Alkylation of Asymmetric Phosphonamidates (Part I)

Abstract

The diastereoselectivity in the alkylations of N-substituted 2-oxo-2-propyl-1,3,2-oxazaphosphorinanes 3a-c is influenced by the bulkiness of the nitrogen substituent. The α-carbanion derivatives of oxazaphosphorinanes 3b,c are unstable in the presence of DMPU and afford unexpected products.

Key words

2-oxo-1,3,2-oxazaphosphorinane - diastereoselective - alkylation - DMPU - carbanion migration

References

• 1a Gréguen C. O’Brien P. Powell HR. Raithby PR. Warren S. J. Chem. Soc., Perkin Trans. 1  1998,  3405 
• 1b Nelson A. Warren S. J. Chem. Soc., Perkin. Trans. 1  1999,  1963 
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• 2b Denmark SE. Chen C.-T. J. Org. Chem.  1994,  59:  2922 
• 2c Denmark SE. Darrow RL. J. Org. Chem.  1990,  55:  5926 
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• 3b Hanessian S. Beaudoin S. Tetrahedron Lett.  1992,  33:  7659 
• 4 Afarinkia K. Angell R. Jones CL. Lowman J. Tetrahedron Lett.  2001,  42:  743 
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5

Typical Experimental Procedure: LDA (3.37 mL, 6.82 mmol) was added to a stirred solution of 3-(diphenylmethyl)-2-propyl-1,3,2-oxazaphosphorinane 2-oxide 3b (1.50 g, 4.55 mmol) in dry toluene (100 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 allylbromide (0.63 mL, 6.82 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 vacuo to give the crude product as a yellow oil. The crude product was purified by column chromatography (50% petroleum ether in EtOAc) to afford pure (2R,1′S)-3-diphenylmethyl-2-(1-ethyl-3-butenyl)-1,3,2-oxazaphos-phorinane 2-oxide 5b as a white solid (650 mg, 39%). Mp 145-146 °C. HRMS: Calcd for C₂₂H₂₈O₂NP [M⁺]: 369.1858. Found: 369.1856. ¹H NMR (360 MHz, CDCl₃): δ = 0.93 (3 H, t, J _H = 7.4, CH₃), 1.35 (1 H, m, CH₂=CHCHH), 1.50-1.80 (5 H, m, PCHCH₂CH₃, CH₂CH₂N), 2.20-2.40 (1 H, m, CH₂=CHCHH), 3.15 (1 H, m, CHHN), 3.30 (1 H, m, CHHN), 4.10 (1 H, m, CHHO), 4.20 (1 H, m, CHHO), 4.95 (2 H, m, CH=CH₂), 5.80 (1 H, m, CH=CH₂), 6.28 (1 H, d,
J _P = 9.8, Ph₂CH), 7.20-7.40 (10 H, m, aromatic H). ³¹P NMR (145.79 MHz, CDCl₃): δ = 35.68. ¹³C NMR (90 MHz, CDCl₃): δ = 12.33 (d, J _P = 11.1, C-2′′), 22.97 (C-5), 26.63 (d, J _P = 5.9, C-1′′), 31.98 (C-2′), 38.58 (d, J _P = 128.40, C1′), 42.41 (C-4), 62.28 (Ph₂CH), 65.63 (C-6), 116.75 (C-4′), 127.80-130.96 (aromatic CH), 141.48 (aromatic C), 136.77 (C-3′). MS (EI): m/z (%) = 369 (78) [M⁺], 314 (20), 287 (42), 286 (89), 180 (38), 168 (41), 167 (100), 166 (37), 165 (80), 152 (51), 118 (19), 105 (23), 91 (62), 77 (22), 55 (47). IR: ν_max(CDCl₃) = 3430, 2965, 1638, 1493, 1452, 1240, 1075, 1048, 994, 919, 805, 730, 702 cm^-1.

6

Data were collected using a Nonius κ_CCD differactometer at 120 K and refined by full-matrix least squares on F². Crystal data: Orthorombic, space group P212121, a = 8.3335(3) Å, b = 11.4440(4) Å, c = 20.5403(8) Å, Z = 4 molecules per cell, D_c = 1.253 Mgm^-3.