Organic Phosphine Catalyzed Reaction Of Allenones To Construct Nitrogen-containing Heterocycle

Nitrogen-containing heterocyclic compounds are widely used in medicine,pesticides,organic synthesis,and other fields,and have been the focus of medicinal chemistry and organic chemistry research.Many drugs and natural products have nitrogen-containing heterocyclic fragments as core structures.In addition,the chiral N-heterocyclic compounds are also the importantly synthetic intermediates,organic catalysts,and chiral ligands in asymmetric synthesis.Since Lu Xiyan’s pioneered the discovery of phosphorus-mediated[3+2]annulation between allenoate and activated olefin in 1995,phosphine-catalyzed cycloaddition reactions have been made remarkable progress.Among them,the phosphine-catalyzed cyclization reaction of electron-deficient allenes and imines is a concise and efficient method for constructing chiral N-heterocycles.This thesis has developed the asymmetric[4+2]cycloaddition reactions betweenα-substituted allenones and imines to construct six-membered N-heterocycles based on the review of phosphine-catalyzed various annulation with electron-deficient allenes.After that,the phosphine-catalyzedδ-addition ofγ-substituted allenones to imines to synthesize conjugated dienes,and the one-pot reaction that phosphine-catalyzedδ-addition and visible light promoted isomerization-cyclization has also been developed for the construction of a series of dihydropyrrole derivatives.In the first part of this thesis,the asymmetric[4+2]cycloaddition making use ofα-substituted allenic ketones as“C4 synthons”has been developed.In the presence of amino acid-derived bifunctional phosphines,a wide range of allenic ketones with functional groups at theα-position were tolerated.A series of chiral sultam-fused tetrahydropyridines bearing a quaternary stereocenter were obtained in high yields with good enantioselectivities（43-99%yield,73-97%ee）.In addition,this organophosphine catalytic system has successfully realized the application of allenones substrate with long-chain alkyl or allyl substitution in theα-position in the asymmetric[4+2]cycloaddition reaction for the first time.This work broadens the range of substrates for organophosphine-catalyzed electron-deficient allenones in the asymmetric[4+2]cycloaddition reaction.In the second part of this thesis,with the attempts of developing a new type of organo phosphine and photo co-catalytic system,the relay catalysis that including phosphine-catalyzedδ-addition and visible light promoted-cyclization was performed betweenγ-substituted allenones and benzosulfonimides for the synthesis of five-membered N-heterocyclics.However,the investigations have shown that the phosphine-catalyzedδ-addition reaction ofγ-substituted allenone to benzosulfonimides was not efficient under blue light condition.Alternatively,an efficient one-pot method was developed for the synthesis of benzosultams with dihydropyrrole skeletons.After the completion of phosphine-catalyzedδ-addition reaction,the blue light（3W）was used with the assistance of photosensitive catalyst Ru（bpy）₃Cl₂·6H₂O and diisopropyl ethyl base,promoting the olefin isomerization-cyclization reaction to provide dihydropyrrole derivatives with good yields and diastereoselectivityies.The chemoselectiveδ-addition reaction to the synthesis of benzosultam compounds with a conjugated diene skeleton was also realized in the presence of organo phosphine catalyst.In summary,this thesis utilized the organo phosphines as efficient catalysts,to catalyze the reactions of electron-deficient allene for the construction of N-heterocycles.The asymmetric[4+2]cycloaddition reaction between benzosulfonimide andα-substituted allenone has been successfully realized.And,the one-pot reaction that phosphine-catalyzed addition,followed by light-accelerated cyclization reaction has also been developed.As a result,nitrogen-containing heterocyclic compounds with diverse structures are efficiently constructed,and the reaction scope of the organo phosphine-catalyzed cyclization reactions using electron-deficient allenes is also expanded.