Abstract
The first part of this thesis describes the use of thiosemicarbazones for dynamic combinatorial chemistry. Building blocks incorporating thiosemicarbazides and acetalprotected aldehydes were synthesised and conditions where these building blocks formed dynamic combinatorial libraries under thermodynamic equilibrium in organic solvents were developed. It was found that addition of nucleophilic species such as hydrazides or thiosemicarbazides increased the rate with which these libraries reached equilibrium. Species showing this behaviour were dubbed equilibrators, and a range of templates were added to these equilibrator-containing libraries, from which ligands for several transition metals (Pd, Ni, and Zn) were identified.
In the second part of this thesis, the discovery that thiosemicarbazones catalyse the
tetrahydropyranylation of alcohols in dichloromethane at room temperature is presented.
This represents the first use, to the best of the author’s knowledge, of thiosemicarbazones
for organocatalysis. Guided by kinetics studies, a range of catalysts were developed and
evaluated, and this showed that thiosemicarbazone catalysts are highly tuneable. The best
thiosemicarbazone catalyst gave a 50-fold higher second-order rate constant than the best
thiourea catalyst reported for this transformation. A dual Hammett plot analysis and
interaction studies by NMR spectroscopy lends support to a reaction mechanism
proceeding via an asynchronous [2+2] cycloaddition.
The third and final part of this thesis describes the development of new bifunctional
organocatalysts for the formation of hydrazones and oximes at neutral pH. New effective
variants of the previously known anthranilic acid-based catalysts were discovered, and via
a virtual breakdown of the structure of already identified catalysts, two new types of
catalysts were discovered: The 2-aminophenols and the 2-(aminomethyl)benzimidazoles.
With aldehyde substrates none of the newly discovered catalysts were as effective as a
previously discovered benzenephosphonic acid, but with aromatic ketones, an otherwise
challenging class of substrates, the 2-(aminomethyl)benzimidazoles showed promising
efficacies, reaching an hitherto unseen 5-fold rate enhancement for hydrazone formation
on model acetophenone at pH 7.4.
In the second part of this thesis, the discovery that thiosemicarbazones catalyse the
tetrahydropyranylation of alcohols in dichloromethane at room temperature is presented.
This represents the first use, to the best of the author’s knowledge, of thiosemicarbazones
for organocatalysis. Guided by kinetics studies, a range of catalysts were developed and
evaluated, and this showed that thiosemicarbazone catalysts are highly tuneable. The best
thiosemicarbazone catalyst gave a 50-fold higher second-order rate constant than the best
thiourea catalyst reported for this transformation. A dual Hammett plot analysis and
interaction studies by NMR spectroscopy lends support to a reaction mechanism
proceeding via an asynchronous [2+2] cycloaddition.
The third and final part of this thesis describes the development of new bifunctional
organocatalysts for the formation of hydrazones and oximes at neutral pH. New effective
variants of the previously known anthranilic acid-based catalysts were discovered, and via
a virtual breakdown of the structure of already identified catalysts, two new types of
catalysts were discovered: The 2-aminophenols and the 2-(aminomethyl)benzimidazoles.
With aldehyde substrates none of the newly discovered catalysts were as effective as a
previously discovered benzenephosphonic acid, but with aromatic ketones, an otherwise
challenging class of substrates, the 2-(aminomethyl)benzimidazoles showed promising
efficacies, reaching an hitherto unseen 5-fold rate enhancement for hydrazone formation
on model acetophenone at pH 7.4.
| Originalsprog | Engelsk |
|---|
| Forlag | Department of Chemistry, Faculty of Science, University of Copenhagen |
|---|---|
| Antal sider | 315 |
| Status | Udgivet - 2015 |