An improved pathway to 6,6-disubstituted fulvenes

Article abstract of DOI:10.1016/j.tetlet.2004.07.058

Pentafulvenes with alkyl and/or aryl substituents at the exocyclic position are formed rapidly in high yields through reaction of crystalline sodium cyclopentadienide directly with the appropriate ketones.

Full text of DOI:10.1016/j.tetlet.2004.07.058

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6741–6744
An improved pathway to 6,6-disubstituted fulvenes
Khalil Chajara and Henrik Ottosson*
Department of Chemistry, Organic Chemistry, PO Box 599, Uppsala University, 751 24 Uppsala, Sweden
Received 12 May 2004; revised 7 July 2004; accepted 13 July 2004
Available online 30 July 2004
Abstract—Pentafulvenes with alkyl and/or aryl substituents at the exocyclic position are formed rapidly in high yields through reac-
tion of crystalline sodium cyclopentadienide directly with the appropriate ketones.
Ó 2004 Elsevier Ltd. All rights reserved.
Fulvenes are an interesting class of cyclic cross-conju-
gated molecules that display a wide range of reactions
with both nucleophiles, electrophiles and various cyclo-
addition partners.1–3 Pentafulvenes also serve as acti-
vated dienes in Diels–Alder reactions and as synthetic
precursors to several biologically occurring com-
pounds.4–6 Further, they are interesting compounds for
theoretical and spectroscopic reasons relating to the
charge distribution and p-electron delocalisation in
cross-conjugated molecules.7,8
tion between cyclopentadiene and carbonyl compounds
such as ketones, aldehydes with acidic a-hydrogens, and
sterically encumbered aldehydes. Even though the yields
when following this pathway are high (45–98%), the
reaction times vary greatly (12min–48h), and the use
of this route with bulky ketones, for example, diaryl
ketones, was not reported.
We now report an improved route to fulvenes in which a
ketone is reacted with crystalline sodium or potassium
cyclopentadienide. Following the recent procedure of
Roesky and co-workers,22 the metal cyclopentadienides
were prepared as white crystals in one-pot, directly
through reaction of the alkali metals with neat dicyclo-
pentadiene. No solvents are needed and no coloured
impurities are observed. This pathway provides alkali
metal cyclopentadienide in higher yields than achieved
under ThieleÕs conditions, and it complements the route
of Little in which the carbonyl compound is activated.
Often, pentafulvenes are prepared by condensation of
cyclopentadiene with ketones or aldehydes under ThieleÕs
conditions using an alkali metal base in an alcohol, pro-
viding the product in modest to good yields.9–17 The
scope and limitation of this method depends on the reac-
tivity of the particular carbonyl compound and on the
stability of the fulvene formed. Whereas the cyclopenta-
dienide part in most transition metal complexes is
strongly bound and not easily substituted,18 cyclopenta-
dienyl copper tributylphosphine and nickelocene are less
stable and more reactive, and represent alternatives to al-
kali metal cyclopentadienides.19 Oda and co-workers
worked out a high yield procedure to 6,6-disubstituted
pentafulvenes using N,N-dialkylamides, instead of
ketones, with organolithium compounds and cyclopen-
tadiene.20
A set of 12 different 6,6-disubstituted fulvenes (Table 1)
was prepared, and all except one were made through
condensation of sodium cyclopentadienide with the
appropriate ketone (Scheme 1). For the synthesis of 10
we used 2-chloroethyl chloroformate, as employed by
Hong et al. (Scheme 2),16 instead of the corresponding
carbonyl compound, ethylene carbonate. Although the
sodium salt is a potent source of cyclopentadienide, its
addition to ethylene carbonate did not yield the desired
product.
Another alternative route towards a range of structur-
ally diverse fulvenes was found by Stone and Little.21
They showed that pyrrolidine promotes fulvene forma-
When compared to previously reported results, the use
of crystalline sodium cyclopentadienide in all cases gives
6,6-disubstituted fulvenes in good to excellent yields
(50–95%) after short reaction times (ꢀ30min). The yield
for fulvene formation is increased by upto 60%, and the
Keywords: Fulvenes; Alkali metal cyclopentadienides.
*
Corresponding author. Tel.: +46-18-471-3809; fax: +46-18-471-
3818; e-mail: henrik.ottosson@kemi.uu.se
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.07.058

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K. Chajara, H. Ottosson / Tetrahedron Letters 45 (2004) 6741–6744
Table 1. Formation of 6,6-disubstituted fulvenes
Fulvene
Yield [%]
R1
R2
Reported
All procedures
This worka
Na+Cpꢁ
1, Phenyl
Phenyl
45b, 54c, 85d
35b
74
82
2, p-Chlorophenyl
3, p-Methoxyphenyl
4, p-Nitrophenyl
5, Methyl
p-Chlorophenyl
p-Methoxyphenyl
p-Nitrophenyl
Phenyl
10b
65
50
16e
45f, 95d
63f
96g, 46h
95i
––
65
82
6, Methyl
7, Methyl
8, Ethyl
p-Fluorophenyl
Methyl
Ethyl
95
95
9, tert-Butyl
R1/R2
10, –O–CH2–CH2–O–
tert-Butyl
Trace
82–85j
84
60
11,
12,
22c, 81k
26l
33
a The yields given are based on the isolated compounds prepared according to the descriptions found under general synthetic procedures.
b Value from Ref. 18.
c Value from Ref. 13.
d Value from Ref. 23.
e Value from Ref. 15.
f Value from Ref. 16.
g Value from Ref. 24.
h Value from Ref. 17.
i Value from Ref. 25.
j Value from Ref. 20.
k Value from Ref. 21.
l Value from Ref. 26.
R1
R2
cyclopentadienide salt is prepared directly from dicyclo-
pentadiene. The improvement in reaction time also
favours the modified procedure towards fulvenes, which
are already available in high yields. For example, the
method of Oda and co-workers was reported to need
5h.20
THF
O
+
Na+
R1
R2
30 min, ∆
Scheme 1.
The reaction with sodium cyclopentadienide is most effi-
cient when carried out in THF for 30min at 60°C. The
progress of the reaction correlates with a colour change
of the solution; from light purple in the beginning to in-
tense brown when completed. This colour change was
observed in the formation of all fulvenes except 10 for
which the colour turned light yellow. Longer reaction
times (6h) lead to dark solutions and lower yields, prob-
ably due to intermolecular cycloadditions or decomposi-
tion of the pentafulvenes. Surprisingly, potassium
cyclopentadienide, which should be more potent than
the sodium salt, gave yields for 1, 2, 5, 6, 10 and 11 that
were lower by 20–30% than those found when the
sodium salt was used, and 3, 4, 7 and 9 could not be
formed with the potassium salt regardless of reaction
time.
O
O
O
CH3CN
30 min, 0 oC
+
Na+
Cl
Cl
O
Scheme 2.
R1
R2
N
H
1)
O
R1
R2
2)
Na+
Scheme 3.
High yields of the fulvenes are also obtained when the
bulk of the ketone increases. Fulvene 11 was produced
in a slightly lower yield than reported by Olah and co-
workers (Table 1), but after shorter reaction time
(30min vs 3h). 6,6-Di-tert-butyl-fulvene 9, which has
not been reported previously in the literature, can prob-
time required is reduced considerably. Diphenylketones
with electron donor groups in para-position can be used,
in addition to those with electron acceptor groups. The
procedure further saves one synthetic operation as the

K. Chajara, H. Ottosson / Tetrahedron Letters 45 (2004) 6741–6744
6743
ably be formed in very low yields as a yellow compound.
Its formation, which required a longer time (3–6h) than
for the other fulvenes, was therefore only verified
through NMR and GCMS of the crude mixture.27 The
use of potassium cyclopentadienide instead of the
sodium salt did not improve the result, but it is likely
that further modifications of the reaction conditions
could lead to a process that gives 9 in reasonable yields.
pared according to the recently published procedure of
Roesky, generally leads to 6,6-disubstituted fulvenes in
higher yields than previously reported and after shorter
reaction times.
General synthetic procedures: Sodium cyclopentadi-
enide was synthesised using the procedure described re-
cently by Roesky and co-workers.22 This procedure
gives white crystals that can be stored at 0°C under
argon for several days. In a typical reaction, sodium cyclo-
pentadienide (11mmol) was added to tetrahydrofuran
(10mL, distilled from sodium) under nitrogen. A solu-
tion of the appropriate ketone (11mmol) in THF was
added dropwise, while stirring. The mixture was then
refluxed for 30min. After extraction with ether, the
organic phase was washed with 5% hydrochloric acid,
dried with sodium sulfate and concentrated. The fulvene
was separated by column chromatography on silica
using pentane as eluent.
Under the conditions of Scheme 1 the reaction between
sodium cyclopentadienide and the aldehydes, pentanal,
butanal and benzaldehyde, did not work. Benzaldehyde
was reduced instead. Moreover, we initially expected
that the potent sodium cyclopentadienide would add to
esters and amides forming fulvenes with hetero-substi-
tuents at the 6-position. However, reactions of sodium
and potassium cyclopentadienide with ethylbenzoate
and the amides N,N-dimethylacetamide, 3-methyl-2-
oxazolidine, 1-methyl-2-pyridone and 1,3-dimethyl-2-
imidazolidinone led to complex mixtures that could not
be separated.
4,40-Dinitrobenzophenone, needed for synthesis of 6,6-
bis(4-nitrophenyl)fulvene, was prepared through nitra-
tion of diphenylmethane followed by oxidation using
tetramethylammonium fluoride and N,N-dimethyl-
acetamide under a positive pressure of oxygen.28,29
The synthesis of 2-cyclopentadienyliden-1,3-dioxolane
10 was carried out at 0°C for 30min.
Since the procedure of Little worked through activation
of the ketone and the present procedure functions
through activation of the cyclopentadienide, a combina-
tion of the two methods could possibly give higher yields
(Scheme 3). We tested those fulvenes that were formed
in yields below 80% when using sodium cyclopentadie-
nide. The combined reaction was carried out both with
reflux in THF for 30min and at room temperature for
1h. However, the results were irregular because im-
proved yields were obtained for 1, 2 and 5, whereas dras-
tic cuts resulted for the others (Table 2). The yield of 3
could be increased to 50%, but only when run overnight
at room temperature with a three-fold excess of sodium
cyclopentadienide. On this occasion, the pyrrolidine was
added to the ketone 1h before the cyclopentadienide.
All compounds were identified by NMR, UV/Vis and
GCMS, and agree with reported literature data.
Acknowledgements
The Wenner-Gren Foundations are acknowledged for a
postdoctoral fellowship to K.C., and the Ingegerd
BerghÕs Foundation is thanked for a materials grant.
In summary, reaction of alkyl and/or aryl substituted
ketones with crystalline sodium cyclopentadienide, pre-
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R1
Na+
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1, Phenyl Phenyl
2, p-Chlorophenyl p-Chlorophenyl
3, p-Methoxyphenyl p-Methoxyphenyl
60
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85
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––
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