Study On The Five-membered Cyclization Of Ortho-alkynyl Substrates Via Radical Mechanisms

Five-membered ring compounds,are the dominant framework for the development of active drugs,especially containing five-membered carbon heterocycles and pentane ringswh which are ubiquitious in nature.such as indoles,furans,and indanones.Developing new and simple synthesis methods of five-membered ring compounds has very important research value and application prospects.It is one of the goals of organic synthesis to explore a new and effective method to construct the five membered ring skeleton.The paper focus on the efficient catalytic model,some cyclization reactions,and the construction of new functional five membered heterocycles or carbon ring frameworks.With high reactivity,the o-Alkynyl substrates can be used to build a five-membered ring skeleton.In this paper,four kinds of ring skeleton have been designed and constructed around o-alkynylanilines,o-alkynylphenols and o-alkynylpropenones.The thesis involves both tert-butyl nitrite and Tongi’s reagents,which can generate nitro radical,nitroso radical and trifluoromethyl radical in different catalytic modes.These reactions were study the reaction conditions,the generality of substrates,the rule of electronic effect,the synthetic utility and the reaction mechanism by silver or copper,which in order to establish the radical five-membered cyclization.The research includes four parts as follows:Firstly,the C（sp²）-H bond nitration of N-sulfonyl protected o-alkynylarylamine was achieved.tert-Butyl nitrite as a radical precursor attacks the unsaturated bond of the benzene through the weak guidance by AgNO₃.5-Nitroindoles were formed through five-membered cyclization while the 7-nitroindoles.The AgNO₃/TBN combination has a high catalytic efficiency,excellent regioselectivity and a good gram-scale amplification experiment.The product structure could be further reduced to the aminoindole or sulfonamidoindole.Secondly,it was proved that the carbonyl oxygen of indazole-2-oxides originated from water.The reaction occurs just only under argon that o-alkynyl-N-methylarylamine by AgNO3/TBN with different from the previous work completely.There are a large number of nitric oxide radicals in the system.The silver oxidized amino groups form nitrogen radical cations,which are then added to the nitric oxide radicals.o-Alkynyl-N-methylarylamine was firstly oxidized to nitrogen radical cations via Ag which added to the nitric oxide radicals from TBN,followed by a five-membered cyclization/nitrosylation to build a new C-N bond and N-N bond,the indazole-2-oxide was finally generated.Thirdly,3-Nitrofuran was synthesized by a radical reaction with extremely unstable and poor universality.The work ingeniously designed the reactant by adding a benzene ring on the alkynylphenol to enlarge the conjugation area,the stable 3-nitronaphthofuran synthesized rapidly with TBN at low temperature,and established a C-O and C-N bonds in one step.Finally,1-Indanones with quaternary carbon centers could was performed from o-alkynyl acrylone,Togni’s reagent and trimethylnitrile silane（TMSCN）under the interaction of Cu（OTf）₂ and phenanthroline ligand via a five-membered cascade cyclization.It has cis-trans isomerism which the alkynyl group into an exocyclic alkenyl group by 5-exo-dig,owing to the cyano steric hindrance is small,cis-form is the main configuration.Synthetic applications have reduced all carbonyl,alkenyl and cyano groups to obtain cyclopentanol through trifluoromethylcyanation.In this dissertation,a new method for the synthesis of polysubstituted 5-/7-nitroindole,indazol-2-oxide,3-nitronaphthalene（benzofuran）and 1-indanone has been established with o-alkynyl derivatives as substrates,and a one-step strategy for the construction of five membered ring skeleton initiated by four kinds of free radicals has been developed.The dissertation has 11 figures,8 tables and 278 references.