The facile generation of aminyl and aminium radicals from N-hydroxypyridine-2-thione carbamates

Abstract

The title compounds were easily prepared from several alkyl-alkenyl amines. The carbamates were variations on the general structure of 1-[butyl(4-pentenyl)carbamoyl)oxy]-2(1H)-pyridinethione 29. These compounds react in a free radical chain process in the presence of hydrogen atom donors to give various butyl (4-pentenyl) aminyl radicals. Once formed, the radicals were either trapped to give the parent amine or cyclized to give substituted 1-butylpyrrolidines. The rate constants for the cyclizations of butyl(4-pentenyl) and butyl (5-methyl-4-hexenyl) aminyl radicals were determined. Therefore, these arrangements can be used as qualitative and quantitative probes for the formation of aminyl radicals. In addition, treatment of selenide 41 with Bu₃SnH, gave amine 30. This was the first conclusive evidence that aminyl radical cyclizations are reversible. The addition of Bronsted acids, such as acetic and trifluoro-acetic acid to the reaction mixtures led to increased yields of cyclization products, presumably through the formation of aminium radicals. The use of t-BuSH and TFA allowed for the preparation of 1-butyl-2,5-dimethylpyrrolidine and 1-butyl-2-methyloctahydroindole. When the hydrogen atom donor was removed from the reaction mixture, the carbon radical was trapped by the precursor carbamate. This gave pyrrolidines with functionality suitable for other transformations. The cyclizations in the presence of TFA proved to be moderately stereoselective at -78°C x (4:1 trans:cis). Finally, it was demonstrated that aminium radicals are formed under extremely mild conditions (saturated NH₄CL/MeOH) which subsequently cyclize to give pyrrolidines.