Ru-catalyzed Asymmetric Transfer Hydrogenation And Synthesis Of Chiral Diamine Ligands

Asymmetric transfer hydrogenation involving transition metals has developed rapidly and become one of the hottest topics in the field of asymmetric synthesis in recent decades.With the development of related research,this hydrogenation system has demonstrated excellent compatibility of various functional groups and therefore,it is widely used in the synthesis of various chiral compounds.Synthesizing chiral alcohols from ketones,as a synthetic route featuring high atomic economy,convenience and environment-friendly,has attracted much attention of academia and industry.Asymmetric transfer hydrogenation of normal ketones can result in alcohols with only one chiral center,limiting its application in practical ways.Alcohols with multi chiral centers can be synthesized by asymmetric hydrogenation of ?-multi functionalized ketones with dynamic kinetic control,while this kind of transformation lacks studies.Therefore,the development of relevant hydrogenation reactions and the design of new ligands and catalysts are greatly important and valuable to organic synthesis and research.In this paper,we focused on the preparation of alcohols containing continuous chiral centers by asymmetric transfer hydrogenation of ?-multi substituted ketones with good dynamic kinetic control at the same time.Furthermore,several chiral diamine ligands with novel structures were designed and synthesized for coordination with metal precursors and in situ hydrogenation.This paper mainly studies the following contents:1.By using chiral Ruthenium-diamine catalytic system,asymmetric transfer hydrogenation ?-substituted ?-keto sulfonamides was studied.A series of ?-hydroxyl sulfonamides were synthesized with high efficiency and excellent stereoselectivity(ee>99%,dr>20:1),providing an efficient way for the preparation of ?-substituted ?hydroxyl sulfonamides.This methodology features mild conditions,easy operation and wide substrate scope and it is of great potential use.2.The asymmetric transfer hydrogenation of y-keto carboxylic acids was studied via combination of dynamic kinetic control and tandem cyclization.y-Butyrolactones was obtained through a one-pot reaction with good yields and great stereoselectivity(up to 92%yield,up to 99%ee,dr>20:1).Strigolactones were prepared by further derivative reaction of hydrogenated product.3.A series of ?-fluoro-?-hydroxyl esters were synthesized by asymmetric transfer hydrogenation of ?-fluoro-?-keto esters with chiral ruthenium-diamine catalyst and HCOOH/Et3N as hydrogen source under mild reaction conditions(up to 92%yield,up to 99%ee,dr>20:1).This transformation provided a new synthetic route for preparing a-fluoro-?-hydroxyl esters.4.A series of novel diamine ligands were designed and prepared.Subsequently,coordination with metal precursors and transfer hydrogenation by in situ coordination were tested.Although no expected results were obtained,our experiments paved a way for future design of new ligands.