Molecules 2010, 15
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CH2P), 3.48 (system AB, J = 15.0 Hz, 1H, CH2Ph), 3.75 (d, J = 11.2 Hz, 3H, (CH3O)2P), 3.77
(d, J = 11.2 Hz, 3H, (CH3O)2P), 3.82 (system AB, J = 15.0 Hz, 1H, CH2Ph), 7.23–7.36 (m, 5 H,
Harom); 13C-NMR (CDCl3) 23.9 (CH2CH2), 28.5 (CH2CH), 35.7 (d, J = 133.6 Hz, CH2P), 53.1
[(CH3O)2P], 53.3 [(CH3O)2P], 54.2 (CH2N), 59.5 (CH2Ph), 73.7 (CHN), 127.4 (Cpara), 128.4 (Cmeta),
129.2 (Cortho), 138.4 (Cipso), 204.8 (C=O); 31P-NMR (CDCl3) δ 25.94; HRMS (CI, CH4) calculated for
C15H23O4NP (MH+) 312.1365, found 312.1287.
(S)-Dimethyl-4-(tert-butyldimethylsilyloxy)-3-N,N-(dibenzylamino)-2-oxobutylphosphonate (10). A
solution of dimethyl methylphosphonate (3.30 g, 26.6 mmol) in anhydrous THF (125 mL), was cooled
at -78 ºC before the slowly addition of n-BuLi 2.15 M in hexanes (12.7 mL, 27.3 mmol). The resulting
solution was stirred at -50 ºC for 1.5 h and then cooled at -78 ºC followed by the addition of a solution
of benzyl ester 9 (2.75 g, 6.7 mmol) in anhydrous THF (125 mL). The reaction mixture was stirred at -
78 ºC for 4 h before the addition of a saturated solution of NH4Cl. The solvent was evaporated under
reduced pressure, the residue was dissolved in water (30 mL) and extracted with ethyl acetate
(3 × 30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and
evaporated under reduced pressure. The crude product was purified by column chromatography using
hexane-ethyl acetate (50:50) as eluent to give the desired product (2.7 g, 81% yield) as a viscous oil.
[α]D = -56.0 (c = 1.17, CHCl3). 1H-NMR (CDCl3) δ 0.09 (s, 3H, (CH3)2Si), 0.12 (s, 3H, (CH3)2Si), 0.93
(s, 9H, (CH3)3C), 2.99 (dd, J = 21.9 Hz, J = 14.5 Hz, 1H, CH2P), 3.48 (dd, J = 21.9 Hz, J = 14.5 Hz,
1H, CH2P), 3.56 (d, J = 11.2 Hz, 3H, (CH3O)2P), 3.63 (d, J = 11.2 Hz, 3H, (CH3O)2P), 3.65 (t,
J = 6.0 Hz, 1H, CHN), 3.78 (system AB, J = 13.4 Hz, 2H, CH2Ph), 3.84 (system AB, J = 13.4 Hz, 2H,
CH2Ph), 4.03 (dd, J = 11.0 Hz, J = 6.1 Hz, 1H, CH2OSi), 4.13 (dd, J = 11.0 Hz, J = 6.1 Hz, 1H,
13
CH2OSi), 7.23–7.35 (m, 10 H, Harom); C-NMR (CDCl3) δ -5.3 [(CH3)2Si], -5.2 [(CH3)2Si], 18.4
[C(CH3)3], 26.2 [CH3)3C], 38.6 (d, J = 130.6 Hz, CH2P), 52.9 [d, J = 6.1 Hz, (CH3O)2P)], 52.9 [d,
J = 6.0 Hz, (CH3O)2P], 55.4 (CH2Ph), 60.1 (CH2OSi), 67.44 (CHN), 127.4 (Cpara), 128.5 (Cmeta), 129.2
(Cortho), 139.4 (Cipso), 201.8 (d, J = 6.1 Hz, C=O); 31P-NMR (CDCl3) δ 24.30; HRMS (CI, CH4)
calculated for, C26H41O5NPSi (MH+) 506.2492, found 506.2575
General procedure for the reduction of β-ketophosphonates (S)-6 and (S)-10 with NaBH4. To a
solution of β-ketophosphonate (S)-6 or (S)-10 (1.0 eq.) in methanol (40 mL) at 0 ºC was added NaBH4
(4.0 equiv.). After 5.0 h, the solvent was evaporated and the residue was diluted with H2O and
extracted with ethyl acetate (3 × 30 mL). The organic layer was dried over Na2SO4 and evaporated in
vacuum. The crude was analyzed by 1H- and 31P-NMR and purified by column chromatography.
General procedure for the reduction of β-ketophosphonates (S)-6 and (S)-10 with LiBH4, DIBAL-H
and catecholborane (CB). To a solution of β-ketophosphonate (S)-6 or (S)-10 (1.0 eq.) in anhydrous
THF (50 mL) was added (2.0 equiv.) of reducing agent at -78 ºC. The reaction mixture was stirred for
5.0 h at -78 ºC, and then was quenched with saturated solution of NH4Cl and extracted with ethyl
acetate (3 × 40 mL). The organic layer was dried over Na2SO4 and evaporated in vacuum. The crude
was analyzed by 1H- and 31P-NMR and purified by column chromatography.
(2S)-1-Benzylpyrrolidin-2-yl)-(2R)-hydroxyethylphosphonate (syn-11). Following the general
procedure, β-ketophosphonate 6 (100 mg, 0.32 mmol) in anhydrous THF (20 mL), was treated with