טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentFrid Liat
SubjectVarious Approaches towards the Creation of Stereodefined
All-Carbon Quaternary Stereocenters
DepartmentDepartment of Chemistry
Supervisor Professor Ilan Marek
Full Thesis textFull thesis text - English Version


Abstract

The stereoselective construction of all-carbon quaternary stereocenters in acyclic systems is one of the most difficult transformations in organic synthesis. There are few methods available for realizing this task in a diastereo- and enantiocontrolled manner, most of them are based on asymmetric catalysis. These methods indeed overcome the challenges imposed by the inherent difficulties in the creation of such centers, but - only one carbon-carbon bond is created between two reagents. Over the past few years, our group was involved in the development of synthetic strategies for the formation of all-carbon quaternary stereocenters in various products, including aldol products. It was achieved with a great efficiency as the desired products were synthesized with good enantio- and diastereoselectivities in a one-pot reaction with the concomitant formation of three new carbon-carbon bonds. This strategy is based on the successive manipulation of ynamide substituted with the oxazolidinone chiral auxiliary. However, during this transformation, the oxazolidinone ring is subjected to a nucleophilic attack by the b hydroxyl group which result in an extremely stable cyclic enamide. This product should be cleaved in order to obtain the aldol product. This manuscript is divided  into two parts. The first part describes our attempts to improve this method, which include various conditions that were applied for the cleavage of the cyclic products, synthesizing new starting materials and investigating their applicability for the reaction sequence. In addition, attempt to expand the reaction scope to other electrophiles is also described.  The second part describes another approach we have considered for the synthesis of all-carbon quaternary stereocenters in general and in aldol product specifically. This approach includes the conjugated addition of organometallic reagent to a-substituted-a'-hydroxy enone derivatives, which may lead to the formation of a,a-disubstituted stereodefined enolates. During this research, optimal conditions were determined and diastereoselective conjugated addition was achieved with good diastereoselectivity. The scope and limitations, and exact reaction mechanism should still be investigated.