טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentTiran Berkovitz
SubjectAll-carbon Quaternary Stereogenic Centers in Acyclic
Systems Through Stereoselective Formation of
Trisubstituted Ketone Enolates
DepartmentDepartment of Chemistry
Supervisor Full Professor Marek Ilan
Full Thesis textFull thesis text - English Version


Abstract


The development of new and highly diastereoselective processes for the creation of carbon-carbon and carbon-heteroatom bonds in acyclic system is one of the most challenging and dynamic areas in organic synthesis. In particular, the stereoselective creation of quaternary stereogenic centers represents one of the most difficult problem to solve due to its steric repulsion between the substituents. An attractive tool in organic synthesis that can lead to the selective generation of quaternary carbon stereocenter (by the formation of new carbon-carbon bond) is the use of organometallic species such as metal enolates. However, although this strategy is well-known, the regio- and stereoselective formation of polysubstituted metal ketone enolates is still a challenging area in organic synthesis, and only one approach for the stereoselective formation of metal ketone enolate (from ketene intermediate) is known.


The goal of this research was to develop an effective approach for the preparation of molecules with four stereogenic centers including one quaternary carbon center from simple starting material (vinyl carbamates), by controlling the regio- and stereochemistry of acyclic polysubstituted ketone enolates. The formation of vinyl carbamate, known in the literature, was easily obtained by classical reported reaction. The nature of the substituent on the alkene was chosen to be a carbamoyl moiety that is known to migrate from one atom to another, as migration plays a critical role in our strategy. By a metalation and addition of an aldehyde possessing an α-stereocenter, stereodefined allylic alcoholates with two stereogenic centers were formed. The stereodefined enolate intermediates were in-situ revealed by a carbamoyl migration that could react with an electrophile. Finally, after studying each of the proposed reaction steps separately and determining the required conditions for each chemical transformation, we succeeded to create compounds with up to four stereogenic centers including one quaternary carbon center from the allylic alcoholate through a carbamoyl migration (enolate formation) and addition of imines or aldehydes, with high diastereomeric ratios and in good isolated yields.