טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentUnger Rozalia
SubjectNew Tandem Reactions for the Construction of Carbocycles
DepartmentDepartment of Chemistry
Supervisor Professor Ilan Marek


Abstract

The construction of Carbon-Carbon bonds is arguably one of the most important operations in organic chemistry, and among them formation of carbocycles. One of these methods is the anionic cyclization of various organometallic compounds. The use of organometallic compounds to create carbon-carbon bonds was developed mostly after the discovery of organomagnesium reagents by Grignard. Since then, reactions which result in the addition of a carbon-metal bond of an organometallic across a carbon-carbon multiple bond, leading to a new organometallic in which the newly formed carbon-metal bond can be used for further synthetic transformation, are called carbometalation reactions.


            If the carbometalation reaction is performed on an asymmetrically substituted double bond, two new sp3 stereogenic centers are created after reaction with an electrophile. Thus, in order to have a powerful reaction in synthetic organic chemistry, it is necessary to control the regio- and diastereoselectivity of this carbometalation reaction.


            We wanted to focus on the construction of polysubstituted carbocycles by reaction of alkynylmetal derivatives to several acylsilanes followed by the tandem Brook-rearrangement and the intramolecular carbocyclization for the formation of five-membered rings.


            Over the years, Reich demonstrated that addition of alkynyllithiums reagents to acylsilane was smoothly followed by a silyl migration and electrophilic trapping to regiospecifically afford siloxy-allenyl products.  However, in-situ addition of an electrophile was necessary to maximize the yield of the Brook rearrangement; without addition of the electrophiles, only minor quantity of expected product was obtained, even when an alkynyl group was used as electron withdrawing group (EWG). 


During our studies, we have found that ZnBr2 can be used successfully as an electrophile to shift quantitatively the equilibrium of the Brook rearrangement (versus the retro-Brook).  Although, more studies are now required to understand the zinc salt effect, we have been able to use this rearrangement for the ene-allene carbocyclization reaction.  When alkynyllithiums- or magnesium derivatives are added to acylsilane, lithium- (or magnesium) alcoholate are obtained quantitatively.  However, even after an extended period of time, the Brook-rearrangement was not observed in a significant amount.


            In contrast, when ZnBr2 was added to the reaction mixture, the rearrangement occurs to give first the corresponding zinc alcoholate, which subsequently undergoes the rearrangement into the allenylzinc bromide.  After stirring for few hours, cyclic product was obtained in good yield and as a unique geometric isomer for the creation of a tertiary and quaternary stereogenic centers.