Organic Chemistry Special Seminar

Nitrogen-centered radical applications remain underexplored due to the lack of convenient methods for their generation. We have improved access to nitrogen-centered radicals based on oxidation of sulfamate esters and sulfamides to provide access to nitrogen-centered radicals that can guide C-H functionalization reactions.

Our directed technology has been inspired by one of the most reliable and powerful known reactions to guide C–H functionalization reactions: the Hofmann-Loffler-Freytag (HLF) reaction, which uses amines or amides as directing groups. Like many of the most robust radical-mediated technologies to direct the activation of tertiary and secondary centers, the HLF reaction is guided through 1,5-hydrogen-atom transfer (HAT) processes, which proceeds through a kinetically-favorable six-membered ring transition state. By contrast, few reports describe 1,6-HAT with a cleavable linker, such as a sulfamate ester, and there are no general strategies to enable masked alcohols to direct functionalization of aliphatic gamma-C-H centers. This talk will outline this novel strategy to harness alcohols to replace C-H bonds at gamma-C-H centers, which are not generally accessible to directed functionalization. This talk will highlight the first generalizable synthetic strategy to functionalize gamma-C-H bonds based on masked alcohols.