Radical Addition-Migration/Cyclization Cascades Of Functionalized Alkenes

The radical reaction is one of the most important tool for the construction of new C-X bonds,including C-C,C-O,C-N,C-S,C-P and C-Si bonds in a simple,efficient,and direct manner.Organic molecules can be synthesized via the rational design of the substrates in a radical process.Recently,the radical cascade reaction has been the research hotspot in organic chemistry due to its good selectivity and highly efficiency.New types of substrates and reaction mechanisms are constantly emerging,which give us a chance to carry out the research with available starting materials in environment friendly,cheap,and atom economical steps.This paper mainly focuses on the development of a series of radical initiated reactions with unsaturated functional alkenes for the synthesis of functional materials,biological and pharmaceutical molecules.We have developed transition-metal or metal-free catalytic radical cascade systems and utilized these systems in the efficient synthesis of complex organic molecules.The work mainly consists of the following two parts:Part I,(a)A novel radical phosphinylation of α,α-diaryl allylic alcohols with arylphosphine oxides was described for the direct preparation of α-aryl-β-phosphinylated carbonyl ketones in medium to good yields via 1,2-aryl migration.In this reaction,formation of new C(Ar)–C(sp~3)and C(sp~3)–P bonds was observed.(b)A metal-free method for direct C(sp~3)–H bond functionalization of simple ethers withα,α-diaryl allylic alcohols is described.The established protocol provides facile access toa-aryl-b-oxyalkylated carbonyl ketones via radical addition and a1,2-arylmigration cascade process.A further application of the product has been demonstrated in the synthesis of a serotonin antagonist.(c)We have developed a powerful and convergent alkylation reaction of diaryl allylic alcohols with carbonyl compounds that involves C(sp~3)-H bond functionalization and a radical addition/1,2-aryl migration cascade.1,5-Diketones were synthesized by using simple ketones.Ester substrates provided both 1,5-diketones andg-acyloxy ketones.Amide substrates led exclusively to the formation ofg-amido ketones.Rewardingly,the utilization of simple carbonyl derivatives as radical precursors complements the set of mostly metal-mediated reactions that employ activated or prefunctionalized compounds.(d)An efficient method for the construction of ketonitriles anda-aryl ketones by tert-butyl peroxybenzoate(TBPB)mediated direct alkylation of acetonitrile withα,α-diaryl allylic alcohols has been developed.The reactions involve C(sp~3)–H functionalization and radical addition/1,2-aryl migration processes under metal-free conditions.(e)We have developed a novel and convergent alkylation reaction of alkanes with allylic alcohols that involves C(sp~3)–H functionalization and radical addition/1,2-aryl migration.The direct utilization of commercially available simple alkanes under metal-free conditions represents a practical and straight-forward route for access to a variety of highly functionalized ketones.(f)A metal-free tandem procedure by using a sulfonylation reaction of aryl allylic alcohols followed by an iodobenzenediacetate(PIDA)-promoted oxidative functionalization has been established.Allylic sulfones,g-ketosulfones,and triflyl allylic alcohols have been constructed in a single operation.The methodology incorporates the sulfonyl(both aryl and triflyl)functionality with a simple work-up procedure.(g)An aqueous catalytic method for double C-S bond formations that involves alcohol derivatives,organic halides,and sodium thiosulfate has been developed.A diverse range of functionalized sulfides,including pharmaceutical and biological derivatives,can be obtained in an efficient and eco-friendly manner under air.The mechanistic studies revealed that this TBAI catalyzed/water-assisted reaction generated a mercaptan species as the key intermediate.Part II,(a)A Cu-mediated/catalyzed selective oxidative dual C–H bond cleavage of an arene and alkylnitrile or acetone is reported.This method provides a novel approach to highly functionalized fluorene and pyrroloindole derivatives,which are useful in pharmaceutical and photoelectronic areas.In this reaction,two new C(sp~3)–C(sp~3)and C(Ar)–C(sp~3)bonds,a quaternary center and a five-membered ring are simultaneously formed.More importantly,this methodology provides chemists an alternative method for designing new pharmaceutical frameworks and photoelectronic devices.(b)A copper-mediated oxycyanomethylation reaction of olefinic amides with acetonitrile was developed for the synthesis of important benzoxazine derivatives.The reactions involve the activation of the C(sp~3)–H bond of acetonitrile and radical cyclization processes for the construction of new C–C and C–O bonds.(c)A palladium-catalyzed tandem C-Br/C-H functionalization and cyclization of alkenes with organohalides is reported.This reaction provides an operationally simple method for the synthesis of various fluorene,pyrroloindole,and benzoxazine derivatives,which are useful pharmaceutical framework and photoelectronic devices.Two new C-C/O bonds,a quaternary carbon center and a new ring,are simultaneously formed in this one-pot reaction.