Transistion metal mediated synthesis of heterocycles

Abstract

The work presented in this thesis illustrates the synthetic utility of transition metal chemistry through the synthesis of nitrogen and phosphorous heterocycles.  A number of amino-dienes substituted with different aromatic groups were obtained from cinnamic acids and cyclised using a stoichiometric zirconium complex (Negishi’s reagent) giving 3-benzyl pyrrolidines in high yield.  The synthesis has also been developed on the solid-support.  From Merrifield resin, the diene framework was synthesised in a combinatorial fashion, cyclised using Negishi’s reagent and cleaved to give carbamate protected 3-benzyl pyrrolidines in good yield and high purity.

The synthesis of the 3-phenyl pyrrolidine pharmacophore has been developed.  The optimum route to the hindered diene and enyne cyclisation precursors was via the radical bromination of α-methyl styrene and subsequent reaction with the appropriate amine source.  Cyclisation with Negishi’s reagent gave the 3-phenyl pyrrolidines in good yield and diastereoselectivity.  Cyclisation of the diene using a catalytic ruthenium source (Grubb’s catalyst) gave the 3-phenyl pyrrole in moderate yield.

A novel approach to the synthesis of 6-membered phosphorous heterocycles has been explored.  Insertion of lithium chloromethyltrimethylsilane into zirconacyclopentadienes followed by phosphorous metathesis yielded the air- and moisture-sensitive λ³-phosphinines.  These were subsequently protected and characterised as their Diels-Alder adducts.  Insertion of lithium chloromethyltrimethylsilane into a zirconacyclopentane followed by phosphorous metathesis and hydrogen peroxide oxidation yielded a novel phosphinic acid.

More information

Identifiers

Catalogue record

Export record

ASCII CitationAtomBibTeXData Cite XMLDublin CoreDublin CoreEP3 XMLEndNoteHTML CitationHTML CitationHTML ListJSONMETSMODSMPEG-21 DIDLOpenURL ContextObjectOpenURL ContextObject in SpanRDF+N-TriplesRDF+N3RDF+XMLRIOXX2 XMLReferReference ManagerSimple Metadata