Copper-Catalyzed Enantioselective Cyanation And Azidation Of Alkenes

The high reactivity and low selectivity of free radicals restrict the development of radical reactions to a certain extent,and the enantioselective control in radical reactions have always been extremely challenging in organic synthetic chemistry.This thesis focuses on the asymmetric radical reactions through copper-catalyzed radical relay strategy to achieve a series of asymmetric difunctionalization of alkenes.This thesis is divided into two parts,the first part focuses on the research of copper-catalyzed enantioselective functionalization of alkenes,including:(1)copper-catalyzed asymmetric phosphinoylcyanation of styrenes;(2)copper-catalyzed asymmetric cyanotrifluoromethylation of alkenyl esters/alkenyl amides;(3)copper-catalyzed asymmetric phosphinoylazidation of styrenes.The second part focuses on the research of copper-catalyzed radical cross-coupling reaction,the copper-catalyzed cross-coupling reaction of sulfonyl radicals with thiyl radicals has been developed.1.Copper-catalyzed asymmetric phosphinoylcyanation of styrenesBased on our group’s research of copper-catalyzed asymmetric functionalization of alkenes through radical relay strategy,the copper-catalyzed reaction of styrenes,diarylphosphines and TMSCN in the presence of a chiral ligand was investigated.The experiment results showed that the phosphinoyl radical was added to the styrenes to generate the benzyl radicals with tert-butyl hydroperoxide as an oxidant,which is then combined with the chiral copper cyanide species.The copper-catalyzed asymmetric phosphinoylcyanation of styrenes was successfully realized under mild conditions through reduction elimination reaction.In this reaction,a series of chiral alkylnitrile compounds containing phosphorus were synthesized,and the resultant β-cyanodiarylphosphine oxides could be easily converted to a series of potential chiral y-amino phosphine ligands.2.Copper-catalyzed asymmetric trifluoromethylcyanation of alkenyl esters/alkenyl amidesCarbon-nitrogen/carbon-oxygen chiral center bond are ubiquitous in natural compounds and drugs,and there are many synthetic methods on the chiral C-O/C-N bond construction,such as the asymmetric reduction and addition reaction of imines/ketones,however,the reaction with a α-amino radical process has been rarely reported.The copper-catalyzed asymmetric trifluoromethylcyanation of alkenyl esters/alkenyl amides had been realized through the combination of chiral copper complex with carbon radical adjacent to hetero atom which was generated from radical addition reaction.The reaction conditions are mild and the functional groups of the substrate are compatible,and a series of chiral alkylnitrile compounds adjacent to nitrogen/oxygen atom were obtained with good to excellent enantioselectivity.3.Copper-catalyzed asymmetric phosphinoylazidation of styrenesIn our previous work,the asymmetric cyanation,arylation and alkynylation of benzyl radical had been realized.In this paper,copper-catalyzed reactions of styrenes,diphenoxyphosphines and TMSN3 in the presence of a chiral ligand were investigated.The experiment results showed that the phosphinoyl radical was added to the styrenes to generate the benzyl radicals,which was then combined with the chiral copper azide species.The copper-catalyzed asymmetric phosphinoylazidation of styrenes through reduction elimination reaction was initially explored,4.Copper-catalyzed cross-coupling reaction of sulfonyl radicals with thiyl radicalsIn this paper,the copper-catalyzed radical cross-coupling reaction of sulfonyl radicals and thiyl radicals which generated from ulfonylhydrazide and thiol respectively had been realized with TBHP as oxidant,and a series of thiosulfonates were successfully synthesized.