Research@StAndrews
 
The University of St Andrews

Research@StAndrews:FullText >
Chemistry (School of) >
Chemistry >
Chemistry Theses >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10023/2609
This item has been viewed 27 times in the last year. View Statistics

Files in This Item:

File Description SizeFormat
Thefulltextofthisdocumentisnotavailable.pdf4.23 kBAdobe PDFView/Open
Title: Lewis base-promoted organocatalysis : O- to C-carboxyl transfer reactions
Authors: Campbell, Craig D.
Supervisors: Smith, Andrew D.
Keywords: Organocatalysis
Lewis base
N-heterocyclic carbene (NHC)
Steglich rearrangement
Carboxyl transfer
Isothiourea
Quarternary amino acid
Butenolide
Issue Date: 30-Nov-2010
Abstract: This work describes the application of a variety of Lewis bases, encompassing predominantly N-heterocyclic carbenes (NHCs), but also the use of imidazoles, aminopyridines, amidines and isothioureas, as effective catalysts in the dearomatisation of heterocyclic carbonates, predominantly the rearrangement of oxazolyl carbonates to their C-carboxyazlactone isomers by means of the Steglich rearrangement. This rearrangement reaction has been investigated extensively, with the development of simplified reaction procedures and the invention of domino cascade protocols incorporating this transformation. In an attempt to understand the mechanism of this O- to C-carboxylation process, a number of interesting observations have been made. Firstly, the class of NHC has an important factor in promoting the rearrangement, with triazolinylidenes being the most effective. Secondly, an interesting chemoselectivity has been delineated using triazolium-derived NHCs, prepared using weak bases (typically Et₃N) or strong metallated bases; both alkyl and aryl oxazolyl carbonates undergo smooth rearrangement with triazolinylidenes derived from strong metallated bases such as KHMDS, while only aryl oxazolyl carbonates undergo rearrangement using Et₃N. Extensive effort has focused towards the development of asymmetric variants of these protocols, primarily towards the design, synthesis and evaluation of chiral NHC precatalysts. To this end, a number of chiral azolium salts have been prepared, encompassing a number of different NHC classes, including C₁- and C₂-imidazolinium salts, C₂-imidazolium salts and a range of triazolium salts. Efforts towards the asymmetric catalysis of the Steglich rearrangement of oxazolyl carbonate substrates have given an optimal 66% ee. Similar rearrangements have been demonstrated with the related furanyl heterocyclic substrate class, producing a mixture of α- and γ-carboxybutenolides. In contrast to the analogous oxazolyl carbonates, the regioselectivity of this rearrangement is dependent upon the nature of the Lewis base employed. Amidines and aminopyridines give a mixture of the α- and γ- regioisomers with generally the α-regioisomer being preferred, while a triazolium-derived NHC gives rise to predominantly the thermodynamically more stable γ-carboxybutenolide. Using amidines or aminopyridines, this rearrangement has been shown to proceed via an irreversible C-C bond-forming process, but in contrast, the rearrangement using the NHC proceeds via an equilibrium process with an optimised regioselectivity of >98:2 for the γ-carboxybutenolide regioisomer over the α-regioisomer. Whilst the asymmetric variant using chiral NHCs has proven unfruitful, rearrangements using a chiral isothiourea have given high levels of regioselectivity towards the α- regioisomer and with excellent levels of enantiodiscrimination (77–95% ee).
URI: http://hdl.handle.net/10023/2609
Type: Thesis
Publisher: University of St Andrews
Appears in Collections:Chemistry Theses



This item is protected by original copyright

This item is licensed under a Creative Commons License
Creative Commons

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

DSpace Software Copyright © 2002-2012  Duraspace - Feedback
For help contact: Digital-Repository@st-andrews.ac.uk | Copyright for this page belongs to St Andrews University Library | Terms and Conditions (Cookies)