Propargyl Cation Induced Semipinacol Rearrangement And Its Synthetic Application Toward Daphniyunnine B

Daphniphyllum alkaloids constitute a large group of polycyclic structurally complex nature products.More than 250 members of this type alkaloid have been isolated and reported in literature to date.As a subclass of Daphniphyllum alkaloids,Calyciphylline A-type alkaloids,with their compelling ?bowl-like? carbon framework and congested vicinal quaternary carbon centers,have posed a formidable challenge toward their syntheses.Although creative endeavors have been taken in the construction of the intricate carbocyclic framework of these alkaloids,no total synthesis has been achieved to date.As an efficient method to construct the quaternary carbon center and introduce a functionalized side chain for further elaboration,intermolecular semipinacol rearrangement induced by carbon-centered electrophile,though still in its infancy,has its great potential in the construction of spirocyclic ring systems containing an all-carbon quaternary center.In search for such a synthetic approach,we noticed the Nicholas reaction,which is a direct transformation for the introduction of propargyl group,would be a suitable choice for inducing the desired rearrangement and introducing a propargyl group for late-stage functionalization.This dissertation describes the synthetic studies of Daphniyunnine B,which are based on a strategy to construct its vicinal quaternary carbon centers by utilizing intermolecular Co-complexed propargylic cation induced semipinacol rearrangement.There are three parts of this dissertation:Part I: The isolation,structural features and bioactivities of Daphniphyllum alkaloids are briefly described in this chapter.The reported synthetic studies towards Calyciphylline A-type alkaloids are also summarized in detail;Part II: These two chapters introduce the development of intermolecular carbon-centered electrophile induced semipinacol rearrangement,specifically the tandem Nicholas/ semipinacol rearrangement reaction.On the basis of our proposal,we have developed a Lewis acid promoted intermolecular Co-complexed propargylic cation induced semipinacol rearrangement,which could provide a wide range of propargyl substituted oxa-,aza-,all-carbon spirocyclic compounds.After an additional four-step transformation,the all-carbon [6,5]-spiro compound could be converted into the A-C-D tricyclic core framework of Daphniyunnine B,which laid the foundation for the further total synthesis of this alkaloid;Part III: Toward the total synthesis of Daphniyunnine B,the following methods are developed to construct the A-C-D-E tetracyclic core framework of this alkaloid: a)An intermolecular Nicholas/semipinacol rearrangement for the construction of E ring and vicinal quaternary carbon centers;b)A Johnson-Claisen rearrangement to introduce a side chain adjacent to the vicinal carbon centers;c)A reductive amination between Bn NH2 and 1,4-dicarbonyl compound to construct the pyrroline ring;d)A ring closing metathesis to construct the seven-membered D ring.Further studies toward the total synthesis of Daphniyunnine B are currently underway in our laboratory.