Supporting Information
Stereochemistry of N-Benzoyl-5-substituted-1-benzazepines Revisited:
Synthesis of the Conformationally Biased Derivatives and Revision of the
Reported Structure
Hidetsugu Tabata, Tetsuya Yoneda, Tomohiko Tasaka, Shigekazu Ito, Tetsuta Oshitari, Hideyo
Takahashi, and Hideaki Natsugari*
Contents
1.
Comparison of anti/syn isomers in the
1
H NMR spectra of IIa-c and IIIa-c.
2
2.
1
H NMR analytical data of Ib (major).
4
3.
VT-NMR spectra at elevated temperatures and determination of
∆G
‡
value between
the anti and syn forms for Ia, IIa, and IIIa.
5
4.
VT-NMR spectra of Ib and Ic at lower temperatures.
6
5.
Energy differences between the conformers determined by DFT calculation.
7
6.
Atomic coordinates for the lowest-energy conformers by DFT calculation. 20
7.
Thermal ellipsoid plots (ORTEP drawing) of compounds Ib, Ic, IIc and IIIa. 27
8.
1
H NMR spectra of Ia and IIa measured in CD
3
OD.
28
9.
1
H-,
13
C-, and 2D-NMR (NOESY, COSY, and HMQC) spectra.
29
1. Comparison of anti/syn isomers in the
1
H NMR spectra of IIa-c and IIIa-c.
Compounds IIa–c:
X : parts per Million : Proton
5.9 5.8 5.7 5.6 5.5 5.4 5.3 5.2 5.1 5.0 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.11.0
Figure S1.
1
H NMR spectra (600 MHz in DMSO-d
6
): (a) IIa, (b) IIb (before separation of the anti/syn
isomers), and (c) IIc. The descriptors a and e are used for the stereochemical arrangement of the proton,
axial and equatorial orientation, respectively. The assignment of the signals from the anti and syn isomers
are shown in blue and red, respectively.
Compounds IIIa–c:
X : parts per Million : Proton
5.55.4 5.3 5.2 5.1 5.0 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.8 0.7 0.6
Figure S2.
1
H NMR spectra (600 MHz in DMSO-d
6
): (a) IIIa, (b) IIIb (before separation of the anti/syn
isomers), and (c) IIIc. The descriptors a and e are used for the stereochemical arrangement of the proton,
axial and equatorial orientation, respectively. The assignment of the signals from the anti and syn isomers
are shown in blue and red, respectively.Unidentified peaks (presumably originating in the trans isomer) in
IIIb and IIIc are marked by x.
2.
1
H NMR analytical data of Ib (major):
Chemical shifts and coupling (Table S1), relation of the coupling of the ring protons (Table
S2), and relation between
3
J values and torsion angles (Table S3).
Table S3. Torsion angles and observed vicinal coupling (
3
J)
H
2eq
-C2-C3-H
3eq
H
2eq
-C2-C3-H
3ax
H
3ax
-C3-C4-H
4eq
H
3ax
-C3-C4-H
4ax
H
2ax
-C2-C3-H
3ax
H
2ax
-C2-C3-H
3eq
H
3eq
-C3-C4-H
4eq
H
3eq
-C3-C4-H
4ax
4.1 (H
2eq
, H
3eq
)
45
6.9 (H
2eq
, H
3ax
)
20
9.6 (H
2ax
, H
3ax
)
170
3.4 (H
2ax
, H
3eq
)
50
4.1 (H
3ax
, H
4eq
)
45
9.6 (H
3ax
, H
4ax
)
170
6.9 (H
3eq
, H
4eq
)
20
4.1 (H
3eq
, H
4ax
)
45
H
4eq
-C4-C5-H
5ax
H
4ax
-C4-C5-H
5ax
3
J (Hz)
3.4 (H
4eq
, H
5ax
)
50
10.3 (H
4ax
, H
5ax
)
180
57
61
178
64
64
177
54
65
84
160
torsion angles
(
º
)
by the X-ray analysis
a
torsion angles
(
º
)
by the Karplus equation
b
3. VT-NMR spectra at elevated temperatures and determination of
∆G
‡
value between
the anti and syn forms for Ia, IIa, and IIIa.
X : parts per Million : Proton
5.45.3 5.2 5.1 5.0 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.8 0.7
Figure S3. VT-NMR of Ia.
X : parts per Million : Proton
6.05.9 5.8 5.7 5.6 5.5 5.4 5.3 5.2 5.1 5.0 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1
Figure S4. VT-NMR of IIa.
∆G
‡
= 68.8 kJ/mol
Tc = 333 K
(in DMSO-d
6
)
∆G
‡
= 69.5 kJ/mol
Tc = 383 K
(in DMSO-d
6
)
X : parts per Million : Proton 5.55.4 5.3 5.2 5.1 5.0 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.8 0.7
N
O
llIa
N(CH
3
)
2
373 K
353 K
333 K
313 K
296 K
393 K
Figure S5. VT-NMR of IIIa.
3. VT-NMR spectra of Ib and Ic at lower temperatures.
X : parts per Million : Proton
5.25.1 5.0 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.80.7
Figure S6. VT NMR of Ib.
∆G
‡
= 71.0 kJ/mol
Tc = 353 K
(in DMSO-d
6
)
X : parts per Million : Proton
5.2 5.1 5.0 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.8