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DOI: 10.1055/s-2005-921902
Synthesis of Two New Azabicyclophosphinic Acids as Constrained Analogues of TPMPA
Publikationsverlauf
Publikationsdatum:
04. November 2005 (online)
Abstract
Utilization of the Polniaszek reagent Cl2PNi-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
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References
Typical Procedure for Cyclization/Oxidation.
To a suspension of AlCl3 (1.3 g, 10 mmol) in CH2Cl2 was added dropwise, at -20 °C and under N2, Cl2PNi-Pr2 (2.0 g,10 mmol) in CH2Cl2. 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 CH2Cl2 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 H2O were added and the aqueous phase was extracted several times with CHCl3. The organic phases were combined, washed with brine, dried over Na2SO4 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.
1H NMR (400 MHz, D2O): 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).
111H NMR (400 MHz, D2O): 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).