Synthesis of Complex Diarylamines through a Ring‐Opening Difunctionalization Strategy**

Abstract

The diarylation and skeletal diversification of unstrained cyclic amines was exploited to expand and modify the favorable properties of this important substrate class with pivotal roles in drug discovery. Cyclic amines were employed in the synthesis of a novel class of amino‐substituted diaryliodonium salts, which were converted to highly functionalized diarylamines through an atom‐efficient one‐pot N‐arylation/ ring opening reaction with external nucleophiles. The reaction proceeds through in situ formation of a diarylammonium intermediate that undergoes a nucleophilic ring opening by cleavage of the strong C‐N bond. A wide variety of diarylamines was obtained through introduction of two different aryl groups of varied electronics, and the retained iodo‐substituent enables downfield diversifications of the products. More than 20 nucleophiles, including amines, phenols, carboxylic acids, thiols and halides, were alkylated with high functional group tolerance, and the strategy proved efficient also in in late‐stage functionalization of natural products and pharmaceuticals.

Transition-Metal-Free C-Diarylations to Reach All-Carbon Quaternary Centers

“…We have previously studied the mechanism in diarylation of heteroatom nucleophiles and supported the proposed S N Ar pathway by isolation of the diaryliodonium intermediate, as well as through DFT studies. − Moreover, β-dicarbonyls are well known nucleophiles for S N Ar reactions under basic reaction conditions. , Based on those results and NMR studies of the current system, we propose that the reaction proceeds by facile deprotonation of the malonate to give enolate I , which might coordinate to the iodine or directly undergo S N Ar reaction to give α-arylated malonate species II (Scheme ). This is quickly deprotonated by the remaining base to give intermediate III , which was observed during low-temperature NMR studies and could also be trapped by HCl in diethyl ether to give II .…”

“…Our group previously reported a novel strategy to enable one-pot, atom-efficient diarylation of heteroatom nucleophiles under transition-metal-free conditions. − The method employs a special type of diaryliodonium salt to unlock S N Ar reactivity, and the approach proved successful in the synthesis of a wide variety of unsymmetric diaryl amines, ethers, and sulfides with the ortho -iodo substituent retained in the products. Herein, we describe the extension of this strategy to carbon nucleophiles to allow for straightforward synthesis of targets bearing an all-carbon quaternary center decorated with two different aryl groups (Scheme D).…”

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

“…These ortho-substituted diaryliodonium salts undergo selective benzocyclizations and arylocyclizations with aromatic acids, leading to 3,4-benzocoumarin skeletons in the presence of palladium catalysts (Scheme 1b). Furthermore, Olofsson and colleagues described an unprecedented reaction pathway using ortho-fluoro-substituted diaryliodonium salts bearing strong electron-withdrawing groups, leading to novel diarylations of N-, O-, and S-nucleophiles [31][32][33]. Building on our great interest in ortho-functionalized diaryliodonium salts and their dual activation capabilities, we sought to incorporate carboxylic ester groups into the structures of ortho-substituted diaryliodonium salts to explore their properties and reactivity.…”