Organozirconium approaches to small molecule synthesis

Abstract

A review of zirconocene mediated intramolecular cocyclisations and the
elaboration of the resultant zirconacycles is presented as a background to the
work presented in this thesis. The first area of novel work is the attempted
intramolecular trapping of zirconocene ?2-alkene complexes, generated by an
unprecedented endocyclic cyclometallation, with a pendant alkyne. A series of
inter- and intramolecular transformations other than the desired transformation
were observed.

The second area of work presented is the synthesis and biological testing
of two ligands for receptors from the NR4A subfamily of orphan nuclear
receptors. Our interest in this area stemmed from previous work in our group on
the zirconocene mediated synthesis of ligands for receptors in the NR5 subfamily.

The third area of research presented is the zirconocene mediated
cocyclisation of a series of novel ynamides and elaboration of the resulting
zirconacyclopentadienes. Also presented in this chapter is the use of the
exocyclic dienes formed through protonolysis of the zirconacyclopentadienes in a
series of Diels-Alder reactions in excellent regio- and stereoselectivity.

The penultimate area of research is the first total synthesis of (+)-mucosin
utilising a zirconocene mediated cocyclisation of a diene followed by the insertion
of an ?-silyl alkyl carbenoid to gain the major diastereoisomer with the correct
stereochemistry of the four contiguous stereocentres. The route taken to
(+)-mucosin can be easily adapted in order for the synthesis of the natural product
(?)-mucosin to be realised.

Finally the well established chemistries of carbenoid insertion and isonitrile
insertion into zirconacyclopentanes are combined in order to furnish a series of
novel cyclohexanones.

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Identifiers

ORCID for Richard J. Whitby: orcid.org/0000-0002-9891-5502

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