In April 2016 Manchester eScholar was replaced by the University of Manchester’s new Research Information Management System, Pure. In the autumn the University’s research outputs will be available to search and browse via a new Research Portal. Until then the University’s full publication record can be accessed via a temporary portal and the old eScholar content is available to search and browse via this archive.

Tertiary thiols via stereospecific α-arylation of lithiated allylic thiocarbamates

Mingat, Gaelle

[Thesis]. Manchester, UK: The University of Manchester; 2014.

Access to files

Abstract

This thesis describes the work carried out on the lithiation and rearrangement of N-aryl- and N-vinyl allylic thiocarbamates, with the aim of preparing a wide range of versatile tertiary thiols. The synthesis of the racemic allylic starting materials has been achieved through in situ [3,3]-sigmatropic rearrangement of O-allylthiocarbamates to their S-counterparts (II.A). The enantioselective version relies either on asymmetric metal catalysis (achiral substrates) or stereospecificity (enantiopure substrates) in the [3,3]-sigmatropic rearrangement. Lithiation followed by N to C aryl migration proceeds in generally good to excellent yields, with both electron-poor and electron-rich rings. The scope and the influence of various substituents at Cα or on the allylic double bond are presented in Section II.B.1. Section II.B.2 proposes a mechanistic pathway and details NMR studies carried out to get structural data in the α-thioallyllithium intermediates. Investigations of the stereospecificity of the rearrangement show that most rings migrate without loss of enantioenrichment in substrates bearing an unsubstituted allylic double bond (II.B.3.a). Complete enantiospecificity with all rings has been achieved in thiocarbamates bearing a cyclohexyl-substituted double bond (II.B.3.b). Section II.C reports the results obtained in the N to C transfer of non-aromatic groups. Excellent enantiospecificities have been achieved in the migration of a vinyl substituent, although yields remain moderate. Higher yields can be obtained but they come along with lower enantiomeric ratios. Section II.D details the transformations undertaken in the rearranged tertiary allylic thiocarbamates. A wide range of tertiary thiols has been obtained with good to excellent yields. Functionalisation of the allylic double bond in these hindered substrates was not straightforward. Eventually, ring-closing metathesis in S-allyl sulfides allows the preparation of biologically interesting 2,5-dihydrothiophenes bearing a highly enantioenriched quaternary centre. Finally, evidence for retentive aryl migration in allylic thiocarbamates is outlined in Section II.E. Circular dichroism experiments were carried out in the derivatised 2,5-dihydrothiophenes and compared with predictions obtained via DFT calculations for both enantiomers of a model compound. The absolute configuration of the 2,5-dihydrothiophenes and their tertiary thiocarbamate precursors has been unambiguously established, confirming a retentive pathway in both aryl and vinyl migrations.

Bibliographic metadata

Type of resource:
Content type:
Form of thesis:
Type of submission:
Degree type:
Doctor of Philosophy
Degree programme:
PhD Chemistry (42 month)
Publication date:
Location:
Manchester, UK
Total pages:
344
Abstract:
This thesis describes the work carried out on the lithiation and rearrangement of N-aryl- and N-vinyl allylic thiocarbamates, with the aim of preparing a wide range of versatile tertiary thiols. The synthesis of the racemic allylic starting materials has been achieved through in situ [3,3]-sigmatropic rearrangement of O-allylthiocarbamates to their S-counterparts (II.A). The enantioselective version relies either on asymmetric metal catalysis (achiral substrates) or stereospecificity (enantiopure substrates) in the [3,3]-sigmatropic rearrangement. Lithiation followed by N to C aryl migration proceeds in generally good to excellent yields, with both electron-poor and electron-rich rings. The scope and the influence of various substituents at Cα or on the allylic double bond are presented in Section II.B.1. Section II.B.2 proposes a mechanistic pathway and details NMR studies carried out to get structural data in the α-thioallyllithium intermediates. Investigations of the stereospecificity of the rearrangement show that most rings migrate without loss of enantioenrichment in substrates bearing an unsubstituted allylic double bond (II.B.3.a). Complete enantiospecificity with all rings has been achieved in thiocarbamates bearing a cyclohexyl-substituted double bond (II.B.3.b). Section II.C reports the results obtained in the N to C transfer of non-aromatic groups. Excellent enantiospecificities have been achieved in the migration of a vinyl substituent, although yields remain moderate. Higher yields can be obtained but they come along with lower enantiomeric ratios. Section II.D details the transformations undertaken in the rearranged tertiary allylic thiocarbamates. A wide range of tertiary thiols has been obtained with good to excellent yields. Functionalisation of the allylic double bond in these hindered substrates was not straightforward. Eventually, ring-closing metathesis in S-allyl sulfides allows the preparation of biologically interesting 2,5-dihydrothiophenes bearing a highly enantioenriched quaternary centre. Finally, evidence for retentive aryl migration in allylic thiocarbamates is outlined in Section II.E. Circular dichroism experiments were carried out in the derivatised 2,5-dihydrothiophenes and compared with predictions obtained via DFT calculations for both enantiomers of a model compound. The absolute configuration of the 2,5-dihydrothiophenes and their tertiary thiocarbamate precursors has been unambiguously established, confirming a retentive pathway in both aryl and vinyl migrations.
Thesis main supervisor(s):
Funder(s):
Language:
en

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:224484
Created by:
Mingat, Gaelle
Created:
30th April, 2014, 14:43:57
Last modified by:
Mingat, Gaelle
Last modified:
1st August, 2014, 09:38:02

Can we help?

The library chat service will be available from 11am-3pm Monday to Friday (excluding Bank Holidays). You can also email your enquiry to us.