Synthesis and structural analysis of a novel iodinated cyclopentadienone via ring-contraction iodination and its application in synthesis of alkyne-functionalized cyclopentadienones

Article abstract of DOI:10.1039/c0cc02543g

The first iodinated cyclopentadienone was isolated and its structure was confirmed by single crystal X-ray analysis. Based on this intermediate, the first direct C-C bond formation on cyclopentadienone ring was achieved. The photo induced intramolecular charge transfer of alkynylated cyclopentadienones was evaluated by solvent polarity effect on their electronic absorption spectra.

Full text of DOI:10.1039/c0cc02543g

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Synthesis and structural analysis of a novel iodinated cyclopentadienone
via ring-contraction iodination and its application in synthesis
of alkyne-functionalized cyclopentadienonesw
Xue-Yi Chen,a Charles Barnes,b Xinyan Bai,a T. C. Sandreczki,a Zhonghua Peng,a
Ekaterina N. Kadnikovaa and J. R. Dias*a
Received 13th July 2010, Accepted 17th September 2010
DOI: 10.1039/c0cc02543g
The first iodinated cyclopentadienone was isolated and its
structure was confirmed by single crystal X-ray analysis. Based
on this intermediate, the first direct C–C bond formation on
cyclopentadienone ring was achieved. The photo induced intra-
molecular charge transfer of alkynylated cyclopentadienones
was evaluated by solvent polarity effect on their electronic
absorption spectra.
Cyclopentadienone derivatives are uniquely valuable inter-
mediate compounds. For example, their 4+2 Diels–Alder
reaction products with dienophiles are difficult to obtain via
any other synthetic route.1 They are also key precursors for
Scheme 1 Reaction conditions: (i) (a) Oxygen-free conditions, (b) in
the synthesis of substituted cyclobutadienes and tetrahedranes.2
the presence of oxygen, (ii) 2.05 equiv. AcCl, 4 equiv. Et3N, THF,
In addition they are important intermediates for various
À 20 1C, 30 min.
pharmaceuticals.3 Due to their low LUMO–HOMO gap of
about 1.6 eV, cyclopentadienone-containing conjugated
systems exhibit unique electrical and optical properties.4 In
this study, our effort was to explore the synthetic methodology
of creating cyclopentadienone-containing conjugated systems
having sp–sp2 linkages.
of 4,6-di-tert-butylresorcinol (1) (Scheme 1). The merit of this
reaction is that the product not only possesses a cyclodienone
structure but also has an iodine atom attached to its five
membered ring. The carbon–iodine bond is known to be
the weakest carbon–halogen bond, so that iodinated cyclo-
pentadienone derivatives are predicted to be among the most
reactive halogenated cyclopentadienones. To date no iodine-
substituted cyclopentadienone has ever been reported.
Cyclopentadienone itself, however, is very elusive due to its
extremely high reactivity and fast dimerization rate.5 For this
reason, cyclopentadienone derivatives are normally generated
in situ and consumed immediately in most reactions.6 As
a result, very little is known about the structures of its
derivatives, and no direct C–C bond formation on the cyclo-
pentadienone ring other than 4+2 cycloaddition has ever been
reported. In contrast to this, we have prepared a useful
cyclopentadienone derivative that is stable enough to be
isolated, characterized and stored under convenient conditions.
The method we have used involves a ring-contraction process.
A ring contraction reaction of 4-aryl-2,6-di-tert-butylphenol
has been reported7 to form various cyclopentadienones in the
presence of oxygen under basic conditions. However this
procedure cannot be applied in our study, where iodine
substitution is essential to extend the conjugation of the
cyclopentadienone ring by further alkylynation. Therefore
we employed a one-pot iodination ring-contraction reaction
Prior to this research, the only synthesis of alkyne-
functionalized cyclopentadienone-like compounds was
achieved by the reaction of its diacetal form,8 and no direct
alkynylation of cyclopentadienone has been reported. In this
study, we report the first synthesis and structural analysis of
iodine-substituted cyclopentadienone and its further reaction
with terminal alkynes.
A hydroperoxylation mechanism for the formation of
cyclopentadienone derivatives from the corresponding phenols
was discovered by Nishinaga and Rieker which was evidenced
by the discovery of epoxide intermediate formed by bubbling
oxygen gas through the reaction mixture.8 In the present study
however, the yield of iodinated cyclopentadienone 3 is much
higher under oxygen-free conditions (B20%) than in the
presence of oxygen (8%), so that the formation of epoxide
intermediate can be excluded. A possible alternative mechanism
for the ring-contraction iodination reaction is shown in
Scheme 2. This reaction begins with normal electrophilic
aromatic substitution to give intermediate (i), most of which
(B75%) retains its aromaticity by ejecting a proton to yield
the major product 4,6-di-tert-butyl-2-iodobenzene-1,3-diol
(2a). However further iodination also takes place on the
2 and 4 positions of the remaining intermediate (i) to give
a Department of Chemistry, University of Missouri-Kansas City,
5100 Rockhill Road, Kansas City, MO 64110, USA.
E-mail: diasj@umkc.edu; Fax: +1 816-235-2284
b Department of Chemistry, University of Missouri-Columbia,
601 S. College Avenue, Columbia, MO 65211, USA
w Electronic supplementary information (ESI) available: General
experimental details, NMR spectra, MS spectrum. CCDC 783904
(2b) and 783905 (3). For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c0cc02543g
c
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Chem. Commun., 2010, 46, 8171–8173 8171

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Scheme 3 Reagents and conditions: Pd(PPh3)2Cl2 (0.5 mol%) CuI
(1 mol%), Et3N 10 equiv., THF, room temperature, oxygen-free
conditions, 3 days, 80–97%.
Table 1 The Sonogashira cross coupling reactions of 3 with
terminal alkynes
Entry
R
Yield (%)
Scheme
2
Possible mechanism for ring-contraction iodination
4a
4b
4c
4d
4e
4f
4g
4h
4i
TMS
n-Butyl
tert-Butyl
Cyclohexanyl
Cyclopentylmethyl
Cyclopropanyl
Phenyl
6-Methoxynaphthalen-2-yl
Phenanthren-9-yl
N,N-Dimethylanlin-4-yl
3,5-Di-tert-butyl-4-methoxyphenyl
o-Tolyl
Ferrocenyl
Pyridin-2-yl
Thiophen-2-yl
Hydroxy(phenyl)methyl
2-Hydroxyethyl
2-((Tetrahydro-2H-pyran-2-yl)oxy)ethyl
3-Hydroxypropyl
Acetyl
95
90
92
85
84
87
97
95
94
91
92
98
reaction.
the triiodocyclohexenedione intermediate (ii), followed by
hydration of one of its ketone to give intermediate (iii). The
ring contraction takes place by 1,2 carbon shift resulting in the
elimination of one iodide on 2 position of intermediate (iii),
followed by deprotonation to give intermediate (iv). Final
product 3 was formed by simultaneous elimination of carbon
dioxide and iodide of intermediate (iv).
4j
4k
4l
After purification of the reaction mixture, two different
1
compounds (2a and 3) were obtained. H NMR and 13C NMR
4m
4n
4o
4p
4q
4r
4s
4t
91
a
a
a
a
a
are consistent with its structure and further confirmative
evidence is obtained by X-ray structural analysis. For
comparison, structures of both 2b and minor product 3 were
analyzed by single crystal X-ray diffraction. The unusual bond
angles for C3–C4–C5 of 3 and C1–C2–C3 of 2b are presumably
caused by the inward squeezing of the tert-butyl on C(4) of 3
and C(2) of 2b, which is similar to the compression of a leaf
spring (Fig. 1). Specifically, the C3–C4–C5 bond angle of 3 is
1131 in comparison to 1081 for all five bond angles of the five
membered ring of tetracyclones,9 and the C1–C2–C3 bond
angle of 2b is 1251.
Remarkably, in the crystal lattice of 3 there are no short
contacts. This indicates that the spatial exclusion of each
individual molecule dominates packing forces. In comparison,
the short contact between the CQO oxygen and a hydrogen
on the tert-butyl group influences crystal packing of 2b
(Fig. S1, ESIw).
80
a
a
4u
Methylacetoxy
a
A mixture of inseparable oligomers or polymers instead of the
cross-coupling product was obtained.
(Scheme 3), which we have reported previously.10 Both reaction
yields (Table 1) and purities of products (see ESIw) are high for
most alkyl-substituted and aryl-substituted terminal alkynes.
For terminal alkynes with strong electron withdrawing groups
(EWG) or thiophene or pyridine substituents, however, this
reaction renders a mixture of inseparable various oligomers or
polymers possibly via 4+2 cyclo-addition (Table 1). Interestingly,
the reaction yield for the cross-coupling of 3 and 3-hydroxy-
propylacetylene is 80%; however, the reaction of 3 with both
hydroxy(phenyl)methylacetylene and 2-hydroxyethylacetylene
gives mixtures of inseparable oligomers or polymers. This
indicates that for ether- or alcohol-functionalized terminal
acetylenes, at least a three-methylene spacer from the oxygen
atom to acetylene is required for this reaction to yield the
desired cross-coupling product.
The cross-coupling reactions of 3 with terminal alkynes were
carried out under oxygen-free Sonogashira reaction conditions
Further investigations of reactions of these EWG substituted
alkynes with 3 were conducted under catalyst free conditions;
no reactions occurred. This indicates that the copper and
palladium catalyst are essential in assisting the 4+2 cyclo-
addition reaction of terminal alkynes bearing EWG groups
with 3 or its alkynylated products.
The electronic absorption spectra of alkynylated cyclopenta-
dienones (lmax = 460–522 nm) exhibit bathochromic shifts in
comparison to unalkynylated compound 3 (lmax = 448 nm), and
Fig. 1 Increase in bond angle for both C3–C4–C5 of 3 and
C1–C2–C3 of 2b is similar to the compression a leaf spring.
c
8172 Chem. Commun., 2010, 46, 8171–8173
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cyclopentadieneones. Electronic absorption spectra of 3, 4e,
4s, 4h, 4j and 4l in seven solvents with different polarities were
measured. The R-band absorption maxima of all substituted
cyclopentadienones exhibit bathochromic shift with the
increase of solvent polarities (Fig. S2, ESIw) in both non-
halogenated solvents and chlorinated solvents. This divergence
can be attributed to the fact that the energy of their charge
separation/transfer excited states were lowered more by
solvent polarity effect than that of ground state energy of
the n orbital of their carbonyl groups. As a result, the alkyl-
substituted ethynyl cyclopentadienones 4s and 4e appeared to
be influenced more by solvent polarity and thus exhibit the
more bathochromic shift in polar solvent in contrast to their
aryl-substituted counterpart. In addition, the polarity of
chlorinated solvents has more influence on Dlmax of substituted
cyclopentadienones than non-halogenated solvents.
Fig. 2 Electronic absorption spectra of substituted cyclopenta-
dieneones in chloroform. The spectrum of each compound is normalized
to its main absorption maximum.
The authors thank a referee for suggesting a more reason-
able mechanism in Scheme 2.
greater bathochromic shifts are observed in aromatic-substituted
ethynyl cyclopentadienone (Fig. 2). Due to the sigma-aromaticity
of its cyclopropanyl substituent, compound 4f also exhibits
greater bathochromic shifts (lmax = 480 nm) than other alkyl
substituted ethynyl cyclopentadienones. Fine tuning of absorption
maxima was achieved by changing the substituent groups. For
example, compound 4j has the longest absorption-maximum
wavelength, at 522 nm, due to the high electron density on its
electron-donating N,N-dimethylanilin-4-yl group.
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The spectral characteristics of the cyclopentadienones are
presented in Table S2 (ESIw). Generally the R band (n - p*
transition) of most enones are weak and poorly defined
(emax o 100),11 however all ethynyl cyclopentadienones
exhibit moderate absorption in that their extinction coefficients
are comparable to that of the benzenoid B-band. Notably, the
R band extinction coefficients of aryl-substituted ethynyl
cyclopentadienones are much higher than their alkyl-substituted
counterparts. This conjugation enhanced R band absorption
can be possibly explained by their resonance stabilized
photoinduced intramolecular charge transfer/charge separation
excited states.
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compounds became essential to probe solvent polarity effect
on stabilization of their ground states and possible charge
transfer/separation excited states as opposed to resonance
stabilization discussed above. Normally since dipole–dipole
interaction and H-bonding lower the ground state energy of n
orbital of carbonyl group, solvatochromic hypsochromic shifts
of R band were observed in aldehydes, ketones and other
carbonyl compounds.11,12 However an opposite trend was
observed in our study of solvent polarity effect on ethynyl
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nchez,
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c
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 8171–8173 8173