Alkylation of Asymmetric Phosphonamidates (Part II)

Abstract

The stereochemistry of the alkylation of phosphon­amidates 1b is influenced mostly by the chirality of the asymmetric phosphorus atom and not by the chirality of the asymmetric carbon atom. In contrast, the stereochemistry of the alkylation of phos­phonamidates 1c is influenced by a combination of the stereochemistry of the chiral phosphorus atom and the stereochemistry of the chiral carbon atom.

Key words

diastereoselective - alkylation - 2-oxo-1,3,2-oxazaphosphorinane

References

• 1 Afarinkia K. Jones CL. Yu H.-W. Synlett  2003,  509 
• 2 Guéguen C. O’Brien P. Powell HR. Raithby PR. Warren S. J. Chem. Soc., Perkin. Trans. 1  1998,  3405 
• 3a Denmark SE. Chen C.-T. J. Am. Chem. Soc.  1995,  117:  11879 
• 3b Denmark SE. Chen C.-T. J. Org. Chem.  1994,  59:  2922 
• 3c Denmark SE. Darrow RL. J. Org. Chem.  1990,  55:  5926 

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Afarinkia, K.; Binch, H. M.; De Pascale, M. E.; Jones, C. L. manuscript in preparation.

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Typical Experimental Procedure: LDA (0.37 mL, 0.74 mmol) was added to a stirred solution of 1b (160 mg, 0.49 mmol) in dry toluene (15 mL) maintained under an argon atmosphere at -78 °C. After 30 min the reaction was warmed to 0 °C and stirring was continued for a further 30 min. The reaction was then cooled to -78 °C and CH₃I (0.056 mL, 0.91 mmol) was added. After 30 min, the cooling bath was removed and the reaction was allowed to warm to r.t. over 60 min. The reaction was quenched by the addition of brine (10 mL) and washed with more brine (2 × 10 mL). The organic layer was then dried over MgSO₄ and the solvent was removed in vacuum to give the crude product as a yellow oil. Column chromatography (10% petroleum ether in EtOAc) afforded a mixed fraction containing 2a and 2b (18.5 mg, 9%) and pure (2R, 1′S, 2′R)-3-benzyl-2-(1′-methyl-2′-phenylpropyl)-1,3,2-oxazaphosphorinane 2-oxide 2a as a yellow oil (84.5 mg, 41%). HRMS: Calcd for C₂₀H₂₆O₂NP [M⁺]: 343.1701. Found: 343.1697. ¹H NMR (360 MHz, CDCl₃): δ = 1.02 (3 H, dd, J _H = 7.3 Hz, J _P = 18.1 Hz, C1′-CH₃), 1.48 (3 H, d, J _H = 6.9 Hz, C2′-CH₃), 1.70 (1 H, m, CHHCH₂N), 1.83 (1 H, m, CHHCH₂N), 2.21 (1 H, m, PCH), 2.95 (1 H, m, CHHN), 3.08 (2 H, m, CHHPh CHHN), 4.10 (1 H, m, CHHO), 4.25 (1 H, m, CHHO), 4.75 (1 H, m, CHHPh), 7.15-7.45 (5 H, m, aromatic H). ³¹P NMR (145.79 MHz, CDCl₃): δ = 35.24. ¹³C NMR (90 MHz, CDCl₃): δ = 14.01 (C1′-CH₃), 21.92 (C3′), 26.63 (C-5), 39.22 (d, J _P = 124 Hz, C-1′), 42.25 (C-4), 44.66 (C-2′), 52.42 (PhCH₂), 67.71 (C-6), 126.75-129.26 (aromatic CH), 138.65 (aromatic C). MS (EI): m/z (%) = 343 (32) [M⁺], 211 (25), 210 (55), 146 (9), 117 (11), 105 (28), 103 (12), 91 (100). IR (CDCl₃):
ν_max = 2959, 1452, 1239, 910 cm^-1.