Aqueous Suzuki–Miyaura Coupling with Ultralow Palladium Loading and Simple Product Separation

^◊ These authors contributed equally to this work.

Abstract

The diphosphine ligand N,N-bis(diphenylphosphanylmethyl)-aniline (bdppma) and PdCl₂ afforded a Suzuki–Miyaura catalyst [(bdppma­)PdCl₂] that was highly efficient at an ultralow catalyst loading (0.001 mol%) in 20:1 H₂O–EtOH. This low catalyst loading in an aqueous solvent system permitted simple product separation by direct filtration without the need for chromatography. The ligand bdppma imparted surprisingly better reactivity than that achieved with other bidentate diphosphine ligands, but the catalytic system had a slightly narrower substrate scope than some similar Pd catalysts reported previously.

Key words

Suzuki–Miyaura reaction - palladium catalysis - ligands - aryl bromides - arylboronic acids - biaryls

• References and Notes

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• 23a [(bdppma)PdCl₂] (1)Bdppma (0.0245 g, 0.05 mmol) and PdCl₂ (0.0089 g, 0.05 mmol) were stirred in DMF (3 mL) for 3 h at r.t. Slow evaporation of the solvent in air afforded yellow blocks of 1·DMF after 2 days. These were collected by filtration, washed with Et₂O, and dried in vacuo; yield: 0.0267 g (80%).IR (KBr): 3049(w), 2924(w), 2869(w), 1671(s), 1595(m), 1493(m), 1435(s), 1419(s), 1384(m), 1335(w), 1313(w), 1200(m), 1187(w), 1160(w), 1100(s), 1028(m), 999(w), 872(m), 852(m), 768(s), 734(s), 691(s), 617(w), 588(w), 509(s), 492(s) cm^–1. ¹H NMR (600 MHz, DMSO-d ₆): δ = 7.98 (t, J = 8.9 Hz, 8 H), 7.95 (s, 0.66 H), 7.60–7.51 (m, 12 H), 6.91 (t, J = 7.8 Hz, 2 H), 6.67 (t, J = 7.1 Hz, 1 H), 6.50 (d, J = 8.0 Hz, 2 H), 4.63 (s, 4 H), 2.89 (s, 2 H), 2.73 (s, 2 H). ¹³C NMR (151 MHz, DMSO-d ₆): δ = 162.3, 149.1, 134.4, 128.7, 128.4, 128.4, 128.3, 120.4, 116.5, 52.1, 51.8, 35.8, 30.8. ³¹P NMR (151 MHz, DMSO-d ₆): δ = 10.84. Anal. Calcd for C₃₅H₃₆Cl₂N₂OP₂Pd: C, 56.81; H, 4.90; N, 3.79. Found: C, 56.47; H, 5.07; N, 3.55.
• 24 X-ray Data Collection and Structural DeterminationX-ray diffraction analysis of a single crystal of 1·DMF was performed on an Agilent Xcalibur CCD X-ray diffractometer using graphite-monochromated Mo Kα (λ = 0.71073 Å) radiation at 173 K. The program CrysAlisPro (Ver. 1.171.36.32, 2013; Agilent Technologies: Santa Clara) was used for the refinement of the cell parameters and the reduction of collected data, while absorption corrections (multi-scan) were applied. Reflection data were also corrected for Lorentz and polarization effects. The crystal structure of 1·DMF was solved by direct methods and refined on F ² by full-matrix least-squares methods with the SHELXTL-2016 program package. The DMF solvent molecule was disordered over two sites with occupancies of 0.7/0.3. All non-H atoms were refined anisotropically. All H atoms were placed in geometrically idealized positions. A summary of the key crystallographic information is given in the SI (Table S1).
• 25 Sheldrick GM. SHELXTL-2016 . Universität Göttingen; Germany: 2016
• 26 1-Biphenyl-4-ylethanone (Table [4], Entry 4); Typical ProcedureA stock solution containing PdCl₂ (1.8 mg, 0.01 mmol) and bdppma (4.9 mg, 0.01 mmol) in DMF (1 mL) was prepared. A Schlenk tube equipped with a magnetic stirrer bar was charged with 4′-bromoacetophenone (199 mg, 1 mmol), PhB(OH)₂ (183 mg, 1.5 mmol), and K₂CO₃ (414 mg, 3 mmol). An aliquot of bdppma/PdCl₂ (1 μL, 0.00001 mmol) was added to the Schlenk tube by syringe, followed by 1:20 EtOH–H₂O (4 mL). The tube was sealed, and the mixture was refluxed with stirring for 1 h. At the end of the reaction, the solution was cooled to r.t., H₂O was added, and the product was isolated by filtration as a white solid; yield: 194 mg (99%); mp 119.5-121.0 °C.¹H NMR (400 MHz, DMSO-d ₆): δ = 8.04 (d, J = 8.4 Hz, 2 H), 7.82 (d, J = 8.4 Hz, 2 H), 7.75 (d, J = 7.1 Hz, 2 H), 7.51 (t, J = 7.3 Hz, 2 H), 7.43 (t, J = 7.2 Hz, 1 H), 2.61 (s, 3 H). ¹³C NMR (151 MHz, DMSO-d ₆): δ = 197.5, 144.5, 138.9, 135.6, 129.1, 128.9, 128.4, 127.0, 126.8, 26.7.