Organocatalytic enantioselective synthesis of C_sp2–N atropisomers via formal C_sp2–O bond amination

Abstract

An organocatalyzed asymmetric synthesis of Csp2–N atropisomers by formal Csp2–O amination has been established from 3-alkynyl-3-hydroxyisoindolinones and 1-methylnaphthalen-2-ols.

Enantioselective Synthesis of Axially Chiral Diaryl Ethers through Chiral Phosphoric Acid-Catalyzed Desymmetric Acylation with Azlactones

“…Extensive research has been conducted on axially chiral molecules with C–C axial frameworks . Very recently, the C -heteroatom axially chiral compounds, such as C–N, C–O, C–B, and N–N axially chiral compounds, have attracted particular interest because of their unique biological properties. Among these, C–O axially chiral compounds, typically diaryl ethers, are prevalent in both natural products and pharmaceuticals (Figure a).…”

Organocatalytic Csp2–O Amination of Quinolin-4(1H)-ones with 3-Alkynyl-3-hydroxyisoindolinones

“…The advancement in asymmetric organocatalysis is continually gaining momentum, making it a more prevalent and impactful tool in the field of organic synthesis . Recently, we successfully established an organocatalytic formal C sp2 –O bond amination of 1-methylnaphthalen-2-ols with 3-alkynyl-3-hydroxyisoindolinones as nitrogen sources, which features a cascade reaction, high atomic economy, and mild conditions, together with obvious substrate dependence and generally moderate yields (Scheme B) . As a part of our ongoing interest in the field of organocatalytic construction of the C sp2 –N bond via formal C sp2 –O bond amination, here we report an organocatalytic formal C sp2 –O bond amination of 2-arylquinolin-4­(1 H )-ones with 3-alkynyl-3-hydroxyisoindolinones (Scheme C).…”

“…Based on our previous work, we proposed a plausible reaction mechanism in Scheme . The NsOH -catalyzed dehydration of 3-hydroxy-3-(phenylethynyl)­isoindolin-1-one 1a affords imine IM-1 .…”

“…Notably, the catalytic atroposelective synthesis of the chiral C–N axis has recently attracted much attention . To continue our efforts in organocatalytic transformations of 3-alkynyl-3-hydroxyisoindolinones, ,, we investigated the enantioselective reaction between 3-hydroxy-3-(phenylethynyl)­isoindolin-1-one 1a and 3-methyl-2-phenylquinolin-4­(1 H )-one 2l in the presence of chiral phosphoric acids ( CPAs ). As shown in Table , the CPA-1 catalyzed the reaction and afforded the ( Z )- 3al in 6% yield with 20% ee.…”