Generation and reactivity of 1,2-cyclohexadiene under mild reaction conditions

Article abstract of DOI:10.1002/ejoc.200900631

An improved method to generate 1,2-cyclohexadienes by fluoride-induced ss-elimination of 6-(trimethylsilyl)cyclohexenyl triflates is presented. This method allows the generation of these highly strained cyclic alienes in good yields and under mild reactio

Full text of DOI:10.1002/ejoc.200900631

FULL PAPER
DOI: 10.1002/ejoc.200900631
Generation and Reactivity of 1,2-Cyclohexadiene under Mild Reaction
Conditions
Iago Quintana,[a] Diego Peña,*[a] Dolores Pérez,[a] and Enrique Guitián*[a]
Dedicated to Professor Luis Castedo on the occasion of his 70th birthday
Keywords: Allenes / Cycloaddition / Strained molecules / Palladium
An improved method to generate 1,2-cyclohexadienes by
der mild reaction conditions, as demonstrated by trapping
fluoride-induced β-elimination of 6-(trimethylsilyl)cyclohex- experiments based on cycloaddition reactions.
enyl triflates is presented. This method allows the generation
of these highly strained cyclic allenes in good yields and un-
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
trophiles and undergo pericyclic reactions such as [2+2] and
[4+2] cycloadditions with alkenes and dienes, respectively.
1,2-Cyclohexadiene (6, Scheme 1) is a highly reactive cyclic
allene.[7] The two most general methods for the generation
of this molecule have for many years involved the base-in-
duced elimination of HX from alkenyl halides and the de-
composition of gem-dihalocyclopropanes by organolithium
reagents (Doering–Moore–Skattebøl reaction).[1] Both
methods are hampered by the use of strong bases and
highly nucleophilic reagents, and this limits their scope.
Fluoride-induced decomposition of compound 4 to gener-
ate 6 was introduced by Shakespeare and Johnson in
1990,[6a] albeit since then, this method has been sporadically
used.[8] Herein, we introduce 6-(trimethylsilyl)cyclohexenyl
triflate (5), which allows the generation of 1,2-cyclohexa-
diene (6) in good yields and under mild reaction conditions
as a result of the excellent leaving group character of the
triflate group.
Introduction
In the last few decades fluoride-induced elimination of
β-substituted organosilanes has emerged as a powerful
method for the generation of unstable short-lived interme-
diates.[1,2] For example, (o-bromophenyl)trimethylsilane (1,
Scheme 1) has been used as a benzyne precursor and avoids
the use of strong bases.[3a] The key advance in the develop-
ment of this methodology was the introduction of o-(tri-
methylsilyl)phenyl triflate (2), as the better leaving group
character of the triflate allows the generation of benzyne in
higher yields and under milder conditions.[3b] This ap-
proach has led to a remarkable revival in the use of benzyne
(3) over the past few years[4,2d] and has also been used for
the efficient generation of other strained molecules such as
cyclohexyne[5] and 1,2,3-cyclohexatriene.[6a]
Scheme 1. Fluoride-induced generation of benzyne (3) and 1,2-cy-
clohexadiene (6).
Results and Discussion
Cyclic allenes containing fewer than eight carbon atoms
are strained molecules that are closely related to arynes and
small cycloalkynes.[1,2] These intermediates are potent elec-
Vinyl triflate 5 was prepared from 2-(trimethylsilyl)cyclo-
hexenone 7 (Scheme 2).[6] Hydride conjugate addition to
this enone with the use of -Selectride followed by aqueous
workup afforded cyclohexanone 8a. Treatment of this com-
pound with LDA at –78 °C and trapping of the resulting
kinetic enolate with N-phenyltrifluoromethanesulfonimide
led to cycloallene precursor 5 in 48% yield. Remarkably,
alkyl-substituted cycloallene precursors such as 9 can be
prepared in good yield by minor modifications of this pro-
cedure.
[a] Departamento de Química Orgánica, Universidad de Santiago
de Compostela,
15782 Santiago de Compostela, Spain
Fax: +34-981-591014
E-mail: diego.pena@usc.es
enrique.guitian@usc.es
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200900631.
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I. Quintana, D. Peña, D. Pérez, E. Guitián
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Scheme 2. Synthesis of 1,2-cyclohexadiene precursors. Reagents
and conditions: (a) i. -Selectride, ii. NH4Cl (aq.) for 8a or MeI
for 8b; (b) i. LDA ii. PhNTf2.
The ability of triflate 5 to form cycloallene 6 was con-
firmed when treatment of 5 with tetrabutylammonium
fluoride (TBAF) in THF at room temperature afforded 1,2-
cyclohexadiene dimer (10) in 78% yield through a [2+2]
cycloaddition of intermediate 6 (Scheme 3).[9]
Figure 1. X-ray structure of compound endo-14.
in the presence of tropone (15) selectively afforded a 96:4
mixture of the endo- and exo- [4+2] cycloaddition adducts
16, respectively, in good yield (75%, Scheme 5). The relative
stereochemistry of compounds endo- and exo-16 was estab-
lished on the basis of 2D NMR spectra (COSY and
NOESY).[13] In a similar way to the reaction with
benzyne,[11b] [6+2] cycloaddition product 17 was also iso-
lated in 13% yield.
Scheme 3. Dimerization of 1,2-cyclohexadiene (6).
Compound 6 was also trapped in Diels–Alder reactions.
The generation of cyclic allene 6 in the presence of furan
(11) led to the isolation of a 95:5 mixture of the endo- and
exo- [4+2] cycloaddition adducts 12, respectively, in 53%
yield (Scheme 4).[10] In the presence of 1,3-diphenylisoben-
zofuran (13) a mixture of endo- and exo-14 was obtained in
66% yield (ratio endo/exo = 80:20). It should be mentioned
that the generation of 6 by treatment of 1-bromocyclohex-
ene with KOtBu in the presence of 13 afforded endo/exo-14
with the same ratio but in 38% yield.[7a] The structure of
endo-14 was confirmed by X-ray diffraction studies (Fig-
ure 1).
Scheme 5. Cycloadditions of 1,2-cyclohexadiene with tropone.
Analogously to arynes, cyclic allenes can be stabilized by
complexation with a transition metal.[14] This opens the
possibility of employing cyclic allenes in transition-metal-
catalyzed reactions.[15] We therefore decided to study the re-
activity of 1,2-cyclohexadiene (6) in the presence of cata-
lytic amounts of a palladium complex. In particular, treat-
ment of triflate 5 with CsF in the presence of dimethyl ace-
tylenedicarboxylate (18) and 5 mol-% of Pd(PPh3)4 in
MeCN at room temperature resulted in the formation of
compounds 19 and 20 in 10 and 19% yield, respectively
(Scheme 6). In the absence of the palladium catalyst these
products were not detected by GC–MS, whereas in the ab-
sence of fluoride the starting material was untouched. The
structure of compound 20 was unambiguously determined
by single-crystal X-ray diffraction studies (Figure 2).
Scheme 4. [4+2] Cycloaddition reactions of 1,2-cyclohexadiene.
These results prompted us to study the reactivity of cy-
cloallene 6 in the presence of other unsaturated compounds
as reaction partners. In this context, the reaction with tro-
pone (15) would be of special interest due to the vast
number of possible peri-, regio- and stereoisomers. It is
known that the reaction of benzyne with tropone affords
periselectively the [4+2] cycloaddition adduct as the major
product, together with small amounts of the [6+2] cycload-
dition product.[11] By contrast, the reaction of tropone with
Scheme 6. Pd-promoted reaction of 1,2-cyclohexadiene with di-
methyl acetylenedicarboxylate.
Presumably, a Pd0 complex promotes the [2+2+2] cyclo-
acyclic allenes usually leads to mixtures of [8+2] and [4+2] addition of one molecule of cycloallene 6 with two mole-
cycloaddition adducts.[12] Treatment of triflate 5 with CsF cules of alkyne 18 to give intermediate 21 (Scheme 7). Sub-
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Generation and Reactivity of 1,2-Cyclohexadiene
Figure 3. X-ray structure of compound endo-24.
Figure 2. X-ray structure of compound 20.
sequent fluoride-induced deprotonation/rearomatization
would give anion 22, which could evolve in two ways: either
by protonation to afford tetrahydronaphthalene 19 or by
conjugate addition to alkyne 18 followed by protonation to
form compound 20. Alternatively, this compound could be
produced through an ene reaction of intermediate 21 and
alkyne 18. Remarkably, this is the first example of the par-
ticipation of strained cyclic allenes in a metal-catalyzed re-
action.
Conclusions
1,2-Cyclohexadienes can be generated and trapped under
mild reaction conditions by means of fluoride-induced β-
elimination of the corresponding 6-(trimethylsilyl)cyclohex-
enyl triflates. This method allows the generation of highly
strained cyclohexallenes with higher efficiencies than classi-
cal approaches. Significantly, cyclic allenes generated by this
method can participate not only in [4+2] cycloadditions
with furan or tropone but also in palladium-promoted
[2+2+2] cycloadditions with alkynes.
Experimental Section
General: All reactions were performed under an argon atmosphere
by using oven-dried glassware and standard Schlenk techniques.
Solvents were dried by distillation from a drying agent before use:
MeCN from CaH2, THF and toluene from Na. TLC was per-
formed on Merck silica gel 60 F254; chromatograms were visualized
with UV light (254 and 360 nm). Flash column chromatography
Scheme 7. Proposed mechanism for the formation of 19 and 20.
We next planned to confirm the ability of triflate 9 to
form 1-methyl-1,2-cyclohexadiene (23, Scheme 8). Indeed,
treatment of triflate 9 with CsF in the presence of diphenyl-
isobenzofuran (13) afforded a mixture of three Diels–Alder
adducts: endo/exo-24 in 56% yield (ratio endo/exo = 68:32),
resulting from the reaction of the methyl-substituted double
bond of the allene with diene 13,[16] and endo-25, resulting
from the reaction of the less-substituted double bond of
cycloallene 23. Remarkably, the other possible [4+2] cyclo-
addition product exo-25 was not detected in the reaction
mixture. As expected, the corresponding dimer of cyclic al-
lene 23 was obtained in the absence of diene 13.[17]
1
was performed on Merck silica gel 60 (ASTM 230–400 mesh). H
and 13C NMR spectra were recorded at 250.13 and 62.83 MHz
(Bruker DPX-250 instrument), 300 and 75 MHz (Varian Mercury-
300 instrument) or 400 and 100 MHz (Varian Mercury-400 instru-
ment), respectively. NOE, NOESY and COSY were recorded with
a
Bruker WM-500 instrument. Low-resolution mass spectra
[LRMS (electron impact, EI)] were determined at 70 eV with an
HP-5988A instrument. High-resolution mass spectra (HRMS) were
obtained with a Micromass Autospec spectrometer. IR spectra were
recorded with a Mattson Cygnus 100 spectrophotometer. GC–MS
analyses were performed with an Agilent 6890N/5973inert instru-
ment with a HP-5MS capillary column. Compound 7 was prepared
from 2-cyclohexenone following
a previously published pro-
cedure.[6] Commercial reagents were used without further purifica-
tion. CCDC-729036 (for endo-14), -729037 (for 20) and -729038
(for endo-24) contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
Synthesis of 1,2-Cyclohexadiene Precursors
2-(Trimethylsilyl)cyclohexanone (8a): -Selectride (1.0  in THF,
3.60 mL, 3.60 mmol) was added dropwise to a solution of 7
(600 mg, 3.57 mmol) in THF (18 mL) at –78 °C. The mixture was
stirred under an argon atmosphere at this temperature for 2 h.
Then, saturated aqueous NH4Cl solution (45 mL) and Et2O
(30 mL) were added, the phases were separated and the aqueous
Scheme 8. [4+2] Cycloaddition reaction of cyclic allene 23.
The stereochemistry of compound endo-24 was con-
firmed by X-ray diffraction studies (Figure 3).
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I. Quintana, D. Peña, D. Pérez, E. Guitián
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layer was extracted with Et2O (2ϫ40 mL). The combined organic
layer was dried with Na2SO4, filtered and concentrated under re-
duced pressure. The residue was purified by column chromatog-
a colourless oil. 1H NMR (300 MHz, CDCl3): δ = 5.68 (dd, J =
5.4, 2.9 Hz, 1 H), 2.28–1.98 (m, 2 H), 1.76–1.45 (m, 4 H), 1.18 (s,
3 H) 0.06 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 156.8
raphy (SiO2; Et2O/hexane, 1:20) to afford 8a (450 mg, 74%) as a (C), 118.3 (J = 320 Hz, CF3), 114.3 (CH), 33.3 (CH2), 27.7 (C),
colourless oil: 1H NMR (400 MHz, CDCl3): δ = 2.36 (m, 1 H),
2.26–2.11 (m, 2 H), 2.01–1.92 (m, 3 H), 1.75–1.60 (m, 3 H), 0.10
(s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 212.5 (C), 45.4
(CH), 41.3 (CH2), 26.5 (CH2), 25.3 (CH2), 23.4 (CH2), –1.6 (3 CH3)
ppm. MS (EI): m/z (%) = 170 (98), 155 (100). HRMS: calcd for
C9H18OSi 170.1127; found 170.1120.
24.8 (CH2), 19.5 (CH3), 17.3 (CH2), –3.5 (3 CH3) ppm. MS (EI):
m/z (%) = 183 (6) [M – Tf], 79 (100). HRMS: calcd. for C10H18OSi
[M – Tf] 183.1160; found 183.1162.
Cycloaddition Reactions of 1,2-Cyclohexadienes
[2+2] Cycloaddition of 1,2-Cyclohexadiene (6): Tetrabutylammo-
nium fluoride (TBAF; 1.0  in THF, 280 µL, 0.28 mmol) was
added dropwise to a solution of 5 (44 mg, 0.14 mmol) in MeCN
(5 mL) at room temperature, and the mixture was stirred at this
temperature for 1 h. Then, H2O (5 mL) and Et2O (5 mL) were
added, the phases were separated and the aqueous layer was ex-
tracted with Et2O (3ϫ5 mL). The combined organic layer was
dried with anhydrous Na2SO4, filtered and concentrated under re-
duced pressure. The residue was purified by column chromatog-
raphy (SiO2, hexane) to afford trans-1,2,3,6,7,8,8a,8b-octahydrobi-
phenylene[9,18] (10; 9 mg, 78%) as a colourless oil. 1H NMR
(300 MHz, CDCl3): δ = 5.39 (s, 2 H), 2.35–2.22 (m, 2 H), 2.16–
2.03 (m, 4 H), 2.01–1.90 (m, 2 H), 1.83–1.72 (m, 2 H), 1.52–1.30
(m, 2 H), 1.23–1.04 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 143.0 (C), 111.1 (CH), 46.8 (CH), 27.5 (CH2), 24.5 (CH2), 21.7
(CH2) ppm. MS (EI): m/z (%) = 160 (73), 117 (100). HRMS: calcd.
for C12H16 160.1252; found 160.1246.
6-(Trimethylsilyl)-1-cyclohexenyl 1-Trifluoromethanesulfonate (5):
nBuLi (2.25  in hexane, 1.65 mL, 3.63 mmol) was added dropwise
to iPr2NH (0.50 mL, 3.80 mmol) at –78 °C, leading to a gel that
was dissolved in THF (6 mL). The mixture was stirred at –78 °C
for 10 min and at room temperature for 20 min. Then, a solution
of 8a (588 mg, 3.46 mmol) in THF (5 mL) was added at –78 °C.
After stirring at –78 °C for 35 min, a solution of PhNTf2 (1.30 g,
3.63 mmol) in THF (5 mL) was added, and the mixture was stirred
at room temperature for 12 h. Then, 5% aqueous NaHCO3 solu-
tion (35 mL) was added, the phases were separated and the aque-
ous layer was extracted with Et2O (2ϫ35 mL). The combined or-
ganic layer was dried with Na2SO4, filtered and concentrated under
reduced pressure. The residue was purified by column chromatog-
raphy (SiO2, pentane) to afford 5 (500 mg, 48%) as a colourless oil.
1H NMR (400 MHz, CDCl3): δ = 5.65 (ddd, J = 5.0, 3.6, 1.7 Hz,
1 H), 2.26–2.02 (m, 2 H), 2.00–1.90 (m, 2 H), 1.70–1.40 (m, 3 H),
0.10 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 152.8 (C),
118.6 (J = 320 Hz, CF3) 115.2 (CH), 28.9 (CH), 25.5 (CH2), 24.1
[4+2] Cycloaddition of 1,2-Cyclohexadiene (6) with Furan (11):
TBAF (1.0  in THF, 0.38 mL, 0.38 mmol) was added dropwise to
a solution of 5 (97 mg, 0.32 mmol) in furan (11, 2.0 mL) at room
temperature, and the mixture was stirred at this temperature for
24 h. Then, the mixture was concentrated under reduced pressure
and the residue was purified by column chromatography (SiO2,
hexane) to afford a mixture of endo/exo-1,4,4a,5,6,7-hexahydro-1,4-
epoxynaphthalene[7d] (endo/exo-12; 25 mg, 53%; 95:5 endo/exo) and
dimer 10 (4 mg, 15%). Data for endo-12: 1H NMR (300 MHz,
CDCl3): δ = 6.34 (dd, J = 5.5, 1.0 Hz, 1 H), 6.02 (dd, J = 5.6,
1.1 Hz, 1 H), 5.57 (s, 1 H), 5.01 (s, 2 H), 2.34 (m, 1 H), 2.16 (m, 1
H), 1.99–1.74 (m, 3 H), 1.52 (m, 1 H), 0.35 (m, 1 H) ppm. MS
(EI): m/z (%) = 148 (19), 91 (100).
(CH ), 21.0 (CH ), –2.1 (3 CH ) ppm. IR (CsI): ν = 2925 cm–1. MS
˜
2
2
3
(EI): m/z (%) = 302 (2), 79 (100). HRMS: calcd. for C10H17F3O3SiS
302.0620; found 302.0620.
2-Methyl-2-(trimethylsilyl)cyclohexanone (8b): -Selectride (1.0  in
THF, 2.86 mL, 2.86 mmol) was added dropwise to a solution of 7
(400 mg, 2.38 mmol) in THF (12 mL) at –78 °C, and the mixture
was stirred at this temperature for 2 h. Then, MeI (0.770 mL,
11.9 mmol) was added, and the mixture was stirred at room tem-
perature for 5 h. Cold saturated NH4Cl solution (30 mL) was
added, the phases were separated and the aqueous layer was ex-
tracted with Et2O (3ϫ20 mL). The combined organic layer was
dried with Na2SO4, filtered and concentrated under reduced pres-
sure. The residue was purified by column chromatography (SiO2;
Et2O/hexane, 1:20) to afford 8b (430 mg, 98%) as a colourless oil.
1H NMR (500 MHz, CDCl3): δ = 2.44–1.89 (m, 4 H), 1.73–1.64
(m, 3 H), 1.53 (m, 1 H), 1.13 (s, 3 H), 0.07 (s, 9 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 214.7 (C), 44.1 (C), 40.9 (CH2), 35.7 (CH2),
[4+2] Cycloaddition of 1,2-Cyclohexadiene (6) with 1,3-Diphenyliso-
benzofuran (13): Finely powdered anhydrous CsF (76 mg,
0.50 mmol) was added to a solution of 5 (60 mg, 0.20 mmol) and
1,3-diphenylisobenzofuran (13; 81 mg, 0.30 mmol) in MeCN/THF
(1:1, 2 mL), and the mixture was stirred at room temperature for
24 h. Then, the mixture was concentrated under reduced pressure
and the residue was purified by column chromatography (SiO2;
25.5 (CH ), 22.5 (CH ), 20.8 (CH ), –2.4 (3CH ) ppm. IR (CsI): ν
˜
2
2
3
3
hexane/CH2Cl2,
9:1)
to
afford
endo/exo-9,10-diphenyl-
(endo/exo-14;
= 1680 cm–1. MS (EI): m/z (%) = 184 (42), 169 (100). HRMS: calcd.
1,2,3,9,9a,10-hexahydro-9,10-epoxyanthracene[7a]
for C10H20OSi 184.1283; found 184.1282.
46 mg, 66%; 80:20 endo/exo) as a colourless oil. Data for endo-14:
6-Methyl-6-(trimethylsilyl)-1-cyclohexenyl 1-Trifluoromethanesul-
1H NMR (250 MHz, CDCl3): δ = 7.91–7.82 (m, 2 H), 7.77–7.66
fonate (9): nBuLi (2.25  in hexane, 1.01 mL, 2.28 mmol) was (m, 2 H), 7.53–7.33 (m, 6 H), 7.24–7.16 (m, 2 H), 7.15–7.07 (m, 2
added dropwise to iPr2NH (0.31 mL, 2.39 mmol) at –78 °C, leading
to a gel that was dissolved in THF (4 mL). The mixture was stirred
at –78 °C for 10 min and at room temperature for 20 min. Then, a
solution of 8b (400 mg, 2.17 mmol) in THF (4 mL) was added at
H), 5.68 (dd, J = 3.3, 3.2 Hz, 1 H), 3.05 (m, 1 H), 1.69–1.52 (m, 2
H), 0.55–0.35 (m, 2 H), 1.82 (m, 1 H), 2.19 (m, 1 H) ppm. 13C
NMR (62.8 MHz, CDCl3): δ = 148.3 (C), 144.4 (C), 144.2 (C),
138.0 (C), 134.8 (C), 128.6 (2 CH), 128.5 (CH), 128.4 (2 CH), 128.2
–78 °C. After stirring at –78 °C for 40 min, a solution of PhNTf2 (2 CH), 127.9 (CH), 127.0 (CH), 126.7 (2 CH), 125.8 (CH), 121.3
(820 mg, 2.28 mmol) in THF (5 mL) was added, and the mixture
was stirred at room temperature for 18 h. Then, 5% aqueous
NaHCO3 solution (30 mL) was added, the phases were separated
(CH), 120.2 (CH), 117.8 (CH), 90.2 (C), 89.8 (C), 48.2 (CH), 26.2
(CH2), 24.9 (CH2), 21.9 (CH2) ppm. MS (CI): m/z (%) = 351 (40),
333 (100). Data for exo-14: 1H NMR (250 MHz, CDCl3): δ = 7.87–
and the aqueous layer was extracted with Et2O (2ϫ25 mL). The 7.61 (m, 4 H), 7.43 (m, 6 H), 7.31–7.22 (m, 2 H), 7.20–6.98 (m, 2
combined organic layer was dried with Na2SO4, filtered and con-
centrated under reduced pressure. The residue was purified by col-
H), 5.62 (m, 1 H), 2.52 (m, 1 H), 2.11 (m, 1 H), 1.92 (m, 1 H),
1.82–1.64 (m, 2 H), 1.39 (m, 1 H), 0.80 (m, 1 H) ppm. MS (CI):
umn chromatography (SiO2, hexane) to afford 9 (350 mg, 51%) as m/z (%) = 351 (38), 333 (100).
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Generation and Reactivity of 1,2-Cyclohexadiene
Cycloaddition of 1,2-Cyclohexadiene (6) with Tropone (15): Finely
powdered anhydrous CsF (74 mg, 0.48 mmol) was added to a solu-
H), 1.99 (m, 1 H), 1.91–1.62 (m, 2 H), 1.08 (s, 3 H), 0.95–0.72 (m,
2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 148.5 (C), 148.2 (C),
tion of 5 (74 mg, 0.24 mmol) and tropone (15; 24 µL, 0.24 mmol) 145.2 (C), 137.8 (C), 135.2 (C), 128.8 (2 CH), 128.6 (CH), 128.4 (2
in MeCN (2.5 mL), and the mixture was stirred at room tempera-
ture for 14 h. Then, the mixture was concentrated under reduced
pressure and the residue was purified by column chromatography
(SiO2; AcOEt/hexane, 1:20) to afford endo/exo-16 (34 mg, 75%;
CH), 128.1 (2 CH), 127.1 (CH), 127.0 (CH), 125.6 (2 CH), 125.3
(CH), 121.5 (CH), 120.4 (CH), 117.7 (CH), 93.1 (C), 89.6 (C), 46.8
(C), 32.7 (CH2), 23.4 (CH2), 21.4 (CH3), 18.2 (CH2) ppm. MS (EI):
m/z (%) = 364 (31), 346 (100). HRMS: calcd. for C27H24O
364.1827; found 364.1819. Data for exo-24: 1H NMR (300 MHz,
1
96:4 endo/exo) and 17 (6.0 mg, 13%). Data for endo-16: H NMR
(300 MHz, CDCl3): δ = 6.75 (dd, J = 11.1, 8.5 Hz, 1 H), 6.62 (ddd, CDCl3): δ = 7.87–7.61 (m, 4 H), 7.56–7.45 (m, 4 H), 7.43–7.31 (m,
J = 8.2, 7.2, 1.0 Hz, 1 H), 6.00 (ddd, J = 8.3, 7.1, 1.1 Hz, 1 H), 3 H), 7.27 (m, 1 H), 7.21–7.02 (m, 2 H), 5.57 (dd, J = 6.2, 3.0 Hz,
5.83–5.70 (m, 2 H), 3.94 (d, J = 6.6 Hz, 1 H), 3.25 (m, 1 H), 2.35 1 H), 2.15–1.92 (m, 2 H), 1.70 (m, 1 H), 1.37–1.09 (m, 3 H), 0.88
(m, 1 H), 2.25–1.96 (m, 2 H), 1.91–1.75 (m, 2 H), 1.55 (m, 1 H), (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 147.7 (C), 147.6
1.08 (m, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 193.0 (C),
148.7 (CH), 139.4 (CH), 132.3 (C), 130.4 (CH), 128.1 (CH), 124.0
(C), 144.9 (C), 137.5 (C), 136.4 (C), 128.3 (2 CH), 128.2 (2 CH),
127.2 (CH), 127.1 (CH), 126.5 (CH), 126.3 (CH), 125.6 (2 CH),
(CH), 60.0 (CH), 41.9 (CH), 41.4 (CH), 28.9 (CH2), 25.5 (CH2), 125.4 (2 CH), 120.3 (CH), 119.8 (CH), 117.1 (CH), 91.8 (C), 89.4
22.5 (CH2) ppm. MS (EI): m/z (%) = 186 (62), 131 (100). HRMS: (C), 46.3 (C), 31.9 (CH2), 20.9 (CH3), 20.7 (CH2), 17.0 (CH2) ppm.
calcd. for C13H14O 186.1044; found 186.1046. Data for 17: 1H MS (EI): m/z (%) = 364 (40), 346 (100). HRMS: calcd. for C27H24O
1
NMR (250 MHz, CDCl3): δ = 6.01–5.83 (m, 2 H), 5.73 (m, 1 H), 364.1827; found 364.1821. Data for endo-25. H NMR (300 MHz,
5.56 (m, 1 H), 5.37 (m, 1 H), 3.39 (m, 1 H), 3.02–2.84 (m, 2 H), CDCl3): δ = 7.81 (dd, J = 7.9, 1.5 Hz, 2 H), 7.68 (dd, J = 8.2,
2.17–2.03 (m, 2 H), 1.85–1.72 (m, 3 H), 0.88 (m, 1 H) ppm. 13C 1.3 Hz, 2 H), 7.50–7.22 (m, 8 H), 7.20–7.11 (m, 2 H), 3.11 (m, 1
NMR (125 MHz, CDCl3): δ = 214.0 (C), 144.1 (C), 128.9 (CH), H), 2.26–1.98 (m, 2 H), 1.84–1.56 (m, 3 H), 1.33 (d, J = 1.7 Hz, 3
125.8 (2 CH), 125.6 (CH), 123.6 (CH), 57.0 (CH), 51.9 (CH), 51.7 H), 0.33 (m, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 146.6
(CH), 25.2 (CH2), 22.0 (CH2), 21.8 (CH2) ppm. MS (EI): m/z (%)
= 186 (70), 131 (100). HRMS: calcd. for C13H14O 186.1044; found
186.1040.
(C), 144.7 (C), 138.0 (C), 137.3 (C), 135.6 (C), 129.8 (2 CH), 128.7
(CH), 128.4 (2 CH), 128.2 (2 CH), 127.9 (CH), 127.8 (C), 127.0 (2
CH), 126.8 (CH), 125.5 (CH), 121.9 (CH), 117.6 (CH), 90.4 (C),
90.1 (C), 48.6 (CH), 31.6 (CH2), 26.2 (CH2), 22.6 (CH2), 19.7 (CH3)
ppm. MS (EI): m/z (%) = 364 (33), 346 (100). HRMS: calcd. for
C27H24O 364.1827; found 364.1818.
Pd-Promoted Reaction of 1,2-Cyclohexadiene (6) with Dimethyl
Acetylenedicarboxylate (18): Finely powdered anhydrous CsF
(94 mg, 0.61 mmol) was added to
a solution of 5 (93 mg,
Supporting Information (see footnote on the first page of this arti-
cle): Determination of the relative stereochemistry of endo-16 and
0.31 mmol), Pd(PPh3)4 (18 mg, 0.015 mmol) and dimethyl ace-
tylenedicarboxylate (DMAD, 18; 94 µL, 0.76 mmol) in MeCN
(3 mL), and the mixture was stirred at room temperature for 22 h.
Then, the mixture was concentrated under reduced pressure, and
the residue was purified by column chromatography (SiO2; Et2O/
hexane, 1:9 to 8:2) to afford 19[19] (11 mg, 10%) as a colourless oil
and 20 (28 mg, 19%) as a white solid. Data for 19: 1H NMR
(250 MHz, CDCl3): δ = 3.88 (s, 6 H), 3.83 (s, 6 H), 2.85–2.73 (m,
4 H), 1.85–1.71 (m, 4 H) ppm. MS (EI): m/z (%) = 332 (100).
HRMS: calcd. for C18H20O8 322.0896; found 332.0895. Data for
20: 1H NMR (250 MHz, CDCl3): δ = 5.14 (d, J = 1.4 Hz, 1 H),
4.39 (m, 1 H), 3.90 (s, 3 H), 3.87–3.81 (m, 12 H), 3.67 (s, 3 H), 3.02
(m, 1 H), 2.70 (m, 1 H), 2.02 (m, 1 H), 1.88–1.71 (m, 3 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 168.0 (C), 167.2 (C), 166.8 (C),
166.3 (C), 166.2 (C), 165.0 (C), 150.9 (C), 139.2 (C), 136.4 (C),
135.5 (C), 135.1 (C), 129.8 (C), 129.4 (C), 123.9 (CH), 53.0 (CH3),
53.0 (CH3), 52.9 (CH3), 52.8 (CH3), 52.5 (CH3), 51.8 (CH3), 39.4
(CH), 26.3 (CH2), 25.2 (CH2), 16.4 (CH2) ppm. MS (EI): m/z (%)
= 474 (8), 207 (100). HRMS: calcd. for C24H26O12 474.1162; found
474.1171.
1
17; copies of the H and 13C NMR spectra.
Acknowledgments
Financial support from the Spanish Ministry of Education and Sci-
ence (MEC) (CTQ2004-05752 and CTQ2007-63244) and the Xunta
de Galicia (DXPCTSUG2007/090 and PGIDIT07PXIB209139PR)
is gratefully acknowledged. D. Peña thanks MEC for the award of
a Ramón y Cajal research contract.
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for endo-24: H NMR (300 MHz, CDCl3): δ = 7.94–7.84 (m, 2 H),
7.72–7.63 (m, 2 H), 7.56–7.40 (m, 5 H), 7.34 (m, 1 H), 7.25 (m, 1
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Eur. J. Org. Chem. 2009, 5519–5524
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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I. Quintana, D. Peña, D. Pérez, E. Guitián
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Received: June 9, 2009
Published Online: September 3, 2009
5524
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Eur. J. Org. Chem. 2009, 5519–5524