The Nature of meso - And pyro -Borate Precatalysts to the VANOL and VAPOL BOROX Catalysts

Article abstract of DOI:10.1055/s-0034-1378707

The structures of the meso- and pyro-borate esters generated by treatment of the VANOL and VAPOL ligands with triphenylborate have been revisited. These species were previously identified as precatalysts that could be in situ converted into VANOL and VAPOL BOROX catalysts by an imine substrate. The complete assignment of all protons for both the meso- and pyro-borate esters of both ligands was aided by the ¹H NMR spectrum of each generated from pentadeuterophenol. There were significant differences between the chemical shifts for certain protons in the meso- and pyro-borate species in both the VANOL and VAPOL derivatives. Optimized structures for the meso-borates and two different isomers of the pyro-borates were determined by DFT calculations for each ligand. For each ligand the cyclic pyro-borate was found to be lower in energy than the corresponding linear pyro-borate at the B3LYP/6-311+G(d,p) level of theory. The structures of the cyclic pyro-borate esters were more consistent with the observed ¹H NMR chemical shifts than the linear pyro-borates for each ligand and thus the structures of the pyro-borates esters of VANOL and VAPOL have been re-assigned as the cyclic isomers.

Full text of DOI:10.1055/s-0034-1378707

SYNLETT
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©
Georg Thieme Verlag Stuttgart · New York
2015, 26, 1606–1614
1606
letter
Synlett
W. Zhao et al.
Letter
The Nature of meso- and pyro-Borate Precatalysts to the VANOL
and VAPOL BOROX Catalysts
Wenjun Zhao
1
) B(OPh)3
(3 equiv)
solvent
Xiaopeng Yin
Anil K. Gupta
Xin Zhang
OPh
55–80 °C, 1 h
B
Ph
Ph
OH
OH
Ph
Ph
O
O
Ph
Ph
O
O
B
OPh
+
O
2
) 0.1 mm Hg
B
William D. Wulff*
55–80 °C, 0.5 h
OPh
Department of Chemistry, Michigan State University,
East Lansing, MI 48824, USA
wulff@chemistry.msu.edu
VANOL
VAPOL
VANOL meso-borate
VAPOL meso-borate
VANOL pyro-borate
VAPOL pyro-borate
Received: 09.03.2015
Accepted after revision: 07.05.2015
Published online: 09.06.2015
by treating the precatalyst mixture with an imine 4 at room
temperature. The overall yield of the BOROX catalyst 5 can
9
DOI: 10.1055/s-0034-1378707; Art ID: st-2015-b0169-l
be quite high since B(OPh) is not removed under the condi-
3
tions for the generation of the precatalyst. Later it was
found that generation of the precatalyst is not necessary as
the treatment of the VAPOL ligand with imine 4 and
Abstract The structures of the meso- and pyro-borate esters generat-
ed by treatment of the VANOL and VAPOL ligands with triphenylborate
have been revisited. These species were previously identified as precat-
alysts that could be in situ converted into VANOL and VAPOL BOROX
catalysts by an imine substrate. The complete assignment of all protons
for both the meso- and pyro-borate esters of both ligands was aided by
the 1H NMR spectrum of each generated from pentadeuterophenol.
There were significant differences between the chemical shifts for cer-
tain protons in the meso- and pyro-borate species in both the VANOL
and VAPOL derivatives. Optimized structures for the meso-borates and
two different isomers of the pyro-borates were determined by DFT cal-
culations for each ligand. For each ligand the cyclic pyro-borate was
found to be lower in energy than the corresponding linear pyro-borate
B(OPh) leads to the formation of the BOROX catalyst 5 in
3
less than ten minutes at room temperature.7
The ratio of the meso-borate 2 to the pyro-borate 3 var-
ies depending on conditions and can range from 10:1 in fa-
vor of the meso-borate 2 to 1:20 in favor of the pyro-borate
8
3
. Under the conditions indicated in Scheme 1 the ratio is
8
typically ca. 1:4 in favor of 3. Neither species could be ob-
tained in completely pure form by crystallization or by sili-
ca gel chromatography since they are hydrolytically sensi-
at the B3LYP/6-311+G(d,p) level of theory. The structures of the cyclic
8
pyro-borate esters were more consistent with the observed 1H NMR
tive and thus were characterized as mixtures. One of the
chemical shifts than the linear pyro-borates for each ligand and thus the
structures of the pyro-borates esters of VANOL and VAPOL have been
re-assigned as the cyclic isomers.
distinctive NMR handles that can be used to characterize
these compounds is the bay proton on carbon 5 (Scheme 2)
of each of the phenanthrene rings which for VAPOL appears
as a doublet at δ = 9.79 ppm (CDCl ) which is well outside
3
Key words meso- and pyro-borate esters, VANOL and VAPOL ligands,
the range of the normal aromatic protons due to the dia-
magnetic anisotropy present in phenanthrenes. Since the
precatalyst consists of a mixture of meso- and pyro-borates
and since all of the protons in each molecule are aromatic,
analysis of the 1H NMR spectrum was quite challenging.
The assignment of the bay protons to the meso- and pyro-
borates was made by an analysis of the precatalyst mixture
prepared from tris-p-tolyl borate (Scheme 2).8 Under the
conditions shown in Scheme 2, a 1:1.3 mixture of borates
was formed, and the VAPOL ligand was completely con-
sumed. A different ratio of borates 6 and 7 was obtained by
VANOL and VAPOL BOROX Catalysts, imine substrate
We have found that chiral BOROX catalysts derived from
the VAPOL (and VANOL) ligand are effective catalysts for a
number of asymmetric reactions including cis-aziridina-
1
2
tions, trans-aziridinations, heteroatom Diels–Alder reac-
3
4
tions, aza-Cope rearrangements, three-component Ugi re-
5
6
actions, and quinoline reductions. The BOROX catalysts
were originally prepared from a precatalyst which was gen-
erated by heating the VAPOL ligand with three equivalents
of B(OPh) for one hour followed by removing all volatiles at
heating VAPOL with four equivalents of B(O-p-Tol) and one
3
3
1,7
the same temperature at 0.133 mbar (Scheme 1). The pre-
catalyst was previously determined to be a mixture of two
compounds that were identified as the meso-borate 2 and
equivalent of H O in toluene at 80 °C for one hour and then
2
removal of all volatiles at 80 °C for 0.5 hours which gave a
1:8.4 ratio of 6/7. This allowed for a correlation of the two
different methyl protons of the tolyl group with a particular
8
the pyro-borate 3. The BOROX catalyst was then generated
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W. Zhao et al.
Letter
1
2
) B(OPh)3
3 equiv)
solvent
(
OPh
OPh
Ph
Ph
OH
OH
55–80 °C, 1 h
Ph
Ph
O
Ph
Ph
O
O
B
OPh
B
O
B
+
O
) Hg (0.1 mm)
55–80 °C, 0.5 h
(S)-VAPOL (1)
meso-borate 2
pyro-borate 3
–
+
[
H imine]
Ph
N
Ph
Ph
B
C
imine 4 (1 equiv)
B(OPh)3, (3 equiv)
solvent
3
OPh
A
2
4
1
O
B
25 °C
25 °C, 10 min
Ph
Ph
O
4
B
–
O
O
O
B
OPh
VAPOL BOROX catalyst 5
Scheme 1
bay proton. The integration of the bay proton at δ = 9.63
ppm against the tolyl methyl group at δ = 2.50 ppm was
found to be 1:1.8 for 6 (1:1.5 expected), and the integration
of bay proton at δ = 9.35 ppm against the tolyl methyl group
at δ = 2.24 ppm was found to be 1:3.5 for 7 (1:3.0 expected).
High resolution mass spectroscopic analysis of the 1:1.3
5
1) B(O-p-Tol))3
4 equiv)
CH2Cl2
(
Hbay
Hbay
B
O
O
Hbay
B
Ph
Ph
OH
OH
55 °C, 1 h
Ph
Ph
O
O
Ph
Ph
O
O
O
+
O
B
2
) Hg (0.1 mm)
Hbay
Hbay
5
Hbay
55 °C, 0.5 h
(S)-VAPOL (1)
meso-borate 6
1:1.3
pyro-borate 7
Hbay = δ 9.77 ppm
Hbay = δ 9.63 ppm
Hbay = δ 9.35 ppm
Htol = δ 2.50 ppm
Htol = δ 2.24 ppm
m/z calcd for
C47H31BO3: 654.2366
found: 654.2376
m/z calcd for
C54H38B2O5: 788.2905
found: 788.2918
R
O
B
Ph
Ph
O
O
O
B
O
R
pyro-borate 8 (R = H)
pyro-borate 9 (R = Me)
Scheme 2
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mixture of 6/7 revealed two parent ions with an intensity
ratio of 1:1.3, and the calculated mass for each ion matched
that expected for the two borates. There was not any evi-
dence to definitively distinguish between the isomeric
pyro-borates 7 and 9 (or 3 and 8). A tentative assignment of
the pyro-borate as the linear structure 3 rather than the cy-
clic structure 8 was made on the basis of the B NMR spec-
trum. Three coordinate borate esters present a broad ab-
sorption at δ = 16–18 ppm and for a 1:8 mixture of 6/7 this
broad absorption appeared as two equal peaks that were
slightly separated. The linear pyro-borate 3 would be ex-
pected to have two different borons, and the symmetric
cyclic pyro-borate 8 would be expected to have a single bo-
ron. However, since the presence of other borate esters in-
In our original publication all of the protons for the
meso-borate 2 and the pyro-borate 3 were not assigned
8
from the mixture of the two. A subsequent effort to do so
began with a consideration of the 1H NMR spectrum of
1:4.3 mixture of 2/3 (Figure 1). There is at most a trace of
the free VAPOL ligand remaining, and thus essentially all of
11
the VAPOL is incorporated into two C -symmetrical species
2
since both bay protons in each species appears as one dou-
blet rather than two. The other two protons that stand out
from the rest of the aromatic protons are the two doublets
at δ = 6.49 and 6.64 ppm (Figure 1). Based on the chemical
shifts, one possibility for these protons is that they are the
ortho hydrogens in the phenoxy groups in the borate esters
2 and 3. However, while the integration of the absorptions
at δ = 6.49 to that at δ = 9.33 ppm is 4:2 and consistent with
the structure 3, the integration of the absorptions at δ =
6.64 to that at δ = 9.60 ppm is also 4:2 and thus not consis-
tent with structure 2.
cluding B(OPh) could not be rigorously excluded, assign-
3
ment of the pyro-borate ester as the linear isomer 3 on this
basis can only be classified as tentative.
1
Figure 1 H NMR spectrum (CDCl ) of a 1:4.3 mixture of meso-borate 2 to pyro-borate 3
3
1
2
) BH3•SMe2 (1 equiv)
C6H5OH or C6D5OH (1 equiv)
toluene, 100 °C, 1 h
Ph
Ph
OH
OH
Ph
Ph
O
O
B
OC6H5(OC6D5)
) 100 °C, Hg (0.5 mm), 0.5 h
(S)-VAPOL (1)
meso-borate 2
meso/pyro = 17:1 (OC6H5)
meso/pyro = 13:1 (OC6D5)
Scheme 3
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If these are in fact the ortho hydrogens of the phenoxy
groups, then one would have to conclude that the spectral
data would likely be most consistent with a mixture of the
linear and cyclic pyro-borates 3 and 8. This prompted a se-
ries of new NMR experiments that would lead to a com-
plete assignment of all of the protons in the two borate spe-
cies and to the reassignment of the linear pyro-borate spe-
cies 3 as the cyclic pyro-borate 8.
We have found that cleaner formation of the meso-bo-
rate 2 can be achieved by heating VAPOL with one equiva-
lent of BH ·SMe complex and one equivalent of phenol in
3
2
toluene at 100 °C and then removal of all volatiles at the
same temperature under vacuum (Scheme 3).10 This gives a
17:1 mixture of meso-/pyro-borate esters. This greatly sim-
plifies the aromatic region of the 1H NMR spectrum as
shown in Figure 2 (a). To even further simplify the aromatic
1
Figure 2 (a) Top: H NMR spectrum (CDCl ) of meso-borate 2 (meso/pyro = 17:1) prepared from VAPOL as shown in Scheme 3 from C H OH.
3
6
5
1
(
b) Bottom: H NMR spectrum (CDCl ) of meso-borate 2 (meso/pyro = 13:1) prepared from VAPOL as shown in Scheme 3 from C D OH.
3
6
5
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region, the meso-borate 2 was prepared in the same way
but with pentadeuterophenol to remove the three protons
of the phenoxy group from the mix (Figure 2, b). The most
interesting fact emerging from the two spectra in Figure 2
is that the doublet at δ = 6.64 ppm is not from the ortho
proton in the phenoxy group of meso-borate 2. Since it is a
doublet integrating to four protons, it can only be assigned
to the ortho protons of the two phenyl groups in the 2- and
made as the linear isomer 3, both the linear and cyclic
structures 3 and 8 need to be considered going forward.
In contrast to the situation for the meso-borate 2, the
most upfield doublet at δ = 6.49 ppm in the pyro-borate is
lost when the pyro-borate is prepared from C D OH (Fig-
ures 3, a vs. 3, b). From the difference of Figures 3 (a) and
(b), the protons from the phenoxy group in the pyro-borate
can be identified as a doublet at δ = 6.49, triplet at δ = 6.99,
and a triplet at δ = 7.05 ppm. A doublet integrating to four
protons for the ortho hydrogens of the phenyl group in the
pyro-borate can only reside in the multiplet at δ = 7.09–
7.18 (Figure 3, b). Thus it is interesting to note that the
ortho hydrogens of the phenyl and phenoxy groups switch
places in the meso- and pyro-borates. The ortho hydrogens
of the phenyl group move from δ = 6.64 ppm in the meso-
borate to δ = 7.09–7.18 ppm in the pyro-borate.
6
5
2′-positions of the VAPOL ligand. By subtraction of the two
spectra, the protons of the phenoxy group in meso-borate 2
can thus be assigned as a doublet at δ = 7.16 ppm, a triplet
at δ = 7.30 ppm, and a triplet at δ = 7.39 ppm.
The pyro-borate complex of VAPOL could be prepared as
an 8:1 mixture with the meso-borate 2 from BH ·SMe and
3
2
phenol as indicated in Scheme 4. In this case, three equiva-
lents of B(OAr) is freshly prepared by heating three equiva-
3
lents of BH ·SMe and 12 equivalents of phenol at 80 °C for
In contrast, the ortho hydrogens of the phenoxy group
move from δ = 7.16 ppm in the meso-borate to δ = 6.49 in
the pyro-borate.
3
2
one h, and then the volatiles and excess phenol are re-
11
moved at 80 °C under vacuum for 0.5 hours. Then the
VAPOL ligand and one equivalent of water are added and
the mixture heated at 80 °C for one hour, and then the vola-
tiles were removed at 80 °C under vacuum. This procedure
gives an 8:1 mixture of pyro-/meso-borates and the spectra
for this mixture prepared from C H OH and C D OH are
In order to gain some insight into the chemical shifts
observed for the meso- and pyro-borates, energy-mini-
mized structures of VAPOL and its borates were determined
at the B3LYP/6-31G(d) level of theory for VAPOL, the meso-
borate 2, both isomers of the pyro-borates 3 and 8, and the
minimized structures are shown in Figure 4. The lowest-en-
ergy structure in the gas phase for the VAPOL ligand was
found to have a dihedral angle of 81.1° between the two
phenanthrene rings. The crystal structure of five different
forms of VAPOL have been determined, and all have dihe-
dral angles in the range of 73.0–88.5°.12 The first issue of
note is that of the two isomeric pyro-borates, the cyclic
pyro-borate 8 is significantly more stable (5.63 kcal/mol)
than the linear pyro-borate 3. A unique feature among the
6
5
6
5
shown in Figures 3 (a) and (b), respectively. Water is added
since the formation of a B–O–B linkage requires one equiva-
lent of water. Note that when commercial B(OPh) is used to
3
prepare the pyroborate, the addition of water is usually not
necessary since commercial B(OPh) is usually partially hy-
3
drolyzed to the point that the formation of both pyro-bo-
7
rates and BOROX catalysts (Scheme 1) are facile. Since the
original assignment of the pyro-borate was only tentatively
BH3•SMe2 (3 equiv)
C6H5OH or C6D5OH (12 equiv)
OC6H5(OC6D5)
Ph
Ph
O
O
B
O
B
1
2
) toluene, 80 °C, 1 h
) 80 °C, 0.5 mm Hg. 0.5 h
OC6H5(OC6D5)
1) B(OAr)3 (3 equiv)
H2O (1 equiv)
pyro-borate 3
Ph
Ph
OH
OH
toluene 80 °C, 1 h
or
2
) 80 °C, Hg (0.5 mm), 0.5 h
OC6H5(OC6D5)
B
Ph
Ph
O
O
(S)-VAPOL (1)
O
B
OC6H5(OC6D5)
pyro-borate 8
pyro/meso = 8:1
Scheme 4
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1
structures is that the cyclic pyro-borate 8 has an ortho hy-
drogen of each phenoxy group pointing directly at the cen-
tral ring of each of the phenanthrene ring systems. The dis-
tance of d = 4.555 Å is in the range of that expected for a
CH–π interaction as defined by the standard practice of
measuring the distance from the carbon bearing the hydro-
gen to the centroid of the arene ring with which it inter-
Thus the computational and H NMR studies both indi-
cate that the better assignment for the pyro-borate species
is the cyclic structure 8 rather than the linear structure 3.
The 11B NMR spectrum of the 8:1 mixture of pyro-/meso-
borates shown in Figure 3 (a) reveals a broad peak at δ =
16.33 ppm with a smaller shoulder peak at δ = 18.26 ppm
(see Supporting Information). This is not necessarily taken
as evidence that the pyro-borate contains two different bo-
rons since the shoulder peak could be due to the presence
of other unidentified three-coordinate borates. Instead, the
assignment is made as the cyclic pyro-borate 8 on the basis
of all of the other evidence gathered in the present study.
The assignment of all of the protons for the meso-borate 2
and the pyro-borate 8 are presented in Table 1 along with
those for phenol and triphenylborate for comparison. The
ortho hydrogens (H ) of the phenoxy groups in B(OPh) are
13–15
acts.
This would explain the upfield shift of the ortho
hydrogens of the phenoxy hydrogens of the pyro-borate
species (δ = 6.49 ppm) relative to those of the meso-borate 2
(δ = 7.16 ppm) if the pyro-borate existed as the cyclic struc-
ture 8. Neither the linear pyro-borate species 3 nor the
meso-borate 2 have any potential CH–π interactions with
distances less than 5.5 Å.
k
3
1
Figure 3 (a) Top: H NMR spectrum (CDCl ) of pyro-borate 3 or 8 (meso/pyro = 1:8) prepared from VAPOL as shown in Scheme 4 from C H OH.
3
6
5
1
(
b) Bottom: H NMR spectrum (CDCl ) of pyro-borate 3 or 8 (meso/pyro = 1:8) prepared from VAPOL as shown in Scheme 4 from C D OH.
3
6
5
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Table 1 1H NMR Data for VAPOL, VAPOL Borates 2 and 8, Phenol, and Triphenylboratea
e
d
e
d
e
d
OH
c
f
c
c
f
f
k
l
i
h
g
b
i
h
g
b
i
h
g
b
a
a
a
k
l
j
j
j
OPh
O
OH
OH
O
O
O
O
B
B
m
B
O
m
k
l
OB(OPh)2
Ph
Ph
Ph
O
m
k
l
m
1
2
8
VAPOL 1
VAPOL meso-borate 2
VAPOL pyro-borate 8
Phenol
B(OPh)
3
H
H
H
H
H
H
H
H
H
H
H
H
a
9.79
7.72
7.67
7.98
7.72
7.86
7.48
6.72
7.00
7.11
–
9.60
7.37
7.61
7.95
7.72
7.83
7.55
6.64
7.00
7.15
7.16
7.39
7.30
9.33
–
–
b
7.68–7.74
7.68–7.74
8.01
–
–
c
–
–
d
–
–
e(f)
f(e)
g
7.82
–
–
7.88
–
–
7.80
–
–
h
7.09–7.18
7.09–7.18
7.09–7.18
6.49
–
–
i
–
–
j
–
–
k
6.85
7.26
6.95
7.15
7.33
7.11
l
–
7.05
H
m
–
6.99
a
3
CDCl as solvent.
at δ = 7.15 ppm and thus the ortho-phenoxy protons in the
meso-borate 2 at δ = 7.16 ppm are in a ‘normal’ position for
an aryl borate ester. It is the ortho hydrogens of the phe-
noxy groups of the pyro-borate 8 that are anomalous with a
chemical shift of δ = 6.49 ppm and as illustrated in the
structures in Figure 4, and this can be accounted for by the
CH–π interaction with the central ring of the phenanthrene
unit.
With regard to the chemical shift of the ortho hydrogens
of the phenyl group (H ), the chemical shift of Hh in the
h
meso-borate 2 (δ = 6.64 ppm) is very close to those of the
free VAPOL ligand 1 (δ = 6.72 ppm). In contrast, the chemi-
cal shift of H in the pyro-borate 8 is shifted downfield to
h
7.09–7.18 ppm. The two phenyl groups in VAPOL 1 and in
the meso-borate 2 are close to parallel and are within the π–
π stacking distance (3.4–3.6 Å). The phenyl rings are offset
such that the ortho hydrogens of these phenyl groups
1
) B(OAr)3 (3 equiv)
H2O (1 equiv)
toluene, 80 °C, 1 h
OPh
B
Ph
Ph
OH
OH
Ph
Ph
O
O
O
O
Ph
Ph
B
OPh +
O
2
) 80 °C, Hg (0.5 mm),
B
0.5 h
OPh
(S)-VANOL (10)
meso-borate 11
pyro-borate 13
pyro/meso = 2.3–2.5:1
Scheme 5
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to the reassignment of the pyro-borates of both ligands as
the cyclic isomers as opposed the linear isomers. This new
information concerning the structures of the pyro-borates
esters of VANOL and VAPOL shed some light on understand-
ing how the mixtures of meso- and pyro-borates are trans-
formed by the presence of an amine or imine base into
boroxinate (BOROX) catalysts due to the similarity between
the structures of the cyclic pyro-borates and the catalysts
suggesting that the cyclic pyro-borates on the pathway to
the boroxinates and this possibility should serve to stimu-
late experiments to test this possibility.
Acknowledgment
This work was supported by a grant from the National Institute of
General Medical Sciences (GM094478).
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1378707. Included are experimen-
1
11
tal procedures, H NMR and B NMR spectra of compounds 2, 8, 11,
and 13 and pdb files for DFT energy-minimized structures for 1–3, 8,
1
0–13.
S
u
p
p
ortioIgnfmr oaitn
S
u
p
p
o
nrtIo
i
g
f
rm oaitn
Figure 4 B3LYP/6-31G(d) optimized structures for VAPOL, the VAPOL
meso-borate 2, the VAPOL linear pyro-borate 3, and the VAPOL cyclic
pyro-borate 8. The relative energies were calculated at the B3LYP/6-
Primary Data
311+G(d,p) level of theory. The structures are visualized by the Mercury
program (C, gray; O, red; B, pink; H, white).
Primary data for this article are available online at http://www.thieme-
connect.com/products/ejournals/journal/ 10.1055/s-00000083 and can
be cited using the following DOI: 10.4125/pd0067th.
P
m
ri arDy at
P
m
ri arDy at
1
04.1
2
5
p/
d
0
0
6
7
htPmr.i ary
D
at
Z
a
heln
1
0
1
C
h
e
mstiry
should be shielded which is consistent with their upfield
shifts. The phenyl groups H in the pyro-borate complex 8
h
are also nearly parallel at a distance of 3.77 Å and are also
offset. However, these protons are deshielded and appear at
δ = 7.09–7.18 ppm.
References and Notes
(1) (a) Antilla, J. C.; Wulff, W. D. J. Am. Chem. Soc. 1999, 121, 5099.
An investigation of the structures in Figure 4 leads to a
(b) Antilla, J. C.; Wulff, W. D. Angew. Chem. Int. Ed. 2000, 39,
possible explanation of this deshielding of the H protons in
h
4518. (c) Zhang, Y.; Lu, Z.; Wulff, W. D. Synlett 2009, 2715.
(d) Mukherjee, M.; Gupta, A. K.; Lu, Z.; Zhang, Y.; Wulff, W. D.
J. Org. Chem. 2010, 75, 5643. (e) Gupta, A. K.; Mukherjee, M.;
Wulff, W. D. Org. Lett. 2011, 13, 5866. (f) Gupta, A. K.;
Mukherjee, M.; Hu, G.; Wulff, W. D. J. Org. Chem. 2012, 77, 7932.
complex 8. The protons H are within H-bonding distance
h
of O1 of the pyro-borate bridge with an O–H distance of
16
2
.457 Å. This distance is uniquely short for complex 8 as
this distance is ca. 0.5–1.0 Å larger for all other structures.
Such an H-bonding interaction would be expected to lead
to deshielding, and an observed shift of ca. 0.5 ppm relative
to the meso-borate 2 would be consistent with this expec-
tation.
A similar type of NMR and computational analysis was
carried out on the meso- and pyro-borates of VANOL, and
the results essentially mirrored those obtained with the
meso- and pyro-borates of VAPOL. In this way the pyro-bo-
rate of VANOL was reassigned as the cyclic pyro-borate 13
(g) Vetticatt, M. J.; Desai, A. A.; Wulff, W. D. J. Org. Chem. 2013,
78, 5142. (h) Guan, Y.; Lopez-Alberca, M. P.; Lu, Z.; Xhang, Y.;
Desai, A. A.; Patwardhan, A. P.; Dai, Y.; Vetticatt, M. J.; Wulff, W.
D. Chem. Eur. J. 2014, 20, 13894.
(2) (a) Desai, A. A.; Wulff, W. D. J. Am. Chem. Soc. 2010, 132, 13100.
(b) Vetticatt, M. J.; Desai, A. A.; Wulff, W. D. J. Am. Chem. Soc.
2010, 132, 13104.
(
(
(
3) Newman, C. A.; Antilla, J. C.; Chen, P.; Predeus, A. V.; Fielding, L.;
Wulff, W. D. J. Am. Chem. Soc. 2007, 129, 7216.
4) (a) Ren, H.; Wulff, W. D. J. Am. Chem. Soc. 2011, 133, 5656.
(b) Ren, H.; Wulff, W. D. Org. Lett. 2013, 15, 242.
(Scheme 5) rather than its linear isomer. The details of this
5) Zhao, W.; Huang, L.; Guan, Y.; Wulff, W. D. Angew. Chem. Int. Ed.
2014, 53, 3436.
analysis can be found in the Supporting Information.
We have determined the complete assignments of the
(6) Desai, A. A.; Guan, Y.; Odom, A. L.; Majumder, S.; Wulff, W. D.;
1
Vetticatt, M. J. Tetrahedron Lett. 2015, 56, 3481.
H NMR signals for the meso-borates and pyro-borates of
(
7) Hu, G.; Gupta, A. K.; Huang, R. H.; Mukherjee, M.; Wulff, W. D.
the vaulted biaryl ligands VANOL and VAPOL. This spectro-
scopic analysis coupled with computational studies has led
J. Am. Chem. Soc. 2010, 132, 14669.
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1606–1614

1
614
Synlett
W. Zhao et al.
Letter
(8) Zhang, Y.; Desai, A.; Lu, Z.; Hu, G.; Ding, Z.; Wulff, W. D. Chem.
(11) Preparation of pyro-Borate 8 (Procedure B)
Eur. J. 2008, 14, 3785.
9) Hu, G.; Huang, L.; Huang, R. H.; Wulff, W. D. J. Am. Chem. Soc.
To a flame-dried 25 mL Schlenk flask equipped with a stir bar
and flushed with nitrogen was added phenol (113 mg, 1.20
(
2009, 131, 15615.
mmol, 12.00 equiv), dry toluene (2 mL), and BH ·SMe2 (2 M in
3
(
10) Preparation of VAPOL-meso-borate 2 (Procedure A)
To a flame-dried 25 mL Schlenk flask equipped with a stir bar
and flushed with nitrogen was added (R)-VAPOL (1, 54 mg, 0.10
mmol, 1.0 equiv), phenol (9.4 mg, 0.10 mmol, 1.0 equiv), dry
toluene (2 mL), and BH ·SMe (2 M in toluene, 0.10 mmol, 1.0
toluene, 150 μL, 0.300 mmol, 3.00 equiv). The flask was sealed,
and the resulting mixture was stirred at 80 °C for 1 h. The vola-
tiles were then carefully removed via high vacuum and left
under high vacuum at r.t. for 0.5 h yielding a white solid. To this
solid was added VAPOL (54 mg, 0.10 mmol, 1.0 equiv), dry
3
2
equiv). The flask was sealed, and the resulting mixture was
stirred at 100 °C for 1 h. The volatiles were then carefully
removed via high vacuum and left under high vacuum at 100 °C
toluene (2 mL), and H O (1.8 μL, 0.10 mmol, 1.0 equiv). The
mixture was stirred at 80 °C for 1 h. The volatiles were carefully
removed via high vacuum and left under high vacuum at 80 °C
2
for 0.5 h. The residue was dissolved in ca. 0.7 mL CDCl and
for 0.5 h. The residue was then dissolved in ca. 0.7 mL CDCl and
3
3
1
transferred to a quartz NMR tube and was subjected to H NMR
transferred to a quartz NMR tube, and the pyro-borate 8 was
11
1
11
and B NMR analysis. To locate the five aromatic protons in the
phenol moiety in the meso-borate 2, procedure A described
above was repeated with phenol-2,3,4,5,6-d5 (10 mg, 0.10
mmol, 1.0 equiv), and the resultant meso-borate 2 was sub-
subjected to H NMR and B NMR analysis. To locate the five
aromatic protons in the phenol moiety in 8, the procedure B
described above was repeated with phenol-2,3,4,5,6-d5 (120
mg, 1.20 mmol, 12.00 equiv). The ratio of pyro-/meso-borates
with phenol was 8:1 and with the pentadeuterophenol was 8:1.
1
11
jected to H NMR and B NMR analysis. The ratio of meso-
pyro-borates with phenol was 17:1 and with the pentadeu-
/
Spectral Data for 8 (from Phenol, Figure 3, a)
1
terophenol was 13:1.
H NMR (500 MHz, CDCl ): δ = 6.49 (d, 4 H, J = 7.8 Hz), 6.99 (tt, 2
3
Spectral Data for 2 (from Phenol, Figure 2, a)
H, J = 7.2, 1.3 Hz), 7.05 (t, 4 H, J = 7.8 Hz), 7.09–7.18 (m, 10 H),
7.68–7.74 (m, 4 H), 7.80 (s, 2 H), 7.82 (d, 2 H, J = 9.0 Hz), 7.88 (d,
2 H, J = 9.0 Hz), 8.01 (dd, 2 H, J = 7.3, 2.0 Hz), 9.29–9.34 (m, 2 H).
1
H NMR (500 MHz, CDCl ): δ = 6.64 (dd, 4 H, J = 8.3, 1.0 Hz), 7.00
3
(t, 4 H, J = 7.8 Hz), 7.13–7.18 (m, 4 H), 7.30 (tt, 1 H, J = 1.1, 7.5
Hz), 7.35–7.40 (m, 4 H), 7.55 (s, 2 H), 7.61 (ddd, 2 H, J = 7.8, 7.0,
Spectral Data for 8 (from Pentadeuterophenol, Figure 3, b)
1
1
2
.0 Hz), 7.72 (d, 2 H, J = 9.0 Hz), 7.83 (d, 2 H, J = 8.5 Hz), 7.95 (dd,
H, J = 7.8, 1.2 Hz), 9.60 (d, 2 H, J = 8.5 Hz).
H NMR (500 MHz, CDCl ): δ = 7.09–7.18 (m, 10 H), 7.68–7.74
3
(m, 4 H), 7.80 (s, 2 H), 7.81 (d, 2 H, J = 9.0 Hz), 7.88 (d, 2 H, J = 9.0
Hz), 8.01 (dd, 2 H, J = 7.3, 2.0 Hz), 9.29–9.34 (m, 2 H).
(12) Price, C. P.; Matzger, A. J. J. Org. Chem. 2005, 70, 1.
(13) Nishio, M. Tetrahedron 2005, 61, 6923.
(14) Plevin, M. J.; Bryce, D. L.; Boisbouvier, J. Nat. Chem. 2010, 2, 466.
(15) Distances for CH–π interactions are defined as described in ref.
14.
Spectral Data for 2 (from Pentadeuterophenol, Figure 2, b)
1
H NMR (500 MHz, CDCl ): δ = 6.64 (dd, 4 H, J = 8.3, 1.0 Hz), 7.00
3
(
7
(
1
t, 4 H, J = 7.8 Hz), 7.15 (t, 2 H, J = 7.3 Hz), 7.37 (ddd, 2 H, J = 8.7,
.0, 1.4 Hz), 7.55 (s, 2 H), 7.61 (ddd, 2 H, J = 7.8, 7.0, 1.0 Hz), 7.72
d, 2 H, J = 9.0 Hz), 7.83 (d, 2 H, J = 8.5 Hz), 7.95 (dd, 2 H, J = 7.8,
.2 Hz), 9.59 (d, 2 H, J = 8.5 Hz).
(16) Hydrogen Bonding in Organic Synthesis; Pihko, P. M., Ed.; Wiley-
VCH: Weinheim, 2009.
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1606–1614