Recent Advances in Catalytic Enantioselective Fluorination Reactions

Abstract

Since the incorporation of fluorine into biologically active compounds often enhances the properties of the parent compounds, there is a considerable demand for efficient enantioselective fluorination reactions. Over the past decade, a range of metal-catalyzed and organocatalyzed fluorination reactions has been developed. Nowadays, fluorine can be catalytically introduced into many compounds in good yield and with high enantioselectivity, and the scope of these reactions is broad. Herein, we review recent progress in the field of catalytic enantioselective fluorination reactions, including their scope and mechanism.

New insights on reaction pathway selectivity promoted by crown ether phase-transfer catalysis: Model ab initio calculations of nucleophilic fluorination

“…Because of the importance of fluorination reactions in the synthesis of compounds of pharmaceutical interest [21][22][23][24], considerable efforts have been made towards the development of efficient fluorination reactions [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. The reaction of fluoride ions with alkyl halides is known to proceed both by S N 2 nucleophilic substitution and E2 elimination pathways.…”

Enantioselective Nucleophile-Catalyzed Synthesis of Tertiary Alkyl Fluorides via the α-Fluorination of Ketenes: Synthetic and Mechanistic Studies

“…1 The catalytic enantioselective α-fluorination of carbonyl compounds has been a subject of particular interest, 2 and an array of versatile methods have been described for the generation of such secondary alkyl fluorides. 3,4 In contrast, except in the case of doubly activated molecules, 2,5 there has been limited progress in the development of effective processes that furnish tertiary α-fluorocarbonyl compounds, 6−8 and we are not aware of any methods that directly afford esters, 9 with the exception of kinetic resolutions. 10 Here, we establish that a planar-chiral nucleophilic catalyst ( PPY* ) can achieve the coupling of a ketene, 11 an electrophilic fluorine source, 12 and an alkoxide, thereby providing such tertiary alkyl fluorides with high enantioselectivity (eq 1).…”

A combination of directing groups and chiral anion phase-transfer catalysis for enantioselective fluorination of alkenes

“…Recently reported general methods for the enantioselective synthesis of allylic fluorides include the reaction of allylic chlorides with palladium catalysts (24,25) as well as the fluorination of allylsilanes using cinchona alkaloid catalysis (26,27). Furthermore, we envisioned that, upon removal of the amide directing group, this method would provide access to enantioenriched β-fluoroamines bearing a fluorinated quaternary center, a privileged bioactive motif and longstanding synthetic challenge (28)(29)(30)(31)(32)(33).…”