Synthesis Of Heterocyclic Skeletons Via Relay Visible Light Photoredox Catalysis

Visible light photoredox catalysis has recently emerged as a powerful synthetic tool to achieve important organic transformations and carbon-carbon or carbon-heteroatom bonds formation.It has displayed remarkable advantages in synthesis of complex and useful heterocyclic frameworks due to its simple operation,mild condition,low catalyst load,step economy and satisfaction of sustainable development.The merger of photoredox catalysis with other catalysis,such as transition-metal catalysis,acid catalysis and organocatalysis,has also been discovered to achieve novel reaction mode or functionalization of inert bonds,which single visible light photoredox catalysis itself is hardly competent.During the last two years,the relay visible-light photoredox catalysis has acted as a span-new model of visible light photoredox catalysis to attract organic synthesis chemist's attention and has grown by leaps and bounds.We have synthetized four different kinds of heterocyclic frameworks via relay visible light photoredox catalysis strategy.Details are as follows:Part I:The functionalization of a cascade of C(sp2)-H/C(sp3)-H bonds in aldehyde hydrazones with simple 2,2-dibromo-1,3-dicarbonyls was achieved via relay visible light photoredox catalysis.The aldehyde hydrazone derivatives first obtained C(sp2)-H functionalization via aminyl radical-polar crossover strategy,subsequently completed the functionalization of C(sp3)-H bond adjacent to nitrogen atom via 6? electrocyclic reaction/[1,5]hydrogen atom transfer and sequentially formed two new carbon-carbon bonds to synthesize complex and bioactive fused dihydropyrazoles and related derivatives with moderate to good yields and excellent regioselectivity under mild reaction conditions.Two oxidative quenching cycles haved been involved in the whole transformation.Part II:A relay visible light photoredox catalysis strategy has been accomplished to synthesize pyrazole framework.This strategy sequentially achieved isoquinoline-derived aldehyde hydrazone derivatives the functionalization of C(sp2)-H bond,intramolecular Mannich reaction,deesterification and aromatization,which afforded rapidly access to complex and biologically important pyrazole scaffold in a step economical manner with high efficiency under mild conditions.Three successive photoredox cycles(one oxidative quenching cycle and two reductive quenching cycles)are engaged in a single reaction with one photocatalyst.We have enriched relay visible light photoredox catalysis,which first combined oxidative quenching cycle with reductive quenching cycle.Part III:We have achieved double Csp3-H bonds cascade functionalization of styrene derivatives and constructed indolo[2,1-a]isoquinoline framework via relay photoredox catalysis strategy.The orth-isoqunoline derived styrenes underwent at least three visible-light photoredox catalytic cycles under[1,5]hydrogen atom transfer assisted to construct indolo[2,1-a]isoquinoline framework with bioactivity.This strategy achieved double C(sp3)-H bond functionalization and sequentially formed two carbon-carbon double bonds from simple materials in efficient and step-economical manner.In mechanism experiments,we found that not noly diethyl 2,2-dibromomalonate could react with orth-isoqunoline derived styrenes to get the corresponding products,but the corresponding diethyl 2-bromomalonate could finish this whole transformation under the optimized condition just with lower yields and longer reaction time.Part IV:In this part,we have selectively achieved 1,2-carbooxygenation and 1,2-carbohalogenation of styrenes to separately construct 2-arylated furan compounds and 1,3-dibromide compounds.Based on the electronic effect of alkenes,we found that the styrenes bearing electron-donating substituents on the aromatic rings uniformly underwent two oxidative quenching cycles to finish the 1,2-carbooxygenation and afforded 2-arylated furan products in satisfying yields;both the electron-withdrawing functionality and relatively weak electron-donating groups on the aromatic rings underwent radical chain reaction under oxidative quenching cycle as a trigger to achieve 1,2-carbohalogenation of styrenes and gave 1,3-dibromide compounds.During the exploration of reaction scope of styrenes,we found some interesting competing experimental phenomenon:for some special electronic density of alkene with one C=C bond,1,2-carbooxygenation and 1,2-carbohalogenation could meanwhile happen and separately got 2-arylated furan compounds and 1,3-dibromide compounds;for other special electronic density of alkene with two C=C bonds,the same alkenes could meanwhile take part in 1,2-carbooxygenation and 1,2-carbohalogenation and got 2-arylated furan and 1,3-dibromide compounds.