Morpholinosulfur Trifluoride (Morph‐DAST)‐Mediated Rearrangement in the Fluorination of Cyclic α,α‐Dialkoxy Ketones toward 1,2‐Dialkoxy‐1,2‐difluorinated Compounds

Abstract

The deoxofluorination of cyclic a,a-dialk-A C H T U N G T R E N N U N G oxy ketones with morpholinosulfur trifluoride (Morph-DAST) resulted in 1,2-dialkoxy-1,2-difluorinated carbo-and heterocyclic compounds. The reaction proceeds via a 1,2-alkoxy migration leading to mixtures of cis-and trans-isomers.

Monofluorination of Organic Compounds: 10 Years of Innovation

“…In 2010, de Kimpe and co-workers developed the rearrangement of cyclic α,α-dialkoxy ketones into 1,2-dialkoxy-1,2-difluorinated compounds using Morph-DAST (Scheme ) . This transformation gave the 1,2-difluorinated compounds in moderate to good yields as a mixture of cis and trans diastereoisomers.…”

Introduction of Fluorine and Fluorine‐Containing Functional Groups

“…Besides DAST, deoxyfluorination and dethiofluorination can be accomplished with several different reagents: pyridinium poly(hydrogen fluoride) (Olah’s reagent),109a,b,d nitrosonium tetrafluoroborate/pyridinium poly(hydrogen fluoride),109c triethylamine tris(hydrogen fluoride) (TREAT⋅HF),109e perfluoro‐1‐butanesulfonyl fluoride (PBSF),135 sulfonyl fluoride/TREAT⋅HF mixture (Scheme ),136 Yarovenko’s reagent,137 Ishikawa’s reagent,138 TFEDMA,139 N , N ′‐dimethyl‐2,2,‐difluroimidazolidine,108a 4‐morpholinosulfur trifluoride,107d, 140 Deoxo‐Fluor,107f, 141 bromine trifluoride,142 and 4‐ tert‐ butyl‐2,6‐dimethylphenylsulfur trifluoride (Fluolead; Figure 2). 143 Deoxo‐Fluor is currently the most commonly used reagent for fluorination reactions and is considered a safer, more thermally stable alternative to DAST, but is similarly moisture sensitive and prone to decomposition to generate toxic HF.…”

6.06 Synthesis of Fluorides

“…39 Enantioinduction is possible through chiral anion exchange with the tetrafluoroborate counterions of F-TEDA-BF 4 to generate a soluble chiral electrophilic fluorinating reagent. The enantioselective fluorocyclization of indoles can be mediated or catalyzed by cinchona alkaloids and an electrophilic fluorinating reagent 10 mol% Pd(OAc) 2 , 2 equivalents PhI(CO 2 tBu) 2 , 5 equivalents AgF, 4 equivalents MgSO 4 , MeCN, 24 High-valent transition metal complexes were investigated as a means to accomplish C-F reductive elimination at sp 3 carbon centers. 41 Stoichiometric alkyl Au(I) complexes can be oxidized with XeF 2 to Au(III) intermediates that undergo reductive elimination to afford the corresponding aliphatic fluorides.…”