Rhodium catalysed hydroacylation reactions in the synthesis of heterocycles

Thesis

Rhodium-catalysed hydroacylation provides a highly atom economic synthesis of ketone products from the combination of aldehydes and multiple bond systems by C-H bond activation. This work evaluates the combination of intermolecular hydroacylation for the synthesis of classical heterocycle precursors and their dehydrative cyclisation to give rise to a range of substituted heterocyclic compounds.

Chapter 1 outlines recent developments in the chemistry of hydroacylation. Particular attention is paid to the various chelation strategies employed in intermolecular hydroacylation. Chapter 2 discusses some relevant and recent developments in the field of pyridine and pyrrole synthesis.

Having established that β-sulphur chelation controlled hydroacylation can be used to synthesise pyridines in Chapter 3; attention was turned to hydroacylation of propargyl amines in Chapter 4. The methodology was expanded to provide a synthesis of γ-amino enones. The hydroacylation reaction and cyclisation is combined in a procedure that utilises thermal Boc-deprotection and cyclisation to give a range of highly-substituted pyrroles.

The regioselectivity of the hydroacylation of propargyl amines is investigated in Chapter 5 by application of statistical Design of Experiments methodology. Optimised conditions were identified with minor improvements in the selectivity of the reaction.

Authors: Ylioja, P

• Publication date: 2011
• DOI: 10.5287/ora-vebaveq8d
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: Oxford University, UK
• Language: English
• Keywords: rhodium; propargylamines; propargyl; enones; hydroacylation; pyrroles
• Subjects: Organic synthesis; Synthetic organic chemistry; Catalysis; Organic chemistry; Heterocyclic chemistry; Organometallic Chemistry