Formation and reactivity of gem-difluoro-substituted pyridinium ylides: Experimental and DFT investigation

In silico reaction screening with difluorocarbene for N-difluoroalkylative dearomatization of pyridines

“…Crystallographic data are deposited at the Cambridge Crystallographic Data Centre under deposition nos. CCDC 2101564 (11), 2101565 (33), 2101566 (40) and 2101567 (51). All of the other data supporting the findings of this study are available in the main text or Supplementary Information.…”

“…Pyridines 2a and 2b, which bear a more nucleophilic nitrogen atom on their structures than those of the imines, exhibited low barriers (1.0 and 1.3 kcal mol −1 , respectively) that are comparable to that of difluorocarbene dimerization. Encouraged by these calculations and by previous reports using pyridines and difluorocarbene 40,41 , we conducted the reaction with 2a, which resulted in an N-difluoroalkylative cycloaddition that involves the dearomatization of the pyridine skeleton to provide the desired fluorinated heterocyclic compound in 70% yield in the crude mixture 42 . However, despite intensive attempts, the product could not be isolated, presumably due to the elimination of the fluoride assisted by the nitrogen atom, which would trigger its further decomposition.…”

An Aza Cyclopropylcarbinyl-Homoallyl Radical Rearrangement–Radical Cyclization Cascade. Synthesis of Dibenzoimidazoazepine and Oxazepine Derivatives

“…In the framework of our research concerning the synthesis of heterocycles via N-ylide reactions, we have recently presented an effective approach to trans -1-aryl-1,11b-dihydroazirino[1,2- d ]dibenz[ b , f ][1,4]oxazepines , and trans- 1-aryl-7,11b-dihydro-1 H -azirino[1,2- a ]dibenzo[ c , f ]azepines, which are excellent precursors of corresponding azomethine ylides and easily undergo stereospecific and stereoselective 1,3-dipolar cycloaddition to CC dipolarophiles with the formation of a great variety of dibenzo[ b , f ]pyrrolo[1,2- d ][1,4]oxazepine and dibenzo[ c , f ]pyrrolo[1,2- a ]azepine derivatives. In this study we have extended our investigations to the replacement of the pyrrole moiety in cycloadducts with an imidazole, via cycloaddition of the heterocyclic azomethine ylides to CN double bond of azirines, and also disclosed a novel aza cyclopropylcarbinyl-homoallyl radical rearrangement–radical cyclization cascade leading to new heterocyclic systems.…”

Copper‐Catalyzed [3+2] Annulation of Pyridinium Ylides with α‐CF3 Ketones: Synthesis of Functionalized 2‐Fluoroindolizines

“…[15] Novikov and coworkers synthesized 3-fluoroindolizines via cycloaddition of gem-difluoro-substituted pyridinium ylides. [16] As early as 2003, Chen and coworkers reported an elegant protocol towards the synthesis of 2-fluoroindolizines via [3 + 2] cyclization of gaseous 1-chloro-2,2,2-trifluoroethane (HCFC-133a) and 1,1,1,2-tetrafluoroethane (HFC-134a) with pyridinium ylides . [17] As reported in the literature, 2-fluoroindolizines with 1,3-disubstituents have been identified as the powerful inhibitor of retinoic acid related orphan receptor γ (RORγ), yet the alternative synthetic methods are few.…”