Direct Deprotonative Functionalization of α,α‐Difluoromethyl Ketones using a Catalytic Organosuperbase

Abstract

Supporting information for this article is given via a link at the end of the document.

Merging Radical Brook Rearrangement and 1,5‐Hydrogen Atom Transfer: Facile Synthesis of Ketone‐Containing ɑ‐Fluoroalkyl Alcohols

“…[1][2][3][4][5] Among various fluorinated compounds, α-fluoroalkyl secondary alcohols are of great importance, and many of them are bioactive; for examples, Befloxatone is a monoamine oxidase inhibitor (A) and compound B is used to treat diseases related to toxic concentrations of iron ions (Scheme 1a). [6,7] Traditional methods for the synthesis of αfluoroalkyl secondary alcohols includes reduction of fluoroalkyl ketones, [8][9][10][11][12][13][14][15][16] nucleophilic addition of fluoroalkyl nucleophiles to aldehydes, [17][18][19][20][21][22][23][24][25] and nucleophilic addition of nucleophiles to fluoroalkyl aldehydes (Scheme 1b). [26][27][28][29][30] In 2012, Hu and coworkers reported a nucleophilic difluoromethylation of aryl ketones and aldehydes with difluoromethyl sulfoximines (Hu's reagents), which produced various α-difluoromethyl benzyl alcohols after a desulfoximination process.…”

One-pot C(sp3)–H difluoroalkylation of tetrahydroisoquinolines and isochromans via electrochemical oxidation and organozinc alkylation

“…6,7 On the other hand, N- and O-heterocycles such as cyclic amines and ethers are of importance because of their ubiquity in pharmaceuticals. 8,9 While addition reactions have been utilized as a typical process for C(sp 3 )–CF 2 bond formation, 10 the C(sp 3 )–H functionalization for introducing carbonylated CF 2 groups into protected and unprotected amines is still limited despite its promising efficiency (Scheme 1). 11 Besides, ethers have never been employed as substrates in this type of reaction.…”

Room temperature deoxofluorination of aromatic aldehydes with XtalFluor-E under highly concentrated conditions

“…2 Recently, difluoromethylene-containing molecules have also been used as synthetic intermediates given that the CF 2 H moiety can be deprotonated. 3…”