Modifying Positional Selectivity in C-H Functionalization Reactions with Nitrogen-Centered Radicals: Generalizable
Melanie A Short1, J Miles Blackburn1, Jennifer L Roizen1
1Department of Chemistry, Duke University, Box 90346, Durham, North Carolina, 27708-0354, USA.
Summary
Nitrogen radicals typically functionalize molecules at specific sites via 1,5-hydrogen-atom transfer (1,5-HAT). New strategies enable these radicals to undergo 1,6-HAT, enabling rare gamma-selective functionalization reactions.
Area of Science:
- Organic Chemistry
- Radical Chemistry
Background:
- Nitrogen-centered radicals are key intermediates in C(sp3)-H functionalization.
- Their reactivity is typically governed by 1,5-hydrogen-atom transfer (1,5-HAT) pathways, directing functionalization to specific positions.
- Generalizable methods to alter this site-selectivity are needed to expand their synthetic utility.
Purpose of the Study:
- To review recent advancements in nitrogen-centered radical chemistry.
- To highlight strategies that enable preferential 1,6-hydrogen-atom transfer (1,6-HAT) pathways.
- To showcase the use of specific templates for achieving gamma-selective functionalization.
Main Methods:
- Review of literature focusing on nitrogen-centered radical reactions.
- Analysis of transformations employing alcohol- and amine-anchored sulfamate esters and sulfamides.
- Examination of strategies that deviate from typical 1,5-HAT selectivity.
Main Results:
- Demonstration of nitrogen-centered radicals engaging in 1,6-HAT pathways.
- Successful application of sulfamate esters and sulfamides as directing templates.
- Achieved rare gamma-selective functionalization reactions, expanding synthetic possibilities.
Conclusions:
- Nitrogen-centered radicals can be directed to undergo 1,6-HAT, challenging the conventional 1,5-HAT selectivity.
- Template-directed strategies offer a generalizable approach to control radical reaction site-selectivity.
- These findings open new avenues for installing diverse functional groups at specific positions within molecules.
Keywords:
hydrogen-atom transfernitrogen-centered radicalsradicalsremote C–H functionalizationsulfamate estersulfamideMore Related Videos
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