Heck-type 5-endo-trig cyclizations promoted by vinylic fluorines: Ring-fluorinated indene and 3H-pyrrole syntheses from 1,1-difluoro-1-alkenes

Gold(I) Carbenes by Retro-Buchner Reaction: Generation and Fate

“…After the retro-Buchner reaction, highly electrophilic gold(I) carbenes Ia and Ib (L = PMe 3 ) react intramolecularly with the alkene through TS Ia–IIa and TS Ib–IIb in highly exothermic processes to form benzylic carbocations IIa and IIb , respectively. Despite being formally a 5-endo-trig cyclization from the perspective of the alkene, 25 this process is rendered kinetically and thermodynamically favorable by the high electrophilicity of the gold(I) carbenes. As expected, the p -OMe group in Ib attenuates the electrophilicity of the gold(I) carbene, raising the energy of TS Ib–IIb and resulting in a less exothermic cyclization.…”

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.…”

“…In 2017, Arvidsson and co-workers reported an operationally simple method for ligand-and additive-free oxidative Heck couplings of aryl boronic acids (57) with ESF (51) (Scheme 10) [65]. The reactions proceeded at room temperature with good chemoselectivity and E-selectivity and offered facile access to a wide range of β-aryl/heteroaryl ethenesulfonyl fluorides (58) from the commercially available boronic acids (57). The products (58) have a "dual warhead" with two electrophilic sites that have been used as covalent enzyme inhibitors and as synthetic reagents [65].…”

“…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].…”