Demonstration of the facile reversibility of fulvene formation

Article abstract of DOI:10.1016/j.tet.2011.03.094

Cleavage of fulvenes under mild conditions and interchange between electron-deficient fulvenes and their constituent cyclopentadienes and imines is demonstrated for the first time. A series of cyclopentadienes and imines are investigated to probe the dependence of fulvene equilibration on structure. The exchange of one fulvene for another is demonstrated in the first reported example of transfulvenation. Finally, the metathesis of two fulvenes to generate all four possible cross products is shown.

Full text of DOI:10.1016/j.tet.2011.03.094

Tetrahedron 67 (2011) 4364e4370
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Tetrahedron
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Demonstration of the facile reversibility of fulvene formation
*
Jeffrey S. Bandar, Rockford W. Coscia, Tristan H. Lambert
Department of Chemistry, Columbia University, 3000 Broadway, New York, NY 10027, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Cleavage of fulvenes under mild conditions and interchange between electron-deficient fulvenes and
their constituent cyclopentadienes and imines is demonstrated for the first time. A series of cyclo-
pentadienes and imines are investigated to probe the dependence of fulvene equilibration on structure.
The exchange of one fulvene for another is demonstrated in the first reported example of trans-
fulvenation. Finally, the metathesis of two fulvenes to generate all four possible cross products is shown.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 12 January 2011
Received in revised form 25 March 2011
Accepted 28 March 2011
Available online 5 April 2011
Keywords:
Fulvenes
Cyclopentadienes
Retro-Knoevenagel
Transfulvenation
Fulvene metathesis
1. Introduction
(a) fulvenes
Alkylidene cyclopentadienes, commonly known as fulvenes,1
are a class of 6 -electron cross-conjugated isomers of benzene
First prepared by Thiele in 1900
6 electron cross conjugated -system
polarized due to aromaticity
useful for cycloadditions, organometallic ligands,
complex molecule synthesis, etc.
p
first prepared by Thiele in 1900 (Fig. 1a).2 In the ensuing 110 years,
fulvenes have been the subject of extensive investigations into their
physical properties, their potential as organometallic ligands, and
their synthetic utility.3 In light of this longstanding and intense
interest in fulvene chemistry, we found it remarkable that the issue
of fulvene cleavage (retrofulvenation) had never been examined.
We became interested in the possibility of facile retrofulvenation
because of its potential to serve as a novel mechanistic platform for
applications ranging from catalysis to dynamic covalent chemistry.
In this article we demonstrate for the first time the cleavage of
fulvenes under mild conditions and the facile interconversion of
fulvenes and their corresponding imines and cyclopentadienes.
Perhaps the most conspicuous feature of fulvenes is the rela-
tively high polarization of the exocyclic olefin and the consequent
electropositive character of the 6-carbon (Fig. 1b). This polarization
is attributed to the fact that cyclopentadienyl anions, and hence the
zwitterionic resonance form of fulvenes, possess aromatic charac-
ter. Indeed, this polarization is such that the exocyclic fulvenic
double bond displays many modes of reactivity analogous to that of
aldehydes and ketones. For example, even simple fulvenes readily
undergo nucleophilic substitution4 at the 6-position and can be
deprotonated to produce vinyl cyclopentadienyl anions (pKa of 6,6-
dimethylfulvene in DMSO¼22.7).5 The analogy between fulvenes
R
fulvenes
R
(b)
fulvene polarization
–
–
+
O
O
+
R
R
R
R
fulvenes
carbonyls
6
R
R
R
R
polarized due to aromaticity
polarized due to atom
electronegativity
of cyclopentadienyl anion
Fig. 1. Fulvenes.
and carbonyls is underscored by the fact that the most common
synthetic approach to fulvenes is by condensation of a cyclo-
pentadiene with an aldehyde or ketone, often via iminium ion ac-
tivation. Indeed, base-promoted condensations have been the
strategy of choice for fulvene synthesis ranging from Thiele’s
original work2 (NaOMe) to the modern approaches of Little6 and
Erden7 (pyrrolidine). As the dehydrative condensation of an acidic
methylene compound with an aldehyde or ketone, this strategy of
fulvene formation is of course an example of the Knoevenagel re-
action. As such, we reasoned that it should, under appropriate
circumstances, be a readily reversible process.
Surprisingly, however, this issue appears not to have been
addressed in the literature. In fact, we know of only one reliable
example of fulvene cleavage: a 1954 report by Taber describing the
* Corresponding author. E-mail address: tl2240@columbia.edu (T.H. Lambert).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.094

J.S. Bandar et al. / Tetrahedron 67 (2011) 4364e4370
4365
Ph
Ph
CO2Me
‘retro-Mannich’ reaction of 1,2,3,4-tetraphenylfulvene in refluxing
Ph
MeO2C
Ph
piperidine (Fig. 2).8 The dynamic interchange of fulvenes and car-
bonyls or imines is wholly unknown. Nevertheless, it seemed to us
a reasonable assumption that sufficiently electron-deficient ful-
venes should be prone to facile cleavage, particularly by nucleo-
philic amine bases. Because of the longstanding importance of
fulvene chemistry and a significant opportunity to enable novel
applications of this unique class of molecules, we decided to in-
vestigate the possibility of achieving facile fulvene reversibility.
N
Ph
9
+
(a)
(b)
Ph
MeO2C
10
CO2Me
+
PhNH2
Ph
8
(a)
time (min)
time (min)
10:9
(b)
solvent
CDCl3
10:9
60
60
2.2:1
2.5:1
10
10
6.5:1
7.0:1
d -THF
8
Scheme 2. Demonstration of fulvene/imine equilibration.
X
FG
+
R
2.2. Effect of substrate structure on fulvene/imine
interchange
facile
fulvene
fulvene
reversibility
cleavage
formation
one example
1954
since 1900
this work
Next, to probe the effect of fulvene structure and amine catalyst
on this process, we prepared cyclopentadienes 11e13, and, along
with cyclopentadiene 8, examined fulvene formation and cleavage
with several imines (Table 1). For these experiments we again ex-
amined by 1H NMR both the forward and reverse reactions in
CDCl3, noting, in each case, the ratio of fulvene to imine at a speci-
fied reaction time that for a number of the substrates (entries 1e6,
9, 10, 15, and 16) corresponded to the time to reach a steady state.
To begin, we examined the effect of imine structure on the for-
mation and cleavage of fulvene 10 (Table 1). In comparison to the
aniline derived imine (entry 1), N-cyclohexylamine (entry 2) and
N-butylamine (entry 3) imines both resulted in decreased reaction
time (20 min) and produced mixtures that slightly favored imine over
fulvene. Interestingly, wefoundthatinalteringtheelectronicprofile of
the imine aryl substituent, both electron-withdrawing (entry 4) and
electron-donating (entry 5) substituents increased reaction time
substantially, although the effect was much greater in the latter case.
Presumably the electron-donating methoxy substituent serves to
hinder both the addition of cyclopentadienyl anion to iminium ion
(forward) and the addition of amine to fulvene (reverse). An extended
timeperiod(12 h)wasalsorequiredwithcinnamaldehydeSchiffbase;
in this case fulvene was completely favored over imine (entry 6). This
bias is likely the result of increased stabilization of the highly conju-
gated 6-vinylfulvene. However, an increased fulvene selectivity was
observed with N-phenylcyclohexylimine as well, although in this case
the forward and reverse reactions did not converge to the same ful-
vene/imine ratios (entry 7). Notably, fulvene formation with this ali-
phatic aldehyde occurred within 10 min, in sharp contrastto reactions
with aryl imines.
FG
+
possible applications
in catalysis or dynamic
covalent chemistry
H2X
X = O or NR
R
Fig. 2. Reversible fulvene formation.
2. Results and discussion
2.1. Demonstration of fulvene/imine interchange
The mechanism of the proposed fulvene aminolysis is essen-
tially that of a retro-Knoevenagel condensation, and involves (1)
addition of an amine to the exocyclic fulvenic olefin, and (2) sub-
sequent expulsion of a cyclopentadienyl anion to form an iminium
ion (Scheme 1). Based on this consideration we expected that those
fulvenes prone to facile cleavage should possess relatively electron-
deficient cyclopentadienyl moieties. Thus we decided to examine
fulvenes prepared from carboxylate-bearing cyclopentadienes,
which are relatively acidic9 and straightforward to prepare (see
Supplementary data).
FG
FG
FG
H2NR'
amine
addition
–
H
+
R'
R'
H
R
N
H
R
N
H
R
1
2
3
Cp–
expulsion
FG
4
FG
–
Fulvene/imine interchange was also observed with tetrahy-
droindene 11, although aniline proved to be a poor participant in this
case and did not result in convergence of the forward and backward
reactionsevenafter48 h(entry8). Werationalizethislowerreactivity
bythedecreasedacidityofthedialkyl-substitutedcyclopentadiene11
versus the diaryl-substituted 8. On the other hand, N-cyclohexyl-
amineandN-butylamineenabledrapidformationandcleavage, again
favoring imine to a slight extent in both cases (entries 9 and 10).
In contrast to the above results, fulvenation dynamics using
cyclopentadiene 12 were rather inconsistent. For instance, N-phe-
nylbenzaldimine and 12 reacted to produce a 2:1 mixture of fulvene
to imine over 48 h (entry 11). However, aniline was not productive
at facilitating the corresponding retrograde reaction. As observed in
entries 12 and 13, changing from N-aryl to N-alkyl substitution
provided greatly increased reaction rate of both fulvene formation
and cleavage, however neither the time to reach stasis nor the ratio
of fulvene to imine was the same for the forward and reverse re-
actions (entries 12 and 13). Further experimentation will be re-
quired to determine the reason for this disparate behavior.
6
+
R'
R'
R
N
R
5
N
H
7
Scheme 1. Mechanism of fulvene/imine equilibration.
In one of our initial experiments to examine fulvene cleavage,
we combined diester diphenylcyclopentadiene 8 with the aniline
Schiff base of benzaldehyde (9) in CDCl3 (Scheme 2). After 60 min,
we observed by 1H NMR an unchanging 2.2:1 mixture of fulvene 10
and imine 9. To investigate whether this mixture was an equilib-
rium ratio, we subjected fulvene 10 to an equivalent of aniline
under the same conditions.10 Immediately, cyclopentadiene 8 and
imine 9 were observed, and after 60 min. the ratio of fulvene to
imine was a constant 2.5:1, suggesting that this is in fact the ap-
proximate thermodynamic ratio. Notably, in THF-d8 the same re-
action came to equilibrium within 10 min as a 6.5e7:1 ratio of
fulvene to imine. To the best of our knowledge, these results rep-
resent the first example of fulvene cleavage under mild conditions
and the first demonstration of a fulvene in equilibrium with its
constituent imine and cyclopentadiene fragments.
Finally, we examined the reaction profile of cyclopentadiene 13,
which bears only a single electron-withdrawing group and was
thus expected to be less reactive than 8, 11, and 12. Indeed, no

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J.S. Bandar et al. / Tetrahedron 67 (2011) 4364e4370
Table 1
reaction was observed in either the forward (reaction of 13 with
Substrate scope studies for fulvene/imine exchange
N-phenylbenzaldimine) or the reverse (reaction of fulvene with
aniline) direction even after 8 days (entry 14). The alkyl amines/
imines on the other hand provided observable albeit slow reaction
in both directions (entries 15 and 16), with the butylamine case
approaching similar ratios in either direction after 8 days (entry 16).
Apparently, cyclopentadienes/fulvenes bearing a single electron-
withdrawing group represent the lower boundary of reactivity for
facile fulvene equilibration with imines.
FG
fulvene
(a)
FG
+
N
R
+
R'NH2
R'
(b)
imine
(I)
R
(F)
CDCl3
,b
Entry
1
Cyclopentadiene
Imine
(a) Time
(b) Time
F:Ia
F:I
60 min
60 min
2.2:1
2.5:1
N
Ph
Ph
2.3. Transfulvenation
20 min
20 min
1:1.6
1:1.9
N
Ph
2
3
4
5
6
7
We recognized that the facile reversibility of fulvene formation
offers the possibility of achieving the heretofore unknown process
of transfulvenation, whereby one fulvene would be mutated into
another. To demonstrate this possibility, we examined the conver-
sion of 6-phenylfulvene 10 (derived from benzaldehyde) to
6-styrenylfulvene 14 (derived from cinnamaldehyde) (Fig. 2). In-
terestingly, when fulvene 10 and the N-phenyl Schiff base of cin-
namaldehyde 15 were simply combined in CDCl3, we observed
conversion to fulvene 14 with the proportion of fulvene 14 in-
creasing to w75% of the total fulvene content over the course of 5
days (Fig. 3a). This fulvene interconversion is particularly notable in
that no amine was added, although we hypothesize that small
c-hex
20 min
20 min
1:2.4
1:2.2
N
Ph
n-Bu
Ph
MeO2C
Ph
CO2Me
120 min
150 min
3.1:1
2.4:1
N
4-NO2-Ph
4-OMe-Ph
Ph
Ph
8
20 h
20 h
2.7:1
2.2:1
N
Ph
12 h
12 h
>20:1
>20:1
N
Ph
10 min
10 min
13.1:1
6.3:1
N
c-hex
Ph
48 h
48 h
1.6:1
4.9:1
N
Ph
8
Ph
CO2Me
20 min
20 min
1:1.8
1:1.3
N
N
Ph
Ph
9
c-hex
n-Bu
CO2Me
11
20 min
20 min
1:2.5
1:1.9
10
48 h
48 h
1.8:1
>20:1
N
Ph
11
12
13
Ph
c-hex
CO2Me
CO2Me
Me
45 min
120 min
1.6:1
5.6:1
N
N
Ph
Ph
c-hex
n-Bu
12
15 min
120 min
1.3:1
3.4:1
8 days
8 days
<1:20
>20:1
N
Ph
14
15
Ph
t-Bu
8 days
8 days
8.3:1
10.1:1
N
N
Ph
Ph
c-hex
n-Bu
CO2Me
13
8 days
8 days
5.1:1
5.7:1
16
a
Fulvene and imine ratios were determined by 1H NMR relative to Bn2O as an
internal standard.
b
The reaction mixtures in entries 2, 3, and 8 contained intermediates in the
amounts of 10, 25, and 7%, respectively, that we believe correspond to intermediate
3 in Scheme 1.
Fig. 3. Demonstration of transfulvenation.

J.S. Bandar et al. / Tetrahedron 67 (2011) 4364e4370
4367
amounts of aniline resulting from imine hydrolysis by adventitious
water may have provided the means for the exchange. With this
thought in mind, we conducted the same experiment with the
addition of 1 equiv of aniline. As expected, the rate of conversion of
10 to 14 was dramatically increased, proceeding to >85% fulvene 14
in just over 1 day (Fig. 3b).
cyclohexylamine, and n-butylamine were freshly distilled over
CaH2 under argon. All other commercial reagents were used as
provided. Flash column chromatography was performed employing
32e63 mm silica gel (Dynamic Adsorbents Inc). Thin-layer chro-
matography (TLC) was performed on silica gel 60 F254 plates (EMD).
1H and 13C NMR were recorded in CDCl3 on Bruker DRX-300,
DRX-400, and DRX-500 spectrometers as noted. Data for 1H NMR
are reported as follows: chemical shift (
d ppm), multiplicity
(s¼singlet, br s¼broad singlet, d¼doublet, t¼triplet, q¼quartet,
m¼multiplet), coupling constant (Hz), integration, and assignment.
Data for 13C NMR are reported in terms of chemical shift. IR spectra
were recorded on a Nicolet Avatar 370 DTGS (Thermo) using NaCl
salt plates. High-resolution mass spectra were obtained from the
Columbia University Mass Spectrometry Facility on JOEL JMS-
HX110 HF mass spectrometer using the indicated ionization mode.
2.4. Demonstration of fulvene metathesis
As a further demonstration of fulvene exchange, we conducted
the metathesis of two fulvenes composed of different cyclo-
pentadienyl and exocyclic moieties (Scheme 3). Thus fulvenes 16
and 17 were combined with 1 equiv of butylamine in CDCl3 at room
temperature. After 19 h we observed by 1H NMR a mixture of ful-
venes 16e19, representing all four possible fulvene products, in
a 1.2:2.2:1.2:1.5 ratio, respectively, along with the N-butylimines 20
and 21. This demonstration of facile fulvene exchange raises the
possibility of developing dynamic covalent chemistry applications
that capitalize on the unique properties of fulvene architectures.
4.2. Synthesis of cyclopentadienes and fulvenes
4.2.1. Dimethyl 4,5-diphenylcyclopenta-3,5-diene-1,3-dicarboxylate
8. To 150 mL anhydrous ethanol was added dimethyl
2-oxo-4,5-diphenylcyclopenta-3,5-diene-1,3-dicarboxylate11 (5.24 g,
15.0 mmol). The solution was then cooled to 0 ꢀC and NaBH4 was
addedportionwiseover10 minwithstirring.Thereactionwasallowed
to continue stirring at this temperature for 15 min and was then
quenched by the addition of 100 mL of water. The mixture was
extracted with EtOAc (250 mL). The organic layer was washed with
brine, dried (MgSO4), and concentrated in vacuo. The crude alcohol
was used in the following step without further purification.
Ph
MeO2C
Ph
CO2Me
Ph
MeO2C
Ph
CO2Me
18
16
1 equiv n-BuNH2
O2N
CO2Me
CO2Me
The crude alcohol was dissolved in THF (200 mL). Acetic anhy-
dride (2.13 mL, 22.5 mmol), triethylamine (3.14 mL, 22.5 mmol),
and 4-(dimethylamino)pyridine (0.183 g, 1.50 mmol) were then
added and the reaction was stirred at room temperature for 2 h.
Water (150 mL) was added and the reaction was extracted with
EtOAc (200 mLꢁ3). The combined organic layers were washed with
brine, dried (MgSO4), and concentrated in vacuo. The crude acetate
was then used without further purification.
fulvene
metathesis
CO2Me
CO2Me
17
19
O2N
compound
relative amount
The crude acetate from the previous step was dissolved in
dichloromethane (200 mL) and 1,8-Diazabicyclo[5.4.0]undec-7-
ene (6.72 mL, 45 mmol) was added. The reaction mixture was
stirred at room temperature for 2 h and then quenched by the
addition of 1 M aqueous HCl (100 mL). This mixture was extracted
with EtOAc (200 mLꢁ3). The combined organic extracts were
washed with brine, dried (Na2SO4), and concentrated in vacuo. The
crude oil was purified by flash chromatography (dichloromethane)
and recrystallized twice from ether to yield the title compound
(2.84 g, 8.49 mmol, 57% yield from ketone) as fine colorless crystals.
1.2
2.2
1.2
1.5
16
17
18
19
1.6
1.0
20 4-NO2-PhCH=NBu
21 PhCH=NBu
Scheme 3. Fulvene metathesis.
3. Conclusions
We have demonstrated for the first time (1) that suitably acti-
vated fulvenes undergo facile aminolysis under mild reaction con-
ditions, (2) that such fulvenes may exist in observable equilibrium
with theirconstituent cyclopentadienes and imines, and (3) that this
equilibrium may be employed for the dynamic interchange of ful-
venes. Given the broad interest fulvenes have long attracted from
chemists of various disciplines, we expect these results may find
useful application in a number of different contexts.
1H NMR (300 MHz, CDCl3)
d 7.20 (m, 6H, ArH), 7.00 (m, 4H, ArH),
3.95 (s, 2H, CH2), 3.68 (s, 6H, CO2CH3); 13C NMR (75 MHz, CDCl3)
164.2, 156.2, 134.0, 133.8, 129.1, 127.8, 127.3, 51.4, 43.1; IR (thin film)
1716, 1489, 1434, 1361, 1207, 1102, 1083, 1003, 741, 698 cmꢂ1; HRMS
(FABþ) m/z¼334.1205 calcd for C21H19O4 [M]þ, found 334.1202.
4.2.2. Dimethyl 4,5,6,7-tetrahydro-1H-indene-2,3-dicarboxylate 11. To
sodium hydride (7 g, 60% in mineral oil, 175 mmol) that had been
washed with pentanes (40 mLꢁ3) was added 300 mL THF. The
resulting suspension was cooled to 0 ꢀC and freshly cracked cyclo-
pentadiene (6.0 mL, 80.4 mmol) was added via syringe. The reaction
flask was warmed to room temperature and stirred for 10 min before
cooling back to 0 ꢀC. After the addition of 1,4-dibromobutane
(9.6 mL, 80.4 mmol), the solution was refluxed overnight. An addi-
tional equivalent of sodium hydride (3.08 g, 80.4 mmol) was added
and the solution was further heated at reflux for 24 h. The reaction
mixture was quenched with H2O (250 mL) and extracted with EtOAc
(200 mLꢁ3). The organic extracts were washed with brine, dried
(Na2SO4), and concentrated in vacuo to give 10.7 g of pale yellow oil.
4. Experimental section
4.1. General information
All reactions were performed using oven-dried glassware under
an atmosphere of dry argon. Non-aqueous reagents were trans-
ferred by syringe under argon. Organic solutions were concentrated
using a Buchi rotary evaporator. Diethyl ether, tetrahydrofuran, and
methylene chloride (CH2Cl2) were dried using a J.C. Meyer solvent
purification
system.
Triethylamine
(Et3N),
aniline,

4368
J.S. Bandar et al. / Tetrahedron 67 (2011) 4364e4370
The crude oil was then used in the following step without further
purification.
olefin isomers (573 mg, 1.96 mmol, 56% yield). NMR data are
reported as the sodium salt of the title compound obtained by
treatment with sodium hydride and extraction with dimethylsulf-
The crude product from the previous step (10.7 g) was added to
100 mLTHF containing 5 g of activated 4 A molecular sieves, and the
oxide. 1H NMR (300 MHz, DMSO)
d
6.16 (d, J¼3.5 Hz, 1H, CpH), 5.37
ꢀ
resulting mixture was stirred at room temperature for 1 h. The dried
solutionwas cannulated intoa flask containing an additional 200 mL
THF, which was then cooled to ꢂ78 ꢀC. After the addition of n-
butyllithium (35.4 mL of 2.5 M solution in hexanes, 88.5 mmol), the
solution was warmed to room temperature and stirred for 30 min,
then cooled back to ꢂ78 ꢀC and treated with methyl chloroformate
(6.8 mL, 88.5 mmol). The reaction solution turned purple as it was
allowed to stir at room temperature for 36 h, after which H2O
(200 mL) was added. The resulting mixture was diluted with Et2O
before being extracted with 1 M NaOH (100 mLꢁ3). The combined
aqueous phase was acidified to pH 1 and extracted with EtOAc
(150 mLꢁ3). Concentration in vacuo yielded the title compound as
a mixture of olefin isomers (600 mg, 2.54 mmol, 3% yield). NMR data
are reported as the sodium salt of the title compound obtained by
treatment with sodium hydride and extraction with water. 1H NMR
(d, J¼3.5 Hz, 1H, CpH), 3.50 (s, 3H, CO2CH3), 3.46 (s, 3H, CO2CH3),
2.95 (quintet, J¼6.9 Hz, 1H, CpC(Me)(Cy)H), 1.70e1.50 (m, 5H, CyH),
1.25e0.82 (m, 6H, CyH), 1.01 (d, J¼6.9 Hz, 3H, CpC(CH3)CyH); 13C
NMR (75 MHz, DMSO) d 168.3, 166.0, 137.5, 116.6, 110.3, 109.4, 106.7,
49.2, 49.0, 44.6, 36.6, 31.33, 29.5, 26.5, 26.4,18.7; IR (thin film) 2926,
2848, 1739, 1709, 1539, 1435,1257 cmꢂ1; HRMS (EIþ) m/z¼292.1675
calcd for C17H24O4 [M]þ, found 292.1661.
4.2.4. Methyl 3-tert-butylcyclopenta-1,3-dienecarboxylate 13. A so-
lution of 6,6-dimethylfulvene6 (22.61 g, 213.0 mmol) in 500 mL
Et2O was cooled to 0 ꢀC and slowly treated with methyllithium
(139.8 mL, 1.6 M in Et2O, 223.0 mmol). The solution was warmed to
room temperature and stirred for 1 h. After cooling back to 0 ꢀC,
methyl chloroformate (32.91 mL, 425 mmol) was added and the
solution was stirred for 1 h. The reaction was then quenched with
500 mL H2O and extracted with Et2O (250 mLꢁ3). The combined
organic extracts were washed with brine, dried (MgSO4), concen-
trated in vacuo, and purified by flash chromatography (10:1 hex-
anes/Et2O) to yield the title compound as a yellow oil (6.43 g,
35.67 mmol, 19% yield) as a mixture of two olefin isomers (3:2 ra-
(300 MHz, D2O)
CO2CH3), 2.66 (m, 2H, eCH2e), 2.45 (m, 2H, eCH2e),1.64 (m, 4H, 2ꢁ
eCH2e); 13C NMR (75 MHz, D2O)
169.5, 169.1, 133.0, 122.9, 119.2,
d 6.42 (s, 1H, CpH), 3.70 (s, 3H, CO2CH3), 3.68 (s, 3H,
d
109.5, 106.9, 50.8, 50.6, 25.5, 24.2, 23.9, 23.7; IR (thin film) 2948,
1739, 1709, 1552, 1430, 1291, 1261, 1217, 1130 cmꢂ1; HRMS (EIþ) m/
z¼236.1049 calcd for C13H16O4 [M]þ, found 236.1048.
tio). 1H NMR (300 MHz, CDCl3)
d
7.50 (q, J¼1.7 Hz, 1H, CpH, minor),
7.31 (q, J¼2.2 Hz, 1H, CpH, major), 6.23 (m, 1H, CpH, major and
minor), 3.80 (s, 3H, CO2CH3, minor), 3.77 (s, 3H, CO2CH3, major),
3.31 (m, 2H eCH2e, major), 3.28 (t, J¼1.6 Hz, 2H, eCH2e, minor),
1.20 (s, 9H, C(CH3)3, major), 1.18 (s, 9H, C(CH3)3, minor); 13C NMR
4.2.3. Dimethyl
3-(1-cyclohexylethyl)cyclopenta-1,3-diene-1,2-di-
carboxylate 12. To a mixture of sodium (5.31 g, 230.9 mmol) in
200 mLTHFat 0 ꢀC was added 30 mL cyclopentadiene (401.8 mmol).
The resulting mixture was stirred at room temperature overnight,
after which it was cooled to 0 ꢀC, treated with methyl chloroformate
(32.98 mL, 428.6 mmol), and then stirred for 2 h at room tempera-
ture. The reaction mixture was filtered through a Celite plug and
concentrated in vacuo to furnish a brown oil. Addition of Et2O
(200 mL) resulted in precipitation of 6.50 g of a crude brown solid
that contained 1,2-dicarboxymethylcyclopentadienyl anion as its
sodium salt.
(75 MHz, CDCl3) d 167.4, 164.7, 156.9, 143.1, 142.9, 137.6, 134.3, 129.1,
124.0, 51.1, 51.0, 40.4, 40.0, 33.8, 32.1, 30.6, 29.6; IR (thin film)
2961, 1713, 1530, 1435, 1357, 1239, 1104 cmꢂ1; HRMS (FABþ)
m/z¼180.1150 calcd for C11H16O2 [M]þ, found 180.1159.
4.2.5. Dimethyl
2-benzylidene-4,5-diphenylcyclopenta-3,5-diene-
1,3-dicarboxylate. Dimethyl 4,5-diphenylcyclopenta-3,5-diene-1,3-
dicarboxylate (50 mg, 0.15 mmol) was dissolved in 1 mL THF.
The crude solid containing this cyclopentadienyl salt (3.00 g)
was dissolved in 200 mL THF and cooled to ꢂ30 ꢀC. Cyclo-
hexanecarboxaldehyde (1.62 mL, 13.4 mmol) and cyclohexylamine
(1.50 mL, 13.4 mmol) were added and the reaction mixture was
allowed to stir for 2 h. Acetic acid (10 mL) was added, and the
resulting mixture was stirred for 30 min before warming to room
temperature and stirring for an additional 15 min. The mixture was
diluted with H2O (200 mL) and extracted with EtOAc (200 mLꢁ3).
The combined organic extracts were washed with brine, dried
(Na2SO4), concentrated in vacuo, and purified directly by flash
chromatography (19:1 hexanes/EtOAc) to yield dimethyl 5-(cyclo-
hexylmethylene)cyclopenta-1,3-diene-1,2-dicarboxylate (978 mg,
3.5 mmol, 3% yield from cyclopentadiene). 1H NMR (300 MHz,
Benzaldehyde (15 mL, 0.15 mmol) and cyclohexylamine (1.7 mL,
0.015 mmol) were added and the reaction mixture was stirred
overnight at room temperature. The solvent was removed in vacuo
and the resulting residue was purified by flash chromatography
(4:1 hexanes/EtOAc) to yield the title compound (52 mg,
0.12 mmol, 80% yield) as bright yellow crystals. 1H NMR (300 MHz,
CDCl3)
6H, ArH), 7.06 (m, 4H, ArH), 3.64 (s, 3H, CO2CH3), 3.02 (s, 3H,
CO2CH3); 13C NMR (75 MHz, CDCl3)
166.3, 165.2, 150.7, 150.6,
d 8.50 (s, 1H, Cp]CHeAr), 7.40e7.50 (m, 5H, ArH), 7.20 (m,
d
145.1, 139.3, 137.0, 134.4, 133.1, 130.3, 129.6, 129.4, 129.2, 128.3,
127.8, 127.6, 127.3, 126.7, 124.5, 51.3, 51.1; IR (thin film) 2948, 1721,
1595,1571,1434,1384,1355,1257,1214,1193,1166,1126,1075,1028,
997, 759, 698 cmꢂ1; HRMS (FABþ) m/z¼422.1518 calcd for C28H23O4
[M]þ, found 422.1524.
DMSO-d6)
d
7.04 (d, J¼10.2 Hz,1H, Cp]CHCy), 6.88 (d, J¼5.4 Hz,1H,
CpH), 6.66 (d of d, J¼1.3, 5.4 Hz, 1H, CpH), 3.75 (s, 3H, CO2CH3), 3.74
(s, 3H, CO2CH3), 2.85 (m, 1H, Cp]CHeCyH), 1.69e1.10 (m, 10H,
4.2.6. Dimethyl 2-(4-nitrobenzylidene)-4,5-diphenylcyclopenta-3,5-
CyH). 13C NMR (75 MHz, CDCl3)
d
164.9, 164.8, 157.3, 140.8, 137.9,
diene-1,3-dicarboxylate. N-(4-Nitrobenzylidene)aniline
(68 mg,
129.6, 129.2, 122.3, 51.8, 40.9, 32.5, 25.6, 25.1.
0.30 mmol) was dissolved in THF (3 mL). Dimethyl 4,5-diphe-
nylcyclopenta-3,5-diene-1,3-dicarboxylate (100 mg, 0.30 mmol)
was then added and the resulting mixture was stirred at room
temperature for 1 h. Solvent was removed in vacuo and the
resulting residue was purified by flash chromatography (4:1 hex-
anes/EtOAc) to yield the title compound (83 mg, 0.18 mmol, 60%
Methyllithium (8.8 mL, 14.4 mmol) was added via a syringe to
a slurry of copper(I) iodide (1.337 g, 7.02 mmol) in 100 mL Et2O at
ꢂ10 ꢀC. The reaction mixture was stirred for 1 h before being cooled
to ꢂ30 ꢀC. A 5 mL solution of 5-(cyclohexylmethylene)cyclopenta-
1,3-diene-1,2-dicarboxylate (978 mg, 3.5 mmol) in Et2O was added
dropwise over 15 min, and the reaction mixture was immediately
quenched with satd NH4Cl (100 mL), acidified to pH 1 with 1 M HCl,
and extracted with EtOAc (100 mLꢁ3). The combined organic ex-
tracts were washed with H2O, brine, and dried over Na2SO4. Con-
centration in vacuo and purification by column chromatography
(19:1 hexanes/EtOAc) furnished the title compound as a mixture of
yield) as a bright orange solid. 1H NMR (300 MHz, CDCl3)
d 8.46 (s,
1H, Cp]CHeAr), 8.29 (d, J¼6.6 Hz, 2H, ArH), 7.63 (d, J¼6.3 Hz, 2H,
ArH), 7.24 (m, 6H, ArH), 7.04 (d, J¼5.1 Hz, 4H, ArH), 3.65 (s, 3H,
CO2CH3), 3.09 (s, 3H, CO2CH3); 13C NMR (75 MHz, CDCl3)
d 165.8,
164.9,152.4, 152.1,147.7,143.2,141.5,140.9, 133.9,132.6,130.7,129.3,
129.1, 128.3, 128.1, 127.5, 126.1, 124.4, 123.3, 51.4, 51.4; IR (thin film)

J.S. Bandar et al. / Tetrahedron 67 (2011) 4364e4370
4369
1721, 1592, 1520, 1435, 1383, 1345, 1258, 1215, 1193, 1165, 995, 849,
756, 699 cmꢂ1; HRMS (FABþ) m/z¼467.1369 calcd for C28H22NO6
[M]þ, found 467.1381.
in vacuo and the resulting residue was purified by flash chroma-
tography (9:1 hexanes/EtOAc) to yield the title compound as a red
oil (100 mg, 74% yield, 2:1 E/Z). 1H NMR (300 MHz, CDCl3)
d 8.23 (s,
1H, Cp]CHeAr E isomer), 7.52 (s,1H, Cp]CHeAr Z isomer), 7.4e7.3
(m, 5H, ArH, E/Z isomers), 3.88 (s, 3H, CO2CH3, E isomer), 3.83 (s, 3H,
CO2CH3, E isomer), 3.79 (s, 3H, CO2CH3, Z isomer), 3.27 (s, 3H,
CO2CH3 Z isomer), 2.51 (m, 2H, eCH2e E isomer), 2.42 (m, 4H, 2ꢁ
eCH2e Z isomer), 2.05 (m, 2H, eCH2e E isomer), 1.77 (m, 4H, 2ꢁ
eCH2e Z isomer),1.69 (m, 2H, eCH2e E isomer),1.49 (m, 2H, eCH2e
4.2.7. Dimethyl 2-(4-methoxybenzylidene)-4,5-diphenylcyclopent-
3,5-diene-1,3-dicarboxylate. Dimethyl 4,5-diphenylcyclopenta-3,5-
diene-1,3-dicarboxylate (50 mg, 0.15 mmol) was dissolved in 1 mL
THF. Anisaldehyde (27 mL, 0.23 mmol) and cyclohexylamine (1.7 mL,
0.015 mmol) were added and the reaction mixture was allowed to
stir overnight at room temperature. Solvent was removed in vacuo
and the resulting residue was purified by flash chromatography
(4:1 hexanes/EtOAc) to furnish the title compound (40 mg,
0.088 mmol, 59% yield) as bright orange crystals. 1H NMR
E isomer). 13C NMR (75 MHz, CDCl3)
d 166.5 Z, 166.4 E, 164.7 Z, 164.3
E, 143.7, 141.8, 141.4, 141.0, 140.0, 139.3, 137.0, 136.1, 135.9, 133.6,
133.4, 130.0, 129.4, 129.1, 128.9, 128.1, 128.0, 125.2, 51.9 E, 51.6 E/Z,
51.3 Z, 26.4 E, 23.8 Z, 23.5 E, 23.0 Z, 22.9 E, 22.3 Z, 22.0 E, 21.7 Z; IR
(thin film) 2939, 2857, 1730, 1713, 1609, 1535, 1435, 1270, 1222,
1122 cmꢂ1; HRMS (EIþ) m/z¼324.1362 calcd for C20H20O4 [M]þ,
found 324.1353. The substitution patterns on the fulvenes were
confirmed by NOESY.
(300 MHz, CDCl3)
d
8.43 (s, 1H, Cp]CHeAr), 7.49 (d, J¼8.7 Hz, 2H,
ArH), 7.21 (m, 6H, ArH), 7.07 (m, 4H, ArH), 6.97 (d, J¼8.7 Hz, 2H,
ArH), 3.87 (s, 3H, CO2CH3), 3.64 (s, 3H, CO2CH3), 3.16 (s, 3H,
ArOCH3); 13C NMR (75 MHz, CDCl3)
d 166.7, 165.5, 161.3, 150.2,
149.7, 145.4, 137.6, 134.8, 133.5, 133.0, 132.8, 129.9, 129.7, 129.3,
129.1, 127.3, 126.5, 124.7, 114.4, 114.0, 113.7, 51.3; IR (thin film) 1719,
1590, 1509, 1433, 1356, 1306, 1255, 1165, 1085, 1027 cmꢂ1; HRMS
(FABþ) m/z¼452.1624 calcd for C29H25O5 [M]þ, found 452.1600.
4.2.11. (E)-Dimethyl 5-benzylidene-3-(1-cyclohexylethyl) cyclopenta-
1,3-diene-1,2-dicarboxylate. Dimethyl 3-(1-cyclohexylethyl)cyclo-
penta-1,3-diene-1,2-dicarboxylate (100 mg, 0.34 mmol) was
dissolved in 4 mL THF. Benzaldehyde (105
mL, 1.03 mmol) and cy-
4.2.8. (E)-Dimethyl 4,5-diphenyl-2-(3-phenylallylidene) cyclopenta-
3,5-diene-1,3-dicarboxylate. Dimethyl 4,5-diphenylcyclopenta-3,5-
diene-1,3-dicarboxylate (50 mg, 0.15 mmol) was dissolved in 1 mL
clohexylamine (8 L, 0.07 mmol) were added and the reaction
m
mixture was stirred at room temperature overnight. Solvent was
removed in vacuo and the resulting residue was purified by flash
chromatography (19:1 hexanes/EtOAc) to yield the title compound
as a deep red oil (130 mg, 0.34 mmol, 100% yield). 1H NMR
THF. trans-Cinnamaldehyde (21
mL, 0.17 mmol) and cyclohexyl-
amine (1.7 L, 0.015 mmol) were added and the reaction was
m
allowed to stir overnight at room temperature. Solvent was re-
moved in vacuo and the resulting residue was purified by flash
chromatography (4:1 hexanes/EtOAc) to yield the title compound
(44 mg, 0.098 mmol, 65% yield) as bright orange crystals. 1H NMR
(300 MHz, CDCl3) d 8.22 (s, 1H, Cp]CHeAr), 7.60e7.56 (m, 2H,
ArH), 7.48e7.40 (m, 3H, ArH), 6.56 (s, 1H, CpH), 3.88 (s, 3H, CO2CH3),
3.83 (s, 3H, CO2CH3), 2.51 (quint, J¼6.9 Hz, 1H, CpCH(CH3)(Cy)),
1.73e1.67 (m, 5H, CyH), 1.39e0.88 (m, 6H, CyH), 1.15 (d, J¼7.0 Hz,
(300 MHz, CDCl3)
d
8.08 (d, J¼12.0 Hz, 1H, Cp]CHeCH]CHPh),
3H, CpCH(CH3)(Cy)); 13C NMR (75 MHz, CDCl3)
d 167.3, 163.8, 151.5,
7.68 (dd, J¼12.3, 15.0 Hz, 1H, Cp]CHeCH]CHPh), 7.56 (m, 2H,
ArH), 7.41 (m, 3H, ArH), 7.23 (m, 7H, Cp]CHeCH]CHPhþArH),
7.05 (m, 4H, ArH), 3.75 (s, 3H, CO2CH3), 3.64 (s, 3H, CO2CH3); 13C
144.2, 143.6, 139.9, 136.5, 131.2, 129.9, 128.7, 124.9, 120.6, 52.0, 51.6,
42.6, 38.3, 31.7, 29.1, 26.6, 26.4, 16.6; IR (thin film) 2926, 2848, 1735,
1709, 1613, 1513, 1430, 1287, 1239, 1222, 1057 cmꢂ1; HRMS (FABþ)
m/z¼380.1988 calcd for C24H28O4 [M]þ, found 380.2000. The sub-
stitution pattern on the fulvene was confirmed by NOESY.
NMR (75 MHz, CDCl3) d 168.6, 165.6, 149.4, 148.2, 146.4, 144.0, 137.4,
136.4, 135.0, 134.2, 130.1, 129.5, 129.2, 129.1, 128.1, 127.8, 127.7, 127.6,
127.5, 125.7, 125.4, 124.5, 52.2, 51.4; IR (thin film) 1702, 1598, 1578,
1434, 1361, 1263, 1220, 1193, 1163, 1086 cmꢂ1; HRMS (FABþ)
m/z¼448.1675 calcd for C30H25O4 [M]þ, found 448.1693.
4.2.12. (E)-Methyl
5-benzylidene-3-tert-butylcyclopenta-1,3-dien-
ecarboxylate. Methyl 3-tert-butylcyclopenta-1,3-dienecarboxylate
(100 mg, 0.56 mmol) was dissolved in 4 mL THF. Benzaldehyde
(0.12 mL, 1.20 mmol) and triethylamine (0.80 mL, 0.60 mmol) were
added and the reaction mixture was stirred at room temperature
for 48 . Solvent was removed in vacuo and the resulting residue was
purified by flash chromatography (19:1 hexanes/EtOAc) to yield the
title compound (130 mg, 0.48 mmol, 86% yield). 1H NMR (300 MHz,
4.2.9. Dimethyl
2-(cyclohexylmethylene)-4,5-diphenylcyclopenta-
3,5-diene-1,3-dicarboxylate. Dimethyl 4,5-diphenylcyclopenta-3,5-
diene-1,3-dicarboxylate (50 mg, 0.15 mmol) was dissolved in 1 mL
THF. Cyclohexanecarboxaldehyde (27
mL, 0.23 mmol) and cyclo-
hexylamine (3.4 L, 0.030 mmol) were added and the reaction
m
mixture was allowed to stir overnight at room temperature. Solvent
was removed in vacuo and the resulting residue was purified by
flash chromatography (4:1 hexanes/EtOAc) to yield the title com-
pound (49 mg, 0.11 mmol, 73% yield) as bright yellow crystals. 1H
CDCl3) d 8.32 (s, 1H, Cp]CHAr), 7.60e7.57 (m, 2H, ArH), 7.50 (d,
J¼1.6 Hz, 1H, CpH), 7.44e7.40 (m, 3H, ArH), 6.57 (d, J¼1.5 Hz, 1H,
CpH), 3.84 (s, 3H, CO2CH3), 1.22 (s, 9H, CpC(CH3)3); 13C NMR
(75 MHz, CDCl3) d 164.4, 157.4, 141.5, 141.3, 140.9, 137.0, 130.8, 129.1,
NMR (300 MHz, CDCl3)
d
7.32 (d, J¼10.8 Hz, 1H, Cp]CHeCy), 7.16
128.6, 126.1, 118.9, 50.9, 32.2, 29.6; IR (thin film) 3061, 2952, 2861,
1700, 1613, 1565, 1504, 1343, 1148, 1052 cmꢂ1; HRMS (FABþ) m/
z¼268.1463 calcd for C18H20O2 [M]þ, found 268.1448. The sub-
stitution pattern on the fulvene was confirmed by NOESY.
(m, 6H, ArH), 6.99 (m, 4H, ArH), 3.69 (s, 3H, CO2CH3), 3.57 (s, 3H,
CO2CH3), 2.63 (m, 1H, Cp]CHeCHR2), 1.82 (m, 5H, CH2), 1.30 (m,
5H, CH2); 13C NMR (75 MHz, CDCl3)
d 168.5, 165.5, 155.5, 149.4,
147.1, 137.0, 134.8, 133.7, 129.3, 129.2, 127.9, 127.8, 127.6, 127.5, 126.6,
124.2, 52.2, 51.3, 40.4, 32.7, 25.8, 25.5; IR (thin film) 2929, 2851,
1724,1704,1623,1434,1391,1365,1258,1234,1220,1194,1171,1144,
4.2.13. Dimethyl 1-(4-nitrobenzylidene)-4,5,6,7-tetrahydro-1H-in-
dene-2,3-dicarboxylate. Dimethyl 4,5,6,7-tetrahydro-1H-indene-
2,3-dicarboxylate (100 mg, 0.42 mmol) was dissolved in 3 mL THF.
4-Nitrobenzaldehyde (190 mg, 1.26 mmol) was then added, fol-
1128, 994, 699 cmꢂ1
;
HRMS (FABþ) m/z¼428.1988 calcd for
C28H29O4 [M]þ, found 428.1980.
lowed by cyclohexylamine (10 mL, 0.08 mmol) and the reaction
4.2.10. Dimethyl 1-benzylidene-4,5,6,7-tetrahydro-1H-indene-2,3-
dicarboxylate. Dimethyl 4,5,6,7-tetrahydro-1H-indene-2,3-dicar-
boxylate (100 mg, 0.42 mmol) was dissolved in 3 mL THF. Benzal-
dehyde (0.13 mL, 1.26 mmol) was added, followed by
mixture was allowed to stir for 48 h at room temperature. Solvent
was removed in vacuo and the resulting residue was purified by
flash chromatography (9:1 hexanes/EtOAc) to yield the title com-
pound as a 3:2 E/Z mixture as a red oil (90 mg, 58% yield). 1H NMR
cyclohexylamine (10
m
L, 0.08 mmol) and the reaction mixture was
(300 MHz, CDCl3)
d 8.24e8.18 (m, 5H, ArH/Cp]CHAr), 7.51e7.42
allowed to stir for 48 h at room temperature. Solvent was removed
(m, 5H, ArH/Cp]CHAr), 3.86 (s, 3H, CO2CH3 E), 3.81 (s, 3H, CO2CH3

4370
J.S. Bandar et al. / Tetrahedron 67 (2011) 4364e4370
E), 3.78 (s, 3H, CO2CH3 Z), 3.30 (s, 3H, CO2CH3 Z), 2.47 (m, 4H, 2ꢁ
eCH2e Z), 2.36 (m, 2H, eCH2e E), 1.90 (m, 2H, eCH2e E), 1.75 (m,
4.6. Fulvene metathesis
4H, 2ꢁ eCH2e Z), 1.65 (m, 2H, eCH2e E), 1.46 (m, 2H, eCH2e E); 13
C
Dimethyl
1-benzylidene-4,5,6,7-tetrahydro-1H-indene-2,3-
NMR (75 MHz, CDCl3)
d
166.2, 165.9, 164.4, 163.7, 147.7, 143.8, 142.9,
dicarboxylate (4.9 mg, 0.015 mmol, 1.7:1.0 E/Z ratio) and dimethyl
2-(4-nitrobenzylidene)-4,5-diphenylcyclopenta-3,5-diene-1,3-
dicarboxylate (7.0 mg, 0.015 mmol) were dissolved in 0.30 mL
142.3, 141.6, 141.3, 139.8, 138.7, 135.9, 133.8, 133.4, 130.6, 130.0,
128.2, 124.2, 123.3, 123.1, 52.1, 51.9, 51.8, 51.7, 26.4, 23.7, 23.4, 22.7,
22.2, 21.8, 21.7; IR (thin film) 2948, 2857, 1735, 1709, 1596, 1522,
1435, 1348, 1265, 1217, 1121 cmꢂ1; HRMS (FABþ) m/z¼369.1212
calcd for C20H19NO6 [M]þ, found 369.1227.
CDCl3 before benzyl ether (2.9
mL, 0.015 mmol in 0.15 mL CDCl3)
and n-butylamine (1.5 L, 0.015 mmol in 0.15 mL in CDCl3) were
m
added as stock solutions. The solution was mixed in an NMR tube
and the reaction progress was monitored by 1H NMR. After 19 h, the
relative fulvene and imine ratios were constant as shown in
Scheme 3. The total amount of dimethyl 2-benzylidene-4,5-
diphenylcyclopenta-3,5-diene-1,3-dicarboxylate and dimethyl 3-
(4-nitrobenzylidene)octahydro-1H-indene-1,2-dicarboxylate were
calculated by integrating the Z isomer and using the E/Z ratio pre-
viously determined in Table 1, entry 10. Chemical shifts used to
determine the final ratios are shown on the spectrum in the pro-
vided Supplementary data.
4.3. pKa Estimation of 8
Dimethyl 4,5-diphenylcyclopenta-3,5-diene-1,3-dicarboxylate
(1.5 mg, 0.0045 mmol) was dissolved in 0.5 mL CD3CN and
2-NH2ebenzimidazole (2.6 mg, 0.0195 mmol) was added. Using
the 1H NMR chemical shifts of fully protonated (3.613 ppm), fully
deprotonated (3.499 ppm) and the observed chemical shift
(3.537 ppm) of the cyclopentadiene methyl esters, the equilibrium
ratio of cyclopentadiene and cyclopentadienyl anion was de-
termined to be 33.3% protonated.12 Thus, the amounts of neutral
cyclopentadiene (0.0015 mmol), deprotonated cyclopentadiene
(0.0030 mmol), neutral 2-NH2ebenzimidazole (0.0165 mmol) and
protonated 2-NH2ebenzimidazole (0.0030 mmol) were obtained.
Using the obtained amounts and the known pKa of 2-NH2ebenzi-
midazole in acetonitrile,13 the pKa of dimethyl 4,5-diphenylcyclo-
penta-3,5-diene-1,3-dicarboxylate was calculated to be 16.52 in
acetonitrile.
Acknowledgements
This work was supported by the National Science Foundation
under CHE-0908176. T.H.L. is grateful for an Alfred P. Sloan Research
Fellowship and Young Investigator Awards from Abbott and
Amgen. J.S.B. is grateful for an NDSEG graduate fellowship.
Supplementary data
4.4. General procedure for fulvene/imine interchange
experiments
Supplementary data associated with this article can be found in
online version at doi:10.1016/j.tet.2011.03.094.
4.4.1. Forward. Stock solutions (1e2 mL) of imine (0.30 M), cyclo-
pentadiene (0.30 M), and benzyl ether (0.30 M) in CDCl3 were
prepared fresh. To an NMR tube, 0.20 mL of each solution was
added and mixed. The fulvene/imine ratio was monitored by 1H
NMR until no change in the ratio was observed.
References and notes
1. Alkylidene cyclopentadienes are technically called ‘pentafulvenes’, which rep-
resent only one of a number of fulvene subclasses. However, in the absence of
additional qualifiers, ‘fulvene’ and ‘pentafulvene’ are generally understood to be
synonymous.
2. (a) Thiele, J. Chem. Ber. 1900, 33, 666e673; (b) Thiele, J.; Balhorn, H. Justus
Liebigs Ann. Chem. 1906, 348, 1e15.
3. For reviews on fulvenes, see: (a) Day, J. H. Chem. Rev. 1953, 53, 167e189; (b)
Bergmann, E. D. Chem. Rev. 1968, 68, 41e84; (c) Neuenschwander, M. In
Chemistry of Double-Bonded Functional Groups; Patai, S., Ed.; Wiley: Chichester,
UK, 1989; Vol. 2, p 1131.
4.4.2. Reverse. Stock solutions (1e2 mL) of fulvene (0.30 M), amine
(0.30 M), and benzyl ether (0.30 M) in CDCl3 were prepared fresh.
To an NMR tube, 0.20 mL of each solution was added and mixed.
The fulvene/imine ratio was monitored by 1H NMR and reported at
the equilibrium time determined for the forward reaction.
4. Numerous examples of nucleophilic addition to fulvenes exist. For selected
€
examples, see: (a) Buchi, G.; Berthet, D.; Decorzant, R.; Grieder, A.; Hauser, A. J.
Org. Chem. 1976, 41, 3208e3209; (b) Suzuka, T.; Ogasawara, M.; Hayashi, T. J.
Org. Chem. 2002, 67, 3355e3359; (c) Hafner, K. Pure Appl. Chem. 1990, 62,
531e540.
4.5. Transfulvenation experiments
€
€
€
5. For examples, see: (a) Nystrom, J.-E.; Bystrom, S. E.; Ristola, T.; Ekstrom, J.
4.5.1. No additional aniline. A solution of dimethyl 2-benzylidene-
€
Tetrahedron Lett. 1988, 29, 4997e5000; (b) Soderberg, B. C.; Austin, L. R.; Davis,
4,5-diphenylcyclopenta-3,5-diene-1,3-dicarboxylate
0.06 mmol) in CDCl3 300 L was added to a solution of N-(3-phe-
nylallyllidene)aniline (12.4 mg, 0.06 mmol) and benzyl ether
(25.3 mg,
C. A. Tetrahedron 1994, 50, 61e76; (c) Knight, D. B.; Hartless, R. L.; Jarvis, D. A. J.
Org. Chem. 1972, 37, 688e692; (d) Hoffmann, H. M. R.; Koch, O. J. Org. Chem.
1986, 51, 2939e2944.
6. Stone, K. J.; Little, R. D. J. Org. Chem. 1984, 49, 1849e1853.
7. Erden, I.; Xu, F.-P.; Sadoun, A.; Smith, W.; Sheff, G.; Ossun, M. J. Org. Chem. 1995,
60, 813e820.
8. Taber, D.; Beker, E. I.; Spoerri, P. E. J. Am. Chem. Soc. 1954, 76, 776e781.
9. We have determined the pKa of 8 to be 16.5 in CD3CN. For reference, the pKa of
triethylamine in CD3CN is 18.8.
m
(11.4 mL, 0.06 mmol) as internal standard in CDCl3 (300 mL total
volume). Reaction progress was followed by 1H NMR over the course
of 5 days.
10. (a) Dawson and coworkers have shown that aniline is an effective catalyst for
transimination of hydrazones and oximes: Dirksen, A.; Dirksen, S.; Hackeng, T.
M.; Dawson, P. E. J. Am. Chem. Soc. 2006, 128, 15602e15603; (b) Dirksen, A.;
Hackeng, T. M.; Dawson, P. E. Angew. Chem., Int. Ed. 2006, 45, 7581e7584.
11. Moore, J. E.; York, M.; Harrity, J. P. A. Synlett 2005, 860e862.
12. Handloser, C. S.; Chakrabarty, M. R.; Mosher, M. W. J. Chem. Educ. 1973, 50,
510e511.
4.5.2. Stoichiometric aniline. A solution of dimethyl 2-benzylidene-
4,5-diphenylcyclopenta-3,5-diene-1,3-dicarboxylate
0.06 mmol) in CDCl3 300 L was added to a solution of N-(3-phe-
nylallyllidene)aniline (12.4 mg, 0.06 mmol), aniline (5.5 L,
0.06 mmol), and benzyl ether (11.4 L, 0.06 mmol) as internal
standard in CDCl3 (300 L total volume). Reaction progress was
followed by 1H NMR over the course of 30 h.
(25.3 mg,
m
m
m
m
€
€
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13. Kaljurand, I.; Kutt, A.; Soovali, L.; Rodima, T.; Maemets, V.; Leito, I.; Koppel, I. A.
J. Org. Chem. 2005, 70, 1019e1028.