Straightforward Transformation of Pentafluorobenzaldehyde into 4-Aryloxy-2,3,5,6-tetrafluorobenzaldehydes

Abstract

A new and practical process leading to 4-aryloxy-2,3,5,6-tetrafluorobenzaldehydes has been developed. The title skeleton is assembled in a convergent fashion from phenols and pentafluorobenzaldehyde via a nucleophilic substitution in the presence of inorganic fluorides. Scope and limitation studies have been conducted, revealing that the methodology is diversity tolerant, facilitating the introduction of various aryl and heteroaryl substituents. Altogether, 12 aldehydes were prepared in 14-93% yield.

Key words

phenols - ethers - fluorine - nucleophilic aromatic substitution - aldehydes

References

• 1a Isanbor C. O’Hagan D. J. Fluorine Chem.  2006,  127:  303 
• 1b Ismail FMD. J. Fluorine Chem.  2002,  118:  27 
• 1c Kirk KL. J. Fluorine Chem.  2006,  127:  1013 
• 1d Sun S. Adejare A. Curr. Top. Med. Chem.  2006,  6:  1457 
• 2a Sessler JL. Seidel D. Angew. Chem. Int. Ed.  2003,  42:  5134 
• 2b Gryko DT. Koszarna B. Eur. J. Org. Chem.  2005,  3314 
• 2c Gryko DT. Piechowska J. Jaworski JS. Gaūzowski M. Tasior M. Cembor M. Butenschön H. New J. Chem.  2007,  31:  1613 
• 2d Shen J. Shao J. Ou Z. E W. Koszarna B. Gryko DT. Kadish KM. Inorg. Chem.  2006,  45:  2251 
• 2e Gryko DT. Koszarna B. Synthesis  2004,  2205 
• 3 Shaw SJ. Elgie KJ. Edwards C. Boyle RW. Tetrahedron Lett.  1999,  40:  1595 
• 4 Elgie KJ. Scobie M. Boyle RW. Tetrahedron Lett.  2000,  41:  2753 
• 5a Weiss R. Puhlhofer F. Jux N. Merz K. Angew. Chem. Int. Ed.  2002,  41:  3815 
• 5b Samaroo D. Soll CE. Todaro LJ. Drain CM. Org. Lett.  2006,  8:  4985 
• 6a Yeager GW. Schissel DN. Synthesis  1991,  63 
• 6b Magdolen P. Mečiarová M. Toma Š. Tetrahedron  2001,  57:  4781 
• 7 Varala R. Ramu E. Alam MM. Adapa SR. Synlett  2004,  1747 
• 8a Beugelmans R. Bigot A. Zhu J. Tetrahedron Lett.  1994,  35:  5649 
• 8b Beugelmans R. Singh GP. Zhu J. Tetrahedron Lett.  1993,  34:  7741 
• 9 Beugelmans R. Bourdet S. Zhu J. Tetrahedron Lett.  1995,  36:  1279 
• 10a Gryko DT. Clausen C. Roth KM. Dontha N. Bocian DF. Kuhr WG. Lindsey JS. J. Org. Chem.  2000,  65:  7345 
• 10b Gryko DT. Koszarna B. Org. Biomol. Chem.  2003,  1:  350 
• 11 Keana JFW. Cai SX. J. Org. Chem.  1990,  55:  3640 
• 12a Bolton R. Sandall JPB. J. Chem. Soc., Perkin Trans. 2  1978,  1288 
• 12b Miller J. Parker AJ. J. Am. Chem. Soc.  1961,  83:  117 
• 13 Loim NM. Kelbyscheva ES. Izv. Akad. Nauk, Ser. Khim.  2004,  1995 
• 14a Vorozhtsov NN. Yakobson GG. Zh. Obshch. Khim.  1958,  28:  40; Chem. Abstr. 1958, 52, 12784 
• 14b Drayton CJ. Flowers WT. Haszeldine RN. J. Chem. Soc. D  1970,  662 
• 14c Schmittling EA. Sawyer JS. J. Org. Chem.  1993,  58:  3229 
• 14d Beugelmans R. Bigot A. Zhu J. Tetrahedron Lett.  1994,  35:  5649 
• 15 Grabchev I. Moneva I. Bojinov V. Guittonneau S. J. Mat. Chem.  2000,  10:  1291