α-Arylation of Aryl Ketones: Expanding the Scope of the Truce-Smiles Rearrangement

Abstract

The Truce-Smiles rearrangement has been applied to the synthesis of substituted α-aryl aryl ketones and the synthetic utility of the products has been demonstrated by the conversion of one of them to the substituted indole 2-(1H-indol-2-yl)phenol.

arylation - ketone - rearrangement - indole - Truce-Smiles

References and Notes

1

New Address: T. J. Snape, School of Pharmacy, Maudland Building, University of Central Lancashire, Preston, PR1 2HE, UK.

2 Millard A. Rathke M. J. Am. Chem. Soc.  1977,  99:  4833 

3 Bella M. Kobbelgaard S. Jørgensen K. J. Am. Chem. Soc.  2005,  127:  3670 

4 Horton D. Bourne G. Smythe M. Chem. Rev.  2003,  103:  893 

5 Mitchell L. Barvian N. Tetrahedron Lett.  2004,  45:  5669 

6 Erickson W. McKennon M. Tetrahedron Lett.  2000,  41:  4541 

7 Snape T. Chem. Soc. Rev.  2008,  in press; DOI:10.1039/B808960D

8

Representative Example - Synthesis of 5
2′-Hydroxyacetophenone (0.5 g, 3.67 mmol), and 1-fluoro-2-nitrobenzene (0.39 mL, 3.67 mmol) were dissolved in DMSO (37 mL). Potassium carbonate (1.27 g, 9.18 mmol) was added and the reaction stirred at r.t. for 17 h. Upon consumption of the starting material (TLC) H₂O (30 mL) was added and the mixture acidified with 1 M HCl (to pH ca. 3). The product was extracted with EtOAc (2 × 30 mL) and the combined organic layers were washed with H₂O (2 × 30 mL) and brine (30 mL), dried (MgSO₄), and the solvent removed in vacuo. The crude product was purified by column chromatography on silica gel (3% EtOAc in toluene) to give the title compound as a yellow solid (614 mg, 65%). R _f = 0.18 (10% EtOAc in PE); mp 111-113 ˚C (EtOAc-toluene). IR: ν_max = 3070 (br OH), 1644 (C=O) cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 11.84 (1 H, s, OH), 8.18 (1 H, dd, J = 1.6, 10.8 Hz, Ar), 7.91 (1 H, dd, J = 2.2, 10.6 Hz, Ar), 7.64 (1 H, td, J = 1.6, 10.0 Hz, Ar), 7.52 (2 H, td, J = 2.0, 10.0 Hz, Ar), 7.32 (1 H, dd, J = 1.6, 10.0 Hz, Ar), 7.02-6.94 (2 H, m, Ar), 4.79 (2 H, s, CH₂). ^¹³C NMR (75 MHz, CDCl₃): δ = 201.2, 162.5, 148.9, 140.4 (C), 136.7, 133.7, 133.6, 129.7, 128.7, 125.3, 119.1 (CH), 119.0 (C), 118.7 (CH), 43.7 CH₂). MS (ES⁺): m/z (%) = 258 (50) [M + H]⁺. HRMS: m/z calcd for C₁₄H₁₂NO₄ [M+H⁺]: 258.0766; found: 258.0786.

9 Bordwell F. Cornforth F. J. Org. Chem.  1978,  43:  1763 

10

Synthesis of 18
1-(2-Hydroxyphenyl)-2-(2-nitrophenyl)ethanone (5, 105 mg, 0.41 mmol) was dissolved in MeOH (4.1 mL). Then,
Pd/C (10 mg, 10 wt%) was added, and the flask evacuated and backfilled with hydrogen (3 cycles). The reaction was then stirred under an atmosphere of hydrogen for 18 h. The reaction was filtered through Celite and eluted with MeOH (10 mL) and the solvent removed in vacuo. The crude product was purified by column chromatography on silica gel (10% EtOAc in PE) to give the title compound as a pale yellow solid (62 mg, 72%). R _f = 0.39 (30% EtOAc in PE); mp 170-172 ˚C (EtOAc-PE). IR: n_max 3500 (OH), 3425 (NH) cm^-¹. ^¹H NMR (300 MHz, CDCl₃): d = 9.22 (1 H, br s), 7.70 (1 H, dd, J = 1.6, 7.8 Hz, Ar), 7.66 (1 H, d, J = 7.8 Hz, Ar), 7.42 (1 H, d, J = 8.1 Hz, Ar), 7.26-7.11 (3 H, m, Ar), 7.04 (1 H, td, J = 1.1, 7.6 Hz, Ar), 6.91 (1 H, dd, J = 0.9, 8.1 Hz, Ar), 6.87 (1 H, m, Ar), 6.00-5.00 (1 H, br s). ^¹³C NMR (75 MHz, CDCl₃): δ = 152.0, 136.4, 134.8 (C), 128.9 (CH), 128.4 (C), 128.3, 122.2, 121.5, 120.4, 120.1 (CH), 119.1 (C), 116.6, 111.0, 100.2 (CH). MS (ES⁺): m/z (%) = 210 [M + H]⁺. HRMS: m/z calcd for C₁₄H₁₂NO [M + H⁺]: 210.0919; found: 210.0920.