Introduction of Fluorine and Fluorine‐Containing Functional Groups

Abstract

Over the past decade, the most significant, conceptual advances in the field of fluorination were enabled most prominently by organo‐ and transition‐metal catalysis. The most challenging transformation remains the formation of the parent CF bond, primarily as a consequence of the high hydration energy of fluoride, strong metal—fluorine bonds, and highly polarized bonds to fluorine. Most fluorination reactions still lack generality, predictability, and cost‐efficiency. Despite all current limitations, modern fluorination methods have made fluorinated molecules more readily available than ever before and have begun to have an impact on research areas that do not require large amounts of material, such as drug discovery and positron emission tomography. This Review gives a brief summary of conventional fluorination reactions, including those reactions that introduce fluorinated functional groups, and focuses on modern developments in the field.

Palladium-Mediated Organofluorine Chemistry

“…The formation of perfluoroalkylphosphine oxides (the coupling reaction was followed by the oxidation of the phosphine), perfluoroalkylarsine or perfluoroalkyl selenide took place. 40, 41 The best results were obtained by using [PdCl 2 (PPh 3 ) 2 ] as catalyst with a small excess of PPh 3 and CsF as aditive (Scheme 7). The use of other palladium sources (such [Pd(PPh 3 ) 4 ] or Pd 2 (dba) 3 ), or other phosphines as ligands led to worse results.…”

“…40, 41 The best results were obtained by using [PdCl 2 (PPh 3 ) 2 ] as catalyst with a small excess of PPh 3 and CsF as aditive (Scheme 7). The use of other palladium sources (such [Pd(PPh 3 ) 4 ] or Pd 2 (dba) 3 ), or other phosphines as ligands led to worse results. 42,43 R F I + R 2 P-SnBu 3 [Pd] ER n = SePh, AsPh 2 R F I + R n E-SnBu 3 [Pd]…”

“…The use of other palladium sources (such [Pd(PPh 3 ) 4 ] or Pd 2 (dba) 3 ), or other phosphines as ligands led to worse results. 42,43 R F I + R 2 P-SnBu 3 [Pd] ER n = SePh, AsPh 2 R F I + R n E-SnBu 3 [Pd]…”

“…A non-comprehensive list of recent reviews is given in references 3-19. 1,[3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Some of the challenges for the preparation of organofluorine derivatives lay on the development of suitable fluorine reagents that are not too reactive, as fluorine itself, or too unreactive because in order to give the desired reaction there is the need of the cleavage of a strong E-F bond. Some of the well developed and useful catalytic reactions for non-fluorinated compounds have been applied to the synthesis of fluoroderivatives but, in many cases, the reactions are not as effective as expected or simply do not work.…”

“…Other metallic catalysts have also been introduced in organofluorine syntesis, specially copper. 3,10,13,[18][19][20] This chapter is intended to give an overview of the synthetic procedures of fluorinated molecules based on the use of palladium complexes, paying attention to the reported studies on the fundamental organometallic reactions that are involved as individual steps in those synthetic procedures. This is specially interesting since the understanding of these steps has allowed to explain the failure of some reactions and to develop new effective processes.…”