Intramolecular Schmidt Reaction Of Acyl Chlorides With Alkyl Azides Followed By Intramolecular Capture Of Intermediates With Alkenes Or Alkynes

The thesis focuses on intramolecular Schmidt reaction of acyl chlorides with alkyl azides: preparation of pyrrolizine by intramolecular capture of intermediates with alkenes or alkynes. The key innovation of the research is the capture of the isocyanate ion and N-acyliminium ion intermediates with an intramolecular alkene or alkyne as the nucleophile, and the efficiency of the conversion was demonstrated with respect to ring construction and bond formation.The dissertation is composed by the following three parts:In the first part, the pyrrolizine alkaloids and the synthetic method to the pyrrolizine skeletons were reviewed. And most strategies for preparation of the substituted pyrrolizines applied proline or its derivatives as the starting materials and generally long synthetic-steps were required. Thus we proposed our approach toward this important unit.In the second part, we describled the design and realization of the method for preparation of substituted pyrrolizines through the intramolecular capture of the isocyanate ion and N-acyliminium ion intermediates from the intramolecular Schmidt reaction of acyl chlorides with alkyl azides. A series of ω-azido carboxylic acids were prepared through a sequence of alkylation with alkyl halides, azidation of the halides and saponification of the esters. The co-azido carboxylic acids were converted to the corresponding bicyclic aza-lactams through the one-pot protocol combining acyl chlorination, Schmidt reaction of acyl chloride followed by capture of the intermediates. Investigation of the conversion with different type substrates was carried with many acids as promoters, and the reactivity of the substrates were also well rationalized.In the last part, the experimental details of the conversion and spectroscopy data were provided, which included the preparation of all the intermediates, the co-azido carboxylic acids, and the one-pot conversion combining with acyl chlorination, Schmidt reaction and capture the intermediates with alkenes or alkynes.