Metal‐free Synthesis of Aryl Amines: Beyond Nucleophilic Aromatic Substitution

Abstract

A mild and metal-free approach to C-N coupling is described that employs diaryliodonium salt electrophiles and secondary aliphatic amine nucleophiles. This reaction results in direct ipso-substitution of the iodonium moiety and unsymmetrical aryl(TMP)iodonium salts are primarily employed. Moreover, arene substituents and substitution patterns that currently pose a challenge to classical metal-free methods are accommodated and the alicyclic amine nucleophiles used here are unprecedented in other contemporary metal-free C-N coupling reactions.

Concerted Nucleophilic Aromatic Substitution Reactions

“…Similar reactions were more recently carried out on cyclic secondary amines by Stuart et al., as well as primary amines, by Olofsson et al. Stuart describes the final step of his proposed reaction mechanism as a reductive elimination whereby Ar−N bonds were created in the same step as the Ar−I bond was being cleaved.…”

“…Similar reactions were more recently carried out [109] on cyclic secondary amines by Stuart et al,aswell as primary amines, [110] by Olofsson et al Stuart describes the final step of his proposed reaction mechanism as ar eductive elimination whereby Ar À Nb onds were created in the same step as the Ar À Ib ond was being cleaved. No computational or Hammett or other analyses of these reactions are available at the time of writing this review, but the analogy to the reactions of Olofsson et al with alcohols is clear.…”

“…On ar elated theme,S anford et al reported am ild deoxyfluorination of phenols 97 via aryl fluorosulfonate intermediates 98. [57] This transformation was found to be compatible with ortho-, meta-, or para-electron-withdrawing groups,a nd could also be applied to electron-neutral and moderately electron-rich substrates to provide fluorinated products [100][101][102][103][104][105][106][107][108][109][110][111].…”

Trimethoxyphenyl (TMP) as a Useful Auxiliary for in situ Formation and Reaction of Aryl(TMP)iodonium Salts: Synthesis of Diaryl Ethers

“…Diaryliodonium salts contain an aryliodonium leaving group that leads to mechanistic advantages over traditional halides: facile oxidative addition to first-row metals (i. e., copper) and increased scope in metal-free reactions (Scheme 1b). [7][8][9] We have an ongoing interest in the development of reactions to synthesize [10,11] and use [7b-d] aryl(TMP)iodonium salts, and herein we describe a methods to generate and use them in situ for phenol arylation. A potential solution is to form the diaryliodonium in situ and exploit the aforementioned advantages of the iodonium leaving group while using more readily abundant starting materials (Scheme 1c).…”

Konzertierte nukleophile aromatische Substitutionen

“…Ähnliche Reaktionen wurden kürzlich an cyclischen sekundären Aminen durch Stuart et al . sowie an primären Aminen durch Olofsson et al .…”