Organocatalytic Aryl–Aryl Bond Formation: An Atroposelective [3,3]-Rearrangement Approach to BINAM Derivatives

Abstract

Herein we disclose an organocatalytic aryl-aryl bond-forming process for the regio- and atroposelective synthesis of 2,2'-diamino-1,1'-binaphthalenes (BINAMs). In the presence of catalytic amounts of axially chiral phosphoric acids, achiral N,N'-binaphthyl hydrazines undergo a facile [3,3]-sigmatropic rearrangement to afford enantiomerically enriched BINAM derivatives in good to excellent yield. This transformation represents the first example of a metal-free, catalytic C(sp(2))-C(sp(2)) bond formation between two aromatic rings with concomitant de novo atroposelective installation of an axis of chirality. Density functional calculations reveal that, in the transition state for C-C bond formation, the phosphoric acid proton of the catalyst is fully transferred to one of the N-atoms of the substrate, and the resulting phosphate acts as a chiral counterion.

Organocatalytic atroposelective synthesis of axially chiral styrenes

“…Among the well-known axially chiral structures, most of the chiral axis is between two aromatic moieties as named biaryl atropisomers. Owing to the importance of this structural motif, the catalytic atroposelective construction of axially chiral biaryls has been intensively investigated123456 and could be accessed by enantioselective oxidative/cross coupling of two aryl counterparts,78910111213 asymmetric construction of an aromatic ring14151617181920 and kinetic resolution/desymmetrization of biaryl compounds (Fig. 1a, left)21222324252627282930313233343536.…”

Catalytic Asymmetric Benzidine Rearrangement

“…These involve a moderately enantioselective oxidative homocoupling of 2naphthylamines. [9,10] We started our studies by reacting hydrazine 1 a in CHCl 3 with different chiral Brønsted acid catalysts. Previously, only one example of an asymmetric benzidine rearrangement was reported by Sannicolò, using three equivalents of camphor sulfonic acid to obtain the product with poor enantioselectivity.…”

Enantiomeric separation of biaryl atropisomers using cyclofructan based chiral stationary phases

“…They represent a major class of axially chiral molecules that have found use in many applications including privileged ligands in asymmetric synthesis[1-4], chiral resolving agents[5], and as pharmaceutical compounds[6,7]. Recently, a variety of novel 2,2′-diamino-1,1′-binaphthalenes[8] as well as 2,2′-aminohydroxy-1,1′-biaryls were synthesized using a transition metal free direct arylation method[9]. _ENREF_5 These new compounds have the potential to be used as chiral ligands in asymmetric synthesis and may possess unique biological activities including antitumor and antimicrobial activities[10].…”