Mechanistic Studies of Intermolecular Catalytic Asymmetric Alkene Bromoesterification Reactions

Created: 2024-07-23 13:26

Last modified: 2024-08-01 14:15

License: Creative Commons: Attribution 4.0

Funding: (none given)

Description

Since 1861, the bromination of alkenes has become one of the most recognisable organic reactions in history. It was instrumental in the beginnings of stereochemistry, and remains a stereocontrolled means of carbon−heteroatom bond formation today. The 21st century has seen the development of catalytic, asymmetric methods, but because of an absence of mechanistic scrutiny, progress has been slow, and there remains much potential for improvement. This thesis describes kinetic investigations into intermolecular, catalytic asymmetric alkene bromoesterification reactions. In Chapter II, the (DHQD)2PHAL catalysed bromoesterification of dialin was evaluated. It was found that the primary amide formed from the stoichiometric bromenium ion source inhibited the reaction. This is the first time that by-product inhibition has been observed in an alkene halofunctionalisation reaction. Moreover, inhibition was surmounted using two methods: either, employing an excess of carboxylic acid nucleophile, or using a bromenium ion source with a non-inhibitory by-product. In Chapter IV, a Brønsted acidic (Rax)-BINOL-derived phosphoric acid catalyst system was evaluated. It was found through kinetic profiling that the catalyst inactivates during the reaction to a bromoalkylated phosphate. 1H and 31P{1H} NMR spectroscopic studies of this elusive side product revealed it as a complex, rotameric mixture of diastereomers. X-ray diffraction studies of a single diastereomer provided an unambiguous, absolute structural confirmation. This is the first synthetic example of a bromophosphatation reaction, where a bromiranium ion reacts with a phosphate nucleophile. In Chapter III, an unusual observation was made during synthesis of the BINOL-derived phosphoric acid catalyst. There was, during the diol phosphorylation step, precipitation of an intermediate phosphorochloridate as a racemate. This was found to be attributable to partial racemisation during the prior deprotection step, alongside an unusual difference in solubility between the racemic, and enantiopure, phosphorochloridates. The implications of this on the syntheses of other phosphoric acids are discussed.

Members

DOI	Description
10.14469/hpc/14447	Chapter 5
10.14469/hpc/14446	Chapter 4
10.14469/hpc/14445	Chapter 3
10.14469/hpc/14444	Chapter 2
10.14469/hpc/14489	VTNA Spreadsheets

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