Abstract
Utilization of the Polniaszek reagent Cl2 PNi -Pr2 /AlCl3 was used on amino dienes to generate new azabicyclophosphinic acid as constrained
analogues of TPMPA.
Key words
phosphorus - bicyclic compounds - cyclizations - medicinal chemistry - receptors
References
Most recent reviews on GABAC and references herein:
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Typical Procedure for Cyclization/Oxidation.
To a suspension of AlCl3 (1.3 g, 10 mmol) in CH2 Cl2 was added dropwise, at -20 °C and under N2 , Cl2 PNi -Pr2 (2.0 g,10 mmol) in CH2 Cl2 . Then, the mixture was stirred at r.t. for 1 h. The mixture was cooled down to -20
°C and N -benzyl diallylamine (936 mg, 5 mmol) in CH2 Cl2 was added dropwise. The mixture was allowed to warm up to r.t., stirred at r.t. for
16 h and refluxed for 1 h. The mixture was cooled down to 0 °C and 10 mL of a solution
of 0.2 M EDTA-sat. NaHCO3 (1:1) was added carefully. The mixture was then stirred at r.t. for 5 h. Then, 100
mL of H2 O were added and the aqueous phase was extracted several times with CHCl3 . The organic phases were combined, washed with brine, dried over Na2 SO4 and concentrated in vacuo to afford a crude yellow oil (2 g). Purification was achieved
by flash chromatography over silica gel using EtOAc-MeOH (100:0 to 80:20) as eluent.
After concentration of the fractions, a yellow paste (1.05 g, 63%) was obtained.
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1 H NMR (400 MHz, D2 O): δ = 3.55 (m, 2 H), 3.03 (m, 2 H), 2.85 (m, 2 H), 1.82 (m, 2 H), 1.40 (m, 2 H).
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1 H NMR (400 MHz, D2 O): δ = 5.87 (d, J = 31.7 Hz, 1 H), 3.79 (d, J = 14.0 Hz, 1 H), 3.56 (d, J = 15.9 Hz, 1 H), 3.42 (dd, J = 12.8 Hz, J = 2.4 Hz, 1 H), 3.01 (m, 1 H), 2.30 (m, 1 H), 2.15 (m, 2 H), 2.00 (m, 1 H), 1.63
(m, 1 H).