טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentIsland Biana
SubjectStereoselective Synthesis of All-Carbon Quaternary
Stereogenic Centers in Acyclic Systems
DepartmentDepartment of Chemistry
Supervisor Professor Ilan Marek
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 is one of the major recurring ambitions in chemical synthesis. The construction of quaternary carbon stereocenters bearing four different non-hydrogen substituents, represents one of the most challenging and dynamic areas in organic synthesis. Most of the current methods produce only one carbon-carbon bond per chemical step and, therefore, may suffer from low efficiency.

In this work, we describe a highly diastereoselective and efficient process in acyclic system for the construction of homoallylic alcohols bearing a quaternary stereocenter. Starting from simple alkynes, the formation of three new carbon-carbon bonds was performed in one chemical step. Our method consists of consecutive, regio and stereocontrolled carbocupration followed by zinc homologation and allylation reactions. In addition, allylation reaction with α-substituted carbonyl compounds gave us homoallylic alcohols containing three consecutive stereocenters, including an all carbon quaternary center, with high diastereoselectivities.

The stereochemistry was rationalized through a Zimmerman -Traxler chair-like transition state, in which the bulky group R3 of aldehydes occupies a less sterically-demanding pseudo-axial position to avoid gauche interactions with the substituents on the double bond.

In addition, having the bulky group R3 in a pseudo-axial position allows a chelated six-membered ring transition state between zinc and the heteroatom. The observed stereoselectivity is consistent with the proposed transition state.