Synthesis and atropisomerism of 2,2′-ortho disubstituted biphenyls

Tetrahedron Letters

Volumn 51, Issue 48, 2010, Pages 6213-6215

  Wang, C H ^a   Reilly, J ^a   Brand, N ^a   Schwartz, S ^a   Alluri, S ^a   Chan, T M ^b   Buevich, A V ^b   Ganguly, A K ^a  

^a Stevens Institute of Technology   (United States)

^b MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Atropisomerism; Radical cyclization

Indexed keywords

BIPHENYL DERIVATIVE;

ARTICLE; CHEMICAL REACTION; CHEMICAL STRUCTURE; HECK REACTION; ISOMERISM; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; RING CLOSING METATHESIS; SYNTHESIS;

EID: 78049381817     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2010.09.010     Document Type: Article

References (18)

1. C.H. Wang, S. Alluri, and A.K. Ganguly Tetrahedron Lett. 50 2009 1879 1881
2. D.K. Rayabarapu, A. Zhou, K.O. Jeon, T. Samarakoon, A. Rolfe, H. Siddiqui, and P.R. Hanson Tetrahedron 65 2009 3180 3188
3. K.C. Majumdar, B. Chattopadhyay, and K. Ray Tetrahedron Lett. 48 2007 7633 7636
4. 3 as solvent with TMS as an internal standard unless otherwise stated. NMR and high resolution mass spectra of all the compounds described in this letter were consistent with the assigned structures. Assignments were further confirmed using 2D NMR and NOE experiments. The figures in parenthesis in all the schemes represent yields in the reactions. It should be noted that the yields reported in this letter are not optimised. The purity of the compounds was established using various chromatographic techniques. Compounds 10, 11, 15, 18, 19, 20, 21, 22, 24, 25, 26, 27, 28, 29, 30, 31, and 32 were not crystalline. All other compounds described in the Letter were crystalline. Crystals were obtained from DCM-hexane for compounds 2, 8, 9, 16, and 23 and from THF-hexane for compounds 12 and 13. The melting points of compounds 2, 8, 9, 12, 13, 16, and 23 were 163-165, 139-141, 214-216, 108-110 (decomposes), >235, 199-200, and 179-181 °C, respectively.
5. Preparation of imine 6. A solution of 5-(trifluoro-methoxy)isatin (500 mg, 2.77 mmol) and 2-bromoaniline (372 mg, 2.77 mmol) in ethanol was refluxed for 6 h. The mixture was evaporated to dryness and the product used for the next step without purification.
6. Preparation of 8. To a solution of 6 (800 mg, 2.08 mmol) in DMF, indium (238.6 mg, 2.08 mmol) and sodium iodide (467 mg, 3.12 mmol) were added. To the stirred reaction mixture cinnamyl bromide (0.41 mL, 3.12 mmol) was added dropwise. After completion of the reaction it was filtered and evaporated to dryness. The crude reaction mixture was extracted with DCM, the organic layer washed with water, dried over anhydrous sodium sulfate, filtered and evaporated, followed by column chromatography to yield compound 8.
7. Example of radical cyclisation: Preparation of 10 and 11. To a solution of 8 (170 mg, 0.34 mmol) in toluene (30 mL), AIBN (11.1 mg, 0.07 mmol)) was added. TBTH (0.10 mL, 0.37 mmol) was then added dropwise to the reaction mixture which was then heated for 1 h at 110 °C at which point another 0.2 equiv of AIBN and 1.1 equiv of TBTH were added. The mixture was evaporated to dryness followed by extraction with DCM. The organic layer was washed with water, dried over anhydrous sodium sulfate and after evaporation purified by column chromatography to obtain pure products.
8. H. Firouzabadi, N. Iranpoor, and F. Ebrahimzadeh Tetrahedron Lett. 47 2006 1771 1775
9. V.K. Yadav, and K.G. Babu Tetrahedron 59 2003 9111 9116
10. A.R. Hajipour, A.R. Falahatia, and A.E. Ruoho Tetrahedron Lett. 47 2006 4191 4196
11. 3(15.3 mg, 0.06 mmol) and triethylamine (0.10 mL, 2.56 mmol) were added. The reaction mixture was refluxed for 24 h and then evaporated to dryness, extracted with DCM and the organic layer washed with water, dried over anhydrous sodium sulfate, filtered, evaporated, followed by column chromatography to yield pure product.
12. 3(25.2 mg, 0.09 mmol) were added. The reaction mixture was stirred under nitrogen to which triethylamine (0.14 mL, 0.96 mmol) and bromobenzene (0.325 mL, 2.56 mmol) were added dropwise. The mixture was refluxed for 2 days, evaporated to dryness and extracted with DCM. The organic layer was washed with water, dried over anhydrous sodium sulfate, filtered, evaporated, followed by column chromatography to yield compound 2.
13. Preparation of 24. To a solution of 23 (100 mg, 0.38 mmol) in DMF, cesium carbonate (246.8 mg, 0.76 mmol), sodium iodide (114 mg, 0.76 mg), and allyl bromide (0.08 mL, 0.84 mmol) were added. The reaction was refluxed for 3 h. The mixture was filtered, evaporated to dryness and extracted with DCM. Compound 24 was obtained using column chromatography of the crude reaction mixture.
14. Example of ring closing metathesis: Preparation of 31. To a solution of 28 (127.9 mg, 0.32 mmol) in DCM, 1st generation Grubbs catalyst (13.3 mg, 0.02 mmol) was added. The reaction was refluxed for 2 h. The reaction mixture was diluted with DCM and washed with water. The organic layer was dried over anhydrous sodium sulfate, filtered, evaporated, and the crude product was chromatographed to yield compound 31.
15. Preparation of 26. To a solution of 23 (300 mg, 1.14 mmol) in DMF, sodium iodide (204.1 mg, 1.36 mmol) and allyl bromide (0.118 mL, 1.36 mmol) were added. The reaction mixture was stirred at room temperature for one day. It was evaporated to dryness and the residue extracted with DCM. The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated to dryness. Purification by column chromatography yielded compound 26.
16. Preparation of 28 (29). To a solution of 26 (250 mg, 0.82 mmol) in DMF (7 mL), cesium carbonate (321.1 mg, 0.99 mmol), sodium iodide (147.7 mg, 0.986 mmol), and benzyl bromide (0.12 mL, 0.99 mmol) were added. The reaction mixture was stirred at room temperature over night, filtered, evaporated and chromatographed to yield 28 (29).
17. PCModel v. 8.5 Serena Software, Bloomington IN 47402-3076.
18. E.L. Eliel, S.H. Wilen, and L.N. Mander Stereochemistry of Organic Compounds 1994 John Wiley and Sons pp 1142-1145