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Synlett 2006(20): 3469-3473  
DOI: 10.1055/s-2006-956480
LETTER
© Georg Thieme Verlag Stuttgart · New York

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;
Further Information

Publication History

Received 28 September 2006
Publication Date:
08 December 2006 (online)

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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

11

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 (Cquat.), 122.8 (CH), 127.6 (CH), 128.5 (CH), 128.6 (CH), 132.8 (CH), 135.3 (CH), 137.3 (Cquat.), 138.2 (Cquat.), 144.6 (CH), 190.5 (Cquat.). 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.

12

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.

15

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

16

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 (Cquat.), 118.7 (Cquat.), 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 (Cquat.), 138.0 (Cquat.), 140.9 (Cquat.), 143.6 (CH), 144.5 (Cquat.), 190.2 (Cquat.). 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.