Sequential Coupling-Isomerization-Coupling Reactions - A Novel Three-Component Synthesis of Aryl Chalcones

Wei-Wei Liao; Thomas J. J. Müller

doi:10.1055/s-2006-956480

LETTER

Sequential Coupling-Isomerization-Coupling Reactions - A Novel Three-Component Synthesis of Aryl Chalcones

Wei-Wei Liao, Thomas J. J. Müller*
Organisch-Chemisches Institut der Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
Fax: +49(6221)546579; e-Mail: Thomas.J.J.Mueller@oci.uni-heidelberg.de;

Abstract

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Abstract

Bromoaryl boronates bear a halide and a dormant organometallic functionality and, therefore, are perfectly suited for sequentially Pd-catalyzed reactions. The microwave-accelerated consecutive reaction of bromoaryl boronates, (hetero)aryl propargyl alcohols, and (hetero)aryl halides furnishes (hetero)aryl chalcones in good yields in the sense of a one-pot coupling-isomerization-coupling sequence.

Keywords

alkynes - catalysis - cross-couplings - isomerizations - microwave reactions

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References

References and Notes

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Typical Procedure (6a, Table 1, Entry 11).
To a magnetically stirred solution of 86 mg (0.30 mmol) of 4a, 42 mg (0.31 mmol) of 5a, 8 mg (12 µmol) of Pd(PPh₃)Cl₂, 2 mg (10 µmol) of CuI, and 16 mg (60 µmol) of PPh₃ in 0.9 mL of degassed THF in a microwave vial under nitrogen were added 48 µL (0.32 mmol) of DBU. Then the sealed vessel was heated by microwave irradiation to 120 °C for 30 min. After cooling to r.t., H₂O was added and the aqueous layer was extracted with EtOAc. The combined organic phases were dried with MgSO₄. The solvents were removed in vacuo and the residue was chromatographed on silica gel to give 64 mg (64%) of the desired product 6a, mp 144-145 °C. ¹H NMR (300 MHz, CDCl₃): δ = 1.36 (s, 12 H), 7.48-7.62 (m, 6 H), 7.79-7.87 (m, 3 H), 8.01-8.04 (m, 2 H). ¹³C NMR (75.5 MHz, CDCl₃): δ = 24.9 (CH₃), 84.0 (C_quat.), 122.8 (CH), 127.6 (CH), 128.5 (CH), 128.6 (CH), 132.8 (CH), 135.3 (CH), 137.3 (C_quat.), 138.2 (C_quat.), 144.6 (CH), 190.5 (C_quat.). MS (70 eV, EI): m/z (%) = 334 (100) [M⁺], 207 (32) [M⁺ - Bpin]. HRMS: m/z calcd for C₂₁H₂₃BO₃: 334.1740; found: 334.1731. Anal. Calcd for C₂₁H₂₃BO₃ (334.2): C, 75.47; H, 6.94. Found: C, 75.36; H, 6.96.

All compounds have been fully characterized by ¹H NMR, ¹³C NMR and DEPT, COSY, NOESY, HETCOR and HMBC NMR experiments, IR, MS, HRMS and/or combustion analyses.

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Without isolation, the yield for the first step is apparently higher than in the optimization (Table [1] , entry 11).

Typical Procedure (7a, Table 3, Entry 11).
To a magnetically stirred solution of 86 mg (0.30 mmol) of 4a, 42 mg (0.31 mmol) of 5a, 8 mg (12 µmol) of Pd(PPh₃)Cl₂, 2 mg (10 µmol) of CuI, and 16 mg (60 µmol) of PPh₃ in 0.9 mL of degassed THF in a microwave vial under nitrogen were added 48 µL (0.32 mmol) of DBU. Then the sealed vessel was heated by microwave irradiation to 120 °C for 30 min. After cooling to r.t. 55 mg (0.31 mmol) of 1a, 63 mg (0.45 mmol) of K₂CO₃, and 0.6 mL of H₂O were added to the reaction mixture, and then the sealed vessel was heated by microwave irradiation to 110 °C for 20 min. After cooling to r.t. H₂O was added and the aqueous layer was extracted with EtOAc. The combined organic phases were dried with MgSO₄. The solvents were removed in vacuo and the residue was chromatographed on silica gel to give 70 mg (76%) of 7a as a yellow solid, mp 120-122 °C. ¹H NMR (300 MHz, CDCl₃): δ = 7.50-7.67 (m, 6 H), 7.70-7.77 (m, 6 H), 7.85 (d, J = 15.6 Hz, 1 H), 8.05-8.02 (m, 2 H). ¹³C NMR (75.5 MHz, CDCl₃): δ = 111.4 (C_quat.), 118.7 (C_quat.), 122.7 (CH), 127.6 (CH), 127.7 (CH), 128.5 (CH), 128.7 (CH), 129.1 (CH), 132.7 (CH), 132.9 (CH), 135.2 (C_quat.), 138.0 (C_quat.), 140.9 (C_quat.), 143.6 (CH), 144.5 (C_quat.), 190.2 (C_quat.). MS (70 eV, EI): m/z (%) = 309 (100) [M⁺], 207 (50) [M⁺ - C₆H₄CN]. Anal. Calcd for C₂₂H₁₅NO (309.4): C, 85.41; H, 4.89; N, 4.53. Found: C, 85.49; H, 4.91; N, 4.58.