Synthesis of some fenchyl-substituted alkenes and enol-ethers containing 3-oxyphenyl substituents by the barton-kellogg reaction

Article abstract of DOI:10.1590/S0103-50532010001000014

The synthesis of one fenchyl-substituted alkene and two enol-ethers, containing 3-oxyphenyl substituents by the Barton-Kellogg reaction is described. The tri-substituted aromatic fenchyl-alkene 1a was prepared in 53percent yield from thiofenchone and a di

Full text of DOI:10.1590/S0103-50532010001000014

J. Braz. Chem. Soc., Vol. 21, No. 10, 1896-1904, 2010.
Printed in Brazil - ©2010 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Synthesis of Some Fenchyl-Substituted Alkenes and Enol-Ethers Containing
3-Oxyphenyl Substituents by the Barton-Kellogg Reaction
Luiz Francisco M. L. Ciscato,a,c Erick L. Bastos,b Fernando H. Bartoloni,a
Wolfgang Günther,c Dieter Weiss,c Rainer Beckertc and Wilhelm Josef Baader*,a
aDepartamento de Química Fundamental, Instituto de Química, Universidade de São Paulo,
05508-000 São Paulo-SP, Brazil
bCentro de Ciências Naturais e Humanas, Universidade Federal do ABC,
09210-170 Santo André-SP, Brazil
cInstitut für Organische Chemie und Makromolekulare Chemie, Friedrich-Schiller Universität Jena,
07737 Jena, Germany
Usando-se a reação de Barton-Kellogg, foram sintetizados um alceno e dois enóis-éteres
fenchyl-substituídos, contendo grupos 3-oxifenila como substituintes. O fenchil-alceno aromático
tri-substituído 1a foi preparado com rendimento de 53% a partir de tiofenchona e um diazoanisol.
A abordagem inversa, baseada no acoplamento entre diazofenchona e tionoésteres aromáticos, foi
utilizada para produzir os enóis-éteres 1b e 1c (rendimentos 95 e 75%, respectivamente). Em todos
os casos foi obtida uma mistura dos isômeros E e Z; a atribuição e quantificação destes isômeros
foram realizadas pela análise dos dados de espectroscopia de RMN assistida por cálculos teóricos
(relação E/Z 1a = 0,72, 1b = 2,2, 1c = 1,8).A reação ocorre com baixa estereosseletividade, levando
à formação preferencial dos diastereoisômeros das olefinas e enóis-éteres, nos quais o substituinte
aromático está localizado ao lado dos dois grupos metila da porção fenchila.
The synthesis of one fenchyl-substituted alkene and two enol-ethers, containing 3-oxyphenyl
substituents by the Barton-Kellogg reaction is described. The tri-substituted aromatic fenchyl-
alkene 1a was prepared in 53% yield from thiofenchone and a diazoanisole; whereas enol-ethers
1b and 1c were obtained (95 and 75% yield, respectively) using an inverse approach based on
diazofenchone and aromatic thionoesters. A mixture of Z and E isomers was obtained in all cases;
isomer attribution and quantification has been carried out by analysis of NMR spectroscopic data
assisted by theoretical calculations (E/Z ratio: 1a = 0.72, 1b = 2.2, 1c = 1.8). Reaction proceeds
with low stereoselectivity leading to the preferential formation of diastereoisomeric olefins and
enol-ethers where the aromatic substituent resides at the side of the two fenchyl methyl groups.
Keywords: Barton-Kellogg olefination, hindered alkenes, diazo compounds, thioketone,
fenchone
Introduction
and bis-fenchylidene, one of the most hindered olefin yet
synthesized, were accomplished with this method.6,10,11 The
reaction consists of the 1,3-dipolar cycloaddition between
a diazo and a thio or selenocarbonyl compound, furnishing
the target alkene after two-fold extrusion of nitrogen and
sulfur/selenium from D3-1,3,4-thia- or selenodiazolines.9
The synthesis of enol-ethers by the BK method has been
scarcely investigated,12,13 and derivatives bearing the
fenchyl group have not yet been described.
The stabilization provided by the fenchyl group to these
alkenes and enol-ethers, can bring new knowledge and
possibilities to areas like organic synthesis and material
science, as well as to chemiluminescence research, where
The chemistry of hindered olefins is a challenging topic
for both synthetic and theoretical chemists.1,2 Strained
alkenes containing the fenchone-type skeleton are chiral
elements in asymmetric synthesis3-5 and model compounds
in the study of structural deformations on double bonds.6
The Barton-Kellogg (BK) reaction, or Barton-Kellogg
(BK) olefination,7-9 is the method of choice for the
efficient preparation of such alkenes. The synthesis of
2-diphenylmethylenefenchane, 2-cyclohexylidenefenchane
*e-mail: wjbaader@iq.usp.br

Vol. 21, No. 10, 2010
Ciscato et al.
1897
they can be used as affordable starting materials for the
synthesis of thermally stable 1,2-dioxetane derivatives.14-16
Therefore, herein we present: (i) the synthesis of the tri-
substituted alkene 1a by conventional BK reaction from
thiofenchone (5a) and diazoalkane 4a, and (ii) the synthesis
of enol-ethers 1b and 1c using the inverse approach for the
BK reaction, i.e., from diazofenchane (4b) and thionoesters
5b and 5c (Schemes 1 and 2).
indicated by discoloration of the mixture and TLC analysis
(Scheme 1). Warming up of the reaction mixture leads
to nitrogen liberation and formation of thiirane 7a as a
colorless solid.A solution of 7a in toluene was treated with
triphenylphosphine and refluxed for 24 h, resulting, after
sulfur extrusion, in a mixture of E/Z isomers of the alkene
1a (overall yield: 53% from 5a). The products were isolated
and characterized by spectroscopic analysis.
Enol-ethers 1b and 1c were prepared by the coupling
of diazofenchane (4b) with thionoesters 3b and 3c
(Scheme 2).12,13 This inverse approach is required because
the conventional BK reaction would require the difficult
preparation of a methoxy-substituted diazomethane
derivative.19 The Bamford-Stevens method was
unsuccessful to convert the corresponding tosylhydrazone
to diazofenchane (4b). Thus, 4b was prepared by oxidation
of fenchylhydrazone (2b) with nickel peroxide and
calcium oxide in dimethoxyethane at −78 °C.20,21 Again,
due to the highly unstable nature of 4b, the yield of this
transformation could only be estimated to be as high as
90% based on the stoichiometry of the subsequent reaction
with the thionoesters. Thionoesters 5b and 5c were prepared
from the corresponding esters with Lawesson’s reagent
in 84% (R = Me) and 45% (R = TBDMS) yields,17,22
and stored at −20 °C after purification by column
chromatography, to avoid polymerization.23 The reaction
Results and Discussion
Treatment of (−)-fenchone (3a) with Lawesson’s
reagent in refluxing xylene afforded (−)-thiofenchone
(5a) in 95% yield (Scheme 1).17 Alternatively, 5a was
prepared by the reaction of 3a with a mixture of H2S/HCl
gas in trimethyl orthoformate (88% yield, orange crystals).
The diazo compound 4a was prepared by the Bamford-
Stevens route from the corresponding tosylhydrazone
2a, using potassium tert-butoxide and pyridine in THF.18
This compound is highly unstable and therefore it was not
isolated or characterized. Reaction yield was estimated in
75% from the stoichiometry of the subsequent reaction
with thiofenchone (Scheme 1). The reaction of 5a with
the deep red diazo compound 4a occurred immediately
at room temperature affording a diastereoisomeric
mixture of D3-1,3,4-thiadiazolinic intermediates 6a, as
Tos
N
N
H
Lawesson's reagent (LR):
O
S
P
S
S
H3CO
P
OCH3
H3CO
S
2a
3a
HC(OH)3
H2S/HCl, 88%
t-BuOK, py
THF, rt
LR, xylenes
reflux, 95%
N2
S
H
H3CO
4a
5a
Et2O, reflux, 5 h, 80%
N
N
H3CO
S
–N2
6a
OCH3
PPh3, toluene
reflux, 24 h
–SPPh3
H
H3CO
H
S
H
53%
(Z)-1a
7a
OCH3
E/Z = 0.72 (E)-1a
Scheme 1. Synthesis of fenchyl-substituted olefin 1a by the Barton-Kellogg reaction.

1898
Synthesis of Some Fenchyl-Substituted Alkenes and Enol-Ethers
J. Braz. Chem. Soc.
between diazofenchane (4b) and thionoesters 5b or 5c was
carried out in a similar manner as described previously
for diazo compound 4a, except that the solution of 6c
in toluene was refluxed with copper-bronze for 6 h after
nitrogen extrusion (Scheme 2). Enol-ethers 1b and 1c were
obtained as mixtures of isomers, with overall yields of 95
and 75%, respectively.
The attribution of NMR signals and quantification of the
E and Z isomers of 1a and 1b was performed as follows. The
1H NMR spectra of 1a featured two singlet signals at 6.15
and 6.16 ppm, which clearly indicate the existence of two
different olefinic hydrogen atoms. The HSQC experiment
(see Figure S1) shows that there are two different sets of
signals corresponding to three methyl groups each: one
group with 1H shifts of 1.27, 1.04 and 0.98 ppm, and another
group at 1.15, 1.14 and 0.95 ppm (Figure S2 and Figure S3).
The integration of the corresponding carbon peaks in the 13C
spectrum showed a slight majority of the first set of methyl
groups. The attribution of E and Z isomers could not be
done by means of a straightforward 1D NOESY spectrum,
because the irradiation intensity at the olefinic hydrogen had
to be very high to produce any detectable nOe signal for the
adjacent methyl groups, causing a broadening of the signal
that prevented the selective excitation of just one hydrogen
atom. The 2D NOESY experiments (see Figure S4)
showed that the hydrogen atom at 6.15 ppm is located
in the proximity of the region of the two methyl groups
with signals at 1.15 and 1.14 ppm, an indication that these
signals correspond to the E isomer. Contrarily, the hydrogen
atom at 6.16 ppm is located in the proximity of only one
methyl group at 1.27 ppm, therefore corresponding to the Z
isomer (see spatial structures in Scheme 1). Consequently,
the signals at 6.15 and 6.16 ppm were attributed to the
The fenchyl-substituted alkene 1a and enol-ethers
1b and 1c were obtained in better yields with the BK
method that by other classical methods of carbon-carbon
double-bond formation. For example, the methylenation
of fenchone by an optimized Wittig reaction was reported
to afford a yield of 5%.24 The same reaction using the
very expensive Tebbe’s reagent gives a yield of only 16%,
showing that the preparation of fenchone-derived olefins
generally occurs with low yields.24 Our own attempts
to prepare these compounds using Wittig and Horner-
Wadsworth-Emmons (HWE) methods failed or resulted in
very poor yields. (−)-Fenchone showed to be not reactive
in HWE conditions, independent of the base used (NaH,
n-BuLi, sec-BuLi, LDA, LiHMDS), with no product
formation detected at all, even after a 24 h reaction time.
Also, the intermolecular McMurry cross-coupling15,25
of methyl 3-methoxybenzoate and (−)-fenchone, in the
presence of either TiCl3/LiAlH4/TEA or TiCl4/Zn, did not
produce reproducible results.26
O
Lawesson's reagent (LR):
H2NN
OCH3
S
P
S
S
RO
H3CO
P
S
OCH3
R = CH
3b
3
2b
3c R = TBDMS
LR, xylenes
reflux
NiO2, CaO
DME, −78 °C
R = CH3, 84%
OR
R = TBDMS, 45%
N
N
S
N2
S
H3CO
OCH3
RO
6b R = CH3
6c R = TBDMS
R = CH
5b
3
4b
5c R = TBDMS
R = CH3, 94%
H3CO
OR
DME, rt
–N2
OCH3
1b
1c
Cu, toluene
reflux, 6 h
–CuS
PPh3, toluene
reflux, 24 h
–SPPh3
(E)-1b
(E)-1c
R = CH3
R = TBDMS
RO
R = CH3, 95%
R = TBDMS, 75%
S
OCH3
7b R = CH3
7c R = TBDMS
1b: E/Z = 2.2
1c: E/Z = 1.8
OR
R = CH
R = TBDMS
(Z)-1b
(Z)-1c
3
Scheme 2. Synthesis of fenchyl-substituted enol-ethers 1b and 1c by the inverse Barton-Kellogg reaction.

Vol. 21, No. 10, 2010
Ciscato et al.
1899
olefinic hydrogen atoms of isomers E and Z, respectively
(E/Z ratio = 0.72). NMR spectra (HMBC, HSQC, NOESY,
HSQC/HMBC) are given in Supplementary Information.
were calculated at the GIAO/IEFPCM/W04P/cc-pVDZ//
pbe1pbe/6-311+G(d,p) level.34 This approach allowed us
to calculate 1H and 13C chemical shifts of 1a and 1b, which
were compared to the experimental data (Figure S8).35
The adjusted coefficients of determination (adj-R2 > 0.99)
1
The evaluation of the H NMR spectrum of 1b also
suggests the presence of two isomers, because there are
two different olefinic methoxy group signals at 3.09 and
3.08 ppm, but only one signal at 3.73 ppm, corresponding
to the aromatic methoxy group of both isomers. The HSQC
spectra (see Figure S5) also corroborate the presence of two
isomers: methyl groups of the fenchyl moiety are observed at
1.45, 1.01 and 0.52 ppm for one isomer, and 1.23 (two signals
together)and 0.56ppm for the other isomer (Figure S2).With
the methyl groups of different isomers localized, selective
excitation 2D- and 1D-NOESY experiments were carried
out to assert the attribution of E and Z isomers of 1b (see
Figures S5 and S6). Selective excitation of the single methyl
groupat1.45resultedinthenOeenhancementofthemethoxy
group signal at 3.09 ppm, identifying it as belonging to the
E isomer (Figure S7). Excitation of the two methyl groups at
1.23 ppm resulted in the NOE enhancement of the signal at
3.08 ppm, therefore belonging to the Z isomer (see structures
in Scheme 2). The integration of the carbon peaks in the
INVGATE 13C NMR spectrum27 revealed an E/Z ratio of 2.2.
The spectrum of 1c showed to be very similar to that of
1b, so E/Z attribution could be performed in analogy to the
former compound. Two sets of three methyl groups could
also be observed in the 1H NMR spectrum, one set with peaks
at 1.50, 1.06 and 0.60 ppm, and another one with two peaks
together at 1.29 and one at 0.63 ppm. For 1b, the two CH3
signals together correspond to the Z isomer; therefore it is
assumed that this is also the case for 1c. An E/Z ratio of 1.8
could be obtained from the integration of these 1H signals.
A quantum chemistry study was carried out in order to
provide further structural evidence on E/Z attribution of 1a
and 1b isomers from spectroscopic data. The equilibrium
geometries, vibrational frequencies and thermochemical
data were obtained using the hybrid generalized
gradient approximation functional PBE1PBE28 with the
6-311+G(d,p) basis set (see Supplementary Information).29
This functional was used because it produced excellent
results in the calculation of bond angles in a dataset of 27
small organic molecules, when compared with other 37
density functionals, including the popular B3LYP.30 Also,
structural parameters of E/Z isomers of bis-fenchylidene
obtained at the PBE1PBE/6-311+G(d,p) level are in good
agreement with both X-ray data as well as theoretical
calculations (see Supplementary Information).31-35 The
optimized structures of E/Z , 1a and 1b are depicted in
Figure 1 and relevant geometry parameters are given in
Table S1 (see Supplementary Information). The isotropic
chemical shielding at H and C nuclei of 1a, 1b and TMS
1
indicate that the predicted d values for both H and 13C
nuclei are in excellent agreement with experimental data.
Figure 1. Optimized structures of E/Z isomers of 1a and 1b.
Conclusions
Sterically-hindered fenchyl-substituted aromatic alkene
1a can be prepared using the Barton-Kellogg method from
thiofenchone and a diazoanisole; whereas enol-ethers 1b
and 1c can be obtained from diazofenchane and aromatic
thionoesters. This approach results in product formation
in better yields than those obtained by classical methods
and can be useful for the synthesis of encumbered alkenes.
Reaction proceeds with low stereoselectivity leading to
the preferential formation of diastereoisomeric olefins and
enol-ethers where the aromatic substituent resides at the
side of the two fenchyl methyl groups.
Experimental
Allreactantswerepurchasedathighestcommercialquality
and used without purification, except otherwise mentioned.
Solvents were purified and dried as described byArmarengo
and Perrin.36 Bulb-to-bulb distillations were made using a
Kugelrohr apparatus (Büchi Glass Oven B-580). Melting
points (°C) were determined in a Kofler hot-stage apparatus

1900
Synthesis of Some Fenchyl-Substituted Alkenes and Enol-Ethers
J. Braz. Chem. Soc.
and uncorrected. NMR spectra were acquired on a Bruker
spectrometerAC-250,DRX-400,orDRX-500(25°C,CDCl3,
tetramethylsilane (TMS) as internal reference). Mass spectra
were obtained on a CG-MS Hewlett-Packard 5890/5988,
MAZ 95 XL or Finnigan MAT SSQ 710.
acid (1.2 mL) in ethanol (8 mL) was refluxed for 8 h.38
After reaching room temperature, the solution was
evaporated in vacuo and Et2O (30 mL) was added to
the residue. The solution was washed with aqueous
solutions of NaOH (10%, 30 mL) and brine (30 mL).
The organic layer was dried (MgSO4) and evaporated in
vacuo, resulting in fenchylhydrazone (3.0 g, 18 mmol,
89% yield), which was recrystallized from heptane at
−20 ºC. A solution of fenchylhydrazone (2.0 g, 12 mmol)
in dry dimethoxyethane (60 mL) was cooled to −78 °C
and a mixture of NiO2 (4 g, 44 mmol) and CaO (1 g,
18 mmol) was added slowly. The resulting suspension
was stirred for 30 min and the temperature was allowed
to reach 0 °C. The suspension containing 4b was filtered
under inert atmosphere and used immediately.
CAUTION: Although no accident occurred during
the progress of this work, diazo compounds are known
to decompose explosively.37 Therefore, all caution should
be taken.
(1R)-2-Thione-1,3,3-trimethylbicyclo[2.2.1]heptane
((−)-thiofenchone, 5a)
Method A: A mixture of (−)-fenchone 3a (1.5 g,
10 mmol) and Lawesson’s Reagent (8.1 g, 20 mmol) was
refluxed in xylene (20 mL) under inert atmosphere for 3 h
and filtered over silica gel (5 cm, heptane). The resulting
orange solution was evaporated in vacuo (0.3 mbar, rt)
until 5a starts to distillate. Xylene was mostly removed by
stirring the solution at temperatures between −50 °C and
room temperature at 0.3 mbar. The product was obtained
in 95% yield (1.6 g, 0.95 mmol) containing small amounts
of residual xylene.
Method B:A mixture of (−)-fenchone (4.0 g, 27 mmol)
and Lawesson’s reagent (6.5 g, 16 mmol) was refluxed under
inert atmosphere for 1 h until it becomes a homogeneous
solution. Thereafter, the mixture was allowed to reach room
temperature and the resulting oil was purified by column
chromatography (SiO2, hexanes/ethyl acetate 9:1), resulting
in 5a (3.1 g, 21 mmol, 78% yield).
Method C:A solution of (−)-fenchone (1.5 g, 10 mmol)
and trimethylorthoformate (12 g, 94 mmol) in dry methanol
(10 mL) was simultaneously bubbled at 0 °C with gaseous
HCl and H2S for 2 h. Ethyl ether (25 mL) was added and
the resulting orange solution washed with water until the
aqueous phase became neutral. The organic layer was dried
(MgSO4) and the solvent evaporated in vacuo. The resulting
orange oil was purified by column chromatography (SiO2,
hexanes), resulting in pure 5a (1.48 g, 8.8 mmol, 88%).
1H NMR (250 MHz, CDCl3, 25 °C): d 1.9-1.6 (m, 4H,
fenchyl H), 1.4-1.2 (m, 3H, fenchyl H), 1.28 (s, 3H, 1-CH3),
1.14 (s, 3H, 3-CH3), 1.10 (s, 3H, 3-CH3) ppm. 13C NMR
(62.9 MHz, CDCl3, 25 °C): d 279.8 (C=S), 66.2 (1-C), 57.7
(3-C), 46.9 (4-C), 43.7 (7-C), 35.4 (6-C), 28.6 (5-C), 26.4
(3-CH3), 25.0 (3-CH3), 19.2 (1-CH3) ppm. mp 22-24 ºC
(reported: 22-24 °C)7-9
1-(Diazomethyl)-3-methoxybenzene (4a)
A solution of 3-methoxybenzaldehyde (1.0 g, 7.3 mmol)
and N-tosylhydrazide (1.4 g, 7.3 mmol) in ethanol
(15 mL) was refluxed for 8 h. After this period, the
resulting solution was evaporated and the residue was
purified by column chromatography (SiO2, hexanes/ethyl
acetate 1:1) resulting in N’-(3-methoxybenzylidene)-
4-methylbenzenesulfonohydrazide 2a (2.2 g, 7.3mmol,
100%). To a solution of 2a (2.2 g, 7.3 mmol) in pyridine
(15 mL) was added t-BuOK (0.8 g, 7.5 mmol). The
mixture was warmed to 60 ºC under stirring, resulting in
a red solution, which was poured into water (100 mL).
The mixture was extracted with Et2O (3 × 30 mL) and the
unified organic layers were dried (MgSO4, 0 °C, 15 min).
After filtration, the deep red solution of 1-(diazomethyl)-
3-methoxybenzene (4a) was used immediately.
O-Methyl 3-methoxybenzothioate (5b)
A mixture of methyl 3-methoxybenzoate (3b, 1.0 g,
6.0 mmol) and Lawesson’s reagent (3.3 g, 8.1 mmol) in dry
xylene (10 mL) was refluxed for 12 hours. The suspension
was filtered in silica gel (5 cm) and the solution evaporated
in vacuo. The resulting yellow oil was purified by column
chromatography (SiO2, hexanes/ethyl acetate 5:1), yielding
5b (0.92 g, 5.0 mmol, 84%) as a bright yellow oil.
3
1H NMR (250 MHz, CDCl3, 25 ºC): d 7.81 (dd, JH,H
4
4
5 Hz, JH,H 2.5 Hz, 1H, Ar, 4-H), 7.76 (t, JH,H 2.5 Hz,
3
1H, Ar, 2-H), 7.31 (t, JH,H 5 Hz, 1H, Ar, 5-H), 7.11 (dd,
3JH,H 5 Hz, JH,H 2.5 Hz, 1H, Ar, 6-H), 4.31 (s, 3H, C(S)
4
OCH3), 3.87 (s, 3H, ArOCH3) . 13C NMR (62.9 MHz,
CDCl3, 25 ºC): d 211.9 (C=S), 159.3 (Ar, 3-C), 139.5
(Ar, 1-C), 129.0 (Ar, 5-C), 121.2 (Ar, 6-C), 119.1 (Ar,
4-C), 113.6 (Ar, 2-C), 59.3 (ArOCH3), 55.4 (C(S)OCH3).
Anal. calc. for C9H10O2S: C 59.32, H 5.53, S 17.59, found:
C 59.22, H 5.53, S 17.53%.
(1R)-2-Diazo-1,3,3-trimethylbicyclo[2.2.1]heptane
(diazofenchane, 4b)
A solution of (−)-fenchone 3a (3.0 g, 20 mmol),
hydrazine hydrate 100% (4.5 g, 20 mmol), and acetic

Vol. 21, No. 10, 2010
Ciscato et al.
1901
O-Methyl 3-(tert-butyldimethylsilyloxy)benzothioate
(5c)
50.46, 49.31, 49.21, 49.06, 48.28, 46.90, 45.79, 45.50,
43.27, 42.70, 42.08, 42.06, 35.43, 34.51, 33.77, 32.07,
29.43, 28.97, 28.63, 27.61 (fenchyl CH and CH2), 26.89,
26.73, 26.41, 26.34, 26.18, 25.94, 25.76, 25.09, 21.06,
19.15, 18.26, 18.10 (fenchyl CH3) . MS (m/z): 288 (M+),
256, 213, 173, 121.
Methyl 3-(tert-butyldimethylsilyloxy)benzoate (3c)
was prepared through microwave irradiation as described
previously.39 To a solution of 3c (3.0 g, 11 mmol) in dry
xylene (50 mL), Lawesson’s reagent (6.1 g, 15 mmol)
was added and the resulting suspension was refluxed for
24 h. The suspension was filtered in silica gel (5 cm) and
the solution evaporated in vacuo. The resulting yellow oil
was purified by column chromatography (SiO2, hexanes/
ethyl acetate 9:1), yielding 5c (1.4 g, 5.9 mmol, 45%) as
a bright yellow oil.
(E,Z)-2-[1-(3-Methoxyphenyl)-methylyliden]-1,3,3-
trimethylbicyclo[2.2.1]heptane (1a)
Triphenylphosphine (0.52 g, 2.0 mmol) was added to a
solution of 7a (5.2 g, 1.8 mmol) in dry toluene (5 mL) and
the resulting mixture refluxed for 24 h. The solution was
cooled to room temperature and 1 mL of methyl iodide was
added, and the resulting suspension kept at 50 °C for 1 h,
filtered and the solvent removed in vacuo. The oily liquid
obtained was purified by column chromatography (Al2O3,
heptane), yielding 1a (0.24 g, 53%) as a clear oil.
In the attributions of the 1H and 13C NMR spectra below,
two chemical shift values have been assigned to several
of the atoms, since a mixture of two diastereoisomers has
been obtained in the synthesis.
1H NMR (400 MHz, CDCl3, 25 ºC): d 7.19-7.13 (m, 1H,
Ar, 5-H), 6.79-6.69 (m, 3H, Ar, 2-H, 4-H, 6-H), 6.16 (Z),
6.15 (E) (s, 1H, HC=C), 3.79 (s, 3H, ArOCH3), 1.88-1.63,
1.58-1.43, 1.38-1.18 (m, 7H, fenchyl H), 1.27, 1.15, 1.14,
1.04, 0.98, 0.95 (s, 9H, fenchyl CH3) . 13C NMR (100 MHz,
CDCl3, 25 ºC): d 160.57, 160.52 (Ar, 3-C), 158.96, 158.83
(olefin fenchyl C), 141.09, 140.78 (Ar, 1-C), 128.41, 128.20
(olefin CH), 122.11, 122.07 (Ar, 5-C), 117.00, 116.46
(Ar, 6-C), 115.11, 114.95 (Ar, 4-C), 111.42, 111.30 (Ar,
2-C), 55.14 (ArOCH3), 55.14, 51.09, 50.64, 49.95, 46.88,
45.20, 43.97, 43.48, 36.40, 36.12, 29.58, 28.64 (fenchyl
CH and CH2), 27.23, 26.25, 25.74, 25.58, 20.32, 19.30
(fenchyl CH3) . MS (m/z): 256 (M+), 213, 173, 159, 121,
115. Anal. Calc. for C18H24O: C 84.32, H 9.44; found:
C 84.41, H 9.51%.
1H NMR (250 MHz, CDCl3, 25 °C): d 7.80 (dt, 3JH,H 7.8
Hz, 4JH,H 2.5 Hz, 1H, Ar, 4-H), 7.68 (t, 4JH,H 2.0 Hz, 1H, Ar,
3
3
2-H), 7.26 (t, JH,H 7.9 Hz, 1H, Ar, 5-H), 7.02 (ddd, JH,H
8.0 Hz, 4JH,H 2.5 Hz, 5JH,H 1.0 Hz, 1H,Ar, 6-H), 4.29 (s, 3H,
C(S)OCH3), 1.01 (s, 9H, SiC(CH3)3), 0.24 (s, 6H, Si(CH3)2).
13C NMR (62.9 MHz, CDCl3, 25 °C): d 211.9 (C=S),
155.4 (Ar, 3-C), 139.6 (Ar, 1-C), 128.5 (Ar, 5-C), 124.5
(Ar, 6-C), 121.8 (Ar, 4-C), 120.3 (Ar, 2-C), 59.3 (OCH3),
25.4 (SiC(CH3)3), 18.2 (SiC(CH3)3), −5.0 (Si(CH3)2). MS
(m/z): 282 (M+), 266, 251, 225, 209, 193, 177, 89. HRMS
(Micro-ESI): m/z calc. for C14H23O2SSi: 283.1188 (M-H)+;
found: 283.1193.
3’-(3-Methoxyphenyl)-1,3,3-trimethylspiro[bicyclo[2.2.1]
heptane-2,2’-thiirane] (7a)
Thiofenchone 5a (0.5 g, 3 mmol) was added to a solution
of 1-diazomethyl-3-methoxybenzene (4a) (generated from
7.3 mmol of 2a) in diethyl ether. The reaction was refluxed
for 5 h, the solvent evaporated in vacuo and the residue
purified by column chromatography (SiO2, heptane/ethyl
acetate 9:1), yielding 7a (0.69 g, 2.4 mmol, 80%) as a clear
oil containing a complex mixture of isomers.
In the attributions of the 1H and 13C NMR spectra below,
more than one chemical shift values have been assigned to
several of the atoms, since a mixture of diastereoisomers
has been obtained in the synthesis.
1H NMR (250 MHz, CDCl3, 25 ºC): d 7.14-7.19 (m, 1H,
Ar, 4-H), 7.01-7.03 (m, 1H, Ar, 2-H), 6.97-7.00 (m, 1H,
Ar, 5-H), 6.73-6.77 (m, 1H, Ar, 6-H), 4.26, 4.08, 3.87 (s,
1H, thiirane H), 3.785, 3.783, 3.780, 3.776 (s, 3H, OCH3),
1.88-1.69, 1.66-1.42 (m, 7H, fenchyl H), 1.318, 1.223,
1.172, 1.142, 1.132, 1.128, 1.097, 1.034, 1.022, 1.002,
0.998, 0.953 (s, 9H, fenchyl CH3) . 13C NMR (125 MHz,
CDCl3, 25 ºC): d 159.45, 159.32, 158.98 (Ar, 3-C), 140.06,
139.69, 138.79, 138.00 (Ar, 1-C), 128.81, 128.71, 128.68,
128.39 (Ar, 5-C), 122.49, 121.95, 121.54 (Ar, 6-C), 116.00,
115.06, 114.87, (Ar, 2-C), 112.56, 112.31, 112.21, 112.17
(Ar, 4-C), 75.82, 75.21, 74.91, 74.78 (fenchyl C-S), 43.66,
43.30, 42.92, 42.75 (HC-S), 52.31, 51.39, 51.06, 50.83,
1-Spiro(1,3,3-trimetilbiciclo[2.2.1]heptyl)-2-methoxy-2-
(3-methoxyphenyl)thiirane (7b)
A solution of diazofenchane 4b (obtained from 2.0 g
fenchylhydrazone, 12 mmol) in DME (10 mL) was
added in small portions at room temperature to O-methyl
3-methoxythiobenzoate 5b (1.1 g, 6.0 mmol). The
reaction was stirred for 20 h and the consumption of the
thionoester was monitored by TLC (Al2O3, heptane/EtAc
20:1). Afterwards, the solvent was evaporated in vacuo
and the residue purified by column chromatography
(Al2O3, heptane/ethyl acetate 20:1), furnishing 7b (1.8 g,
5.6 mmol, 94%) as a pale yellow oil.
In the attributions of the 1H and 13C NMR spectra below,
more than one chemical shift values have been assigned to

1902
Synthesis of Some Fenchyl-Substituted Alkenes and Enol-Ethers
J. Braz. Chem. Soc.
several of the atoms, since a mixture of diastereoisomers
has been obtained in the synthesis.
(E,Z)-tert-Butyl-(3-[methoxy-[1,3,3-trimethyl-
bicyclo[2.2.1]-yliden]-methyl]-phenoxy)dimethylsilane
(1c)
1H NMR (250 MHz, CDCl3, 25 ºC): d 7.31-7.05 (m,
3H, Ar, 2-H, 4-H, 5-H), 6.88-6.82 (m, 1H, Ar, 6-H), 3.851,
3.842, 3.836, 3.823 (s, 3H, ArOCH3), 3.177, 3.153, 3.080,
3.052 (s, 3H, S-C-OCH3), 2.00-0.75 (m, 7H, fenchyl H),
1.48, 1.37, 1.21, 1.19, 1.08, 1.00, 0.99, 0.95, 0.94 (s, 9H,
fenchyl CH3) . 13C NMR (62.9 MHz, CDCl3, 25 ºC): d
159.44, 159.38, 159.23, 156.70 (Ar, 3-C), 141.24, 140.84,
139.28, 138.60 (Ar, 1-C), 128.96, 128.75, 128.61, 128.28
(Ar, 5-C), 124.00, 123.28, 121.98, 121.42 (Ar, 6-C), 117.28,
116.56, 114.90, 114.44 (Ar, 2-C), 113.52, 113.25, 113.18
(Ar, 4-C), 95.50, 94.96 (S-C-OCH3), 81.22, 80.62, 80.32,
80.18 (fenchyl C-S), 55.30, 55.23, 55.03, 54.74 (ArOCH3),
53.47, 51.98, 50.95, 50.39 (S-C-OCH3), 45.64, 44.86,
44.44, 43.91, 43.26, 42.77, 41.31, 41.00, 37.48, 37.40,
32.77, 32.09, 32.01, 31.87, 31.72, 31.45, 31.41, 29.50,
28.97, 28.75, 28.52 (fenchyl CH and CH2), 27.01, 26.60,
25.91, 25.77, 25.65, 24.97, 24.18, 23.01, 22.68, 21.93,
21.71, 20.70 (fenchyl CH3). MS (m/z): 318 (M+), 303, 286,
271, 257, 237, 217.
A solution of diazofenchane 4b (obtained from 0.70 g
fenchylhydrazone, 4.2 mmol) in DME (10 mL) was
added in small portions at room temperature to O-methyl
3-(tert-butyldimethylsilyloxy)-benzothioate 5c (0.95 g,
3.4 mmol). The reaction mixture was stirred for 12 h and
the consumption of the thionoester was monitored by TLC
(Al2O3, heptane/EtAc 20:1). The solvent was evaporated
and the oily residue obtained dissolved in dry toluene
(30 mL), added 2.5 g (9.5 mmol) of triphenylphosphine and
the mixture refluxed for 10 h. After cooling to rt, addition
of 3 mL of methyl iodide, filtration and evaporation, the
residue was purified by column chromatography (Al2O3,
heptane/ethyl acetate 20:1) yielding 1c (0.68 g, 2.4 mmol,
75%) as a clear oil containing a mixture of the E and Z
isomers.
In the attributions of the 1H and 13C NMR spectra below,
two chemical shift values have been assigned to several
of the atoms, since a mixture of two diastereoisomers has
been obtained in the synthesis.
(E,Z)-2-[1-Methoxy-(3-methoxyphenyl)-methylyliden]-
1,3,3-trimethylbicyclo[2.2.1]heptane (1b)
1H NMR (250 MHz, CDCl3, 25 °C): d 7.18-7.14
(m, 1H, Ar, 5-H), 6.88-6.75 (m, 3H, Ar, 2-H, 4-H, 6-H),
3.155, 3.152 (s, 3H, OCH3), 1.90-1.00 (m, 7H, fenchyl
H), 1.50, 1.29, 1.06, 0.63, 0.60 (s, 9H, fenchyl CH3), 0.99
(s, 9H, SiC(CH3)3), 0.19 (s, 6H, Si(CH3)2) . 13C NMR
(62.9 MHz, CDCl3, 25 °C): d 154.92 (Ar, 3-C), 147.31,
146.05 (olefin COCH3), 138.37, 138.28 (Ar, 1-C), 137.97,
137.80 (Ar, 5-C), 128.27 (Ar, 4-C), 124.43, 124.17 (Ar,
6-C), 122.58 (Ar, 2-C), 119.70 (olefin fenchyl C), 56.12,
55.81 (OCH3), 51.10, 50.37, 48.64, 48.47, 47.04, 45.71,
45.25, 43.16, 37.32, 36.14, 31.86, 30.13 (fenchyl CH and
CH2), 29.00 (SiC(CH3)3), 26.54, 25.34, 25.06, 21.18, 20.98,
18.18 (fenchyl CH3), 25.67 (SiC(CH3)3), −5.0 (Si(CH3)2).
MS (m/z): 386 (M+), 371, 317, 235, 73. Anal. calc. for
C24H38O2Si: C 74.55, H 9.91; found: C 74.70, H 9.97%.
To a solution of 7b (1.1 g, 6.0 mmol) in dry toluene
(20 mL) was added copper powder (3.0 g) and this
suspension was stirred and refluxed for 6 hours. After
filtration and concentration, the oily liquid obtained was
purified by column chromatography (SiO2, heptane/ethyl
acetate 5:1) yielding 1b (1.6 g, 5.7 mmol, 95%) as a clear
oil, which was formed by a mixture of E and Z isomers.
In the attributions of the 1H and 13C NMR spectra below,
two chemical shift values have been assigned to several
of the atoms, since a mixture of two diastereoisomers has
been obtained in the synthesis.
1H NMR (250 MHz, CDCl3, 25 °C): d 7.15-7.09 (m,
1H, Ar, 5-H), 6.80-6.72 (m, 3H, Ar, 2-H, 4-H, 6-H), 3.73
(s, 3H, ArOCH3), 3.09, 3.08 (s, 3H, C=COCH3), 1.82-
1.53, 1.52-1.27 (m, 7H, fenchyl H), 1.45, 1.23, 1.01, 0.56,
0.52 (s, 9H, fenchyl CH3) . 13C NMR (62.9 MHz, CDCl3,
25 °C): d 158.92, 158.86 (Ar, 3-C), 147.43, 146.13 (olefin
COCH3), 138.68, 138.54 (Ar, 1-C), 137.92, 137.79 (Ar,
5-C), 128.32, 128.27 (Ar, 6-C), 123.54 (Ar, 4-C), 116.18
(Ar, 2-C), 113.46 (olefin fenchyl C), 56.20, 55.89 (olefin
OCH3), 55.15 (ArOCH3), 51.15, 50.40, 48.66, 48.48, 47.04,
45.70, 45.29, 43.18, 37.33, 36.16, 30.17, 26.53 (fenchyl
CH and CH2), 25.76, 25.72, 25.35, 25.08, 21.19, 20.92
(fenchyl CH3) . MS (m/z): 286 (M+), 271, 257, 243, 217,
135. Anal. calc. for C19H26O2: C 79.68, H 9.15; found:
C 79.17, H 9.26%.
Computational details
Gaussian03 was used for all calculations.40 All
geometries were optimized at the pbe1pbe/6-311+G(d,p)
theoretical level.28 To model the solvent effect (chloroform),
CPCM-SCRF (self-consistent reaction field) procedure
was employed.41 Stationary points were characterized
as minima by vibrational analysis. All reported energies
include zero-point energy (ZPE) as well as thermal
corrections (T = 298.15 K) from frequency calculations.
Gauge invariant atomic orbitals (GIAO) method was used
to calculate isotropic chemical shielding.42,43 Calculations
were carried out using the WP04 functional, a version

Vol. 21, No. 10, 2010
Ciscato et al.
1903
of the B3LYP functional explicitly reparameterized
for the calculation of chemical shifts in chloroform,44
with Dunning’s cc-pVDZ basis.34 WP04 functional was
invoked by specifying the BLYP keyword and adding
iop (3/76 = 1000001189, 3/77 = 0961409999, 3/78 =
0000109999) to the keyword line. The theoretical NMR
chemical shifts were calculated as the difference isotropic
shielding constants with respect to tetramethylsilane
(GIAO/WP04/cc-pVDZ//pbe1pbe/6-311+G(d,p))
1H shielding = 31.79, 13C shielding = 188.78). Solvent
effects in GIAO calculations were modeled by the
IEFPCM-SCRF method.45 The IEFPCM-SCRF method
was used to model solvent (chloroform) effects, which are
known to be of great importance in such calculations.34 The
IEFPCM was used because it has been successfully used
in association with the W04P functional in the accurate
prediction of 1H and 13C chemical shifts in chloroform.34
7. Barton, D. H. R.; Smith, E. H.; Willis, B. J.; J. Chem. Soc. D
1970, 1226.
8. Kellogg, R. M.; Tetrahedron 1976, 32, 2165.
9. Buter, J.; Wassenaar, S.; Kellogg, R. M.; J. Org. Chem. 1972,
37, 4045.
10. Cullen, E. R.; Guziec, F. S., Jr.; Hollander, M. I.; Murphy, C.
J.; Tetrahedron Lett. 1981, 22, 4563.
11. Back, T. G.; Barton, D. H. R.; Britten-Kelly, M. R.; Guziec, F.
S., Jr.; J. Chem. Soc., Perkin Trans. 1 1976, 2079.
12. Schmidt, U.; Kabitzke, K.; Boie, I.; Osterroht, C.; Chem. Ber.
1965, 98, 3819.
13. Hartke, K.; Kumar, A.; Koester, J.; Henssen, G.; Kissel, T.;
Kaempchen, T.; Chem. Ber. 1982, 115, 3096.
14. Baader, W. J.; Bastos, E. L. In Science of Synthesis: Houben-
Weyl Methods of Molecular Transformations; Berkessel, A.,
ed.; Thieme-Chemistry: Stuttgart, 2008, Vol. 38, p. 323.
15. Bastos, E. L.; Ciscato, L. F. M. L.; Weiss, D.; Beckert, R.;
Baader, W. J.; Synthesis 2006, 1781.
Supplementary Information
16. Baader, W. J.; Stevani, C. V.; Bastos, E. L. In The Chemistry of
Peroxides; Rappoport, Z., ed.; Wiley: Chichester, 2006, p. 1211.
17. Ozturk, T.; Ertas, E.; Mert, O.; Chem. Rev. 2007, 107, 5210.
18. Farnum, D. G.; J. Org. Chem. 1963, 28, 870.
19. Pezacki, J. P.; Wood, P. D.; Gadosy, T. A.; Lusztyk, J.;
Warkentin, J.; J. Am. Chem. Soc. 1998, 120, 8681.
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HSQC, HMBC and NOESY NMR spectra, theoretical
coordinates for the equilibrium geometries and vibrational
frequencies of 1a and 1b are available free of charge at
http://jbcs.sbq.org.br, as PDF file.
Acknowledgments
21. Okazaki, R.; Inoue, K.; Inamoto, N.; Tetrahedron Lett. 1979,
20, 3673.
We thank Fundação de Amparo à Pesquisa do
Estado de São Paulo (FAPESP) for research grants
(W. J. B. 2006/03420-7, E. L. B. 2007/00684-6) and for
a PhD fellowship (F. H. B. 2005/58320-4), Conselho
Nacional de Pesquisa e Desenvolvimento (CNPq)
for a PhD fellowship for L. F. M. L. C., as well as,
Deutscher Akademischer Austauschdienst (DAAD) and
Coordenadoria de Aperfeiçoamento de Pessoal de Ensino
Superior (CAPES) for an international fellowship for
L. F. M. L. C. (BEX 1132/04-0).
22. Weiss, D.; Gaudig, U.; Beckert, R.; Synthesis 1992, 751.
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24. Pine, S. H.; Shen, G. S.; Hoang, H.; Synthesis 1991, 165.
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P. Y.; Tetrahedron Lett. 2002, 43, 3645.
26. Bastos, E. L.; PhD Thesis, Universidade de São Paulo, Brazil,
2004, available in: http://capesdw.capes.gov.br/capesdw/
resumo.html?idtese=200427233002010191P0.
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28. Perdew, J. P.; Burke, K.; Ernzerhof, M.; Phys. Rev. Lett. 1996,
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Submitted: April 14, 2010
Published online: June 23, 2010
FAPESP helped in meeting the publication costs of this article.