Modifying Positional Selectivity in C–H Functionalization Reactions with Nitrogen-Centered Radicals: Generalizable Approaches to 1,6-Hydrogen-Atom Transfer Processes

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 Introduction2 Transformations that Rely on Structural Constraints or Weakened C–H Bonds to Favor 1,6-HAT Processes3 Sulfamate Esters Engage Selective 1,6-HAT Processes4 Expansion to 1,6-HAT Processes with Masked Amine Substrates5 Conclusions and Outlook

Iodine-Based Reagents in Oxidative Amination and Oxygenation

“…It is noteworthy that although several methods for the sulfamate ester guided selective functionalization of a C-H bond, which were designed based on the concept of the HLF reaction, were recently been reported under metal-free-conditions. 35,36 The present method is the first example of a C-H amination.…”

Recent Advances in Photoredox‐Mediated Radical Conjugate Addition Reactions: An Expanding Toolkit for the Giese Reaction

“…Cognizant of the emergence of sulfamyl radical‐directed halogen‐ [167, 168] and group‐transfer reactions, [169–171] Roizen and co‐workers, [172] Duan and co‐workers, [173] and Shu et al [174] have demonstrated that sulfamate esters [175] can serve as direct precursors to radicals under photochemical conditions (Scheme 45). The accessed sulfamyl radicals guide Giese reactions based on remarkable 1,6‐HAT processes, which proceed with site‐selectivity that has been historically inaccessible.…”

Photochemically Mediated Nickel-Catalyzed Synthesis of N-(Hetero)aryl Sulfamides

“… , In drug discovery, sulfamides can be valuable analogues of sulfamate, sulfonamide, urea, carbamate, and amide functional groups . In reactions, N , N ′-disubstituted sulfamides are useful as chiral auxiliaries, as organocatalysts, as reagents to promote dehydration, as precursors to sterically encumbered carbon–carbon bonds, and as directing groups for C–H functionalization processes . Despite the potential of this valuable functional group, sulfamides may be underutilized due to limitations in practical methods for their preparation. − …”