Supplementary Materials: A One-Pot Tandem Strategy in Catalytic Asymmetric Vinylogous Aldol ...

50 Pages·2016·1.45 MB·English

Molecules 2016, 21, 842; doi:10.3390/molecules21070842 S1 of S50
Supplementary Materials: A One-Pot Tandem
Strategy in Catalytic Asymmetric Vinylogous Aldol
Reaction of Homoallylic Alcohols
Xufeng Hou, Zhenzhong Jing, Xiangbin Bai and Zhiyong Jiang
1. General Information
1.1. General Procedures and Methods
Experiments involving moisture and/or air sensitive components were performed under a
positive pressure of nitrogen in oven-dried glassware equipped with a rubber septum inlet.
Dried solvents and liquid reagents were transferred by oven-dried syringes or hypodermic syringe
cooled to ambient temperature in a desiccator. Reactions mixtures were stirred in 10 mL sample
vial with Teflon-coated magnetic stirring bars unless otherwise stated. Moisture in non-volatile
reagents/compounds was removed in high vacuo by means of an oil pump and subsequent purging
with nitrogen. Solvents were removed in vacuo under ~30 mmHg and heated with a water bath at
30–35 °C using Changcheng rotary evaporator with Changcheng aspirator. The condenser was
cooled with running water at 0 °C.
All experiments were monitored by analytical thin layer chromatography (TLC). TLC was
performed on pre-coated plates, 60 F254. After elution, plate was visualized under UV illumination at
254 nm for UV active material. Further visualization was achieved by staining KMnO4, ceric
molybdate, or anisaldehyde solution. For those using the aqueous stains, the TLC plates were heated
on a hot plate.
Columns for flash chromatography (FC) contained silica gel 200–300 mesh. Columns were
packed as slurry of silica gel in petroleum ether and equilibrated solution using the appropriate
solvent system. The elution was assisted by applying pressure of about 2 atm with an air pump.
1.2. Instrumentations
Proton nuclear magnetic resonance (1H-NMR), carbon NMR (13C-NMR), and fluorous
(19F-NMR) spectra were recorded in CDCl3 otherwise stated. Chemical shifts are reported in parts
per million (ppm), using the residual solvent signal as an internal standard: CDCl3 (1H-NMR: δ 7.26,
singlet; 13C-NMR: δ 77.0, triplet). Multiplicities were given as: s (singlet), d (doublet), t (triplet), q
(quartet), quintet, m (multiplets), dd (doublet of doublets), dt (doublet of triplets), and br (broad).
Coupling constants (J) were recorded in Hertz (Hz). The number of proton atoms (n) for a given
resonance was indicated by nH. The number of carbon atoms (n) for a given resonance was indicated
by nC. HRMS was reported in units of mass of charge ratio (m/z). Mass samples were dissolved in
CH3CN (HPLC Grade) unless otherwise stated. Optical rotations were recorded on a polarimeter
with a sodium lamp of wavelength 589 nm and reported as follows; [α]T°C (c = g/100 mL, solvent).
λ
Melting points were determined on a melting point apparatus.
Enantiomeric excesses were determined by chiral High Performance Liquid Chromatography
(HPLC) analysis. UV detection was monitored at 254 nm, 230 nm and 210 nm at the same time.
HPLC samples were dissolved in HPLC grade isopropanol (IPA) unless otherwise stated.
Molecules 2016, 21, 842; doi:10.3390/molecules21070842 S2 of S50
1.3. Materials
All commercial reagents were purchased with the highest purity grade. They were used
without further purification unless specified. All solvents used, mainly petroleum ether (PE) and
ethyl acetate (EtOAc) were distilled. Anhydrous DCM and CH3CN were freshly distilled from CaH2
and stored under N2 atmosphere. THF, Et2O, tert-butylbenzene and toluene were freshly distilled
from sodium/benzophenone before use. Anhydrous methanol and etanol were distilled from Mg.
All compounds synthesized were stored in a −20 °C freezer and light-sensitive compounds were
protected with aluminium foil.
2. Characterization of Adducts
O R2 OH
R1 CF
3
5a:R1= Ph
R2= Ph

Figure S1. HPLC spectra of 5a.
Molecules 2016, 21, 842; doi:10.3390/molecules21070842 S3 of S50
O R2 OH
R1 CF
3
5b:R1=Ph
R2= 4-CF Ph
3
VWD1 A, 波波=254 nm (BXB-2\BXB8026003300.D)
mAU 10.778
250
200 15.470
150
100
50
0
2 4 6 8 10 12 14 16 18 min
VWD1 A, 波波=254 nm (BXB-2\BXB7075003304.D)
mAU 15.514
1000
800
600
400
200 10.922
0
0 2 4 6 8 10 12 14 16 18 min
Figure S2. HPLC spectra of 5b.
O R2 OH
R1 CF
3
5c:R1= Ph
R2=4-FPh

VWD1 A, 波波=254 nm (BXB-2\BXB7074003224.D)
mA8U0 0 11.302 12.596
700
600
500
400
300
200
100
0
2 4 6 8 10 12 14 min
VWD1 A, 波波=254 nm (BXB-2\BXB7073003222.D)
mA16U0 0 11.252
1400
1200
1000
800
600
400
2000 12.596
2 4 6 8 10 12 14 min
Figure S3. HPLC spectra of 5c.
Molecules 2016, 21, 842; doi:10.3390/molecules21070842 S4 of S50
O R2 OH
R1 CF
3
5d:R1=Ph
R2=4-ClPh

VWD1 A, 波波=254 nm (BXB-2\HSN5023RAC03261.D)
归1一40化0 6.835
1200
1000 9.085
800
600
400
200
0
2 4 6 8 10 min
VWD1 A, 波波=254 nm (BXB-2\BXB7081003263.D)
归一化 9.126
1750
1500
1250
1000
750
500
2500 6.756
0 2 4 6 8 10 min
Figure S4. HPLC spectra of 5d.
O R2 OH
R1 CF
3
5e:R1=Ph
R2= 4-BrPh

VWD1 A, 波波=254 nm (BXB-2\JZZ18064003048.D)
mA14U0 0 7.085
1200
1080000 12.713
600
400
200
0
2 4 6 8 10 12 14 min

Figure S5. HPLC spectra of 5e.
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O R2 OH
R1 CF
3
5f:R1=Ph
R2=3-FPh

VWD1 A, 波波=254 nm (BXB-2\BXB7080003225.D)
mAU 11.337
800 13.231
600
400
200
0
2 4 6 8 10 12 14 min
VWD1 A, 波波=254 nm (BXB-2\BXB7079003223.D)
mA12U0 0 11.277
1000
800
600
400
2000 13.190
2 4 6 8 10 12 14 min
Figure S6. HPLC spectra of 5f.
O R2 OH
R1 CF
3
5g:R1=Ph
R2= 3-ClPh

Figure S7. HPLC spectra of 5g.
Molecules 2016, 21, 842; doi:10.3390/molecules21070842 S6 of S50
O R2 OH
R1 CF
3
5h:R1= Ph
R2=2-FPh

VWD1 A, 波波=254 nm (ZG -1\ZG5027-R003852.D)
mA1U6 0 9.461
112400 11.891
100
80
60
40
20
0

0 2 4 6 8 10 12 min
VWD1 A, 波波=254 nm (ZG -1\ZG5027-CJJ33855.D)
mA20U0 0 9.421
1750
1500
1250
1000
750
500
2500 11.881
0 2 4 6 8 10 12 min
Figure S8. HPLC spectra of 5h.
O R2 OH
R1 CF
3
5i:R1=Ph
R2=4-MePh

VWD1 A, 波波=254 nm (BXB-2\BXB7078003235.D)
mA20U0 0 6.394
1750 9.970
1500
1250
1000
750
500
250
0
2 4 6 8 10 12 min
VWD1 A, 波波=254 nm (BXB-2\BXB7077A003229.D)
mAU 10.768
2000
1500
1000
500
6.730
0

0 2 4 6 8 10 12 min
Figure S9. HPLC spectra of 5i.
Molecules 2016, 21, 842; doi:10.3390/molecules21070842 S7 of S50
O R2 OH
R1 CF
3
5j:R1=Ph
R2=3-MePh

VWD1 A, 波波=254 nm (BXB-2\BXB7084003265.D)
归1一80化0 9.403 10.755
1600
1400
1200
1000
800
600
400
200
0
2 4 6 8 10 12 min
VWD1 A, 波波=254 nm (BXB-2\BXB7081003264.D)
归一化 11.018
1600
1400
1200
1000
800
600
400
2000 9.466
2 4 6 8 10 12 min
Figure S10. HPLC spectra of 5j.
O R2 OH
R1 CF
3
5k:R1=Ph
R2=2-naphtyl

Figure S11. HPLC spectra of 5k.
Molecules 2016, 21, 842; doi:10.3390/molecules21070842 S8 of S50
O R2 OH
R1 CF
3
5l:R1=Ph
R2=2-thienyl

Figure S11. HPLC spectra of 5l.
O R2 OH
R1 CF
3
5m:R1=Ph
R2=Et

VWD1 A, 波波=254 nm (JZZ-3\JZZ19065R003528.D)
mAU 7.339 8.153
500
400
300
200
100
0

0 2 4 6 8 min

Figure S12. HPLC spectra of 5m.
Molecules 2016, 21, 842; doi:10.3390/molecules21070842 S9 of S50
O R2 OH
R1 CF
3
5n:R1= 4-FPh
R2=Ph

Figure S13. HPLC spectra of 5n.
O R2 OH
R1 CF
3
5o:R1= 4-ClPh
R2=Ph

VWD1 A, 波波=254 nm (JZZ-3\JZZ18092A003285.D)
mA2U5 0 10.789
200
150 17.533
100
50
0

0 2.5 5 7.5 10 12.5 15 17.5 20 min
VWD1 A, 波波=254 nm (BXB-2\BXB8052003850.D)
mA12U0 0 16.650
1000
800
600
400
200 10.963
0

0 2.5 5 7.5 10 12.5 15 17.5 20 min
Figure S14. HPLC spectra of 5o.
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O R2 OH
R1 CF
3
5p:R1=3-FPh
R2= Ph

Figure S15. HPLC spectra of 5p.
O R2 OH
R1 CF
3
5q:R1=3-ClPh
R2= Ph

Figure S16. HPLC spectra of 5q.