Cyclizations Of Photogenerated(Aza-)ortho-Quinone Methides And Visible-Light-Driven Atroposelective Minisci Reactions

Heterocyclic compounds,especially nitrogen-and oxygen-containing heterocyclic compounds,are widely found in natural products,drugs and functional materials.So the efficient and precise construction and post-modification of these compounds has been an important area of research in the synthetic chemistry.(Aza)-ortho-quinone methides are a versatile class of intermediates with high reactivity and wide application in many fields of chemistry and biology.It has been widely used for the synthesis of various oxygen-or nitrogen-containing heterocyclic compounds due to its high propensity for rearomatization and its ability to undergo a variety of cycloaddition or nucleophilic addition reactions.In addition,with the rapid development of visible light photoredox catalysis,Minisci reaction can be carried out under milder conditions and exhibits good functional group compatibility under photocatalytic conditions,providing effective access to the synthesis of diverse aza-aromatic compounds and the late-modification of complex drug molecules.This dissertation presents a detailed survery on the relevant research results in the two aforementioned areas;and describes our studies on the synthesis of nitrogen-and oxygen-containing heterocyclic compounds through the visible lightdriven radical-mediated in situ generation of(aza)-ortho-quinone methide intermediates and the visible light-induced asymmetric Minisci reaction.Firstly,we have used a visible light-driven radical-mediated approach to in situ generate aza-orthoquinone methides,and afforded a series of benzoxazine compounds by the intermolecular(4+2)cyclization reaction between the active intermediates and aldehydes with good diastereoselectivity under mild conditions.In addition,we used aldehydes derived from Probenecid and Lithocholic acid in the reaction and smoothly introduced fragments of such drug molecules into the benzoxazine skeleton.Moreover,we have also explained the origin of diastereoselectivity of the products by DFT calculations.Based on the above work,we have also achieved the synthesis of tetrahydroquinazolines using hexahydro-1,3,5-triazinane as a C-2 synthon via the intermolecular(4+2)cyclization reaction with visible light-driven in situ-generated aza-ortho-quinone methides.The reaction has good functional group tolerance and the important fluorine-containing scaffolds in pharmaceutical chemistry can be introduced into the target products by selecting appropriate fluoroalkyl radical sources.Moreover,we have carried out some studies on the reaction mechanism(fluorescence quenching experiments,control experiments)and have proposed a possible reaction pathway.Next,we have used visible light-driven radical-mediated approach to in situ generate orthoquinone methides,and have achieved the photoredox/Br?nsted acid sequence-catalyzed(4+3)cyclization of the reactive intermediate with 2-indolylmethanol as C-3 synthon to synthesize a series of seven-membered oxygen-heterocyclic compounds.In addition,we also used chiral phosphoric acid as Br?nsted acid catalyst,and obtained chiral seven-membered oxygen-containing heterocyclic compounds with good yield and enantioselectivity by photoredox/chiral phosphoric acid sequence catalysis strategy.Finally,we have used photoredox and chiral phosphoric acid cooperative catalysis strategy to achieve asymmetric Minisci reaction of aza-aromatic compounds and α-amino acid derived redoxactive esters,and achieved the simultaneous construction of the central chirality and axial chirality of a series of aza-aromatic compounds under mild conditions.Moreover,we have converted the obtained axially chiral products into chiral organocatalysts and applied them to the asymmetric addition reaction of diethylzinc reagents to aryl aldehydes with good enantioselectivity.