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21st June 2010 @ 04:56
Preparation of a strong achiral Brønsted acid, intended for pretests for the acid-catalysed Pictet-Spengler reaction

Reaction Scheme


Table1


Start time: 1:30 AM 21/06/2010
End time: 9:45 AM 22/06/2010

Procedure: [1]
To a mixture of (+/-)-BINOL (172 mg, 600 µmol) and Et3N (585 µL, 425 mg, 4.20 mmol, 7 eq.) in DCM (3 mL) was added POCl3 (110 mg, 67 µL, 720 µmol, 1.2 eq.) and DMAP (147 mg, 1.20 µmol, 2 eq.) at 0°. The mixture was warmed to room temperature and stirred for5 h, instead of 1 h (starting material MW38 needed additional time for another purification step).
- Added propionitrile (3 mL) and TfNH2 MW38 (179 mg, 1.20 mmol, 2 eq.) and heated reaction mixture to 100°C for 15 h

Work-up: quenched with water, extracted with Et2O, washed with aq. NaHCO3 and 4 N HCl, dried over Na2SO4, concentrated

- TLC (hexane:EA = 1:1) Rf = 0.48; TLC (EA 100%) Rf = 0.66; stain: ceric ammonium molybdate, KMnO4, reference: BINOL (B)
TLC1
TLC2
TLC3

- purification by column chromatography (silica gel; hexane:EA = 1:1, then EA 100%)

Result:
51 mg pale brown solid – product??

Analytical data:
1 H NMR & 13C NMR - unspecific signals
19F NMR: signal match to reference [1] Data: 19F_NMR MW39-1
31P NMR: 4 major signals -> mixture?, lowfield shift of the signals compared to reference [1] Data: 31P_NMR MW39-1.jpg
IR - no characteristic signals for SO2 or sulfonamide Data: IR MW39-1
MS -> still waiting for it...


-> repeat experiment MW39-2


References:
[1] “Design of Chiral N-Triflyl Phosphoramide as a Strong Chiral Brønsted Acid and Its Application to Asymmetric Diels-Alder Reaction", D. Nakashima and H. Yamamoto, J. Am. Chem. Soc. 2006, 128, 30, 9626–9627.


Procedure from reference: [1]

General Procedure for Synthesis of Chiral Phosphoramide (2, 3):
To a solution of BINOL derivatives (0.6 mmol) in dichloromethane (3 mL) were added Et3N (585 μL, 4.2 mmol), POCl3 (67 μL, 0.72 mmol) and DMAP (147 mg, 1.2 mmol) at 0 °C. After being stirred for 1 hour at room temperature, EtCN (3 mL) was poured to the reaction and TfNH2 (179 mg, 1.2 mmol) was added at room temperature. Then the reaction was stirred at 100 °C for 12 hours. The reaction was quenched with H2O and extracted with Et2O twice. Combined organic layer was washed with sat. aq NaHCO3, then washed with aq 4N HCl twice. Resultant organic layer was dried over anhydrous Na2SO4, filtered and concentrated. Purification of the crude product by column chromatography on silica gel (eluent: hexane-dichloromethane-Et2O) provided phosphoramide which may be salt. The product was extracted with aq 4N HCl again, dried over anhydrous Na2SO4 and filtered. The concentration of the solution provided the desired phosphoramide.
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Attached Files
Reaction Scheme
Table1
TLC1
TLC2
TLC3
IR MW39-1
19F_NMR MW39-1
31P_NMR MW39-1.jpg