Applications Of Heteroatom-Centered Radical Cyclization Reactions To The Synthesis Of Nitrogen-Containing Heterocycles

Free radical reactions constitute a basic type of organic reactions and play an important role in modern organic synthesis.The initiation of heteroatom-centered radicals and the synthetic applications of their reactions are still challenging tasks in comparison with the extensive studies and wide applications of carbon-centered radicals in organic chemistry.This dissertation deals with the initiation and cyclization reactions of N-alkoxyamidyl/iminoxyl/ sulfonyl radicals,which have been applied to the synthesis of some structurally important heterocycles.This thesis is divided into the following six chapters:Chapter 1: The classification,generation methods and reaction types of heteroatom-centered radicals as well as the Baldwin-Beckwith rules on free radical cyclization are briefly introduced,followed by a brief review on the generations and reactions of N-alkoxyamidyl/iminoxyl/sulfonyl radicals.Chapter 2: A green and efficient aerobic oxidation reaction has been developed by using CuCl/air as the catalytic oxidation system and easily prepared alkyne-tethered N-alkoxyamides as the substrates.By using this protocol,a series of structurally novel 2,3-dihydro-9H-isoxazolo[2,3-b]isoquinolin-9-ones and 3,4-dihydro-[1,2]oxazino[2,3-b]isoquinolin-10(2H)-ones have been efficiently prepared via the in situ-produced N-alkoxyamidyl radical-mediated 5/6-exo-dig cyclizations.The reaction mechanism was revealed and validated by intermediate detection,isotope labeling,kinetic isotope effect and EPR(electron paramagnetic resonance)experiments.Chapter 3: A novel and facile method to vicinal oxycyanation and aminocyanation of unactivated alkenes bearing oximes has been achieved via iminoxyl radical-promoted dichotomous 5-exo-trig cyclizations.A variety of potentially bioactive cyano-featured isoxazolines and cyclic nitrones can be facilely synthesized with CuCN as the commercially available cyanating reagent and TBHP as the environmentally friendly oxidant.Chapter 4: A metal-free approach for the synthesis of structurally important isoxazoline/cyclic nitrone-featured methylenes has been developed through the iminoxyl radical-promoted oxyalkenylation and aminoalkenylation of intramolecular alkenes.This protocol employs unsaturated ketoximes as the substrates and TEMPO as the iminoxyl radical initiator as well as the ?-hydrogen acceptor for the Cope-like elimination.Chapter 5: A sulfonyl radical-promoted cascade annulation under metal-free conditions has been realized with sulfinic acids as the sulfonating reagent,TBHP as the sulfonyl radical initiator,and 2-alkynyl arylazides as the substrates.By using this strategy,a range of potentially bioactive 3-sulfonylindoles have been efficiently synthesized via vicinal sulfonamination of alkynes.Chapter 6: Conclusion and outlook.