Planar Chiral Ferrocene Lithium Amide Bases: A New Generation of Bases for Asymmetric Synthesis

The design and preparation of a new class of planar chiral ferrocenyl lithium amide bases is described. Work commenced on preparing N./V-dimethyl-l-ferrocenylethylamine derivatives. Electrophilic amination was attempted with a variety of reagents, but no diamines were ever obtained. The introduction...

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Main Author: Arnall-Culliford, Jennifer
Format: Thesis (University of Nottingham only)
Language:English
Published: 2002
Subjects:
Online Access:https://eprints.nottingham.ac.uk/59224/
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author Arnall-Culliford, Jennifer
author_facet Arnall-Culliford, Jennifer
author_sort Arnall-Culliford, Jennifer
building Nottingham Research Data Repository
collection Online Access
description The design and preparation of a new class of planar chiral ferrocenyl lithium amide bases is described. Work commenced on preparing N./V-dimethyl-l-ferrocenylethylamine derivatives. Electrophilic amination was attempted with a variety of reagents, but no diamines were ever obtained. The introduction of a boronic acid group was also attempted, but no products were isolated. Finally, nitration followed by reduction was investigated, but again proved unsuccessful, resulting only in the preparation of a dimer of the starting amine, 2,2'-bis-[ 1 -(//, A-dimethylamino)-ethyl]-l, l'-biferrocenyl. Our attention turned to derivatives of MN-diisopropylferrocene carboxamide. Metallation, followed by quenching with iodine gave Af,N-diisopropyl-2- iodoferrocene carboxamide. Copper(I) oxide mediated coupling of the iodide with either acetic acid or phthalimide gave access to ortho-oxygen and nitrogen donor groups. A new class of planar chiral bases (N-alkyl-(2- alkoxyferrocenyl)methylamines) were prepared from this starting material by reduction of the amide, followed by substitution of the diisopropylamine with a range of primary amines. Assays were carried out using the deprotonation of 4-tert-butylcyclohexanone and trapping of resultant enolate with TMSC1. Bases having a plane of chirality as the only stereochemical element, disappointingly, gave nearly racemic silyl enol ether, however low optical purities were recorded for bases consisting of both central and planar chirality. A non-chelating planar chiral lithium amide base was prepared (^S}-A^-rer/-butyl-(2-methylfen'ocenyl)-t methylamine, however this too gave nearly racemic silyl enol ether in the assay reaction. The synthesis of planar chiral azaferrocenyl bases was attempted by sequential complexation of lithiated pyrrole-2-methanol and lithium pentamethyl- cyclopentadienide with iron(II) chloride, followed by acylation of the pendant alcohol. However, all attempts to substitute the acetate with an amine proved unsuccessful.
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spelling nottingham-592242025-02-28T12:15:43Z https://eprints.nottingham.ac.uk/59224/ Planar Chiral Ferrocene Lithium Amide Bases: A New Generation of Bases for Asymmetric Synthesis Arnall-Culliford, Jennifer The design and preparation of a new class of planar chiral ferrocenyl lithium amide bases is described. Work commenced on preparing N./V-dimethyl-l-ferrocenylethylamine derivatives. Electrophilic amination was attempted with a variety of reagents, but no diamines were ever obtained. The introduction of a boronic acid group was also attempted, but no products were isolated. Finally, nitration followed by reduction was investigated, but again proved unsuccessful, resulting only in the preparation of a dimer of the starting amine, 2,2'-bis-[ 1 -(//, A-dimethylamino)-ethyl]-l, l'-biferrocenyl. Our attention turned to derivatives of MN-diisopropylferrocene carboxamide. Metallation, followed by quenching with iodine gave Af,N-diisopropyl-2- iodoferrocene carboxamide. Copper(I) oxide mediated coupling of the iodide with either acetic acid or phthalimide gave access to ortho-oxygen and nitrogen donor groups. A new class of planar chiral bases (N-alkyl-(2- alkoxyferrocenyl)methylamines) were prepared from this starting material by reduction of the amide, followed by substitution of the diisopropylamine with a range of primary amines. Assays were carried out using the deprotonation of 4-tert-butylcyclohexanone and trapping of resultant enolate with TMSC1. Bases having a plane of chirality as the only stereochemical element, disappointingly, gave nearly racemic silyl enol ether, however low optical purities were recorded for bases consisting of both central and planar chirality. A non-chelating planar chiral lithium amide base was prepared (^S}-A^-rer/-butyl-(2-methylfen'ocenyl)-t methylamine, however this too gave nearly racemic silyl enol ether in the assay reaction. The synthesis of planar chiral azaferrocenyl bases was attempted by sequential complexation of lithiated pyrrole-2-methanol and lithium pentamethyl- cyclopentadienide with iron(II) chloride, followed by acylation of the pendant alcohol. However, all attempts to substitute the acetate with an amine proved unsuccessful. 2002-12-13 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/59224/1/251971.pdf Arnall-Culliford, Jennifer (2002) Planar Chiral Ferrocene Lithium Amide Bases: A New Generation of Bases for Asymmetric Synthesis. PhD thesis, University of Nottingham. amide bases; electrophilic amination; chiral bases
spellingShingle amide bases; electrophilic amination; chiral bases
Arnall-Culliford, Jennifer
Planar Chiral Ferrocene Lithium Amide Bases: A New Generation of Bases for Asymmetric Synthesis
title Planar Chiral Ferrocene Lithium Amide Bases: A New Generation of Bases for Asymmetric Synthesis
title_full Planar Chiral Ferrocene Lithium Amide Bases: A New Generation of Bases for Asymmetric Synthesis
title_fullStr Planar Chiral Ferrocene Lithium Amide Bases: A New Generation of Bases for Asymmetric Synthesis
title_full_unstemmed Planar Chiral Ferrocene Lithium Amide Bases: A New Generation of Bases for Asymmetric Synthesis
title_short Planar Chiral Ferrocene Lithium Amide Bases: A New Generation of Bases for Asymmetric Synthesis
title_sort planar chiral ferrocene lithium amide bases: a new generation of bases for asymmetric synthesis
topic amide bases; electrophilic amination; chiral bases
url https://eprints.nottingham.ac.uk/59224/