Atroposelective Synthesis of Biaryl Diamines and Amino Alcohols via Chiral Phosphoric Acid Catalyzed para-Aminations of Anilines and Phenols

Abstract

A versatile method for atroposelective synthesis of chiral biaryl diamines and amino alcohols has been developed via para-amination of anilines and phenols with azodicarboxylates enabled by chiral phosphoric acid catalysis. Meanwhile, highly efficient kinetic resolution of the racemic biaryl anilines has also been realized through these reactions, giving selectivity factor up to 246. The gram-scale reaction and facile derivatizations of the chiral products well demonstrate the potential of these reactions in the development of novel chiral ligands and catalysts.

Recent Advances in (Dynamic) Kinetic Resolution and Desymmetrization Catalyzed by Chiral Phosphoric Acids

“…Recently, our group was interested in the enantioselective construction of atropoisomers via CPA-catalyzed asymmetric para-aminations of aniline derivatives with azodicarboxylates. [23] In the work of atroposelective synthesis of biaryl-type diamine and amino alcohol derivatives, we realized the kinetic resolution of a series of 2-substituted biaryl aniline substrates, which possessed axial chirality (Scheme 14). [23a] Asymmetric paraselective amination of one of the enantiomer of 34 with dibenzyl azodicarboxylate 35 in the presence of CPA-3 provided excellent KR performances, producing both recovered anilines (S)-34 and the amination products (R)-35 with high enantioselectivities.…”

Synthesis of N‐Aryl‐ and N‐Alkenylhydrazides through C(sp2)−N Bond Construction

“…Yang and co‐workers disclosed a CPA‐catalyzed protocol for the synthesis of axis‐chiral diaryl diamines 89 and amino alcohols 90 through para‐ selective hydrazidation using biaryl aniline 87 and phenols 88 (Scheme 17). [35] When screening conditions for the synthesis of axis‐chiral diaryl diamines 89 , they investigated a range of solvents to find that CHCl 3 was optimal; toluene or ether led to triazane byproduct 91 . A dual H‐bonding activation reaction mode I was proposed to explain the para ‐selectivity.…”

A Versatile Method for Kinetic Resolution of Protecting‐Group‐Free BINAMs and NOBINs through Chiral Phosphoric Acid Catalyzed Triazane Formation

“…In our previous report of atroposelective construction of biaryl diamines via asymmetric para ‐amination of anilines with azodicarboxylate enabled by CPA catalysis, [20a] we observed the N ‐amination triazane [22] products were generated as the major products when the para ‐positions of anilines were blocked. Accordingly, we envisioned that if these reactions could be utilized for the kinetic resolution of axially biaryl amines, such as BINAMs and NOBINs.…”