New applications of organocatalysis
New applications of organocatalysis, in particular the use of the bicyclic amidine DBN (1,5-diazabicyclo[4.3.0]non-5-ene) and then iodide as nucleophilic catalysts for Friedel-Crafts reactions, have been investigated. Firstly, the use of amidines and guanidines as nucleophilic catalysts is reviewed....
Main Author: | |
---|---|
Other Authors: | |
Published: |
University of Bath
2011
|
Subjects: | |
Online Access: | https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.547629 |
id |
ndltd-bl.uk-oai-ethos.bl.uk-547629 |
---|---|
record_format |
oai_dc |
spelling |
ndltd-bl.uk-oai-ethos.bl.uk-5476292019-03-14T03:24:47ZNew applications of organocatalysisTaylor, James EdwardBull, Steven ; Williams, Jonathan2011New applications of organocatalysis, in particular the use of the bicyclic amidine DBN (1,5-diazabicyclo[4.3.0]non-5-ene) and then iodide as nucleophilic catalysts for Friedel-Crafts reactions, have been investigated. Firstly, the use of amidines and guanidines as nucleophilic catalysts is reviewed. Amidines and guanidines are traditionally thought of as strong, non-nucleophilic bases. However, there is increasing evidence to suggest that amidines and guanidines are actually strong nucleophiles and can act as catalysts in a number of reactions. The development of the first organocatalytic Friedel-Crafts acylation reaction is then described. It was found that DBN catalyses the regioselective C2-acylation of pyrroles and C3-acylation of indoles using acyl chlorides. The protocol was shown to work for a wide range of aromatic and alkyl acyl chlorides, as well as for a number of protected pyrroles and substituted indoles. The synthetic utility of the methodology was demonstrated with the synthesis of the non-steroidal anti-inflammatory drug Tolmetin. Detailed mechanistic studies have confirmed that DBN acts as a nucleophilic catalyst in the reaction, forming an N-acyl DBN intermediate with the acyl chloride. The structure of the intermediate has been confirmed by X-ray crystallographic analysis of an N-acyl DBN species as its tetraphenylborate salt. As the N-acyl DBN tetraphenylborate salt was found to be bench stable, the use of such salts as alternatives to acyl chlorides was investigated. A number of crystalline and air stable N-acyl DBN tetraphenylborate salts were synthesised and were shown to act as acylating agents towards a wide range of nucleophiles, including primary and secondary amines, sulfonamides, and alcohols. The DBN hydrotetraphenylborate side-product could be conveniently removed from the reaction mixtures by filtration, allowing pure acylated products to be isolated without the need for column chromatography. Finally, whilst investigating the Friedel-Crafts acylation of pyrroles, it was found that lithium iodide was a highly active catalyst for the process. Preliminary mechanistic studies suggest that the iodide acts as a nucleophilic catalyst towards acyl chlorides to form an acyl iodide intermediate in the reaction541.39organocatalysisUniversity of Bathhttps://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.547629Electronic Thesis or Dissertation |
collection |
NDLTD |
sources |
NDLTD |
topic |
541.39 organocatalysis |
spellingShingle |
541.39 organocatalysis Taylor, James Edward New applications of organocatalysis |
description |
New applications of organocatalysis, in particular the use of the bicyclic amidine DBN (1,5-diazabicyclo[4.3.0]non-5-ene) and then iodide as nucleophilic catalysts for Friedel-Crafts reactions, have been investigated. Firstly, the use of amidines and guanidines as nucleophilic catalysts is reviewed. Amidines and guanidines are traditionally thought of as strong, non-nucleophilic bases. However, there is increasing evidence to suggest that amidines and guanidines are actually strong nucleophiles and can act as catalysts in a number of reactions. The development of the first organocatalytic Friedel-Crafts acylation reaction is then described. It was found that DBN catalyses the regioselective C2-acylation of pyrroles and C3-acylation of indoles using acyl chlorides. The protocol was shown to work for a wide range of aromatic and alkyl acyl chlorides, as well as for a number of protected pyrroles and substituted indoles. The synthetic utility of the methodology was demonstrated with the synthesis of the non-steroidal anti-inflammatory drug Tolmetin. Detailed mechanistic studies have confirmed that DBN acts as a nucleophilic catalyst in the reaction, forming an N-acyl DBN intermediate with the acyl chloride. The structure of the intermediate has been confirmed by X-ray crystallographic analysis of an N-acyl DBN species as its tetraphenylborate salt. As the N-acyl DBN tetraphenylborate salt was found to be bench stable, the use of such salts as alternatives to acyl chlorides was investigated. A number of crystalline and air stable N-acyl DBN tetraphenylborate salts were synthesised and were shown to act as acylating agents towards a wide range of nucleophiles, including primary and secondary amines, sulfonamides, and alcohols. The DBN hydrotetraphenylborate side-product could be conveniently removed from the reaction mixtures by filtration, allowing pure acylated products to be isolated without the need for column chromatography. Finally, whilst investigating the Friedel-Crafts acylation of pyrroles, it was found that lithium iodide was a highly active catalyst for the process. Preliminary mechanistic studies suggest that the iodide acts as a nucleophilic catalyst towards acyl chlorides to form an acyl iodide intermediate in the reaction |
author2 |
Bull, Steven ; Williams, Jonathan |
author_facet |
Bull, Steven ; Williams, Jonathan Taylor, James Edward |
author |
Taylor, James Edward |
author_sort |
Taylor, James Edward |
title |
New applications of organocatalysis |
title_short |
New applications of organocatalysis |
title_full |
New applications of organocatalysis |
title_fullStr |
New applications of organocatalysis |
title_full_unstemmed |
New applications of organocatalysis |
title_sort |
new applications of organocatalysis |
publisher |
University of Bath |
publishDate |
2011 |
url |
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.547629 |
work_keys_str_mv |
AT taylorjamesedward newapplicationsoforganocatalysis |
_version_ |
1719001858751594496 |