357274-85-2Relevant articles and documents
4-Difluoromethylated quinoline synthesis via intramolecular S N2′ reaction of α-trifluoromethylstyrenes bearing imine moieties
Mori, Takashi,Ichikawa, Junji
, p. 1206 - 1207 (2004)
Intramolecular cyclization of o-methyleneamino-substituted α-trifluoromethylstyrenes is promoted by DBU and a catalytic amount of KCN to provide 4-(difluoromethyl)quinolines. The reaction proceeds via (i) the generation of carbon nucleophiles from the imi
Catalytic Enantioselective Synthesis of Heterocyclic Vicinal Fluoroamines by Using Asymmetric Protonation: Method Development and Mechanistic Study
Ashford, Matthew W.,Xu, Chao,Molloy, John J.,Carpenter-Warren, Cameron,Slawin, Alexandra M. Z.,Leach, Andrew G.,Watson, Allan J. B.
supporting information, p. 12249 - 12255 (2020/08/21)
A catalytic enantioselective synthesis of heterocyclic vicinal fluoroamines is reported. A chiral Br?nsted acid promotes aza-Michael addition to fluoroalkenyl heterocycles to give a prochiral enamine intermediate that undergoes asymmetric protonation upon rearomatization. The reaction accommodates a range of azaheterocycles and nucleophiles, generating the C?F stereocentre in high enantioselectivity, and is also amenable to stereogenic C?CF3 bonds. Extensive DFT calculations provided evidence for stereocontrolled proton transfer from catalyst to substrate as the rate-determining step, and showed the importance of steric interactions from the catalyst's alkyl groups in enforcing the high enantioselectivity. Crystal structure data show the dominance of noncovalent interactions in the core structure conformation, enabling modulation of the conformational landscape. Ramachandran-type analysis of conformer distribution and Protein Data Bank mining indicated that benzylic fluorination by this approach has the potential to improve the potency of several marketed drugs.
Photoredox Generation of Carbon-Centered Radicals Enables the Construction of 1,1-Difluoroalkene Carbonyl Mimics
Lang, Simon B.,Wiles, Rebecca J.,Kelly, Christopher B.,Molander, Gary A.
supporting information, p. 15073 - 15077 (2017/11/20)
Described is a facile, scalable route to access functional-group-rich gem-difluoroalkenes. Using visible-light-activated catalysts in conjunction with an arsenal of carbon-radical precursors, an array of trifluoromethyl-substituted alkenes undergoes radical defluorinative alkylation. Nonstabilized primary, secondary, and tertiary radicals can be used to install functional groups in a convergent manner, which would otherwise be challenging by two-electron pathways. The process readily extends to other perfluoroalkyl-substituted alkenes. In addition, we report the development of an organotrifluoroborate reagent to expedite the synthesis of the requisite trifluoromethyl-substituted alkene starting materials.
