Heavily Substituted Atropisomeric Diarylamines by Unactivated Smiles Rearrangement of N‐Aryl Anthranilamides

Abstract

Diarylamines find use as metal ligands and as structural components of drug molecules, and are commonly made by metal-catalyzed C-N coupling. However, the limited tolerance to steric hindrance of these couplings restricts the synthetic availability of more substituted diarylamines. Here we report a remarkable variant of the Smiles rearrangement that employs readily accessible N-aryl anthranilamides as precursors to diarylamines. Conformational predisposition of the anthranilamide starting material brings the aryl rings into proximity and allows the rearrangement to take place despite the absence of electron-withdrawing substituents, and even with sterically encumbered doubly ortho-substituted substrates. Some of the diarylamine products are resolvable into atropisomeric enantiomers, and are the first simple diarylamines to display atropisomerism.

N−C Axially Chiral Anilines: Electronic Effect on Barrier to Rotation and A Remote Proton Brake

“…Quite recently, Clayden et al. reported the synthesis of a focused library of axially chiral N ‐aryl‐2‐ tert ‐butyl‐6‐methylanilines (diaryl amines), their crystal structures and two examples of rotational barriers . However, there is no mention on such electronic effect.…”

Concerted Nucleophilic Aromatic Substitution Reactions

“…Prior to this most recent work, Clayden et al had studied extensive alternative applications of these aryl transfer reactions,notably in ring-expansion reactions, [78][79][80][81][82][83] for example,with substrates 240, 241. [78] Although Hammett plots are not reported for these series,t he analogy to the amino acid cases just discussed make it highly likely that they follow cS N Ar pathways through transition states 244.Inthe presence of dimethylpropyleneurea (DMPU) and lithium diisopropylamide (LDA), ring-expanding isomerisation was effected with excellent retention of stereochemistry.Thus,the initially generated benzyllithium is configurationally stable for the period needed to carry out the rearrangement.…”

Konzertierte nukleophile aromatische Substitutionen

“…In diesen Fällen übernimmt der Schritt der Enolatbildung diese Rolle. Dieser jüngsten Arbeit vorangehend haben Clayden et al umfangreiche alternative Anwendungen dieser Aryltransferreaktionen untersucht, insbesondere bei Ringexpansionsreaktionen,[78][79][80][81][82][83] z. B. mit den Substraten 240 und 241 [78].…”