Synthesis of α-Substituted Diphenylphosphinocarboxylic Acids and Their Palladium Complexes

Abstract

A general and efficient synthesis of α-substituted phosphinoacetic acids using simple esters and diphenylchlorophosphine–borane as readily available starting materials is here described. The formation and structure of the corresponding palladium complex derived from 2-ethyl diphenylphosphinoacetic acid is also reported.

Key words

phosphine - carboxylic acids - P,O-ligands - palladium - homogeneous catalysis

• References and Notes

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• 8 General Experimental Procedure n-BuLi (3.75 mL for 1.6 M solution in hexane or 2.40 mL for 2.5 M solution in hexane, 6.00 mmol, 1.2 equiv) was added to a solution of i-Pr₂NH (0.98 mL, 7.00 mmol, 1.4 equiv) in THF (1.50 mL) at 0 °C under nitrogen atmosphere and stirred for 30 min. Then, the reaction mixture was cooled down to –78 °C, and a solution of the corresponding ester (5.00 mmol, 1 equiv) in THF (25.00 mL) was added dropwise. The resulting mixture was stirred at –78 °C for 1 h. In a separate flask, a mixture of Ph₂PCl (2.75 mL, 14.85 mmol, 2.97 equiv) and BH₃·THF (15.00 mL, 1 M, 15.00 mmol, 3 equiv) in Et₂O (9.30 mL) was stirred for 30 min at room temperature and subsequently added dropwise to the reaction mixture at –78 °C. The reaction was warmed up to room temperature and stirred over the time period indicated for each example. Next, the reaction was quenched with H₂O (0.30 mL) and Et₃N (0.50 mL) and evaporated to dryness. The resulting crude was dissolved in CH₂Cl₂ (30 mL) and washed with sat. aq NaCl solution (30 mL). The organic layer was dried over anhydrous MgSO₄, filtered, and concentrated under reduced pressure. The crude was then purified by column chromatography to obtain the desired product.
• 9 Analytical Data for Representative Products Methyl 2-Ethyl Diphenylphosphinoacetate–borane (1) Yield 73%; mp 74–76 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.92–7.85 (m, 2 H), 7.75–7.65 (m, 2 H), 7.57–7.38 (m, 6 H), 3.41 (s, 3 H), 3.36 (td, J = 11.5, 3.1 Hz, 1 H), 2.00–1.84 (m, 1 H), 1.82–1.67 (m, 1 H), 0.96 (t, J = 7.3 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 170.8 (d, J = 3.6 Hz), 133.8 (d, J = 9.5 Hz), 132.8 (d, J = 9.1 Hz), 131.9 (d, J = 2.5 Hz), 131.6 (d, J = 2.5 Hz), 128.9 (d, J = 2.5 Hz), 128.7 (d, J = 2.6 Hz), 127.9 (d, J = 54.4 Hz), 126.3 (d, J = 53.9 Hz), 52.0 (s), 46.5 (d, J = 26.3 Hz), 21.8 (s), 13.7 (d, J = 12.6 Hz). ³¹P NMR (162 MHz, CDCl₃): δ = 23.03 (d, J = 72.1 Hz). ¹¹B NMR (128 MHz, CDCl₃): δ = –39.00 (br). IR: ν = 2402, 1720, 1435, 1259, 1236, 1062, 741, 692, 478 cm^–1. HRMS (FD): m/z calcd for C₁₇H₂₂BO₂P [M]⁺: 300.1445; found: 300.1451. Methyl 2-Phenyl Diphenylphosphinoacetate–borane (4) Yield 56%; mp 125–127 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.98–7.89 (m, 2 H), 7.63–7.53 (m, 3 H), 7.53–7.42 (m, 3 H), 7.40–7.32 (m, 2 H), 7.32–7.16 (m, 5 H), 4.87 (d, J = 12.2 Hz, 1 H), 3.59 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 168.7, 133.6 (d, J = 9.2 Hz), 132.9 (d, J = 8.9 Hz), 131.8 (d, J = 2.5 Hz), 131.3 (d, J = 2.4 Hz), 130.6 (d, J = 3.1 Hz), 130.1 (d, J = 4.4 Hz), 128.5 (d, J = 10.3 Hz), 128.4 (d, J = 10.0 Hz), 128.1 (d, J = 2.5 Hz), 128.0 (d, J = 2.0 Hz), 127.2 (d, J = 54.4 Hz), 126.3 (d, J = 53.5 Hz), 52.4, 51.1 (d, J = 25.2 Hz). ³¹P NMR (162 MHz, CDCl₃): δ = 25.66 (d, J = 47.7 Hz). ¹¹B NMR (128 MHz, CDCl₃): δ = –38.51 (br). IR: ν = 2376, 2348, 1733, 1433, 1209, 1100, 1055, 1029, 727, 690, 510 cm^–1. HRMS (EI): m/z calcd for C₂₁H₁₉O₂P [M – BH₃]⁺: 334.1117; found: 334.1116.
• 10 The reaction of methyl butyrate with chlorodicyclohexylphosphine provided, under the standard reaction conditions, methyl 2-ethyl dicyclohexylphosphinoacetate–borane (1a) in 10% isolated yield. The yield of this reaction has not been optimized. For analytical data, see the Supporting Information.
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