Synthesis and one-electron oxidation chemistry of stable β,β-dimesityl enols with heteroaryl substituents

Article abstract of DOI:10.1515/znb-2003-0910

Four novel stable enols (one characterized by X-ray crystal structure analysis) were synthesized and investigated under oxidative conditions to yield benzofurans. Depending on the donor qualities of the heteroaryl substituent the reaction following the one-electron oxidation could be stopped on the stage of the cyclohexadienyl cation whose lifetime was measured. Oxidation potentials were determined for the enols, the enolates and the α-carbonyl radicals. Oxidation of benzofurans yielded dimeric species or intramolecular cyclization products.

Full text of DOI:10.1515/znb-2003-0910

Synthesis and One-Electron Oxidation Chemistry of Stable
β,β-Dimesityl Enols with Heteroaryl Substituents
Michael Schmittela, Mukul Lala, Wolfdieter A. Schenkb, Michael Hagelb,
Nicolai Burzlaffb, and Anja Langelsc
a Organische Chemie 1 der Universita¨t Siegen, Fachbereich 8,
Adolf-Reichwein-Str., 57068 Siegen, Germany
b Institut fu¨r Anorganische Chemie der Universita¨t Wu¨rzburg,
Am Hubland, D-97074 Wu¨rzburg, Germany
c Institut fu¨r Organische Chemie der Universita¨t Wu¨rzburg,
Am Hubland, D-97074 Wu¨rzburg, Germany
Reprint requests to Prof. Dr. M. Schmittel. Fax: +49(0)271-740-3270.
E-mail: schmittel@chemie.uni-siegen.de
Z. Naturforsch. 58b, 877 – 884 (2003); received May 19, 2003
Four novel stable enols (one characterized by X-ray crystal structure analysis) were synthesized
and investigated under oxidative conditions to yield benzofurans. Depending on the donor qualities
of the heteroaryl substituent the reaction following the one-electron oxidation could be stopped on
the stage of the cyclohexadienyl cation whose lifetime was measured. Oxidation potentials were
determined for the enols, the enolates and the α-carbonyl radicals. Oxidation of benzofurans yielded
dimeric species or intramolecular cyclization products.
Key words: Stable Conjugated Enols, One-Electron Oxidation, Radical Cations, Benzofurans,
Cyclic Voltammetry
Introduction
The reactivity of enol and enol ether radical
cations [1, 2] is being extensively investigated due to
their pivotal role played in DNA damage [3], in im-
portant biological transformations [4] carried out by
coenzyme B12 dependent enzymes (such as diol dehy-
dratase), and in Ribonucleotide Reductase [5]. While
enol ether radical cations can readily be prepared from
their neutral precursors, such a simple oxidative strat-
egy is precluded for enols as these constitute mostly
fleetingly existing tautomers of carbonyl compounds.
The last 20 years, however, have witnessed a steadily
increasing knowledge about the synthesis and struc-
Chart 1.
tures of isolable enols [6 – 8] which paved the way for ther oxidized to the α-carbonyl cation [13], the fate of
direct studies on the reactivity patterns of enol radi- which has been investigated only rarely. The present
cal cations in solution [9 – 11]. As the primary reac- study seeks to shed light on the role of good donor
tion of enol radical cations, both in solution and in the substituents, such as thiophene, and furan, on the re-
enzyme, should be controlled by the competition of dox potential data of heteroaryl substituted enols and
deprotonation vs. electron transfer, the importance of on the reactivity of intermediates involved in the oxi-
hydrogen bonding on both the deprotonation rate con- dation.
stant and the redox potential (oxidation potentials are
The one electron oxidation chemistry of aryl or alkyl
lowered by more than 500 mV) [12] is crucial. After enols has been extensively studied [9 – 11]. A working
deprotonation the resultant α-carbonyl radical is fur- model has been proposed and is as follows: enol radical
c
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M. Schmittel et al. · Stable Conjugated Enols
Chart 2.
emental analysis). The infra-red spectra (recorded in
KBr) of enols E1 – E4 exhibited sharp O-H absorption
bands just below 3500 cm−1 while for ketone K5 no O-
H absorption was observed but instead a C=O absorp-
tion at 1644 cm−1. Such a shift to lower wave number
is indicative of a strong conjugation between the car-
bonyl group and the N-methyl pyrrole.
A sharp OH signal was observed in 1H NMR spectra
of enols E1 – E4 between 5.01 and 5.12 ppm, while the
mesityl rings in all four β,β-dimesityl enols showed
coalescence phenomena due to the hindered rotation
which is a common feature of these enols [17]. How-
ever in K5, no such coalescence was registered for the
mesityl groups. The methine proton was observed at
6.08 ppm being slightly shifted upfield compared to the
usual range (6.11 to 6.13 ppm) for such ketones. A 13C
NMR signal at 192.4 ppm for the C=O signal confirms
the tautomerization of enol E5 to K5 and equally high-
lights the strong conjugative effect of the pyrrole ring.
Scheme 1. Schematic representation of the mechanism
of benzofuran formation upon oxidation of stable enols
[9 – 11].
cation E•+ formed after one-electron oxidation under-
goes a fast deprotonation leading to the sterically en-
cumbered α-carbonyl radical R•. This α-carbonyl rad-
ical is further oxidized to α-carbonyl cation C+ which
undergoes a fast Nazarov type cyclization to form the
cation X+. Benzofuran derivative are finally formed af-
ter a fast 1,2-methyl shift followed by deprotonation.
The present investigation will demonstrate that with
R = heteroaryl donor a significant retardation of the
X+ → Y+ rearrangement occurs while it is rapid with
a heterocyclic acceptor substituent.
X-ray crystal structure analyses
Results and Discussion
For E2 and K5 crystals suitable for X-ray analy-
sis were obtained. Some of the bond distances, angles
and torsional angles of E2 (Table 1, Table 2) and K5
(Table 3) are tabulated below. The data will be com-
pared with those of other solid state structures of enols
[18 – 20].
It is apparent that E2 exists as enol both in solid
(Fig. 1a) as well as in solution. The solid state structure
reveals that the length of the double bond between C(1)
and C(2) is remarkably longer (i.e. 3.0 pm) than for the
phenyl [20] or anthryl substitued enol [18].
Synthesis
β,β-Dimesityl enols E1 – E4 were synthesized ac-
cording to an approach introduced by Fuson et al. [14]
and also used by Rappoport et al. [15] that had ear-
lier been used successfully for the preparation of
E6 [12]. Accordingly, dimesityl ketene [16], prepared
from dimesitylacetic acid, was reacted with appropri-
ate Grignard or lithium reagents. The enols E1 – E4
were obtained in tautomerically pure form after col-
umn chromatography or recrystallization.
Attempts to synthesize E5 were unsuccessful; in-
stead the tautomeric ketone K5 was isolated in 7%
yield besides E7 and a plethora of unidentified mostly
polymeric products.
The dihedral angles between C(1)-C(2)-C(21)-
C(26), C(1)-C(2)-C(11)-C(12) and C(2)-C(1)-C(31)-
C(32) indicate that both mesityl rings and the tetrahy-
drobenzothienyl group are twisted out of the plane
of the double bond. The C(2)-C(1)-C(31)-C(32) angle
(23.7◦) is smaller than in enols with phenyl (33.3◦) or
Characterization
The structure of the enols was established based on anthryl substitution (62.5◦). A reason for the small tor-
their spectral data (IR, H NMR, 13C NMR and el- sion angle may be the much stronger overlap of the
1
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M. Schmittel et al. · Stable Conjugated Enols
879
Table 1. Some important bond lengths [pm] and angles [◦] in Table 3. Some important bond angles [◦] observed for K5 in
enol E2.
solid state.
C(1)-O
C(1)-C(2)
C(1)-C(31)
134.9 (5)
136.9 (5)
146.6 (5)
C(31)-C(32)
C(32)-C(33)
C(33)-C(34)
144.5 (7)
144.9 (6)
135.7 (6)
C(2)-C(1)-O
C(2)-C(1)-C(51)
121.1 (2)
116.4 (2)
O-C(1)-C(51)
122.4 (2)
C(1)-C(2)-C(11)
C(11)-C(2)-C(21) 121.0 (3)
C(1)-C(2)-C(21)
O-C(1)-C(2)
O-C(1)-C(31)
119.6 (3)
C(2)-C(1)-C(31)
C(2)-C(31)-C(32)
C(31)-C(32)-C(33)
C(32)-C(33)-C(34)
126.7 (3)
125.6 (3)
108.5 (5)
113.7 (4)
119.1 (3)
119.0 (3)
114.2 (3)
Table 2. Some important torsional angles [◦] in E2.
O-C(1)-C(2)-C(21)
11.1 (5)
60.1 (5)
−156.3 (4)
−0.8 (5)
53.6 (5)
C(1)-C(2)-C(21)-C(26)
C(2)-C(1)-C(31)-C(32)
C(31)-C(32)-C(33)-C(34)
C(1)-C(2)-C(11)-C(12)
Fig. 2. Representative cyclic voltammogram of enols, here
shown with E1, in acetonitrile at 100 mV s−1
.
copper(II) triflate (Cu(OTf)2, E1/2 = 0.67 VFc) or
nitrosonium hexafluoroantimonate (NOSbF6, Epa
=
0.79 VFc). The preparative oxidation of most of the
donor substituted enols E1 – E5 led to polymerized
products, with only the benzofuran B1 being isolated
from E1 in yields up to 68% after 3 h. In contrast, ox-
idation of E6 with NOSbF6 smoothly provided benzo-
furan B6 in 73% yield after 1 min.
Cyclic voltammetry investigations
Fig. 1. ORTEP drawings of a) enol E2, and b) ketone K5.
Cyclic voltammetry investigation of enols E1 – E4
exhibited an irreversible oxidation wave at Epa
=
tetrahydrobenzothienyl moiety with the double bond
that is reflected by a rather short distance (146.6 pm)
between C(1)-C(31). The anti conformation for the OH
group was established by the riding method [21, 22].
0.46– 0.58 VFc at 100 mV s−1 in acetonitrile. The ir-
reversibility of the oxidation signal suggests a rapid
follow-up reaction of the enol radical cation which is
most likely deprotonation [10]. No reversible or par-
tially reversible wave for the benzofuran derivative was
detected during the cyclic voltammograms of E1 – E4
as seen for aryl/alkyl enols [9]. Instead, in addition to
the first wave assigned to the oxidation of enols E1 –
E4 an irreversible oxidation wave at rather high an-
odic potential (∆Epa = 0.9 – 1.3 V) was found. Recent
investigations [23] propose that the second wave can
be assigned to the oxidation of the cyclohexadienyl
cations X+ which are persistent intermediates in the
oxidative transformation of electron-rich enols.
The crystal structure of K5 (Fig. 1b) confirms that
E5 was received as a ketone tautomer (in agreement
with other spectroscopic data in solution) with a length
of 153.4 pm for the C(1)-C(2) bond. A strong conjuga-
tion between the pyrrole ring and the carbonyl group
is apparent from the dihedral angle O1-C(1)-C(51)-N1
(4.1◦) and a short single bond C(1)-C(51) (145.9 pm),
in particular when compared with the bonds C(2)-
C(31) and C(2)-C(41) (153.7 and 153.8 pm). The C(1)-
C(51) bond was also found to be shorter than in phenyl-
substituted 2,2-dimesitylethanone (152.1 pm) [20].
The cyclic voltammogram (cv) of ketone K5 exhib-
ited an irreversible oxidation wave at Epa = 1.48 VFc
which is consistent with comparable substrates [9].
Enols E1 – E4 were transformed to the correspond-
Preparative scale oxidation
Preparative scale one-electron oxidations of the
enols E1 – E4, E6 were performed by addition of ing enolates A1 – A4 by addition of tetramethylam-
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M. Schmittel et al. · Stable Conjugated Enols
Table 4. Oxidation potentials of the enols by cyclic voltam- Table 5. Absorption, half-life and rate constant for cations
metry at 100 mV s−1 in acetonitrile. X+ at room temp.
System
Epa (E)
[VFc
E1/2 (A)
[VFc
Epa (R•)
Epa (X+)
Cation
λmax [nm]
t1/2 [min]
k [10−2 min−1
]
X1+
X3+
X4+
512
501
509
18.4
7.2
17.3
3.78
9.60
4.00
]
]
[VFc
]
[VFc
]
1
2
3
4
0.53
0.46
0.58
0.50
−0.78
−0.77
−0.99
−0.78
0.24
0.27
nd
1.80
1.64
1.89
1.79
0.27
monium hydroxide (1 equiv.). The cv’s of A1 – A4
exhibited two waves in the oxidative scan, the first
wave of which was reversible and was assigned to re-
versible oxidation of the enolate to the α-carbonyl rad-
ical R• (persistent). In contrast, the second wave cor-
responding to the oxidation of the radical R• to the
α-carbonyl cation C+ (Table 4) was irreversible in-
dicative of a fast follow-up reaction of C+. The oxida-
tion potentials of X+ show a reduced electron-donating
effect of the 3-thienyl group with respect to the
Fig. 3. UV/vis spectrum of the decay of X3+ obtained by
other heteroaryl substituents that is also visible with oxidizing E3 with copper(II) triflate.
enols E.
decay. The decay of X3+ proved to be more rapid
than that of X1+ in line with higher oxidation poten-
tial of X3+ (this indicates a reduced stabilization of the
cation) and the tendency of thiophene to undergo elec-
trophilic substitution in position 2 over 3.
UV/vis kinetic investigations
Both, the reactions with Cu(OTf)2 and the cyclic
voltammetric investigations revealed a intensely red
colored species upon oxidation of enols E1 – E4 or ox-
idation of the enolates A1 – A4. The UV/vis investiga-
tions showed a persistent species with λmax = 501 to
512 nm, which through analogy to electron-rich aryl
systems [23] and NMR could be assigned as cation
X+, for which the [1,2]-methyl shift constitutes the
In contrast, the rapid oxidative formation of B6
within 1 min illustrates that an acceptor heterocyclic
substituent triggers a rapid rearrangement of X+ to fi-
nally afford the benzofuran.
Oxidation of benzofuran B1,B6
1
rate determining step. H NMR investigations showed
In contrast to our earlier observations [11] that
C-2 substituted benzofurans exhibit reversible oxida-
tion waves in cyclic voltammetry studies, only a par-
typical signals both in the aromatic (7.50 pppm) and
aliphatic region (1.96– 1.98 ppm) in line with H NMR
1
on X+ with R = 3,4-dimethoxyphenyl [23]. The [1,2]-
methyl shift is significantly slowed down by electron
donating substituents in α-position [24], such as the
3,4-dimethoxyphenylsubstituent, with k (X+ → Y+) =
2.28·10−2 min−1(t1/2 = 30.4 min) [23]. In all spectra,
the formation of an isobestic point indicated the clean
interconversion of the cation X+ to B, as the increasing
wave at λmax = 312– 327 nm can be assigned to the
benzofurans. This could be verified from the UV/vis
spectrum of pure B1 exhibiting λmax = 327 nm. The
problems to obtain benzofurans B (except for B1) from
preparative oxidation must hence be a consequence of
rapid follow-up reactions (apparently polymerization)
of B under oxidative conditions.
tially reversible wave was observed for B1 at E1/2
=
0.68 VFc. In addition to the oxidation wave, a reduc-
tion wave at Epc = 0.45 VFc was observed which could
not arise from reduction of B1•+ and hence must de-
rive from a follow up product. Preparative scale ox-
idation of the benzofuran B1 with one equivalent of
copper(II) triflate furnished the isolated dimer BT1 in
90% yield. Electrochemical oxidation of this product
indeed revealed a potential of 0.45 VFc, thus indicating
that BT1 is the follow up oxidation product of B1 in
the cyclic voltammetry investigation.
The mechanism for this dimerization is similar to
the electrocoupling reactions of aromatic compounds
The kinetic decay of cations X+ was monitored at and thiophenes [25– 27]. Thus the bithiophene deriva-
501– 512 nm at room temp. and followed a first-order tive BT1 is formed by dimerization of the thiophene
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881
Table 6. Data for the X-ray crystal structure determination of
E2 and K5.
Compound
E2
K5
Empirical formula
Formula weight
Temperature
C28H32OS
416.60
293(2) K
C25H29NO
359.49
293(2) K
˚
˚
Wavelength
0.70930 A
0.70930 A
Crystal system
Space group
Unit cell dimensions [A]
orthorhombic
Pcab (No. 61)
a = 8.809(2),
orthorhombic
Pcab (No. 61)
a = 11.431(2),
Chart 3.
Chart 4.
˚
b = 17.664(4), b = 15.469(6),
c = 30.579(6),
c = 23.463(4),
3
3
˚
˚
Volume
Z
4758(2) A
4148.9(18) A
8
8
Density (calculated)
Absorption coefficient
F(000)
Crystal size [mm3]
Θ range for data collection
Index ranges
1.163 mg/mm3 1.151 mg/mm3
0.152 mm−1
1792
0.069 mm−1
1552
0.8×0.6×0.3 0.6×0.5×0.5
◦
2.37 to 20.93◦
0 ≤ h ≤ 11,
0 ≤ k ≤ 15,
0 ≤ l ≤ 23
2222
type radical cations B1•+ followed by double deproto-
nation.
As for B1 the cyclic voltammetric investigation of
B6 revealed an irreversible oxidation wave (Epa
0.99 VFc) indicative of a fast follow-up reaction.
At higher potential an additional wave was recorded
that at scan rates > 100 mV s−1 became reversible
(E1/2 = 1.35 VFc). In presence of trifluoroacetic acid
the first wave disappeared, providing a new irreversible
2.30 to 22.94
0 ≤ h ≤ 9,
0 ≤ k ≤ 19,
0 ≤ l ≤ 33
3296
3296
0.0000
=
Reflections collected
Independent reflections
R(int)
2222
0.0000
Refinement
Full-matrix least-squares on F2
Psi-scans
Absorption correction
Max. and min. transmission
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2σ(I)]
0.9983 and 0.8989
3295 / 24 / 321 2215 / 0 / 252
1.041
1.077
wave at Epa = 1.29 VFc while the wave at E1/2
=
R1 = 0.0679,
wR2 = 0.1963
R1 = 0.0876,
wR2 = 0.2214
0.680
R1 = 0.0382,
wR2 = 0.0988
R1 = 0.0450,
wR2 = 0.1450
0.134
1.35 VFc remained undisturbed. In presence of 2,6-
di-tert-butylpyridine both waves remained unaffected.
These results are consistent with the following mech-
anistic hypothesis: upon one-electron oxidation of B6
a distonic radical cation is formed that after a second
one-electron oxidation undergoes a 1,2-methyl shift
followed by deprotonation. The resultant BF6 is fur-
ther oxidized at E1/2 = 1.35 VFc.
R indices (all data)
Largest diff. −pe3ak
˚
and hole [eA
]
and −0.446
and −0.118
Acetonitrile used for the cyclic voltammetry investigations
and the one-electron oxidation reactions was of HPLC qual-
ity (Riedel-de Haen) and distilled from CaH2.
Melting points were recorded with a Bu¨chi Smp-20
apparatus. Infrared Spectra: Perkin-Elmer 1605 FT-IR in-
frared spectrophotometer. 1H NMR spectra: Bruker AC 200
(200 MHz), Bruker AC 250 (250 MHz), tetramethylsilane
as internal standard; 13C NMR: Bruker AC 200 (50 MHz),
[D]chloroform and tetramethylsilane as internal standard.
Mass spectra: MAT 90, Finnigan; MAT 8200, Finnigan.
Combustion analyses for elemental composition were per-
formed by the Analytical Division of the Institute of Inor-
ganic Chemistry, University of Wu¨rzburg (Carlo Erba 1106).
Conclusion
The presence of a five-membered heteroaromatic
ring not only affects the oxidation potentials of enols,
but also the follow-up processes of these enols. The
electron donating ability of the five-membered hetero-
cycles (containing oxygen and sulfur) lowers the oxi-
dation potential and also stabilizes the X+ to such an
extent that other follow up reactions may predominate
leading to polymerization rather than to benzofuran
formation.
Cyclic voltammetry experiments: The cyclic voltammetry
experiments were performed with a potentiostat Model 362
(Princeton Applied Research) and recorded using an x,y,t
recorder Modell PM 8271 (Philips). The electrochemical cell
Experimental Section
Reagents were purchased from standard chemical sup- was equipped with a platinum disc (1.0 mm diameter) work-
pliers and were used without further purification. Dime- ing electrode, a platinum auxiliary electrode and a silver wire
sitylketene was prepared as described in the literature [16]. as reference electrode. The measurements were taken at 5 –
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882
M. Schmittel et al. · Stable Conjugated Enols
10 mM concentration and ferrocene (Fc) was used as internal 128.24, 129.33, 129.88, 130.31, 132.15, 134.19, 134.67,
reference (0.39 V vs. SCE).
136.34, 136.79, 137.52, 137.64, 138.92, 139.31, 145.25. –
28H32OS (416.62): calcd. C 80.72, H 7.74, S 7.70; found
C
C 80.48, H 7.78, S 7.89.
2,2-Dimesityl-1-(2-thienyl)ethenol (E1)
n-Butyllithium (7.44 ml, 1.60 M in THF, 11.9 mmol) was
added dropwise to an ice-cold solution of thiophene (940 µl,
1.00 g, 11.9◦mmol) in 40 ml of dry THF. The solution was
2,2-Dimesityl-1-(3-thienyl)ethenol (E3)
Butyllithium (2.5 M, 4.3 ml, 11 mmol) was added drop-
stirred at 0 C for 15 min, then at r.t. for 30 min. A solu- wise to 3-bromothiophene (3.1 g, 11 mmol) at −70 ◦C in dry
tion of dimesityl ketene (3.31 g, 11.9 mmol) in dry THF THF (30 ml). After 2 h a crude solution of dimesitylketene
(20 ml) was added to the reaction mixture and stirred for (11 mmol) in 15 ml THF was added to the reaction mix-
◦
5 h at r.t. The reaction was quenched with NH4Cl (sat. aq., ture at −70 C and the reaction was stirred for 12 h at r.t.
30 ml) solution, extracted with Et2O (3×20 ml), dried over After quenching with water the reaction mixture was ex-
Na2SO4 (anhyd.) and concentrated. The crude product was tracted with ether, washed with saturated NaHCO3, dried
purified by column chromatography with cyclohexane/ethyl over Na2SO4 (anhyd.) and concentrated. The crude product
acetate, 3:1 as eluent yielding a partially pure solid which was purified with column chromatography with a mixture of
was recrystallized◦from ethanol (2.30 g, 6.34 mmol, 53%). hexane and ether as eluent (10% ether) yielding a colorless
E1: Mp 152 – 155 C. – IR (KBr): ν = 3487 (s, OH), 2916 crystalline solid (78%). E3: 1H NMR (CDCl3, 200 MHz):
˜
(s, CH), 1608 (s), 1585 (s), 1555 (m), 1438 (s), 1374 (s), δ = 2.18 (s, 6 H, p-Mes-CH3), 2.23 and 2.28 (2s, 12 H, o-
1264 (m), 1210 (s) 1160 (s), 1012 (s), 896 (s), 855 (s) cm−1
.
Mes-CH3), 5.09 (s, 1H, OH), 6.64 (dd, J = 1.0, 5.0 Hz, 1H,
1
– H NMR (CDCl3, 250 MHz,): δ = 1.99, 2.17, 2.25, 2.27 4’-H), 6.73 (bs, 2H, Mes-H), 6.88 (bs, 2H, Mes-H), 7.01 (dd,
(coalescence, 18 H, Mes-CH3), 5.12 (s, 1 H, OH), 6.76 (s, J = 3.1, 5.0 Hz 1H, 5’-H), 7.35 (dd, J = 1.0, 3.1 Hz, 1H, 2’-
2 H, Mes-H), 6.85 (dd, 1 H, J = 3.8, 5.0 Hz, 4’-H), 6.90 H). – 13C NMR (CDCl3, 50 MHz ): δ = 20.68, 20.72, 20.80,
(s, 2 H, Mes-H), 6.93 (dd, 1 H, J = 1.2, 3.8 Hz, 3’-H), 20.88, 20.91, 20.98, 111.13, 124.94, 127.36, 129.24, 132.38,
7.16 (dd, 1 H, J = 1.2, 5.0 Hz, 5’-H). – 13C NMR (CDCl3, 135.08, 136.05, 136.97, 137.49, 138.43, 139.11, 146.06. –
63 MHz) δ = 20.73, 20.81, 20.87, 20.91, 111.50, 126.29, C24H26OS (362.53): calcd. C 79.51, H 7.23, S 8.85; found
126.55, 127.52, 129.42, 129.93, 130.21, 132.21, 134.60, C 79.45, H 7.70, S 8.42.
136.47, 136.98, 138.41, 138.77, 139.21, 144.87. – C24H26OS
2,2-Dimesityl-1-(2-furyl)-ethenol (E4)
(362.52): calcd. C 79.51, H 7.23, S 8.85; found C 79.39,
H 7.35, S 9.00.
n-Butyllithium (9.20 ml of a 1.6 M in n-hexane) was
added to an ice-cooled solution of furan (1.06 ml, 1.00 g,
14.7 ◦mmol) in dry THF (40 ml). The solution was stirred
at 0 C for 30 min. A solution of dimesitylketene (4.09 g,
2,2-Dimesityl-1-(4,5,6,7-tetrahydrobenzo[b]thien-2-yl)
ethenol (E2)
A solution of dimesityl ketene (1.28 g, 4.61 mmol) 14.7 mmol) in dry THF (30 ml) was added to the solution
was added to the Grignard reagent prepared freshly and stirred for additional 2 h at 0 ◦C and at r.t. for 4 h. The
from 2-bromo-4,5,6,7-tetrahydrobenzo[b]thiophene (1.00 g, reaction was quenched with NH4Cl (sat aq. 45 ml) solution,
4.61 mmol) in dry Et2O (15 ml). The reaction mixture was extracted with Et2O (3×25 ml), dried over Na2SO4 (anhyd.)
refluxed for 4 – 5 h. The reaction was quenched with NH4Cl and concentrated. The crude product was chromatographed
(sat. aq. 30 ml) solution after cooling, extracted with Et2O with cyclohexane/ethylacetate (3:1) to furnish the pure prod-
(3 × 25 ml), dried over Na2SO4 (anhyd.) and concentrated. uct as a brown solid (3.54 g, 10.2 mmol−, 170%). E4: M.p.
◦
˜
A partially pure product was obtained by column chromatog- 152 – 155 C. – IR (KBr): ν = 3484 cm (s, OH), 2916
raphy with n-hexane/ethyl acetate (10:1) which was recrys- (s, CH), 2849 (m), 1654 (w), 1619 (m), 1608 (m), 1543 (s),
tallized from EtOH yielding the pure product as a brown 1479 (s), 1437 (m), 1197 (s), 1161 (s), 1067 (s), 1015 (s),
1
solid (560 mg, 1.34 mmol, 29%). E2: Mp. 176 – 179 ◦C. – 854 (s), 745 (s). – H NMR (CDCl3, 200 MHz): δ = 1.97,
˜
IR (KBr): ν = 3498 (m, OH), 2927 (s, CH), 2852 (m, CH), 2.17, 2.25 and 2.27 (4 s, coalescence, 18 H, Mes-CH3),
1642 (m, C=C), 1610 (C=C arom), 1440 (s), 1310 (m), 1238 5.10 (s, 1 H, OH), 5.99 (dd, 1 H, J = 0.8, 3.5 Hz, 3’-H),
(m), 1160 (m), 1129 (m), 1006 (m), 850 (s) cm−1. – 1H NMR 6.28 (dd, 1 H, J = 1.8, 3.5 Hz, 4’-H), 6.76 (s, 2H, Mes-
(CDCl3, 250 MHz): δ = 1.76 (m, 4 H, 5’-H, 6’-H), 2.07, 2.14 H), 6.87 (s, 2 H, Mes-H), 7.32 (dd, 1H, J = 0.8, 1.8 Hz,
and 2.26 (3s, 18 H, coalescence, Mes-CH3), 2.46 (t, 2 H, 5’-H). – 13C NMR (CDCl3, 63 MHz ): δ = 20.70, 20.73,
J = 5.6 Hz, 4’-H), 2.62 (t, 2 H, J = 5.6 Hz, 7’-H), 5.01 (s, 1 20.79, 20.82, 20.85, 106.73, 110.96, 111.37, 112.15, 129.25,
H, OH), 6.67 (s, 1H, 3’-H), 6.77 (s, 2H, Mes-H), 6.87 (s, 2H, 129.83, 130.22, 132.09, 134.74, 135.89, 137.17, 138.26,
Mes-H). – 13C NMR (CDCl3, 50 MHz): δ = 20.75, 20.81, 138.95, 141.55, 142.09, 149.46. – C24H26O2 (346.47): calcd.
20.94, 21.00, 21.33, 22.85, 23.45, 25.00, 25.36, 110.60, C 83.20, H 7.56; found C 83.13, H 7.53.
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M. Schmittel et al. · Stable Conjugated Enols
883
2,2-Dimesity1-(N-methylpyrrol-2-yl)-ethanone (K5)
ringes to each test tube. After both compounds had dissolved,
the one-electron oxidant solution was given to the enol solu-
tion. After 1 min sat. aq. NaHCO3 (1 ml) and CH2Cl2 (5 ml)
were added. The organic layer was washed twice with sat.
aq. NaCl (2×10 ml), dried (Na2SO4) and the solvent was re-
moved in vacuo. The pure benzofuran B1 (8.4 mg, 23 µmol,
73%) was obtained by chromatography on silica gel (cyclo-
hexane/dichloromethane, 3:1) as a light yellow solid. – IR
n-Butyllithium (1.6 M in n-hexane, 7.70 ml, 12.3 mmol)
was added dropwise to an ice-cooled solution of N-
methylpyrrole (1.10 ml, 1.00 g, 12.3 mmol) in dry THF
(20 ml). After 90 min a solution of dimesitylketene (3.42 g,
12.3 mmol) in dry THF (25 ml) was added and the reac-
tion mixture was stirred for additional 2 h at 0 ◦C and 1.5 h
at r.t. The reaction mixture was quenched with NH4Cl so-
lution (sat. aq., 30 ml), extracted with Et2O (3 × 25 ml),
dried over Na2SO4 (anhyd.) and concentrated. The crude
product was chromatographed with n-hexane/ethyl acetate
(3:1) as eluent yielding the ketone K5◦(288 mg, 800 µmol,
˜
(neat): ν = 2920 (s, C-H), 2861 (m), 1579 (s), 1508 (w), 1459
(m), 1436 (m), 1372 (w), 1239 (m), 1129 (m), 1046 (m), 930
(w), 851 (m) cm−1. – 1H NMR (CDCl3, 200 MHz): δ = 1.86
(s, 3H, p-Mes-CH3), 2.00 (s, 6H, p-Mes-CH3), 2.38 (s, 6H,
4, 6-Bf-CH3), 2.58 (s, 3H, 7-Bf-CH3), 6.78 (s, 1H, 5-Bf-H),
6.98 (s, 2H, Mes-H), 7.04 (dmc, 1 H, J = 8.1 Hz, 3’-H), 7.11
(ddd, 1 H, J = 7.4, 5.3, 1.0 Hz, 5’-H), 7.46 (ddd, 1 H, J = 8.1,
7.4, 1.6 Hz, 4’-H), 8.69 (ddd, 1 H, J = 5.3, 1.6, 1.0 Hz,
6’-H). – 13C NMR (CDCl3, 50 MHz ): δ = 11.70, 17.06,
19.06, 20.22, 21.13, 117.64, 120.28, 121.67, 124.67, 126.49,
128.28, 128.92, 130.13, 130.31, 133.83, 136.23, 137.05,
137.41, 147.20, 149.63, 149.84, 154.27. – HRMS (70 eV):
m/z calcd. 335.1936 [M+]; found: 335.1938[M+].
˜
7%) as yellow solid, Mp. 148 – 150 C – IR (KBr) ν =
2919 cm−1 (m, C-H), 1644 (vs, C=O), 1608 (s), 1522 (s);
1455 (s), 1366 (s), 1240 (s), 1209 (s), 1094 (s), 1063 (s),
850 (vs). – 1H NMR (CDCl3, 200 MHz): δ = 2.05 (s, 12
H, o-Mes-CH3), 2.23 (s, 6 H, p-Mes-CH3), 3.95 (s, 3 H,
N-CH3), 6.01 (dd, 1 H, J = 2.4, 4.1 Hz, 3’-H), 6.08 (s,
1 H, C-H), 6.69 (dd, J = 1.7, 4.1 Hz, 4’-H), 6.77 (s, 5
H, Mes-H and superimposed 5’-H). – 13C NMR (CDCl3,
63 MHz): δ = 21.11, 21.69, 38.14, 55.72, 108.36, 118.64,
130.65, 130.74, 131.80, 135.23, 136.21, 137.79, 192.80. –
C25H29NO (359.49): calcd. C 83.52, H 8.13, N 3.90; found
C 83.16, H 8.14, N 3.71.
5,5’-Bis-[2-(3-mesityl-4,6,7-trimethylbenzo[b]furyl)]-2,2’-
bithiophene (BT1)
A solution of Cu(OTf)2 (7.7 mg, 21 µmol) in acetonitrile
(3 ml) was added to a solution of benzofuran B1 (7.7 mg,
21 µmol) in acetonitrile (3 ml). After 30 min 2 ml of sat.
aq. NaHCO3 were added, and after extraction with 15 ml
of CH2Cl2 the organic layer was washed twice with sat. aq.
NaCl (2 × 10 ml), dried over Na2SO4 (anhyd.) and concen-
trated. The pure benzofuran dimer BT1 (6.8 mg, 9.5 µmol,
90%) was obtained by chromatography on silica gel (cyclo-
hexane/dichloromethane, 3:1) as an intense yellow solid. –
1H NMR (CDCl3, 200 MHz): δ = 1.91 (s, 6 H, p-Mes-CH3),
2.00 (s, 12 H, o-Mes-CH3), 2.36 and 2.39 (2s, 12 H, 4,6-Bf-
CH3), 2.48 (s, 6 H, 7-Bf-CH3), 6.75 (s, 2 H, Bf-H-5), 6.87 (d,
2 H, J = 3.9 Hz, H-3’), 6.90 (d, 2 H, J = 3.9 Hz, H-4’), 6.98
(s, 4 H, Mes-H). – 13C NMR (CDCl3, 50 MHz): δ = 11.38,
17.12, 19.12, 20.24, 21.30, 115.93, 117.02, 117.78, 124.15,
124.33, 126.36, 128.33, 128.46, 129.24, 132.19, 133.06,
136.92, 137.73, 137.86, 144.98, 153.74. – HRMS (70 eV):
m/z calcd. 718.2939 [M+]; found 718.2926[M+].
3-Mesityl-2-(2-thienyl)-4,6,7-trimethylbenzo[b]furan (B1)
A solution of Cu(OTf)2 (41.7 mg, 115 µmol) in acetoni-
trile (3 l) was added to a solution of E1 (20.8 g, 57.4 µmol)
in 3 l of acetonitrile. After 3 h sat. aq. NaHCO3 (2 ml) was
added. After extraction with Et2O (3 × 10 ml) the organic
layer was washed twice with sat. aq. NaCl (2×15 ml), water
(10 ml) and dried over Na2SO4 (anhyd.) and concentrated.
The crude product was chromatographed over silica gel using
cyclohexane/dichloromethane (3:1) yielding the benzofuran
derivative B1 as a yellow −so1lid (14.1 mg, 39.1 µmol, 68%).
˜
– IR (Film): ν = 2919 cm (m, C-H), 2849 (w), 1652 (w),
1608 (w, C=C), 1506 (m), 1456 (m), 1375 (m), 1260 (w),
1114 (m), 1017 (m), 909 (m), 850 (m), 732 (m). – 1H NMR
(CDCl3, 250 MHz): δ = 1.92 (s, 3H, p-Mes-CH3), 2.02 (s,
6H, o-Mes-CH3), 2.37 and 2.39 (2 s, 6 H, 4, 6-Bf-CH3), 2.49
(s, 3 H, 7-Bf-CH3), 6.76 (s, 1 H, 5-Bf-H), 6.95 (dd, 1 H,
J = 3.8, 5.0 Hz, 4’-H), 7.00 (s, 2 H, Mes-H), 7.14 (mc, 2
H, 3’-H, 5’-H). – 13C NMR (CDCl3, 50 MHz ): δ = 11.38,
17.12, 19.09, 20.24, 21.30, 115.39, 117.02, 123.63, 125.12,
125.33, 126.27, 127.24, 128.40, 128.49, 129.45, 132.85,
133.06, 137.82, 137.92, 145.67, 153.65. – HRMS: (70 eV):
calcd. 360.1548 [M+]; found 360.1553 [M+].
Crystal structure analyses of E2 and K5.
Details for crystal data, data collection, and refinement
are given in Table 6. X-ray data were collected on an Enraf-
Nonius-CAD4. The structures were solved using SHELXS-
86 and SHELXL-93.
3-Mesityl-2-(2-pyridyl)-4,6,7-trimethylbenzo[b]furan (B6)
Crystallographic data (excluding structure factors) for the
E6 (11.6 mg, 32.4 µmol) and NOSbF6 (17.2 mg, structures reported in this paper have been deposited with the
64.8 µmol) were separately weighed into different test tubes. Cambridge Crystallographic Data Centre as supplementary
3 ml of acetonitrile were added by means of gas-tight sy- publication no. CCDC 213535.
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884
M. Schmittel et al. · Stable Conjugated Enols
These data can be obtained free of charge via Acknowledgements
www.ccdc.cam.uk/const/retrieving.html (or from the Cam-
bridge Crystallographic Data Centre, 12 Union Road, GB-
Cambridge CB2 1EZ, UK, fax: (+44)1223-336-033; or
e-mail: deposit@ccdc.cam.ac.uk).
We are indebted to the Fonds der Chemischen Industrie
and the Deutsche Forschungsgemeinschaft for generous fi-
nancial support.
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