Dedicated to Prof. Brian M. Stoltz as an early celebration of his 50th birthday
Abstract
Nitrogen-centered radicals are powerful reaction intermediates owing in part to their
ability to guide position-selective C(sp3 )–H functionalization reactions. Typically, these reactive species dictate the site
of functionalization by preferentially engaging in 1,5-hydrogen-atom transfer (1,5-HAT)
processes. Broadly relevant approaches to alter the site-selectivity of HAT pathways
would be valuable because they could be paired with a variety of tactics to install
diverse functional groups. Yet, until recently, there have been no generalizable strategies
to modify the position-selectivity observed in these HAT processes. This Synpacts article reviews transformations in which nitrogen-centered radicals preferentially
react through 1,6-HAT pathways. Specific attention will be focused on strategies that
employ alcohol- and amine-anchored sulfamate esters and sulfamides as templates to
achieve otherwise rare γ-selective functionalization reactions.
1 Introduction
2 Transformations that Rely on Structural Constraints or Weakened C–H Bonds to Favor
1,6-HAT Processes
3 Sulfamate Esters Engage Selective 1,6-HAT Processes
4 Expansion to 1,6-HAT Processes with Masked Amine Substrates
5 Conclusions and Outlook
Key words hydrogen-atom transfer - remote C–H functionalization - radicals - nitrogen-centered
radicals - sulfamate ester - sulfamide