Combining Organocatalysis with Central‐to‐Axial Chirality Conversion: Atroposelective Hantzsch‐Type Synthesis of 4‐Arylpyridines

Abstract

Suitably substituted enantioenriched 4-aryl-1,4dihydro-pyridines prepared by an organocatalytic enantioselective Michael addition were oxidized with MnO 2 into axially chiral 4-arylpyridines with central-to-axial chirality conversion. Moderate to complete percentages (cp) were observed, and amodel for the conversion of chirality is discussed.

Central‐to‐Axial Chirality Conversion Approach Designed on Organocatalytic Enantioselective Povarov Cycloadditions: First Access to Configurationally Stable Indole–Quinoline Atropisomers

“…We then moved to evaluate the reaction scope of the two‐step synthetic sequence (Scheme ). In each example, Povarov adduct 3 was isolated and fully characterized prior to the oxidation step in order to evaluate the corresponding cp factor of the atropisomeric quinoline 4 . Variations of the amine portion of N‐arylimines 1 showed that methyl and methoxy substituents were very well tolerated in the Povarov reaction as well as in the oxidation step, albeit with slight decrease in the isolated yields of the final products ( 4 cc – ec ).…”

“…More recently, central‐to‐axial chirality conversion, hypothesized by Berson in 1955 and first demonstrated by Meyers in 1984, has been successfully applied to a restricted number of substrates possessing central chirality, prone to be turned into axially chiral molecules . In this context, a pioneering work by Bressy, Bugaut, Rodriguez and co‐workers for the preparation of enantioenriched atropisomeric 4‐arylpyridines (Scheme a) has disclosed the potential of the combination of enantioselective organocatalytic methodologies with the oxidative central‐to‐axial chirality conversion approach.…”

Inversion of the Axial Information during Oxidative Aromatization in the Synthesis of Axially Chiral Biaryls with Organocatalysis as a Key Step

“…In fact, a bulky base such as potassium hexamethyldisilazide gave excellent enantioselectivity (96 % ee ), whereas lower enantioselectivity (89 % ee ) was observed in the case of a smaller base such as KOMe. Thus, the deprotonation proceeds selectively from R‐inside conformer, affording biaryl 7 with R a axial chirality …”

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.…”