טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentPisarevsky Evgeni
SubjectDiscovery and Design in Oxidative Chemistry
DepartmentDepartment of Chemistry
Supervisor Professor Alex.m Szpilman
Full Thesis textFull thesis text - English Version


Abstract

Part 1: Organocatalytic oxidation of alcohols to esters:

Organocatalysis presents a novel approach to economic, environmentally friendly, and practical synthesis in modern chemistry. The approach has existed more than century, but the hidden potential was discovered only in the past decade. After conceptualization of the field in 2000, the growth in this domain of research has been tremendous.[1] The number of publications on this topic increased from singles to hundreds per year. Additionally, many other fields in chemistry were influenced by organocatalysis and have been inspired to develop additional, novel methods based on this concept. The formation of esters presents one of the common, ubiquitous transformations in organic chemistry. Classical esterification is almost always accomplished by oxidation of alcohols to aldehydes or acids, and subsequent acylation. Additionally, modern methods of esterification have recently been developed using catalysts based on transition metals which can transform some alcohols directly to esters. However, very few examples exist based on organocatalysis which can effect the direct transformation of alcohols to esters. Most organocalytic methods are based on the use of NHC’s. In our lab we have decided to develop new method of esterification that includes all the advantages of organocatalysis and to try to give an answer to number of challenges as synthesis of esters directly from alcohols, reaction in mild conditions, non-activated alcohols using. Our research concentrated on the integration of TEMPO as an organocatalyst for esterification methods.


Part 2: Oxidative alkylation

Creative thinking is a crucial step in developing new chemical synthetic methods. The umpolung concept is one of these creative approaches in organic chemistry. The concept introduces the “reverse” reactivity vis a vis common chemical reactivity patterns. A successful umpolung method thus offers a strategic alternative to the synthetic chemist. Molecules may be synthesized that are inaccessible using classical synthetic methods.

In our laboratory we focused on an umpolung method for activation of the carbon to carbonyls for nucleophilice attack by metalloorganic nucleophile such as alkylzinc/alkylaluminum. The strategy is based on the activation of the α carbon by withdrawing electrons using an oxidant. Historically this can be done via an enamine strategy (Scheme I, Enaminylium) or direct activation through oxygen (Scheme I, Enoxylium).


Scheme I:

 

After literature and experimental screening of oxidants it was found that hypervalent iodine may potentially serve as an effective reagent for this transformation. Hydroxyl (tosyloxy) iodobenzene(Koser's reagent)  was found to be the optimal oxidant in combination with an organozinc or organoaluminium reagents.