Organocatalytic Enantioselective Protonation For Photoreduction Of Activated Ketones And Ketimines Induced By Visible Light

For chiral compounds with a single stereocenter,the two enantiomers often exhibit differentphysiological activities in pharmacology,toxicology and so on.It is an attractive method to synthesize optically pure compounds via asymmetric catalysis.At the same time,as a sustainable and abundant energy source,the use of visible light has become one of the major challenges in the new century.Visible light-induced chemical conversion can efficiently convert light energy into chemical energy,and the reaction has the advantages of green,pollution-free and mild conditions.So the development of asymmetric catalysis and visible light catalytic co-catalytic mode,in recent years has also been a large number of scientific researchers attention.Over the past few decades,a range of powerful strategies have been established for asymmetricreduction of simple ketones.But in sharp contrast,the variant of the direct transformation of 1,2-diketones to optical enrichedα-hydroxy ketones,which are key structural motifs in many bioactive molecules and used creatively as chiral building blocks for asymmetric synthesis,has been less developed.Asymmetric catalytic reduction of 1,2-dione is the simplest and most effective method for the preparation of chiralα-hydroxy ketones.However,evaluating the potential of the system is complicated by product racemisation under severe conditions,so it is still an unresolved problem to improve its selectivity.In this thesis,the first catalytic asymmetric photoreduction of 1,2-diketones andα-keto ketiminesunder visible light irradiation is reported.A transition-metal-free synergistic catalysis platform harnessing dicyanopyrazine-derived chromophore(DPZ)as the photoredox catalyst and a non-covalent chiral organocatalystis effective for these transformations.With the flexible use of a chiral Br?nsted acid or base in H~+transfer interchange to control asymmetric protonation,a variety of chiralα-hydroxy ketones andα-amino ketones were obtained with high yields and enantioselectivities.Significant challenges in this task include the existence of a racemic background process occurring directly via the intrinsic redox catalytic cycle,the difficulty of the enantioselective manipulation of the small H atom to generate the stereocenter,and the possible racemization of the C-O stereocenter.