Asymmetric Nucleophilic Addition to Vinylphosphonates (Part III)

Abstract

Preparation of both diastereomers of enantiomerically pure asymmetric vinylphosphonamidates 4a and 4b, and nucleophilic addition of carbon nucleophiles to them is reported.

enantioselective - asymmetric - nucleophilic addition - cuprate - 2-oxo-1,3,2-oxazaphosphorinane - vinylphosphonates

References

1 Afarinkia K. Binch HM. De Pascale E. Synlett  2000,  1769 

2 Afarinkia K. Binch HM. Forristal I. Synlett  2000,  1771 

3a Denmark SE. Chen C.-T. J. Org. Chem.  1994,  59:  2922 

3b Denmark SE. Darrow RL. J. Org. Chem.  1990,  55:  5926 

3c Gordon NJ. Evans SA. J. Org. Chem.  1993,  58:  5293 

4 Afarinkia K. Binch HM. Modi C. Tetrahedron Lett.  1998,  39:  7419 

5

Typical experimental procedure. Compound 5c: Isopropyl magnesium chloride (2 M solution in THF, 3.6 mL, 7.25 mmol) was added to a stirred suspension of CuI (0.69 g, 3.6 mmol) in dry Et₂O (6.4 mL), maintained under a dry argon atmosphere at -40 °C. After 45 minutes, the solution was cooled to -78 °C and TMSCl (0.46 mL, 3.62 mmol) was added followed after 10 min by TMEDA (0.55 mL, 3.62 mmol) and then a solution of (1′R,2S) 3-(1′-phenylethyl)-2-oxo-2-(1-propenyl)-1,3,2-oxazaphosphorinane (0.16 g, 0.60 mmol) in dry THF (2M, 6.4 mL). Reaction was monitored by TLC (EtOAc as eluant) and was found to be complete after 3 hours. The reaction mixture was quenched by addition of sat aqueous NH₄Cl (50 mL) and filtered through Celite^®. Solid was washed with ethyl acetate (50 mL). The organic and aqueous phases of the filtrate were separated and the aqueous phase was washed with ethyl acetate (3 × 30 mL). The combined organic extracts were washed with brine and then dried over MgSO₄. Evaporation of solvent afforded a green oil. The crude product was taken up in a minimum quantity of ethyl acetate and filtered through a short pad of silica (Merck 9385), The filtrate and the washings were stripped of solvent and then treated with a solution of TBAF in THF (5 mL). After 1 h, solvent was removed and the residue was directly chromatographed on silica gel (Merck 9385) using EtOAc as eluent to afford a white solid product (0.10 g, 0.34 mmol, 56%) which by NMR analysis contained a mixture of diastereomers. Crystallisation from petroleum ether (bp fraction 60-80 °C) afforded the major diastereomer as colourless plates; mp 76-78 °C; ¹H NMR (CDCl₃, 360 MHz) δ 0.87 (3 H, d, J = 7 Hz, CH₃ of iPr), 0.91 (3 H, d, J = 7 Hz, CH₃ of iPr), 1.04 [3 H, d, J = 7 Hz, (CH₃)CH(iPr)], 1.49 [3 H, d, J = 7 Hz, (CH₃)CHPh], 1.53-2.02 [6 H, m, ring CH₂, CH₂P, CHMe₂, MeCH(iPr)], 2.77-2.88 and 2.95-3.03 (2 H, m, CH₂N), 3.98-4.24 (2 H, m, CH₂O), 5.05 (1 H, qd, J _H = 7.2, J _P = 14 Hz, MeCHPh), 7.22-7.58 (5 H, m, ArH); ³¹P{H} NMR (CDCl₃, 145 MHz) δ 33.2; ¹³C{H} NMR (CDCl₃, 162 MHz) δ 16.60 [(CH₃)CH(iPr)], 16.73 [d, J _P = 4 Hz, (CH₃)CHPh], 17.84 and 19.57 (2 × CH₃ of iPr), 26.52 (d, J _P = 4 Hz, C-5), 30.07 (d, J _P = 124 Hz, PCH₂), 33.46 (d, J _P = 14 Hz, CHMe₂), 33.72 [d, J _P = 4, MeCH(iPr)], 39.30 (d, J _P = 10 Hz, C-4), 51.7 (d, J _P = 4 Hz, MeCHPh), 66.5 (d, J _P = 7 Hz, C-6), 127.1-128.2 (4 × aromatic C); m/z 309 (M⁺).