Fluolead

Introduction

Fluorination is a very useful strategy in the design and synthesis of bioactive compounds, since the special nature of fluorine can confer enhanced binding interactions, metabolic stability and desirable physical properties to a molecule. In fact, approximately 5–15% of the total number of drugs launched in the past 50 years were fluorinated compounds and this percentage has noticeably increased in the past five years.[ ¹ ] Recently, a novel deoxofluorinating agent, 4-tert-butyl-2,6-dimethylphenylsulfur trifluoride (named Fluolead™, 1) has been reported.[2] [3] Fluolead™ is a versatile reagent with relative high thermal and hydrolytic stability that fluorinates a broad range of substrates, generally more efficiently and selectively than currently available deoxofluorinating agents, such as diethylaminosulfur trifluoride (DAST), Deoxo-Fluor™ and other related reagents.[ ^2,3,6,14 ] In addition, it can be obtained from commercial sources or be easily prepared in two steps from commercial available 5-tert-butyl-m-xylene (Scheme [1]).[2] [5] Because it is versatile, efficient, shelf-stable, easy-to-handle, and relative highly safe, Fluo­lead™ is expected to be widely used in both academic and industrial areas.[ ² ]

Scheme 1

• References

• 1 Hagmann WK. J. Med. Chem. 2008; 51: 4359
• 2 Umemoto T, Singh RP, Xu Y, Saito N. J. Am. Chem. Soc. 2010; 132: 18199
• 3 Umemoto T, Xu Y. US Patent 7,265,247 B1, 2007
• 4a Fukumura K, Sonoda H, Hayashi H, Kusumoto M. US Patent 6,686,509 B2, 2004
• 4b Kirsch P, Bremer M, Huber F, Lannert H, Ruhl A, Lieb M, Wallmichrath T. J. Am. Chem. Soc. 2001; 123: 5414
• 4c Chang Y, Tewari A, Adi A.-I, Bae C. Tetrahedron 2008; 64: 9837
• 5 Xu W, Martinez H, Dolbier WR. Jr. J. Fluorine Chem. 2011; 132: 482
• 6 Umemoto T, Singh RP. US Patent 7,501,543 B2, 2009
• 7a Van der Puy MJ. J. Fluorine Chem. 1979; 13: 365
• 7b Hasek WR, Smith WC, Engelhardt VA. J. Am. Chem. Soc. 1960; 82: 543
• 8a Posner GH, Haines SR. Tetrahedron Lett. 1985; 26: 5
• 8b Lal GS, Pez GP, Pesaresi JR, Prozonic FM. Cheng H. J. Org. Chem. 1999; 64: 7048
• 9 Bresciani S, O’Hagan D. Tetrahedron Lett. 2010; 51: 5795
• 10a Haffner CD, McDougald DL, Reister SM, Thompson BD, Conlee C, Fang J, Bass J, Lenhard JM, Croom D, Secosky-Chang MB, Tomaszek T, McConn D, Wells-Knecht K, Johnson PR. Bioorg. Med. Chem. Lett. 2005; 15: 5257
• 10b Koo KD, Kim MJ, Kim S, Kim K.-H, Hong S.-Y, Hur G.-C, Yim HJ, Kim GT, Han HO, Kwon OH, Kwon TS, Koh JS, Lee C.-S. Bioorg. Med. Chem. Lett. 2007; 15: 4167
• 11 Singh RP, Umemoto T. J. Org. Chem. 2011; 76: 3113
• 12 Hugenberg V, Fröhlich R, Haufe G. Org. Biomol. Chem. 2010; 8: 5682
• 13a Dechamps I, Pardo GD, Cossy J. Synlett 2007; 263
• 13b Dechamps I, Pardo GD, Cossy J. Eur. J. Org. Chem. 2007; 4224