Synthesis of bifunctional 2-aminodmap/prolinamide organocatalysts and their use in asymmetric michael reaction to afford warfarin


Thesis Type: Postgraduate

Institution Of The Thesis: Middle East Technical University, Faculty of Arts and Sciences, Department of Chemistry, Turkey

Approval Date: 2012

Thesis Language: English

Student: Hasan Ufuk Akkoca

Supervisor: CİHANGİR TANYELİ

Abstract:

In the first part of this thesis, the construction of the novel bifunctional proline-(1R,2R)-2-aminoDMAP organocatalyst backbone is described. Target compound has both Lewis base and Brønsted acid catalaphoric sites. The Lewis base site is synthesized via selective mono-N-pyridilization of trans-(1R,2R)-cyclohexane-1,2-diamine by Cu catalysis and Brønsted acid site is subsequently introduced by anchoring L-proline unit. In the second part, catalytic activities of organocatalysts are tested in asymmetric Michael addition reaction between a cyclic 1,3-dicarbonyl compound 4-hydroxycoumarin and various α,β-unsaturated ketones to afford optically active warfarin as anticoagulants, in one step. Reaction parameters such as solvent, temperature, equivalency, and cocatalyst were screened. Enantiomeric excess value (ee) up to 72% is attained.