Multiple Reaction Channels of (N-Acyl-N-alkylcarbamoyl)oxyl Radicals from N-Acyl PTOC Carbamates

Article abstract of DOI:10.1021/jo00089a023

N-Acyl-N-alkyl-N'-hydroxypyridine-2-thione carbamates (N-acyl PTOC carbamates) 1 are prepared in good to excellent yield by reactions of N-acylcarbamoyl chlorides with N-hydroxypyridine-2-thione sodium salt.Methods for production of the requisite carbamoyl chlorides by reaction of a secondary amide with trimethylsilyl triflate followed by treatment with phosgene were optimized.Precursors 1 react in radical chain reactions to give the title radicals (2) that can further react by several pathways.Decarboxylations of radicals 2 give amidyl radicals, and this method is excellent for production of acetamidyl radicals and in particular the N-methylacetamidyl radical which is difficult to prepare by other routes. 5-Exo cyclizations of amidyl radicals produced by decarboxylation of 2 give, ultimately, lactams and N-acylpyrrolidines. 1,5-Hydrogen transfer reactions of 2 to give α-amide radicals compete with decarboxylation; cyclization of an α-amide radical thus formed also is reported.The Lewis acid MgBr2 can reduce the 1,5-hydrogen atom transfer reaction apparently by a chelation effect on the precursor that leads to production of radical 2 in a conformation unfavorable for hydrogen atom transfer.By appropriate experimental design, radicals 2 often can be directed toward one desired reaction, and several relative rate constants for reactions of 2 necessary for such design were determined in this work.