33; H, 1.89; N, 9.83. Found: C, 39.25;
H, 1.89; N, 9.92.
Anti-adduct 45 (from the adduct mixture). 1H NMR: δ 7.41
(3H, m), 7.05 (2H, m), 3.51 (2H, s), 1.65 (6H, s), 1.58, 6H, s),
1.49 (3H, s).
Anti-adduct 38 (colorless crystals). Mp: 129-131 °C but
turning pink first at 125 °C. IR: 1805 (m), 1750 (s). 1H
NMR: δ 7.47-7.41 (3H, m), 7.31-7.27 (2H, m), 1.91 (3H, s).
13C NMR: δ 155.3, 129.6, 129.5, 129.1, 125.5, 92.0, 86.4, 20.7.
MS: 429 (0.9), 427 (2), and 425 (0.8) all M+, 392 (0.8), 390
(0.4), 275 (0.6), 273 (2), 271 (1), 258 (3), 256 (20), 254 (64), 252
(100), 250 (63), 221 (5), 219 (21), 217 (44), 215 (34), 186 (0.8),
184 (8), 182 (25), 180 (26), 119 (38), 91 (21), 64 (13). Anal.
Calcd for C14H8Cl5N3O2: C, 39.33; H, 1.89; N, 9.83. Found:
C, 39.34; H, 1.93; N, 10.03. The structure of 38 was deter-
mined by X-ray crystallography.19
(10r )-10-Br om o-5,8-d ih yd r o-5,6,7,8,10-p en t a m et h yl-2-
p h en yl-5,8-m eth a n o-1H-[1,2,4]tr ia zolo[1,2-a ]p yr id a zin e-
1,3(2H)-d ion e (46). The same procedure as for 44/45 was
followed except that PTAD was used as the dienophile. Anti-
adduct 46 (colorless crystals after preparative TLC). Mp: >95
°C dec. IR: 1778 (m), 1725 (s). 1H NMR: δ 7.36 (5H, m), 1.82
(6H, s), 1.75 (6H, s), 1.74 (3H, s). 13C NMR: δ 158.9, 134.2,
131.1, 129.1, 128.4, 125.4, 81.5, 21.7, 11.4, 11.1. MS: 391 (1)
and 389 (1) both M+, 256 (1), 216 (34), 214 (36), 135 (100).
The structure of 46 was determined by X-ray crystallography.19
(7r )- (47) a n d (7s)-7-Br om o-2,2,3,3-tetr a cya n o-1,4,5,6,7-
p en ta m eth ylbicyclo[2.2.1]h ep t-5-en e (48). The same pro-
cedure as for 44/45 was followed except that TCNE was used
as the dienophile. Syn-adduct 47 (from the adduct mixture).
1H NMR: δ 1.91 (6H, s), 1.83 (6H, s), 1.66 (3H, s).
(3ar,4r,7a,7ar,8s)- (39) an d (3ar,4r,7r,7ar,8r )-8-Br om o-
3a ,4,7,7a -tetr a h yd r o-2-p h en yl-4,7-m eth a n o-1H-isoin d ole-
1,3(2H)-d ion e (40). The same procedure as for 11/12 was
followed except that NBS was used as the halogen source. Syn-
adduct 39 (colorless solid from CH2Cl2/hexane). Mp: 194.5-
196 °C. IR: 1715. 1H NMR: δ 7.47-7.37 (3H, m), 7.14 (2H,
br d, J ) 7.0 Hz), 6.32 (2H, t, J ) 2.1 Hz), 4.15 (1H, t, J ) 1.3
Hz), 3.88 (2H, dd, J ) 1.8, 2.5 Hz), 3.52 (2H, m). NOE data:
6.32 (7.14, 0.8%; 4.15, 1.5%; 3.52, 3%), 4.15 (6.32, 0.6%; 3.52,
3%), 3.88 (3.52, 4%), 3.52 (6.32, 3%; 4.15, 6%; 3.88, 4%). 13C
NMR: δ 176.2, 135.2, 131.6, 129.1, 128.8, 126.5, 61.4, 50.7,
44.0. MS: 319 (23) and 317 (24) both M+, 238 (9), 173 (100),
146 (7), 144 (7), 129 (16), 119 (11), 91 (33), 65 (32). HRMS
calcd for C15H12NO2 (M+ - Br): 238.0867, found 238.0862.
Anti-adduct 48 (colorless solid after preparative TLC). Mp:
>150 °C dec. IR: 2248. 1H NMR (CDCl3/C6D6): δ 2.00/1.51
(3H, s), 1.86/2.29 (6H, s), 1.72/1.03. 13C NMR: δ 144.2, 111.4,
111.1, 86.8, 69.0, 48.1, 24.0, 12.2, 10.1. MS: no M+, 216 (13),
214 (16), 135 (100), 128 (59), 119 (25), 81 (2), 79 (7).
(3a r,4r,7r,7a r,8r )-3a ,4,7,7a -Tetr a h yd r o-8-iod o-2-p h en -
yl-4,7-m eth an o-1H-isoin dole-1,3(2H)-dion e (49). The same
procedure as for 11/12 was followed except that N-iodosuccin-
imide was used as the halogen source. Anti-adduct 49
(colorless crystals from hexane/CH2Cl2). Mp: 211-212.5 °C.
IR: 1707. 1H NMR: δ 7.47-7.38 (3H, m), 7.12 (2H, br d, J )
6.9 Hz), 6.29 (2H, t, J ) 1.8 Hz), 4.02 (1H, br s), 3.69 (2H, m),
3.57 (2H, dd, J ) 1.5, 2.9 Hz). NOE data: 6.29 (7.12, 0.7%;
3.69, 4%), 4.02 (3.69, 3%; 3.57, 6%), 3.69 (6.29, 4%; 4.02, 5%;
3.57, 2%), 3.57 (4.02, 11%; 3.69, 5%). 13C NMR: δ 174.7, 134.3,
131.4, 129.1, 128.8, 126.4, 53.4, 42.6, 41.0. MS: 365 (33, M+),
238 (39), 210 (17), 192 (41), 174 (19), 173 (48), 129 (16), 119
(16), 95 (11), 91 (65), 69 (39), 65 (100), 57 (43), 55 (42). HRMS
calcd for C15H12NO2 (M+ - I): 238.0867, found 238.0859. The
structure of 49 was confirmed by X-ray crystallography.19
(10r )-5,8-Dih yd r o-10-iod o-2-p h en yl-5,8-m et h a n o-1H -
[1,2,4]tr ia zolo[1,2-a ]p yr id a zin e-1,3(2H)-d ion e (50). The
same procedure as for 49 was followed except that PTAD was
used as the dienophile. Anti-adduct 50 (colorless crystals from
EtOAc/hexane). Mp: 133-134 °C. IR: 1713. 1H NMR: δ
7.48-7.34 (5H, m), 6.47 (2H, t, J ) 1.8 Hz), 5.16 (2H, q, J )
1.7 Hz), 4.41 (1H, br s). 13C NMR: δ 157.6, 130.7, 129.1, 128.6,
125.4, 70.2, 30.0. MS: 367 (12, M+), 254 (8), 241 (18), 240
(20), 192 (69), 177 (17), 151 (5), 121 (24), 119 (62), 93 (23), 91
(24), 79 (20), 65 (100), 64 (19). HRMS calcd for C13H10IN3O2:
366.9818, found 366.9799. The structure of 50 was determined
by X-ray crystallography.19
(7s)-7-Iod ob icyclo[2.2.1]h e p t -5-e n e -2,2,3,3-t e t r a n i-
tr ile (51). The same procedure as for 49 was followed except
that TCNE was used as the dienophile. Anti-adduct 51
(colorless crystals after treatment with charcoal from hexane/
CH2Cl2). Mp: 176 °C dec, 183-185 °C. IR: 2252. 1H NMR:
δ 6.71 (2H, nar m), 4.44 (1H, br s), 4.11 (2H, q, J ≈ 1.7 Hz).
13C NMR (CD3COCD3): δ 139.1, 113.4, 112.2, 63.2, 44.9, 30.3.
MS: 320 (8, M+), 192 (47), 166 (4), 128 (13), 76 (13), 65 (100).
HRMS calcd for C11H5N4 (M+ - I): 193.0514, found 193.0515.
Anal. Calcd for C11H5IN4: C, 41.28; H, 1.57; N, 17.50.
Found: C, 41.27; H, 1.58; N, 17.68. The structure of 51 was
determined by X-ray crystallography.19
Anti-adduct 40 (colorless solid from CH2Cl2/hexane). Mp:
188-189 °C. IR: 1716, 1594. 1H NMR: δ 7.47-7.37 (3H, m),
7.12 (2H, br d, J ) 7.0 Hz), 6.26 (2H, nar m), 4.06 (1H, br s),
3.66 (2H, m), 3.47 (2H, dd, J ) 1.5, 2.9 Hz). NOE data: 6.26
(7.12, 1.1%; 3.66, 3%), 4.06 (3.66, 3%; 3.47, 5%), 3.66 (6.26,
4%; 4.06, 5%; 3.47, 3%), 3.47 (4.06, 9%; 3.66, 4%). 13C NMR:
δ 174.8, 132.5, 131.5, 129.1, 128.8, 126.4, 63.2, 51.9, 42.8.
MS: 319 (63) and 317 (66) both M+, 238 (19), 173 (100), 146
(5), 144 (5), 129 (11), 119 (6), 91 (12), 65 (33). HRMS calcd for
C
15H12NO2 (M+ - Br): 238.0867, found 238.0863.
(10s)- (41) a n d (10r )-10-Br om o-5,8-d ih yd r o-2-p h en yl-
5,8-m eth a n o-1H-[1,2,4]tr ia zolo[1,2-a ]p yr a d izin e-1,3(2H)-
d ion e (42). The same procedure as for 39/40 was followed
except that PTAD was used as the dienophile. Syn-adduct 41.
1H NMR (nonaromatic signals from the adduct mixture): δ
6.53 (2H, br t, J ) 2.1 Hz), 5.07 (2H, m), 4.27 (1H, nar m).
Anti-adduct 42 (colorless crystals from CH2Cl2/hexane).
Mp: 170-170.5 °C. IR: 1719. 1H NMR: δ 7.45-7.34 (5H,
m), 6.47 (2H, dt, J ) 0.5, 1.9 Hz), 5.15 (2H, q, J ) 1.9 Hz),
4.51 (1H, nar m). 13C NMR: δ 158.8, 130.9, 129.6, 129.2, 128.7,
125.4, 68.9, 55.2. MS: 321 (11) and 319 (12) both M+, 240
(28), 202 (6), 200 (6), 177 (7), 146 (62), 144 (64), 121 (20), 119
(50), 91 (19), 78 (16), 65 (100), 64 (14). HRMS calcd for
C
13H10N3O2 (M+ - Br): 240.0772, found 240.0757. The
structure of 42 was determined by X-ray crystallography.19
(7s)-7-Br om ob icyclo[2.2.1]h ep t -5-en e-2,2,3,3-t et r a n i-
tr ile (43). The same procedure as for 39/40 was followed
except that TCNE was used as the dienophile. Anti-adduct
43 (colorless crystals from hexane/CH2Cl2). Mp: 215.5-217
°C. IR: 2254. 1H NMR: δ 6.70 (2H, nar m), 4.48 (1H, br s),
4.13 (2H, nar m). 13C NMR (CD3COCD3): δ 137.3, 113.0,
112.1, 61.4, 56.7, 45.9. MS: no M+, 193 (5), 166 (12), 146 (73),
144 (75), 128 (10), 76 (17), 65 (100). HRMS calcd for C11H5N4
(M+ - Br): 193.0514, found 193.0515. The structure of 43
was determined by X-ray crystallography.19
(3ar,4r,7r,7ar,8r )-3a,4,7,7a-Tetr ah ydr o-8-iodo-4,5,6,7,8-
p en ta m eth yl-2-p h en yl-4,7-m eth a n o-1H-isoin d ole-1,3-d i-
on e (52). The same procedure as for 27 was followed except
that I2 was used as the halogen source. Anti-adduct 52 (pale
yellow solid after preparative TLC, but still contaminated by
some unreacted NPM). Mp: 105-108 °C. IR: 1717. 1H
NMR: δ 7.43 (3H, m), 7.04 (2H, d, J ) 7.3 Hz), 3.13 (2H, s),
1.81 (3H, s), 1.60 (6H, s), 1.51 (6H, s). NOE data: 3.13 (1.81,
4%; 1.51, 1%), 1.81 (3.13, 12%; 1.51, 0.7%).13C NMR: δ 175.1,
140.8, 134.1, 129.1, 128.6, 126.4, 86.4, 62.5, 45.9, 25.3, 14.0,
11.7. MS: 435 (1, M+), 308 (14), 173 (100), 135 (35), 127 (2),
117 (22).
(3ar,4r,7r,7ar,8s)- (44) an d (3ar,4r,7r,7ar,8r )-8-Br om o-
3a ,4,7,7a -tetr a h yd r o-4,5,6,7,8-p en ta m eth yl-2-p h en yl-4,7-
m eth a n o-1H-isoin d ole-1,3-d ion e (45). The same procedure
as for 27 was followed except that NBS was used as the
halogen source. Syn-adduct 44 (colorless solid). Mp: 140-
142 °C. IR: 1713. 1H NMR (C6D6): δ 7.41 (3H, m), 6.99 (2H,
d), 2.24 (2H, s), 1.49 (6H, s), 1.38 (6H, s), 1.11 (3H, s). NOE
data: 2.24 (1.38, 0.7%; 1.11, 3%), 1.38 (2.24, 5%; 1.11, 2%),
1.11 (2.24, 11%; 1.49, 0.7%). 13C NMR: δ 175.3, 137.7, 132.1,
129.2, 128.6, 126.5, 94.1, 61.5, 48.2, 21.7, 12.4, 11.6. MS: 389
(6) and 387 (6) both M+, 308 (8), 216 (25), 214 (27), 173 (3),
135 (100).
(10r )-5,8-Dih ydr o-10-iodo-5,6,7,8,10-pen tam eth yl-2-ph en -
yl-5,8-m et h a n o-1H -[1,2,4]t r ia zolo[1,2-a ]p yr id a zin e-1,3-

946 J . Org. Chem., Vol. 62, No. 4, 1997
Wellman et al.
(2H)-d ion e (53). The same procedure as for 52 was followed
except that PTAD was used as the dienophile. Anti-adduct
53 (gray solid). IR: 1777 (m), 1723 (s). 1H NMR (C6D6): δ
7.40 (2H, m), 7.01 (2H, m), 6.90 (1H, m), 1.76 (6H, s), 1.75
(3H, s), 1.51 (6H, s). 13C NMR (C6D6): δ 159.5, 136.6, 131.9,
129.4, 128.5, 126.0, 82.8, 69.8, 25.9, 12.9, 11.8.
Ack n ow led gm en t. This work was supported by a
grant from the Natural Sciences and Engineering
Research Council of Canada.
Su p p or tin g In for m a tion Ava ila ble: X-ray structures for
16, 18, 26, 27, 29, 30, 38, 42, 43, 46, and 49-51 and 13C NMR
spectra of 6, 11, 12, 15-21, 23-31, 35-40, 42-44, 46, and
48-54 (49 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
(7s)-2,2,3,3-Tetr a cya n o-7-iod o-1,4,5,6,7-p en ta m eth ylbi-
cyclo[2.2.1]h ep t-5-en e (54). The same procedure as for 52
was followed except that TCNE was used as the dienophile.
Anti-adduct 54 (gray solid). IR: 2247. 1H NMR (C6D6): δ 1.75
(3H, s), 1.27 (6H, s), 1.10 (6H, s). 13C NMR (C6D6): δ 147.8,
111.7, 111.1, 74.5, 70.2, 44.8, 28.0, 12.3, 11.6.
J O961710J