טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentTom Targel
SubjectChiral Induction Using a Novel Umpolung Alkylation
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DepartmentDepartment of Chemistry
Supervisor Professor Szpilman Alex.m
Full Thesis textFull thesis text - English Version


Abstract

Alkyl groups are probably the most common groups encountered in organic molecules. While these groups may or may not contain other functional groups, alkylation reactions are extremely important in organic chemistry. Being a fundamental process, alkylation methodologies are abundant, and alkyl groups can be transferred as carbocations (e.g. SN1 reactions) or carbanions (e.g. Grignard reactions).


One classic example is alkylation of 1,3-dicarbonyl compounds. This reaction employs compounds such as diketones, β-ketoesters and β-ketoamides as nucleophile precursors (the nucleophile being their enolate forms), and alkyl halides as electrophilic alkylating agents.


Recently, our group has reported a new approach to alkylate ketones while reversing the traditional roles of the carbonyl compound and the alkylating agent, making the former an electrophile and the latter a nucleophile. Such a process, reversing the common reactivity pattern, is called "Umpolung". In this reaction, the carbonyl compound's reactivity is inversed by the hypervalent iodine Koser's reagent, and the alkylating agent is dialkylzinc.


Surveying the literature showed that alkylating chiral substrates such as Evans' β-ketoimides using a base and different alkyl halides proceeds with low diastereomeric ratios. Therefore, a new diastereoselective alkylation reaction of such compounds could be a reasonable alternative to the classic approach.


We found that applying our recently reported Umpolung reaction on chiral β-ketoimides affords the diastereomerically pure monoalkylated products in yields ranging from 40% to 80%, and the reaction itself proceeds with diastereoselectivities between 3:1 to 18:1.