Synthesis of Axially Chiral Biaryl‐2‐amines by Pd^II‐Catalyzed Free‐Amine‐Directed Atroposelective C−H Olefination

Abstract

A simple and ubiquitously present group, free amine, is used as a directing group to synthesize axially chiral biaryl compounds by PdII‐catalyzed atroposelective C−H olefination. A broad range of axially chiral biaryl‐2‐amines can be obtained in good yields with high enantioselectivities (up to 97 % ee). Chiral spiro phosphoric acid (SPA) proved to be an efficient ligand and the loading could be reduced to 1 mol % without erosion of enantiocontrol in gram‐scale synthesis. The resulting axially chiral biaryl‐2‐amines also provide a platform for the synthesis of a set of chiral ligands.

Enantioselective synthesis of indole‐based unnaturalβ‐Alkynylα‐amino acid derivatives via chiral phosphoric acid catalysis

“…To test the feasibility of our design, we began our studies with the enantioselective C-3 functionalization of indole substrate 1a with the β,γ-alkynyl-α-imino ester 2a (see the supporting information) in the presence of 10 mol% chiral spirocyclic phosphoric acid (S)-A1 developed by our group [41][42][43][44][45][46][47][48] in dichloromethane at room temperature. Fortunately, the transformation proceeded smoothly and the corresponding product, a chiral indole-β-alkynylα-amino acid derivative, was obtained in 61% yield with 35% ee within 4 h (Table 1, entry 1).…”

“…37 Moreover, in 2010, the Bolm group reported an enantioselective organocatalytic synthesis of quaternary α-amino acids bearing a -CF 3 unit via chiral Brønsted acid catalysis. 38 Here, we envisioned to develop an organocatalytic asymmetric synthesis of indole-based unnatural β-alkynyl-α-amino acid derivatives with the chiral phosphoric acid [39][40][41][42][43][44][45][46][47][48] as a catalyst (Scheme 1D), and the strategy is atom-economical and the reaction proceeds without any additives. The significant challenge is to select suitable chiral catalysts to control regioselectivity and stereoselectivity during this asymmetric transformation.…”

Twofold C−H Activation‐Based Enantio‐ and Diastereoselective C−H Arylation Using Diarylacetylenes as Rare Arylating Reagents

“…Tr eatment of 3 with MeOTf followed by LAH reduction afforded diarylphosphine oxide 34 in moderate yield and low diastereoselectivity,a nd each diastereomer was obtained in 95:5 e.r. Pd-catalyzed phenylation of the diastereomeric mixture of 34 gave the corre- Photophysical properties of selected products (3,4,7,9, and 31)w ere next examined (Figure 1). These compounds typically exhibited three absorption bands in the UV-Vis spectroscopy,r anging from 225 to 317 nm.…”

“…Thee ffectiveness of CÀHb ond activation-based generation of axially chirality has been witnessed by the increasing number of reports in the past decade.Early work focused on palladium-catalyzed C À Ha ctivation, [3] and the majority of recent studies takes advantage of size-increasing effect via dynamic kinetic transformation of arenes that already bear an axis. [4] Our group also realized biaryl synthesis by alternative dynamic kinetic transformation of the coupling reagent (alkynes). [5] Direct arylation of arenes with concurrent generation of an axis seems amore straightforward protocol.…”

Coordination-assisted, transition-metal-catalyzed enantioselective desymmetric C–H functionalization

“…33 Recently, they demonstrated the highly efficient synthesis of axially chiral biaryl-2-amines by Pd-catalyzed atroposelective C-H olefination using SPA L20 as the chiral ligand (Scheme 13). 34 Notably, free amine was used as the directing group, giving a variety of chiral biaryl-2-amines in good yields with high enantioselectivities.…”