Copper-catalyzed Atom Transfer Radical Cyclization Of Unactivated Halides

Halogen atom transfer radical addition reactions provide a simple,efficient and atom economical means for olefin functionalization and carbon-carbon bond construction.Research in this line is of conspicuous synthetic significance.One important application of halogen transfer radical addition in organic synthesis is the synthesis of cyclic compounds by atom transfer radical cyclization,which has attracted great attention of synthetic chemists during the past 30 years.In this thesis,the copper-catalyzed atom transfer cyclization reactions involving unactivated alkyl iodides and bromides were studied,and the content is divided into following three chapters.In the first chapter,the major progress made on the halide atom transfer radical addition during the past half century is reviewed,with an emphasis on the evolvement of copper-catalyzed atom transfer radical cyclization and the recent advances on the application of photocatalysis to atom transfer radical addition reactions.Chapter 2 and Chapter 3 describe the research work of this thesis.The results are summarized as follows:（1）The iodine atom transfer radical cyclization of unsaturated alkyl iodides was realized under blue light irradiation by using[Cu（N^N）（P^P）]PF₆complexes as photocatalyst.It was found that water has a great beneficial effect on the reaction.The reaction did not occur under 455 nm blue light irradiation in pure acetonitrile,but when a large amount of water was added into the reaction system,the iodine transfer cyclization products were generated in good yield.The addition of water rendered the[Cu（N^N）（P^P）]PF₆complex to precipitate from the solvent,and as a result,it performed the catalytic role in the form of the heterogeneous catalyst.This may be a major reason why water can facilitate the reaction.（2）The catalytic system of Cu Br and Me₆-TREN was applied to enable the bromine atom transfer radical cyclization of unactivated alkyl bromides at elevated temperature.This protocol is applicable to secondary bromides,which can be converted to secondary as well as cyclized primary bromides in high yield.For primary bromides,adding Vc and K₂CO₃into the reaction system greatly improved the reaction,and as such,cyclized primary and secondary bromides were generated as well from the corresponding primary bromide precursors.