Phenylboronic Acid as Efficient and Eco-Friendly Catalyst for the One-Pot, Three-Component Synthesis of α-Aminophosphonates under Solvent-Free Conditions

Gaurao D. Tibhe; Mercedes Bedolla-Medrano; Carlos Cativiela; Mario Ordóñez

doi:10.1055/s-0032-1316558

Synlett, Table of Contents

Synlett 2012; 23(13): 1931-1936
DOI: 10.1055/s-0032-1316558

letter

Phenylboronic Acid as Efficient and Eco-Friendly Catalyst for the One-Pot, Three-Component Synthesis of α-Aminophosphonates under Solvent-Free Conditions

Gaurao D. Tibhe

^aCentro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, México, Fax: +52(777)3297997 Email: palacios@ciq.uaem.mx

,

Mercedes Bedolla-Medrano

^aCentro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, México, Fax: +52(777)3297997 Email: palacios@ciq.uaem.mx

,

Carlos Cativiela

^bDepartamento de Química Orgánica, ISQCH, Universidad de Zaragoza–CSIC, 50009 Zaragoza, Spain

,

Mario Ordóñez*

^aCentro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, México, Fax: +52(777)3297997 Email: palacios@ciq.uaem.mx

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Abstract

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Abstract

A simple, mild, and efficient one-pot, three-component synthetic method has been developed for the preparation of α-aminophosphonates using phenylboronic acid as catalyst under solvent-free conditions at 50 °C. The process involves the reaction of carbonyl compounds (aldehydes or ketones) with benzylamine and dimethyl phosphite. A wide range of carbonyl compounds are compatible with this reaction, producing tertiary and quaternary α-aminophosphonates in moderated to excellent yields in short time.

Key words

α-aminophosphonates - one-pot three-component reaction - phenylboronic acid - solvent-free conditions

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References

References and Notes
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34 In a typical experiment, to a mixture of aldehyde or ketone (2.5 mmol) and benzylamine (2.5 mmol) was added PhB(OH)₂ (10 mol%). The reaction mixture was stirred at r.t. for 15 min. After this time, dimethyl phosphite (2.6 mmol) was added, and the reaction mixture was stirred at 50 °C for a specific period of time (see Tables 1 and 2), and the progress of the reaction was monitored by TLC. The crude was purified by flash chromatography with EtOAc–hexane (70:30), obtaining the pure α-aminophosphonates. ¹H NMR, ¹³C NMR, ³¹P NMR, and HRMS data for some newly obtained α-aminophosphonates are as follows. Compound 1c: white solid; mp 55–57 °C. ¹H NMR (400 MHz, CDCl₃): δ = 2.20 (br s, 1 H, NH), 3.55 [d, J _HP = 10.8 Hz, 3 H, (CH₃O)₂P]. 3.74 [d, J _HP = 10.4 Hz, 3 H, (CH₃O)₂P], 3.80 (AB system, J = 13.2 Hz, 2 H, CH₂Ph), 3.89 (s, 3 H, CH₃O), 3.90 (s, 3 H, CH₃O), 3.98 (d, J _HP = 19.6 Hz, 1 H, CHP), 6.86–7.00 (m, 3 H, HAr), 7.23–7.33 (m, 5 H, HAr). ¹³C NMR (100 MHz, CDCl₃): δ = 51.3 (d, J _CP = 16.7 Hz, CH₂Ph), 53.5 [d, J _CP = 6.1 Hz (CH₃O)₂P], 53.8 [d, J _CP = 7.5 Hz (CH₃O)₂P], 56.1 (CH₃O), 56.2 (CH₃O), 59.1 (d, J _CP = 154.7 Hz, CHP), 111.5, 111.9, 121.4 (d, J _CP = 7.6 Hz), 127.3, 128.0, 128.5, 128.6, 139.5, 149.2, 149.5. ³¹P NMR (80 MHz, CDCl₃): δ = 27.03. HRMS (FAB⁺): m/z calcd for C₁₈H₂₅NO₅P: 366.1470; found: 366.1467. Compound 1d: yellow liquid. ¹H NMR (400 MHz, CDCl₃): δ = 2.20 (br s, 1 H, NH), 3.51 [d, J _HP = 10.4 Hz, 3 H, (CH₃O)₂P], 3.56 (AB system, J = 13.2 Hz, 1 H, CH₂Ph), 3.74 (AB system, J = 13.2 Hz, 1 H, CH₂Ph), 3.78 [d, J _HP = 10.8 Hz, 3 H, (CH₃O)₂P], 3.80 (s, 3 H, OCH₃), 4.68 (d, J _HP = 21.1 Hz, 1 H, CHP), 6.90 (d, J _HH = 8.4 Hz, 1 H, HAr), 7.01 (t, J _HH = 7.2 Hz, 1 H, HAr), 7.20–7.31 (m, 6 H, HAr), 7.53–7.56 (m, 1 H, HAr). ¹³C NMR (100 MHz, CDCl₃): δ = 51.6 (d, J = 16.8 Hz, CH₂Ph), 51.7 (d, J _CP = 156.6 Hz, CHP), 53.4 [d, J _CP = 6.5 Hz (CH₃O)₂P], 53.9 [d, J _CP = 6.6 Hz (CH₃O)₂P], 55.8 (CH₃O), 111.0 (d, J _CP = 2.2 Hz), 121.2 (d, J _CP = 3.0 Hz), 124.4, 127.2, 128.4, 128.6, 129.0 (d, J _CP = 5.6 Hz), 129.1 (d, J _CP = 3.0 Hz), 139.8, 158.0 (d, J _CP = 7.3 Hz). ³¹P NMR (80 MHz, CDCl₃): δ = 27.66. HRMS (FAB⁺): m/z calcd for C₁₇H₂₃NO₄P: 336.1365; found: 336.1378. Compound 1e: yellow liquid. ¹H NMR (400 MHz, CDCl₃): δ = 3.47 [d, J _HP = 10.4 Hz, 3 H, (CH₃O)₂P], 3.53 (AB system, J = 13.2 Hz, 1 H, CH₂Ph), 3.78 (AB system, J = 12.8 Hz, 1 H, CH₂Ph), 3.79 [d, J _HP = 10.4 Hz, 3H, (CH₃O)₂P], 3.96 (d, J _HP= 20.8 Hz, 1 H, CHP), 6.75–6.86 (m, 2 H, HAr), 7.16–7.25 (m, 3 H, HAr), 7.26–7.33 (m, 4 H, HAr). ¹³C NMR (100 MHz, CDCl₃): δ = 51.0 (d, J _CP = 18.0 Hz, CH₂Ph), 53.7 [d, J _CP = 6.7 Hz, (CH₃O)₂P], 54.1 [d, J _CP = 6.9 Hz (CH₃O)₂P], 58.8 (d, J _CP = 155.0 Hz, CHP), 114.9 (d, J _CP = 5.1 Hz), 115.8 (d, J _CP = 2.9 Hz), 120.4 (d, J _CP = 7.9 Hz), 127.1, 128.3, 128.4, 129.6 (d, J _CP = 1.8 Hz), 136.3 (d, J _CP = 2.8 Hz), 139.1, 157.6 (d, J _CP = 2.8 Hz). ³¹P NMR (80 MHz, CDCl₃): δ = 27.19. HRMS (FAB⁺): m/z calcd for C₁₆H₂₁NO₄P: 322.1208; found: 322.1219. Compound 1f: yellow liquid. ¹H NMR (400 MHz, CDCl₃): δ = 2.30 (br s, 1 H, NH), 3.52 (AB system, J = 13.6 Hz, 1 H, CH₂Ph), 3.59 [d, J _HP = 10.8 Hz, 3 H, (CH₃O)₂P], 3.73 [d, J _HP = 10.4 Hz, 3 H, (CH₃O)₂P], 3.79 (AB system, J = 13.6 Hz, 1 H, CH₂Ph), 4.03 (d, J _HP = 20.0 Hz, 1 H, CHP), 7.22–7.38 (m, 9 H, HAr). ¹³C NMR (100 MHz, CDCl₃): δ = 51.3 (d, J = 16.7 Hz, CH₂Ph), 53.7 [d, J _CP = 7.6 Hz, (CH₃O)₂P], 54.0 [d, J _CP = 6.0 Hz, (CH₃O)₂P], 58.7 (d, J _CP = 154.7 Hz, CHP), 127.5, 128.5, 128.7, 129.0, 130.1 (d, J _CP = 6.1 Hz), 134.0 (d, J _CP = 4.5 Hz), 134.2 (d, J _CP = 4.5 Hz), 139.0. ³¹P NMR (80 MHz, CDCl₃): δ = 26.20. HRMS (FAB⁺): m/z calcd for C₁₆H₂₀ClNO₃P: 340.0869; found: 340.0872. Compound 1g: yellow liquid. ¹H NMR (400 MHz, CDCl₃): δ = 2.06 (br s, 1 H, NH), 3.51 [d, J _HP = 10.4 Hz, 3 H, (CH₃O)₂P], 3.66 (AB system, J = 13.2 Hz, 1 H, CH₂Ph), 3.78 [d, J _HP = 10.4 Hz, 3 H, (CH₃O)₂P], 3.86 (AB system, J = 13.2 Hz, 1 H, CH₂Ph), 4.40 (d, J _HP = 18.4 Hz, 1 H, CHP), 7.09–7.38 (m, 9 H, HAr), 7.66 (d, J _HH = 2.0 Hz 1 H, HAr), 9.10 (br s, NH). ¹³C NMR (100 MHz, CDCl₃): δ = 51.5 (d, J _CP = 16.7 Hz, CH₂Ph), 51.6 (d, J _CP = 162.3 Hz, CHP), 53.6 [d, J _CP = 7.6 Hz, (CH₃O)₂P], 53.9 [d, J _CP = 7.6 Hz, (CH₃O)₂P], 109.7, 111.7, 119.5, 119.9, 122.3, 124.7 (d, J _CP = 7.6 Hz), 127.0, 127.3, 128.5, 128.6, 136.5, 139.7. ³¹P NMR (80 MHz, CDCl₃): δ = 27.89. HRMS (FAB⁺): m/z calcd for C₁₈H₂₂N₂O₃P: 345.1368; found: 345.1369. Compound 1i: yellow liquid. ¹H NMR (400 MHz, CDCl₃): δ = 0.76 (d, J _HH = 6.4 Hz, 3 H, CH₃), 0.91 (d, J _HH = 7.2 Hz, 3 H, CH₃), 1.48–1.55 (m, 2 H, CH₂), 1.60 (br s, 1 H, NH), 1.84–1.88 (m, 1 H, CH), 2.93–2.99 (m, 1 H, CHP), 3.79 [d, J _HP = 10.8 Hz, 3 H, (CH₃O)₂P], 3.80 [d, J _HP = 10.0 Hz, 3 H, (CH₃O)₂P], 3.86 (AB system, J = 13.2 Hz, 1 H, CH₂Ph), 4.00 (AB system, J = 13.2 Hz, 1 H, CH₂Ph), 7.23–7.35 (m, 5 H, HAr). ¹³C NMR (100 MHz, CDCl₃): δ = 21.5 (CH₃), 23.6 (CH₃), 24.6 (d, J _CP = 11.7 Hz, CH), 39.4 (d, J _CP = 2.2 Hz, CH₂), 52.1 (d, J _CP = 147.9 Hz, CHP), 52.5 (d, J _CP = 3.7 Hz, CH₂Ph), 52.9 [d, J _CP = 6.5 Hz, (CH₃O)₂P], 53.0 [d, J _CP = 7.3 Hz, (CH₃O)₂P], 127.3, 128.5, 128.6, 140.3. ³¹P NMR (80 MHz, CDCl₃): δ = 32.58. HRMS (FAB⁺): m/z calcd for C₁₄H₂₅NO₃P: 286.1572 found: 286.1570. Compound 1j: yellow liquid. ¹H NMR (400 MHz, CDCl₃): δ = 1.06 [s, 9 H, (CH₃)₃C], 1.7 (br s, 1 H, NH), 2.57 (d, J _HP = 15.6 Hz, 1 H, CHP), 3.76 [d, J _HP = 10.4 Hz, 3 H, (CH₃O)₂P], 3.78 (AB system, J = 12.4 Hz, 1 H, CH₂Ph), 3.79 [d, J _HP = 10.8 Hz, 3H, (CH₃O)₂P], 4.05 (AB system, J = 12.4 Hz, 1 H, CH₂Ph), 7.23–7.38 (m, 5 H, HAr). ¹³C NMR (100 MHz, CDCl₃): δ = 27.7 [d, J _CP = 6.5 Hz, (CH₃)₃C], 35.4 [d, J _CP = 7.3 Hz, C(CH₃)₃], 52.1 [d, J _CP = 6.6 Hz, (CH₃O)₂P], 52.8 [d, J _CP = 7.3 Hz, (CH₃O)₂P], 55.4 (d, J _CP = 2.2 Hz, CH₂Ph), 64.5 (d, J _CP = 138.5 Hz, CHP), 127.3, 128.5, 128.6, 140.4. ³¹P NMR (80 MHz, CDCl₃): δ = 31.99. HRMS (FAB⁺): m/z calcd for C₁₄H₂₅NO₅P: 286.1572; found: 286.1565. Compound 1k: yellow liquid. ¹H NMR (400 MHz, CDCl₃): δ = 1.88 (br s, 1 H, NH), 3.67–3.82 [m, 8 H, (CH₃O)₂P, CHP, and CH₂Ph], 3.97 (AB system, J = 13.4 Hz, 1 H, CH₂Ph), 6.12–6.17 (m, 1 H, CH), 6.62 (d, J _HH = 16.0 Hz, 1 H, CH), 7.26–7.41 (m, 10 H, HAr). ¹³C NMR (100 MHz, CDCl₃): δ = 51.5 (d, J _CP = 16.1 Hz, CH₂Ph), 53.7 [d, J _CP = 6.6 Hz, (CH₃O)₂P], 53.9 [d, J _CP= 7.3 Hz, (CH₃O)₂P], 57.7 (d, J _CP = 155.1 Hz, CHP), 124.1 (d, J _CP = 6.6 Hz, CH), 126.8, 127.4, 128.2, 128.5, 128.7, 128.8, 134.9 (d, J _CP = 14.0 Hz, CH), 136.5, 139.5. ³¹P NMR (80 MHz, CDCl₃): δ = 27.06. HRMS (FAB⁺): m/z calcd for C₁₈H₂₃NO₃P: 332.1416; found: 332.1420. Compound 2b: yellow liquid. ¹H NMR (400 MHz, CDCl₃): δ = 1.02 (t, J _HH = 7.2 Hz, 3 H, CH₃), 2.07–2.21 (m, 2 H, CH₂CH₃ and NH), 2.40–2.50 (m, 1 H, CH₂CH₃), 3.51 [d, J _HP = 10.0 Hz, 3 H, (CH₃O)₂P], 3.70 (AB system, J = 13.2 Hz, 1 H, CH₂Ph), 3.72 [d, J _HP = 10.4 Hz, 3 H, (CH₃O)₂P], 3.76 (AB system, J = 12.8 Hz, 1 H, CH₂Ph), 7.24–7.45 (m, 8 H, HAr), 7.70–7.73 (m, 2 H, HAr). ¹³C NMR (100 MHz, CDCl₃): δ = 7.9 (d, J _CP = 6.1 Hz, CH₃), 27.3 (CH₂), 46.7 (d, J _CP = 9.1 Hz, CH₂Ph), 53.2 [d, J _CP = 7.6 Hz, (CH₃O)₂P], 53.5 [d, J _CP = 6.0 Hz, (CH₃O)₂P], 64.4 (d, J _CP = 142.6 Hz, CHP), 127.1, 127.3 (d, J _CP = 3.1 Hz), 128.1, 128.2, 128.3, 128.5, 139.0, 140.8. ³¹P NMR (80 MHz, CDCl₃): δ = 29.92. HRMS (FAB⁺): m/z calcd for C₁₈H₂₅NO₃P: 334.1572; found: 334.1581. Compound 2d: yellow liquid. ¹H NMR (400 MHz, CDCl₃): δ = 1.80–1.87 (m, 1 H, CH₂), 2.09–2.25 (m, 2 H, CH₂), 2.32–2.43 (m, 1 H, CH₂), 2.78–2.85 (m, 2 H, CH₂), 3.45 [d, J _HP = 10.0 Hz, 3 H, (CH₃O)₂P], 3.51 (AB system, J = 12.0 Hz, 1 H, CH₂Ph), 3.70 (AB system, J = 12.4 Hz, 1 H, CH₂Ph), 3.75 [d, J _HH = 10.8 Hz, 3H, (CH₃O)₂P], 7.13–7.33 (m, 8 H, HAr), 7.76–7.80 (m, 1 H, HAr). ¹³C NMR (100 MHz, CDCl₃): δ = 20.3 (d, J _CP = 3.1 Hz, CH₂), 30.2 (CH₂), 30.4 (CH₂), 47.0 (d, J _CP = 12.1 Hz, CH₂Ph), 53.7 [d, J _CP = 7.6 Hz, (CH₃O)₂P], 54.1 [d, J _CP = 7.6 Hz, (CH₃O)₂P], 60.2 (d, J _CP = 148.7 Hz, CHP), 126.2 (d, J _CP = 3.0 Hz), 127.1, 127.7 (d, J _CP = 3.0 Hz), 128.4, 128.5, 128.8 (d, J _CP = 4.6 Hz), 128.9, 129.6, 139.8 (d, J _CP = 6.1 Hz), 140.6. ³¹P NMR (80 MHz, CDCl₃): δ = 30.52. HRMS (FAB⁺): m/z calcd for C₁₉H₂₅NO₃P: 346.1572; found: 346.1568. Compound 2e: dark brown oil. ¹H NMR (400 MHz, CDCl₃): δ = 2.17 (br s, 1 H, NH), 2.30–2.43 (m, 1 H, CH₂), 2.59–2.70 (m, 1 H, CH₂), 3.00–3.05 (m, 2 H, CH₂), 3.52 (AB system, J = 12.8 Hz, 1 H, CH₂Ph), 3.60 [d, J _HP = 10.4 Hz, 3 H, (CH₃O)₂P], 3.70 (AB system, J = 12.4 Hz, 1 H, CH₂Ph), 3.72 [d, J _HP = 10.4 Hz, 3 H, (CH₃O)₂P], 7.20–7.33 (m, 8 H, HAr), 7.49–7.52 (m, 1 H, HAr). ¹³C NMR (100 MHz, CDCl₃): δ = 30.6 (d, J _CP = 3.0 Hz, CH₂), 32.2 (CH₂), 46.9 (d, J _CP = 12.1 Hz, CH₂Ph), 53.6 [d, J _CP = 7.6 Hz, (CH₃O)₂P], 54.3 [d, J _CP = 6.0 Hz, (CH₃O)₂P], 69.7 (d, J _CP = 154.7 Hz, CHP), 125.1, 125.7 (d, J _CP = 3.0 Hz), 126.7, 127.1, 128.3, 128.5, 128.7, 140.2, 140.5, 145.0 (d, J _CP = 7.6 Hz). ³¹P NMR (80 MHz, CDCl₃): δ = 29.41. HRMS (FAB⁺): m/z calcd for C₁₈H₂₃NO₃P: 332.1416; found: 332.1431. Compound 2f: brown solid; mp 85–87 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.80 (br s, 1 H, NH), 3.12 (dd, J = 16.4, 7.2 Hz, 2 H, CH₂), 3.53 (dd, J = 16.4, 13.2 Hz, 2 H, CH₂), 3.77 [d, J _HP = 10.4 Hz, 3 H, (CH₃O)₂P], 3.78 [d, J _HP = 10.4 Hz, 3H, (CH₃O)₂P], 3.84 (s, 2 H, CH₂Ph), 7.16–7.25 (m, 9 H, HAr). ¹³C NMR (100 MHz, CDCl₃): δ = 41.0 (d, J _CP = 6.1 Hz, CH₂), 48.4 (d, J _CP = 6.1 Hz, CH₂Ph), 53.4 [d, J _CP = 6.0 Hz, (CH₃O)₂P], 64.3 (d, J _CP = 156.3 Hz, CHP), 124.6, 127.0, 128.2, 128.4, 140.5, 140.6, 140.8. ³¹P NMR (80 MHz, CDCl₃): δ = 32.42. HRMS (FAB⁺): m/z calcd for C₁₈H₂₃NO₃P: 332.1416; found: 332.1431. Compound 2i: yellow liquid. ¹H NMR (400 MHz, CDCl₃): δ = 0.99 (t, J _HH = 7.2 Hz, 3 H, CH₃CH₂), 1.31, (d, J _HP = 16.0 Hz, 3 H, CH₃), 1.65–1.78 (m, 2 H, CH₂CH₃ and NH), 1.81–1.91 (m, 1 H, CH₂CH₃), 3.80 [d, J _HP = 10.4 Hz, 3 H, (CH₃O)₂P], 3.82 [d, J _HP = 10.4 Hz, 3H, (CH₃O)₂P], 3.83 (AB system, J = 12.4 Hz, 1 H, CH₂Ph), 3.90 (AB system, J = 12.4 Hz, 1 H, CH₂Ph), 7.21–7.38 (m, 5 H, HAr). ¹³C NMR (100 MHz, CDCl₃): δ = 7.2 (d, J _CP = 7.6 Hz, CH₃), 20.6 (CH₃), 27.4 (CH₂), 47.6 (CH₂Ph), 52.9 [d, J _CP = 7.6 Hz, (CH₃O)₂P], 53.2 [d, J _CP= 7.6 Hz, (CH₃O)₂P], 57.1 (d, J _CP = 141.1 Hz, CP), 127.1, 128.4, 128.6, 141.2. ³¹P NMR (80 MHz, CDCl₃): δ = 34.32. HRMS (FAB⁺): m/z calcd for C₁₃H₂₃NO₃P: 272.1416; found: 272.1417. Compound 2j: yellow liquid. ¹H NMR (400 MHz, CDCl₃): δ = 0.99 (t, J _HH = 8.0 Hz, 6 H, CH₃CH₂), 1.71–1.85 (m, 5 H, CH₂CH₃ and NH), 3.80 [d, J _HP = 10.8 Hz, 6 H, (CH₃O)₂P], 3.85 (s, 2 H, CH₂Ph), 7.22–7.38 (m, 5 H, HAr). ¹³C NMR (100 MHz, CDCl₃): δ = 7.7 (d, J _CP = 6.1 Hz, CH₃), 25.8 (d, J _CP = 4.5 Hz, CH₂), 47.3 [d, J _CP = 3.0 Hz, (CH₃O)₂P], 52.7 (d, J _CP = 9.1 Hz, CH₂Ph), 60.6 (d, J _CP = 136.5 Hz, CHP), 127.0, 128.3, 128.5, 141.2. ³¹P NMR (80 MHz, CDCl₃): δ = 30.61. HRMS (FAB⁺): m/z calcd for C₁₄H₂₅NO₃P: 286.1572; found: 286.1575.

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