טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentZohar Eilnor
SubjectC-H and C-C Bond Formation as a New and General Approach
for the Preparation of Chiral Cyclopropanes
DepartmentDepartment of Chemistry
Supervisors Professor Ilan Marek
Professor Amnon Stanger


Abstract

The synthesis of enantiomerically enriched cyclopropanes can mainly be achieved by the use of either of two classes of reagents: (1) the halomethylmetal-mediated cyclopropanation reactions and (2) the transition metal-catalyzed decomposition of diazo compounds. However, these method suffers major drawbacks. Therefore, in this research, we have developed an entirely different and general approach from those previously presented, by exploring the reactivity of cyclopropenes.


First, the diastereoselective hydro- and carbo- metallation of racemic cyclopropenylcarbinols were investigated and both reactions showed high diastereoselectivity. The hydrometallation reaction occurs with LiAlH4 in Et2O allows an easy and straightforward preparation of anti-cyclopropylcarbinols as single isomer. Whereas, in the carbometallation reaction, syn or anti cyclopropylcarbinols can be obtained, depending on the nature of the organometallic reagent being used.


An interesting preparation of deuteriated dienes in excellent yields as unique geometrical isomers was developed via the deuterio-cyclopropylaluminum species being obtained in the reduction of cyclopropenylcarbinols.


A new route for the preparation of enantiomerically pure (R)-cyclopropenylcarbinol derivatives was achieved by applying the kinetic resolution conditions of  the Sharpless epoxidation on racemic cyclopropenylcarbinols.


Chiral cyclopropanes can also be obtained by attaching a sulfinyl group on the cyclopropenyl ring. Preliminary studies on the diastereoselective carbometallation showed moderate selectivities.


Moreover, deprotonation of the acidic hydrogen in cyclopropenylsulfoxides followed by alkylation with various electrophiles leads to chiral methylenecyclopropane derivatives with high diastereoselectivity even when bearing three chiral contiguous centers.