Enantioselective recognition of amines with an atropisomeric 1,8-bisphenolnaphthalene

Article abstract of DOI:10.1016/j.tet.2011.07.001

1,8-Bis[5′(2′-hydroxy-4′-methylbiphenyl)]naphthalene, 2, was prepared from 1,8-dibromonaphthalene and 4-methoxy-2-methylphenylboronic acid in four steps with 51% overall yield. The axially chiral anti-isomer of 2 is stable to racemization at room temperat

Full text of DOI:10.1016/j.tet.2011.07.001

Tetrahedron 67 (2011) 6799e6803
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Tetrahedron
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Enantioselective recognition of amines with an atropisomeric
1,8-bisphenolnaphthalene
*
Marwan W. Ghosn, Christian Wolf
Department of Chemistry, Georgetown University, Washington, DC 20057, USA
a r t i c l e i n f o
a b s t r a c t
1,8-Bis[50(20-hydroxy-40-methylbiphenyl)]naphthalene, 2, was prepared from 1,8-dibromonaphthalene
and 4-methoxy-2-methylphenylboronic acid in four steps with 51% overall yield. The axially chiral
anti-isomer of 2 is stable to racemization at room temperature and the free energy of activation for the
conversion of the anti-isomer to the syn-form was determined as 110.0 kJ/mol at 77.1 ꢀC. At submillimolar
concentration, enantiopure 2 can be used as circular dichroism sensor to detect a wide range of chiral
amines.
Article history:
Received 30 May 2011
Received in revised form 30 June 2011
Accepted 1 July 2011
Available online 6 July 2011
Keywords:
Atropisomers
Ó 2011 Elsevier Ltd. All rights reserved.
1,8-Bisphenolnaphthalenes
Dynamic stereochemistry
Enantioselective recognition
Circular dichroism
1. Introduction
enantiomers (Fig. 1).7 We believe that this finding will have im-
portant implications to chiral ligand development for asymmetric
Although the synthesis of 1,10-binaphthyl-2,20-diol (BINOL) was
first reported in 1873 it took another 100 years until this prime
example of a C2-symmetric bidentate atropisomer gained consid-
erable attention.1 Since the mid 1970s, BINOL and its derivatives
have found extensive use in numerous asymmetric reactions, mo-
lecular recognition studies, and other applications.2 The intriguing
structure of BINOL and its success as a chiral ligand and reagent in
asymmetric synthesis has propelled the development of countless
analogues that vary in stereoelectronic properties and bite angle.
For many years, the synthesis of axially chiral 1,8-
bisphenolnaphthalenes has been pursued due to the apparent
structural analogy to BINOL and the associated promise in asym-
metric catalysis and other areas. However, the incorporation of
sufficient steric bulk into the chiral 1,8-bisphenolnaphthalene
framework to halt rotation about the arylearyl axes and concom-
itant racemization has proven difficult.3 Accordingly, few stereo-
dynamic 1,8-bisphenolnaphthalenes, such as 1, have been reported
to date and used in racemic form.4 Based on our experience with
the synthesis and atropisomerization of chiral biaryls and triaryls5
and 1,8-diheteroarylnaphthalene-derived sensors,6 we recently
found that incorporation of steric bulk proximate to the arylearyl
bonds in axially chiral 1,8-bisphenolnaphthalenes affords isolable
catalysis, recognition, and other fields. We now wish to report the
first example of an application of a conformationally stable, axially
chiral anti-1,8-bisphenolnaphthalene.
2. Results and discussion
The synthesis of 1,8-bis[50(20-hydroxy-40-methylbiphenyl)]
naphthalene, 2, began with the quantitative formation of 1,8-bis(20-
methyl-40-methoxyphenyl)naphthalene, 4, via palladium(0) cata-
lyzed Suzuki coupling of 4-methoxy-2-methylphenylboronic acid,
3, and 1,8-dibromonaphthalene (Scheme 1). The efficiency of this
reaction is quite remarkable as it requires two consecutive Suzuki
couplings and the construction of two sterically crowded arylearyl
bonds. Based on 1H NMR analysis, 4 was produced as a 3:1 mixture
OH
OH
OH OH
OHC
CHO Ph
Ph
1
2
* Corresponding author. Tel.: þ1 202 687 3468; fax: þ1 202 687 6209; e-mail
address: cw27@georgetown.edu (C. Wolf).
Fig. 1. Structures of axially chiral 1,8-bisphenolnaphthalenes.
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.07.001

6800
M.W. Ghosn, C. Wolf / Tetrahedron 67 (2011) 6799e6803
OMe OMe
OMe OMe
1
O
OH
HO
H
OH
HO
Ph
OH
Br Br
I
I
OMe
Ph
Ph
Ph
k1
k2
Ph
Ph
BnNMe3 ICl2
k2
k1
0.8
0.6
0.4
0.2
0
Pd(PPh3)4, K3PO4
>99%
ZnCl2, AcOH
67%
B(OH)2
3
>95 %de
5
4
(anti/syn = 3:1)
(
,
M M
)-isomer
meso form
(P,P)-isomer
Pd(PPh3)4
K3PO4, 87%
PhB(OH)2
OH OH
OMe OMe
Ph
Ph
Ph
Ph
BBr3
89%
time(min)
1200
0
300
600
900
2
anti-
6
anti-
>99 %de
>99 %de
Fig. 2. Change in the mole fractions of (ꢁ)-2 (blue), (þ)-2 (orange) and syn-2 (green)
during heating at 77.1 ꢀC.
Scheme 1. Synthesis of 1,8-bisphenolnaphthalene anti-2.
intramolecular process and the rotational energy barrier is mostly
controlled by steric effects although electronic contributions are
known to play a minor role.8 The syn/anti-ratio of 2 at equilibrium
was determined as 0.46 and the reversible first-order reaction ki-
netics were simulated and analyzed according to Vriens.9 The free
energy of activation for the conversion of the anti-isomer to the
of anti- and syn-isomers. Iodination of the diastereomeric mixture
of 4 with benzyltrimethylammonium dichloroiodate and Suzuki
coupling with phenylboronic acid proceeded with 67% and 87%
yield. The anti-isomers of 1,8-bis(20-methyl-40-methoxy-50-iodo-
phenyl)naphthalene, 5, and 1,8-bis(60-methoxy-40-methyl-30-bi-
phenyl)naphthalene, 6, were isolated in >95% and >99%
diastereomeric excess, respectively. Finally, deprotection of 6 with
boron tribromide furnished the desired 1,8-bisphenolnaphthalene
2 in 89% yield. Overall, this approach furnishes racemic anti-2 in
four steps with 51% overall yield.
We found that the enantiomers and the meso syn-isomer of 2
can be resolved by chiral HPLC on Chiralpak AD (see SD). To avoid
time-consuming preparative HPLC on a chiral column, the suit-
ability of several chiral auxiliaries for large scale separation of
the enantiomers of 2 was examined. We were pleased to find that
syn-intermediate,
77.1 ꢀC. As expected, the Gibbs activation energy for the reversed
process,
Gssyn/anti, is slightly lower and was calculated as
D
Gsanti/syn, was determined as 110.0 kJ/mol at
D
107.7 kJ/mol (see SD). Accordingly, the incorporation of two methyl
groups into the ortho-positions of the triaryl framework of 1, which
rapidly racemizes at room temperature, generates a conformation-
ally stable scaffold that does not show a sign of racemization after
stirring in solution at 20 ꢀC after 24 h.10
Having determined the stability of 2 to rotation about the chiral
axes at room temperature, we decided to investigate the three-
dimensional structure of this atropisomer. A single crystal of anti-
2 was obtained by slow evaporation of a dichloromethane solu-
tion.11 Crystallographic analysis revealed that the two cofacial
phenol rings are almost perfectly aligned. The separation between
esterification of racemic 2 with N-Boc-L-tryptophan generates
dia-stereomeric diester derivatives 7 that can be separated by flash
chromatography on silica gel (Scheme 2). Hydrolysis of the isolated
diastereomers gave quantitative amounts of bisphenol 2 in enan-
tiomerically pure form.
the centroids of the two phenol rings, which are splayed by 19.5ꢀ,
ꢀ
was determined as 3.5 A, indicating substantial
p
-overlap (Fig. 3).
O
O
OH OH
R
Ph
O
O
R
Ph
O
O
Ph
Ph
HN
7
(P,P,S,S)-
O
7
(M,M,S,S)-
OH
N
H
DCC, DMAP, 91%
2
racemic
1. Chromatographic
separation of
diastereomers
Fig. 3. Single crystal structure of anti-2.
2. HCl, then KOH, >99%
O
O
OH OH
The CD spectrum of enantiopure bisphenol 2 undergoes a re-
markable change in the presence of base (Fig. 4). For example,
deprotonation of (þ)-2 results in a dramatic red shift of the nega-
tive Cotton effect at higher wavelength and the corresponding
bisphenolate has a large reversed amplitude at 290 nm. We found
that addition of chiral amines to the bisphenolate regenerates the
original CD spectrum. This proceeds with high stereoselectivity and
therefore allows enantioselective CD sensing of the amine used.
The reciprocity of the chiral recognition process was observed with
different analytes, including 1-phenylethylamine (Fig. 5).
Using the bisphenoxide of (ꢁ)-2 as sensor, we observed that the
negative CD amplitude at 290 nm is more readily regenerated upon
titration with (R)-1-phenylethylamine, (R)-8, than with (S)-8. The
opposite trend was obtained when the bisphenoxide of (þ)-2 was
Ph
HN
R=
Ph
N
H
2
enantiopure
Scheme 2. Resolution of 2 via formation of diastereomeric tryptophan derivatives.
Preparative isolation of the levorotatory enantiomer of 2 en-
abled us to monitor the racemization kinetics at 77.1 ꢀC by chiral
HPLC separation of cooled aliquots (Fig. 2). Interconversion of the
enantiomers of triaryls, such as 2, proceeds via a diastereomeric
meso intermediate and involves two rotations about the pivotal
arylearyl bonds obeying reversible first-order kinetics. This is an

M.W. Ghosn, C. Wolf / Tetrahedron 67 (2011) 6799e6803
6801
mdeg
80
250
(mdeg)
40
125
0
0
mol/L
0.2
0.05
0.1
0.15
0
-40
(nm)
480
240
300
360
420
-80
-125
-250
mdeg
80
40
Fig. 4. CD spectra of dextrorotatory (blue) and levorotatory (orange) enantiomers of 2
(9.45ꢂ10ꢁ5 M, ACN). The dashed lines show the CD spectra upon treatment with
sodium tert-butoxide.
0
0
mol/L
0.004 0.008 0.012 0.016
-40
mdeg
80
-80
Fig. 7. Change in the CD amplitude at 290 nm of the bisphenoxide of (ꢁ)-2 upon
addition of aliphatic amines. Top: (R)-15 (blue) and (S)-15 (red). Bottom: (R,R,R,S)-16
(blue) and (S,S,S,R)-16 (red). The concentration of 2 was 9.45ꢂ10ꢁ5 M in acetonitrile.
40
0
-40
-80
mol/L
0.06
0
0.02
0.04
A (mAU)
2000
mdeg
80
1000
40
mol/L
0.06
0
0
0.02
0.04
RT (min)
0
-40
0
2
4
6
8
10
12
-80
Fig. 8. HPLC chromatogram showing the separation of the stereoisomers of 2.
Fig. 5. Change in the CD amplitude at 290 nm of the bisphenoxides of (ꢁ)-2 (top) and
(þ)-2 (bottom) upon addition of (R)-8 (blue) and (S)-8 (red). The concentration of 2
was 9.45ꢂ10ꢁ5 M in acetonitrile.
room temperature and readily available in enantiopure form.
Crystallographic analysis revealed that 2 has a C2-symmetric
structure suitable for enantioselective interactions with chiral
substrates. The intense CD spectra of the enantiomers of 2 undergo
significant changes upon deprotonation that are reversible when
hydrogen bond donors are added in excess. Titration of the enan-
tiopure bisphenoxide of 2 with a wide range of amines showed that
this process is stereoselective and can be utilized for enantio-
differentiation of aliphatic and aromatic chiral substrates. We be-
lieve that the structural analogy of the C2-symmetric 1,8-
bisphenolnaphthalene framework introduced herein to BINOL
and its derivatives is likely to lead to future applications in chiral
recognition and asymmetric catalysis. These studies are currently
underway in our laboratories.
employed in the same titration experiment. Screening of several
other aromatic and aliphatic amines gave similar results, which
highlights the general usefulness of this enantioselective recogni-
tion approach (Figs. 6 and 7).12
NH2
NH2
NH2
NH2
Ph
Ph
Ph
H2N
NH2 Ph
NH2
NH2
10
11
12
8
9
NH2
NH2
13
14
H2N
4. Experimental section
4.1. Synthetic procedures
15
16
Fig. 6. Structures of amines tested. Only one enantiomer is shown.
All reagents and solvents were used as purchased without fur-
ther purification. All reactions were carried out under nitrogen
atmosphere and anhydrous conditions. Products were purified by
flash chromatography on SiO2 (particle size 0.032e0.063 mm).
NMR spectra were obtained at 400 MHz (1H NMR) and 100 MHz
3. Conclusion
In summary, we have described the synthesis of axially chiral
1,8-bisphenolnaphthalene 2, which is stable to racemization at

6802
M.W. Ghosn, C. Wolf / Tetrahedron 67 (2011) 6799e6803
(
13C NMR) using CDCl3 as solvent. Chemical shifts are reported in
10H), 7.91 (d, J¼8.1 Hz, 2H). 13C NMR:
¼20.3, 115.9, 124.2, 125.0,
d
parts per million relative to TMS.
127.5, 128.6, 128.8, 129.2, 129.9, 130.3, 130.9, 135.3, 135.8, 137.2,
137.8, 139.4, 150.7. Anal. Calcd for C36H28O2: C, 87.78; H, 5.73.
Found: C, 88.04; H, 5.79.
4.1.1. 1,8-Bis(20-methyl-40-methoxyphenyl)naphthalene (4). A solu-
tion of 1,8-dibromonaphthalene, (1.29 g, 4.5 mmol), 2-methyl-4-
methoxyphenylboronic acid, 3, (2.24 g, 13.5 mmol), Pd(PPh3)4
(0.78 g, 0.68 mmol), and K3PO4, (4.30 g, 20.0 mmol) in 50 mL tol-
uene was stirred at 110 ꢀC for 18 h. The resulting mixture was
allowed to come to room temperature, quenched with water and
extracted with CH2Cl2. The combined organic layers were dried
over MgSO4 and concentrated in vacuo. Purification by flash chro-
matography on silica gel (CH2Cl2/hexanes 2:3) afforded 1.66 g
(4.5 mmol, >99%) of off-white crystals containing syn- and anti-
isomers of 4 in a ratio of approximately 1:3.
4.2. Resolution of the enantiomers of 2
The stereoisomers of 2 are separable on a CHIRALPAK AD col-
umn using hexanes/isopropyl alcohol (9:1) as mobile phase
(Fig. 8>/>). The first eluted enantiomer appears at 7.2 min, while the
second elutes at 8.9 min. The syn-intermediate elutes last at
10.5 min. For quantitative analysis, the ratio of the absorption co-
efficients of the diastereomers, aanti/asyn, was determined as 1.43.
To avoid time-consuming preparative chiral HPLC, several chiral
auxiliaries were examined for large scale separation of the enan-
tiomers of 2 through the formation of diastereomers. We were
pleased to find that esterification of racemic 2 with N-Boc-(S)-
tryptophan generates diastereomeric diester derivatives that can be
separated by chromatographic separation. Finally, the di-
astereomers were hydrolyzed to regenerate free bisphenols 2 in
enantiomerically pure form.
1H NMR:
d¼1.76 (s, 4.6H), 1.83 (s, 1.4H), 3.69 (s, 4.4H), 3.71 (s,
1.4H), 6.28e6.39 (m, 4H), 6.66 (d, J¼8.2 Hz, 0.5H), 6.87 (d, J¼8.2 Hz,
1.5H), 7.16 (d, J¼6.8 Hz, 2H), 7.46 (dd, J¼6.8, 8.0 Hz, 2H), 7.89 (d,
J¼8.0 Hz, 2H). 13C NMR:
¼20.9, 21.0, 55.1, 55.2, 109.9, 110.3, 114.3,
d
114.4, 124.8, 125.0, 128.5, 129.0, 130.2, 130.4, 131.0, 131.6, 132.3,
134.8, 134.9, 135.2, 135.4, 136.5, 136.9, 139.5, 157.6, 158.1. Anal. Calcd
for C26H24O2: C, 84.75; H, 6.57. Found: C, 84.74; H, 6.61.
4.1.2. 1,8-Bis(20-methyl-40-methoxy-50-iodophenyl)naphthalene
(5). To a solution of 4 (0.18 g, 0.49 mmol) in 8 mL of acetic acid,
benzyltrimethylammonium dichloroiodate (0.38 g, 1.08 mmol), and
zinc dichloride (0.15 g, 1.08 mmol) dissolved in 8 mL of acetic acid
were added dropwise over 30 min, and the mixture was stirred at
55 ꢀC for 20 h. It was then cooled to 0 ꢀC, carefully quenched with
water and extracted with CH2Cl2. The combined organic layers
were washed with 1 M sodium thiosulfate, dried over MgSO4, and
concentrated in vacuo. Purification by flash chromatography on
silica gel (hexanes/CH2Cl2 3:1) afforded 0.20 g (0.33 mmol, 67%) of 5
as a white solid.
4.2.1. 1,8-Bis(60-N-Boc-(S)-tryptophan-40-methyl-30-biphenyl)naph-
thalene (7). A solution of 6 (0.17 g, 0.35 mmol), N-Boc-(S)-trypto-
phan (0.24 g, 0.77 mmol), N,N0-dicyclohexylcarbodiimide (0.17 g,
0.81 mmol), and DMAP (0.05 g, 0.42 mmol) was stirred in 5 mL of
dichloromethane for 16 h at room temperature. The resulting sus-
pension was directly subjected to gradient flash chromatography
on silica gel (dichloromethane/ethyl acetate 70:1 to 60:1) to afford
0.18 g (0.17 mmol, 49%) and 0.16 g (0.15 mmol, 42%) of the first and
second eluted diastereomers of 7 as white solids.
1H NMR (first eluted isomer):
d
¼1.43 (s, 6H), 1.50 (s, 18H), 3.22
(m, 4H), 4.26 (m, 1H), 5.01 (m, 1H), 5.63 (s, 2H), 6.79 (s, 2H),
1H NMR:
d
¼1.86 (s, 6H), 3.83 (s, 6H), 6.41 (s, 2H), 7.15 (d,
6.97e7.28 (m, 26H), 7.94 (d, J¼8.1 Hz, 2H), 9.33 (s, 2H). 13C NMR:
J¼6.9 Hz, 2H), 7.27 (s, 2H), 7.48 (dd, J¼6.9, 8.1 Hz, 2H), 7.92 (d,
d
¼20.1, 28.3, 54.5, 80.0, 109.8, 111.3, 118.7, 119.5, 121.9, 122.0, 123.3,
J¼8.1 Hz, 2H). 13C NMR:
d
¼20.7, 56.2, 82.0, 111.2, 125.0, 129.0, 130.2,
124.9, 127.0, 127.7, 128.4, 128.7, 121.9, 123.3, 124.9, 127.0, 127.7, 128.7,
129.8, 131.2, 136.2, 137.3, 138.1, 140.5, 145.5, 155.2, 170.9. Anal. Calcd
for C68H64N4O8: C, 76.67; H, 6.06; N, 5.26. Found: C, 76.44; H, 6.16;
N, 5.62.
134.9, 136.8, 137.5, 137.6, 138.3, 156.2. Anal. Calcd for C26H22I2O2: C,
50.35; H, 3.58. Found: C, 50.15; H, 3.52.
4.1.3. 1,8-Bis(60-methoxy-40-methyl-30-biphenyl)naphthalene (6). A
solution of 5 (0.20 g, 0.32 mmol), phenylboronic acid (0.12 g,
0.96 mmol), Pd(PPh3)4 (0.055 g, 0.048 mmol), and K3PO4 (0.31 g,
1.44 mmol) in 5 mL of toluene was stirred at 110 ꢀC for 18 h. The
resulting mixture was allowed to come to room temperature,
quenched with water and extracted with CH2Cl2. The combined or-
ganic layers were dried over MgSO4 and concentrated in vacuo. Puri-
fication by flash chromatography on silica gel (CH2Cl2/hexanes 1:2)
afforded 0.14 g (0.28 mmol, 87%) of 6 as a white solid.
1H NMR (second eluted isomer):
d
¼1.40 (s, 18H), 1.70 (s, 6H),
3.12 (m, 4H), 4.82 (m, 1H), 5.02 (m, 1H), 6.65 (s, 2H), 6.88 (s, 2H),
7.11e7.31 (m, 18H), 7.51 (m, 2H), 7.92 (d, J¼8.2 Hz, 2H), 8.41 (s, 2H).
13C NMR:
d
¼20.1, 28.3, 54.5, 80.0, 109.8, 111.1, 118.7, 119.5, 122.0,
122.9, 123.1, 124.9, 127.3, 127.9, 128.2, 128.8, 130.3, 131.5, 135.2,
136.0, 136.1, 137.2, 138.1, 140.51, 145.7, 155.46, 170.4. Anal. Calcd for
C68H64N4O8: C, 76.67; H, 6.06; N, 5.26. Found: C, 76.43; H, 6.27; N,
5.42.
A suspension of the first eluted diastereomer of 7 (0.040 g,
0.038 mmol) in 3.8 M KOH (10 mL, 4:1 ethanol/water) was stirred
for 3 h at room temperature. The resulting mixture was quenched
with 0.5 mL of concentrated HCl at 0 ꢀC. It was then extracted with
dichloromethane, and the combined organic layers were washed
with brine, dried over MgSO4, and concentrated in vacuo. The crude
mixture was then subjected to flash chromatography on silica gel
1H NMR:
d
¼1.70 (s, 6H), 3.67 (s, 6H), 6.36 (s, 2H), 7.00 (s, 2H),
7.21e7.31 (m, 6H), 7.38 (dd, J¼7.5, 7.7 Hz, 4H), 7.45e7.52 (m, 6H), 7.92
(d, J¼8.2 Hz, 2H). 13C NMR:
¼20.7, 55.5, 125.1, 126.3, 126.5, 127.9,
d
128.6,129.2,130.2,130.6,130.9,134.8,135.3,136.4,138.6,139.1,154.7.
Anal. Calcd for C38H32O2: C, 87.66; H, 6.19. Found: C, 87.42; H, 6.47.
4.1.4. 1,8-Bis(60-hydroxy-40-methyl-30-biphenyl)naphthalene (2). To
using dichloromethane as mobile phase to afford 0.019 g
a
solution of 1,8-bis(20-methyl-40-methoxy-50-phenylphenyl)
(0.038 mmol, 99%) of enantiopure (ꢁ)-2 as a white solid. The same
procedure was used to obtain (þ)-2 from the second eluted di-
astereomer of 7.
naphthalene, 6 (0.14 g, 0.28 mmol) in 10 mL of anhydrous CH2Cl2 at
0
ꢀC, BBr3 (1.67 mL, 1.67 mmol) was added dropwise and the
mixture was stirred for 16 h at room temperature. The reaction was
carefully quenched with isopropyl alcohol followed by addition of
water, and extracted with CH2Cl2. The combined organic layers
were dried over MgSO4 and concentrated in vacuo. Purification by
flash chromatography on silica gel (CH2Cl2) afforded 0.12 g of 2
(0.25 mmol, 89%) as a white solid.
4.3. UV, CD, and Polarimetry
The CD instrument was purged with nitrogen for 20 min.
Spectra were collected at room temperature between 270 and
390 nm with a standard sensitivity of 100 mdeg, a data pitch of
0.5 nm, a band width of 1 nm, a scanning speed of 500 nm sꢁ1 and
a response of 0.5 s using a quartz cuvette (1 cm path length).
1H NMR:
7.25 (d, J¼7.0 Hz, 2H), 7.36 (dd, J¼6.8, 7.2 Hz, 2H), 7.42e7.51 (m,
d¼1.66 (s, 6H), 5.01 (s, 2H), 6.45 (s, 2H), 6.89 (s, 2H),

M.W. Ghosn, C. Wolf / Tetrahedron 67 (2011) 6799e6803
6803
Polarimetric measurements at 21.5 ꢀC allowed for the de-
until the original bisphenol CD spectrum was recovered. Ellipticites
at 290 nm were then plotted against the concentration of added
amine enantiomers.
termination of the specific rotation ½a D
ꢃ
as 354ꢀ for the enantiomer
eluted first from Chiralpak AD, and ꢁ355ꢀ for the more strongly
retained enantiomer (Fig. 9).
Acknowledgements
Abs (AU)
2
This material is based upon work supported by the National
Science Foundation under CHE-0910604.
Supplementary data
1.5
1
Details of kinetic studies, NMR spectra of the products, and CD
analyses. Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tet.2011.07.001.
References and notes
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nm)
0
190
290
390
49 0
mdeg
250
125
0
nm
420
240
300
360
-125
-250
Fig. 9. Top: UV spectrum of 2 (1.02ꢂ10ꢁ3 M, hexanes/IPA 1:1). Bottom: CD spectra of
dextrorotatory (blue) and levorotatory (orange) enantiomers of 2 (9.45ꢂ10ꢁ5 M, ACN).
4.4. Crystallization and X-ray diffraction
Single crystal X-ray analysis was performed at 100 K using
a Siemens platform diffractometer with graphite monochromated
ꢀ
Mo K
a
radiation (
l
¼0.71073 A). Data were integrated and corrected
using the Apex 2 program. The structures were solved by direct
methods and refined with full-matrix least-square analysis using
SHELX-97-2 software. Non-hydrogen atoms were refined with an-
isotropic displacement parameters.
A crystal of 2 was obtained by slow evaporation of a solution of
10.0 mg of 2 in 5 mL of CH2Cl2. Crystal structure data for 2: formula
C36H28O2, M¼492.61, crystal dimensions 0.15ꢂ0.15ꢂ0.15 mm,
7. Ghosn, M.; Wolf, C. J. Org. Chem. 2011, 76, 3888e3897.
8. Dynamic Stereochemistry of Chiral Compounds; Wolf, C., Ed.; RSC: Cambridge,
2008; p 89.
ꢀ
ꢀ
monoclinic, space group P21/c, a¼11.3010 (23) A, b¼11.8081 (24) A,
3
ꢀ
ꢀ
c¼19.1846 (40) A,
b
¼96.897 (3), V¼2541.53 A , Z¼4,
9. Vriens, G. N. Ind. Eng. Chem. 1954, 669e671.
rcalcd¼1.2872 g cmꢁ3
.
10. We note that it is possible that the HPLC method used to monitor the stereo-
chemical integrity of enantiopure 2 could not have detected formation of 1e2%
of the minor enantiomer and the meso intermediate. The isolated enantiomers
of 2 can be stored at room temperature for several months without showing
measurable racemization.
4.5. Enantioselective sensing studies
Prior to each use, the CD instrument was purged with nitrogen
for 20 min. Spectra were collected between 240 and 600 nm with
a standard sensitivity of 100 mdeg, a data pitch of 0.5 nm, a band
width of 0.5 nm, a scanning speed of 1000 nm sꢁ1, and a response of
0.5 s using a quartz cuvette (1 cm path length). The concentration of
11. Crystallographic data (excluding structure factors) for the structures in this
paper have been deposited with the Cambridge Crystallographic Data Center as
supplementary publication CCDC 821187. Copies of the data can be obtained,
free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK,
(fax: þ44-(0)1223-336033 or e-mail: deposit@ccdc.cam.ac.Uk).
12. For CD analysis of amines with chiral metal complexes, see: (a) Nieto, S.; Lynch,
V. M.; Anslyn, E. V.; Kim, H.; Chin, J. Org. Lett. 2008, 10, 5167e5170; (b) Nieto, S.;
Lynch, V. M.; Anslyn, E. V.; Kim, H.; Chin, J. J. Am. Chem. Soc. 2008, 130,
9232e9233; (c) Nieto, S.; Dragna, J. M.; Anslyn, E. V. Chem.dEur. J. 2010, 16,
227e232.
(ꢁ)-2 was 9.45ꢂ10ꢁ5 M in ACN. To 2000
L of (ꢁ)-2, 4 equiv of
m
NatBuO (0.521 M in DMSO) were added to generate the bisphen-
oxide of (ꢁ)-2, which was titrated with several amine substrates