Special chiral C2-symmetric endo-biarylnorbornane: Synthesis and structure illustration

Article abstract of DOI:10.1002/cjoc.201400162

A highly efficient and practical synthesis for strained special scaffold of chiral endo-biarylnorbornane starting from available norbornadione was achieved with direct stereoselective dehydroxylation of tertiary alcohol as the key step, and the structure was illustrated by X-ray structural analysis. Synthesis for strained special scaffold of chiral endo-biarylnorbornane starting from available norbornadione was achieved with direct stereoselective dehydroxylation of tertiary alcohol as the key step, and the structure was illustrated by X-ray structural analysis. Copyright

Full text of DOI:10.1002/cjoc.201400162

FULL PAPER
DOI: 10.1002/cjoc.201400162
Special Chiral C2-Symmetric endo-Biarylnorbornane:
Synthesis and Structure Illustration
Chonglin Cai, Ruigang Chen, Jun He, Juntao Feng,* and Xing Zhang
Research and Development Center of Biorational Pesticide, Northwest A&F University and Shaanxi Research
Center of Biopesticide Engneering and Technology, YangLing, Shaanxi 712100, China
A highly efficient and practical synthesis for strained special scaffold of chiral endo-biarylnorbornane starting
from available norbornadione was achieved with direct stereoselective dehydroxylation of tertiary alcohol as the
key step, and the structure was illustrated by X-ray structural analysis.
Keywords endo-biarylnorbornane, stereoselective dehydroxylation, synthesis design, X-ray diffraction, chiral
auxiliaries
Introduction
heptane.
Developing novel chiral auxiliaries with special
structure is very important for drug discovery,[1] asym-
metric catalysis[2] and valuable natural product synthe-
sis.[3] In our pursuit in the synthesis of interesting chiral
auxiliaries, norbornane(bicyclo[2,2,1]heptane) frame-
work has aroused our attentions.[4] In fact, the special
scaffold has received constant attention from research-
ers in a range of fields including medicinal chemistry,[5]
peptidomimetics,[6] asymmetric synthesis[7] and organic
synthesis,[8-14] functional material synthesis.[15]
It has been well documented that norbornene, nor-
bornadiene, or norbornanone systems in general show
high exo-facial selectivity in the electrophilic, nucleo-
philic, or cyclic additions, and the explanations to it in-
clude steric effects that the ethano bridge is larger than
the methano bridge, torsional effect that is relieved by
exo attack but increased by endo attack in the transition
state, pyramidalization of the sp2 carbons toward the
endo directions leading to the favored attack on the
convex face of the pyramidalized sp2 carbons and so on.
Since norbornene, norbornadiene, or norbornanone and
their derivatives are versatile synthetic building blocks
for further skeletal conversions, the high exo selectivity
has been applied to development of a variety of useful
stereospecific or stereoselective reactions in synthesis of
exo-facial selective compounds,[8] while for the synthe-
sis and structure illustration of endo-facial substituted
strained norbornane, there are seldom reports about it.
In our previous work, we have synthesized the novel
norbornane based bicyclo[2,2,1]heptane-endo,endo-2,5-
diol[16] and in this work we will report the sythesis of
more strained structure endo,endo-biarylbicyclo[2,2,1]-
Experimental
General methods
2,5-Norbornadione 1 is prepared by the methods re-
ported.[17,18] All solvents and reagents were purified by
standard techniques. Crude products were purified by
column chromatography on silica gel of 200 meshes.
Optical rotations were obtained on Jasco Dip 360 digital
1
polarimeter. H and 13C NMR spectra were recorded on
a Brucker Avance 600. Chemical shifts are reported in
parts per million with respect to internal TMS. HRMS
spectra were recorded on Ser# microOTOF-QII10280
mass spectrometers. Mass spectra were recorded on
Thermo Fannigan Polaris Q Mass spectrometers oper-
ating at a direct inlet system or GC/MS. X-ray crystal-
lographic data were analyzed through Bruker AXS
GMBH SMART APEX II X-ray diffractometer. A sin-
gle crystal of 5 was obtained by the slow evaporation
from solution of n-hexane.
Preparation of (1R,2R,4R,5R)-exo,exo-2,5-di(2-meth-
oxy)phenylbicyclo[2,2,1]heptane-endo,endo-2,5-diol
(4)
A 50 mL three-neck round-bottom flask under N2 gas
equipped with magnetic stirrer and thermometer was
charged with dry THF (5 mL) and magnesium powder
(1.4 g, 57.6 mmol). Under stirring, ortho-bromoanisole
(9 g, 48 mmol) in THF (15 mL) was added carefully at a
rate sufficient to maintain a gentle reflux, then the reac-
tion was continued to reflux for 1 h and cooled to r.t. To
the solution was added dione 1 (1.5 g, 12 mmol) in THF
(5 mL) at r.t., then the reaction was refluxed at 60 ℃
*
E-mail: fengjt@nwsuaf.edu.cn
Received March 26, 2014; accepted June 17, 2014; published online July 3, 2014.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201400162 or from the author.
Chin. J. Chem. 2014, 32, 645—649
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
645

Cai et al.
FULL PAPER
for 2 h. After cooling to r.t., cold sat. NH4Cl (20 mL)
was added carefully. The mixture was stirred for 10 min,
the aqueous layer was extracted with Et2O (15 mL×4).
The combined organic layers were dried (MgSO4) and
the solvent was removed under reduced pressure. The
residue was purified by column chromatography on sil-
ica (hexanes∶EtOAc＝1∶1, V∶V), bis-tertiary alco-
hol 4 was afforded. Yield 3.35 g (81%); white crystals;
moved and the stirring was continued for an additional
24 h. The reaction was quenched with cold water (18
mL), and dichloromethane was removed under reduced
pressure. The aqueous solution was neutralized by addi-
tion of aqueous NaOH, and then extracted with di-
chloromethane (20 mL×4). The organic layer was
washed with brine, and dried over Na2SO4. After re-
moving the solvent, the residue was purified by a short
column chromatography on silica (hexanes∶EtOAc＝
3∶1, V∶V) to give bisphenol 6. Yield: 0.86 g (95%);
white crystals; m.p. 152－155 ℃; [α]2D0 ＋32 (c 1.00,
MeOH); 1H NMR (600 MHz, MeOD) δ: 6.59－6.94 (m,
8H, Ph-H), 4.79 (s, 2H, 2Ar-OH), 3.25 (s, 2H, 2Ar-C-H),
2.66 (s, 2H, 2 bridgehead), 1.69 (s, 2H, bridge), 1.43－
1.54 (m, 4H, 2CH2); 13C NMR (150 MHz, MeOD) δ:
156.06 (Ar), 128.40 (Ar), 128.28 (Ar), 126.18 (Ar),
118.20 (Ar), 114.39 (Ar), 41.94 (Ar-CH), 40.08
(bridgehead), 29.31 (bridge), 25.36 (CH2); EIMS m/z:
280 [M]＋; HRMS (TOF ESI) calcd for C19H20O2 [M＋
Na]＋ 303.1356, found 303.1361.
1
m.p. 140－142 ℃; [α]2D0 ＋36 (c 1.00, MeOH); H
NMR (600 MHz, CDCl3) δ: 6.92－7.31 (m, 8H, ArH),
4.21 (s, 2H, 2 bridgehead), 3.93 (s, 6H, 2OCH3), 2.76－
2.78 (m, 2H, endo-CH2), 2.73 (s, 2H, 2OH), 2.11－2.17
(m, 2H, exo-CH2), 1.64 (s, 2H, bridge); 13C NMR (150
MHz, CDCl3) δ: 157.20 (Ar), 136.01 (Ar), 127.93 (Ar),
125.00 (Ar), 120.48 (Ar), 111.43 (Ar), 78.86 (Ar-C-OH),
55.33 (Ar-OCH3), 45.99 (bridgehead), 39.27 (CH2),
37.90 (bridge); EIMS m/z: 339 [M−1]＋; HRMS (TOF
ESI) calcd for C21H24O4 [M＋Na]＋ 363.1567, found
363.1572.
Preparation of (1R,2R,4R,5R)-endo,endo-2,5-di(2-
methoxy)phenylbicyclo[2,2,1]heptane (5)
Preparation of (1R,2R,4R,5R)-exo,exo-2,5-meth-
oxy)naphthylbicyclo[2,2,1]heptane-endo,endo-2,5-
diol (10)
To a stainless autoclave with polytef liner equipped
with magnetic stirrer was added bis-tertiary alcohol 4 (1
g, 2.94 mmol), Pd-C (10%, 200 mg), dry ethanol (120
mL) and 8 drops of 70% aqueous HClO4. The autoclave
was purged three times with H2 and the pressure was set
to 2 atm, and dehydroxylation was performed at room
temperature for 24 h. After carefully releasing the H2,
the reaction mixture was neutralized with solid Na2CO3
and filtrated. The solvent was removed under reduced
pressure. The crude product thus acquired was purified
by a short column chromatography on silica (hexane∶
dichloromethane＝3∶1, V∶V) to give biarylnorbor-
nane as a mixture of two isomers, of which, 95.24% was
endo-biarylnorbornane 5. Through recrystallization
from hexane, pure endo-biarylnorbornane 5 was af-
forded. Yield 0.6 g (67%); white crystals; m.p. 123－
To a 250 mL round-bottom flask equipped with
magnetic stirrer under N2 gas was added 1-bromo-2-
methoxynaphthalene (7.11 g, 30 mmol) and dry THF
(70 mL), then 13.3 mL n-butyl lithium (2.27 mol/L in
hexane) was added with stirring at −78 ℃. After the
mixture was stirred for 30 min at −78 ℃, 2, 5-nor-
bornadione 1 (1 g, 8 mmol) was added and the stirring
was continued over night while the temperature was
slowly raised to r.t. The reaction was poured into cold
sat. NH4Cl (70 mL), and then extracted with Et2O (60
mL×4). The organic layer was washed with brine, and
dried over Na2SO4. After removing the solvent, the
residue was treated by column chromatography on silica
(hexanes∶EtOAc＝3∶1, V∶V), two chromatographic
bands were acquired and GC-MS showed that each of
the two bands probably contained two isomers, total
four isomers were 1.65 g (yield 47%). EIMS m/z: 440
[M]＋ or 438 [M−2H]＋
1
125 ℃; [α]2D0 ＋39 (c 1.00, MeOH); H NMR (600
MHz, CDCl3) δ: 6.83－7.24 (m, 8H, ArH), 3.80 (s, 6H,
2OCH3), 3.37 (s, 2H, Ar-C-H), 2.72 (s, 2H, 2 bridge-
head), 2.73 (s, 2H, 2OH), 1.80 (s, 2H, bridge), 1.65－
1.70 (m, 2H, endo-CH2), 1.50－1.55 (m, 2H, exo-CH2);
13C NMR (150 MHz, CDCl3) δ: 158.61 (Ar), 130.83
(Ar), 128.56 (Ar), 126.65 (Ar), 119.67 (Ar), 110.15 (Ar),
55.17 (Ar-OCH3), 42.53 (bridge), 42.22 (Ar-CH), 41.11
(bridgehead), 26.07 (CH2); EIMS m/z: 308 [M] ＋ ;
HRMS (TOF ESI) calcd for C21H24O2 [M ＋Na] ＋
331.1669, found 331.1659.
Preparation of (1R,2R,4R,5R)-exo,exo-2,5-dinaph-
thylbicyclo[2,2,1]heptane-endo,endo-2,5-diol (12)
12 was prepared according to the procedure given
for compound 10. Yield 62%; white crystals; m.p. 154
1
－56 ℃; [α]2D0 ＋42 (c 1.00, MeOH); H NMR (600
MHz, THF-d8) δ: 5.52－7.07 (m, 14H, napth-H), 1.37－
1.40 (d, J＝15 Hz, 2H, 2 bridgehead), 1.16－1.17 (s, 2H,
bridge), 0.44－0.47 (m, 4H, 2CH2); 13C NMR (150
MHz, THF-d8) δ: 142.88 (Ar), 133.60 (Ar), 130.13 (Ar),
126.80 (Ar), 126.48 (Ar), 125.60 (Ar), 122.97 (Ar),
122.58 (Ar), 122.32 (Ar), 119.34 (Ar), 77.37 (Ar-C-OH),
45.73 (bridgehead), 38.86 (CH2), 36.44 (bridge); EIMS
m/z: 380 [M]＋; HRMS (TOF ESI) calcd for C27H24O2
[M＋Na]＋ 403.1669, found 403.1674.
Preparation of (1R,2R,4R,5R)-endo,endo-2,5-di(2-
hydroxy)phenylbicyclo[2, 2, 1]heptane (6)
To a 50 mL round-bottom flask under N2 gas
equipped with magnetic stirrer was added endo-biaryl-
norbornane 5 (1 g, 3.25 mmol) and 18 mL dry di-
chloromethane, then BBr3 (1.2 mL, 12 mmol) was
added with stirring at −78 ℃. After the mixture was
stirred for 30 min at −78 ℃, the cooling bath was re-
646
www.cjc.wiley-vch.de
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2014, 32, 645—649

Special Chiral C2-Symmetric endo-Biarylnorbornane: Synthesis and Structure Illustration
Preparation of (1R,2R,4R,5R)-endo,endo-2,5-di(2-
methoxy)naphthylbicyclo[2,2,1]heptane (11)
the result showed that the bis-tertiary alcohol 4 was
completely converted to a pure product diene 3. But
only after 2 h of drying with anhydtate Na2SO4, GC-MS
showed one side-product with m/z 324 [M]＋ appeared,
we speculate that the structure of the side-product may
be like 9, but we failed to separate it out and character-
ize it.
11 was prepared according to the procedure given
for compound 5. Starting material was bis-tertiary alco-
hol 10 (mixture of four isomers: 1 g, 2.27 mmol). Prod-
ucts were treated by column chromatography on silica
(hexane∶dichloromethane＝3∶1, V∶V), two chro-
matographic bands were acquired and GC-MS showed
that each of the two bands probably contained two iso-
mers, total four isomers were 0.38 g (yield 41%). EIMS
m/z: 408 [M]＋.
Scheme 2 Synthesis of the chiral endo-biphenylnorbornane 5
through dehydration reaction and hydrogenation
O
OMe
MeOPhMgBr
THF, reflux
Preparation of (1R,2R,4R,5R)-endo,endo-2,5-dinaph-
thylbicyclo[2,2,1]heptane (13)
O
1
MeO
OH
(1R,4R)
13 was prepared according to the procedure given
for compound 5. Yield 19%; white crystals; m.p. 134－
OH
4
MeO
1
136 ℃; [α]2D0 ＋41 (c 1.00, MeOH); H NMR (600
MHz, CDCl3) δ: 7.41－8.12 (m, 14H, ArH), 3.96－4.00
(s, 2H, Ar-CH), 2.95 (s, 2H, bridgehead), 2.11 (s, 2H,
bridge), 1.80－1.90 (m, 4H, 2CH2); 13C NMR (150
MHz, CDCl3) δ: 137.60 (Ar), 134.17 (Ar), 133.18 (Ar),
128.89 (Ar), 126.81 (Ar), 125.50 (Ar), 125.26 (Ar),
124.98 (Ar), 124.68 (Ar), 124.45 (Ar), 44.54 (Ar-C),
43.03 (bridge), 42.86 (bridgehead), 26.62 (CH2); EIMS
m/z: 348 [M]＋; HRMS (TOF ESI) calcd for C27H24 [M
＋Na]＋ 371.1770, found 371.1778.
(MeSO2)2O, Et3N
r.t.
H2
Pd/C
MeO
3
unstable
OH
OMe
OMe
MeO
MeO
9
5
side-product
(1R,2R,4R,5R)
Results and Discussion
As scheme 1 showed, our initial synthetic approach
designed toward diphenylbicyclo[2,2,1] 5 was started
from the known chiral 2,5-norbornadione 1.[17-20] But
although the dienolization with KHMDS followed by
treatment with PhNTf2 gave a satisfactory yield of bis-
triflate 2, Pd(0)-catalyzed coupling of 2 with Grignard
reagent[17,19] for diene 3 was unsuccessful.
Since diene 3 is too sensitive to be present after
chromatography over silica, we intended to carry on
hydrogenation with Pd on charcoal at once when the
immediate dehydration product which contained diene 3
was quickly washed by 10% aqueous HCl to remove
residual triethylamine, the result was still only trace of
endo-biarylnorbornane 5 afforded.
Efforts to synthesize the endo-biarylnorbornane 5
from diol 7[16] through nucleophilic substitution to
p-toluenesulfonate 8 with 2-methoxyphenyl lithium at
different temperature within −78 ℃ to 0 ℃ was also
unsuccessful (Scheme 3).
Scheme 1 Synthesis of the chiral endo-biphenylnorbornane 5
through coupling reaction
O KHMDS, PhNTf2
-78 °C
OTf
MeOPhMgBr
PdCl2(dppf)
TfO
Scheme 3 Synthesis of the chiral endo-biphenylnorbornane 5
through nucleophilic substitution to p-toluenesulfonate
2
1
O
(1R,4R)
OMe
MeO
OMe
OMe
MeO
H2
OTs
OH
Li
-78 °C to 0 °C
Pd/C
TsO
TosCl
HO
3
5
unstable
8
7
(1R,2R,4R,5R)
OMe
As Scheme 2 showed, an alternative effort was made
to synthesize biarylnorbornane 5 through the reaction of
aryl Grignard reagents with dione 1, then dehydration of
bis-tertiary alcohol 4 with methanesulfonate anhydride
and triethylamine at room temperature to afford diene 3.
In the dehydration reaction, we found diene 3 is a struc-
ture with high instability. After 30 min of dehydration
reaction, we tested the product immediately by GC-MS,
MeO
5
(1R,2R,4R,5R)
At last we try to reach endo-biarylnorbornane 5
Chin. J. Chem. 2014, 32, 645—649
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
647

Cai et al.
FULL PAPER
through direct dehydroxylation of the bis-tertiary alco-
hol 4 on the condition of hydrogenation with Pd on
charcoal and HClO4 as catalysis[21] and fortunately it
was successful (Scheme 4), endo-biarylnorbornane 5
was afforded with a considerably high yield of 67%. At
first it was not certain that biarylnorbornane 5 acquired
by the methods was endo-conformation though we be-
lieve the product through hydrogenation of diene 3 with
Pd on charcoal is.[19,20] So the product was mixed with
that from hydrogenation of diene 3 and subjected to
GC-MS. The test showed the two products had same
conformation. Our explanation to the phenomenon is
that tertiary alcohol reacts with HClO4 to form carboca-
tion intermediate that is plannar because of its sp2 hy-
dridization, which makes hydrogen attack the carboca-
tion at C2 or C5 to give saturated norbornane with high
exo-selectivity so that Ar-C5 or Ar-C2 will form a bond
with endo-direction. The endo-biarylnorbornane 5 was
subjected to X-ray structural analysis, and the result is
shown in Figure 1 and Table 1.
Table 1 X-ray crystallographic data of the chiral endo-biaryl-
norbornane 5
Subject
Formula
Data
C21H24O2
Monoclinic
P2(1)
Crystal system
Space group
Cell length/nm
Cell angle/(°)
Cell volume/nm3
Z
a 1.0203(8), b 0.7485(6), c 1.1343(10)
α 90.00, β 106.886(13), γ 90.00
0.82891
2
μ/mm−1
0.078
CCDC depository no. 993604
As Scheme 5 showed, we also synthesized bis-
tertiary alcohols 10 and 12 with yields of 47% and 62%
respectively through the reaction of aryllithium with
dione 1, and endo-biarylnorbornanes 11 and 13 were
afforded with yields of 41% and 19% by direct
dehydroxylation of bis-tertiary alcohols 10 and 12. Both
the bis-tertiary alcohol 10 and endo-biarylnorbornane 11
acquired were probably the mixture of four conforma-
tional isomers. Comparing with the bis-tertiary alcohols
4, 12, and endo-biarylnorbornanes 5, 13 with only one
conformation, we can infer that the steric effects of
ethano bridge and methano bridge can not stop the free
rotation of benzene ring which attaches to C2 and C5 of
norbornane, but once the benzene ring is joined to
Scheme 4 Synthesis of the chiral endo-biphenylnorbornane 5
through direct dehydroxylation of the bis-tertiary alcohol
OMe
HClO4, Pd/C
H2
MeO
OH
OH
4
OMe
OH
Scheme 5 Synthesis of the chiral binaphthylnorbornane skele-
ton
HO
MeO
BBr3
5
6
Ar-Br
(1R,2R,4R,5R)
(1R,2R,4R,5R)
Ar
OH
O
Ar
HO
H2
Ar-Li
Ar
11 or 13
Pd/C, HClO4
1
O
Ar
10 or 12
OMe
(1R,2R)
10, 11:
Ar =
Ar =
12, 13:
MeO
OMe
OH
OMe
OMe
OH
10
(four isomers)
Figure 1 X-ray crystal structure of the chiral endo-biarylnor-
bornane 5.
11
(four isomers)
Demethylating endo-biarylnorbornane 5 by BBr3,
bisphenol 6 was afforded with a yield of 95%. The
bisphenol 6 is a very stable structure, when it was dis-
solved in toluene and refluxed violently for 8 h, the re-
salt showed it have no loss in weight and no change in
structure and specific rotation.
OH
OH
13
12
(one isomer)
(one isomer)
648
www.cjc.wiley-vch.de
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2014, 32, 645—649

Special Chiral C2-Symmetric endo-Biarylnorbornane: Synthesis and Structure Illustration
Ganji, P.; Ibrahim, H. J. Org. Chem. 2012, 77, 511; (c) Šala, M.;
ortho-substituting group like methoxy group, the
rotation will be stopped by ethano bridge and methano
bridge. For instance, the methano bridge of bis-tertiary
alcohol 10 may prevent the methoxy group and benzo
group on the benzene ring from passing by so that each
2-methoxy-naphthyl group can be attached to C2 or C5
with two conformations and two 2-methoxy-naphthyl
group will be sure to give four conformational isomers.
Due to the same reasons, the endo-biarylnorbornane 11
also has four conformational isomers. While for
compounds 4, 12, 5 and 13 with only one ortho-
substituting group being joined to the benzene, the other
side of the benzene ring still can rotate to pass by the
ethano and methano bridge, so that these compounds
have only one isomer.
Hřebabecky, H.; Dračínský, M.; Masojı, M.; Palmab, A. M.; Neyts,
J.; Holy, A. Tetrahedron 2009, 65, 9291; (d) Kentaro, K. O.; Muna-
kata, K.; Tsubota, T.; Kanto, M.; Nagahora, K. S. K.; Yokomori, Y.
Tetrahedron 2012, 68, 6211; (e) Hrebabeck, H.; Dejmek, M.; Salaa,
M.; Kaiserov, H. M.; Dracínsk, M.; Leyssenb, P.; Johan, N. J.;
Nencka, R. Tetrahedron 2012, 68, 3195; (f) Sun, M.; Ma, Y.-N.; Li,
Y.-M.; Tian, Q.-P.; Yang, S.-D. Tetrahedron Lett. 2013, 54, 5091; (g)
Šala, M.; Palma, A. M.; Hřebabecky, H.; Nencka, R.; Dračinský, M.;
Pieter, L. P.; Neyts, J.; Holy, A. Bioorg. Med. Chem. 2010, 18, 4374;
(h) Šala, M.; Hřebabecký, H.; Leyssen, P.; Dejmek, M.; Dračinský,
M.; Palma, A. M.; Neyts, J.; Nencka, R. Bioorg. Med. Chem. Lett.
2012, 22, 1963.
[6] (a) Cremonesi, G.; Piero, D. P.; Forni, A.; Rosa, C. L. Tetrahedron
2013, 69, 1175; (b) Hackenberger, P. R.; Schiffers, I.; Runsink, J.;
Bolm, C. J. Org. Chem. 2004, 69, 739.
[7] (a) Sajid, M.; Kehr, G.; Wiegand, T.; Eckert, H.; Schwickert, C.;
Pöttgen, R.; Cardenas, A. J.; Warren, T. H.; Fröhlich, R.; Daniliuc, C.
G.; Erker, G. J. Am. Chem. Soc. 2013, 135, 8882; (b) Poo, M. L.;
Barcina, J. O.; Martínez, A.; Expósito, M.; Vega, J. F.; Salazar, J. M.;
Reyes, M. L. Macromolecules 2006, 39, 7479; (c) Berkessel, A.;
Schröder, M.; Sklorz, C. A.; Tabanella, S.; Vogl, N.; Lex, J.;
Neudörfl, J. M. J. Org. Chem. 2004, 69, 3050; (d) Berkessel, A.;
Menche, D.; Sklorz, C. A.; Schrder, M.; Paterson, I. Angew. Chem.,
Int. Ed. 2003, 42, 1032; (e) Vandyck, K.; Matthys, B.; Willen, M.;
Robeyns, K.; Meervelt, L. V.; Eycken, J. V. Org. Lett. 2006, 8, 363.
[8] Niwayama, S.; Cho, H.-J.; Masoud, M. Z.; Whittlesey, B. R. J. Org.
Chem. 2010, 75, 3775.
Conclusions
In summary, we describe a highly efficient and prac-
tical synthesis for strained special scaffold of chiral
endo-biarylnorbornane starting from available norborna-
dione. The structure of the product was illustrated by
X-ray structural analysis. It is expected that these novel
C2-symmetric scaffold will find many applications in
the fields such as asymmetric catalysis, medicinal
chemistry and functional material synthesis. Also the
stereoselective preparation of saturated alkane used in
the paper by direct dehydroxation of tertiary alcohol
may give a valuable reference for the synthesis of other
chemicals.
[9] Martínez, A. G.; Vilar, E. T.; Fraile, A. G.; Cerero, S.; Morillo, C.
Tetrahedron Lett. 2011, 52, 1762.
[10] Sevov, C. S.; Hartwig, J. F. J. Am. Chem. Soc. 2013, 135, 2116.
[11] Ho, F.; Li, Y.-X.; Mathey, F. Organometallics 2012, 31, 8456.
[12] Darvatkar, N. B.; Wankhede, K. S.; Bhilare, S. V.; Deorukhkar, A. R.;
Raut, D. G.; Vaidya, V. V.; Trivedi, G. K.; Salunkhe, M. M. J.
Heterocycl. Chem. 2010, 47, 1004.
[13] Squire, S.; Sutti, A.; Durand, G.; Conlan, X. A.; Henderson, L. C.
New J. Chem. 2013, 37, 1895.
[14] Clinet, A.; Chaignaud, M.; Clinet, J.-C.; Dunach, E. Flavour Fragr.
J. 2013, 28, 53.
[15] (a) Noelia, C.-M.; Heras, M. R. C.; Blázquez, M. M.; Barcina, J. O.;
Martı´nez, A. G.; Salvador, M. R. T. Org. Lett. 2007, 9, 2943; (b)
Chou, T.-C.; Hwa, C. L.; Lin, J. J.; Liao, K. C.; Tseng, J. C. J. Org.
Chem. 2005, 70, 9717; (c) Barcina, J. O.; Heras, M. R. C.; Mba, M.;
Aspe, R. G.; Noelia, H.-G. J. Org. Chem. 2009, 74, 7148.
[16] Cai, C. L.; Xia, C. G. Synthesis 2006, 14, 2297.
Acknowledgement
This work was supported by National Natural Sci-
ence Foundation of China (Nos. 30971934, 31272074).
References
[1] (a) Zhang, C.; Liu, H.-R.; Qing, Y. Q.; Chang, J.; Sun, X. Chin. J.
Chem. 2013, 31, 154; (b) Sun, W.; Tian, L.-J.; Qi, H.; Jiang, D.;
Wang, Y.; Li, S.; Xiao, J.-H.; Yang, X.-H. Chin. J. Chem. 2013, 31,
1144.
[17] Hayashi, T.; Ueyama, K.; Tokunnaga, N.; Yoshida, K. J. Am. Chem.
Soc. 2003, 125, 11508.
[2] (a) Zhang, R.; Wang, D.; Xu, Q.; Jiang, J.-J.; Shi, M. Chin. J. Chem.
2012, 30, 1295; (b) Qian, H.-Y.; Yan, S.-H.; Cui, X.-L.; Pi, C.; Liu,
C.; Wu, Y.-J. Chin. J. Chem. 2013, 31, 992.
[18] Weissfloch, A.; Azerad, R. Bioorg. Med. Chem. 1994, 2, 493.
[19] Vandyck, K.; Matthys, B.; Willen, M.; Robeyns, K.; Meervelt, L. V.;
Eycken, J. V. Org. Lett. 2006, 8, 363.
[3] (a) Song, Z.-J.; Shi, Y.; Jin, R.-H.; Lin, J.-R.; Tian, W.-S. Chin. J.
Chem. 2012, 30, 2595; (b) Nie, L.; Yang, R.; Zhang, C.-H.; Yin,
H.-C.; Yan, S.-G.; Lin, J. Chin. J. Chem. 2012, 30, 460.
[4] Lowe, A. J.; Long, B. M.; Pfeffer, F. M. Chem. Commun. 2013, 49,
3376.
[20] (a) Fletcher, S. R.; Baker, R.; Chambers, M. S.; Hobbs, S. C.;
Mitchell, P. J. J. Chem. Soc., Chem. Commun. 1993, 1216; (b)
Fletcher, S. R.; Baker, R.; Chambers, M. S.; Herbert, R. H.; Hobbs,
S. C.; Thomas, S. R.; Verrier, H. M.; Watt, A. P.; Ball, R. G.. J. Org.
Chem. 1994, 59, 1771.
[5] (a) Luethi, E.; Nguyen, K. T.; Bürzle, M.; Blum, L. C.; Suzuki, Y.;
Hediger, M.; Reymond, J. L. J. Med. Chem. 2010, 53, 7236; (b)
[21] Sitaram, P.; Jayanta, K. M.; Usha, R. G. J. Org. Chem. 1994, 59,
2687.
(Pan, B.; Qin, X.)
Chin. J. Chem. 2014, 32, 645—649
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
649