Synthesis Of Pyrrolidine Via Schmidt Reaction Of Acyl Chlorides And Asymmetric Transfer Hydrogenation Of α-Azido Cinnamates

Organic azides are very important compounds, which have been widely used in synthetic chemistry and pharmaceutical industry.This thesis focuses on the reaction of organic azides, and it describes the preparation of pyrrolidine via the intramolecular Schmidt reaction of acyl chlorides with azides followed by intermolecular nucleophilic capture of the intermediates, and the asymmetric transfer hydrogenation of α-azido cinnamates.In the first part, a brief review on the conversion of organic azides to pyrrolidines was summarized, and the transformation of organic azides to chiral amines was also addressed.In the second part, the intramolecular Schmidt reaction of acyl chlorides with alkyl azides and the intermolecular capture of the isocyanate ion and N-acyliminium ion intermediates with several nucleophilic species have been designed and realized. The full optimization of the reaction conditions includes the exploration of the acidic promoters, nucleophiles, reaction temperature and solvents. Five azido carboxylic acids were successfully converted to the desired pyrrolidines via four different intermolecular nucleophilic reagents. Furthermore, the reaction mechanism was investigated by quantum chemistry, aiming on the rearrangement of aminodiazonium ion intermediate. Finally, the calculation results agreed well with the experimental results.In the third part, we explored the asymmetric reduction of α-azido cinnamates with several chiral catalysts. The conversion of azido group to amine could be easily realized under the hydrogenation conditions, however the reduction of alkene failed. The enamine intermediate was hydrolyzed to a ketone, which was further reduced to the α-hydroxy ester.11 α-hydroxy esters were prepared, with yield up to 99% and ee up to 90%.