Organocatalyzed Enantioselective Fluorocyclizations

Abstract

Enantioenriched fluorinated heterocycles can be prepared through fluorocyclizations of prochiral indoles (see scheme; Ts=tosyl, Bn=benzyl, Boc=tert-butoxycarbonyl). More than twenty examples for this cascade fluorination-cyclization, which is catalyzed by cinchona alkaloids and employs N-fluorobenzenesulfonimide as the electrophilic fluorine source have been explored, and an unprecedented catalytic asymmetric difluorocyclization has also been identified.

Metal Carbides as Alternative Electrocatalyst Supports

“…60 Various tryptamine derivatives underwent electrophilic fluorination/cyclization using N -fluorobenzenesulfonamide (NFSI) in the presence of 20 mol% of Sharpless’s (DHQ) 2 PHAL ligand (Scheme 36). Conditions using a stoichiometric amount of chiral ligand gave enantioselectivities up to 90% (not shown).…”

Catalytic Aminohalogenation of Alkenes and Alkynes

“…59 (8) The first enantioselective intramolecular aminofluorination was reported by Gouverneur and co-workers in 2011. 60 Various tryptamine derivatives underwent electrophilic fluorination/ cyclization using N-fluorobenzenesulfonamide (NFSI) in the presence of 20 mol% of Sharpless's (DHQ) 2 PHAL ligand (Scheme 36). Conditions using a stoichiometric amount of chiral ligand gave enantioselectivities up to 90% (not shown).…”

Enantioselective Fluoroamination: 1,4‐Addition to Conjugated Dienes Using Anionic Phase‐Transfer Catalysis

“…While electrophilic fluorination of olefins with oxygen nucleophiles has been wellprecedented, [8,9] reports using nitrogen nucleophiles have been rare. [10][11][12] Previous examples of enantioselective aminofluorination reactions of isolated olefins have been disclosed, but to the best of our knowledge the analogous transformation utilizing 1,3-dienes is unknown. Herein we report the first catalytic asymmetric 1,4-aminofluorination of conjugated dienes using chiral-anion phase-transfer catalysis.…”

“…By lowering the stoichiometry of the base in the reaction, the enantioselectivity could be further improved to 89 % ee with full conversion of the starting material in fluorobenzene (entry 10). Subsequent solvent and concentration screening revealed that a,a,a-trifluorotoluene (PhCF 3 ) was the ideal solvent for the transformation (entries [11][12][13][14], affording 2 a in 96 % ee with complete conversion of the starting material (entry 13).…”