Design and Development of a New Chelating Bis(phosphinite)-Based Palladium(II) Catalyst and Its Application to the Heck Reaction

Abstract

A new sterically demanding and bulky bis(phosphinite) ligand derived from salicylaldehyde and 2-amino-3-hydroxy ­pyridine and its palladium(II) complex has been synthesized and characterized. The utility of this palladium complex has been de­monstrated in the Heck reaction between a variety of aryl halides and olefin substrates.

palladium - Heck reaction - phosphorus - alkenes - cross-coupling

References and Notes

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13

All chemicals were obtained from commercial sources and used without further purification. All solvents were dried and distilled prior to use according to literature procedures. All known compounds were characterized by comparing their physical data with those in the literature. FT-IR spectra were recorded on a Perkin-Elmer spectrophotometer using KBr discs. ¹H NMR spectra were recorded on a Bruker (300 MHz) spectrophotometer using CDCl₃ as solvent and TMS as the internal standard. ³¹P[¹H] NMR were recorded on a Bruker 400 MHz instrument using 85% H₃PO₄ as an internal standard. FAB(MS) was obtained using a VG-AUTOSPEC Micromass (UK) equipment using MNBA as matrix. ( Z )-2-(2-Hydroxybenzlideneamino)pyridine-3-ol (1): 2-Amino-3-hydroxypyridine (2.11 g, 19.16 mmol) and salicylaldehyde (2.34 g, 19.16 mmol) in EtOH (60 mL) were stirred for 16 h at r.t. to give a brick-red suspension. The reaction mixture was concentrated (20 mL) and filtered under vacuum, washed with n-hexane and dried to afford a brick-red powder (2.96 g, 72%); mp 180 °C; ¹H NMR (300 MHz, CDCl₃): δ = 9.42 (s, 1 H, CH=N, pyridine), 8.03 (d, J = 6 Hz, 1 H, N=CH), 7.55-6.93 (overlapping m, 6 H, Ar-H); IR (KBr): 3442 (n OH), 3048 (ν C-H), 2924 (n C-H aliphatic), 1620 (n C=N- aliphatic), 1570 (C=N- of C₅H₅N), 1528 (m), 1458 (s), 1287 (m), 1182 (s), 1133 (m), 1091 (m), 1024 (w), 905 (w), 764 (m), 546 (m), 477 (w) cm^-1; MS (EI⁺): m/z [M⁺] calcd for C₁₂H₁₀N₂O₂: 214.23; found: 214. 2-(2-Hydroxybenzylamino)pyridine-3-ol (2): To a stirred brick-red suspension of Schiff’s base (1, 2.95 g, 13.8 mmol) in MeOH (40 mL), solid NaBH₄ (2.47 g, 65.3 mmol) was added in small portions gradually over a period of 4 h to give an almost colorless solution. The reaction mixture was quenched with cold H₂O, the product extracted with CH₂Cl₂ (3 × 75 mL) and dried over anhydrous Na₂SO₄. Removal of the solvent under reduced pressure afforded the desired compound as an off-white crystalline solid (1.96 g, 66%); mp 108-110 °C; ¹H NMR (300 MHz, CDCl₃): δ = 7.60 (d, J = 6 Hz, 1 H, Ar-H), 7.26-7.17 (m, 2 H, Ar-H), 6.79-6.74 (m, 3 H, Ar-H), 6.42-6.35 (m, 1 H, Ar-H), 5.58 (unresolved m, 1 H, NH), 4.47 (d, J = 6 Hz, 2 H, CH₂); IR (KBr): 3415 (ν OH + ν NH merging), 3058 (ν C-H Ar), 2925 (ν C-H aliphatic), 1621 (s), 1579 (w), 1518 (s), 1452 (m), 1352 (w), 1255 (s), 1185 (m), 1105 (m), 1039 (m), 848 (w), 755 (s), 580 (w), 534 (w) cm^-1; MS (EI⁺): m/z [M⁺] calcd for C₁₂H₁₂N₂O₂: 216.23; found: 216. N -[2-(Dicyclohexylphosphinooxy)benzyl]-3-(dicyclohexylphoshinooxy)pyridin-2-amine ( 3): Diol (2, 290 mg, 1.34 mmol) and chlorodicyclohexylphosphine (623 mg, 2.68 mmol) were dissolved in freshly distilled dry THF (40 mL) under high-purity nitrogen. To this suspension at r.t., a THF solution (5 mL) of Et₃N (272 mg, 2.69 mmol) was added dropwise over a period of 30 min via a syringe. Immediately, a white precipitate formed. The reaction mixture was stirred at r.t. overnight, filtered under nitrogen and the solvent was removed under reduced pressure to give a colorless sticky compound. Trituration with n-pentane (10 mL) initiated the formation of a white precipitate which was filtered and dried under vacuum to yield the desired ligand (334 mg, 41%); mp 126-128 °C; ¹H NMR (300 MHz, CDCl₃): δ = 7.58 (d, J = 6 Hz, 1 H, Ar-H), 7.18-7.05 (m, 2 H, Ar-H), 6.90-6.70 (m, 3 H, Ar-H), 6.45-6.38 (m, 1 H, Ar-H), 5.82 (unresolved m, 1 H, NH), 4.50 (d, J = 6 Hz, 2 H, CH₂); ³¹P [¹H] NMR (162 MHz, CDCl₃): d = 70.58 (s); IR (KBr): 3387 (ν NH), 3061 (ν Ar C-H), 2926 and 2847 (ν C-H antisymmetric and symmetric of c-Hex), 1613 (s), 1585 (w), 1524 (s), 1445 (m), 1346 (w), 1254 (s), 1183 (m), 1118 (m), 1068 (w), 999 (w), 960 (w), 939 (w), 887 (m), 844 (w), 752 (m), 723 (w), 695 (w), 593 (w), 511 (m), 485 (w); MS(FAB): m/z [M⁺] calcd for C₃₆H₅₄N₂O₂P₂: 608; found: 443 [M⁺¹ⁿ - 2 × C₆H₁₁]. Dichloro{ N -[2-(dicyclohexylphosphinooxy)benzyl]-3-(dicyclohexylphoshinooxy)pyridin-2-amine}palladium(II) (4): To a solution of [Pd(MeCN)₂Cl₂] (125 mg, 0.48 mmol)in CH₂Cl₂ (15 mL), the bis(phos-phinite) ligand (294 mg, 0.48 mmol) was added under a nitrogen atmosphere. The resultant orange solution was stirred for 2 h at r.t. to give a brown solution. The solution was filtered through celite, concentrated (5 mL) and PE (40-60 °C fraction; 5 mL) was added to precipitate the product as a pale yellow crystalline solid (330 mg, 87%); ¹H NMR (300 MHz, CDCl₃): δ = 7.90-6.60 (m, 7 H, Ar-H), 4.65 (d, J = 6 Hz, 2 H, CH₂), 2.60-0.95 (m, 44 H, 4 × C₆H₁₁); ³¹P[¹H] NMR (162 MHz, CDCl₃): δ = 112.84 (s); IR (KBr): 3382 (ν NH), 3059 (ν Ar C-H), 2927 and 2850 (ν C-H antisym-metric and symmetric of c-Hex), 2312 (w), 1735 (w) (s), 1590 (m), 1520 (w), 1446 (s), 1347 (w), 1248 (m), 1211 (w), 1176 (w), 1112 (w), 1043 (w), 1005 (w), 970 (w), 919 (w), 887 (w), 849 (w), 818 (w), 753 (m), 570 (w), 527 (w), 448 (w), 408 (w) cm^-1; MS(FAB): m/z [M⁺] calcd for C₃₆H₅₄N₂O₂Cl₂P₂Pd: 785; found: 750 [M⁺¹ⁿ - Cl], 553 [M⁺¹ⁿ - Cl-PCy₂].

14

General Procedure for the Heck Reaction: Aryl halide (0.50 mmol), olefinic substrate (0.60 mmol), n-Bu₃N (0.60 mmol) and catalyst (0.025 mmol, 5 mol%) were placed sequentially in a two-necked Schlenk flask, followed by the addition of DMF (2 mL), under a nitrogen atmosphere. The reaction mixture was stirred, gradually allowed to warm to ambient temperature for the specified reaction time (Table [1] ). After completion, the reaction mixture was diluted with H₂O, the product was extracted with EtOAc (3 × 10 mL) and the resultant organic layer was dried over anhydrous Na₂SO₄. After removal of the solvent, the residue was subjected to column chromatographic separation on silica gel using EtOAc and hexane mixtures to afford the Heck product in high purity.