Publication:
Study of the asymmetric Boekelheide rearrangement reaction for 2-alkyl pirydines

Consultable a partir de

2025-10-01

Date

2020

Authors

Bacaicoa García, Sara

Publisher

Acceso embargado / Sarbidea bahitua dago
Trabajo Fin de Máster / Master Amaierako Lana

Project identifier

Abstract

It is widely known that the biological activity of a molecule can be strongly determined by its chirality. In organic and pharmaceutical chemistry, very commonly, the synthesised compounds must be stereochemically pure due to its interest as bioactive molecules. There are several strategies for obtaining non-racemic products. In this work, the focus is on two methods: chiral auxiliary and chiral metallic catalysis. The Boekelheide rearrangement reaction is a [3,3]-sigmatropic rearrangement of pyridyl N-oxides to corresponding 2-(1-hydroxy)alkyl pyridines. Both asymmetric synthesis strategies, chiral auxiliary and chiral metallic catalysis, were applied to this reaction with the aim of inducing stereocontrol. The interest of this project relies on developing new methods for obtaining stereochemically pure compounds that could broaden knowledge in this field of organic chemistry. The limited literature about the Boekelheide rearrangement also motivatesthis work. In this Master Thesis, it has been demonstrated that the chiral auxiliary strategy was extremely efficient in the diastereoselective Boekelheide rearrangement reaction. The HPLC measurements indicate that it has been achieved excellent stereocontrol with an enantiomeric ratio of 99/1, leading to 98% enantiomeric excess for the pyridylglycol synthesised by this method. Synthetic procedures were designed to have access to all the substrates needed in this work. After each synthetic step, the products were purified by flash column chromatography, with its subsequent structural analysis by Nuclear Magnetic Resonance of 1H and 13C. Although all the synthetic pathways have given very good results, they can be widely improved in order to obtain enantiopure 2-(1-hydroxy)alkyl pyridine derivatives and is worthy of more research. Unfortunately, the chiral metallic catalysis strategy did not direct the stereocontrol of the Boekelheide rearrangement, rendering a racemate.

Description

Keywords

Asymmetric synthesis, Stereocontrolled synthesis, Boekelheide rearrangement reaction, 2-alkyl pyridine, Chiral auxiliary, Evans auxiliary, Chiral catalysis, Enantiomeric excess (e.e.), Organic chemistry, Synthetic chemistry

Department

Faculty/School

Escuela Técnica Superior de Ingeniería Agronómica y Biociencias / Nekazaritzako Ingeniaritzako eta Biozientzietako Goi Mailako Eskola Teknikoa

Degree

Máster Universitario en Química Sintética e Industrial por la Universidad de Valladolid; la Universidad del País Vasco / Euskal Herriko Unibertsitatea y la Universidad Pública de Navarra, Kimika Sintetiko eta Industrialeko Masterra Valladolideko Unibertsitatean; Universidad del País Vasco / Euskal Herriko Unibertsitatea eta Nafarroako Unibertsitate Publikoa

Doctorate program

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