Metal-Free Synthesis of α-Aminophosphonates from Tertiary Amines and P(O)H Compounds via a Cross-Dehydrogenative Coupling Reaction

Abstract

The various α-aminophosphonates have been prepared from tertiary aromatic and aliphatic amines with P(O)H compounds via a tert-butyl hydroperoxide mediated cross-dehydrogenative coupling reaction, eliminating the need for transition-metal catalysts. The oxidation of tertiary amine by tert-butyl hydroperoxide generates an iminium cation intermediate. A further addition of P(O)H compound to iminium cation gives the desired product.

Key words

tert-butyl hydroperoxide - α-aminophosphonates - tertiary aromatic amines - tertiary aliphatic amines - dialkyl H-phosphonate

• References and Notes

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• 15 Experimental Procedure for the Synthesis of α-Aminophosphonate 3: Tributylamine (1; 1.5 mmol, 3 equiv), diethyl H-phosphonate (2; 0.5 mmol, 1 equiv), TBHP (1 or 2 equiv, 70% in water) and MeCN (2.5 mL) were sequentially placed in a round-bottom flask at room temperature. The reaction mixture was heated at 80 °C with stirring under an argon atmosphere for 24 hours. Upon completion, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography using petroleum ether/EtOAc (20:1 to 2:1, v/v) as eluent to give the corresponding product 3 (CAS no: 875228-32-3) (ref. 9) as a light-yellow oil (144.5 mg, 90%). ¹H NMR (500 MHz, CDCl₃): δ = 4.07–3.98 (m, 4 H), 2.89–2.83 (m, 1 H), 2.63–2.49 (m, 4 H), 1.55–1.48 (m, 3 H), 1.33–1.17 (m, 15 H), 0.87–0.80 (m, 9 H). ¹³C NMR (125 MHz, CDCl₃): δ = 61.5 (d, J = 7.4 Hz), 60.8 (d, J = 7.8 Hz), 58.3 (d, J = 134.0 Hz), 51.7 (d, J = 3.5 Hz), 31.7 (s), 29.9 (d, J = 7.2 Hz), 20.4 (d, J = 12.7 Hz), 20.3 (s), 16.6 (d, J = 5.4 Hz), 16.5 (d, J = 5.9 Hz), 14.1 (s), 13.9 (s). ³¹P NMR (202 MHz, CDCl₃): δ = 29.7. HRMS: m/z [M+Na]⁺ calcd for C₁₆H₃₆NNaO₃P⁺: 344.2325; found: 344.2326.