New Synthetic Methodologies for Hypervalent Iodine(III)-Mediated Atom-transfer Reactions

Hypervalent iodine(III) compounds are attractive reagents in organic synthesis. The main advantages include their low cost and low toxicity. In particular, they have been used as atom-transfer reagents to introduce nucleophiles such as chloride and fluoride into organic compounds. In chapter two, a one-pot synthetic method was designed to introduce a variety of nucleophiles into the 2-position of 1,3-dicarbonyl compounds using fluoroiodane. Chloride, methoxy and ethoxy groups were introduced into a series of 1,3-dicarbonyl compounds in moderate to high yields (32-90 %). The advantage of this method is that only one hypervalent iodine(III) reagent is required to introduce a range of different nucleophiles into the 2-position of 1,3-dicarbonyl compounds, whereas previous methods required a different hypervalent iodine(III) reagent for each nucleophile. Unfortunately, the introduction of either a trifluoromethyl or a trifluoroethoxy group proved unsuccessful due to the low nucleophilicity and steric bulk of these nucleophiles.

In chapter three a catalytic method was developed to introduce chlorine into 1,3-dicarbonyl compounds using 2-(2-iodophenyl)propan-2-ol under mild reaction conditions and in good yields (73-76 %). This methodology was applied to the tosyloxylation and fluorination of a β-ketoester with limited success. However, when hexafluoroisopropanol (HFIP) was employed as a solvent, the stoichiometric fluorination was possible. A range of 2-fluoro-1,3-dicarbonyl compounds was synthesised in good to excellent yields using fluoroiodane in HFIP, without the need for Et3N.3HF. 1H NMR studies provided evidence for the activation of fluoroiodane by hydrogen bonding, due to the formation of a hydrogen bonding adduct between fluoroiodane and HFIP.

Finally, three chiral iodoarenes were synthesised in chapter four and investigated in the enantioselective chlorination of 1,3-dicarbonyl compounds. Only a small enantiomeric excess was obtained due to issues with background chlorination and hydroxylation. The Gilmour system, employing cesium choride and Selectfluor was explored and preliminary work showed no evidence of a competing background reaction.