Radical Reactions In Heterocyclic Compounds, And ¦Â ~ 2 - Synthesis Of Amino Acids In The Applications

Classification:O62In recent years,the application of controllable radical reactions in organic synthesis attracts the interests of organic chemists.Radical reaction conditions are often mild and neutral,and many functional groups are unaffected under these conditions.Given these great advantages,synthetic chemists are trying to develop radical reactions for complex nature product synthesis.Our group previously reported a series of Lewis acid-catalyzed stereoselective atom/group transfer radical cyclization reactions in the synthesis of carbocycles.The objectives of this thesis include:(1) to develop methods for the synthesis of heterocycles and apply them in the synthesis of key intermediates of nature products; (2) to explore an intermolecular radical addition reaction to C=N double bond and its application in theβ²-amino acid synthesis.Many nature products with a pyrrolidine core structure exhibit great biological activities and stereoselective construction of pyrrolidine structures has become an important topic in organic synthesis.In this thesis,a diphenyl diselenide-promoted phenylseleno group transfer radical cyclization reaction has been developed for the formation of 3,4-trans pyrrolidinones in high stereoselectivity without any Lewis acid catalyst.The effects of different N-protecting groups and allylic substituents have been explored.Using this method,a key intermediate of nature product isocynometrine has been successfully prepared.The Et₂AlCl-promoted phenylseleno group transfer radical cyclization reaction has also been employed in the synthesis of 3-(1-hydroxyalkyl)-pyrrolidinone in high yield and high stereoselectivity.Different Lewis acids and substituents were explored. The choice of Et₂AlCl is the key for the good yield and high stereoselectivity of this reaction.Compared with the known synthetic routes for pyrrolidine derivatives,our method shows impressive efficiency and high stereoselectivity.It was attempted to apply the phenylseleno group transfer radical cyclization reaction to the synthesis of oxygen-heterocycles.Arctigenin and its derivatives with aγ-butylactone core structure exhibit good biological activities.Model studies with cinnamyl benzoylacetate showed that the cyclization productγ-butylactone was obtained in 45%yield under phenylseleno group transfer radical cyclization condition. The cyclization precursor of arctigenin was prepared effectively through a convergent synthetic route from vanillin;however,it failed to cyclize under radical cyclization conditions.The bulky substituent ofβ-ketoester may increase the energy of the required transition state and make the cyclization disfavored.Asymmetric synthesis ofβ²-amino acids is an interesting field in organic synthesis.A novel effective Ag-catalyzed intermolecular C=N bond radical addition reaction has been developed and applied to asymmetric synthesis ofβ²-amino acids. For substrates bearing alkyl substituents,the reaction gave high yield and high de value,and the stereoselectivity was realized through the use of a chiral auxiliary.The reaction mechanism was investigated using TEMPO as a radical trap,and the reaction was found likely proceed through a radical pathway.This new reaction represents a promising tool for the preparation of some important building blocks such asβ^2,3-amino acids for peptidomimetics research.