Regioselective formation of amidocarboxy-substituted free radicals

Abstract

Factors affecting the production of amidocarboxy-substituted free radicals have been investigated by examining reactions of derivatives of valine and sarcosine. Variations in the regioselectivity of reactions of these compounds are exemplified by the reactions of N-benzoylvaline methyl ester (4a) and N-benzoylsarcosine methyl ester (12a) with sulphuryl chloride and N-bromosuccinimide. Whereas the reaction of (4a) with sulphuryl chloride involves hydrogen-atom transfer from the β-position of (4a) with subsequent chlorine incorporation to give (4g), in direct contrast the reaction with N-bromosuccinimide proceeds via hydrogen-atom abstraction from the α-position of (4a) and yields the dibromide (4d). N-Benzoylsarcosine methyl ester (12a) reacts with N-bromosuccinimide to give the α-bromosarcosine derivative (12b), whereas with sulphuryl chloride the product is the N-chloromethylglycine derivative (12c). These studies indicate that amidocarboxy-substituted radicals such as (3a) and (13) are considerably more stable than the tertiary alkyl radical (1a) and the amidosubstituted radical (14), respectively, but hydrogen-atom transfer reactions may afford the less stable products if electrophilic radicals are involved in the hydrogen-atom abstraction and if there is little development of radical character in the reaction transition state.