Studying the scope of a formal 5-endo-trig cyclization involving allyl transfer: proline derivatives

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Journal Title

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Volume Title

Kemian tekniikan korkeakoulu | Master's thesis

Date

2019-12-17

Department

Major/Subject

Fibre and Polymer Engineering

Mcode

CHEM3024

Degree programme

Master's Programme in Chemical, Biochemical and Materials Engineering

Language

en

Pages

67+16

Series

Abstract

This master’s thesis further investigates and broadens a novel synthetic pathway for the generation of substituted 3-pyrrolidinones. The investigated procedure is undoubtedly remarkable since the utilized amino-acid derivatives undergo a 5-endo-trig cyclization, which according to Baldwin’s rules is disfavored. In this study, different amino acids were protected on the amine nitrogen atom to prevent eventual undesired side reactions. Subsequently, these species are converted into their β-ketonitrile derivatives, which are then reacted with benzaldehyde to form corresponding enone systems. The nitrile electron withdrawing group has been selected from among other EWGs in previous studies. The final cyclization step is conducted in the presence of a palladium catalyst, ligand and amine additive. Furthermore, the diastereoselectivity of the synthesized heterocycles was determined. Particularly interesting is the allyl group shift which accompanies the formation of the heterocyclic ring. Additionally, enone derivatives without the nitrile group are produced in order to examine the influence of EWGs on the cyclization progress. Unfortunately, the reaction does not occur, and thus no cyclic products are obtained. The examined ring closure is a feasible method for the production of multisubstituted 3-pyrrolidinone rings, which can serves as skeleton structures to which other molecules can be attached in order to form more complex molecules.

Description

Supervisor

Koskinen, Ari

Thesis advisor

Heikinheimo, Annakaisa

Keywords

asymmetric synthesis, pyrrole derivatives, ring closure reactions, allylic compounds, palladium, catalysis

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