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Title: Rhodacyclopentanones as versatile catalytic intermediates for the synthesis of complex scaffolds
Author: McCreanor, Niall G.
ISNI:       0000 0004 6057 9157
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2016
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The catalytic generation of rhodacyclopentanone intermediates from readily accessible substituted cyclopropane precursors and feed stock CO has enabled the synthesis of a range of complex structures. Access to these 'sp3-rich' intermediates relies on a directing group strategy which facilitates their regioselective formation. This directing group controlled approach has enabled the development of multicomponent (3+1+2) cycloadditions between aminocyclopropanes, CO and tethered alkenes to deliver N-heterobicyclic ketones. The employment of a cationic Rh(I)-catalyst facilitated reversible formation of the rhodacyclopentanone intermediate, which was key to obtaining high levels of diastereocontrol for systems with substitution on the alkene tether. Studies on 1,2-disubstituted cyclopropane systems revealed regiodivergent processes, which are controlled by the stereochemistry of the cyclopropane (cis vs. trans). Investigations have also been conducted on systems containing tethered 1,2-disubstituted alkenes to generate products with three new C-C bonds and three new stereo genic centres. Observations during the studies summarised above have led to the identification of a second family of methodologies, where the rhodacyclopentanone is trapped by an appropriate nucleophile. Initially, an intermolecular protocol was established and moderate yields of yamino acid derivatives have been achieved by reaction of Cbz-protected aminocyclopropanes with alcohol or phenol nucleophiles. In concurrent studies, an intramolecular system was developed using urea based substrates; this afforded 7-membered enamides in high yields with excellent selectivity. Interestingly, the oxidation level of the cyclic products was dependent on the aminocyclopropyl substituents. Directed rhodacyclopentanone formation has also been extended to methylaminocyclopropane and cyclopropanamide systems, wherein the directing group forms a 6- or 4-membered chelate to the metal. This has provided a platform for the development of (3+1+2) cycloadditions for these substrate classes. Finally, whilst probing oxidative insertion into methylaminocyclopropanes, a C-C bond activation triggered hydroacylation protocol was discovered. This process results in the atom economic assembly of a-amino-substituted cyclopentanones from methylaminocyclopropane substrates.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available