Diverse Modes of Reactivity of 6-(Chloromethyl)-6-methylfulvene

Article abstract of DOI:10.1002/ejoc.201700442

The title compound exhibits a number of modes of reactivity toward nucleophiles/bases owing to the presence of several electrophilic and potentially nucleophilic sites in the molecule. We explored the reactions of 6-(chloromethyl)-6-methylfulvene with oxygen and nitrogen nucleophiles and bases as well as a carbon-based nucleophile (an enamine) and realized all possible reactivity modes predicted on the basis of electrophilic and nucleophilic positions in this compound.

Full text of DOI:10.1002/ejoc.201700442

A Journal of
Accepted Article
Title: Diverse modes of reactivity of 6-chloromethyl-6-methylfulvene
Authors: Ihsan Erden, Scott Gronert, Gabriel Cabrera, Necdet Coskun,
and Marco Tapken
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700442
Link to VoR: http://dx.doi.org/10.1002/ejoc.201700442
Supported by

European Journal of Organic Chemistry
10.1002/ejoc.201700442
FULL PAPER
Diverse modes of reactivity of 6-(chloromethyl)-6-methylfulvene
[
a]
[b]
[a]
[c]
[a]
Ihsan Erden * , Scott Gronert * ,Gabriel Cabrera , Necdet Coskun , and Marco Tapken
Dedicated to Professor Waldemar Adam on the occasion of his 80th birthday
Abstract: The title compound exhibits a number of reactivities
toward nucleophiles/bases owing to the presence of several
electrophilic and potentially nucleophilic sites in the molecule. We
explored the reactions of 6-(chloromethyl)-6-methylfulvene with
oxygen- and nitrogen nucleophiles and bases as well as a carbon-
based nucleophile (an enamine) and realized all possible reactivity
modes predicted on the basis of electrophilic and nucleophilic
positions in this compound
that the highly reactive chloromethyl group extends the number
of electrophilic sites, as well as providing increased CH-acidity at
C-7 to, perhaps, allow an unprecedented aldol condensation
with a carbonyl electrophile via an “Umpolung” reaction (Scheme
1).
Introduction
Fulvenes represent a class of compounds that exhibits
arguably the most diverse reactivity of any cyclic polyolefin
known to date. In addition to their well-documented
Scheme 1. Possible modes of reactions of 1; C-6 and C-7: electrophilic (2, 3);
C-7: C-H acid, nucleophilic after deprotonation (4); C-5 and C-2: nucleophilic
after nucleophilic attack at C-6 (2).
1
2
3
cycloadditions as well as singlet oxygen chemistry, fulvenes
can partake as excellent two-electron acceptors and donors in
1
reactions with nucleophiles as well as electrophiles. Though
Herein we report on three different patterns of reactivity of 1
with nucleophiles and electrophiles, including an aldol
condensation at C-7, qualifying it as one of the most versatile
fulvenes reported to date.
their dipole moments are modest in magnitude,4 the exocyclic
double bond is highly polarizable since the corresponding
resonance structure imparts 6-Hückel aromatic character to the
cyclopentadienyl ring. We recently demonstrated through
experimental and computational work that the fulvenyl group is a
particularly activating allylic group in S
compound, 6-(chloromethyl)-6-methylfulvene (1), exhibits an
unusually high S 2 reactivity when compared to other allylic and
N
2 reactions.5 The title Results and Discussion
The first nucleophile we tried was the methoxide ion (MeO-).
N
benzylic halides: it reacts 30 times faster with KI/acetone than
benzyl chloride at room temperature. The known activation of
Though the CH
2
Cl group in 1 is an exceptionally reactive
substrate for S 2 reactions, the result was somewhat surprising:
N
N
negatively charged S 2 transitions states by allyl or benzyl
the product that was isolated in 62% yield was the dimethyl
groups is dramatically accentuated by the fulvenyl group since it
is particularly effective in delocalizing negative charge due to
some cyclopentadienide character in the transition state.
acetal of cyclopentadienylpropanone (both isomers, 8 and 9)
(
Scheme 2). It is also surprising that acetal formation occurs
under basic conditions, though acetals are formed from carbonyl
compounds under acid catalysis. To the best of our knowledge,
the present case is the second example of acetal formation
under basic conditions. The first reported example was
encountered in the methoxide promoted Cannizzaro reaction of
The typical modes of reaction of fulvenes are three-fold: (a)
nucleophilic attack at the exocyclic double bond (C-6); hard
6
nucleophiles such as Grignard and organolithium reagents,
sulfur ylids and also LiAlH
7
8
4
have been reported to attack C-6,
resulting in C-6-alkylation, cyclopropanation and reduction,
respectively; (b) electrophilic attack occurs at C-1 preferentially,
though this mode of reaction has been studied to a lesser
benzaldehyde to give benzaldehyde dimethyl acetal as a very
minor product (2%).10 The formation of the latter was ascribed to
+
an oxonium intermediate (CH
3
O =CHPh) of the type 7 (vide
9
extent; (c) cycloadditions involving the cyclopentadienyl ring. 6-
infra). A mechanism, consistent with our result is depicted in
(Chloromethyl)-6-methylfulvene (1) has the added advantage in
Scheme 2. Evidently, the methoxide ion preferentially attacks the
2
fulvene C-6, rather than CH Cl, and the resulting
cyclopentadienide displaces the chloride to form 1-methoxy-1-
methylspiro[2.4]hepta-2,4-diene (6).
Considering the fact that the cyclopentadienyl group in 6 is
an excellent two-electron acceptor, the presence of the methoxyl
[
[
[
a]
Department of Chemistry and Biochemistry, San Francisco State
University, 1600 Holloway Avenue, San Francisco, CA 94132, USA
E-mail: ierden@sfsu.edu
Department of Chemistry, Virginia Commonwealth University, 1001
West Main Street, Richmond, Virginia 23284, USA
E-mail: sgronert@vcu.edu
group on the spirocyclopropyl ring renders
6
a
push-pull
b]
c]
molecule that undergoes facile ring opening to intermediate 7.
11
Uludağ University, Department of Chemistry, 16059 Bursa-Turkey
Supporting information for this article is given via a link at the end of
the document
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700442
FULL PAPER
OMe-
Cl
ketones are more reluctant to undergo condensation with
cyclopentadienyl anions generated with weaker bases.14
Cl
MeO
Obviously NaOMe at room temperature was not basic enough to
affect fulvene synthesis. When NaOEt in EtOH was used (as in
OMe
15
the original Thiele fulvene synthesis) , the corresponding
-
trapping products 15 and 16 were obtained. (Scheme 4).
1
5
6
OMe
OMe
OMe
OMe
+
O Me
MeO-
MeOH
+
-
Scheme 4. Generation of 7 with NaOEt and condensation with acetophenone.
9
8
7
Scheme 2. Nucleophilic addition of NaOMe onto 1: acetal formation under
basic conditions.
-
Nucleophilic attack of MeO at the exocyclic double bond of
6
,6-dimethylfulvene was reported to give the Thiele ether16
whose structure had remained an enigma till Shamma et al.
reported an elaborate degradative scheme, including
hydrogenolysis and ozonolysis to elucidate its structure as 19
The mixture of the isomeric acetals 8 and 9 was isolated when
the crude mixture was not subjected to aqueous work-up without
acid wash. However, in another run, when the work-up included
17
(
Scheme 5). We found that the structure of Thiele’s ether could
be secured much more directly by a Diels-Alder reaction with
tetracyanoethylene (TCNE). The NMR spectral data and HRMS
analysis of the cycloadduct 20 allowed the assignment of its
structure in an unequivocal manner.
extraction
with
dilute
HCl,
the
unprotected
12
cyclopentadienylpropanones 10 and 11 were isolated. Next,
the validity of the mechanism in Scheme 2 was tested by
conducting the experiment under the same conditions in the
presence of a ketone, in hopes of capturing intermediate 7 via
fulvene formation. Gratifyingly, in the presence of acetone, the
corresponding fulvene 13 was indeed isolated after acidic work
up. (Scheme 3).
Scheme 5. Synthesis of Thiele ether (17) and its Diels-Alder adduct 18 with
TCNE.
Substrate 1 was also of interest in terms of its reactivity
toward the enamine derived from acetone. In
a recent
communication we reported on the formal [6+2] dipolar
cycloadditions of fulvenes with acetone enamine leading to 1,2-
18
dihydropentalenes. The question whether 1 would react with a
carbon nucleophile such as N-isopropenylpyrrolidine (formed in
situ from pyrrolidine and acetone) at C-6 leading to a 1,2-
Scheme 3. Trapping of cyclopentadienyl anion intermediate 7 via fulvene
formation; ii) hydrolysis of the acetals 8+9 give 1-cyclopentadienylpropan-2-
ones 10 and 11.
N
dihydropentalene, or at the chloromethyl group in an S 2
reaction was readily tested when the title compound was reacted
with 20% pyrrolidine in acetone. The product composition was
sensitive to temperature of the reaction. When the reaction was
Fulvene 13 underwent isomerization to a single compound, 14,
with pyrrolidine in MeOH, or with EtO /EtOH. The Z configuration
of the exocyclic double bond carrying the carbonyl group was
3
run at room temperature with excess acetone in CH CN, a
-
mixture of two products, 21 (bright yellow) and 22 (orange), were
isolated in a ratio of 1.5:1, respectively (combined isolated yield
64%). Their structures were secured by NMR and HRMS data.
a
assigned based on the remarkably downfield shift for H in 14 at
13
7
.1 ppm.
When acetophenone was used in the condensation of 7 with
acetone, only 8+9 were isolated. It is known that aromatic
In the same reaction both reactivity patterns were observed: S
N
2
reaction at the CH Cl group led to 21 (product type 3, Scheme 1),
2
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700442
FULL PAPER
whereas deprotonation at the chloromethyl group and aldol
condensation with acetone furnished 22 (Scheme 6).
N+
Cl
Cl
Cl
N
Cl
+
H
-
N
N
,
CH CN
3
1
24
25
1
+
acetone, r.t.
21
22
Cl
H
1
2
N
N
-
N
Scheme 6. S 2 reaction and aldol condensation of 1 with pyrrolidine and
acetone.
23
26
To the best of our knowledge, compound 22 represents the first
aldol condensation product derived from a fulvene. Evidently,
Scheme 8. 1,2-Dihydropentalene formation from
cycloaddition with N-isopropenylpyrrolidine 24.
1 via a dipolar 6+2
the increased CH-acidity of the CH
2
Cl group and the stability of
19
the resulting carbanion were responsible for its formation.
Computations at the M062x/6-311+G** level indicate that the
chlorine increases the acidity (gas phase) of 1 by 7 kcal/mol
compared to dimethylfulvene.19
Dihydropentalene 23 appeared to be a suitable substrate for
exploring the possibility of preparing the elusive ‘homopentalene’
by tandem deprotonation at C-2 (dihydropentalene numbering)
When the above reaction was repeated under the same
condition, but at 60 oC, in addition to small amounts of 22, the
with base and intramolecular S 2 displacement of the chloride.
N
Treatment of 23 with DBU in CH Cl for 12h and purification by
2
2
1
,2-dihydropentalene 23 was formed as the major product (33%
preparative layer chromatography on silica gel gave 27 in 63%
yield. The same product was obtained with DBU under the same
conditions in acetone solvent, with the only by-product being
mesityl oxide, however, the reaction was complete after 1h in
this solvent (Scheme 9).
after chromatography). This result was expected based on our
recent report on the formal [6+2] dipolar cycloadditions of
fulvenes with enamines leading to 1,2-dihydropentalenes.
Compound 1 obviously constitutes a special case in that it not
20
only contains an electrophilic fulvene C-6, but also the CH
2
Cl
that is not only electrophilic, but also a C-H acid (Scheme 7).
Scheme 7. 1,2-Dihydropentalene formation from 1 and in situ generated N-
isopropenylpyrrolidine.
The 1,2-dihydropentalene 23 is formed via attack of N-
isopropenylpyrrolidine at C-6 of 1, followed by a stepwise 6+2
cycloaddition with loss of pyrrolidine.
With the isolation of compound 23 we have realized all three
types of reactions of 1 with nucleophiles: a) attack at C-6 by
Scheme 9. Conversion of 23 to 27 via a “homologous E1cB” mechanism.
-
N
MeO , followed by intramolecular S 2; a) nucleophilic attack at
C-6 by an enamine as part of a dipolar [6+2] cycloaddition onto
the fulvene ring; b) S 2 substitution at the CH Cl group by
Cl) and aldol
N
2
3
When the reaction was conducted in CDCl , we observed 30%
deuterium incorporation onto C-7 in 27. This latter result is
indicative of a mechanism akin to the E1cB reaction21 except the
pyrrolidine; c) deprotonation at the acidic C-7 (CH
condensation with acetone.
2
present case represents a homolog of the aforementioned
reaction because the result is not an alkene but a cyclopropane
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700442
FULL PAPER
ring. The “homologous E1cB reaction” we observed in the case
of 23 is reminiscent of the Ramberg-Bäcklund22 and Favorskii23
reactions leading to three-membered rings via carbanions
initially, as well as the quadricyclane forming 1,3-elimination via
a sulfone-stabilized carbanion in a 3-bromo-5-phenylsulfonyl
substituted tricyclo[2.2.1.02,6]heptyl system.24 It is worthy of note
H
H
B-
27
28
29
that the proton signal for H-8 gives a doublet of doublets in pure
3
2
7-H with J values 5.0 and 2.0 Hz for coupling to H-9 and H-7
B-
respectively. In the 27-H/27-D mixture, in addition to the doublet
H
H
of doublets, for H-8, there is a doublet, superimposed on the dd
3
with a J value of 5.0 Hz for coupling to H-9 (see Supp. Info.).
-
In an attempt to affect isomerization of the exocyclic double
bond with base in order to obtain the elusive
homodihydropentalene
(1,1a-dihydrocyclopropa[c]pentalene),
B-H
o
B-H
we heated 27 in DMSO in the presence of t-BuOK at 60 C.
Under these conditions, a mixture of isomeric 4,6- and 5,7-
dimethyl-1H-indenes,26 28 and 29, respectively, were obtained
32
33
(
Scheme 10).
Scheme 12. Mechanism for the base-promoted isomerization of 27 to 28 and
9.
2
The preference for deprotonation of the methyl group in 23
rather than the ring methylene group is supported by
calculations at the M062x/6-311+G** level. The methyl group is
predicted to be more acidic by approximately 3 kcal/mol in the
gas phase. The origin of the preference is unclear, but
deprotonation at the methyl group allows for folding in the 5-
membered ring, which relieves some steric strain.
Scheme 10. Base-catalyzed isomerization of 27 to 28 and 29.
When the mesylate, generated in situ from dihydropentalene 30 Conclusions
was treated with DBU in acetonitrile at room temperature
overnight, a 60:40 mixture of 28/29 and 27 was formed,
We have uncovered three modes of reactivity of a 6-
respectively (Scheme 11).
(chloromethyl)fulvene (1): i) direct attack at fulvene C-6 and
spiro[2.4]hepta-4,6-diene formation, ii) S 2 at the chloromethyl
N
group iii) deprotonation at CH
application of ‘Type 2’ attack (Scheme 1) is the dipolar 6+2
cycloaddition of an enamine with leading to 1,2-
dihydropentalene. Base-promoted dehydrochlorination of 23
follows novel homologous E1cB mechanism with
2
Cl, aldol condensation. A special
1
a
a
a
cyclopentadienyl anion as intermediate. The resulting unusual
bridged spiro[2.4]hepta-4,6-diene system 27 was isomerized
with base to the isomeric 4,6- and 5,7-dimethylindenes 28 and
Scheme 11. Alternative method for the generation of 27 and 28/29 from
alcohol 30 via mesylate 31.
N
29. Except for the S 2 and aldol condensation modes, all other
nucleophilic attacks at C-6 proceed through a cyclopentadienyl
anion intermediate. Compound 1 was shown to occupy a unique
status among fulvenes in terms of its multitude of reactivity
patterns. Moreover, we were able to elucidate the structure of
Thiele ether 19 by a single experiment, a Diels-Alder reaction
with TCNE.
The formation of the isomeric dimethylindenes 28 and 29
can be rationalized in terms of base abstraction of the allylic
proton in 27, initial formation of the cyclopentadienyl anion
followed by protonation to give 32. The latter then undergoes a
base catalyzed aromatization to give the tautomeric
dimethylindenes 28 and 29 (Scheme 12).
Experimental Section
General. 1H and 13C NMR spectra were recorded on a 500 MHz NMR
3
spectrometer, using CDCl as solvent and TMS as internal standard,
unless specified otherwise. Most column chromatographic separations
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700442
FULL PAPER
were carried out on a flash chromatography system using 40-60 mm
silica gel columns using ethyl acetate/n-hexane solvent mixtures. For
preparative TLC, silica gel (grade 60 PF254) was used. All reactions were
conducted under an atmosphere of dry nitrogen or argon. Non-
deuterated solvents were dried and distilled prior to use. Pyrrolidine is an
exceptionally foul-smelling and toxic compound and should be handled
with care in a well-ventilated hood. Fulvenes are oxygen- and heat-
sensitive compounds; all reactions should be carried out under a nitrogen
or argon atmosphere. Fulvenes used in this study were prepared by a
new method we recently developed.15d Exact masses of all new products
by high resolution mass spectra (HRMS) were determined at the San
Francisco State University Mass Spectrometry Facility.
product. This was further purified via flash chromatography on silica gel
(70/30 hexanes/EtOAc) to give 13 as a bright yellow oil (0.215 g, 61.4%).

H
(500 MHz, CDCl
J= 5.0 Hz, =C4-H), 6.31 (narrow m, 1H, =C1-H), 3.5 (s, 2H, CH
6H, CH );  (125 MHz, CDCl ) 206.6, 149.2, 142.4, 138.2, 132.1, 122.0,
3
) 6.52 (dd, 1H, J= 5.0, 2.0 Hz, =C3-H), 6.33 (d, 1H,
2
), 2.16 (s,
3
C
3
118.8, 48.9, 29.4, 23.1, 22.9; HRMS (ESI) m/z calculated for C11H
15O+
(M+H)+ 163.1078, found 162.1118.
(Z)-1-(4-Isopropylidene)cyclopent-2-en-1-ylidene)propan-2-one (14).
A solution of NaOEt (10% w/w) in ethanol (15 ml), was prepared using
sodium and dry ethanol. At 0 oC and under inert gas, 13 (0.355 g, 2.2
mmol) was added via syringe. The solution was then stirred for 48 h at
room temperature. After diethyl ether (60 mL) was added, the organic
2
-(2,2-Dimethoxypropyl)cyclopenta-1,3-diene
(8)
and
1-(2,2-
dimethoxypropyl)cyclopenta-1,3-diene (9)
layer was washed with NaHCO
MgSO . The solvent was removed through rotary evaporation to provide
crude. This was further purified via column chromatography with hexane
to give the product as a colorless oil (0.306g, 86% yield).  (500 MHz,
CDCl ) 7.1 (d, 1H, J= 5.5 Hz, =CH), 6.39 (d, 1H, J= 5.5 Hz, =CH), 6.12 (s,
1H, =CH-exocyclic), 3.52 (s, 2H, CH C=O), 1.87 (s, 3H, CH ), 1.84 (s, 3H,
CH );  (125 MHz, CDCl ) 198.1, 163.2, 144.4, 138.8, 135.6, 129.5,
3
and brine (2 X 20ml) and then dried over
4
A solution of NaOMe (5% w/w) in MeOH (15 mL) was prepared using
sodium and dry methanol. At 0 oC and under nitrogen, 6-(chloromethyl)-
H
6
-methylfulvene (1) (0.236 g, 1.68 mmol) was added via a syringe. The
solution was then stirred for 2 h at room temperature. After 60 ml of
diethyl ether was added, the organic layer was washed with NaHCO and
brine (2 X 20ml each) and then dried over MgSO . The solvent was
rotovapped. The crude product was purified by flash chromatography
50% hexanes/EtOAc) on silica gel to give a mixture of both isomers 8
and 9 (0.171g, 61%) in a ratio of 1:1 (by 1H NMR) as a colorless oil; 
3
2
3
3
3
C
3
115.2, 36.1, 31.4, 22.1, 21.1; HRMS (ESI) m/z calculated for C11H
15O+
(M+H)+ 163.1078, found 163.1117.
4
(
H
(
(
2
E)-1-(3-Phenylethylidene)cyclopenta-1,4-dien-1-yl)propan-2-one
15) and (Z)-1-(3-phenylethylidene)cyclopenta-1,4-dien-1-yl)propan-
-one (16)
(
(
(
500 MHz, CDCl
m, 1H), 6.3 (m, 1H), 6.28 (2, 1H), 6.15 (s, 1H), 3.25 (s, 6H, CH
s, 6H, CH O), 2.99 (m, 2H, Cp-CH ), 2.97 (m, 2H, Cp-CH ), 2.74 (s, 2H,
-CMe(OMe) ), 2.71 (s, 2H, CH -CMe(OMe) ), 1.24 (s, 3H,
C(OMe) ), 1.21 (s, CH C(OMe) );  (125 MHz, CDCl ) 144.03,
3
) signals for both isomers 6.51 (m, 1H), 6.4 (m, 1H), 6.4
3
O), 3.24
3
2
2
CH
CH
2
3
2
2
2
A solution of 6-(chloromethyl)-6-methylfulvene (1) (0.355 g, 2.53 mmol) in
dry EtOH (2 mL) at room temperature under inert gas was treated
sequentially with of acetophenone (0.5 mL) and freshly prepared NaOEt
2
3
2
C
3
1
4
(
44.02, 135.5, 133.3, 132.2, 131.9, 130.0, 129.7, 101.6, 48.3, 48.2, 44.2,
1.3, 37.9, 37.0, 21.3; HRMS (ESI) m/z calculated for C10H16NaO
2
+
(
2.1 equivalents). The solution was then stirred for 24
temperature. After dichloromethane (60 mL) was added, the organic
layer was washed with dilute HCl, NaHCO and brine (2 X 20ml each)
and then dried over MgSO . The solvent was removed in vacuo to
h at room
M+Na)+ 191.1043, found 191.1057. .
3
1
-(Cyclopenta-1,3-dien-1-yl)propan-2-one (10) and 1-(cyclopenta-1,4-
4
dien-1yl)propan-2-one (11)
provide the crude product. This was further purified via flash
chromatography on silica gel (70/30 hexane/EtOAc) to give a mixture of
A solution of NaOMe (5% w/w) in MeOH (15 mL) was prepared using
both isomers (0.260g, 46% yield) as a bright yellow oil. 
H
(500 MHz,
sodium and dry methanol. At 0 oC and under N
CDCl ), both isomers 15 and 16 (~1:1), 7.4 (m, 10H, Ph-H), 6.6 (dd, 1H,
2
, 6-(chloromethyl)-6-
3
methylfulvene (1) (0.30 g, 2.15 mmol) was added via a syringe. The
solution was then stirred for 4 h at room temperature. After 60 ml of
dichloromethane was added, the organic layer was washed with dilute
J= 5.5, 2.0 Hz, =CH), 6.43 (dd, 1H, J= 5.5, 1.5 Hz, =CH), 6.42 (s, 1H,
=CH), 6.34 (dd, 1H, J= 5.5, 1.5 Hz, =CH), 6.18 (dd, 1H, J= 5.5, 2.0 Hz,
=CH), 5.98 (s, 1H, =CH), 3.52 (s, 2H, CH
2.50 (s, 3H, CH C=O), 2.49 (s, 3H, CH C=O), 2.19 (s, 3H, CH
3H, CH );  (125 MHz, CDCl ) 206.6, 206.5 (C=O), 149.3, 149.27, 143.3,
2 2
C=O), 3.43 (s, 2H, CH C=O),
HCl, NaHCO
3
and brine (2 X 20 ml each) and then dried over MgSO
4
.
3
3
3
), 2.13 (s,
The solvent was evaporated in vacuo to provide the crude product. This
3
C
3
was purified via flash chromatography on silica gel (50/50 hexane/EtOAc)
143.25, 142.3, 142.1, 139.5, 139.2, 133.3, 133.0, 129.4, 129.3, 128.4,
128.2, 128.1, 125.2,122.6, 121.8, 45.9, 45.88, 29.7, 29.5, 22.8, 22.6;
HRMS (ESI) m/z calculated for
to give a slightly yellow oil (0.148 g, 56.3%). 
H 3
(500 MHz, CDCl ) signals
16
C H
17O+ (M+H)+ 225.1235, found
for both isomers, 6.42-6.49 (m, 3H), 6.36 (m, 1H), 6.33 (s, 1H), 6.20 (s,
1
2
H), 3.53 (s, 2H, CH
H, Cp-CH ), 2.97 (s, 2H, Cp-CH
(125 MHz, CDCl ) 206.7 (C=O), 205.6 (C=O), 140.5 (=C-CH
=C-CH ), 134.5 (C=CH, 134.3 (C=CH), 132.7 (C=CH), 132.3 (C=CH),
30.6 (C=CH), 130.2 (C=CH), 45.9, 45.3, 43.8, 41.7, 29.4, 29.3; HRMS
11O+ (M+H)+ 123.0765, found 123.0804
2
-C(CH
3
)=O), 3.49 (s, 2H, CH
2
-C(CH
), 2.17 (s, 3H, CH
), 139.2
3
)=O), 3.01 (s,
225.1272.
2
2
), 2.18 (s, 3H, CH
3
3
);

C
3
2
5
-(Prop-1-ene-2-yl)bicyclo[2.2.1]hept-5-ene-2,2,3,3-tetracarbonitrile
(
1
2
(20)
(ESI) m/z calculated for C
8
H
To a solution of tetracyanoethylene (TCNE, 128 mg, 1 mmol) in CH
2 2
Cl
(
5 mL) a solution of 19 (178.14 mg, 0.99 mmol) in CH Cl (2 mL) was
2
2
2
-Acetonyl-6,6-dimethylfulvene (13)
added dropwise at room temperature. After stirring the mixture at rt for 10
min, the solvent was rotovapped and the product purified by column
A solution of 6-(chloromethyl)-6-methylfulvene (1) (0.30 g, 2.15 mmol) in
dry EtOH (20 mL) at room temperature under inert gas was treated
sequentially with dry acetone (1 mL) and freshly prepared NaOEt (2.2
equivalents). The solution was then stirred for 24h at room temperature.
After dichloromethane (60 mL) was added, the organic layer was washed
chromatography on silica gel, eluting with CH
of product.  (500 MHz, CDCl ) 6.43 (dd, 1H, J= 4.5, 1.5 Hz, =CH), 4.57
(dd, 1H, J= 2.5, 1.5 Hz, CH), 4.40 (dd, 1H, J= 4.5, 2.5 Hz, CH), 3.13 (s,
3H, OCH ), 1.80 (s, 3H, =CCH ), 1.79 (s, 3H, =CCH ), 1.45 (s, 3H, CH ),
1.36 (s, 3H, CH );  (125 MHz, CD Cl ) 159.2 (=C-C(OMe)Me , 137.4
(Me C=C), 129.9 (=CH), 125.3 (Me C=), 112.1 (C≡N), 112.0 (C≡N),
111.7 (C≡N), 111.3 (C≡N), 73.9 (Me COMe), 55.9 (CH), 55.4 (OCH ),
2 2
Cl to give 200 mg (85%)
H
3
3
3
3
3
3
C
2
2
2
with dilute HCl, NaHCO
3
and brine (2 X 20 ml each) and then dried over
2
2
MgSO . The solvent was evaporated in vacuo to provide the crude
4
2
3
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700442
FULL PAPER
4
(
3
9.8 (CH), 47.1 (C-CN), 46.6 (C-CN), 26.1 (=CCH
MeOC(CH ); HRMS (ESI-) m/z calculated for
05.1401, found 305.1408.
3
), 23.2 (=CCH
3
), 19.5
(m, 1H, =CH
2
), 3.08 (dm, J= 16.0 Hz, B part of an AB system, C(4)H),
O- [M-1]-
2.96 (d, J= 16 Hz, A part of an AB system, 1H, C(4)H), 1.84 (dd, J= 3.5,
1.5 Hz, 1H, C(2)H), 1.68 (d, J= 3.5 Hz, 1H, C(2)H), 1.47 (s, 3H, CH ). 
40.5 (C=C), 134.9 (C=CH), 134.8 (C=C), 133.3 (C=CH), 119.0 (C=CH),
06.1 (C=CH ), 49.9 (C-4), 37.4 (C-1), 29.9 (C-3), 28.7 (C-2), 21.6 (CH ).
3
)
2
C
18
H
17
N
4
3
C
1
1
1
-(2-(Cyclopenta-2,4-dien-1-ylidene)propyl)pyrrolidine (21) and 5-
2
3
+
+
HRMS (ESI) m/z calculated for C11
H12 (M ) 144.0939, found 144.0936, .
((4,4-dichloro-3-methylbut-3-en-2-ylidene)cyclopenta-1,3-diene (22)
4,6- and 5,7-Dimethyl-1H-indenes 28 and 29, respectively
To a solution of dry acetone (0.232 g, 0.294 mL, 4 mmol) in acetonitrile
3 mL), a solution of pyrrolidine (0.4 mmol, 0.035 mL) in acetonitrile (1
(
mL) was slowly added. To the resulting mixture, 1 (0.28 g, 2 mmol) in
acetonitrile (1 mL) was added, and the solution stirred at rt overnight. The
To a solution of 27 (0.2 g, 1.4 mmol) in DMSO (5 mL) was added at rt t-
BuOK (156 mg,1.4 mmol), and the mixture heated at 60 oC for 30 min.
After cooling the solution to rt, water (20 mL) was added and the product
mixture was neutralized with acetic acid at 0 oC, H
O (25 mL) was added,
and the mixture extracted with ether (3x10 mL). After washing with
NaHCO and brine, the organic layer was dried over MgSO and the
2
4
extracted with diethyl ether (2x15 mL). After drying over MgSO , the
3
4
solvent rotovapped and the product purified by preparative TLC on silica
gel (n-hexane) to give 0.13 g (65%) of a mixture of 28 and 29 as a
colorless liquid. The spectral date of the product mixture agreed well with
those reported in reference 24.
solvent rotovapped. The residue was purified by preparative TLC on
silica gel, eluting with 15% EtOAc/hexane. Top fraction (red oil, 36 mg,
1
2
CH
1
2
C
0%) was compound 22. 
H, =CH), 2.222 (s, 3H, CH
);  (125 MHz, CDCl
34.1 (C=C), 127.8 (C=CH), 122.8 (C=CH), 116.1 (C=CH), 116.0 (C=CH),
H
(500 MHz, CDCl
), 2.221 (s, 3H, CH
3
) 149.3 (C=C), 143.1 (C=C), 142.3 (C=C),
3
) 6.6 (m, 2H, =CH), 6.48 (m,
3
3
), 2.13 (d, J= 1.5 Hz, 3H,
3
C
Formation of 28/29 from 1-(hydroxymethyl)-1,3-dimethyl-1,2-
dihydropentalene (30) via in situ generated mesylate 31
9.4 (CH
3
), 23.1 (CH
3
3
), 15.1 (CH ). HRMS (ESI) m/z calculated for
+
+ 35
11
H
13Cl (M , Cl) 180.0706, found 180.0700.
To a solution of 3018 (122 mg, 0.75 mmol) in acetonitrile (5 mL) of
methanesulfonyl chloride), (1.7 g, 1.5 mmol) was added at 0 oC. To this
The second fraction was
characterized as 21.  (500 MHz, CDCl
CH), 6.45 (m, 1H, =CH), 3.5 (s, 2H, CH
H, CH ), 1.8 (m, 4H, ring-CH );  (125 MHz, CDCl
43.2 (C=C-5), 131.8 (C=C-2), 130.9 (C=C-3), 121.4 (C=C-1), 120.4
), 54.6 (N-CH -ring), 23.8 (ring-CH ), 20.1 (CH ).
HRMS (ESI) m/z calculated for
18N+ (M+H)+ 176.1395, found
a
yellow liquid (56 mg, 16%) and was
) 6.6 (m, 1H, =CH), 6.5 (m, 4H,
), 2.5 (m, 4H, N-CH ), 2.3 (s,
) 150.8 (C=C-6),
mixture, of DBU (0.46g, 3 mmol) was added, and the mixture stirred at rt
for 2h. The crude 1H NMR spectrum showed the formation of a 60:40
mixture of 28/29 and 27, respectively. They were separated by flash
chromatography on silica gel (hexanes). The fraction containing 28/29
was identical to that obtained from 27 with t-BuOK/DMSO.
H
3
=
3
1
2
2
3
2
C
3
(C=C-4), 60.4 (N-CH
2
2
2
3
12
C H
1
76.1434.
Acknowledgements
1
-(Chloromethyl)-1,3-dimethyl-1,2-dihydropentalene (23)
Financial support of this work by funds from the National
Institutes of Health (Grant No. SC1 GM082340) is gratefully
acknowledged. S. G. acknowledges support from the National
Science Foundation (CHE-1565852). The mass spectrometry
work at SFSU was in part supported by a grant from the National
Science Foundation (CHE-1228656) and is gratefully
acknowledged. Mr. Tapken acknowledges a travel grant by the
DAAD (German Academic Exchange Service) “Go out!”
Program for his study visit at SFSU. Mr. Cabrera acknowledges
NIH MBRS-RISE (R25-GM059298) and NIH-MS-PhD Bridge (R-
To a solution of of 6-(chloromethyl)-6-methylfulvene (1) (0.84 g, 6.00
mmol) in 20 mL of dry acetone, pyrrolidine (128 mg, 1.8 mmol) was
added with a syringe. The solution was refluxed under nitrogen for 2
hours. After allowing the solution to cool to room temperature, glacial
acetic acid (1 mL) was added dropwise. After adding ether (60 mL), the
mixture was extracted with saturated aqueous solutions of NaHCO
NaCl (2x20 mL, respectively), then dried over MgSO . The solvent was
rotovapped and the product purified by preparative TLC on silica gel to
afford 540 mg (50% yield) of 23 as an orange liquid.  (500 MHz, CDCl
.78 (dd, J= 5=.0, 1.5 Hz, 1H, C=C(5)-H), 6.2 (d, J= 5.0Hz, 1H, C=C(4)-
H), 5.95 (d, J= 1.5 Hz, 1H, C=C(6)-H), 3.61 (d, B part of an AB system,
J= 10.5 Hz, 1H, CH Cl), 3.5 (d, A part of an AB system, J= 10.5 Hz, 1H,
CH Cl), 3.2 (d, A part of an AB system, J= 19 Hz, 1,H, C(2)H ), 2.8 (d, B
part of an AB system, J= 19 Hz, 1,H, C(2)H ), 2.2 (s, 3H, C=CCH ), 1.4
) 155.2 (C=C), 154.9 (C=C), 139.6
C=CH), 114.8 (C=CH), 111.0 (C=CH), 57.7 (C-2), 54.2 (CH Cl), 43.1 (C-
). HRMS (ESI) m/z calculated for C11 14Cl (M+H,
3
and
4
H
3
)
6
25-GM048972) scholarships. Dr. Coskun acknowledges a
2
BIDEP-2219 fellowship from the Turkish Scientific and
Technological Research Council (TUBITAK). We also thank Dr.
Robert Yen, SFSU, for the HRMS spectra.
2
2
2
3
3 C 3
(s, 3H, CH );  (125 MHz, CDCl
(
2
Supporting Information. Supporting information ( H and 13C
NMR spectra of 13, 14, 15, 16, 20, 21, 22, 23, 27, complete
reference 19, as well as computational data) associated with this
article can be found in the online version at
1
1
), 24.7 (CH
3
), 17.0 (CH
3
H
3
5Cl)+ 181.0786, found 181.0779,
3
-Methyl-5-methylidenetricyclo[4.3.0.01,3]nona-6,8-diene (27)
2 2
Cl
, cooled to -78 oC,
Toa solution of 23 (0.4 g, 2.2 mmol) in 5 mL of CH
DBU (0.34 g, 2.2 mmol) dissolved in CH Cl (1 mL) was added dropwise.
The mixture was warmed up to room temperature and stirred by
preparative TLC on silica gel (hexanes) to give 0.20 g (63%) of a
2
2
Keywords: Fulvenes / Nucleophilic addition/ Dipolar
cycloaddition/ 1,2-Dihydropentalene / E1cB
colorless liquid. When the reaction was repeated in CDCl
same conditions, 30% deuterium incorporation onto C-7 was observed.
(500 MHz, CDCl ) 6.6 (dd, J= 5.0, 2.0 Hz, 1H, C(8)-H), 6.4 (d, J= 2.0
Hz, 1H, C(7)-H), 6.3 (d, J= 5.0 Hz, 1H, C(9)-H), 5.14 (m, 1H, =CH ), 4.9
3
under the
[1]
For reviews, see: (a) P. Yates, Advanced Alicyclic Chemistry; Academic
Press: New York, 1968; Vol. 2, p 59-184. (b) E. D. Bergman, Chem.
Rev. 1968, 68, 41-84. (c) J. H. Day, Chem. Rev. 1963, 53, 167-189. (d)

H
3
2
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700442
FULL PAPER
K. P. Zeller, Pentafulvenes, in Methoden der Organischen Chemie;
[21] L. A. Paquette, Acc. Chem. Res. 1968, 209-216.
1985; Vo1.5/2c, pp 504-684. (e) M. Neuenschwander, Fulvenes, in
[22] (a) F. G. Bordwell, Acc. Chem. Res. 1970, 3, 281-290. (b) F. G.
Bordwell, R. R. Frame, R. G. Scamehorn, J. G. Strong, S. Meyerson, J.
Am. Chem. Soc. 1967, 89, 6704-6711.
The Chemistry of Double-Bonded Functional Groups; S. Patai, Ed.;
John Wiley: New York, 1989; pp 1131-1268.
[
2]
(a) K. N. Houk, L. J. Luskus, J. Org. Chem. 1973, 38, 3836-3843. (b) K.
N. Houk L. J. Luskus, N. S. Bhacca, J. Am. Chem. Soc. 1970, 92,
[23] S. J. Cristol, K. J. Harrington, M. S. Singer, J. Am. Chem. Soc. 1966, 88,
1529-1532.
6
392-6394. (c) K. N. Houk,. L. C. Dunn, Tetrahedron Lett. 1978, 37,
[24] E. Marechal, P. Evrard, P. Sigwalt, Bull. Soc. Chim. Fr. 1969, 1981-
1989.
3411-3414. (d) B.-C. Hong, Y.-J. Shr, J.-L. Wu, A. K. Gupta, K. J. Lin,
Org Lett. 2002, 4, 2249-2252. (e) B.-C. Hong, J.-L. Wu, A. K. Gupta, M.
S. Hallur, J.-H. Liao, Org. Lett. 2004, 6, 3453-3456, and references
cited therein.
[
[
3]
4]
I. Erden, J. Basada, D. Poli, G. Cabrera, F. Xu, S. Gronert, Tetrahedron
Lett. 2016, 57, 2190-2193, and references cited therein.
(a) G. W. Wheland, D. E. Mann, J. Chem. Phys. 1949, 17, 264-268; (b)
P. A. Baron, R. D. Brown, F. R. Burden, P. J. Domaille, J. E. Kent, J.
Mol. Spectrosc. 1972, 43, 410-410; (c) P. Swiderek, M. Michaud, L.
Sanche, J. Chem. Phys. 1995, 103, 8424-8432; (d) C. Dahlstrand, K.
Yamazaki, K. Kilsa, H. Ottosson, J. Org. Chem. 2010, 75, 8060-8068;
(
e) E. Kleinpeter, A. Fettke, Tetrahedron Lett. 2008, 49, 2776-2781.
[
[
5]
6]
I. Erden, S. Gronert, J. R. Keeffe, J. Ma, N. Ocal, C. Gärtner, L. L.
Soukup, J. Org. Chem. 2014, 79, 6410-6418.
(a) K. Ziegler, W. Schäfer, Ann, 1934, 511, 101-109. (b) W. F. Little, R.
C. Koestler, J. Org. Chem. 1967, 26, 3247-3250. (c) G. Büchi, D.
Berthet, R. Decorzant, A. Grieder, A. Hauser, J. Org. Chem. 1984, 41,
3208-3209. (d) K. Antczak, J. Kingston, A. G. Fallis, Can. J. Chem.
1984, 62, 2451-2455.
[
[
7]
8]
W.-D. Schroer, W. Friedrichsen, Ann. 1978, 1648-1654.
(a) K. Ziegler, H. G. Gellert, H. Martin, K. Nagel, J. Schneider, Ann.
Chem. 1954, 589, 91-121. (b) K. Hafner, Ann. Chem. 1957, 606, 79-89.
(
d) D. D. Sternbach, J. W. Hughes, D. F. Burdi, J. Org. Chem. 1984, 49,
01-202.
2
[
9]
(a) I. Erden, C. Gärtner, Tetrahedron Lett. 2009, 50, 2381-2383. (b) J.
Baumgartner, H. Weber, Chirality, 2001, 13, 159-163. (c) W. Adam, L.
Hadjiarapoglou, A. Meffert, Tetrahedron Lett. 1991, 32, 6697-6700.
[
[
10] C. G. Swain, A. L. Powell, T. J. Lynch, S. R. Alpha, R. P. Dunlap, J. Am.
Chem. Soc. 1979, 101, 3584-3587.
11] In
a few cases, 1-alkoxyspiro[2.4]hepta-4,6-diene derivatives have
been isolated, however, neither of these carry an additional methyl
group on C-1: (a) R. A. Moss, C. M. Young, L. A. Perez, K. Krogh-
Jespersen, J. Am. Chem. Soc. 1981, 103, 2413-2415. (b) A. H. Amaro,
K. Grohmann, J. Am. Chem. Soc. 1975, 97, 5946-5948. (c) A. I.
D’yachenko, L. G. Menchikov, O. M. Nefedov, Izv. Akad Nauk, Ser.
Khim. 1985, 709-711.
[
[
12] 1-Alkyl-1-cyclopentadienylpropan-2-ones have been reported and the
relevant 1HNMR signals are in agreement with our parent system
(
10/11), except for the olefinic region where the cyclopentadienyl
signals have been reported at 6.1 ppm in the 1-methyl derivative,
though in our case they give rise to several signals ranging from 6.1-6.4
ppm: B. S. Ong, T.-K. Chan Heterocycles 1977, 7, 913-918.
13] J. E. Månsson, T. Olsson, O. Wennerström, Acta. Chem. Scand. B
1979, 33, 307-308.
[
[
14] J. L. Kice, F. M. Parham, J. Am. Chem. Soc. 1958, 80, 3792-3797.
15] (a) J. Thiele, Chem. Ber. 1900, 33, 666. (b) J. Thiele, Justus Liebigs
Ann. Chem. 1906, 348, 1.(c) I. Erden, F.-P. Xu, A. Sadoun, W. Smith, G.
Sheff, M. Ossun, J. Org. Chem. 1995, 60, 813–820. (d) N. Coskun, I.
Erden, Tetrahedron, 2011, 67, 8607-8614, and references cited therein.
16] (a) J. Thiele, H. Balhorn, Justus Liebigs Ann. Chem. 1906, 348, 1-15.
[
[
[
(
b) D. M. Fenton, M. J. Hurwitz, J. Org. Chem. 1963, 28, 1646-1651.
17] M. Shamma, J. P. Giannetti, R. B. Henry, A. Melbardis, Tetrahedron
963, 19, 1409-1413.
18] N. Coskun, J.;Ma, S. Azimi, C. Gärtner, I. Erden, Org. Lett. 2011, 52,
952-5955.
1
5
[
[
19] M. J. Frisch, Gaussian09; Gaussian, Inc.: Wallingford, CT, 2009.
20] J. R. Keeffe, W. P. Jenks, J. Am. Chem. Soc. 1983, 105, 265-269, and
references cited therein.
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700442
FULL PAPER
Entry for the Table of Contents (Please choose one layout)
Layout 1:
FULL PAPER
Key Topic Nucleophilic additions to fulvenes
Ihsan Erden*, Scott Gronert*, Gabriel Cabrera, Necdet Coskun,
and Marco Tapken
Page No. – Page No.
Diverse modes of reactivity of 6-(chloromethyl)-6-
methylfulvene
[
[
[
a]
b]
c]
Department of Chemistry and Biochemistry, San Francisco State
University, 1600 Holloway Avenue, San Francisco, CA 94132, USA
E-mail: ierden@sfsu.edu
Department of Chemistry, Virginia Commonwealth University, 1001
West Main Street, Richmond, Virginia 23284, USA
E-mail: sgronert@vcu.edu
Uludağ University, Department of Chemistry, 16059 Bursa-Turkey
Supporting information for this article is given via a link at the end of
the document
This article is protected by copyright. All rights reserved.