Wed, Apr. 24, 2019, 4:30pm
Edward C Taylor Auditorium, Frick B02
Host: Todd Hyster
Alcohol and Amine Derivatives Guide Position-Selective C–H Functionalization Reactions
Free radical reactions represent an important and versatile class of chemical transformations. Nitrogen-centered radical applications remain underexplored due to the lack of convenient methods for their generation. Recent advances have improved access to nitrogen-centered radicals through photoredox-mediated oxidation of two such directing groups: amides and sulfonamides. Guided by this approach, we hypothesized that alcohols, masked as sulfamate esters, and amines, masked as sulfamides, could engage in photoredox-mediated oxidation to furnish nitrogen-centered radicals that could guide C–H functionalization reactions.
Moreover, our directed technology has been inspired by one of the most reliable and powerful known reactions to guide C–H functionalization reactions: the Hofmann–Löffler–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 traceless linker, such as an alcohol masked as a sulfamate ester or an amine masked as a sulfamide, and there are no general strategies to enable masked alcohols or amines to direct functionalization of aliphatic
y-C(sp3)–H centers. This talk will outline this novel strategy to harness alcohols and amines to replace C–H bonds at y-C(sp3)–H centers, which are not generally accessible to directed functionalization. We will demonstrate that C–H abstraction can be robustly coupled with varied functionalization reactions. This talk will highlight the first generalizable synthetic strategy to functionalize y-C(sp3)–H bonds based on masked alcohols or amines, to push the boundaries of organic chemistry at a fundamental level and benefits drug discovery.