Efficient Suzuki-Miyaura Coupling of Deactivated Aryl Chlorides Catalyzed by an Oxime Palladacycle

Abstract

Aryl chlorides are efficiently cross-coupled with aryl boronic acids using 0.25 mol% of 4,4′-dichlorobenzophenone oxime derived palladacycle as precatalyst in the presence of 1 mol% of [HP(t-Bu)₃]BF₄ as ligand, K₂CO₃ as base, TBAOH as additive, and DMF as solvent under conventional thermal or MW irradiation conditions. Under these simple reaction conditions a wide array of deactivated and hindered aryl chlorides react cleanly to afford in high yields functionalized biaryl derivatives.

palladacycles - boronic acids - cross-coupling - biaryls - Suzuki reaction

References and Notes

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At this point, the efficiency of the previously tested phosphane ligands with TBAOH as additive was tested again, showing in all cases lower activities. For example, P(t-Bu)₃ only led to a 31% isolated yield of 4a.

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Typical Procedure for the Suzuki Coupling under MW Irradiation Conditions (Table 2, Entry 3)
A freshly stock soln of catalyst 1 (150 µg, 0.019 mmol) in DMF (2.5 mL) and [HP(t-Bu)₃]BF₄ (110 g, 0.0375 mmol) in DMF (2.5 mL) were previously prepared and used. A 10 mL MW vessel was charged with K₂CO₃ (1.5 mmol, 207 mg), TBAOH (0.15 mmol, 120 mg), PhB(OH)₂ (1.88 mmol, 225 mg), catalyst 1 (250 µL of the stock soln, 0.0019 mmol, 15 µg, 0.5 mol% Pd), [HP(t-Bu)₃]BF₄ (250 µL of the stock soln, 0.00375 mmol, 11 µg), 4-chloroanisole (0.75 mmol, 92 µL), and DMF (1.5 mL). The vessel was sealed with a pressure lock, and the mixture was heated in air at 130 ˚C by a MW irradiation of 40 W for 20 min in a CEM Discover MW reactor. After allowing the reaction to cool down to r.t., the mixture was filtered through a pad of Celite and poured into an excess of H₂O (5 mL) and extracted with Et₂O (3 × 5 mL). The combined organic phases were washed with H₂O (3 × 5 mL), dried (MgSO₄), and evaporated. The obtained crude product was purified by recrystallization in MeOH-H₂O (3:1), yielding 102 mg of pure 4-methoxybiphenyl (4a, 74%) as a white solid; mp 89-93 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 7.57-7.51 (m, 4 H, ArH), 7.42 (t, J = 7.5 Hz, 2 H, ArH), 7.30 (t, J = 7.2 Hz, 1 H, ArH), 6.98 (d, J = 8.7 Hz, 2 H, ArH), 3.86 (s, 3 H, CHO). MS (EI, 70 eV): m/z (%) = 184 (100) [M⁺], 169 (49) [M⁺ - Me], 141 (49), 139 (13), 115 (35).

<A NAME="RG27309ST-18A">18a</A>

p-Biphenylacetic acid(felbinac) and 2-ethyl-4-biphenylacetic acid with dimethylaminoethanol-(namoxyrate) are anti-inflamatory and analgesic drugs, respectively: USP Dictionary of USAN and International Drugs names.

<A NAME="RG27309ST-18B">18b</A> p-Biphenylacetamides have been used as mesogenic arms in porphyrin thermotropic liquid crystals: Michaeli S. Hugerat M. Levanon H. Bernitz M. Natt A. Neumann R. J. Am. Chem. Soc.  1992,  114:  3612