Multi-component synthesis using zirconium

Abstract

The research described in this thesis focuses on different areas of organozirconium chemistry.

Firstly, four compounds with a cis-bicyclo[3.3.0]oct-2-ene backbone were synthesised to target orphan nuclear receptors LRH-1 and SF-1. The key reaction to construct the bicyclo[3.3.0]oct-2-ene involved the zirconocene-mediated cyclisation of 1,6-enynes (prepared via multi-step synthetic routes) followed by further elaboration with the insertion of a 1,1-dihalide alkyl carbenoid and a lithium phenyl acetylide.

Secondly, a wide range of benzyl carbenoids were inserted into unsaturated zirconacycles which afforded the corresponding alkene product after a low temperature quench. For the clean synthesis of dienes from the reaction, efficient zirconocene traps were discovered (chloroform and benzyl chloride), the former of which was used for the synthesis of a range of diene compounds. The traps were found to facilitate the decomplexation of zirconocene from zirconocene η2-alkene complexes which are formed after endocyclic cyclometallation of the benzyl-inserted zirconacycle.

Finally, the novel reactivity of benzyl chloride with zirconocene η2-alkene complexes was explored, the scope of the reaction examined and mechanistic investigations undertaken. Ultimately the reaction allowed for the development of a novel one-pot three-component coupling reaction synthesising tri-substituted alkenes with a benzyl substituent. The reaction involved the insertion of alkenyl carbenoids into benzylzirconocene followed by transmetallation to zinc for addition of an aldehyde or for coupling with an aryl halide.

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Identifiers

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

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