טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentMasarwa Ahmad
SubjectTowards the Enantioselective Preparation of Chiral
Alkylidenecyclopropropanes
DepartmentDepartment of Chemistry
Supervisor Professor Ilan Marek
Full Thesis textFull thesis text - English Version


Abstract

Over the last few decades, the chemistry of racemic methylenecyclopropane and alkylidenecyclopropane derivatives in the presence of transition-metal catalysts has been explored extensively. The reactive nature of these compounds is commonly attributed to the strained double bond. The mode of ring opening (at the distal C3-C4 bond or at the proximal C2-C3 bond) depends mainly on the choice of catalyst. The regioselectivity of the addition of an organometallic derivative RM across the exomethylene double bond C1-C2 depends on the nature of both the organometallic and the alkylidenecyclopropane derivative. Furthermore, the presence of a carbon stereocenter on the cyclopropyl ring may lead to a transfer of chirality to the final product. The presence of quaternary stereocenters in the alkylidenecyclopropane would be particularly interesting, as insertion into the distal bond may be inhibited completely. Unfortunately, as a result of inherent difficulties with their preparation, the availability of enantiomerically enriched methylenecyclopropanes and alkylidenecyclopropanes with quaternary stereocenters is rather limited and much challenged.

Therefore, we have been interested to develop new strategies for the preparation of enantiomerically pure cyclopropene and alkylidenecyclopropane derivatives. Initially, our strategy relies on the copper-catalyzed addition of Grignard reagent to enantiomerically enriched cyclopropenylcarbinol. The preparation of optically pure heterosubstituted alkylidenecyclopropanes from cyclopropenylcarbinol via a [2, 3]- and [3, 3]-heteroatom sigmatropic rearrangement was also described. In all cases, alkylidenecyclopropane derivatives were obtained in high yields and enantioselectivity.