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Synlett 2010(3): 427-432  
DOI: 10.1055/s-0029-1218580
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

α-Arylation and Alkynylation of Cyclic α-Iodoenones Using Palladium-Catalyzed Cross-Coupling Reactions with Trifluoroborate Salts

Kemilla Gueogjiana, Fateh V. Singha, Jesus M. Penaa, Monica F. Z. J. Amarala, Hélio A. Stefani*a,b
a Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brazil
Fax: +55(11)38154418; e-Mail: hstefani@usp.br;
b Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brazil
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Publikationsverlauf

Received 28 September 2009
Publikationsdatum:
22. Dezember 2009 (online)

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Abstract

An expeditious synthesis of α-aryl- and α-alkynylcyclohexenones is described and illustrated by palladium-catalyzed cross-coupling reaction of cyclic α-iodoenones with potassium aryltrifluoroborate salts. This procedure offers easy access to α-arylated and alkynylated cyclohexenones functionalized with electron-­donor and -acceptor substituents in good yields.

Key words

cross-coupling reaction - cyclic α-iodoenones - α-substituted enones

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General Procedure for the Cross-Coupling Reaction of Aryltrifluoroborate Salts with 2-Iodocyclohex-2-enone (Table 3, Entry 1)
To a round-bottomed flask containing phenyltrifluoroborate salt (0.5 mmol), 2-iodocyclohex-2-enone (0.5 mmol), K2CO3 (1.5 mmol), and PdCl2 (5 mol%) was added a mixture of 1,4-dioxane (4 mL) and degassed H2O (1.0 mL). The reaction mixture was allowed to stir at 80 ˚C for 5 h. After this time, the mixture was cooled to r.t., diluted with EtOAc (10 mL), and washed with sat. aq NH4Cl (3 × 10 mL). The organic phase was separated, dried over MgSO4, and concentrated under vacuum. The residue was purified by flash chromatography on silica gel using hexane-EtOAc (8:2) as the eluent.
Selected Spectral and Analytical Data for 2-Phenylcyclo-hex-2-enone (4a)
Yield 80%. ¹H NMR (300 MHz, CDCl3): δ = 7.28-7.40 (m, 5 H), 7.06 (t, 1 H, J = 4.1 Hz), 2.53-2.64 (m, 4 H), 2.09-2.17 (m, 2 H). ¹³C NMR (75 MHz, CDCl3): δ = 197.9, 147.9, 140.3, 136.5, 128.5, 127.9, 127.5, 39.0, 26.5, 22.9. LRMS: m/z (%) = 172 (100) [M+], 144 (64), 130 (26), 115 (82), 103 (16), 71 (12), 63 (14), 51 (15). IR (KBr): ν = 1662, 2933, 3016 cm-¹. Mp 93-94 ˚C (lit.¹³ 92-93 ˚C).

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General Procedure for the Cross-Coupling Reaction of Alkynyltrifluoroborate Salts with 2-Iodocyclohex-2-enone (Table 4, Entry 1) To a round-bottomed flask containing phenylethynyltri-fluoroborate salt (0.5 mmol), 2-iodocyclohex-2-enone
(0.5 mmol), K2CO3 (1.5 mmol), and PdCl2 (5 mol%) was added a mixture of 1,4-dioxane (4 mL) and degassed H2O (1.0 mL). The reaction mixture was allowed to stir at 80 ˚C for 7 h. After this time, the mixture was cooled to r.t, diluted with EtOAc (10 mL), and washed with sat. aq NH4Cl (3 × 10 mL). The organic phase was separated, dried over MgSO4, and concentrated under vacuum. The residue was purified by flash chromatography on silica gel using hexane-EtOAc (8:2) as the eluent.
Selected Spectral and Analytical Data for 2-(Phenyl-ethynyl)cyclohex-2-enone (6a)
Yield 73%. ¹H NMR (300 MHz, CDCl3): δ = 7.61-7.64 (m, 2 H), 7.24-7.38 (m, 3 H), 6.47 (t, J = 1.89 Hz, 1 H), 2.48-2.57 (m, 2 H), 2.34-2.44 (m, 2 H), 1.89-1.98 (m, 2 H). ¹³C NMR (75 MHz, CDCl3): δ = 171.5, 153.3, 150.7, 131.4, 128.6 (2 C), 127.2, 123.7 (2 C), 122.4, 105.6, 62.4, 32.5, 23.0, 21.0. LRMS: m/z (%) = 196 (100) [M+], 167 (44), 152 (17), 118 (19), 95 (22), 83 (27), 77 (16).

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General Procedure for the Cross-Coupling Reaction of Phenyltrifluoroborate Salt with 2-Iodoen-2-ones (Table 5, Entry 1)
To a round-bottomed flask containing phenyltrifluoroborate salt (0.5 mmol), (S)-1-benzoyl-5-iodo-2-isopropyl-2,3-dihydropyrimidin-4 (1H)-one (0.5 mmol), K2CO3 (1.5 mmol), and PdCl2 (5 mol%) was added a mixture of 1,4-dioxane (4 mL) and degassed H2O (1.0 mL). The reaction mixture was allowed to stir at 80 ˚C for 2 h. After this time, the mixture was cooled to r.t., diluted with EtOAc (10 mL), and washed with sat. aq NH4Cl (3 × 10 mL). The organic phase was separated, dried over MgSO4, and concentrated under vacuum. The residue was purified by flash chromatography on silica gel using hexane-EtOAc (8:2) as the eluent.
Selected Spectral and Analytical Data for ( S )-1-Benzoyl-2-isopropyl-5-phenyl-2,3-dihydropyrimidin-4 (1 H )-one (8a)
Yield 65%. ¹H NMR (300 MHz, CDCl3): δ = 7.48-7.59 (m, 6 H), 7.42 (dd, J = 7.5, 1.3 Hz, 2 H), 7.27-7.34 (m, 3 H), 6.66 (d, J = 4.4 Hz, 1 H), 5.67 (s, 1 H), 2.36-2.43 (m, 1 H), 1.09 (d, J = 6.7 Hz, 3 H), 1.01 (d, J = 6.9 Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 168.4, 163.4, 134.3, 133.4, 132.9, 131.4, 128.6 (2 C), 128.2 (2 C), 128.1 (2 C), 128.0, 127.5 (2 C), 116.6, 68.9, 32.8, 18.2, 17.4. LRMS: m/z (%) = 320 (1) [M+], 277 (14), 105 (100), 89 (2), 77 (28), 51 (4), 43 (2). IR: ν = 3396, 3053, 2992, 2859, 1652, 1607 cm-¹. Mp 173.2-174.8 ˚C.