supporting information ester derivatives. derived imines ... · 6500 me b o o ome o 3gii. 8.0 7.5...
TRANSCRIPT
Supporting Information
One-pot catalytic asymmetric borylation of unsaturated aldehyde-
derived imines; functionalisation to homoallylic boronate carboxylate
ester derivatives.
Alba Pujol, Adam D. J. Calow, Andrei S. Batsanov and Andrew Whiting
1. ReactIR studies on in situ imine formation
2. Chiral HPLC
3. 1H, 13C, 11B NMR spectra
4. Crystallographic structures and data
5. References
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2015
1. ReactIR studies on in situ imine formation
R
O
1
H2NPh
Ph(1.0 equiv)
3Å-MS, iPrOH, r.t.R
N
4
Ph
Ph
Scheme 1 Formation of α,β-unsaturated imines in iPrOH.
Standard conditions: To an oven-dried two-necked flask, fitted with the IR probe, enal (2.0
mmol) was added to a stirring solution of solvent (8.0 mL) and 3 Å-molecular sieve beads
(2.0 g, oven-dried at 250 ºC for >48 h prior to use), under argon at 25 ºC. Once the C=O peak
had plateaued (observed through PC-interface), showing maximum intensity, amine (2.0
mmol) was added and the reaction was carried out for 0.5 – 24 h. The in situ-formed imine
was then utilised without purification by using a needle-syringe combination.
Representative graphical output of the reaction between Cinnamaldehyde 1a and benzhydryl
amine (see standard conditions).
Reaction profile of 2-Hexenal 1d and benzhydryl amine (see standard conditions).
Reaction profile of Crotonaldehyde 1g and benzhydryl amine (see standard conditions).
Reaction profile of (2E)-3-(Thiophen-2-yl)prop-2-enal 1j and benzhydryl amine (see standard
conditions).
2. Chiral HPLC
Sample chromatograms: 1) Racemic standard; 2) Optimised asymmetric reaction (IPA, (R)-
DM BINAP as ligand, unless otherwise stated).
BOO
OMe
O
3aii
MeO
B
OMe
OOO
3bii
Optimised asymmetric reaction (THF/MeOH, (R)-DM-BINAP as ligand)
BOO
OMe
O
3dii
Cl
B
OMe
OOO
3eii
Optimised asymmetric reaction (THF/MeOH, (R)-DM-BINAP as ligand)
BOO
OMe
O
3fii
BOO
OMe
O
3gii
OMe
BO O
O
3iii
Stereochemical assignments
The relative stereochemistry of each chiral compound can be determined through the use of
chiral HPLC (see above). In addition, the absolute stereochemistry of each product is
assumed to be consistent with previous studies in our group,1 whereby derivatisation and
X-ray analysis allowed for the absolute stereochemistry of the respective compounds to be
assigned. This was later supported by derivatisation of such compounds into known
pharmaceuticals,2 whereby the absolute stereochemistry was consistent with those
independently verified by this work.1
3. 1H, 13C and 11B NMR spectra
It is important to note that samples 6a-c, 7b and 7d could not be purified due to their inherent
instability. Therefore, the crude 1H-NMR spectra of 6a-c, 7b and 7d are listed below.
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-100
0
100
200
300
400
500
600
700
800
900
1000
1100
Crude 1H-NMR showing the presence of 6a
Ph O
BOO
6a
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.5f1 (ppm)
0
200
400
600
800
1000
1200
1400
1600
1800
2000
2200
2400
2600
2800
p-OMePh O
BOO
6b
Crude 1H-NMR showing the presence of 6b 4a
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-50
0
50
100
150
200
250
300
350
400
450
500
550
600
650
O
BOO
6c
Crude 1H-NMR showing the presence of 6c 4a
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
-100
0
100
200
300
400
500
600
700
800
900
1000
1100
1200
1300
1400
1500
p-OMePh
BOO
7bO
OCrude 1H-NMR showing the presence of 7b 4a
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)
-200
0
200
400
600
800
1000
1200
1400
1600
1800
2000
2200
2400
2600
2800
3000
3200
3400
3600
3800
Pr
BOO
7dO
O
Crude 1H-NMR showing the presence of 7d 4a
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
14000
15000
16000
Ph
BOO
OEt
O
3ai
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-200
0
200
400
600
800
1000
1200
1400
1600
1800
2000
2200
2400
2600
2800
3000
Ph
BOO
OEt
O
3ai
-25-20-15-10-5051015202530354045505560f1 (ppm)
-1500
-1000
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
6500
7000
7500
Ph
BOO
OEt
O
3ai
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
Ph
BOO
OMe
O
3aii
0102030405060708090100110120130140150160170f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
Ph
BOO
OMe
O
3aii
510152025303540455055606570f1 (ppm)
-1000
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
Ph
BOO
OMe
O
3aii
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
p-OMePh
BOO
OMe
O
3bii
0102030405060708090100110120130140150160170f1 (ppm)
-200
0
200
400
600
800
1000
1200
1400
1600
1800
2000
2200
2400
p-OMePh
BOO
OMe
O
3bii
46810121416182022242628303234363840424446485052545658606264f1 (ppm)
-500
0
500
1000
1500
2000
p-OMePh
BOO
OMe
O
3bii
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
14000
15000
16000
Pr
BOO
OMe
O
3dii
0102030405060708090100110120130140150160170f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
6500
7000
Pr
BOO
OMe
O
3dii
-25-20-15-10-50510152025303540455055606570f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
Pr
BOO
OMe
O
3dii
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)
-20
0
20
40
60
80
100
120
140
160
180
200
220
240
260
280
300
320
p-ClPh
BOO
OMe
O
3eii
0102030405060708090100110120130140150160170f1 (ppm)
-100
0
100
200
300
400
500
600
700
800
900
1000
1100
1200
1300
1400
1500
p-ClPh
BOO
OMe
O
3eii
68101214161820222426283032343638404244464850525456f1 (ppm)
-2000
-1500
-1000
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
6500
7000
p-ClPh
BOO
OMe
O
3eii
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
Et
BOO
OMe
O
3fii
0102030405060708090100110120130140150160170f1 (ppm)
0
500
1000
1500
2000
2500
3000
3500
Et
BOO
OMe
O
3fii
-5051015202530354045505560f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
Et
BOO
OMe
O
3fii
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
6500
Me
BOO
OMe
O
3gii
0102030405060708090100110120130140150160170f1 (ppm)
-200
0
200
400
600
800
1000
1200
1400
1600
1800
2000
2200
2400
2600
2800
3000
Me
BOO
OMe
O
3gii
051015202530354045505560f1 (ppm)
-1000
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
6500
Me
BOO
OMe
O
3gii
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
-2000
-1000
0
1000
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6000
7000
8000
9000
10000
11000
12000
13000
14000
15000
16000
17000
18000
19000
20000
21000
22000
23000
24000
OMe
BO O
O
3iii
-505101520253035404550556065f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000OMe
BO O
O
3iii
-100102030405060708090100110120130140150160170f1 (ppm)
0
500
1000
1500
2000
2500
3000
3500
4000
4500
OMe
BO O
O
3iii
4. Crystallographic data
Figure X1. X-ray molecular structure of compound 4a at 120 K. Here and below, atomic
displacement ellipsoids are drawn at 50% probability level.
Figure X2. X-ray molecular structure of compound 4b at 120 K.
Figure X3. X-ray molecular structure of compound 4e at 120 K.
Figure X4. Two independent molecules in the crystal structure of compound 4h at 120 K.
Figure X5. X-ray molecular structure of compound 4j at 120 K; the thiophene ring is disordered
between two opposite orientations in 4:1 ratio (minor atom positions are primed).
5. References
1. A. D. J. Calow, A. Batsanov, A. Pujol, C. Solé, E. Fernández, A. Whiting, Org. Lett., 2013, 15, 4810-4813
2. A. D. J. Calow, E. Fernández, A. Whiting, Org. Biomol. Chem., 2014, 12, 6121-6127.