| In this thesis,the intramolecular Schmidt reaction of ω-azido valeryl chloride followed by an intermolecular nucleophilic capture of the rearrangement products was explored,and the conversion was employed as a key step for synthesis of pyrrolophenanthridine alkaloids.It includes the following three parts:1.A brief review of the synthesis of pyrrolophenanthridine alkaloids;2.Intramolecular Schmidt rearrangement of co-azido valeryl chloride and intermolecular nucleophilic capture of the rearrangement ions;3.Synthesis of Assoanine and related pyrrolophenanthridine alkaloids using Schmidt rearrangement of ω-azido valeryl chloride.In first chapter,the synthesis research of pyrrolophenanthridine alkaloids was reviewed.The pyrrolophenanthridine alkaloids possess important physiological activities,which attracted many attentions from synthetic chemists.The most common strategy for their synthesis was relied on the construction of B-ring of the A-B-C-D skeleton as the final ring-closing reaction.In addition,some researchers had developed the ultimate cyclization of A-ring or D-ring for the synthesis of pyrrolophenanthridine alkaloids.Although the reported strategies could provide effective routes to the alkaloids,there still remained some problems,where long synthetic routes,unavailable substrates and harsh reaction conditions should limit their utility.Therefore,it is still necessary to develop new efficient and practical methods for the synthesis of these alkaloids.In second chapter,the Schmidt rearrangement of ω-azido valeryl chloride and the intermolecular nucleophile capture of its rearrangement products,isocyanate ion and N-acyliminiun ion,were explored.Firstly,the research of Lewis acid promoted reaction of theω-azido valeryl chloride and arenes from Chaturvedi’s group was introduced,which was contradictory with our continuous research on the Schmidt reaction of alkyl azides with carboxylic acids.To clarify the reaction process,the Schmidt reaction of ω-azido valeryl chloride followed by addition of a nuclephile for intermolecular capture of the rearrangement products were designed and carried out.The results indicated that the intermolecular Friedel-Crafts reaction of co-azido valeryl chloride with arenes would not occur in the presence of Lewis acids or Bronsted acids,the direct Schmidt reaction of ω-azido valeryl chloride would be preferred.The ω-azido valeryl acids,the acid promoters,the nucleophiles and the addition order were investigated.According to the experiments,the intramolecular Schmidt reaction of ω-azido valeryl chloride occurred firstly,then the rearrangement ions were attacked by employing the additional nucleophile reagents,producing the aza five-member ring products.The carbon nucleophiles could effectively capture the two rearrangement products,isocyanate ion and N-acyliminiun ion,and the electrically neutral products could be easily isolated.While the oxygen nucleophiles and nitrogen nucleophiles,for examples,alcohols and amines,could only effectively reacted with the isocyanate ion from the rearrangement reaction.In third chapter,the synthesis of Assoanine and related pyrrolophenanthridine alkaloids using Schmidt reaction of ω-azido valery chloride as the key step was explored.The synthesis started from the isochroman-3-one,which was converted to the rearrangement precursor 3-3 by treatment of it with HBr,NaN3 and LiOH.Subsequently,the Schmidt reaction of 3-3 in the presence of the five aromatic compounds was studied,efficiently producing the five N-benzyl oxo-indoles.Then the biaryl coupling reaction of the indoline was extensively explored.Finally,Reduction of3-14c twice would afford the 3-20,which was converted to Assoanine and Oxoassoanine through the Pd catalyzed Heck reaction.Also,the 1-benzyl-2-oxoindole 3-14d was used as the key material for synthesis of Anhydrolycorine and Anhydrolycorine,and it was successful by using the similar synthetic route. |
