Chiral selection in hydrogen atom transfer reactions

Abstract

This thesis describes an attempt to demonstrate enantioselectivity in free-radical hydrogen transfer reactions and was designed to test a novel extension of the Hammond Postulate. It is proposed that the rates of two related reactions which are thermodynamically identical but kinetically distinct should differ most when the processes are thermoneutral since the transition state is remote from both reactant and product. Bysynthesis and subsequent oxidation of suitable chiral hydroxamic acids a series of persistent chiral acyl nitroxide radicals ArCON(R)O has been made. By reacting such a series of nitroxide radicals with suitable chiral benzylic alcohols ArCHOHR it was hoped that by varying the nature of, the bond strength of the alcohol would come within the compass of the 0-H bond strengths of ArCON(R)OH. It was predicted that such an alcohol should show a maximum in a plot of enantioselectivity vs. 0-H bond strength.The target molecules for this work were optically active N-alkylbenzohydroxamic acids in which the akyl substituent was both chiral and tertiary. Substitution of electron withdrawing and releasing groups, ranging from into the aroyl group of the hydroxamic acid and subsequent oxidation of the latter allowed the synthesis of radicals with varying bond strengths. UV-visible, e.s.r. and CD spectra were determined for these radicals. 0-H bond strengths of the hydroxamic acids were estimated using an e.s.r. technique which determined the equilibrium position for hydrogen atom transfer between the hydroxamic acid and a standard di-t-alkyl nitroxide radical which forms a bond of known strength to hydrogen. These estimated values range from 76 to 79 kcal mol. Enantoselectiviy was searched for in two ways. The first employed UV spectroscopy to determine the second order rate constants for the four possible reaction pairs of chiral nitroxide enantiomers with benzylic alcohol enantiomers. The second method involved reaction of racemic alcohol with chiral radical and subsequent examination of enantiomeric excess by high performance liquid chromatography (HPLC); two approaches to this are described. In the majority of cases studied, however, enantioselectivity was immeasurably small. In the case of 2-methyl-l-phenylpropan-l-ol, a small enantiomeric excess was observed but further work is needed to substantiate these results. Small chiral discriminations were observed in the oxidation reactions of only one alcohol. These results were insufficient to investigate the extension of the Hammond Postulate as originally planned.