Scalable Approach to Fluorinated Heterocycles with Sulfur Tetrafluoride (SF₄)

Abstract

A general approach to fluorinated (hetero)aromatic derivatives is elaborated. The key reaction is a deoxofluorination of substituted acetophenones with sulfur tetrafluoride (SF 4 ). In contrast to previous deoxofluorination methods, this transformation is fast, scalable (up to 70 g), and high-yielding. More than 100 novel or previously hardly accessible fluorinated heterocycles, interesting for medicinal chemistry and agrochemistry, were synthesized.

Bismuth‐Mediated α‐Arylation of Acidic Diketones with ortho‐Substituted Boronic Acids

“…Good yields are also obtained for boronic acids featuring ortho-substituents other than methyl (24)(25)(26)(27)(28)(29)(30)(31), with very electron donating (24), very electron withdrawing (29,30) and very sterically demanding ( 25) groups all well tolerated. Notably, ortho-chlorophenyl substituted 28 was previously prepared via a three-step sequence consisting of S N Ar, nitro reduction and subsequent diazotisation/deamination.…”

“…In contrast, α-arylated fluoroalkyl diones are valued as key precursors to biologically relevant heterocycles, including pyrazoles, isoxazoles and pyrimidines (Scheme 1B). [22][23][24][25] Together, these arylated fluoroalkyl heterocycles account for over 4 500 patented compounds with indications including obesity, inflammation, cancer and Huntington's disease.…”

“…Notably, nearly 10 000 (60 %) of the compounds claimed in >120 agrochemical patents bear at least one ortho substituent on the aryl moiety (Scheme 1A), a feature which significantly hinders cross‐coupling approaches to this motif (see below). In contrast, α‐arylated fluoroalkyl diones are valued as key precursors to biologically relevant heterocycles, including pyrazoles, isoxazoles and pyrimidines (Scheme 1B) [22–25] . Together, these arylated fluoroalkyl heterocycles account for over 4 500 patented compounds with indications including obesity, inflammation, cancer and Huntington's disease.…”

Fluorine-Containing Prolines: Synthetic Strategies, Applications, and Opportunities

“…Finally, acidic hydrolysis of the diketopiperazine moiety in a sealed vial gave the needed amino acid 87 in 37% yield. Although the product was obtained in a 1 g scale, toxicity of SF 4 /HF system , prevented wide use of this protocol in the future.…”

Theoretical study on the mechanism of the benzaldehyde deoxyfluorination by sulfuryl fluoride and tetramethylammonium fluoride

“…This work might provide a theoretical basis to design and develop high active reagents for the deoxyfluorination of C-O/C=O bonds. [43,[45][46][47]…”