טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentLevin Anat
SubjectStereoselective Preparation of Metalated Enynes and Allyl
Zirconium Species
DepartmentDepartment of Chemistry
Supervisor Professor Ilan Marek


Abstract

    Recently, organozirconium derivatives have emerged as being synthetically useful reagents or intermediates in organic synthesis where vinyl metals can serve as building blocks for organic target molecules.

    It is known that Negishi reagent can induce in some cases multipositional regioisomerization of non-conjugated dienes. In our research group, a method for the preparation of conjugated dienes was developed by a reaction between the Negishi reagent and a non-conjugated diene. The process is accompanied by a double bond migration along the alkyl chain towards the second double bond. Further β-elimination affords the desired dienylzirconium species. The zirconocene moiety can be located at internal and terminal position of the metalated diene that is produced.

     In this manuscript, we will describe how we tried to develop a method for the preparation of metalated conjugated dienes in a E,E-geometry by starting with a non-conjugated dienes bearing a leaving group at the terminal position. These dienes systems went through an isomerization-elimination reaction to give in a single-pot operation the corresponding metalated dienyl zirconium derivatives. Since enynes can be found in many living organisms, metalated enynes are also very important intermediates in organic synthesis. Therefore we also developed a process of addition-β-elimination on conjugated enyne derivatives, to produce the corresponding metalated conjugated enyne at the vinylic position.

    Finally, the pathway of isomerization-β-elimination was also found to be useful for the conversion of ω-heterosubstituted alkenes into substituted allylzirconocene species. Although several methods exist for the preparation of allylzirconocene species, the synthesis of substituted allylmetal remains difficult and relatively inefficient. We have developed a new and straightforward route to substituted allylzirconocene moieties, composed of a reaction between the Negishi reagent and non-conjugated heterosubstituted olefins. This process was also accompanied by a double bond migration (like in the non conjugated diene case) along the alkyl chain followed by β-elimination to afford the desired allylzirconium species, which can further react with different electrophiles. The double bond migration was found to be unlimited by the chain length, while the method is generalized for a broad spectrum of substrates.