טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentGilboa Noga
SubjectPreparation and Stereochemistry of Homoallylic Alcohols
Containing Quaternary Stereocenters
DepartmentDepartment of Chemistry
Supervisor Professor Ilan Marek
Full Thesis textFull thesis text - English Version


Abstract

The development of new and highly stereoselective processes for the creation of carbon-carbon and carbon-heteroatom bonds was, and still is, one of the main problems of chemical synthesis. The construction of quaternary stereocenters, represents one of the most challenging and dynamic areas in organic synthesis.

In this manuscript, we primarily study the addition of allyl metal species to various aldehydes. We describe the diastereoselective preparation of homoallylic alcohols containing a quaternary stereocenter in a one-pot reaction. In addition, to have a better understanding of the stereochemical pathway, we have also performed computational chemistry calculation to explain our experimental results. The stereochemical aspects of the reaction of  g, g'-disubstituted allylzinc  with various carbonyl compounds shows, for the first time, that an axial arrangement was by up to 4 kcal/mol preferred over an equatorial in the Zimmerman -Traxler chair-like transition state.

 The extension of our method was successfully applied to ketones as the electrophilic partner of the reaction. In this reaction three new carbon-carbon bonds as well as two consecutive stereocenters, including quaternary and all-carbon quaternary centers were formed with high diastereoselectivities.

 Finally, the allylation reaction of a-chiral carbonyl compounds led us to obtain homoallylic alcohols in high diastereoselectivities containing three consecutive stereocenters, including an all-carbon quaternary center. The stereochemical outcome of the reaction determined X-ray analysis. Theoretical calculations support six - membered ring transition state stabilized by chelation between zinc and oxygen. The observed stereoselectivity is consistent with this proposed transition state.

A key feature common in this work is the use of commercially available and simple starting materials.