(I)以二氯甲烷及四氯化碳衍生的“類亞甲體”導引羰基烯化和烯類及酯類的三元環化(II)以1,1-二氯乙烯直接將酮丙烯化(III)(+)-Retronecine 的合成研究

Abstract

Abstract The thesis is divided into three parts. In the first part, we wish to report protocols whereby TiCl4-Mg-promoted oxidative additions of CH2Cl2 and CCl4 can be directed to form methylene- and dichloromethylene carbenoids, respectively. With access to these systems, we explored the best conditions for the direct coupling of these methylene carbenoids with C=O and C=C double bonds. Not only can these ambiphilic carbenoids be directed to serve as highly nucleophilic methylenation equivalents in methylenation of ketones, aldehydes, and esters but they also seem to serve as highly electrophilic species in alken-cyclopropanations and ester-cyclopropanations. To further demonstrate the synthetic utility of TiCl4-Mg bimetallic complex, in the second part, we concentrated on the allenation of ketones with vinylidene carbenoid derived from TiCl4-Mg-CH2=CCl2-THF and the methoxymethylenation of ketones with methoxymethylene carbenoid derived from TiCl4-Mg-(MeO)CHCl2-THF, leading to allene and vinyl methyl ether derivatives, respectively. In the third part, we turned our attention to the asymmetric synthesis of (+)-Retronecine. To develop an efficient and practical route, we examined the use of L-(+)-tartaric acid as a cheap starting material. A facile construction of a [3.3.0] bicyclic framework, which might serve as a synthetic intermediate toward (+)-Retronecine, has been realized by virtue of the development of a three-step strategy involving coupling of (E)-2-bromo-4-amino-2-butenol with tartaric acid, silylation of diol, and application of the metal-halogen exchange to promote an intramolecular coupling of vinylbromide with imide. Further efforts will direct toward elaboration of this bicyclic intermediate into (+)-Retronecine.