Reaction of 2,2-bis(trifluoromethyl)-1,1-dicyanoethylene with 6,6-dimethylfulvene: Cycloadditions and a rearrangement

Article abstract of DOI:10.1021/jo0265333

Reaction of 2,2-bis(trifluoromethyl)-1,1-dicyanoethylene (BTF;1) with 6,6-dimethylfulvene (2) affords the expected Diels-Alder cycloadduct, 7-(1-methylethylidene)-3,3-bis(trifluoromethyl)bicyclo[2.2.1]- hept-5-ene-2,2-dicarbonitrile (3), in good yield. The cycloadduct 3 is unstable and exists in equilibrium with the starting materials in less polar solvents. In more polar environment, the [4 + 2] adduct 3 either reverts to starting materials, or, in a competing process, is converted to the formal [2 + 2] adduct, 2-(1-methylethylidene)-7,7- bis(trifluoromethyl)bicyclo[3.2.0]hept-3-ene-6,6-dicarbonitrile (6). In the presence of acid, 3 is converted to a third isomeric form, 1,3a,5,6-tetrahydro- 7-methyl-5,5-bis(trifluoromethyl)-4H-indene-4,4-dicarbonitrile (8). Both 6 and 8 are formed with complete regiospecificity. Quantum mechanical calculations and X-ray crystallographic studies of this ensemble of reactions by BTF, and the analogous set of reactions by its progenitor, tetracyanoethylene (TCNE), reveal several interesting facets. The conversion of 3 to 6 occurs in certain polar solvents, in the presence of silica gel and alumina, as well as in the solid state. Single crystals of 3 were observed by X-ray crystallography to undergo crystal-to-crystal rearrangement to 6. The conversion of 3 to 8 proceeds by the initial retro-Diels -Alder reaction followed by isomerization of the fulvene to 1-isopropenyl-1,3-cyclopentadiene that then reacts with BTF to give the alternative Diels-Alder product as a single regioisomer. A hybrid density functional theory (DFT) method at the B3LYP/6-31G(d) level of theory gave calculated relative energies of 0.0, -9.0, and -18.8 kcal/mol for 3, 6, and 8, respectively. The same method was also used to correctly predict the regiochemical outcome of the cycloaddition of BTF with 1-isopropenyl-1,3-cyclopentadiene. Finally, an explanation is offered for the preference of the persubstituted cyanoolefins BTF and TCNE to add to the exocyclic diene portion of 1-isopropenyl-1,3-cyclopentadiene and the contrasting preference of 2-acetyloxy-2-propenenitrile to add to the endocyclic diene.

Full text of DOI:10.1021/jo0265333

Rea ction of 2,2-Bis(tr iflu or om eth yl)-1,1-d icya n oeth ylen e w ith
6,6-Dim eth ylfu lven e: Cycloa d d ition s a n d a Rea r r a n gem en t
Michael H. Howard,*,† Victor Alexander,‡ William J . Marshall,§ D. Christopher Roe,§ and
Ya-J un Zheng‡
Central Research & Development Department and Corporate Center for Analytical Sciences,
DuPont Company, Experimental Station, Wilmington, Delaware 19880, and DuPont Agricultural
Products, Stine-Haskell Research Center, 1094 Elkton Road, Newark, Delaware 19711
michael.h.howard-1@usa.dupont.com
Received October 7, 2002
Reaction of 2,2-bis(trifluoromethyl)-1,1-dicyanoethylene (BTF; 1) with 6,6-dimethylfulvene (2) affords
the expected Diels-Alder cycloadduct, 7-(1-methylethylidene)-3,3-bis(trifluoromethyl)bicyclo[2.2.1]-
hept-5-ene-2,2-dicarbonitrile (3), in good yield. The cycloadduct 3 is unstable and exists in
equilibrium with the starting materials in less polar solvents. In more polar environment, the
[4 + 2] adduct 3 either reverts to starting materials, or, in a competing process, is converted to the
formal [2 + 2] adduct, 2-(1-methylethylidene)-7,7-bis(trifluoromethyl)bicyclo[3.2.0]hept-3-ene-6,6-
dicarbonitrile (6). In the presence of acid, 3 is converted to a third isomeric form, 1,3a,5,6-tetrahydro-
7-methyl-5,5-bis(trifluoromethyl)-4H-indene-4,4-dicarbonitrile (8). Both 6 and 8 are formed with
complete regiospecificity. Quantum mechanical calculations and X-ray crystallographic studies of
this ensemble of reactions by BTF, and the analogous set of reactions by its progenitor,
tetracyanoethylene (TCNE), reveal several interesting facets. The conversion of 3 to 6 occurs in
certain polar solvents, in the presence of silica gel and alumina, as well as in the solid state. Single
crystals of 3 were observed by X-ray crystallography to undergo crystal-to-crystal rearrangement
to 6. The conversion of 3 to 8 proceeds by the initial retro-Diels-Alder reaction followed by
isomerization of the fulvene to 1-isopropenyl-1,3-cyclopentadiene that then reacts with BTF to give
the alternative Diels-Alder product as a single regioisomer. A hybrid density functional theory
(DFT) method at the B3LYP/6-31G(d) level of theory gave calculated relative energies of 0.0, -9.0,
and -18.8 kcal/mol for 3, 6, and 8, respectively. The same method was also used to correctly predict
the regiochemical outcome of the cycloaddition of BTF with 1-isopropenyl-1,3-cyclopentadiene.
Finally, an explanation is offered for the preference of the persubstituted cyanoolefins BTF and
TCNE to add to the exocyclic diene portion of 1-isopropenyl-1,3-cyclopentadiene and the contrasting
preference of 2-acetyloxy-2-propenenitrile to add to the endocyclic diene.
In tr od u ction
antagonists of the γ-aminobutyric acid (GABA) receptor.3a
Since certain of these gem-dinitriles exhibit toxicity to
invertebrate pests at levels comparable to commercial
insecticides, there is interest in structure-activity rela-
tionships, and a unified pharmacophore model has been
developed.3b The perfluoroalkyldicyanoolefins, a much
less-studied subclass of polycyanolefins, have similarly
exhibited intriguing chemical behavior.4 This subclass,
as exemplified by 2,2-bis(trifluoromethyl)-1,1-dicyanoet-
hylene (BTF; 1),5 is characterized by additional modes
of reactivity not seen in other cyanoolefins. While both
TCNE (4) and BTF (1) are highly electrophilic, their
Cya n oolefin Rea ctivity. The discovery of tetracy-
anoethylene1 (TCNE) over 40 years ago spurred a sus-
tained interest in the chemistry of polycyanoolefins that
has revealed many varied and unique modes of reactiv-
ity.2 On a practical level, cycloadducts of polycyanoolefins
are noteworthy for their biological activity.3 Polycyclic
dinitriles have been identified as a novel class of potent
* To whom correspondence should be addressed. Current address:
DuPont Agricultural Products, Stine-Haskell Research Center, 1094
Elkton Road, Newark, DE 19711. Tel: 302-451-4796. Fax: 302-366-
5738.
† Central Research & Development Department.
(3) (a) Rauh, J . J .; Benner, E.; Schnee, M. E.; Cordova, D.; Holyoke,
C. W.; Howard, M. H.; Bai, D.; Buckingham, S. D.; Hutton, M. L.;
Hamon, A.; Roush, R. T.; Sattelle, D. B. Br. J . Pharmacol. 1997, 121,
1496-1505. (b) Rauh, J . J .; Holyoke, C. W.; Kleier, D. A.; Presnail, J .
K.; Benner, E. A.; Cordova, D.; Howard, M. H.; Hosie, A. M.;
Buckingham, S. D.; Baylis, H. A.; Sattelle, D. B. Invertebr. Neurosci.
1997, 3, 261-268.
‡ Agricultural Products Department.
§ Corporate Center for Analytical Sciences.
(1) Cairns, T. L.; Carboni, R. A.; Coffman, D. D.; Engelhardt, V. A.;
Heckert, R. E.; Little, E. L.; McGreer, E. G.; McKusick, B. C.;
Middleton, W. J .; Scribner, R. M.; Theobald, T. W.; Winberg, H. E. J .
Am. Chem. Soc. 1958, 80, 2775-2778.
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J . Synthesis 1987, 11, 959-978.
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10.1021/jo0265333 CCC: $25.00 © 2003 American Chemical Society
Published on Web 11/21/2002
120
J . Org. Chem. 2003, 68, 120-129

Reaction of BTF with 6,6-Dimethylfulvene
SCHEME 1a
behaviors diverge as a consequence of the latter com-
pound’s enhanced polarizability and greater steric de-
mand. Cyanoolefins are known to be reactive enophiles,
but BTF undergoes ene reactions with terminal, unac-
tivated alkenes via allylic hydrogen transfer, while TCNE
is unreactive toward such substrates.6 Early spectropho-
tometric studies of TCNE showed it to have the highest
electron affinity of any π-acid studied up to that time.7
Electron-rich aromatic rings undergo electrophilic sub-
stitution by both BTF and TCNE. Ketones react via their
enol tautomers with TCNE and added catalyst or with
BTF without added catalystsa consequence of the even
higher electron affinity of BTF.8 In [2 + 2] cycloadditions
with enol ethers8b and vinyl sulfides,9 BTF reacts 3 orders
of magnitude faster than TCNE. The rate difference
between the two cyanoolefins in Diels-Alder reactions
is much less pronounced since the acceleration due to the
electronic effect of the CF3 groups in 1 is largely canceled
out by the concomitant increase in steric hindrance.5,10
F u lven e Ch em istr y. The diverse reactivity of ful-
venes made them the subject of considerable interest
from both a mechanistic and synthetic standpoint over
the entire 20th century.11 Possessing a cyclic diene
system cross-conjugated with an exocyclic double bond,
these trienes are isomeric with the corresponding ben-
zenoid series. The resonance energy of fulvene is ap-
proximately 12 kcal/mol, considerably less than that of
benzene.12 The reactivity of fulvenes therefore falls
somewhere between that observed in aromatic and ole-
finic systems.13 Fulvenes are versatile partners in cy-
cloaddition reactions with olefins and can serve as 2π,
4π, or 6π species depending on the substitution pattern
of the reacting components.11a With so many modes of
reaction available to each partner, the outcome of the
interaction of BTF with fulvenes seemed bound to
produce challenges to mechanistic and theoretical un-
derstanding.
a
Conditions: hexanes, rt (R ) CF3); acetone, -60 °C (R ) CN).
the mildly exothermic reaction. Analysis of the precipi-
tate showed it to be the [4 + 2] cycloadduct 3.
In less-polar solvents, the [4 + 2] adduct 3 exists in
equilibrium with its starting materials. The ratio of the
[4 + 2] product 3 to the fulvene 2 is easily measured using
1H NMR spectroscopy to compare the integrals for well-
separated peaks of each compound in either the vinyl or
methyl region. The equilibrium constant (Keq) for 3 was
determined to be 11.2 M-1 in toluene-d8 at 20 °C, and
this value is very close to that observed in other less-
polar solvents such as CDCl3 and benzene-d6. In these
solvents, the cycloadduct 3 is stable for over 1 month. In
acetone, a solvent of intermediate polarity, no Diels-
Alder reaction is observed between 1 and fulvene 2 at
room temperature, in contrast to the reaction of 2 with
TCNE (4), which occurs rapidly. When dissolved in more
polar solvents, 3 reverts to a mixture of starting materials
1 and 2 and a rearrangement product (vide infra) that is
formed in a competing process.
Single crystals of 3 can be obtained by careful crystal-
lization from diethyl ether/petroleum ether or, more
easily, by sublimation under high vacuum at slightly
elevated temperature. X-ray crystallography of the single
crystals gave the structure shown in Figure 1a.
Reaction of 6,6-dimethylfulvene (2) with equimolar
TCNE also gives the expected [4 + 2] cycloadduct 5 as
shown in Scheme 1.14 A transient dark blue color was
noted in the acetone solution as the reactants were
mixed. A solvent-dependent equilibrium for this reaction
is evident from the NMR spectrum of the product. The
equilibrium constant in acetone-d6 is 11.5 at room tem-
perature. X-ray diffraction of single crystals of this
compound gave the structure shown in Figure 1b.
Based on an accumulating wealth of successful prece-
dents for its use in the study of Diels-Alder reactions,
we decided to use B3LYP/6-31G(d) method to examine
the reaction between 6,6-dimethylfulvene and the two
cyanoolefins under consideration in this work.15-18 The
bond lengths and angles for the calculated transitions
states for the reaction of fulvene 2 with the two cyanoole-
fins and ethylene are given in Table 1. Several attempts
to locate biradical intermediates using UB3LYP/6-31G-
Resu lts
Diels-Ald er Rea ction . Addition of BTF (1) to a
bright yellow solution of 6,6-dimethylfulvene (2) in hex-
anes (Scheme 1) results in a transient red color indicative
of a charge transfer complex between the two species.
Once a stoichiometric amount of BTF has been added,
the yellow color fades and a white solid precipitates from
(6) Huisgen, R.; Bru¨ckner, R. J . Org. Chem. 1991, 56 (5), 1679-
1681.
(7) Merrifield, R. E.; Phillips, W. D. J . Am. Chem. Soc. 1958, 80,
2778-2782.
(8) (a) Bru¨ckner, R.; Huisgen, R. Tetrahedron Lett. 1991, 32 (16),
1871-1874. (b) Bru¨ckner, R.; Huisgen, R. Tetrahedron Lett. 1990, 31
(18), 2557-2560.
(9) Bru¨ckner, R.; Huisgen, R. Tetrahedron Lett. 1990, 31 (18), 2561-
2564.
(10) Bru¨ckner, R.; Huisgen, R. Tetrahedron Lett. 1994, 35 (20),
3285-3288.
(14) (a) Kresze, G.; Rau, S.; Sabelus, G.; Goetz, H. Annalen 1961,
648, 57-63. (b) Smith, W. B.; Biesemeier, S.; Deavenport, D. L. J . Org.
Chem. 1971, 36 (19), 2853-2855. (c) Knight, D. B.; Hartless, R. L.;
J arvis, D. A. J . Org. Chem. 1972, 37, (5), 688-692.
(15) (a) Houk, K. N.; Gonzalez, J .; Li, Y. Acc. Chem. Res. 1995, 28
(2), 81-90. (b) Dewar, M. J . S.; Olivella, S.; Stewart, J . J . P. J . Am.
Chem. Soc. 1986, 108 (19), 5771-5779.
(11) (a) Neuenschwander, M. In Chemistry of Double-bonded Func-
tional Groups; Patai, S., Ed.; Wiley: Chichester, U.K., 1989; Vol. 2,
pp 1131-1268. (b) Zeller, K.-P. In Houben-Weyl, Methoden der Orga-
nischen Chemie; Georg Thieme Verlag: Stuttgart, Germany, 1985; Vol.
5/2c, pp 504-508. (c) Yates, P. Adv. Alicycl. Chem. 1968, 2, 59-184.
(d) Hamb, F. L. Org. Chem. Bull. 1966, 38 (1), 1-6. (e) Day, J . H. Chem.
Rev. 1953, 53, 167-189.
(16) Goldstein, E.; Beno, B.; Houk, K. N. J . Am. Chem. Soc. 1996,
118, (25), 6036-6043.
(12) Day, J . H.; Oestreich, C. J . Org. Chem. 1957, 22, 214-216.
(13) Hafner, K.; Ha¨fner, K. H.; Ko¨nig, C.; Kreuder, M.; Ploss, G.;
Schulz, G.; Sturm, E.; Vo¨pel, K. H. Angew. Chem., Int. Ed. Engl. 1963,
2 (3), 123-134.
(17) J ursic, B. S. THEOCHEM 1995, 358, 139-43.
(18) Tian, J .; Houk, K. N.; Klaerner, F. G. J . Phys. Chem. A 1998,
102 (39), 7662-7667.
J . Org. Chem, Vol. 68, No. 1, 2003 121

Howard et al.
F IGURE 2. Calculated potential energy surface for the Diels-
Alder reactions of 6,6-dimethylfulvene with BTF (a) and TCNE
(b) at the B3LYP/6-31G(d) level of theory.
SCHEME 2. Rea r r a n gem en t of th e Nor bor n en es 3
a n d 5 to th e Bicyclo[3.2.0]h ep ten es 6 a n d 7a
F IGURE 1. X-ray crystal structures of (a) 7-(1-methyleth-
ylidene)-3,3-bis(trifluoromethyl)bicyclo[2.2.1]hept-5-ene-2,2-di-
carbonitrile (3), (b) 7-(1-methylethylidene)bicyclo[2.2.1]hept-
5-ene-2,2,3,3-tetracarbonitrile (5), (c) 2-(1-methylethylidene)-
7,7-bis(trifluoromethyl)bicyclo[3.2.0]hept-3-ene-6,6-dicarbonitrile
(6), and (d) 1,3a,5,6-tetrahydro-7-methyl-5,5-bis(tri-fluorometh-
yl)-4H-indene-4,4-dicarbonitrile (8).
TABLE 1. Ca lcu la ted Geom etr ica l P a r a m eter s for th e
Tr a n sition Sta tes of th e Diels-Ald er Rea ction s of
6,6-Dim eth ylfu lven e w ith Eth ylen e, TCNE, a n d BTF
parameter
ethylene
TCNE
BTF
a
Conditions: see text.
forming C- - -C bond (Å)
2.204
2.204
2.114
2.112
1.890a
2.664b
timation of the stability of the product. The same
consideration applies to the reaction of TCNE and fulvene
angle around C2 (deg)
angle around C3 (deg)
354.5c
354.4c
349.2c
349.0c
359.0d
337.6e
2.
a
C3-C4 (see Supporting Information for atom numbering).
b C1-C2 (see Supporting Information for atom numbering). c Angle
around the dienophilic C-atom. For a planar carbon center, the
Rea r r a n gem en t of th e Diels-Ald er P r od u ct. On
standing in polar solvents such as methyl sulfoxide
(DMSO) and acetonitrile, the [4 + 2] product 3 gradually
converts in low yield to a new structure (Scheme 2), along
with starting materials 1 and 2 from retro-Diels-Alder
reaction. Combustion analysis of the new product gave
the same elemental composition as the starting material.
The 1H NMR spectrum of the new product in CDCl3
indicated that a skeletal rearrangement had occurred.
The two sets of multiplets in the range 6.63-6.71 ppm
for the two vinyl protons (H5, H6) of 3 were replaced by
two well-separated signals, one at 6.9 ppm (doublet, 1H)
and the other at 6.0 ppm (doublet of doublets, 1H).
Furthermore, the signals at 4.34 (s, 1H) and 3.99 (t, 1H)
ppm due to the bridgehead protons (H1 and H4, respec-
tively) of 3 were replaced by signals at 4.24 (dd, 1H) and
4.06 (d, 1H) ppm in the new product. Unequivocal
assignment of structure 6 to the new product was
obtained by single-crystal X-ray crystallography (Figure
1c).
d
angle is 360°. Angle around the dienophilic C-atom with the two
CN groups attached. e Angle around the dienophilic C-atom with
the two CF3 groups attached.
(d) failed, indicating the reaction in the gas phase is
probably concerted.
The calculated potential energy surface is schemati-
cally displayed in Figure 2. The theoretical calculations
indicate relatively deep minima that we attribute to
π-complexes based on the experimentally observed color
changes noted above. The intermolecular distance in the
π-complex of BTF and fulvene is longer than that in the
complex of TCNE and fulvene. A graphical rendering of
the calculated π-complex is included in the Supporting
Information.
The calculated reaction barrier for the reaction of BTF
and fulvene 2 is about 8.2 kcal/mol. The overall reaction
is calculated to be exothermic; however, the heat of
reaction appears to be underestimated. Since the calcu-
lated forward barrier is very reasonable, the underesti-
mation of the heat of reaction must be due to underes-
We have found that the fastest and highest yielding
method for converting 3 to 6 is contact with silica gel.
Passing the [4 +2 ] product 3 through a column of silica
122 J . Org. Chem., Vol. 68, No. 1, 2003

Reaction of BTF with 6,6-Dimethylfulvene
TABLE 2. Ca lcu la ted Rela tive En er gies (k ca l/m ol) a t th e B3LYP /6-31G(d ) Level of Th eor y
SCHEME 3. Acid -Ca ta lyzed Con ver sion of
gel using ethyl acetate/hexanes as eluent gives a 90%
yield of 6. The same result was obtained on contacting
solutions of 3 with acidic, neutral or basic alumina. The
fused-ring cyclobutane product 6 is stable and does not
revert to 3 upon heating (see the Experimental Section),
nor is there any evidence for the presence of the fulvene
2 seen in solutions of purified 6.
Nor bor n en es 3 a n d 5 to Tetr a h yd r oin d en es 8 a n d
9, Resp ectivelya
Rearrangement of the TCNE [4 + 2] adduct 5 to the
formal [2 + 2] adduct 7 occurs in polar media but is much
more sluggish than in the BTF case. For instance,
treatment of 5 with silica gel under the same conditions
used to convert 3 to 6 gave only 25% yield of material
that was a 1:1 mixture of 5 and 7. Results from density
functional theory calculations of the rearrangement
products 6 and 7 are presented in Table 2. While both
rearrangements reactions are exothermic, the process
leading to 6 is more favorable by 4.1 kcal/mol.
It is also worth noting that solid samples of 3 undergo
clean conversion to 6 after standing at room temperature
for as little as a few days, with or without exposure to
ambient light. The solid state rearrangement of the
microcrystalline precipitate from the reaction of BTF with
2 was verified by powder diffraction studies. By contain-
ing a single crystal of 3 in a sealed glass capillary, the
formation of crystals of 6 was observed to occur adjacent
to the original crystal of 3. Photographic images of the
crystal-to-crystal transformation are included in the
Supporting Information.
a
Conditions: see text.
Conversion of the TCNE Diels-Alder adduct 5 to an
analogous cycloadduct 9 (Scheme 3) proceeds more slowly
than in the BTF case. No reaction occurs between 5 and
p-toluenesulfonic acid in chloroform at room temperature,
but after 1 h at reflux clean conversion to 9 was obtained.
This compound has been reported previously by isolation
from a mixture obtained by TCNE trapping of mixed
isomers resulting from kinetic protonation of the carban-
ion of 2.14c
The calculated relative energies of these unexpected
cycloadducts (8 and 9) were considerably lower than those
of the corresponding fulvene cycloaddition products (3
and 5) and are reported in Table 2.
Given the necessity of acid catalysis to effect the
conversion of 3 to fused bicycle 8, the likely mechanism
of the reaction involves the intermediacy of 1-isopropenyl-
1,3-cyclopentadiene (see the Discussion). To gain a better
understanding of the regiochemical outcome of this
reaction, the transition state for the Diels-Alder reaction
between 1-isopropenyl-1,3-cyclopentadiene (Chart 1) and
BTF (1) was located using a hybrid density functional
theory method at the B3LYP/6-31G(d) level of theory.
Two alternative Diels-Alder reaction pathways were
investigated. One involves reaction with the endocyclic
diene system (a) and the other involves reaction with the
exocyclic double bond and the adjacent ring double bond
(b). The calculated structures and relative energies of the
transition states are shown in Figure 3. According to the
calculations, the Diels-Alder reaction involving the
exocyclic double bond is favored by about 13.7 kcal/mol.
The calculated preference for the transition state leading
Alter n a tive Diels-Ald er Rea ction . In the presence
of certain acids, a different pathway becomes available
to the [4 + 2] cycloadduct 3. While 3 is stable for extended
periods in chloroform, exposure to strong protic acids
(hydrochloric acid, trifluoroacetic acid, and p-toluene-
sulfonic acid) results in conversion to an entirely new
product (Scheme 3). In chloroform solution containing
either excess or substoichiometric amounts of these acids,
1
all peaks in the H NMR spectrum of 3 (including those
of equilibrium partner 2) disappear and are replaced
cleanly by an isomeric structure that is distinct from the
formal [2 + 2] cycloadduct 6. Acetic acid was not effective
in promoting the conversion. Conversion of 3 to the new
product is best achieved in 18 h by use of 20 mol % of
p-toluenesulfonic acid. Single-crystal X-ray crystallogra-
phy of the new product established the unexpected
structure 8 shown in Figure 1d.
J . Org. Chem, Vol. 68, No. 1, 2003 123

Howard et al.
carbons (C3 and C2, respectively) in 3 may be further
manifestations of this strain. The bond angles and
lengths in the TCNE cycloadduct 5 show the same trends
as in the BTF cycloadduct 3.
Despite this structural similarity, the TCNE cycload-
duct 5 is more stable than the BTF adduct 3 in all
solvents studied. For instance, in chloroform solution
BTF adduct 3 shows appreciable dissociation, whereas
the TCNE adduct 5 has an equilibrium constant for
association of 32 × 103 M-1 in the same solvent.14a Also,
5 exists in a stable equilibrium with 2 in acetone while
3 undergoes cycloreversion to 2 in less than 2 days.
To gain insight into the reaction of the cyanoolefins 1
and 4 with the fulvene 2, quantum mechanics calcula-
tions were carried out. The mechanism of Diels-Alder
reactions has been intensively investigated by computa-
tional methods.15 The hybrid density functional theory
with the 6-31G(d) basis set (B3LYP/6-31G(d) level of
theory) has been demonstrated to be an effective method
in dealing with the Diels-Alder reaction.16 The B3LYP/
6-31G(d) method also gives reasonable activation barrier
for the Diels-Alder reaction of cyclopentadiene with 1,1-
dicyanoethylene.17 The retro-Diels-Alder reaction of
isopropylidenenorbornene was recently studied by the
B3LYP/6-31G(d) method: the computational results, in
conjunction with experimental observation of stereospeci-
ficity, support a synchronous concerted mechanism.18
F IGURE 3. Transition states and relative energies for the
reaction of the endocyclic (a) and exocyclic (b) diene system of
1-isopropenyl-1,3-cyclopentadiene with BTF (1).
CHART 1. Str u ctu r es of 6,6-Dim eth ylfu lven e
Ta u tom er s (a ) 1-Isop r op en yl-1,3-cyclop en ta d ien e,
(b) 2-Isop r op en yl-1,3-cyclop en ta d ien e, a n d
TCNE Ad d u ct (c) 2-Isop r op en yl-5,5,6,6-
tetr a cya n on or bor n en e
From the theoretical calculations, the most interesting
feature of the potential energy surfaces (Figure 2) is the
existence of relatively deep minima attributable to
π-complexes. The π-complex formed between TCNE and
fulvene is more stable than that of BTF and fulvene,
which is consistent with the trend reported for the
π-complexes of TCNE and BTF with aromatic π-bases.5,7
As expected, the intermolecular distance in the π-com-
plex of BTF and fulvene is longer than that in the
complex of TCNE and fulvene (3.3-3.4 versus 3.2 Å). The
relative orientation of the BTF and TCNE to fulvene in
these π-complexes suggests that the dominant interac-
tions in these complexes to be between the HOMO of
fulvene and the LUMO of the BTF and TCNE.
to the tetrahydroindene ring system is consistent with
the observed formation of 8 as the sole product.
Discu ssion
The reaction of 6,6-dimethylfulvene with BTF and
TCNE to give the [4 + 2] cycloadducts 3 and 5, respec-
tively, is expected on the basis of frontier molecular
orbital theory19 which predicts the dominant interactions
in this reaction to be between the HOMO of the fulvene
and the LUMO of the olefins.20 In certain solvents, these
products exist in equilibrium with their respective start-
ing materials. The reversibility of Diels-Alder reactions
of fulvenes was established by Kohler,21 who observed
that in dilute solution the cycloadducts with maleic
anhydride dissociate almost completely. We observed a
strong solvent dependence for the reaction of BTF (1)
with fulvene 2. While the forward reaction occurs readily
in nonpolar solvents to give Diels-Alder product 3, no
reaction occurs in solvents of intermediate to high polar-
ity.
The crystal structure of 3 reveals some striking fea-
tures. The one-atom bridge (C7) forms a 95° angle with
the bridgehead carbons (C1 and C4). The strain energy
that accompanies this very acute angle may account for
the instability of this structure. The slightly elongated
single bonds (1.59-1.60 Å) between the bridgehead
carbons and the trifluoromethyl- and cyano-bearing
The results from density functional theory treatment
of the reactions between fulvene 2 and ethylene, TCNE
(4) and BTF (1) show strong contrast between the
transition state for the first two dienophiles and that of
the more polarizable perfluoroalkylcyanoolefin. The geo-
metrical parameters from the calculated transition states
are given in Table 1. The reaction of fulvene 2 with TCNE
is concerted in the gas phase, and the two developing
C-C bonds in the transition state are around 2.11 Å. In
the reaction with BTF, the calculated transition-state
bond lengths differ by 0.75 Å and the angles around the
dienophilic carbon atoms differ by 22 degrees. Compared
to the TCNE reaction, the developing bond between the
diene carbon atom and the gem-bis(trifluoromethyl)-
substituted carbon atom of BTF is shorter still by another
0.2 Å while the gem-dicyano-substituted carbon atom is
barely distorted from planarity. This evidence indicates
that fulvene 2 and BTF combine in a highly asynchronous
Diels-Alder reaction. Similar findings have recently been
reported for other polar asymmetrical Diels-Alder reac-
(19) Fleming, I. Frontier Orbitals and Organic Chemical Reactions;
Wiley: London, 1976.
(20) Houk, K. N.; George, J . K.; Duke, R. E., J r. Tetrahedron 1974,
30 (4), 523-533.
(21) Kohler, E. P.; Kable, J . J . Am. Chem. Soc. 1935, 57 (5), 917-
918.
124 J . Org. Chem., Vol. 68, No. 1, 2003

Reaction of BTF with 6,6-Dimethylfulvene
Unimolecular solid-state organic reactions are rare.27
X-ray crystallographic analysis of single crystals of the
reaction components in a solid-state transformation can
yield valuable insight into the extent that the required
atomic motions force deformation in the reaction cavity.28
Single crystal-to-single-crystal reactions are referred to
as topotactic when at least one crystallographic axis is
maintained between the starting material and the
product.27f Sublimation of the crystalline material in the
capillary tube experiment prevents us from determining
any such details about the physical rearrangement of the
solid. Comparison of the crystal packing in structures 3
and 6 did not reveal structural similarities. Because pure,
intact crystals of 3 can also be grown by sublimation of
the microcrystalline precipitate from the Diels-Alder
reaction, we do not believe that the rearrangement of 3
to 6 is occurring during the sublimation process in the
capillary. Rather, we propose that a solid-state transfor-
mation of 3 to 6 at the surface of the crystal is ac-
companied by deterioration of the reactant lattice thereby
allowing the newly formed product 6 to sublime and
reform adjacent to the original crystal. To the best of our
knowledge, this reaction is the first example of a dipolar
rearrangement occurring in the solid state. In the mid-
1980s, magic angle spinning 13C NMR studies proved that
the degenerate Cope rearrangements of the well-studied
bullvalene system occur in the crystalline state.29
The structure of the tetrahydroindene products 8 and
9 and the conditions under which they are formed suggest
that an alternative [4 + 2] cycloaddition manifold is
available when the fulvene 2 undergoes acid-catalyzed
isomerization. Under neutral conditions, the 1- and
2-isopropenyl-1,3-cyclopentadiene tautomers (Chart 1)
are very minor contributors and 6,6-dimethylfulvene (2)
accounts for 98% of the equilibrium mixture.30 At el-
evated temperatures, tetra- and pentamethylene fulvene
have been shown to undergo isomerization.31 In strong
acid, fulvenes protonate at 2-position32 and tautomeriza-
tion then leads to the isomeric triene intermediate
1-isopropenyl-1,3-cyclopentadiene, shown in Scheme 4.
The acid-catalyzed isomerization of cross-conjugated
2 to give the fully conjugated 1-isopropenyl-1,3-cyclopen-
tadiene has been reported by Oku and co-workers.33
Reaction of 2-acetyloxy-2-propenenitrile (10) with 2 gave
11 (Scheme 5) as the minor component in a mixture with
the normal [4 + 2] cycloadduct (12). In this case the
captodative cyanoolefin34 behaves as would be expected
F IGURE 4. Proposed zwitterionic intermediate in the conver-
sion of norbornene 3 to bicyclo[3.2.0]heptene 6.
tions.17,22 The calculated structures for the products are
in good agreement with the X-ray crystal structures, with
the calculated C1-C2 and C3-C4 distances (1.627 and
1.596 Å, respectively) being slightly longer than the ex-
perimentally determined distances for 3.
In competition with the equilibrium between the
bridged bicyclic product 3 and the starting materials 1
and 2 is the conversion to the isomeric ring-fused
cyclobutane 6. The rate and extent of the conversion of
3 to 6 depends on the polarity of the medium. Empirical
measurements of solvent polarity such as ET have
provided valuable insights into the mechanisms of me-
dium-dependent organic reactions.23 None of the rear-
rangement product 6 is formed in less polar solvents such
as toluene (ET 33.9), benzene (ET 34.5), and chloroform
(ET 39.1). In acetone (ET 42.2) the bridged bicycle 3 simply
undergoes an irreversible retro-Diels-Alder reaction. The
rearrangement product 6 is finally formed in polar
solvents DMSO (ET 45.0) and acetonitrile (ET 46.0),
although the process is complicated by competing retro-
Diels-Alder reaction of 3. These observations, combined
with the excellent conversion of 3 to 6 in the presence of
silica gel and alumina, point to the importance of polarity
of the medium and therefore suggest a dipolar mecha-
nism.
Two earlier mechanistic studies of the reactions of
fulvenes with electron-deficient olefins provide precedent
for the BTF reaction. The weak effect of solvent polarity
on the rate of reaction of 4-methyl-1,2,4-triazoline-3,5-
dione with 6,6-diphenylfulvene led Olsen to conclude that
the intermediate species was likely a resonance hybrid
having both zwitterionic and diradical character.24 Sup-
port for a zwitterionic mechanism comes from the labora-
tory of Laszlo where a strong dependence of reaction rate
on solvent dielectric was observed in the fascinating
cascade reaction between 6,6-dicyclopropylfulvene and
TCNE.25
We favor a zwitterionic intermediate of the form
depicted in Figure 4 in which the two ends of the dipole
are highly stabilized through charge delocalization. Huis-
gen has presented strong evidence for analogous dipolar
intermediates in the reaction of BTF with enol ethers.8b,9
We also used theoretical methods to examine the
zwitterionic intermediate in solution. The Onsager sol-
vation model26 was used and the dielectric constant used
is that of DMSO (ca. 46.7). The calculated structure at
the HF/6-31G(d) level using the Onsager solvation model
is consistent with the proposed zwitteronic intermediate.
(27) (a) Desiraju, G. R.; Goud, B. S. In React. Solids: Past, Present
Future; Boldyrev, V. V., Ed.; Blackwell, Oxford, U.K., 1996; pp 223-
236. (b) Toda, F. In Reactivity in Molecular Crystals; Ohashi, Y., Ed.;
VCH Publishers: Weinheim, 1993; pp 177-201. (c) Curtin, D. Y.; Paul,
I. C. Chem. Rev. 1981, 81 (6), 525-541. (d) Curtin, D. Y.; Paul, I. C.;
Duesler, E. N.; Lewis, T. W.; Mann, B. J .; Shiau, W.-I. Mol. Cryst. Liq.
Cryst. 1979, 50 (1-4), 25-41. (e) Paul, I. C.; Curtin, D. Y. Accounts
Chem. Res. 1973, 6 (7), 217-225. (f) Keating, A. E.; Garcia-Garibay,
M. A. Mol. Supramol. Photochem. 1998, 2 (Organic and Inorganic
Photochemistry), 195-248.
(28) Kim, J . H.; Hubig, S. M.; Lindeman, S. V.; Kochi, J . K. J . Am.
Chem. Soc. 2001, 123 (1), 87-95.
(29) Meier, B. H.; Earl, W. L. J . Am. Chem. Soc. 1985, 107 (19),
5553-5555.
(22) Garcia, J . I.; Martinez-Merino, V.; Mayoral, J . A.; Salvatella,
L. J . Am. Chem. Soc. 1998, 120 (10), 2415-2420.
(23) (a) Reichardt, C., Ed.; Solvents and Solvent Effects in Organic
Chemistry, 2nd ed.; VCH Verlagsgesellschaft: Weinheim, Fed. Rep.
Ger, 1988. (b) Reichardt, C. Angew. Chem. 1979, 91 (2), 119-131.
(24) Olsen, H. Angew. Chem., Int. Ed. Engl. 1982, 21 (5), 383-384.
(25) Cornelis, A.; Laszlo, P. J . Am. Chem. Soc. 1975, 97 (1), 244-
245.
(30) Knox, G. R.; Pauson, P. L. J . Chem. Soc. 1961, 4610-4615.
(31) Nair, V.; Kumar, S. Tetrahedron 1996, 52, 4029-4040.
(32) Olah, G. A.; Reddy, P. V.; Prakash, G. K. S. In The Chemistry
of the Cyclopropyl Group; Rappoport, Z., Ed.; J ohn Wiley & Sons Ltd.:
Chichester, U.K., 1995; Vol. 2, pp 813-859.
(33) Oku, A.; Nozaki, Y.; Hasegawa, H.; Nishimura, J .; Harada, T.
J . Org. Chem. 1983, 48 (23), 4374-4377.
(26) Onsager, L. J . Am. Chem. Soc. 1936, 58, 1486-1493.
J . Org. Chem, Vol. 68, No. 1, 2003 125

Howard et al.
SCHEME 4. P r op osed Mech a n ism for th e
Acid -Ca ta lyzed Con ver sion of Nor bor n en e 3 to
Tetr a h yd r oin d en e 8 in Ch lor ofor m Solu tion
SCHEME 5. Rea ction of 6,6-Dim eth ylfu lven e (2)
w ith 2-Acetyloxy-2-p r op en en itr ile33 a
F IGURE 5. Transition states and relative energies for the
reaction of the endocyclic (a) and exocyclic (b) diene system of
1-isopropenyl-1,3-cyclopentadiene with 2-acetyloxy-2-propene-
nitrile (10).
a
Formation of the minor product (11) is suppressed by addition
of pyridine to the reaction mixture.
Our acid-catalyzed conversion of the TCNE cycloadduct
5 to the indene product 9, while slower than the analo-
gous reaction in the BTF series, provides clean access to
a product that was previously only obtained as a mixture
with two other isomeric structures. In addition to a 66%
yield of 9 and a 10% yield of 5 from the TCNE reaction
with the resulting C8H10 triene isomer mixture obtained
upon kinetic protonation of the carbanion of 6,6-dimeth-
ylfulvene, a 25% yield of 2-isopropenyl-5,5,6,6-tetracy-
anonorbornene (Chart 1) was also reported.14c Although
the authors of the study made no comment on the matter,
it is interesting that their results show that TCNE adds
to the endocyclic diene system of 2-isopropenyl-1,3-
cyclopentadiene to give 2-isopropenyl-5,5,6,6-tetracy-
anonorbornene, while adding to the opposite diene system
in 1-isopropenyl-1,3-cyclopentadiene to give 9. These
results are consistent with our explanation based on
dienophile structure (above) and also confirm that the
greater steric hindrance of 1-isopropenyl-1,3- cyclopen-
tadiene relative to 2-isopropenyl-1,3-cyclopentadiene pre-
vents access to the normally more reactive endocyclic
diene system by these two tetrasubstituted cyanoolefins.
The two cyanoolefins, BTF (1) and 2-acetyloxy-2-
propenenitrile (10), add with opposite regiospecificities
to the same diene, 1-isopopenyl-1,3-cyclopentadiene. To
examine the transition state of the latter reaction, we
again turned to hybrid density functional theory at the
B3LYP/6-31G(d) level of theory. The same two alternative
Diels-Alder pathways as in the BTF reaction were
investigated, one involving reaction with the endocyclic
diene system and the other involving reaction with the
exocyclic double bond and the adjacent ring double bond.
The calculated structures and relative energies of the
transition states for the 2-acetyloxy-2-propenenitrile
reaction are shown in Figure 5. According to our calcula-
tions, addition of 10 to the endocyclic diene system of
1-isopropenyl-1,3-cyclopentadiene is favored by 6.5 kcal/
mol. Thus, the density functional theory predictions for
both reactions are consistent with experimental observa-
tions.
for a normal, less reactive dienophile and adds to the
inner-ring diene system of 1-isopropenyl-1,3-cyclopenta-
diene to give 11 in what is most likely a synchronous
cycloaddition.
The regioselectivity of the cycloaddition leading to 11
can be qualitatively explained by the fact that cyclopen-
tadiene is a better dienophile than 1,3-butadiene. For
instance, the experimentally measured activation energy
for the reaction between cyclopentadiene and ethylene
is about 5 kcal/mol lower than that of 1,3-butadiene (22.5
vs 27.5 kcal/mol).35 Thus, reaction of 11 with 1-isopro-
penyl-1,3-cyclopentadiene occurs at the cyclopentadiene
moiety. However, the reaction of the tetrasubstituted
cyanoolefin BTF is sterically more demanding. Therefore,
cycloaddition of BTF (1) occurs at the less crowded
exocyclic diene moiety.
The formation of the tetrahydroindene 8 is itself a
regiospecific process: the BTF adds so as to minimize
steric interactions between the CF3 groups and the
bridgehead methine (H3a). The high conformational
demand of the trifluoromethyl groups (A value ) 2.4-
2.5 kcal/mol) relative to the cyano groups (0.2 kcal/mol)
is most likely the determining factor.36 The same sense
of regiochemistry is observed in the [4 + 2] product from
the reaction of BTF with styrenes.37 The preference for
orienting the cyano-bearing end of BTF toward the more
crowded end of the diene system is also operative in
linear dienes as well: see, for example, the case of 2,4-
dimethyl-1,3-pentadiene, which reacts with BTF to give
the product cyclohexene regioisomer in which the carbon
bearing the cyano groups is attached to the carbon
bearing the gem-dimethyl groups.10
(34) (a) Viehe, H. G.; J anousek, Z.; Merenyi, R.; Stella, L. Acc. Chem.
Res. 1985, 18 (5), 148-154. (b) Viehe, H. G.; Merenyi, R.; Stella, L.;
J anousek, Z. Angew. Chem. 1979, 91 (12), 982-997.
(35) (a) Walsh, R.; Wells, J . M. J . Chem. Soc., Perkin Trans. 2 1976
(1), 52-55. (b) Rowley, D.; Steiner, H. Discuss. Faraday Soc. 1951,
10, 198-213.
(36) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds;
J ohn Wiley & Sons: New York, 1994.
(37) Bru¨ckner, R.; Huisgen, R.; Schmid, J . Tetrahedron Lett. 1990,
31 (49), 7129-7132.
The calculations suggest that both orientations of the
2-acetyloxy-2-propenenitrile transition state (Figure 5)
are relatively late compared to the corresponding BTF
126 J . Org. Chem., Vol. 68, No. 1, 2003

Reaction of BTF with 6,6-Dimethylfulvene
transition states (Figure 3). The two forming C-C bonds
are 2.742 (for the bond forming to C2 of 10) and 1.965 Å
(for the bond forming to C1 of 10) in Figure 5a and 2.143
(for the bond forming to C1 of 10) and 2.349 Å (for the
bond forming to C2 of 10) in Figure 5b. Similarly, the
two forming C-C bonds are 2.359 (for the bond forming
to C2 of BTF) and 2.098 Å (for the bond forming to C1 of
BTF) in Figure 3a and 2.988 (for the bond forming to C1
of BTF) and 2.122 Å (for the bond forming to C2 of BTF)
in Figure 3b.
Exp er im en ta l Section
Gen er a l Meth od s. Melting points were in open capillaries
and are uncorrected. All reactions were carried out under an
atmosphere of dry nitrogen. Reagent grade solvents were
purchased from commercial sources and used as received. 6,6-
Dimethylfulvene was either prepared by the literature method38
or purchased from Aldrich Chemical Co. Cyclopentadiene was
obtained by cracking the dimer according to the literature
procedure.39 TCNE (Aldrich) was recrystallized from 1,2-
dichloroethane. Reactions were monitored by thin-layer chro-
matography (TLC) using glass-backed silica gel TLC plates.
Visualization was done with iodine vapor and/or staining with
phosphomolybdic acid (PMA, 5% solution in ethanol) followed
by heating. Concentrations were performed by rotary evapora-
tion using water aspirator vacuum. Low-pressure chromatog-
raphy (LPC) was carried out by applying air pressure to Pyrex
columns packed with EM Science silica gel 60 (0.040-0.063
mm particle size, 230-400 mesh). Routine 1H NMR spectra
Con clu sion s
The perfluoroalkyldicyanoolefin BTF (1) reacts rapidly
with 6,6-dimethylfulvene (2) to give the [4 + 2] cycload-
dition product 3. The cycloadduct exists in equilibrium
with the starting materials in certain solvents. Density
functional theory calculations of the Diels-Alder reaction
suggest an asynchronous process with much greater
formation of C3-C4 than C1-C2 in the transition state
leading to 3.
While the BTF adduct 3 exists in a stable equilibrium
with its precursors in less-polar solvents, it converts to
the formal [2+2] adduct 6 in certain polar solvents and
on contact with silica gel or alumina. Although a mech-
anism involving a radical species cannot be unequivocally
ruled out based on the evidence at hand, the necessity
of a polar medium to effect the conversion of the bridged
bicycle 3 to the fused-ring cyclobutane system of 6
suggests a zwitterionic intermediate stabilized by delo-
calization of the positive charge over the pentadiene
system of the fulvene ring and the negative charge over
the geminal-dicyano moiety. The rearrangement of 3 to
6 also occurs upon standing at room temperature in the
absence of solvent. An experiment designed to determine
whether this transformation is topotactic was compli-
cated by the fact that the two compounds could not be
observed as a solid solution.
In the presence of acid, an entirely different reaction
manifold becomes available to the kinetic product 3. The
BTF present in the equilibrium mixture reacts with the
fulvene isomer, 1-isopropenyl-1,3-cyclopentadiene, to give
the indene 8. The process by which 8 is formed is
regiospecific in two senses. First, given the choice be-
tween the diene system consisting of the two double
bonds in the cyclopentadiene ring or the diene consisting
of the exocyclic double bond and the adjacent endocyclic
bond, the BTF adds across the latter diene system. This
regiospecificity is opposite to that seen for the captodative
cyanoolefin, 2-acetyloxy-2-propenenitrile, and is predicted
by density functional theory calculations. Second, BTF
adds so as to give exclusively the regioisomer in which
the bulky CF3 groups are placed away from the more
hindered bridgehead carbon.
The cycloaddition product 5 from the reaction of
tetracyanoethylene with 6,6-dimethylfulvene undergoes
the same rearrangement and alternative Diels-Alder
reactions as the BTF cycloadduct 3, albeit at slower rates.
As reported in other reactions of BTF with olefinic
systems, greater polarizability and the steric demand of
the trifluoromethyl groups result in rate acceleration
relative to TCNE. Hybrid density functional theory
performed well in modeling the transition states and
predicting the relative energies of the products.
were recorded at 500 MHz. Broad-band H decoupled 13C NMR
1
spectra were recorded at 125 MHz. 19F NMR spectra were
1
recorded at 377 MHz. H chemical shifts are reported in ppm
downfield from internal tetramethylsilane. 13C chemical shifts
are reported in ppm relative to CDCl3 (77.0 ppm). Freon-11
was used as an internal standard for 19F spectra. Significant
1H NMR data are tabulated in order: multiplicity (s, singlet;
d, doublet; t, triplet; q, quartet; dist., distorted; br, broad),
number of protons, coupling constant(s) in hertz (Hz), assign-
ment.
X-r a y Diffr a ction Stu d ies (Str u ctu r es). All of the crystal
structure data were collected using a Rigaku RU300 diffrac-
tometer (Mo KR radiation) equipped with a Raxis-II image
plate detector and MSC low-temperature unit. No absorption
corrections were applied. A total of 180° of ω-scans were
performed for each compound with a crystal-to-plate distance
of 85 mm. The structures were solved by direct methods
(MULTAN or teXsan)40 and the final refinement was done
using the Z-refinement package.40 Refinement by full-matrix
least squares on F with the R-indices defined as R1 )
Σ(||Fo| - |Fc||)/Σ|Fo| and Rw ) [Σw(|Fo| -|Fc|)2/Σw|Fo| ]1/2 with
2
w proportional to [σ2(I) + 0.0009I2] -1/2. For the final refine-
ments, the hydrogen atoms were idealized close to the previ-
ously refined positions. Atomic scattering factors were taken
from the International Tables for X-ray Crystallography, Vol.
IV.
Th eor etica l P r oced u r es. All calculations were carried out
using either the Gaussian 94 or 98 programs.42 Geometry
optimization and transition state search were carried out using
the B3LYP hybrid density functional theory method43 with the
6-31G(d) basis set. Frequency calculations were carried out
to characterize the Diels-Alder transition states.
(38) Stone, K. J .; Little, R. D. J . Org. Chem. 1984, 49 (11), 1849-
1853.
(39) Korach, M.; Nielsen, D. R.; Rideout, W. H. Dihydroxycyclopen-
tene. In Organic Syntheses; Baumgarten, H. E., Ed.; J ohn Wiley and
Sons: New York, 1973; Collect. Vol. V, pp 414-418.
(40) TeXsan Structure Solution Software; Molecular Structure
Corp.: 1985, 1992.
(41) Calabrese, J . C. Z Structure Solution Software; E. I. DuPont
de Nemours & Co.: Wilmington, Delaware, 1994.
(42) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J . R.; Zakrzewski, V. G.; J . A. Montgomery,
J .; Stratmann, R. E.; Burant, J . C.; Dapprich, S.; Millam, J . M.; Daniels,
A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; J . Tomasi; Barone, V.;
Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford,
S.; Ochterski, J .; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma,
K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J . B.;
Cioslowski, J .; Ortiz, J . V.; Stefanov, B. B.; Liu, G.; Liashenko, A.;
Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J .; Keith,
T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.;
Challacombe, M.; Gill, P. M. W.; J ohnson, B.; Chen, W.; Wong, M. W.;
Andres, J . L.; Gonzalez, C.; Head-Gordon, M.; Replogle, E. S.; Pople,
J . A. Gaussian, Revision A.5; Gaussian, Inc.: Pittsburgh, PA, 1998.
(43) (a) Becke, A. D. J . Chem. Phys. 1993, 98 (7), 5648-5652. (b)
Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B: Condens. Matter 1988, 37
(2), 785-789.
J . Org. Chem, Vol. 68, No. 1, 2003 127

Howard et al.
7-(1-Meth yleth yliden e)-3,3-bis(tr iflu or om eth yl)bicyclo-
[2.2.1]h ep t-5-en e-2,2-d ica r bon itr ile (3). 2,2-Bis(trifluoro-
methyl)-1,1-dicyanoethylene5 (1; 1.88 g, 8.78 mmol) was added
dropwise via syringe over 1 min to a magnetically stirred
solution of 6,6-dimethylfulvene (2; 1.0 g, 9.4 mmol) in hexanes
(10 mL) at room temperature. As each drop was added a bright
red color was noted, which then quickly dissipated. A white
precipitate began to form before the addition was complete.
After 10 min the reaction mixture was filtered. The collected
precipitate was washed with hexanes and pumped under high
vacuum. Yield: 2.0 g (71%). Mp: 104-105 °C. IR (KBr
used to calculate the orthorhombic cell parameters: a )
14.592(1) Å, b ) 14.909(1) Å, c ) 11.280(1) Å. For Z ) 8, the
calculated density is 1.268 g/mL and µ(Mo) ) 0.75 cm-1. The
full-matrix least squares refinement of 325 parameters in
space group P212121 (no. 19) converged at R1 ) 0.048, Rw )
0.051 with the goodness of fit ) 2.49. The data/parameter ratio
was 8.70. An ORTEP diagram is shown in Figure 1b with
thermal ellipsoids drawn to the 50% probability level.
2-(1-Meth yleth yliden e)-7,7-bis(tr iflu or om eth yl)bicyclo-
[3.2.0]h ep t-3-en e-6,6-d ica r bon itr ile (6). Silica gel (5 g) was
added to a solution of the bridged bicycle (3) (1.85 g, 5.78 mmol)
in CH2Cl2 (25 mL), and the solvent was removed by rotary
evaporation. The resulting powder was applied to a column
containing 150 g of silica gel slurry-packed in hexanes. The
column was eluted with 10% EtOAc in hexanes (2 L) to give
1.66 g (90%) of pure cyclobutane (6) as a white powder after
evaporation of the eluent. Mp: 90-91 °C. IR (KBr press): 2253
press): 2249 (w), 1274 (s), 1245 (m), 1233 (m), 1206 (s) cm-1
.
The 1H NMR spectrum of this product in CDCl3 indicated it
to be a mixture of the desired bicycle (3) and 6,6-dimethylful-
vene (2) in a ratio of 91:9, respectively. The NMR spectroscopic
1
data for 3 only are reported here. H NMR (500 MHz, CDCl3)
δ: 1.63 (s, 3H, CH3), 1.73 (s, 3H, CH3), 3.99 (t, J ) 2.3 Hz,
1H, H4), 4.34 (s, 1H, H1), 6.63-6.68 (m, 1H, H5), 6.68-6.71
(m, 1H, H6). 13C NMR (125 MHz, CDCl3) δ: 19.71 (CH3), 20.01
(CH3), 38.75 (C2), 48.08 (C4 or C1), 57.75 (C1 or C4), 66.91
(septet, J ) 24 Hz, C3), 111.74 (CN), 112.42 (CN), 121.45 (C1′),
122.23 (q, J ) 288 Hz, CF3), 122.71 (q, J ) 288 Hz, CF3), 135.82
(C5), 137.67 (C7), 139.35 (C6). 19F NMR (377 MHz, CDCl3) δ:
-63.69 (q, J ) 13 Hz, 3F), -58.36 (q, J ) 13 Hz, 3F). MS
(APCI, negative ion): m/z 320 (M+), 273, 214. Anal. Calcd for
1
(w), 1329 (m), 1283 (s), 1208 (s), 1197 (m) cm-1. H NMR (400
MHz, CDCl3) δ: 1.72 (s, 3H, H10), 1.88 (s, 3H, H9), 4.06 (d,
J ) 8.2 Hz, 1H, H1), 4.24 (dd, J ) 2.0, 8.2 Hz, 1H, H5), 6.00
(dd, J ) 3, 5 Hz, 1H, H4), 6.94 (d, J ) 5 Hz, 1H, H3). NOE-
difference experiment (400 MHz, CDCl3): irradiation of the
singlet at δ 1.88 caused enhancement of the doublet at δ 6.94
(H3), irradiation of the singlet at δ 1.72 caused enhancement
of the doublet at δ 4.06 (H1). 13C NMR (100 MHz, CDCl3, peak
assignments based on HETCOR experiments) δ: 21.22 (C2′),
21.87 (C3′), 34.11 (C6), 39.88 (C1), 51.51 (C5), 58.72 (septet,
J ) 26.9 Hz, C7), 109.76 (CN), 111.51 (CN), 120.95 (q, J )
285 Hz, CF3), 122.64 (q, J ) 285 Hz, CF3), 126.03 (C4), 132.92
(C2), 133.78 (C1′), 140.79 (C3). 19F NMR (377 MHz, CDCl3) δ:
-69.40 (q, J ) 10.7 Hz, 3F), -64.46 (q, J ) 10.7 Hz, 3F). MS
(APCI, negative ion): m/z 320 (M+), 293, 214. Anal. Calcd for
C
14H10N2F6: C, 52.51; H, 3.15; N, 8.75; F, 35.60. Found: C,
52.65; H, 3.01; N, 8.76; F, 35.67.
The product was crystallized from Et2O/petroleum ether at
0 °C to give X-ray quality crystals. X-ray data for C14H10N2F6
(3) were collected at -50 °C using a colorless crystal with
dimensions of ∼ 0.25 × 0.35 × 0.40 mm. A total of 6239
reflections were collected and merged using Z41 (Rm ) 0.021)
to yield 2974 unique reflections with I > σ3(I). All of the
observed data were used to calculate the triclinic cell param-
eters: a ) 12.442(1) Å, b ) 12.661(1) Å, c ) 8.621(1) Å, R )
90.118(6)°, â ) 99.075(5)°, and γ ) 94.220(3)°. For Z ) 4, the
calculated density is 1.592 g/mL and µ(Mo) ) 1.47 cm-1. The
full-matrix least squares refinement of 397 parameters in
space group P-1 (no. 2) converged at R1 ) 0.040, Rw ) 0.044
with the goodness of fit ) 1.58. The data/parameter ratio was
7.41. An ORTEP diagram is shown in Figure 1a with thermal
ellipsoids drawn to the 50% probability level.
C
14H10N2F6: C, 52.51; H, 3.15; N, 8.75; F, 35.60. Found: C,
52.32; H, 3.38; N, 8.69; F, 35.51.
A small sample of the product was crystallized from Et2O/
petroleum ether to give X-ray quality crystals. X-ray data for
C
14H10N2F6 (6) were collected at -52 °C using a colorless
crystal with dimensions of ∼0.35 × 0.15 × 1.10 mm. A total
of 3127 reflections were collected and merged using Z41 (Rm
)
0.039) to yield 1090 unique reflections with I > σ3(I). All of
the observed data were used to calculate the triclinic cell
parameters: a ) 9.357(3) Å, b ) 12.235(4) Å, c ) 6.691(2) Å,
R ) 99.86(6)°, â ) 109.11(2)°, and γ ) 85.38(3)°. For Z ) 2,
X-ray quality crystals of 3 could also be obtained by water-
cooled, coldfinger sublimation of the microcrystalline precipi-
tate from the Diels-Alder reaction at 0.06 mmHg vacuum with
heating to 35 °C in an oil bath.
the calculated density is 1.492 g/mL and µ(Mo) ) 1.38 cm-1
.
The full-matrix least squares refinement of 199 parameters
in space group P-1 (no. 2) converged at R1 ) 0.068, Rw ) 0.066
with the goodness of fit ) 1.85. The data/parameter ratio was
5.43. An ORTEP diagram is shown in Figure 1c with thermal
ellipsoids drawn to the 50% probability level.
7-(1-Meth yleth ylid en e)bicyclo[2.2.1]h ep t-5-en e-2,2,3,3-
tetr a ca r bon itr ile (5).14 A solution of TCNE (1.48 g, 11.6
mmol) in acetone (15 mL) was added dropwise over 10 min to
a solution of 2 (1.34 g, 12. 6 mmol, 109 mol %) in acetone (20
mL) at -60 °C. A white precipitate formed in approximately
5 min. The reaction mixture was allowed warm to room
temperature over 4 h. The clear, colorless solution was cooled
to -30 °C, and the resulting precipitate was collected by
filtration and washed with hexanes. The analytically pure
white solid (1.95 g, 72%) thus obtained had spectroscopic data
identical to those previously reported for bicycle 5. Mp: 137-9
X-r a y Diffr a ction Ca p illa r y Exp er im en t. In an attempt
to determine if the transformation from 3 to 6 occurs as a
topotactic rearrangement, a single crystal of 3 was mounted
and sealed in a glass capillary. For this experiment, crystals
were obtained by the sublimation procedure given above in
the experimental procedure for 3.
First, the cell parameters of the singular piece were quickly
matched to those of 3 using a Bruker CCD system. The
capillary was then stored at room temperature for 14 days
when it was observed that the same crystal was reduced in
size and two smaller pieces had started to form near the
endpoints of the original crystal. By translating the capillary
to center first the original crystal and then the smaller
crystallites, the unit cell parameters for the original piece and
one of the smaller pieces were determined. While the cell
parameters for the larger original piece still matched those of
3, the smaller subset of reflections from the newly sublimed
crystals matched the cell parameters of 6. After 6 weeks of
storage at room temperature, the transformation was observed
to be complete. The original crystal was gone and the two
smaller crystallites had grown in size. The unit cell parameters
of both the two individual crystals were matched to 6.
°C dec (lit.14a mp 138-9 °C). IR (KBr press): 2252 cm-1 1H
.
NMR (500 MHz, CDCl3) δ: 1.82 (s, 6H), 4.45 (t, 2H, J ) 2.0
Hz, H1/H4), 6.77 (t, 2H, J ) 2.0 Hz, H5/H6). 13C NMR (125
MHz, CDCl3) δ: 20.08 (CH3), 46.07 (C2/C3), 55.11 (C1/C4),
110.81 (CN), 111.41 (CN), 127.37 (C1′ or C7), 135.46 (C7 or
C1′), 137.98 (C5/C6). MS (APCI, negative ion): m/z 234 (M•),
128. Anal. Calcd for C14H10N4: C, 71.78; H, 4.30; N, 23.92.
Found: C, 71.87; H, 4.34; N, 24.05.
X-ray quality crystals of 5 were grown by slow diffusion of
hexanes into an ethyl acetate solution of the above solid at
room temperature. X-ray data for C14H10N4 (5) were collected
at -100 °C using a colorless crystal with dimensions of
∼0.26 × 0.37 × 0.40 mm. A total of 13704 reflections were
collected and merged using Z41 (Rm ) 0.020) to yield 2838
unique reflections with I > σ3(I). All of the observed data were
128 J . Org. Chem., Vol. 68, No. 1, 2003

Reaction of BTF with 6,6-Dimethylfulvene
Sta bility Test of Cyclobu ta n e (6). The bicyclic cyclobu-
tane product 6 (12 mg) was placed in a 5 mm NMR tube and
dissolved in 0.6 mL of DMSO-d6. The 1H NMR spectrum at
room temperature showed only the cyclobutane product 6 with
to yield 4626 unique reflections with I > σ3(I). All of the
observed data were used to calculate the triclinic cell param-
eters: a ) 12.842(1) Å, b ) 18.551(1) Å, c ) 9.302(1) Å, R )
98.26(1)°, â ) 96.85(1)°, and γ ) 71.46(1)°. For Z ) 6, the
calculated density is 1.539 g/mL and µ(Mo) ) 1.42 cm-1. The
full-matrix least squares refinement of 715 parameters in
space group P-1 (no. 2) converged at R1 ) 0.036, Rw ) 0.039
with the goodness of fit ) 1.90. The data/parameter ratio was
6.43. An ORTEP diagram is shown in Figure 1d with thermal
ellipsoids drawn to the 50% probability level.
1
no detectable fulvene present. H NMR (500 MHz, DMSO-d6)
δ: 1.66 (s, 3H), 1.85 (s, 3H), 4.28 (d, 1H, J ) 8.2 Hz), 4.48 (br
d, 1H, J ) 8.1 Hz), 6.12 (dd, 1H, J ) 3.1, 5.4 Hz), 7.06 (d, 1H,
J ) 5.6 Hz).
The tube was immersed in an oil bath at 100 °C for 15 min
1
and then cooled to room temperature. The H NMR spectrum
was recorded and showed a mixture of cyclobutane 6 and 6,6-
dimethylfulvene (2) in a ratio of 73:27, respectively (based on
integration of the proton signals in the vinyl region of the
spectrum). The NMR tube was then immersed in an oil bath
at 120 °C for 20 min and then cooled to room temperature.
The 1H NMR spectrum was recorded and showed a mixture
of cyclobutane 6 and 6,6-dimethylfulvene (2) in a ratio of 1:1.
Finally, the NMR tube was immersed in an oil bath at 140 °C
for 15 min, then cooled to room temperature. The 1H NMR
spectrum was recorded and showed a mixture of cyclobutane
6 and 6,6-dimethylfulvene (2) in a ratio of 24:76, respectively.
No peaks attributable to the formal [6 + 2] adduct were
observed.
Treatment of 3 with acetic acid (200 mol %) in CDCl3 did
not produce any detectable amount of 8 after 9 d at room
temperature. Treatment of 3 with trifluoroacetic acid (200 mol
% or 40 mol %) in CDCl3 for 16 h at room temperature gave a
mixture of 8 and 6 in a ratio of 78:22, respectively.
3a ,6-Dih yd r o-7-m eth yl-1H-in d en e-4,4,5,5-tetr a ca r bon i-
tr ile (9).14c To a solution of bridged bicycle 5 (300 mg, 1.3
mmol) in CDCl3 (15 mL) was added p-toluenesulfonic acid
monohydrate (49 mg, 0.26 mmol). The mixture was heated at
reflux for 1 h, diluted with CH2Cl2 (25 mL), and washed with
saturated aqueous NaHCO3 (2 × 20 mL). The combined
organic phase was washed, dried (Na2SO4), filtered, and
concentrated by rotary evaporation to give 0.27 g of the desired
product as a brown oil. The crude product was purified by LPC
(eluting with 100% hexanes then 10% EtOAc in hexanes) to
give 170 mg (56%) of pure 9 as a white solid: mp 97-8 °C
(lit.14c mp 92-3 °C). IR (KBr press): 2255 cm-1. 1H NMR (500
MHz, CDCl3) δ: 1.80 (s, 3H), 3.07, 3.30 (AB pattern, J AB ) 18
Hz, 2H, H1), 3.13-3.22 (m, 2H, H6), 4.08 (s, 1H, H3a), 5.98-
6.02 (m, 1H, H3), 6.31-6.35 (m, 1H, H2). 13C NMR (125 MHz,
CDCl3, APT pulse sequence with C and CH2 indicated by (+)
and CH and CH3 by (-)) δ: 18.37 (CH3), 36.67 (+), 38.00 (+),
38.74 (+), 41.55 (+), 50.52 (C3a), 108.38 (+), 110.92 (+), 111.03
(CN), 111.29(+), 121.39 (+), 124.57 (-), 129.89 (+), 136.66 (-).
MS (APCI, negative ion): m/z (M-). Anal. Calcd for C14H10N4:
C, 71.78; H, 4.30; N, 23.92. Found: C, 71.59; H, 4.30; N, 24.03.
1,3a ,5,6-Tetr a h yd r o-7-m eth yl-5,5-bis(tr iflu or om eth yl)-
4H-in d en e-4,4-d ica r bon itr ile (8). To a solution of bridged
bicycle (3) (1.0 g, 3.1 mmol) in CDCl3 (20 mL) was added
p-toluenesulfonic acid monohydrate (119 mg, 0.62 mmol). The
mixture was stirred at room temperature for 18 h, diluted with
CH2Cl2 (20 mL), and washed with saturated aqueous NaHCO3
(2 × 20 mL). The separate aqueous layers were back-extracted
with CH2Cl2 (20 mL), and the combined organic phase was
washed with brine (30 mL), dried (Na2SO4), filtered, and
concentrated by rotary evaporation to give 0.94 g of the desired
product as a light brown semisolid. The crude product was
combined with the products obtained from two earlier runs of
this experiment (100 mg and 430 mg scale, respectively) and
purified by LPC (eluting with 100% hexanes then 10% EtOAc
in hexanes) to give 1.05 g (69%) of pure tetrahydroindene 8
as a white solid. Mp: 81-82 °C. IR (KBr press): 2256 (w),
Ack n ow led gm en t. Dedicated to Professor Henry
Rapoport (November 16, 1918-March 6, 2002). We
thank Mr. Fred Davidson, Mr. J ohn C. Groce, Mr. Bruce
A. Lockett, and Dr. Steven K. Gee for high-field NMR
work, Dr. J oseph C. Calabrese for X-ray crystallographic
determination of structures 3 and 6, and Professors Rolf
Huisgen (University of Mu¨nchen), Pierre Laszlo (Uni-
versity of Liege), J ohn Scheffer (University of British
Columbia), and Tommy Liljefors (Royal Danish School
of Pharmacy) for helpful discussions.
1
1289 (s), 1271 (s), 1231 (s), 1221 (s), 1204 (s) cm-1. H NMR
(500 MHz, CDCl3) δ: 1.78 (s, 3H, CH3), 2.61, 2.66 (AB pattern,
J AB ) 19 Hz, 2H, H6), 3.07, 3.23 (AB pattern, J AB ) 20 Hz,
2H, H1), 3.89 (s, 1H, H3a), 5.94-5.99 (m, 1H, H3), 6.23-6.28
(m, 1H, H2). 13C NMR (125 MHz, CDCl3) δ: 18.81 (CH3), 30.84
(C6), 36.58 (C1), 38.15 (C4), 51.41 (C3a), 56.83 (septet, J )
25.7 Hz, C5), 110.58 (endo-CN), 111.75 (exo-CN), 122.91 (q,
J ) 288 Hz, exo-CF3), 123.23 (q, J ) 288 Hz, endo-CF3), 123.84
(C7 or C7a), 125.52 (C3), 131.25 (C7 or C7a), 136.27 (C2). 19F
NMR (377 MHz, CDCl3) δ: -68.73 (q, J ) 11 Hz, 3F), -66.21
(q, J ) 11 Hz, 3F). MS (APCI, negative ion): m/z 320 (M+),
291, 222, 214. Anal. Calcd for C14H10N2F6: C, 52.51; H, 3.15;
N, 8.75; F, 35.60. Found: C, 52.56; H, 3.05; N, 8.78; F, 35.81.
A small sample of the product was crystallized from Et2O/
hexanes to give X-ray quality crystals. X-ray data for C14H10N2F6
(8) were collected at -100 °C using a colorless crystal with
dimensions of ∼0.23 × 0.24 × 0.28 mm. A total of 11050
reflections were collected and merged using Z41 (Rm ) 0.035)
Su p p or tin g In for m a tion Ava ila ble: Crystallographic
structure determination of 3, 5, 6, and 8 (CIF); calculated
structures of the π-complexes of BTF and TCNE with 2;
photographs of the crystal-to-crystal conversion of 3-6; num-
bering scheme for 3 and 5-9. This material is available free
of charge via the Internet at http://pubs.acs.org.
J O0265333
J . Org. Chem, Vol. 68, No. 1, 2003 129