Aerobically-initiated C(sp3)-H bond amination through the use of activated azodicarboxylates.

André Shamsabadi,Antoine Maruani,Nehaal Ahmed,Vijay Chudasama

doi:10.1039/d0ob01562h

André Shamsabadi, Antoine Maruani + Show 2 more

Open Access

https://doi.org/10.1039/d0ob01562h

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Abstract

Significant advancements in C-N bond formation via C-H bond functionalisation have made it a staple in the production of nitrogen-containing compounds in both industry and academia. However, transition metal-free synthesis, particularly in the case of C(sp3)-N formation, has remained a significant challenge to the synthetic community. Herein we report a procedure for α-C(sp3)-H amination of ethereal compounds through use of azodicarboxylates as the nitrogen source and freely-available atmospheric oxygen to access ethereal radical intermediates via aerobic C-H activation. The use of fluorinated alcohols as solvent is observed to greatly increase the efficiency of the reaction and we show experimentally and theoretically the key role of H-bonding between fluorinated alcohols and azodicarboxylates. Calculations of the condensed Fukui functions of a H-bonded fluorinated alcohol-azodicarboxylate complex correlates with a significantly increased susceptibility of azodicarboxylates to undergo reaction with radicals, which informs a number of recent reports in the literature.

Highlights

The drive to develop efficient and direct transformations for the construction of complex molecules is always at the forefront of research in synthetic organic chemistry.[1]
Scheme 2 Previously reported peroxide-initiated synthesis of adduct 6aa requiring a vast excess of THF 1a
We anticipate that the interaction we detail between fluorinated alcohols and azodicarboxylates will provide new opportunities for X–N bond formations, in radical-based synthesis

Summary

Introduction

The drive to develop efficient and direct transformations for the construction of complex molecules is always at the forefront of research in synthetic organic chemistry.[1]. We report a procedure for α-C(sp3)– H amination of ethereal compounds through use of azodicarboxylates as the nitrogen source and freely-available atmospheric oxygen to access ethereal radical intermediates via aerobic C–H activation.

Results

Conclusion