The Research On Schmidt Reaction Of Aldehydes With An Azido Amine And Total Synthesis Of (±)-antofine

This thesis focused on the Schmidt reaction of alkyl azides, and two central contents were included:(1) Schmidt reaction of aromatic aldehydes with an azido amine, and (2) design of Schmidt reaction of acyl chlorides with alkyl azides and its application in the attempt on total synthesis of antofine. In the first part, the exclusive1,2-aryl migration was observed in the Schmidt reaction of aromatic aldehydes with3-azido-N-tosylpropan-1-amine, then the formal metal-free N-arylation of aromatic aldehydes was achieved. In the second part, the substrate of the intramolecular Schmidt reaction of acyl chlorides was designed, and migration of methine group was controlled. Then the N-acyliminium ion was obtained as intermediate and was captured in situ by the aromatic ring to benzoindolizidine. The conversion was employed to the attempt on the total synthesis of antofine.In chapter1, we presented a full review on the Schmidt reaction of aldehydes and its application in synthesis of natural products.In chapter2, the design and realization of aryl-migration Schmidt reaction of aryl aldehyde is described. The exclusive migration of an aryl group over hydride was observed, with the formal N-arylation of formamides being obtained in good to excellent yields. Furthermore, an aliphatic aldehyde was also converted to the N,N-disubstituted formamide in excellent yield as formal N-alkylation product.In chapter3, the Schmidt reaction of acyl chlorides with alkyl azides with excellent control of migration of methine group was accounted. The important features of the conversion include the following:(1) wonderful efficiency of conversion was demonstrated in bond formation (three new bonds created) and ring construction (two new rings); and (2) the reaction proceeded through a three-step sequence to afford the benzoindolizidine unit, which included acylchlorination, Schmidt rearrangement, and etectrophilic addition of the N-acyliminium ion to the aromatic ring. Then the attempt to employ this conversion to the total synthesis of antofine was undertaken.