PALLADIUM-CATALYZED [1,3] O→C REARRANGEMENT OF PYRANS TOWARDS FUNCTIONALIZED CYCLOHEXANONES

Barker, Thomas A (2012) PALLADIUM-CATALYZED [1,3] O→C REARRANGEMENT OF PYRANS TOWARDS FUNCTIONALIZED CYCLOHEXANONES. PhD thesis, University of Sheffield.

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Abstract

Functionalised cyclohexanones are prepared from cyclic enol ethers via a Pd-catalysed [1,3] O→C rearrangement reaction. A variety of -arylketones are generated with excellent diastereocontrol and yield when basic phosphine ligands are used. In contrast, a Lewis acid is required to promote rearrangement of alkyl-substituted enol ether systems. These reactions proceed in excellent yield, but exhibit poor diastereocontrol. Attempts towards an asymmetric [1,3] O→C rearrangement reaction through the useof chiral phosphine ligands are also described. After screening a wide range of ligands only tBu-Phox has provided reasonable levels of enantiocontrol (84% yield, 49% ee). The preparation of enantiomerically enriched enol ethers is also described. Unfortunately, when applied to the rearrangement chemistry, two enantiopure enol ethers have each provided racemic cyclic ketones. Aspects of the reaction mechanism are described, which resulted in the development of a kinetic resolution protocol. This led to the preparation of enantiopure enol ethers (>95% ee) and cyclic ketones. Finally, initial chemistry into the development of a new rearrangement paradigm utilizing a cyclobutadieneiron tricarbonyl mofit is discussed. Although late stage intermediates are prepared, the desired enol ethers could not be prepared, potentially due to the lability of the substrates.