Deoxygenation of hydroquinones as a general route to norbornane-fused aromatic systems: An entry into substituted and functionalized dimethano- and methanoanthracenes

Article abstract of DOI:10.1021/jo202023w

A high-yielding route to substituted and functionalized dimethanoanthracenes by the Pd-catalyzed deoxyenation of the corresponding hydroquinone precursors is described. Attempts were made to deoxygenate the 9,10-dimesylate, ditosylate, and ditriflate deri

Full text of DOI:10.1021/jo202023w

Article
pubs.acs.org/joc
Deoxygenation of Hydroquinones as a General Route to
Norbornane-Fused Aromatic Systems: An Entry into Substituted and
Functionalized Dimethano- and Methanoanthracenes
Prasad Ganji and Hasim Ibrahim*
Centre for Synthesis and Chemical Biology, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin
4, Ireland
S
* Supporting Information
ABSTRACT: A high-yielding route to substituted and functionalized
dimethanoanthracenes by the Pd-catalyzed deoxyenation of the
corresponding hydroquinone precursors is described. Attempts were
made to deoxygenate the 9,10-dimesylate, ditosylate, and ditriflate
derivatives of anti-dimethanoanthracene 1a, and it was found that under
the studied conditions only the ditriflate 8a gave the corresponding
deoxygenated aromatic scaffold. Optimization of the reaction conditions identified the Pd(OAc)2/dppf tandem as a suitable
catalytic system for this transformation. The presented strategy was further extended to a novel and efficient synthetic route to
methanoanthracenes employing a one-pot Pd-catalyzed deoxygenation/hydrogenation sequence.
Scheme 2. Synthetic Strategies to anti-
Dimethanoanthracenes
INTRODUCTION
■
Dimethanoanthracenes have been utilized as rigid building
blocks for molecular tweezers and clips,1 rigid cavitands,2 and
highly robust radical-cations.3 Notably, the removal of the σh
plane in C2h-symmetrical anti-dimethanoathracenes 1 by the
desymmetrization of the 9 and 10 positions, for instance, leads
to C2-symmetrical compounds that have found application as
catalyst precursors in a number of asymmetric catalytic
processes (Scheme 1).4−8
Scheme 1. Chiral anti-Dimethanoanthracenes 2 (R1 ≠ R2)
from the Desymmetrization of 1
leads to anti-dimethanoanthracene 1a (R = H) in a moderate
yield.9 However, the harsh reaction conditions (85% H3PO4,
110 °C, 16 h) are incompatible with the synthesis of other
substituted, functionalized, and acid-sensitive analogues. Other
approaches, including the double DA reaction of 1,3-cyclo-
pentadiene with “dibenzyne”, generated formally from 1,2,4,5-
tetrabromobenzene and n-butyllithium, gave diene 4 as an
inseparable mixture of syn/anti-isomers.10
We report here on a general route to dimethanoanthracenes
by the Pd-catalyzed deoxygenation of readily accessible
hydroquinone precursors via the corresponding ditriflates and
extend this methodology to a novel and efficient synthetic route
to methanoanthracenes.
D4-symmetrical metalloporphyrin catalysts derived from
resolved 9-acyl-anti-dimethanoanthracenes of type 2 have
been employed successfully in a number of asymmetric
transformations, including asymmetric epoxidation,4 asymmet-
ric cyclopropanation,4f,5 asymmetric aziridination,6 asymmetric
C−H activation,7 and asymmetric Diels−Alder (DA) reac-
tions.4b,8
In ongoing projects in our laboratory exploiting nonracemic
anti-dimethanoanthracenes of type 2 in asymmetric trans-
formations, we required multigram quantities of sterically
engineered analogues of 1.
A literature survey revealed several approaches to this class of
arenes, which are summarized in Scheme 2. Halterman
reported that the dehydration of diol 3 with 85% H3PO4
Received: October 14, 2011
Published: December 2, 2011
© 2011 American Chemical Society
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The deoxygenation of 8a was scaled up to 10 mmol without
problems, and 1a was obtained in 91% yield (Table 2, entry
1).17
We then proceeded to test other substituted and
functionalized dimethanoanthracene ditriflates 8b−f, which
were synthesized according to Schemes 4 and 5, and results
from these investigations are summarized in Table 2.
RESULTS AND DISCUSSION
■
Efforts to deoxygenate hydroquinone 53 were made by
converting it to the dimesylate 6, ditosylate 7, and ditriflate
8a in good yields (Scheme 3). Attempts to deoxygenate
Scheme 3. Synthesis of anti-Dimethanoanthracene-Derived
Disulfonates from Hydroquinone 5
Scheme 4. Synthesis of Ditriflates 8b−d
disulfonates 6, 7, and 8a under the Sajiki deoxygenation
conditions using Mg metal in the presence of NH4OAc in
MeOH under Pd/C catalysis,11 as well as the Ni-catalyzed
hydrogenolysis of 7 with NaBH4,12 failed or gave 1a in trace
amounts. Furthermore, attempts to deoxygenate 6 by Sajiki’s
Pd/C-catalyzed hydrogenolysis under hydrogen atmosphere
employing diethylamine as a SET agent also failed to give 1a.13
We then focused on the deoxygenation of ditriflate 8a, as the
Pd-catalyzed detriflation of aryl and vinyl triflates has been
documented.14 Our initial detriflation was carried out using
reaction conditions similar to those reported by Snieckus,
consisting of the Pd(OAc)2/PPh3 catalytic system in
conjunction with the HCO2H/Et3N tandem as the reducing
agent.15
Scheme 5. Synthesis of Ditriflates 8e−i from the
Corresponding Enedione Precursors 12e−i
Using a higher Pd(OAc)2 loading of 16 mol % and an excess
in the reducing agent, we were pleased to find that arene 1a was
formed in 76% yield after 24 h (Table 1, entry 1). However,
efforts to lower the high catalyst loading to 10 mol % in
palladium resulted in a tripling of the reaction time (entry 2).
We then examined other phosphine ligands and found that 1,1′-
bis(diphenylphosphino)ferrocene (dppf) greatly accelerated
the reaction (Table 1, entries 3 and 4).16 Moreover, we were
able to lower the Pd loading even further to 1 mol % and
observed in 1 h a complete conversion to the product, which
was isolated in an excellent yield of 95% (entry 5). Efforts to
further reduce the amount of the reducing agent resulted in a
sluggish conversion (entries 6 and 7).
Table 1. Pd-Catalyzed Hydrogenolysis of Ditriflate 8a
a
entry
Pd(OAc)2 (mol %)
L (loading) (mol %)
HCO2H/Et3N (equiv)
time (h)
yield (%)
1
2
3
4
5
6
7
16.0
10.0
4.0
PPh3 (32.0)
PPh3 (20.0)
dppf (4.0)
dppf (2.0)
dppf (1.0)
dppf (1.0)
dppf (1.0)
16.0/24.0
16.0/24.0
16.0/24.0
16.0/24.0
16.0/24.0
8.0/12.0
4.0/6.0
24
72
0.5
1
76 (≥98)
78 (≥98)
86 (≥98)
87 (≥98)
95 (≥98)
91 (≥98)
92 (≥98)
2.0
1.0
1
1.0
32
1.0
60
a
Yield of isolated product after short-pad column chromatography; conversion, determined by 1H NMR of the crude product, is given in
parentheses.
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a
Table 2. Pd-Catalyzed Deoxygenation of Ar(OTf)2
Figure 1. Crystal structure of ketone 1d drawn with 50% thermal
ellipsoids.
deoxygenation conditions using 2.0 mol % of catalyst gave the
detriflated dodecachloro arene 1e in 66% yield (Table 2, entry
5).
The hydroquinone precursor of diene ditriflate 8f has been
used as a bis-dienophile in supramolecular chemistry, and we
were interested in examining if 8f could be deoxygenated under
our conditions.2b Monitoring this reaction by TLC analysis, we
observed the formation of several spots which converged into
one spot after 28 h. Examination of the crude 1H NMR
spectrum revealed that detriflation had taken place; however,
this was accompanied by the hydrogenation of the double
bonds to give 1a in 72% isolated yield (Table 2, entry 6).20
The fact that the detriflation of 8f occurred with concomitant
alkene hydrogenation encouraged us to exploit this detriflation/
hydrogenation sequence in a short and efficient synthetic route
to methanoanthracenes starting from commercially available
naphthoquinone.21 Thus, DA reactions of cyclopentadiene and
spirocyclopropane-annulated and 5,5-dimethoxy analogues to
naphthoquinone gave enediones 12g−i, which were converted
to the corresponding ditriflates 8g−i using the KHMDS/
PhNTf2 triflation conditions (method A, Scheme 5).22
A subsequent Pd-catalyzed one-pot detriflation/hydrogena-
tion sequence using 5 mol % of Pd(OAc)2/dppf furnished
methanoanthracenes 1g−i in good yields (Table 2, entries 7−
9).
a
Reaction conditions: Pd(OAc)2/dppf (cat.), HCO2H (16 equiv),
Et3N (24 equiv), DMF, 70 °C.
The sterically congested bis(spirocyclopropane) ditriflate 8b
and bis(spirocyclopentane) ditriflate 8c were prepared
according to a route identical to that used for ditriflate 8a in
high overall yields (Scheme 4).
In analogy, the synthesis of keto ditriflate 8d involved first
the DA reaction of p-benzoquinone with 5,5-dimethoxycyclo-
pentadiene,18 followed by a second DA reaction of the obtained
endo-9,9-dimethoxy-1,4-methanonaphthalene with cyclopenta-
diene, which proceeded to give exclusively the endo,anti,endo-
bis-DA adduct 9c. Subsequent hydrogenation and treatment
with bromine gave, due to the acidic conditions in the latter
reaction, the hydrolyzed keto hydroquinone 11c, which upon
triflation furnished the keto ditriflate 8d in a good yield
(Scheme 4).
The observed Pd-catalyzed hydrogenation of the double
bonds proceeds presumably under transfer-hydrogenation
conditions.23 However, it is not clear at present if this reduction
is occurring in parallel or after the detriflation event and if it is
proceeding under homogeneous or heterogeneous catalytic
conditions.24
The deoxygenation of sterically hindered ditriflates 8b and 8c
using the Pd(OAc)2/dppf catalytic system required a higher
catalyst loading of 5 mol %, and longer reaction times were
needed to obtain arenes 1b and 1c in 72% and 95% yields,
respectively (Table 2, entries 2 and 3).
Treatment of 8d with 2 mol % of Pd(OAc)2/dppf gave after
2 h the detriflated keto anti-dimethanoanthracene 1d in 67%
yield (Table 2, entry 4). We were able to obtain crystals suitable
for X-ray analysis, and the structure of 1d is shown in Figure 1.
The synthesis of ketone 1d clearly demonstrates that our
approach is general, providing for the first time access to
functionalized anti-dimethanoanthracenes.
In order to demonstrate that our approach is also applicable
to syn-dimethanoanthracenes, we chose to subject the
dodecachloro ditriflate 8e to our deoxygenation conditions.
Ditriflate 8e was prepared by the triflation of the literature-
known enedione precursor 12e19 using the Tf2O/py triflation
conditions (method B, Scheme 5). Subjecting 8e to our
CONCLUSION
■
In summary, we have described a general and efficient
procedure for the synthesis of norbornane-fused aromatic
systems utilizing an initial DA reaction between cyclo-
pentadienes and readily available quinones to install the carbon
skeleton, followed by an aromatization/triflation/deoxygena-
tion sequence. This unified approach allowed the preparation of
substituted and functionalized dimethanoanthracenes in high
overall yields and provided a novel and efficient route to
methanoanthracene utilizing, to best of our knowledge, an
unexploited Pd-catalyzed deoxygenation/hydrogenation se-
quence. Current investigations are focused on the desymme-
trative asymmetric hydrogenolysis of the reported ditriflates,
and results from these studies will be reported in due course.
EXPERIMENTAL SECTION
General Remarks. All air- and moisture-sensitive reactions were
conducted under a dry nitrogen atmosphere in oven-dried glassware,
■
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using standard syringe/cannula transfer techniques. Unless specified,
all reagents and starting materials were purchased from commercial
sources and used as received. Freshly distilled cyclopentadienes were
used in DA reactions. Pyridine was purified by distillation over KOH,
and triethylamine was stored over KOH for 24 h prior to use. DMF
was purified by distillation over CaH2. Dichloromethane, THF, and
diethyl ether were obtained from a solvent purification system, and the
remaining solvents were used as received. Thin-layer chromatography
was performed on aluminum sheets (silica gel 60 F254). Detection was
by UV and by coloration with ceric ammonium molybdate (CAM) or
vanillin. Flash column chromatography was performed using silica gel
60 (230−400 mesh). The following compounds were prepared
according to literature procedures: spiro[2.4]hepta-4,6-diene,25
spiro[4.4]nona-1,3-diene,26 5,5-dimethoxycyclopenta-1,3-diene,18 5,3a
9b,4c 12e,19 12f,27 12g,28 and 12h.29
NMR spectra were recorded on 300, 400, and 500 MHz FT
spectrometers at room temperature. All NMR spectra are referenced
relative to the solvent residual peak. NMR peak assignments are based
on 2D NMR experiments (gCOSY, HSQC). The relative stereo-
chemistry of DA adduct 9c was assigned on the basis of a 1D NOSEY
experiment. Melting points were recorded in open capillaries and are
uncorrected. Infrared spectra were recorded at room temperature on
KBr plates. High-resolution mass spectra were obtained by electro-
spray ionization (ESI) or electron impact (EI) in positive ion mode.
Elemental analyses are expressed as percentage values.
evaporated under reduced pressure to give the crude product, which
was recrystallized from hot benzene (10 mL) to afford the title
compound as a cream crystalline solid (6.0 g, 74%). Mp: 203−208 °C.
IR (KBr, cm−1): 3070, 1697, 1628, 1292. 1H NMR (400 MHz,
CDCl3): δ 0.40 (dd, J = 9.2, 6.0 Hz, 4 H, CH2 cyclopropyl), 0.56 (dd, J
= 9.2, 6.0 Hz, 4 H, CH2 cyclopropyl), 2.73 (s, 4 H, CHCHCO), 3.07
(s, 4 H, CHCO), 6.29 (s, 4 H, CHCH). 13C NMR (100 MHz,
CDCl3): δ 6.7, 8.2, 45.2, 53.2, 54.1, 136.4, 212.4. MS (ESI): [M − H]+
291.4. Anal. Calcd for C20H20O2 (292.14): C, 82.16; H, 6.89. Found:
C, 82.13; H, 6.84.
endo-9,9-Dimethoxy-1,4,4a,8a-tetrahydro-1,4-methanonaph-
thalene-5,8-dione. To a stirred suspension of p-benzoquinone (0.5 g,
4.6 mmol) in toluene (5 mL) at 0 °C was added a solution of 5,5-
dimethoxycyclopentadiene (1.75 g, 13.8 mmol) in toluene (2 mL),
and the reaction mixture was stirred at 70 °C for 12 h. The reaction
mixture was evaporated under reduced pressure to give the crude
product, which was recrystallized from hot isopropanol (5 mL) to
afford the title compound as a white crystalline solid (810 mg, 76%).
Mp: 78−82 °C. IR (KBr, cm−1): 2955, 1687, 1620, 1485, 1265, 1142.
1H NMR (400 MHz, CDCl3): δ 3.13 (s, 3 H, OCH3), 3.24 (s, 3 H,
OCH3), 3.42 (d, J = 1.5 Hz, 2 H, CHCO), 3.48 (d, J = 1.8 Hz, 2 H,
CHCHCO), 6.08 (virtual t, J = 2.2 Hz, 2 H, CHCH), 6.61 (s, 2 H,
CHCHCO). 13C NMR (100 MHz, CDCl3): δ 46.9, 50.0, 50.1, 52.2,
117.0, 133.2, 142.6, 198.7. HRMS (EI): C13H14O4 [M + H]+ calcd,
234.0892; found, 234.0882.
9,10-Bis(methanesulfonyloxy)-1,2,3,4,5,6,7,8-octahydro-1,4:5,8-
anti-dimethanoanthracene (6). Hydroquinone 5 (2.42 g, 10.0
mmol) was placed in an oven-dried Schlenk tube, and then Et3N
(2.4 g, 24.0 mmol) and dry CH2Cl2 (20 mL) were added via a syringe.
To this stirred suspension was added dropwise CH3SO2Cl (2.7 g, 24.0
mmol) at 0 °C over 10 min, and the resulting reaction mixture was
stirred at room temperature for 2 h. The precipitate formed was
filtered off, and the filtrate was diluted with CH2Cl2 (20 mL) and
washed with H2O (2 × 20 mL). The organic layer was evaporated
under reduced pressure to give the crude product, which was triturated
with methanol (10 mL) to give the title compound as a white solid
(2.96 g, 75%). Mp: 230−235 °C. IR (KBr, cm−1): 2962, 1465, 1301.
1H NMR (300 MHz, CDCl3): δ 1.27−1.30 (m, 4 H, CHH), 1.51−
1.54 (m, 2 H, CHH bridge), 1.77−1.80 (m, 2 H, CHH bridge), 1.89−
1.92 (m, 4 H, CHH), 3.26 (s, 6 H, CH3), 3.62 (s, 4 H, CH). 13C NMR
(100 MHz, CDCl3): δ 26.2, 38.4, 42.0, 49.4, 135.0, 140.8. HRMS
(ESI): C18H22O6S2 [M + Na]+ calcd, 421.0756; found, 421.0768. Anal.
Calcd for C18H22O6S2 (398.49): C, 54.25; H, 5.56. Found: C, 54.52;
H, 5.51.
9,10-Bis(p-toluenesulfonyloxy)-1,2,3,4,5,6,7,8-octahydro-1,4:5,8-
anti-dimethanoanthracene (7). Hydroquinone 5 (2.42 g, 10.0
mmol) was placed in a Schlenk tube, and then Et3N (2.4 g, 24.0
mmol) and dry CH2Cl2 (20 mL) were added via a syringe. To this
stirred suspension was added portion wise TsCl (4.7 g, 24.0 mmol) at
0 °C over 10 min, and the reaction mixture was stirred at room
temperature for 2 h. The precipitate formed was filtered, and the
filtrate was diluted with CH2Cl2 (20 mL). The filtrate was washed with
water (2 × 20 mL) and evaporated under reduced pressure to give the
crude product, which was titurated with methanol (10 mL) to give the
title compound as a white solid (4.40 g, 80%). Mp: 220−226 °C. IR
(KBr, cm−1): 2926, 1593, 1333. 1H NMR (300 MHz, CDCl3): δ
1.10−1.12 (m, 4 H, CHH), 1.25−1.28 (m, 2 H, CHH bridge), 1.38−
1.41 (m, 2 H, CHH bridge), 1.68−1.70 (m, 4 H, CHH), 2.47 (s, 6 H,
CH3), 3.18 (bs, 4 H, CH), 7.35 (d, J = 8.0 Hz, 4 H, ArH), 7.82 (d, J =
8.0 Hz, 4 H, ArH). 13C NMR (100 MHz, CDCl3): δ 21.7, 26.0, 41.9,
49.2, 128.4, 129.7, 133.5, 135.5, 140.8, 145.2. HRMS (ESI):
C30H30O6S2 [M + Na]+ calcd, 573.1382; found, 573.1384. Anal.
Calcd for C30H30O6S2 (550.08): C, 65.43; H, 5.49. Found: C, 65.29;
H, 5.40.
endo,anti,endo-11,11-Dimethoxy-1,4,4a,5,8,8a,9a,10a-octahy-
dro-1,4:5,8-dimethanoanthracene-9,10-dione (9c). To a suspension
of endo-9,9-dimethoxy-1,4,4a,8a-tetrahydro-1,4-methanonaphthalene-
5,8-dione (1.0 g, 4.2 mmol) in toluene at 0 °C was added freshly
distilled cyclopentadiene (415 mg, 6.3 mmol). The reaction mixture
was heated at 70 °C for 3 h, allowed to cool to room temperature, and
then stirred at 0 °C for 1 h. The precipitate formed was filtered and
washed with chilled toluene (2 mL) to give the title compound as a
white crystalline solid (982 mg, 85%). Mp: 154−158 °C. IR (KBr,
cm−1): 2965, 1678, 1635, 1427, 1290. 1H NMR (500 MHz, CDCl3): δ
1.34 (d, J = 8.6 Hz, 1 H, CHH bridge), 1.52 (d, J = 8.6 Hz, 1 H, CHH
bridge), 2.93 (s, 2 H, CHCO), 3.04 (s, 2 H, CHCO), 3.10 (s, 3 H,
OCH3), 3.18 (s, 3 H, OCH3), 3.28−3.33 (m, 2 H, CHCHCO), 3.33−
3.38 (m, 2 H, CHCHCO), 6.14 (virtual t, J = 2.2 Hz, 2 H, CHCH),
6.29 (virtual t, J = 1.8 Hz, 2 H, CHCH). 13C NMR (75 MHz,
CDCl3): δ 48.9, 49.5, 50.0, 51.7, 52.2, 53.5, 116.9, 134.5, 136.0, 212.1.
MS (ESI): [M + H]+ 301.4. Anal. Calcd for C18H20O4 (300.34): C,
71.98; H, 6.71. Found: C, 71.90; H, 6.73.
endo-11,11-Dimethoxy-1,4,4a,9a-tetrahydro-1,4-methanoan-
thracene-9,10-dione (12i). To a solution of 1,4-naphthoquinone
(316 mg, 2.0 mmol) in CH2Cl2 at 0 °C was added freshly prepared
5,5-dimethoxycyclopentadiene (504 mg, 4.0 mmol). The reaction
mixture was stirred at room temperature for 12 h and evaporated
under reduced pressure to give the crude product, which was purified
by flash column chromatography (SiO2; pentane/EtOAc, 90:10) to
obtain the title compound as a white solid (369 mg, 65%). Mp: 137−
1
140 °C. IR (KBr, cm−1): 2971, 1673, 1641. H NMR (400 MHz,
CDCl3): δ 3.19 (s, 3 H, OCH3), 3.32 (s, 3 H, OCH3), 3.62−3.65 (m,
2 H, CHCHCO), 3.66−3.68 (m, 2 H, CHCO), 6.07 (t, J = 2.1 Hz, 2
H, CHCH), 7.70 (dd, J = 5.8, 3.4 Hz, 2 H, ArH), 8.03 (dd, J = 5.8,
3.4 Hz, 2 H, ArH). 13C NMR (100 MHz, CDCl3): δ 48.1, 50.2, 50.5,
52.3, 117.2, 126.9, 133.6, 134.1, 136.2, 197.2. HRMS (ESI): C17H16O4
[M]+ calcd, 285.1127; found, 285.1140. Anal. Calcd for C17H16O4
(284.31): C, 71.82; H, 5.67. Found: C, 71.62; H, 5.67.
General Procedure for the Hydrogenation of Diels−Alder
Adducts (GP I). A Schlenk tube containing a suspension of DA
adducts 9a−c, 5% Pd/C (5 mol %) or 10% Pd/C (10 mol %), and
EtOAc was connected to a 5 gallon balloon containing H2, equipped
with a three-way tap. The reaction mixture was degassed by three
vacuum/hydrogen cycles and stirred under H2 atmosphere for 24−48
h. The hydrogenated products were obtained by filtration of the
reaction mixture through a short pad of silica gel using chloroform as
the eluent.
e n d o , a n t i , e n d o - 1 1 , 1 2 - B i s [ s p i r o ( c y c l o p r o p y l ) ] -
1,4,4a,5,8,8a,9a,10a-octahydro-1,4:5,8-dimethanoanthracene-
9,10-dione (9a). To a stirred suspension of p-benzoquinone (3.0 g,
27.0 mmol) in benzene (30 mL) was added freshly distilled
spiro[2.4]hepta-4,6-diene (7.6 g, 81.0 mmol) at 0 °C via a syringe
over 10 min. The resulting reaction mixture was refluxed for 24 h and
e n d o , a n t i , e n d o - 1 1 , 1 2 - B i s [ s p i r o ( c y c l o p r o p y l ) ] -
1,2,3,4,4a,5,6,7,8,8a,9a,10a-dodecahydro-1,4:5,8-dimethanoan-
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thracene-9,10-dione (10a). According to GP I, DA adduct 9a (3.9 g,
13.4 mmol), EtOAc (10 mL), and 5% Pd/C (71 mg, 0.67 mmol) were
stirred under H2 atmosphere for 24 h. The title compound was
isolated as a white solid (3.74 g, 98%). Mp: 221−224 °C. IR (KBr,
mmol). The title compound was isolated as a pale yellow solid (357
1
mg, 74%). Mp: 294−298 °C. IR (KBr, cm−1): 3350, 3032, 1516. H
NMR (300 MHz, CD3OD): δ 1.12−1.17 (m, 2 H, CH2), 1.27−1.32
(m, 2 H, CH2), 1.45 (d, J = 8.8 Hz, 1 H, CHH bridge), 1.58 (d, J = 8.8
Hz, 1 H, CHH bridge), 1.84−1.87 (m, 2 H, CH2), 2.07−2.10 (m, 2 H,
CH2), 3.41 (s, 2 H, CH), 3.56 (s, 2 H, CH). 13C NMR (75 MHz,
CD3OD): δ 21.8, 26.1, 40.0, 43.8, 48.4, 125.5, 133.5, 137.2, 205.0.
HRMS (ESI): C16H16O3 [M − H]+ calcd, 255.1029; found, 255.1021.
General Procedure for the Preparation of Ditriflates from
Hydroquinones (GP III). In an oven-dried Schlenk tube were placed
hydroquinone 11a−11d, anhydrous pyridine (3−6 equiv), and dry
CH2Cl2 under N2, and the reaction mixture was cooled to −10 °C
using an ice−acetone bath. To this stirred suspension was added a
solution of Tf2O (2.4 equiv) in dry CH2Cl2 over 15 min via a syringe.
The reaction mixture was allowed to warm to room temperature and
stirred for 12 h. Water was added to the reaction mixture and extracted
with CH2Cl2. The combined organic layers were washed with 10%
aqueous HCl and water, dried over Na2SO4, and evaporated under
reduced pressure to afford the crude product, which was carried to the
next step without further purification.
1
cm−1); 2966, 1679, 1225. H NMR (400 MHz, CDCl3): δ 0.58 (s, 8
H, CH2 cyclopropyl), 1.38−1.45 (m, 4 H, CHH), 1.74−1.78 (m, 4 H,
CHH), 2.08 (s, 4 H, CHCHCO), 3.10 (s, 4 H, COCH). 13C NMR
(100.0 MHz, CDCl3): δ 5.9, 6.5, 25.3, 35.2, 48.5, 54.0, 214.5. HRMS
(EI): C20H24O2 [M]+ calcd, 296.1776; found, 296.1773. Anal. Calcd
for C20H24O2 (296.40): C, 81.04; H, 8.16. Found: C, 80.98; H, 8.13.
e n d o , a n t i , e n d o - 1 1 , 1 2 - B i s [ s p i r o ( c y c l o p e n t y l ) ] -
1,2,3,4,4a,5,6,7,8,8a,9a,10a-dodecahydro-1,4:5,8-dimethanoan-
thracene-9,10-dione (10b). According to GP I, DA adduct 9b (400
mg, 1.1 mmol), EtOAc (3 mL), and 10% Pd/C (12 mg, 0.11 mmol)
were stirred under H2 atmosphere for 48 h. The title compound was
isolated as a white solid (385 mg, 95%). Mp: 279−281 °C. IR (KBr,
1
cm−1): 2958, 1698, 1254. H NMR (400 MHz, CDCl3): δ 1.27−1.29
(m, 4 H, CH2), 1.48−1.77 (m, 20 H, CH2), 2.30 (s, 4 H, CHCHCO),
2.98 (s, 4 H, CHCO). 13C NMR (100 MHz, CDCl3): 24.8, 25.9, 26.0,
29.9, 30.8, 50.3, 53.5, 58.2, 216.0. HRMS (ESI): C24H32O2 [M]+ calcd,
353.2481; found, 353.2497. Anal. Calcd for C24H32O2 (352.51): C,
81.77; H, 9.15. Found: C, 81.66; H, 9.03.
9,10-Bis(trifluoromethanesulfonyloxy)-1,2,3,4,5,6,7,8-octahydro-
1,4;5,8-anti- dimethanoanthracene (8a). According to GP III,
hydroquinone 5 (2.42 g, 10 mmol) and pyridine (2.37 g, 30 mmol)
in CH2Cl2 (50 mL) were reacted with Tf2O (6.7 g, 24 mmol). The
title compound was isolated as a pale yellow solid (4.6 g, 91%). Mp:
endo,anti,endo-11,11-Dimethoxy-1,2,3,4,4a,5,6,7,8,8a,9a,10a-
dodecahydro-1,4:5,8-dimethanoanthracene-9,10-dione (10c). Ac-
cording to GP I, DA adduct 9c (1.0 g, 3.3 mmol), EtOAc (5 mL),
and 10% Pd/C (34 mg, 0.33 mmol) were stirred under H2 atmosphere
for 24 h. The title compound was isolated as a white solid (0.95 g,
98%). Mp: 157−161 °C. IR (KBr, cm−1): 2931, 1687, 1243. 1H NMR
(400 MHz, CDCl3): δ 1.23−1.31 (m, 2 H, CH2), 1.32−1.42 (m, 2 H,
CH2), 1.42−1.45 (m, 2 H, CH2 bridge), 1.55−1.58 (m, 2 H, CH2),
1.76 (d, J = 10.5 Hz, 2 H, CHH), 2.66 (s, 2 H, CHCHCO), 2.84 (s, 2
H, CHCHCO), 2.86 (s, 2 H, CHCO), 3.11 (s, 2 H, CHCO), 3.27 (s,
3 H, OCH3), 3.30 (s, 3 H, OCH3). 13C NMR (100 MHz, CDCl3): δ
22.8, 25.1, 39.8, 43.8, 44.2, 50.6, 50.8, 51.6, 53.8, 111.8, 214.0. MS
(ESI): [M + H]+ 305.2. Anal. Calcd for C18H24O4 (304.16): C, 71.03;
H, 7.95. Found: C, 71.28; H, 7.98.
General Procedure for the Preparation of Hydroquinones
(GP II). Diones 10a−c and CHCl3 were placed in an oven-dried
Schlenk tube under N2, and the reaction mixture was cooled to 0 °C.
To this stirred suspension was added dropwise a solution of Br2 (1
equiv) in CHCl3 (2 −20 mL) over 10 min. The reaction mixture was
stirred at room temperature for 2 h, and the HBr produced in the
reaction was blown off by bubbling N2 through the reaction mixture
for 10 min. The resulting suspension was stirred at −10 °C for 1 h.
The precipitate formed was filtered and washed with chilled CHCl3 to
give hydroquinones 11a−c.
1
229−232 °C. IR (KBr, cm−1): 2962, 1612, 1213. H NMR 400 MHz,
CDCl3): δ 1.25−1.28 (m, 4 H, CH2), 1.56−1.59 (m, 2 H, CHH
bridge), 1.81−1.84 (m, 2 H, CHH bridge), 1.94−1.97 (m, 4 H, CH2),
3.63 (s, 4 H, CH). 13C NMR (100 MHz, CDCl3): δ 25.8, 41.9, 49.5,
120.4 (q, J = 320 Hz), 135.7, 140.7. MS (ESI): [M + H]+ 507.1. Anal.
Calcd for C18H16F6O6S2 (506.02): C, 42.69; H, 3.18. Found: C, 42.71;
H, 3.17.
9,10-Bis(trifluoromethanesulfonyloxy)-11,12-di[spiro-
(cyclopropyl)]-1,2,3,4,5,6,7,8-octahydro-1,4;5,8-anti-dimethanoan-
thracene (8b). According to GP III, hydroquinone 11a (2.0 g, 6.8
mmol) and pyridine (3.2 g, 40.8 mmol) in CH2Cl2 were reacted with
Tf2O (4.6 g, 16.3 mmol). The title compound was isolated as a pale
yellow solid (3.53 g, 93%). Mp: 232−234 °C. IR (KBr, cm−1): 2983,
1426, 1209. 1H NMR (400 MHz, CDCl3): δ 0.51−0.60 (m, 8 H, CH2
cyclopropyl), 1.38−1.42 (m, 4 H, CHH), 2.13−2.15 (m, 4 H, CHH),
2.92 (s, 4 H, CH). 13C NMR (100 MHz, CDCl3): δ 6.3, 7.4, 26.2, 45.8,
47.2, 120.2 (q, J = 309.4 Hz), 135.8, 140.5. HRMS (ESI): calcd,
559.0684; found, 559.0671. Anal. Calcd for C22H20F6O6S2 (558.06):
C, 47.31; H, 3.61. Found: C, 47.40; H, 3.73.
9,10-Bis(trifluoromethanesulfonyloxy)-11,12-di[spiro-
(cyclopentane)]-1,2,3,4,5,6,7,8-octahydro-1,4;5,8-anti-dimetha-
noanthracene (8c). According to GP III, hydroquinone 11b (350
mg, 1.0 mmol) and pyridine (474 mg, 6.0 mmol) in CH2Cl2 were
reacted with Tf2O (676 mg, 2.4 mmol). The title compound was
isolated as a pale yellow solid (583 mg, 95%). Mp: 231−234 °C. IR
(KBr, cm−1): 2958, 1520, 1201. 1H NMR (400 MHz, CDCl3): δ
1.22−1.30 (m, 8 H, CH2 cyclopentyl), 1.43−1.57 (m, 8 H, CH2
cyclopentyl), 1.58−1.62 (m, 4 H, CHH), 1.97−2.12 (m, 4 H, CHH),
3.12 (bs, 4 H, CH). 13C NMR (100 MHz, CDCl3): δ 25.4, 25.5, 25.9,
31.4, 32.1, 49.6, 69.8, 120.2 (q, J = 320 Hz), 137.0, 141.1. HRMS
(ESI): C26H28F6O6S2 [M + Na]+ calcd, 637.1129; found, 637.1159.
9,10-Bis(trifluoromethanesulfonyloxy)-11-keto-1,2,3,4,5,6,7,8-oc-
tahydro-1,4;5,8-anti-dimethanoanthracene (8d). According to GP
III, hydroquinone 11c (281 mg, 1.1 mmol) and pyridine (522 mg, 6.6
mmol) in CH2Cl2 (5 mL) were reacted with Tf2O (744 mg, 2.64
mmol). The title compound was isolated as a pale yellow solid (388
9,10-Dihydroxy-11,12-bis[spiro(cyclopropyl)]-1,2,3,4,5,6,7,8-octa-
hydro-1,4:5,8-anti-dimethanoanthracene (11a). According to GP
II, dione 10a (3.0 g, 10 mmol) was reacted with Br2 (1.6 g, 10 mmol)
in CHCl3 (30 mL). The title compound was isolated as a pale yellow
solid (2.86 g, 96%). Mp: 292−296 °C. IR (KBr, cm−1): 3406, 3032,
1
1508. H NMR (300 MHz, CD3OD): δ 0.04−0.09 (m, 8 H, CH2
cyclopropyl), 0.81−0.83 (m, 4 H, CHH), 1.61−1.64 (m, 4 H, CHH),
2.39 (s, 4 H, CH). 13C NMR (100 MHz, CD3OD): δ 5.6, 6.6, 26.5,
44.1, 45.3, 132.7, 136.9. HRMS (EI): C20H22O2 [M + H]+ calcd,
295.1698; found, 295.1684. Anal. Calcd for C20H22O2 (294.38): C,
81.60; H, 7.53. Found C, 81.52; H, 7.51.
9,10-Dihydroxy-11,12-bis[spiro(cyclopentyl)]-1,2,3,4,5,6,7,8-octa-
hydro-1,4:5,8-anti-dimethanoanthracene (11b). According to GP
II, dione 10b (400 mg, 1.13 mmol) in CHCl3 (4 mL) was reacted with
Br2 (180 mg, 1.13 mmol). The title compound was isolated as a pale
yellow solid (388 mg, 97%). Mp: 328−330 °C. IR (KBr, cm−1): 3455,
1
mg, 68%). Mp: 212−215 °C. IR (KBr, cm−1): 2987, 1685, 1535. H
1
2971, 1602. H NMR (300 MHz, CD3OD): δ 1.05−1.14 (m, 4 H,
NMR (400 MHz, CDCl3): δ 1.27−1.34 (m, 2 H, CHH), 1.51−1.55
(m, 2 H, CHH), 1.66 (d, J = 9.3, 1 H, CHH bridge), 1.90 (d, J = 9.4
Hz, 1 H, CHH bridge), 1.96−2.07 (m, 2 H, CHH), 2.21−2.33 (m, 2
H, CHH), 3.62 (s, 2 H, CH), 3.71 (s, 2 H, CH). 13C NMR (100 MHz,
CDCl3): δ 21.6, 25.8, 42.0, 45.5, 49.3, 120.3 (q, J = 344 Hz), 133.1,
135.6, 141.2, 200.1. HRMS (ESI): C18H14F6O7S2 [M + Na]+ calcd,
542.9982; found, 542.9976.
CH2 cyclopentyl), 1.26 (virtual t, J = 7.2 Hz, 4 H, CH2 cyclopentyl),
1.43−1.53 (m, 8 H, CH2 cyclopentyl), 1.56−1.69 (m, 4 H, CHH),
1.93 (d, J = 8.1 Hz, 4 H, CHH), 2.98 (bs, 4 H, CH). 13C NMR (75
MHz, CD3OD): 25.1, 25.7, 25.8, 31.4, 32.2, 47.8, 67.8, 133.2, 138.1.
HRMS (ESI): C24H30O2 [M + H]+ calcd, 351.2324; found, 351.2329.
9,10-Dihydroxy-11-keto-1,2,3,4,5,6,7,8-octahydro-1,4:5,8-anti-di-
methanoanthracene (11c). According to GP II, dione 10c (500 mg,
1.6 mmol) in CHCl3 (5 mL) was reacted with Br2 (260 mg, 1.6
9,10-Bis(trifluoromethanesulfonyloxy)perchloro-1,4:5,8-syn-di-
methanoanthracene (8e). According to GP III, enedione 12e (300
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Article
mg, 0.4 mmol) and pyridine (220 mg, 2.7 mmol) in CH2Cl2 (5 mL)
were reacted with Tf2O (314 mg, 1.1 mmol). The title compound was
isolated as a pale yellow solid (212 mg, 50%). Mp: >300 °C. IR (KBr,
cm−1): 2837, 1612, 1409, 1219. 13C NMR (100 MHz, CDCl3): δ 82.0,
113.5, 120.1 (q, J = 321 Hz), 137.3, 138.4, 140.1. MS (ESI): [M + H]+
916.4. Anal. Calcd for C18Cl12F6O6S2 (915.74): C, 23.61. Found: C,
23.70.
General Procedure for the Preparation of Ditriflates from
Enediones (GP IV). In an oven-dried Schlenk tube were placed
enedione (12f−i), anhydrous THF (10−20 mL), and PhNTf2 (2.4
equiv) under N2. The reaction mixture was cooled to −78 °C,
KHMDS (0.5 M in THF, 2.5 equiv) was added via a syringe dropwise
over 10 min, and the resulting mixture was stirred at −78 °C for 2 h.
The reaction mixture was poured into water and extracted with Et2O
(2×). The combined organic layers were washed with 1 N aqueous
NaOH solution and water, dried over Na2SO4, and evaporated under
reduced pressure to afford the crude product, which was purified by
flash column chromatography.
General Procedure for the Deoxygenation of Ditriflates (GP
V). In an oven-dried Schlenk tube were placed ditriflate 8a−i,
HCO2H (16 equiv), dry Et3N (24 equiv), and anhydrous DMF under
N2. The reaction mixture was degassed by three vacuum/nitrogen
cycles, followed by the addition of Pd(OAc)2 (1−5 mol %) and dppf
(1−5 mol %). The resulting mixture was stirred at 70 °C for 1−48 h,
cooled to room temperature, diluted with brine, and extracted with
EtOAc (3 × 10−100 mL). The combined organic layers were washed
with brine and evaporated under reduced pressure to give the crude
product, which was purified either by filtration through a short pad of
silica gel using pentane as the eluent or by flash column
chromatography to afford arenes 1a−i.
1,2,3,4,5,6,7,8-Octahydro-1:4,5:8-anti-dimethanoanthracene4b
(1a). According to GP V, ditriflate 8a (5.06 g, 10.0 mmol), HCO2H
(7.36 g, 6.0 mL, 160 mmol), dry Et3N (24.29 g, 33.5 mL, 240 mmol),
anhydrous DMF (50 mL), Pd(OAc)2 (22.5 mg, 0.1 mmol, 1 mol %),
and dppf (55.4 mg, 0.1 mmol, 1 mol %) were stirred at 70 °C for 1 h.
The title compound was isolated as a white solid (1.91 g, 91%).
11,12-Bis[spiro(cyclopropyl)]-1,2,3,4,5,6,7,8−octahydro-1:4,5:8-
anti-dimethanoanthracene (1b). According to GP V, ditriflate 8b
(558 mg, 1.0 mmol), HCO2H (736 mg, 0.60 mL, 16 mmol), dry Et3N
(2.43 g, 3.35 mL, 24 mmol), anhydrous DMF (5 mL), Pd(OAc)2
(11.3 mg, 0.05 mmol, 5 mol %), and dppf (27.7 mg, 0.05 mmol, 5 mol
%) were stirred at 70 °C for 28 h. The title compound was isolated as a
white solid (190 mg, 72%). Mp: 162−164 °C. IR (KBr, cm−1): 2996,
1639, 1412. 1H NMR (300 MHz, CDCl3): δ 0.34−0.44 (m, 4 H, CH2
cyclopropyl), 0.45−0.54 (m, 4 H, CH2 cyclopropyl), 1.04−1.33 (m, 4
H, CHH), 1.88−2.12 (m, 4 H, CHH), 2.53 (s, 4 H, CH), 6.90 (s, 2 H,
Ar-H). 13C NMR (75.0 MHz, CDCl3): δ 5.5, 6.3, 26.6, 28.7, 44.1,
112.5, 144.0. HRMS (ESI): C20H22 [M]+ calcd, 262.1722; found,
262.1734.
9,10-Bis(trifluoromethanesulfonyloxy)-1,4,5,8-tetrahydro-1,4:5,8-
anti-dimethanoanthracene (8f). According to GP IV, enedione 12f
(240 mg, 1.0 mmol) was treated with PhNTf2 (900 mg, 7.92 mmol),
and KHMDS (0.5 M in THF, 4.7 mL, 2.5 mmol) in anhydrous THF
(20 mL). The title compound was obtained after purification by flash
column chromatography (SiO2; pentane/Et2O, 99:1) as a white solid
1
(480 mg, 76%). Mp: 182−186 °C. IR: 2938, 1630, 1225. H NMR
(400 MHz, CDCl3): δ 2.28−2.35 (m, 4 H, CH2), 4.09−4.11 (m, 4 H,
CH), 6.77−6.85 (m, 4 H, CHCH). 13C NMR (100 MHz, CDCl3):
δ 48.7, 70.0, 120.3 (q, J = 320 Hz), 137.4, 142.9, 145.0. MS (ESI): [M
+ H]+ 503.14. Anal. Calcd for C18H12F6O6S2 (502.40): C, 43.03; H,
2.41. Found: C, 43.32; H, 2.39.
9,10-Bis(trifluoromethanesulfonyloxy)-1,4-methanoanthracene
(8g). According to GP IV, enedione 12g (448 mg, 2.0 mmol) was
treated with PhNTf2 (1.71 g, 4.8 mmol) and KHMDS (0.5 M in THF,
10 mL, 5 mmol) in anhydrous THF (20 mL). The title compound was
obtained after purification by flash column chromatography (SiO2;
pentane/Et2O, 99:1) as a white solid (740 mg, 76%). Mp: 85−89 °C.
IR (KBr, cm−1): 2444, 2294, 1406, 1337. 1H NMR (400 MHz,
CDCl3): δ 2.30 (d, J = 8.2 Hz, 1 H, CHH), 2.39 (dt, J = 8.2, 1.4 Hz, 1
H, CHH), 4.25−4.44 (m, 2 H, CH), 6.85 (virtual t, J = 1.7 Hz, 2 H,
CHCH), 7.65 (dd, J = 6.4, 3.2 Hz, 2 H, ArH), 7.96 (dd, J = 6.4, 3.2
Hz, 2 H, ArH). 13C NMR (100 MHz, CDCl3): δ 48.5, 64.9, 120.3 (q, J
= 320 Hz), 121.4, 126.6, 128.1, 136.6, 141.9, 141.93. HRMS (ESI):
C17H10O6F6S2 [M + Na]+ calcd, 510.9721; found, 510.9708.
9,10-Bis(trifluoromethanesulfonyloxy)-11-[spiro(cyclopropyl)]-
1,4-methanoanthracene (8h). According to GP IV, enedione 12h
(250 mg, 1.0 mmol) was treated with PhNTf2 (0.86 g, 2.4 mmol) and
KHMDS (0.5 M in THF, 5 mL, 2.5 mmol) in THF (10 mL). The title
compound was obtained after purification by flash column
chromatography (SiO2; pentane/Et2O, 99:1) as a white solid (369
mg, 72%). Mp: 102−106 °C. IR (KBr, cm−1): 2988, 2306, 1422, 1265.
1H NMR (400 MHz, CDCl3): δ 0.60 (dd, J = 9.4, 6.6 Hz, 2 H, CHH
cyclopropyl), 0.79 (dd, J = 9.5, 6.5 Hz, 2 H, CHH cyclopropyl), 3.81
(virtual t, J = 1.7 Hz, 2 H, CH), 6.88 (virtual t, J = 1.9 Hz, 2 H, CH
CH), 7.65 (dd, J = 6.4, 3.2 Hz, 2 H, ArH), 7.97 (dd, J = 6.4, 3.2 Hz, 2
H, ArH). 13C NMR (100 MHz, CDCl3): δ 8.2, 8.5, 53.7, 61.4, 120.3
(q, J = 320 Hz), 121.5, 126.5, 128.1, 136.3, 141.1, 141.8. HRMS (ESI):
C19H12O6F6S2 [M + Na]+ calcd, 536.9877; found, 536.9868.
9,10-Bis(trifluoromethanesulfonyloxy)-11,11-dimethoxy-1,4-
methanoanthracene (8i). According to GP IV, enedione 12i (284
mg, 1.0 mmol) was treated with PhNTf2 (0.86 g, 2.4 mmol) and
KHMDS (0.5 M in THF, 5 mL, 2.5 mmol) in THF (10 mL). The title
compound was obtained after purification by flash column
chromatography (SiO2; pentane/Et2O, 99:1) as a white solid (372
mg, 68%). Mp: 93−96 °C. IR (KBr, cm−1): 2837, 2254, 1409, 1219.
1H NMR (400 MHz, CDCl3): δ 3.09 (s, 3 H, OCH3), 3.30 (s, 3 H,
11,12-Bis[spiro(cyclopentyl)]-1,2,3,4,5,6,7,8-octahydro-1:4,5:8-
anti-dimethanoanthracene4c (1c). According to GP V, ditriflate 8c
(500 mg, 0.81 mmol), HCO2H (597 mg, 0.49 mL, 12.9 mmol), dry
Et3N (1.97 g, 2.70 mL, 19.4 mmol), anhydrous DMF (5 mL),
Pd(OAc)2 (9.1 mg, 0.041 mmol, 5 mol %), and dppf (22.5 mg, 0.041
mmol, 5 mol %) were stirred at 70 °C for 48 h. The title compound
was isolated as a white solid (240 mg, 95%).
1,2,3,4,5,6,7,8-Octahydro-1,4:5,8-anti-dimethanoanthracene-11-
one (1d). According to GP V, ditriflate 8d (250 mg, 0.48 mmol),
HCO2H (353 mg, 0.29 mL, 7.7 mmol), dry Et3N (1.16 g, 1.60 mL,
11.5 mmol), anhydrous DMF (2 mL), Pd(OAc)2 (2.2 mg, 0.01 mmol,
2 mol %), and dppf (5.3 mg, 0.01 mmol, 2 mol %) were stirred at 70
°C for 2 h. The title compound was isolated as a white solid (72 mg,
67%). Mp: 172−176 °C. IR (KBr, cm−1): 2968, 2870, 1790, 1606. 1H
NMR (400 MHz, CDCl3): δ 1.08−1.15 (m, 2 H, CH2), 1.25−1.37 (m,
2 H, CH2), 1.43−1.53 (m, 1 H, CHH bridge), 1.63−1.76 (m, 1 H,
CHH bridge), 1.79−1.95 (m, 2 H, CH2), 2.05−2.22 (m, 2 H, CH2),
3.24−3.29 (m, 2 H, CH), 3.32−3.34 (m, 2 H, CH), 7.08 (s, 2 H, Ar-
H). 13C NMR (100 MHz, CDCl3): δ 22.7, 27.1, 43.8, 47.7, 49.1, 114.4,
137.8, 147.0, 205.3. HRMS (EI): C16H16O [M]+ calcd, 224.1201;
found, 224.1198.
1,2,3,4,5,6,7,8,11,11,12,12-Dodecachloro-1,4:5,8-syn-dimetha-
noanthracene (1e). According to GP V, ditriflate 8e (200 mg, 0.23
mmol), HCO2H (169 mg, 0.14 mL, 3.7 mmol), dry Et3N (558 mg,
0.77 mL, 5.5 mmol), anhydrous DMF (2 mL), Pd(OAc)2 (1.0 mg,
0.005 mmol, 2 mol %), and dppf (2.6 mg, 0.005 mmol, 2 mol %) were
stirred at 70 °C for 1 h. The title compound was isolated as a white
solid (94 mg, 66%). Mp: >300 °C. IR (KBr, cm−1): 2918, 1620, 1350,
1226. 1H NMR (300 MHz, CDCl3): δ 6.25 (s, 2 H, Ar-H). 13C NMR
(100 MHz, CDCl3): δ 82.2, 112.0, 128.5, 138.2, 143.5. HRMS (EI):
C16H2Cl12 [M]+ calcd, 613.6419; found, 613.6419.
1,2,3,4,5,6,7,8-Octahydro-1:4,5:8-anti-dimethanoanthracene4b
from 8f (1a). According to GP V, ditriflate 8f (400 mg, 0.8 mmol),
HCO2H (588 mg, 0.48 mL, 12.8 mmol), dry Et3N (1.93 g, 2.7 mL,
19.2 mmol), anhydrous DMF (5 mL), Pd(OAc)2 (3.6 mg, 0.016
mmol, 2 mol %), and dppf (8.9 mg, 0.016 mmol, 2 mol %) were
stirred at 70 °C for 28 h. The title compound was isolated as a white
solid (120 mg, 72%).
OCH3), 4.46 (t, J = 2.1 Hz, 2 H, CH), 6.63−6.85 (m, 2 H, CHCH),
7.68 (dd, J = 6.4, 3.2 Hz, 2 H, ArH), 8.01 (dd, J = 6.4, 3.2 Hz, 2 H,
ArH). 13C NMR (100 MHz, CDCl3): δ 51.2, 52.3, 52.4, 120.3 (q, J =
320 Hz), 121.4, 126.5, 126.7, 128.2, 137.1, 138.0, 138.3. HRMS (ESI):
C19H14O8F6S2 [M + Na]+ calcd, 570.9932; found, 570.9911.
1,2,3,4-Tetrahydro-1,4-methanoanthracene21a (1g). According
to GP V, ditriflate 8g (200 mg, 0.41 mmol), HCO2H (301 mg, 0.24
516
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mL, 6.5 mmol), dry Et3N (995 mg, 1.37 mL, 9.8 mmol), anhydrous
DMF (2 mL), Pd(OAc)2 (4.5 mg, 0.02 mmol, 5 mol %), and dppf
(11.4 mg, 0.02 mmol, 5 mol %) were stirred at 70 °C for 24 h. The
title compound was isolated by flash column chromatography (SiO2;
pentane) as a white solid (62 mg, 78%).
L.; Jan, S.-T.; Abdulwali, A. H.; Standlee, D. J. Tetrahedron 1997, 53,
11277−11296. (d) Berkessel, A.; Frauenkron, M. J. Chem. Soc., Perkin
Trans. 1 1997, 2265−2266. (e) Zhang, R.; Yu, W.-Y.; Wong, K.-Y.;
Che, C.-M. J. Org. Chem. 2001, 66, 8145−8153. (f) Berkessel, A.;
Kaiser, P.; Lex, J. Chem.Eur. J. 2003, 9, 4746−4756.
11-[Spiro(cyclopropyl)]-1,2,3,4-tetrahydro-1,4-methanoanthra-
cene (1h). According to GP V, ditriflate 8h (250 mg, 0.48 mmol),
HCO2H (354 mg, 0.29 mL 7.7 mmol), dry Et3N (1.17 g, 1.61 mL,
11.5 mmol), anhydrous DMF (2 mL), Pd(OAc)2 (5.4 mg, 0.024
mmol, 5 mol %), and dppf (13.3 mg, 0.024 mmol, 5 mol %) were
stirred at 70 °C for 24 h. The title compound was isolated by flash
column chromatography (SiO2; pentane) as a white solid (87 mg,
82%). Mp: 177−181 °C. IR (KBr, cm−1): 2253, 1636, 1403, 1096. 1H
NMR (400 MHz, CDCl3): δ 0.43−0.66 (m, 4 H, CH2 cyclopropyl),
1.36−1.40 (m, 2 H, CHH), 1.98−2.27 (m, 2 H, CHH), 2.61−2.83 (m,
2 H, CH), 7.37 (dd, J = 6.2, 3.3 Hz, 2 H, Ar-H), 7.55 (s, 2 H, Ar-H),
7.76 (dd, J = 6.2, 3.3 Hz, 2 H, Ar-H). 13C NMR (100 MHz, CDCl3): δ
6.1, 7.0, 27.9, 44.2, 48.8, 118.1, 124.7, 127.6, 132.7, 147.3. MS (ESI):
[M + H]+ 221.4. Anal. Calcd for C17H16 (220.1): C, 92.68; H, 7.32.
Found: C, 92.39; H, 7.66.
(5) (a) Che, C.-M.; Huang, J.-S.; Lee, F.-W.; Li, Y.; Lai, T.-S.; Kwong,
H.-L.; Teng, P.- F.; Lee, W.-S.; Lo, W.-C.; Peng, S.-M.; Zhou, Z.-Y. J.
Am. Chem. Soc. 2001, 123, 4119−4129. (b) Ferrand, Y.; Le Maux, P.;
Simonneaux, G. Org. Lett. 2004, 6, 3211−3214. (c) Lai, T.-S.; Chan,
F.-Y.; So, P.-K.; Ma, D.-L.; Wong, K.-Y.; Che, C.-M. Dalton Trans.
2006, 4845−4851. (d) Le Maux, P.; Juillard, S.; Simonneaux, G.
Synthesis 2006, 1701−1704. (e) Nicolas, I.; Le Maux, P.; Simonneaux,
G. Tetrahedron Lett. 2008, 49, 5793−5795. (f) Nicolas, I.; Roisnel, T.;
Le Maux, P.; Simonneaux, G. Tetrahedron Lett. 2009, 50, 5149−5151.
(6) (a) Lai, T.-S.; Che, C.-M.; Kwong, H.-L.; Peng, S.-M. Chem.
Commun. 1997, 2373−2374. (b) Liang, J.-L.; Huang, J.-S.; Yu, X.-Q.;
Zhu, N.; Che, C.-M. Chem.Eur. J. 2002, 8, 1563−1572.
(7) (a) Thu, H.-Y.; Tong, G. S.-M.; Huang, J.-S.; Chan, S. L.-F.;
Deng, Q.-H.; Che, C.-M. Angew. Chem., Int. Ed. 2008, 47, 9747−9751.
(b) Liang, J.-L.; Yuan, S.-X.; Huang, J.-S.; Che, C.-M. J. Org. Chem.
2004, 69, 3610−3619. (c) Liang, J.-L.; Yuan, S.-X.; Huang, J.-S.; Yu,
W.-Y.; Che, C.-M. Angew. Chem., Int. Ed. 2002, 41, 3465−3468.
11,11-Dimethoxy-1,2,3,4-tetrahydro-1,4-methanoanthracene
(1i). According to GP V, ditriflate 8i (200 mg, 0.36 mmol), HCO2H
(268 mg, 0.22 mL, 5.8 mmol), dry Et3N (880 mg, 1.21 mL, 8.7 mmol),
anhydrous DMF (2 mL), Pd(OAc)2 (4.0 mg, 0.018 mmol), and dppf
(10.0 mg, 0.018 mmol) were stirred at 70 °C for 24 h. The title
compound was isolated by flash column chromatography (SiO2;
pentane/Et2O, 95:5) as a white solid (61 mg, 62%). Mp: 182−185 °C.
(8) Berkessel, A.; Erturk, E.; Laporte, C. Adv. Synth. Catal. 2006, 348,
̈
223−228.
(9) Reported yields for the dehydration of diol 3 are 45% and 57% in
refs 4a and 4b, respectively. Several attempts at this reaction gave, in
our hands, yields of 30% or lower.
1
IR (KBr, cm−1): 3054, 2411, 1231. H NMR (400 MHz, CDCl3): δ
(10) Benkhoff, J.; Boese, R.; Klarner, F.-G. Liebigs Ann. 1997, 501−
̈
1.23−1.26 (m, 2 H, CHH), 2.15−2.24 (m, 2 H, CHH), 3.11 (s, 3 H,
CH3), 3.36 (s, 3 H, CH3), 3.40−3.46 (m, 2 H, CH), 7.39 (dd, J = 6.2,
3.3 Hz, 2 H, Ar-H), 7.58 (s, 2 H, Ar-H), 7.77 (dd, J = 6.2, 3.3 Hz, 2 H,
Ar-H). 13C NMR (100 MHz, CDCl3): δ 25.7, 46.2, 50.0, 51.5, 117.8,
119.1, 124.8, 127.6, 132.9, 144.13. HRMS (ESI): C17H18O2 [M + Na]+
calcd, 277.1204; found, 277.1208.
516. These authors also reported that the same mixture was obtained
in a low yield by the DA reaction of bismethylenenorbornene with
norbornadiene followed by DDQ dehydrogenation.
(11) (a) Sajiki, H.; Mori, A.; Mizusaki, T.; Ikawa, T.; Maegawa, T.;
Hirota, K. Org. Lett. 2006, 8, 987−990. (b) Mori, A.; Mizusaki, T.;
Ikawa, T.; Maegawa, T.; Monguchi, Y.; Sajiki, H. Chem.Eur. J. 2007,
13, 1432−1441.
ASSOCIATED CONTENT
■
(12) (a) Wang, F.; Chiba, K.; Tada, M. J. Chem. Soc., Perkin Trans. 1
1992, 1897−1900. (b) Kogan, V. Tetrahedron Lett. 2006, 47, 7515−
7518.
S
* Supporting Information
1H NMR and 13C NMR spectra of all compounds in the
Experimental Section, and X-ray data for compound 1d. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(13) Mori, A.; Mizusaki, T.; Ikawa, T.; Maegawa, T.; Monguchi, Y.;
Sajiki, H. Tetrahedron 2007, 63, 1270−1280.
(14) For a recent review, see: Cacchi, S.; Morera, E.; Ortar, G. Org.
Synth. 2011, 88, 260−290.
(15) Fu, J.-M.; Snieckus, V. Can. J. Chem. 2000, 78, 905−919.
(16) For use of diphosphine ligands, and specifically dppf, in the
detriflation of aryl triflates, see: (a) Cacchi, S.; Ciattini, P. G.; Morera,
E.; Ortar, G. Tetrahedron Lett. 1986, 27, 5541−5544. (b) Saa, J. M.;
Dopico, M.; Martorell, G.; Garcia-Raso, A. J. Org. Chem. 1990, 55,
991−995. (c) Cabri, W.; De Bernardinis, S.; Francalanci, F.; Penco, S.;
Santi, R. J. Org. Chem. 1990, 55, 350−353.
AUTHOR INFORMATION
Corresponding Author
* hasim.ibrahim@ucd.ie
■
ACKNOWLEDGMENTS
This work was supported by a UCD Ad Astra Scholarship to
P.G., the CSCB, and in part by SFI (07/RFP/CHEF394). We
■
(17) Reactions conducted with up to 35 g of 8a gave comparable
yields.
thank Dr. Helge Muller-Bunz (UCD) for X-ray structure
̈
(18) Hoffmann, G. G.; Klein, H. Chem. Ber. 1986, 119, 514−523.
(19) Watson, A. J.; O’Brien, M. E.; Brooker, M. D.; Jones, D. S.;
Etzkorn, M. Acta Crystallogr. 2007, E63, o3565−o3565.
(20) Pd-catalyzed transfer-hydrogenation of ditriflate 8e was not
observed, presumably due to the congested and electron-deficient
nature of the tetrasubstituted alkenes.
(21) (a) Paddon-Row, M. N.; Patney, H. K. Synthesis 1986, 328−330.
(b) Carrupt, P.-A.; Berchier, F.; Vogel, P. Helv. Chim. Acta 1985, 68,
1716−1729.
(22) Gao, S.; Wang, Q.; Chen, C. J. Am. Chem. Soc. 2009, 131, 1410−
1412.
analysis of ketone 1d, Drs. Jimmy Muldoon (UCD) and
Yannick Ortin (UCD) for NMR spectra, and Dr. Paul Evans
(UCD) for helpful discussions.
REFERENCES
■
(1) For example, see: Klarner, F.-G.; Kahlert, B. Acc. Chem. Res. 2003,
̈
36, 919−932, and references therein.
(2) (a) Stoermer, M. J.; Butler, D. N.; Warrener, R. N.; Weerasuria,
K. D. V.; Fairlie, D. P. Chem.Eur. J. 2003, 9, 2068−2071. (b) Butler,
D. N.; Smits, R.; Evans, D. A. C.; Weerasuria, K. D. V.; Warrener, R. N.
Tetrahedron Lett. 1996, 37, 2157−2160.
(23) For a leading reference on the Pd-catalyzed reduction of alkenes
under transfer-hydrogenation conditions, see: Brunel, J. M. Synlett
2007, 330−332, and references therein.
(3) (a) Rathore, R.; Kochi, J. K. J. Org. Chem. 1995, 60, 4399−4411.
(b) Rathore, R.; Burns, C. L.; Deselnicu, M. I. Org. Synth. 2005, 82, 1−
9.
(4) (a) Halterman, R. L.; Jan, S. T. J. Org. Chem. 1991, 56, 5253−
5254. (b) Halterman, R. L.; Jan, S.-T.; Nimmons, H. L.; Standlee, D. J.;
Khan, M. A. Tetrahedron 1997, 53, 11257−11276. (c) Halterman, R.
(24) For a Pd-catalyzed one-pot Heck olefination/hydrogenation
sequence, see: Geoghegan, K.; Kelleher, S.; Evans, P. J. Org. Chem.
2011, 76, 2187−2194.
(25) Bartsch, R. A.; Lee, J. G. J. Org. Chem. 1991, 56, 2579−2582.
517
dx.doi.org/10.1021/jo202023w | J. Org. Chem. 2012, 77, 511−518

The Journal of Organic Chemistry
Article
(26) Gilbert, J. C.; Hou, D.-R.; Grimme, J. W. J. Org. Chem. 1999, 64,
1529−1534.
(27) Mehta, G.; Padma, S.; Karra, S. R.; Gopidas, K. R.; Cyr, D. R.;
Das, P. K.; George, M. V. J. Org. Chem. 1989, 54, 1342−1346.
(28) Singh, V. K.; Raju, B. N. S.; Deota, P. T. Synth. Commun. 1988,
18, 567−574.
(29) Valderrama, J. A.; Espinoza, O.; Gonzalez, M. F.; Tapia, R. A.;
́
Rodríguez, J. A.; Theoduloz, C.; Schmeda-Hirschmann, G. Tetrahedron
2006, 62, 2631−2638.
518
dx.doi.org/10.1021/jo202023w | J. Org. Chem. 2012, 77, 511−518