Visible-Light Mediated Asymmetric Reduction Of Para-quinone Methide Intermediates

α,α-Diarylketones are a distinct class of molecules with diverse biological properties and are found in natural products,organic functional materials,and pharmaceuticals.The difficulty in producing these tertiary centers sited at the α-position of carbonyl compounds stems from the product containing more acidic α-H than the starting material,causing the racemization via enolization under basic or acidic conditions.Therefore,a simple and practical strategy for producing diverse α,α-diarylketone derivatives with high enantioselectivities from abundant feedstocks is highly desirable.para-Quinone methides(p-QMs)as electrophiles are important intermediates in many medicinal chemistry and biosynthesis processes.The 1,6-conjugate addition of p-QMs are an effective method for constructing polyfunctionalized diarylmethine chiral centers.In this thesis,a visible light-promoted and phosphoric acid-catalyzed multicomponent reaction has been developed base on p-QMs chemistry.The reaction involved a one-pot reaction of two processes,the visible light-promoted in situ production of p-QMs intermediates and the chiral phosphoric acid-catalyzed asymmetric hydrogenation reduction of p-QMs intermediates.A series of α,α-diaryl ketones with high enantioselectivity were successfully constructed.The thesis’ s main content is divided into two sections,as follows:Part Ⅰ: Chemical structural characterization of p-QMs and progress of research on 1,6-conjugate addition reactions are presented.The main review of organocatalytic and transition metal-catalyzed asymmetric 1,6-conjugate addition of p-QMs is from 2018 to2022.Part Ⅱ: Visible light-promoted and phosphoric acid-catalyzed multicomponent one-pot reactions of alkyne-carbonyl metathesis/transfer hydrogenation of arylalkyne,benzoquinones and Hantzsch ester were developed.A series of chiral α,α-diaryl ketone products were obtained in good yields with good enantioselectivity through the screening of catalysts,Hantzsch ester,solvents,temperatures and additives.In this reaction,three new chemical bonds,C=O,C-C and C-H,were generated,providing a new synthetic method for chiral α,α-diaryl ketones.Furthermore,this asymmetric catalytic method can be applied to the synthesis or modification of complex bioactive molecules including florylpicoxamid and BRL-15572 analogues.