Tandem Semipinacol/Intramolecular Schmidt Reaction And Its Application In The Synthesis Of Alkaloids

The core innovation of this thesis involves the TiCl₄-mediated-tandem Semipinacol rearrangement / intramolecular Schmidt reaction ofα-siloxy-epoxy-azide leading to a versatile and efficient approach to azaquaternary units. It consists of three parts: reviews on the research of Schmidt reaction, the design and realization of the Semipinacol rearrangement / intramolecular Schmidt reaction and the application of this tandem reaction in the synthetic study of Isococculidine and Dihydrocomosidine.Chapter 1 reviews the research of Schmidt reaction. It includes two parts: 1. The methodologies of Schmidt reaction and relative reactions. 2. Its applications in the total synthesis of nitrogen-contained natural products.Chapter 2 is aiming at the construction of azaquaternary tricyclic structure. We have designed the tandem Semipinacol rearrangement / Schmidt reaction including the tandem Semipinacol rearrangement / intermolecular Schmidt reaction, the tandem Semipinacol rearrangement / intermolecular Schmidt reaction with hydroxyl azide and the tandem Semipinacol rearrangement / intramolecular Schmidt reaction ofα-epoxy-hydroxy-azides. They were tried but failed to give positive results. At last, the TiCl₄-mediated-tandem Semipinacol rearrangement / intramolecular Schmidt reaction was realized with the protection of the hydroxyl group in theα-epoxy-hydroxy-azides. This tandem reaction can provide the functional azaquaternary units with diastereoselectivity and occurs twice rearrangements with high yield under the same reaction conditions. As its applications, it was used to construct the A-B-C core structure of erythrinan, and homoerythrinan alkaloids. Additionally, the tandem reaction was used as the key reaction to build the tricyclic-nucleus 2-46 in Stemonamine and Isostemonamine.Chapter 3 is another important part of this thesis. This part described the application of TiCl₄-mediated-tandem Semipinacol rearrangement / intramolecular Schmidt reaction as the key reaction to the synthetic study of Isococculidine and Dihydrocomosidine. We used the tosylhydrazone 3-6 or the substitute 3-9 as the starting material and successfully constructed the A-B-D core structure 3-43 of the above two alkaloids by the use of the tandem reaction. The relative stereochemistry of the two carbons located at the fusion positions of the A-B ring, which is consistent with the natural products. Compound 3-43 would be used to close the C ring after some typical transformations. It laid a firm foundation for the total synthesis of the above alkaloids.