Carbotrifluoromethylations of C−C Multiple Bonds (Excluding Aryl‐ and Alkynyltrifluoromethylations)

Abstract

Organofluorine chemistry has become an expanding area of research in organic chemistry and drug design. The synthesis of fluorine-containing molecules has received high significance in synthetic chemistry. Trifluoromethylative difunctionalizations of carbon-carbon multiple bonds with the simultaneous introduction of a CF 3 group and another function have considerable relevance. Because of the high importance of carbon-carbon bond-forming reactions in organic synthesis, carbotrifluoromethylations are considered to be a field of synthetic chemistry of increasing importance. Our current goal in this review is to summarize recent developments of various trifluoromethylation reactions (excluding aryl-and alkynyl-trifluoromethylations) taking into consideration several main approaches, such as alkenyltrifluoromethylation, alkyltrifluoromethylation, carbonyltrifluoromethylation, and cyanotrifluoromethylation reactions.

The Role of Small Molecules Containing Fluorine Atoms in Medicine and Imaging Applications

“…A modified version of pitavastatin 9 has been used for positron emission tomography (PET) imaging in vivo by incorporating a fluorine-18 atom [59]. Ezetimibe (Zetia ® ) 8 [53] is a drug that combats high cholesterol by targeting Niemann-Pick C1-like 1 protein (NPC1L1), thus lowering low-density lipoprotein (LDL); it features two p-fluoro substituents to block other sites on the ring from metabolic oxidation and improves metabolic stability [12,56]. Figure 5 shows the structure of ezetimibe 8 and highlights the blocking of sites because of fluorine atoms.…”

“…Fluorine’s high electronegativity, 4.0 on the Pauling scale, offers it other advantages over similarly sized atoms and functional groups when incorporated into small molecules. The C-F bond is considered the strongest bond in organic chemistry due to the electronegativity difference between the two atoms [ 11 , 12 ]. In addition, the highly electronegative nature of fluorine often alters the dipole moment of the overall molecule.…”

Copper-Catalyzed Synthesis of 4-CF3-1,2,3-Triazoles: An Efficient and Facile Approach via Click Reaction

“…Since the time of its discovery in strategies to optimize the pharmacological properties of drug candidates [ 1 , 2 , 3 , 4 ], incorporation of the trifluoromethyl group has become a promising approach to discover new and/or improve existing bioactive compounds [ 5 , 6 , 7 , 8 ]. Although several valuable methods have been developed for the synthesis of trifluoromethyl-substituted compounds [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ], methods that incorporate this group in an efficient and regiospecific manner remain in high demand [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ], especially in the case of heterocyclic compounds [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ].…”

Studies on Fluorofunctionalization of Some Functionalized Alkene Scaffolds

“…While the fluorination of organic derivatives is an all-time relevant issue of synthetic chemistry, there is a permanent need for the development of methodologies enabling the construction of new fluorinated chemical entities. Fluorofunctionalization can be accomplished by several ways, including direct fluorination [10][11][12] or the incorporation of synthetically versatile fluorinated building blocks [13,14] and functional groups, for example, trifluoromethylations [15][16][17][18][19]. Principally, depending on the type of the fluorinating agent, three possible approacheselectrophilic, radical or anionicexist to introduce fluorinecontaining substituents into organic substrates [20].…”