Synthesis Of Chiral Quinoxalinone Derivatives Based On Asymmetric Hydrogen Transfer One-pot Method And Dynamic Kinetic Resolution

As a kind of important chemicals,chiral nitrogen-containing compounds are inseparable from chiral nitrogen-containing compounds in medicine,pesticides,materials and so on.As a typical nitrogen-containing heterocyclic compound,quinoxalone compounds play an important role in drugs.It is not only an important skeleton structure of many drug molecules,but also an intermediate in the synthesis process of many drug molecules.Therefore,the synthesis of chiral quinoxalone compounds has important research value.Asymmetric Mannich reaction is an important chemical means to synthesize this kind of nitrogen-containing compounds.However,most of the Mannich products reported in studies have been monochiral or adjacent two handed products.Therefore,we hope to obtain 1,3 distal two handed quinoxalone compounds in one pot by combining asymmetric hydrogen transfer reaction.Dynamic kinetic resolution is also an efficient and green method to construct two handed compounds.Therefore,we also synthesized 1,3-position two handed quinoxalone compounds via dynamic kinetic resolution asymmetric transfer hydrogenation.The two methods have the advantages of mild conditions,good selectivity and easy to deal with.In this paper,the asymmetric Mannich reaction was carried out with DMF as solvent and L-proline as catalyst at 25?,and then kept at 25?with HCOOH:Et₃N=5:2(azeotrope)as hydrogen source.,the asymmetric hydrogen transfer reaction was carried out in the presence of N-[(1R,2R)-1,2-diphenyl-2-(2-(4-methylbenzyloxy)ethylamino)ethyl]-4-methylbenzenesulfonamide(chlorine)ruthenium(II)catalyst.We obtained a series of chiral 3-(2-hydroxypropyl)-3,4-dihydroquinoxalin-2(1H)-one derivatives with excellent dr(up to 99:1 dr)and very high ee values(>99%ee)and good yields(up to 69%)and performed the relevant structural characterisation of all products.In this paper,a method of dynamic kinetic resolution-asymmetric hydrogen transfer was developed to construct 1,3 bichiral quinolinones.This method was carried out at 25?under argon protection with N-[(1R,2R)-1,2-diphenyl-2-(2-(4-methylbenzyloxy)ethylamino)ethyl]-4-Methylbenzenesulfonamide(chloro)ruthenium(II)as catalyst,ethyl acetate as reaction solvent and HCOOH:Et₃N=5:2 as hydrogen source to synthesize 1,3 chiral 3-(2-hydroxypropyl)-3,4-dihydroquinoxalin-2(1H)-one derivatives and the related structures of a series of target products were characterized.