Kinetic Resolution of Axially Chiral 5- or 8-Substituted Quinolines via Asymmetric Transfer Hydrogenation

Abstract

An efficient kinetic resolution of axially chiral 5- or 8-substituted quinoline derivatives was developed through asymmetric transfer hydrogenation of heteroaromatic moiety, simultaneously obtaining two kinds of axially chiral skeletons with up to 209 of selectivity factor. This represents the first successful application of asymmetric transfer hydrogenation of heteroaromatics in kinetic resolution of axially chiral biaryls.

Atroposelective Synthesis of Axially Chiral Biaryls by Palladium‐Catalyzed Asymmetric C−H Olefination Enabled by a Transient Chiral Auxiliary

“…[1] Accordingly,g reat efforts have been devoted to the efficient synthesis of these chiral frameworks, [2] including asymmetric coupling of two arenes by oxidative dimerization or cross-coupling, [3] atroposelective aryl formation by cycloaddition, [4] asymmetric ringopening of bridged biaryls, [5] asymmetric transfer hydrogenation, [6] stereoselective functionalization of prochiral or racemic biaryls, [7,8] and others. [1] Accordingly,g reat efforts have been devoted to the efficient synthesis of these chiral frameworks, [2] including asymmetric coupling of two arenes by oxidative dimerization or cross-coupling, [3] atroposelective aryl formation by cycloaddition, [4] asymmetric ringopening of bridged biaryls, [5] asymmetric transfer hydrogenation, [6] stereoselective functionalization of prochiral or racemic biaryls, [7,8] and others.…”

Organocatalytic Asymmetric Methodologies towards the Synthesis of Atropisomeric N-Heterocycles

“…Probably inspired by the CPA catalyzed hydrogenation of quinoline derivatives reported by Rueping and coworkers, 50b Zhou and co-workers established a practical method to synthesize enantioenriched tetrahydroquinoline derivatives 82 and 84, displaying a stereogenic axis, from the corresponding heteroaromatic racemic precursors rac-80 or rac-83 (Scheme 19). 51 Combining organocatalysts A (for structure see Scheme 1) or U with Hantzsch ester derivatives 81 in a kinetic resolution process, high levels of enantioselectivity could be obtained with regards to products 82 and 84 and recovered starting materials 80 and 83. In particular, 5-arylquinolines rac-83 required further optimization of the catalytic system.…”

Enantioselective Synthesis of Biaryl Atropisomers by Pd‐Catalyzed C−H Olefination using Chiral Spiro Phosphoric Acid Ligands

“…This protocol relies on the use of aldehyde as DG, thereby is incompatible with quinoline‐derived atropoisomers. Notably, the synthesis of quinoline‐derived atropoisomers itself is much more challenging than their naphthalene analogues, because the lower conformational stability resulted from much less steric hindrance of nitrogen lone pair and therefore prone to racemization (Figure b) . Herein, we reported the use of spiro phosphoric acids (SPAs) as chiral anionic ligands to enable the Pd‐catalyzed atroposelective C−H olefination to prepare axially chiral quinoline‐derived biaryls.…”

“…Owing to the importance of tetrahydroquinoline derivatives in numerous bioactive natural products and pharmaceuticals, the reduction of the resulting axially chiral quinolines was conducted. We were pleased to find that tetrahydroquinoline ( S )‐ 5 was obtained in 98 % yield with complete retention of chirality [Eq.…”