Radical Addition/Cyclization Reactions Of Unsaturated Hydrocarbons And Carbon Radicals

The radical-mediated C-C bond forging reactions are a class of the most valuable strategies for the construction of functional molecules,so that are intensively used in drug synthesis and preparation of materials and represent a desirable supplement to transition-metal catalyzed coupling reactions.In recent years,a novel series of C-C and C-heteroatom bond construction reactions exploiting C-centered radicals as intermediates were prosperously reported.However,the formation of C-centered radicals usually requires harsh conditions,and their activities are seldom subservient,which makes their synthetic applications seriously limited.Therefore,the generation of C-centered radicals under mild conditions for selective transformations is a research direction with importance.This thesis focuses on the generation and selective transformation of alkyl radicals,and developed a series of radical coupling and addition reactions by hiring transition-metal catalysts that tune the reactivity of radical intermediates.The efficient synthesis of functionalized amides and amines is also accomplished.The main research contents are as follows:1.Claisen rearrangement cascade reaction of propargylic alcohols and AIBN is established by using AIBN as a cyanogen source via the coordination of a radical with a metal catalyst tuning radical reactivity.Under the optimal reaction conditions of 5 mol%Cu(CH3CN)4BF4 and 10 mol%4-nitrophenylboronic acid,N-cyanoalkyl amides containing alkynyl could be obtained from secondary propargyl alcohols and AIBN in a yield up to 95%.In addition,N-cyanoalkyl amides containing allene could be obtained from primary propargyl alcohol by using 10 mol%AgOTf as a catalyst.The mechanism study demonstrated that ketenimine was the key intermediate of the radical reaction.Meanwhile,the 18O-labeling experiment showed that the oxygen atom of the carbonyl group in the amides originated from propargyl alcohols.2.Claisen rearrangement radical cascade reaction of allylic alcohols and AIBN is established by using AIBN as a cyanogen source via the coordination effect of the metal catalyst tuning radical reactivity.N-cyanoalkyl amides containing alkenyl could be obtained in 54-95%yields under the conditions of 5 mol%Cu(CH3CN)4BF4,10 mol%3,5-(CF3)2C6H3B(OH)2,DME,and 100℃ for 12 h.The coordination effect of the metal not only facilitates the selective radical-radical cross-coupling to generate the ketenimines holding higher electrophilicity but also plays a key role in promoting the Claisen rearrangement by intercepting ketenimines with allylic alcohols.3.An iron-catalyzed reductive dicarbofunctionalization reaction of alkenes is established by using AIBN as a cyanogen source and in-situ iminium ion as an alkylating agent via electron-shuttle catalysis of the metal catalyst.When using FeSO4·7H2O/DCyPE as a catalyst,NaI as an electron transfer reagent,and MgBr2·Et2O as an additive,a series of functional alkyl amines could be obtained from simple olefin,AIBN,secondary amine and paraformaldehyde in 24-85%yields.The reaction not only introduces two important functional groups but also simultaneously constructs two alkyl-alkyl bonds on a variety of electron-deficient and electron-rich alkenes.This transformation shows high step economy,good substrate adaptability,and functional group tolerance.4.A difunctionalization/cycloamination reaction of aminodienes is established by using benzyl halide as a precursor of benzyl radical via C-N bond activation.Polysubstituted pyrrolidine derivatives could be obtained in 37-80%yields under the conditions of 10 mol%NiCl2/DPPP,20 mol%BnCl,anisole,and 130℃.What’s more,a series of piperidine,morpholine,and tetrahydroisoquinoline derivatives could be obtained in the presence of 10 mol%NiCl2/DPPP and 30 mol%I2 via the formation of an amine-iodine CT complex.