Synthesis Of Optically Pure 1,3 Diols Based On Asymmetric Hydrogen Transfer And Kinetic Resolution Of Dihydroquinolinones

In our lives,any life,including animals,plants and various microorganisms,cannot live without the concept of chirality.Among such substances as chiral compounds,the 1,3-diphenylpropane-1,3-diol and 1,3-chiral-tetrahydroquinolinol compounds are used in dyes,preservatives,perfumes,pesticides and various pathogens,etc.The research field has wide range of applications and in-depth exploration.At present,the long distance between the chiral centers makes the synthesis of remote bimanual substances challenging.Usually,the method of asymmetric hydrogenation is used to synthesize chiral 1,3-diol compounds and chiral1,3-tetrahydroquinolinol compounds.This method achieve the hydrogenation process of the raw materials by hydrogen pressurization,so the requirements for experimental devices and equipment are relatively strict.At the same time,the hydrogenation in high pressure has the risk of explosion,the safety and stability of the experiment need to be improved.Therefore,we hope to synthesize the target product by a method of milder conditions,easier operation,lower cost and in line with the concept of green environmental protection.This paper intends to use asymmetric hydrogen transfer method to synthesize 1,3-diol compounds,which has the advantages of mild conditions,low energy consumption and high conversion rate.Secondly,we use the method of kinetic resolution to prepare chiral1,3-tetrahydroquinolinol compounds.This method has the advantages of good selectivity,easy purification,and short reaction time.In this work,the method of asymmetric transfer hydrogenation transfer is used to synthesis a series of 1,3 diol compounds properties with high enantioselectivity(up to99%),diastereo-selectivity(up to 99:1)and high yield(up to 92%).In this method,we used Ru Cl[(S,S)-Ts DPEN](Mesitylene)as the catalyst,HCOOH/Et₃N(1:1)as the hydrogen source,and dichloromethane(DCM)as the solvent at 40 ^oC.The structure of all products was characterized by ¹H-NMR,¹³C-NMR,and HRMS,the enantioselectivity and diastereoselectivity of the products were characterized by HPLC.Based on asymmetric hydrogen transfer,a method for kinetic resolution of quinolinones to synthesize corresponding chiral 1,3-tetrahydroquinolinols is developed in this paper.Ru Cl[(R,R)-Ts DPEN](p-Cymene)is used as the catalyst,HCOONa is as the hydrogen source in the solution of DCE:H₂O(1:4)at 20°C,a series of 1,3-chiral tetrahydroquinolin-4-ol derivatives groups are synthesized with extremely high ee value(up to 99%),high dr value(up to 99:1)and good yield(up to 46%).And 2-phenyl-2,3-dihydroquinolin-4(1H)-one derivative is got with good recovery rate(48%)and enantioselectivity(up to 93%ee).The structure of all products was characterized by ¹H-NMR,¹³C-NMR,the enantioselectivity and diastereoselectivity of the products were characterized by HPLC.