Heck-type 5-endo-trig cyclization promoted by vinylic fluorines: synthesis of 5-fluoro-3H-pyrroles

Abstract

A 5-endo-trig alkene insertion proceeds under palladium catalysis via aminopalladium species starting from 3,3-difluoroallyl ketone O-pentafluorobenzoyloximes, providing a facile access to 5-fluoro-3H-pyrroles.

Transition metals in organic synthesis: Highlights for the year 2005

“…(31)) [436] and of alkenes with O-pentafluorobenzoylamidoximes [437] were reported. Intramolecular Heck reactions [394,[438][439][440][441][442] were used as the key step toward an array of synthetic targets for example, stephacidin A [443], 1-epi aglycon of cripowellins A and B [444], hamigeran B [202], mensacarcin [445], (−)-galanthamine and (−)-morphine [446], gelsemine [447], 5-substituted azepino [3,4-b]indoles [448], komaroviquinone and faveline methyl ether [449], pseudopteroxazole [450], diazonamide A [75], 4,7-azaindoles [451], substituted tryptophans (Eq.…”

Density functional study of the complete pathway for the Heck reaction with palladium diphosphines

“…Since its independent discovery in the early 1970s by Heck [1] and Misoroki [2], the Heck reaction has been widely used as a tool for organic synthesis because of its importance in the direct attachment of olefinic groups to aromatic rings [3][4][5][6][7][8][9][10][11]. Numerous review articles on various aspects of the Heck and other cross-coupling reactions with palladium catalysts have been published [10][11][12][13][14][15][16][17][18][19][20][21][22].…”

Pd-Catalyzed Mizoroki-Heck Reactions Using Fluorine-Containing Agents as the Cross-Coupling Partners

“…The products 52 proved to be selectively addressable bis-electrophiles for sulfur(VI) fluoride exchange (SuFEx) click chemistry, in which either the alkenyl moiety or the sulfonyl fluoride group could be exclusively attacked by nucleophiles under defined conditions, making these simple cores attractive for covalent drug discovery [60]. Pd-Catalyzed intramolecular cyclization of O- (3,3-difluoroallyl)phenyl triflate (41) and 3,3-difluoroallyl ketone oximes (46) by the Mizoroki-Heck reactions of the polarized carbon-carbon double bonds of the 1,1-difluoro-1-alkene moieties was accomplished (Scheme 7) [45,57,58]. In the first step of the reactions, an arylpalladium or aminopalladium intermediate (42 or 47) bearing a 2,2-difluorovinyl group is formed from 41 or 46, respectively.…”

“…Then, intermediate 42 or 47 undergoes a 5-endo-trig alkene insertion and subsequent β-fluorine elimination to afford ring-fluorinated indene (45) or 3H-pyrroles (49). In both cases, the CF2 unit was very essential for the cyclization as the corresponding monofluoroalkene, fluorine-free alkene, dichloroalkene, and dibromoalkene didn't give the cyclized products under the same reaction conditions [57,58].…”

“…Pd-Catalyzed intramolecular cyclization of O- (3,3-difluoroallyl)phenyl triflate (41) and 3,3-difluoroallyl ketone oximes (46) by the Mizoroki-Heck reactions of the polarized carbon-carbon double bonds of the 1,1-difluoro-1-alkene moieties was accomplished (Scheme 7) [45,57,58]. In the first step of the reactions, an arylpalladium or aminopalladium intermediate (42 or 47) bearing a 2,2-difluorovinyl group is formed from 41 or 46, respectively.…”