Nucleophilic Amination and Etherification of Aryl Alkyl Thioethers

Abstract

A transition-metal-free protocol capable of synthesizing diarylated aniline derivatives is reported. This method could be further employed to prepare aryl alkyl ethers. A wide range of thioethers, anilines, as well as alcohols were tolerated thanks to the mild reaction conditions. The strength of our method was demonstrated by performing a gram-scale reaction (20 mmol) followed by conversion of the nitrile group into synthetically useful aldehyde, ketone, and carboxylic acid.

Metal‐Free Selective C−S Bond Cleavage of Thioethers to Access β‐Alkoxy Carbonyl Compounds

“…However, only a few reports on the metal‐free transformations for the construction of C−O bond have been demonstrated in this field [3] . In 2018, Zhao and Wang group developed a t ‐BuOK‐promoted C(sp 2 )−S bond cleavage of cyano‐substituted aryl‐methyl thioethers and C−O bond formation to prepare aryl‐alkyl ethers, but with very limited thioether substrates (Figure 1a) [3a] . After that, the construction of C−O bond through the Cs 2 CO 3 ‐mediated C(sp 2 )−S bond cleavage of arylsulfonium salts was also reported by Wang and co‐workers, however, only substrates containing strong electron‐withdrawing groups could be applied in this strategy (Figure 1b) [3b] .…”

Recent Progress in Amination Enabled by Transition-Metal-Free C(sp2)–O/C(sp2)–S Bond Cleavage Strategy

“…In 2018, we reported an example of the nucleophilic amination of alkyl cyanoaryl thioethers 35 mediated by KHMDS (Scheme 9). 25 Although the nucleophilicity of ani-…”

Electrophotocatalytic SNAr Reactions of Unactivated Aryl Fluorides at Ambient Temperature and Without Base

“…Nucleophilic aromatic substitution (S N Ar) reactions have long been an important strategic tool for organic synthesis, enabling the direct arylation of nucleophilic substrates . Classically, S N Ar reactions operate on activated arenes 3 bearing strongly electron‐withdrawing functionality (EWG, Figure A) . While such reactions have great utility, such substituents are often not synthetically desirable and thus represent a significant limitation for this reaction class.…”

“…[1,2] Classically,S N Ar reactions operate on activated arenes 3 bearing strongly electron-withdrawing functionality (EWG, Figure 1A). [3][4][5][6][7][8] While such reactions have great utility,s uch substituents are often not synthetically desirable and thus represent asignificant limitation for this reaction class.Onthe other hand, several reports have described S N Ar reactions with unactivated substrates 4 through the use of strong bases and high reaction temperatures. [9][10][11][12][13] Unfortunately,m any complex substrates are not compatible with such conditions, which thus precludes the broad adoption of these methods.As such, the development of S N Ar reactions that occur on unactivated substrates at ambient temperature without the need for strongly basic reagents has presented as ignificant challenge.…”