N Hybrid Alpha-(aryl) Alkylene - Ring Ketone Method Of Research And Its Application In Total Synthesis Of Allopumiliotoxin267a

α-Alkylidene cycloketones such as aza-cycloketones are common features of many bioactive compounds. Few methods reported are effective to construct these motifs in a stereospecific and controllable manner.In this dissertation we developed a new method on synthesis of these structures via the intramolecular nucleophilic acyl substitution (INAS) reaction based on I-Li exchange of the vinyl iodide.The reaction parameters of the synthesis of 3-alkylidene-piperidin-4-one via INAS were investigated in terms of solvent effects, lithiating reagent, additive, solvent and the ester group. This startegy was applied to the synthesis of the 3-alkylidene-piperidin-4-ones with multiple substitution patterns and rich structural diversity.The utility of the above synthetic methodology was demonstrated in our total synthesis of allopumiliotoxin 267A. The chiral amine 273 was prepared by diastereoselective alkylation using Evans' auxiliary, followed by Swern oxidation, Corey-Fuchs reaction and Mitsunobu reaction. Epoxide 269 was synthesized from 1, 4-butanediol. The key intermediate 272 was obtained by alkylation-epoxide ring-operning of 269 with 273. The INAS reaction was carried out on 272 which yield 231 smoothly, the subsequent reduction of 231 led to the target molecule allopumiliotoxin 267A. This is one of the shortest route on the total synthesis of the allopumiliotoxin 267 A.In addition, we prepared a couple of pyrrole-2-boronic acids for X-ray crystallography study.