Axial Chirality at the Boron-Carbon Bond: Synthesis, Stereodynamic Analysis, and Atropisomeric Resolution of 6-Aryl-5,6-dihydrodibenzo[ c,e][1,2]azaborinines

Article abstract of DOI:10.1021/acs.joc.9b01550

6-Aryl-5,6-dihydrodibenzo[c,e][1,2]azaborinines display restricted rotation at the boron-carbon aryl bond, yielding conformational isomers or atropisomers. The stereodynamic processes were monitored by variable-temperature NMR (D-NMR), dynamic enantioselective HPLC (D-HPLC), or kinetic racemization measurements. The absolute configuration of stable atropisomers (compound 1d, ΔG_rac = 26.0 kcal·mol^-1) was determined by TD-DFT simulation of the electronic circular dichroism (ECD) spectra. The racemization energy of 1d is more than 12 kcal·mol^-1 smaller than its isostere 9-(2-methylnaphthalen-1-yl)phenanthrene.

Full text of DOI:10.1021/acs.joc.9b01550

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Featured Article
Axial Chirality at The Boron-Carbon Bond: Synthesis,
Stereodynamic Analysis and Atropisomeric Resolution
of 6-Aryl-5,6-dihydrodibenzo-[c,e]-[1,2]-azaborinines.
Andrea Mazzanti, Maria Boffa, Emanuela Marotta, and Michele Mancinelli
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01550 • Publication Date (Web): 19 Jul 2019
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HOMO-LUMO gap, providing an access to molecules with
Axial Chirality at The Boron-Carbon Bond:
Synthesis, Stereodynamic Analysis and
Atropisomeric Resolution of 6-Aryl-5,6-
dihydrodibenzo-[c,e]-[1,2]-azaborinines.
chemiluminescent properties. Azaborines have been shown to
be effective organic light-emitting diodes (OLEDs)2 and
organic field-effect transistors (OFETs).3 Moreover, these
types of organic compounds are important for the design of
additional structures with biological functions for the research
of new drugs candidates.4 The latter concept is very interesting
because the trivalent structure of the boron can give an
alternative electrostatic contact with the enzymatic targets.
Recently, 2-aryl-2,1-borazaronaphthalenes (i.e. the isosters of
a 2-aryl-1-naphthalenes compounds) have shown to yield
atropisomeric structures, configurationally stable at ambient
temperature.5 Following this previous work, we have analyzed
the boron-carbon stereogenic axis in the analogues of 9-aryl-
phenanthrene (and 1-aryl-naphthalenes as well) 6-aryl-5,6-
dihydrodibenzo-[c,e]-[1,2]-azaborinines (1a-1d in Scheme 1),
where the B-N moiety has been reversed with respect to the
previous compounds.
Andrea Mazzanti, Maria Boffa, Emanuela Marotta and
Michele Mancinelli*
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Department of Industrial Chemistry “Toso Montanari”,
University of Bologna,
Viale del Risorgimento 4, Bologna 40136, Italy
michele.mancinelli@unibo.it
RECEIVED DATE (will be automatically inserted after
manuscript is accepted).
Bz
Bz
N
Ar
Ar
B
Previous work
Ar
Ar
B
HN
Ph
This work
Abstract. 6-Aryl-5,6-dihydrodibenzo[c,e][1,2]azaborinines
display restricted rotation at the boron-carbon aryl bond,
yielding conformational isomers or atropisomers. The
stereodynamic processes were monitored by variable
temperature NMR (D-NMR), dynamic enantioselective
HPLC (D-HPLC) or kinetic racemization measurements.
The absolute configuration of stable atropisomers
(compound 1d, ΔG≠rac =26.0 kcal mol-1) was determined by
TD-DFT simulation of the electronic circular dichroism
(ECD) spectra. The racemization energy of 1d is more than
12 kcal mol-1 smaller that its isoster 9-(2-
methylnaphthalen-1-yl)-phenanthrene.
Ph
1a
1b
1c
1d
Ar = o-tolyl
Ar = o-ethylphenyl
Ar = 2-isopropoxy-1-naphthyl
Ar = 2-methyl-1-naphthyl
9-aryl-phenanthrene
isosteric carbon compound
Scheme 1. Compounds 1a-1d.
Result and discussion
As in the paradigmatic case of biphenyls,6 when an
unsymmetrically ortho-substituted aryl ring is bound to the
boron in compounds 1a-1d (Scheme 1), it is skewed out of the
plane because of the steric hindrance between the ortho
substituent and the NH and CH in positions 5 and 7, thus
implying the formation of two enantiomeric conformations.
The thermal stability of these conformational enantiomers
relies on the steric hindrance of the ortho-substituent,7 and by
the peculiar features of the carbon-boron bond, as this was
found to be significantly longer than a carbon-carbon bond
(1.58 vs 1.49 Å).5
Introduction
Azaborines are part of a class of chemical compounds that
has emerged in the recent past, affecting many research field.1
The azaborine moiety replaces a C=C bond with a B-N bond
within any molecular structure to obtain isosteric and
isoelectronic architectures. The polarity of the B-N bond
imparts different chemical and physical properties to the
molecular structure. Due to the large electronegativity
difference, π electrons are mainly shifted towards the nitrogen,
leading to slightly less aromatic and less stable compounds.
The inclusion of heteroatoms and π-conjugated fragments is a
strategy that allows to find new materials with unique
functions, because the presence of the unbalanced electron
distribution changes the electronic and photophysical
properties of potential organic semiconductors. The
replacement of one or more of the carbon atoms in polycyclic
aromatic hydrocarbons (PAHs) with boron decreases the
DFT calculations were preliminary run on compound 1a (Ar =
ortho-tolyl) using B3LYP8 and the 6-31G(d) basis set. The
optimized geometries (see Figure 1) suggest that in the two
skewed conformations6b the ortho-tolyl ring is displaced out of
the plane by |61|° or by |110|° (N-B-Cq-Cortho dihedral angle, ϕ
in Figure 1), with C-B bond length of 1.58 Å. The threshold
transition state for the interconversion of the atropisomeric
pair was calculated as 10.8 kcal mol-1, and it corresponds to
the rotation of the ortho-methyl over the NH (TS0 in Figure
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Eyring equation (Table 1). The experimental value is well
1). This rotational barrier should be easily monitored by the
dynamic-NMR (D-NMR) technique in the presence of a
chirality probe, such as the ethyl group in compound 1b.
Compounds 1a-1d were prepared by modifying a synthetic
procedure that has been recently reported.9 The key step of the
reproduced by DFT calculation performed on compound 1a,
taking into account the slightly larger steric hindrance of the
ethyl group with respect to methyl (B = 7.4 kcal mol-1 for Me
and 8.7 kcal mol-1 for Et).7
Cl
synthesis is
a Friedel-Crafts reaction that yields the
B
intermediate 2, using BCl3 and AlCl3 (Scheme 2).10 The use of
different nucleophilic aryl groups, e.g. Grignard reagents,
allowed the synthesis of compounds 1a-1d.
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NH2
HN
BCl3, AlCl3
toluene
reflux
2
dry Et2O
+25 °C
ArMgBr
Ar
B
1a
Ar = o-tolyl
Ar = o-ethylphenyl
Ar = 2-isopropoxy-1-naphthyl
1d
HN
1b
1c
=
Ar 2-methyl-1-naphthyl
1a-d
Scheme 2. Synthesis of compounds 1a-1d
B
HN
k (s-1)
T (°C)
1b
4300
580
+25
+3
Figure 1. Ground and transition states for compound 1a
(only the M atropisomer is shown, relative energies in kcal
mol-1).
300
93
-3
It has been reported that the use of a glovebox was mandatory
because of the sensitivity of intermediate 2 to air and moisture.
To make the preparation available to standard laboratory
equipment, we have modified this procedure to be performed
“one-pot”, by generating in situ both intermediate 2 and the
Grignard reagent. The synthetic procedure was optimized on
product 1a (see Experimental section), but this compound was
unsuitable for the NMR determination of the CB rotational
barrier because of the absence of any chirality probe.11
Compound 1b, bearing an ortho-ethylphenyl group as probe of
chirality, was prepared and analyzed by means of D-NMR
spectroscopy (Figure 2, left). At ambient temperature the
signal of the CH2 was a quartet, thus implying fast rotation in
the NMR time scale. On lowering the temperature, the signal
reached the coalescence point at 15 °C, and eventually split
into two signals below 40 °C (ABX3 spin system). Line
shape simulation allowed to determine the rate constants for
the dynamic process at the different temperatures, hence the
activation free energy (12.6 ± 0.15 kcal mol-1) by means of the
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<1
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-60
2.70 2.60 2.50 ppm
Figure 2. Left: variable temperature NMR spectra of the
CH2 signal of compound 1b (600 MHz in CD2Cl2). Right: line
shape simulation of the ABX3 system with the corresponding
rate constants.
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Compound 1c has a higher steric hindrance with respect to
temperatures, corresponding to a half-life time of 30 days at
+25 °C. This value has to be compared with that of the isoster
9-(2-methylnaphthalen-1-yl)phenanthrene (3, Grac > 38 kcal
mol-1, see SI for details), yielding a G > 12 kcal mol-1.
This large difference is a direct consequence of the longer C-B
bond with respect to C-C.
1b due to the presence of the 2-isopropoxy-1-naphthyl group.
D-NMR analysis showed there was not exchange between the
two diastereotopic CH3 signals of isopropyl up to +120 °C.
When analyzed on chiral stationary phase HPLC (CSP-HPLC)
at +25 °C, compound 1c showed two resolved
chromatographic peaks for the two atropisomers, but the
presence of a plateau between the peaks suggested that on-
column racemization took place.12 The chromatographic runs
were then recorded in the +15  +45 °C range (continuous
cyan lines in Figure 3), and the kinetic rate constants were
evaluated through line shape simulation of the chromatograms
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B
HN
(dashed red lines in Figure 3). The ΔG≠ derived by Eyring
13
equation was 21.8 ± 0.2 kcal∙mol-1 (Figure S4), corresponding
to a life time of ≈1000 s at +25 °C.14
1d
1 2
1100
T = +15 °C
1100
mAu
900
T = +25 °C
mAu
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O
B
HN
Figure 4. Top: CSP-HPLC chromatogram of compound 1d
(ChiralPak AD–H 250x4.6 mm, n-hexane/iso-propanol 97:3, 1
mL·min-1) Bottom: ECD spectra of the two atropisomers (in
CH3CN).
1c
-100
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4.5
min
1100
mAu
900
mAu
900
T = +40 °C
T = +45 °C
Table 1. Experimental and calculated free energy barriers in
700
500
300
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700
500
kcal mol-1.
Compd
1a
1b
ΔG≠
10.8
13.2
21.5
ΔG≠
exp.
calc.
not determinable
12.6 (D-NMR, 30  +3°C)
21.8 (D-HPLC, +25  +45°C)
26.0 (kinetic racemization,
+45+50°C)
300
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1c
4
4.5 min -100
3.5
4
4.5
min
-100 3.5
1d
3
25.3
38.0
> 38.1 (146.5°C)
Figure 3. Dynamic-HPLC chromatograms for compound 1c
on CSP column (cyan lines, ChiralPak AD–H, n-hexane/iso-
propanol 95:5 v/v, 1 mL·min-1). Red dashed lines are the
simulated chromatograms.
The absolute configuration of the two atropisomers of 1d
was assigned by the simulation of ECD spectrum based on
time-dependent density functional theory (TD-DFT).15
A
Compound 1d was therefore prepared to further increase the
steric hindrance and to obtain thermally stable atropisomers.
In this case the CSP-HPLC analysis showed two well-
separated peaks (Figure 4, top), and a semi-preparative
approach allowed to resolve the two atropisomers and to
record their ECD spectra (Figure 4, bottom). The racemization
rate was derived by kinetic analysis at +45 and +50°C (Figure
S5 of SI). A sample of enantiopure atropisomer was heated
and the racemization process was followed by analytical CSP-
HPLC (Figure S5 of SI). A racemization barrier of 26.0 ±0.2
kcal mol-1 (DFT calculated value was 25.3 kcal∙mol-1) was
derived from the rate constants determined at the two different
conformational search suggested the existence of four
conformations, with very similar energies, due to the different
dihedral angles of the two phenyl rings in position 2 and 4
(Figure S3 of SI). The theoretical ECD spectra of the four
ground state conformations (Figure 5) were obtained with four
different
functionals
(CAM-B3LYP,16
ωB97X-D,17
BH&HLYP18 and M06-2x19) with the same 6-311++G(2d,p)
basis set, in order to have data redundancy, and to enhance
reliability. The spectra simulated for the four conformations
have similar shapes, with a negative band between 220 and
250 nm and one positive between 190 and 210 nm. As a
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In summary, we have shown that 6-Aryl-5,6-
consequence, the Boltzmann-averaged ECD spectrum will not
be very sensitive to variations of the conformational ratio.
dihydrodibenzo[c,e][1,2]azaborinines yield configurationally
stable atropisomers when bearing an hindered ortho-
substituted aryl ring such as 2-methylnaphthalene. However,
the racemization energy of compound 1d is more than 12 kcal
mol-1 smaller that its isoster 9-(2-methylnaphthalen-1-yl)-
phenanthrene 3.
150
150
∆ɛ
GS1
GS2
GS3
GS4
CAM-B3LYP
BH&HLYP
GS1
GS2
GS3
GS4
∆ɛ
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240
290
340
390
nm
nm
390
190
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290
340
Experimental section:
-50
-100
-150
-50
-100
-150
NMR Spectroscopic data. NMR spectra were recorded
using a spectrometer operating at a field of 14.4 T (600 MHz
1
for H, 150.8 for 13C, 192.4 for 11B). Chemical shifts are
reported in ppm (δ) relative to TMS as an internal standard.
The 150.8 MHz 13C spectra were acquired under proton
decoupling conditions with a 36000 Hz spectral width, 5.5 µs
(60° tip angle) pulse width, 1 s acquisition time and 9 s delay
time. The long relaxation time was needed to observe some
quaternary carbons. A line broadening function of 1–2 Hz was
applied before the Fourier transformation. 13C signals were
assigned by DEPT-135 sequence. Variable temperature NMR
spectra were recorded as previously reported.20 The rate
constants were derived from line shape simulations (QCPE
DNMR6 program),21 and the free energies of activation (ΔG≠)
were obtained by means of the Eyring equation. Within the
experimental uncertainty, the latter values were found
essentially invariant in the examined temperature range, thus
implying an almost negligible activation entropy ΔS≠. HRMS
were performed with an ESI-QTOF spectrometer at the CIGS
facility, Modena, Italy.
150
∆ɛ
150
∆ɛ
ωB97-XD
M06-2X
GS2
GS1
GS3
GS4
GS2
GS1
GS3
GS4
100
100
50
50
0
0
190
240
290
340
390
190
240
290
340 nm 390
nm
-50
-100
-150
-50
-100
-150
Figure 5. Computed spectra for the four conformations of the
M atropisomer of compound 1d. Calculations were obtained
using the same 6-311++G(2d,p) basis set.
The conformationally averaged spectra, obtained using the
ZPE corrected enthalpies suggested by B3LYP/6-31G(d)
optimization, are in good agreement with the experimental
spectrum of the first eluted atropisomer, to which the M
absolute configuration can be assigned (Figure 6).
Calculations:
The ground state and transition states geometries were
obtained using the Gaussian 16 rev A.03 series of programs,22
with standard optimization parameters. The calculations
employed the B3LYP hybrid-DFT functional8 and the 6-
31G(d) basis set. Vibrational analysis was performed to
validate the ground states (zero imaginary frequencies) and the
transition states (one imaginary frequency). Visual inspection
of the corresponding normal mode23 confirmed the
identification of the correct transition states. Where not
explicitly indicated, the reported energies are uncorrected
electronic energies. TD-DFT calculations were performed by
means of the hybrid functionals BH&HLYP18 and M06-2x,19
the long-range correlated ωB97X-D that includes empirical
dispersion,17 and CAM-B3LYP that includes long-range
correction using the Coulomb Attenuating Method.16 The 6-
311++G(2d,p) was used for all the TD-DFT calculations. For
each simulation, 70 transitions were calculated and the spectra
were obtained by applying Gaussian shapes (half linewidth at
half height= 0.25 eV). The Boltzmann averaged UV spectrum
was red-shifted in order to match the experimental UV
spectrum (see ESI), and the same correction was applied to the
simulated ECD spectra. A vertical scale factor was used in
order to match the intensity of the most intense band of the
experimental ECD spectrum.
20
mdeg
15
20
mdeg
15
Experimental
BH&HLYP
Experimental
CAM-B3LYP
10
5
10
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0
0
nm
400
190
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390
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nm
-5
-5
-10
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-25
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-15
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mdeg
15
20
mdeg
15
10
5
Experimental
Experimental
M06-2X
10
5
ωB97-XD
0
0
190
240
290
340
390
nm
nm
390
190
240
290
340
-5
-5
-10
-15
-20
-25
-10
-15
-20
-25
ECD Spectra were recorded at +25 °C in far-UV HPLC-
grade acetonitrile solutions. The concentrations of the samples
(about 10-4 M) were tuned by dilution of a mother solution to
obtain a maximum absorbance of about 0.8 ÷ 1.0 in the UV
spectrum using a 0.2 cm path length. The ECD spectra were
recorded in the 190-400 nm interval as the average of 16
spectra.
Figure 6. Experimental and calculated ECD of 1d. The
calculated spectra have been red shifted by 14, 16, 15 and 14
nm and multiplied by a scale factor of 0.25, 0.19, 0.31, and
0.27 for CAM-B3LYP, BH&HLYP, ωB97X-D and M06-2x,
respectively. The experimental spectrum (black) is that of the
first eluted atropisomer (Figure 4).
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Materials: 2,4,6-triphenylaniline, 2-bromo-1-naphthol, 2-
7.72 (m, 2H), 7.74 (dd, J = 7.4, 0.9 Hz, 1H), 7.97 (bs, NH),
8.59 (d, J = 8.2 Hz, 1H), 8.67 (d, J = 1.9 Hz, 1H). 13C{1H}-
NMR (150.8 MHz, CD2Cl2, 53.52 ppm, +25 °C): δ 16.4
(CH3), 29.6 (CH2), 121.9 (CH); 122.5 (CH), 124.1 (Cq), 124.9
(CH), 126.4 (CH), 127.1 (CH), 127.2 (CH), 127.8 (CH), 128.2
(CH), 128.4 (CH), 128.9 (CH), 129.4 (CH), 129.7 (CH), 131.3
(CH), 132.5 (Cq), 133.0 (CH), 134.2 (Cq), 135.4 (Cq), 136.7
(CH), 138.5 (Cq), 139.1 (Cq), 141.2 (Cq), 147.3 (Cq). 11B-
NMR (192.4 MHz, CDCl3, BF3∙Et2O = 0 ppm, +25 °C): δ
38.33. HRMS(ESI-QTOF). Calcd. for C32H27BN [M+H]+
436.2231. Found: 436.2233.
methyl-1-bromonaphthalene, 2-ethyl-1-bromobenzene were
commercially available, and were used as received. 9-(2-
methylnaphthalen-1-yl)phenanthrene (3) was prepared
according to the literature.24
General procedure for the preparation of 6-Aryl-5,6-
dihydrodibenzo[c,e][1,2]azaborinines 1a-1d.
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Preparation of compounds 1a-1d was carried out in a two-
necked flask under nitrogen atmosphere. The reflux condenser
was fitted with a drying tube packed with calcium chloride. To
a dry toluene solution (20 mL) of 2,4,6-triphenylaniline (0.500
g, 1.56 mmol), BCl3 (4.7 mL, 1 M solution in n-hexane, 3 eq)
was added dropwise at 0 °C. A precipitate formed when the
BCl3 solution was added, but it gradually dissolved, and the
reaction mixture became clear again. It was then heated to
reflux for 30 min under stirring, and cooled again to ambient
temperature. Thereafter, a catalytic amount of AlCl3 (2 mol%)
was added and the reaction mixture was refluxed again for 18
hours, to obtain compound 2. The crude was dried under
vacuum to remove the solvent, any traces of water and volatile
components such as hydrogen chloride and boron chloride.
The green solid obtained after evaporation, was dissolved by
addition of dry Et2O (24 mL). A solution of the appropriate
Grignard reagent (4 mL, 0.5 M in Et2O, freshly prepared in
another two-necked flask) was then added to intermediate 2.
The resulting mixture was left under magnetic stirring for 1
hour at ambient temperature. The reaction was quenched with
H2O and extracted with Et2O (3  20 mL) and the organic
layers were dried over MgSO4. They were filtered first on a
plug of silica gel and then on a plug of celite with EtOAc as
eluent. The crude compound was purified by chromatograpy
on silica gel (petroleum ether/EtOAc 19:1). Analytically pure
samples of compounds 1a-1d were obtained by reverse phase
semi-preparative HPLC with a Phenomenex Synergi Polar –
RP 80 Å column (250x10 mm, ACN:H2O 90:10 v/v).
6-(7-isopropoxynaphthalen-1-yl)-2,4-diphenyl-5,6-
dihydrodibenzo[c,e][1,2]azaborinine 1c.
1
Yield: 34% (273 mg). H-NMR (600 MHz, CD2Cl2, 5.33
ppm, +25 °C): δ 1.116 (d, J = 6.1 Hz, 3H), 1.122 (d, J = 6.1
Hz, 3H), 4.60 (sept, J = 6.1 Hz, 1H), 7.23 (qt, J = 6.8, 1.3 Hz,
1H), 7.30 (td, J = 6.8, 1.0 Hz, 1H), 7.35 (d, J = 9.1 Hz, 1H),
7.37-7.44 (m, 3H), 7.45-7.57 (m, 3H), 7.54 (t, J = 7.6 Hz, 2H),
7.62 (dd, J = 8.3, 1.2 Hz, 2H), 7.70 (dd, J = 6.9, 1.2 Hz, 1H),
7.74 (d, J = 1.9 Hz, 1H), 7.79-7.86 (m, 4H), 7.9 (d, J = 9.0 Hz,
1H), 8.29 (bs, NH), 8.74 (d, J = 8.3 Hz, 1H), 8.84 (d, J = 1.9
Hz, 1H). 13C{1H}-NMR (150.8 MHz, CDCl3, 77.36 ppm, +25
°C): δ 22.1 (CH3), 22.2 (CH3), 71.2 (CH), 116.4 (CH), 122.0
(CH), 122.5 (CH), 123.3 (CH), 124.2 (Cq), 125.7 (CH), 126.2
(CH), 127.1 (CH), 127.2 (CH), 128.06 (CH), 128.09 (CH),
128.4 (CH), 128.9 (CH), 129.2 (Cq), 129.3 (CH), 129.8 (CH),
130.1 (CH), 131.2 (CH), 132.4 (Cq), 135.8 (Cq), 136.8 (CH),
137.7 (Cq), 138.6 (Cq), 138.8 (Cq), 141.3 (Cq), 158.2 (Cq).
11B-NMR (192.4 MHz, CDCl3, BF3∙Et2O = 0 ppm, +25 °C): δ
38.64. HRMS(ESI-QTOF). Calcd. for C37H31BNO[M+H]+
516.2493. Found: 516.2496.
6-(2-methylnaphthalen-1-yl)-2,4-diphenyl-5,6-
dihydrodibenzo[c,e][1,2]azaborinine 1d.
1
Yield: 36% (265 mg). H-NMR (600 MHz, CD2Cl2, 5.33
2,4-diphenyl-6-(o-tolyl)-5,6-
dihydrodibenzo[c,e][1,2]azaborine 1a.
ppm, +25 °C): δ 2.39 (s, 3H), 7.27 (qd, J = 6.8, 1.2 Hz, 1H),
7.36-7.46 (m, 5H), 7.46-7.54 (m, 3H), 7.56 (t, J = 7.5 Hz, 2H),
7.62 (dd, J = 8.3, 1.2 Hz, 2H), 7.65 (dd, J = 7.5, 1.3 Hz, 1H),
7.76 (d, J = 2.0 Hz, 1H), 7.82-7.88 (m, 5H), 7.27 (bs, NH),
8.77 (d, J = 8.3 Hz, 1H), 8.87 (d, J = 1.7 Hz, 1H). 13C{1H}-
NMR (150.8 MHz, CDCl3, 77.36 ppm, +25 °C): δ 22.9 (CH3),
122.1 (CH), 122.6 (CH), 124.4 (Cq), 124.6 (CH), 125.4 (CH),
126.6 (CH), 127.20 (CH), 127.22 (CH), 127.9 (CH), 128.1
(CH), 128.2 (CH), 128.5 (CH), 128.6 (CH), 128.8 (CH), 129.0
(CH), 129.4 (CH), 129.7 (CH), 131.5 (Cq), 131.6 (CH), 132.6
(Cq), 133.1 (bs, Cq), 134.4 (Cq), 135.6 (Cq), 136.6 (CH),
137.0 (bs, Cq), 138.45 (Cq), 138.48 (Cq), 139.0 (Cq), 141.2
(Cq). 11B-NMR (192.4 MHz, CDCl3, BF3∙Et2O = 0 ppm, +25
°C): δ 39.40. HRMS(ESI-QTOF). Calcd. for C35H27BN
[M+H]+ 472.2231. Found: 472.2228. Semi-preparative CSP-
HPLC resolution was obtained with Chiralpak-AD-H column
(250x21.2mm, n-hexane/iso-propanol 97:3 v/v, 20 ml/min).
1
Yield: 35% (230 mg). H-NMR (600 MHz, CD2Cl2, 5.33
ppm, +25 °C): δ 2.20 (s, 3H), 7.10 (t, J = 7.4 Hz, 1H), 7.14 (d,
J = 7.5 Hz, 1H), 7.19 (td, J = 7.6, 1.6 Hz, 1H), 7.26-7.31 (m,
2H), 7.34 (tdd J = 7.5, 1.8, 1.3 Hz, 1H), 7.37-7.50 (m, 5H),
7.46-7.50 (m, 2H), 7.59 (d, J = 2.1 Hz, 1H), 7.66-7.72 (m,
3H), 7.77 (dd J = 7.4, 1.2 Hz, 1H), 7.89 (bs, NH), 8.58 (d, J =
8.3 Hz, 1H), 8.66 (d, J = 2.1 Hz, 1H). 13C{1H}-NMR (150.8
MHz, CD2Cl2, 53.52 ppm, +25 °C): δ 22.6 (CH3), 121.8 (CH),
122.5 (CH), 123.9 (Cq), 124.7 (CH), 126.3 (CH), 127.0 (CH),
127.0 (CH), 128.1 (CH), 128.18 (CH), 128.3 (CH), 128.8
(CH), 129.3 (CH), 129.7 (CH), 131.2 (CH), 132.4 (Cq), 132.9
(CH), 134.1 (Cq), 135.3 (Cq), 136.5 (CH), 138.4 (Cq), 139.0
(Cq), 140.5 (Cq), 141.1 (Cq). 11B-NMR (192.4 MHz, CDCl3,
BF3∙Et2O = 0 ppm, +25 °C): δ 38.13. HRMS(ESI-QTOF).
Calcd. for C31H25BN [M+H]+ 422.2075. Found: 422.2071.
1-bromo-2-(propan-2-yloxy)naphthalene
791088-70-5)25
(4,
CAS:
6-(2-ethylphenyl)-2,4-diphenyl-5,6-
dihydrodibenzo[c,e][1,2]azaborine 1b.
1-Bromo-2-naphthol (2.23 g, 10 mmol) was dissolved in
DMSO (20 mL), and a solution of KOH (3 mL, 4 M, 12
mmol) was added. The reaction was stirred at room
temperature for about 15 minutes. Once the anion was formed,
perceptible by a change of colour, 2-iodopropane (2 mL, 20
mmol) was added. The reaction was left under stirring for two
1
Yield: 32% (217 mg). H-NMR (600 MHz, CD2Cl2, 5.33
ppm, +25 °C): δ 1.05 (t, J = 7.6 Hz, 3H), 2.51 (q, J = 7.6 Hz,
2H), 7.11 (td, J = 7.2, 1.1 Hz, 1H), 7.19 (d, J = 7.6 Hz, 1H),
7.24 (td, J = 7.7, 1.2 Hz, 1H), 7.26-7.32 (m, 2H), 7.33-7.46
(m, 5H), 7.47-7.50 (m, 2H), 7.60 (d, J = 2.0 Hz, 1H), 7.68-
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hours and monitored by TLC. The reaction was quenched with
cold water and extracted with EtOAc (50 mL x 3). The
combined organic phase was dried over of magnesium
sulphate and solvent removed in vacuum. The crude product
was purified with a silica chromatographic column (petroleum
Stereodynamics and Conformational Analysis by Dynamic NMR and
Theoretical Calculations. Eur. J. Org. Chem. 2010, 2035–2056.
12) a) D'Acquarica, I.; Gasparrini, F.; Pierini, M.; Villani, C.; Zappia, G.
Dynamic HPLC on Chiral Stationary Phases: A Powerful Tool for The
Investigation of Stereomutation Processes, J. Sep. Sci. 2006, 29, 1508–
1516. b) Sabia, R; Ciogli, A.; Pierini, M.; Gasparrini, F. Villani, C.
Dynamic High Performance Liquid Chromatography on Chiral
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Investigation of the Stereodynamics of Axially Chiral 1,8-Bis(2,2‘-
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syn/anti-Isomers. J. Phys. Chem. A, 2003, 107, 815–817. d) Wolf, C.;
Hochmuth, D. H.; König, W. A.; Roussel, C. Influence of Substituents on
the Rotational Energy Barrier of Axially Chiral Biphenyls, II. Liebigs
Ann. Chem. 1996, 357–363. e) Wolf, C.; König, W. A., Roussel, C.
Influence of Substituents on the Rotational Energy Barrier of
Atropisomeric Biphenyls – Studies by Polarimetry and Dynamic Gas
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Dynamic Stereochemistry of Chiral Compounds, Principles and
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13) Cirilli, R.; Costi, R.; Di Santo, R.; La Torre, F.; Pierini, M.; Siani, G.
Perturbing Effects of Chiral Stationary Phase on Enantiomerization
Second-Order Rate Constants Determined by Enantioselective Dynamic
High-Performance Liquid Chromatography: A Practical Tool to Quantify
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NJ :John Wiley & Sons, pp. 1–82.
1
ether/DCM, 9:1). Yield = 97%, 2.57 g. H-NMR (600 MHz,
CDCl3, TMS, +25 °C): δ 1.36 (d, J = 6.1 Hz, 6H), 4.59 (q, J =
6.1 Hz, 1H), 7.14 (d, J = 8.9 Hz, 1H), 7.33 (t J = 7.5 Hz, 1H),
7.50 (t J = 7.6 Hz, 1H), 7.67 (d J = 8.9 Hz, 1H), 7.70 (d, J =
8.3 Hz, 1H), 8.21 (d, J = 8.5 Hz, 1H). 13C{1H}-NMR (150.8
MHz, CDCl3, 77.36 ppm, +25 °C): δ 22.7 (2CH3), 73.6 (CH),
111.7 (Cq), 117.9 (CH), 124.7 (CH), 124.7 (CH), 126.7 (CH),
127.7 (CH), 128.2 (CH), 128.9 (CH), 130.4 (Cq), 133.6 (Cq),
152.9 (Cq). HRMS(ESI-QTOF). Calcd. for C13H14OBr
[M+H]+ 265.0223. Found: 265.0227
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Supporting Information Available: Figures S1-S9, UV and
1
ECD spectra of 3, H, 13C, DEPT of 1a-1d and 4, 11B spectra of
1a-1d, computational details for 1a-1d and 3. This material is
available free of charge via the Internet at http://pubs.acs.org.
ACKNOWLEDGMENTS. AM, EM and MM thank the University of
Bologna (RFO funds 2017 and 2018). We thank Dr. Alessia Ciogli,
University of Rome “La Sapienza” for the simulation of the D-HPLC
spectra. ALCHEMY Fine Chemicals
& Research (Bologna,
15) a) Superchi, S.; Scafato, P.; Górecki, M.; Pescitelli, G. Absolute
Configuration Determination by Quantum Mechanical Calculation of
Chiroptical Spectra: Basics and Applications to Fungal Metabolites.
Curr. Med. Chem. 2018, 25, 287–320. b) Pescitelli, G.; Bruhn, T. Good
Computational Practice in the Assignment of Absolute Configurations by
TDDFT Calculations of ECD Spectra. Chirality 2016, 28, 466–474 c)
Laurent, A. D.; Jacquemin, D. TD‐DFT benchmarks: A Review Int. J.
Quantum Chem. 2013, 113, 2019–2039. d) Jacquemin, D.; Wathelet, V.;
Perpète, E. A.; Adamo, C. Extensive TD-DFT Benchmark: Singlet-
Excited States of Organic Molecules. J. Chem. Theory Comput. 2009, 5,
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www.alchemy.it) is acknowledged for a gift of chemicals.
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