DDQ-Mediated Cross-Dehydrogenative-Coupling Reaction of Secondary Amines with Dialkyl Phosphonates

Abstract

This work reports a DDQ-mediated cross-dehydrogenative-coupling reaction of secondary amines with dialkyl phosphonates under mild conditions. This reaction proceeds efficiently without involving visible light or transition-metal catalysis. This new approach provides efficient access to biologically important α-aminophosphonates.

Key words

DDQ - cross-dehydrogenative-coupling - phosphonylation - allylic amines - dialkyl phosphonates - aminophosphonates

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• 12 α-Aminophosphonates 3; General Procedure A Schlenk tube charged with secondary amine 1 (0.2 mmol) and DDQ (0.24 mmol, 1.2 equiv) was purged three times with argon. Anhyd toluene (2.0 mL) and phosphite 2 (0.36 mmol, 1.8 equiv) were added, and the mixture was stirred at 80 °C under Ar for 48 h. When the reaction was complete (TLC), the mixture was washed with sat. aq Na₂CO₃, concentrated, and purified by column chromatography (silica gel).
• 13 Diethyl {(2E)-1-[(4-Bromophenyl)amino]-3-phenylprop-2-en-1-yl}phosphonate (3a) Viscous oil; yield: 78 mg (92%). ¹H NMR (400 MHz, CDCl₃): δ = 7.46–7.16 (m, 7 H), 6.67 (dd, J = 15.9, 4.8 Hz, 1 H), 6.62–6.50 (m, 2 H), 6.23 (dt, J = 16.0, 5.4 Hz, 1 H), 4.41 (dd, J = 19.4, 6.6 Hz, 2 H), 4.29–4.06 (m, 4 H), 1.30 (td, J = 7.1, 4.6 Hz, 6 H). ¹³C NMR (101 MHz, CDCl₃): δ = 145.48 (d, J = 12.5 Hz), 136.00 (d, J = 3.2 Hz), 133.11 (d, J = 12.3 Hz), 131.93, 128.53, 127.93, 126.51 (d, J = 1.8 Hz), 122.83 (d, J = 4.6 Hz), 115.36 (d, J = 8.5 Hz), 110.15, 63.44 (d, J = 7.1 Hz), 63.08 (d, J = 7.2 Hz), 54.71, 53.18, 16.43 (t, J = 5.2 Hz). ³¹P NMR (162 MHz, CDCl₃): δ = 21.92. MS (ESI): m/z = 424.1 [M + H]⁺.