Radical NHC Catalysis

Radical/radical cross-coupling reactions represent an efficient and straightforward approach for the construction of chemical bonds and accordingly have drawn increasing attention over the past decades. In order to achieve synthetically useful transformations, a persistent radical should be coupled with a transient radical in accordance with the persistent radical effect (PRE). However, known transient radicals outnumber by far the known types of free persistent radicals, which limits the widespread application of the PRE, until today. Thus, the development of efficient cross-coupling reactions between transient radicals has been in focus, and meanwhile transition-metal catalysis has been successfully implemented to artificially prolong radical lifetimes, allowing their utilization in formal radical/radical cross-couplings. Complementary research in the field recently uncovered that organocatalytically generated NHC-derived ketyl radicals are a type of catalytically generated free persistent radicals. NHC-catalyzed radical transformations of aldehydes and carboxylic acid derivatives have enabled the disclosure of an ever-increasing number of interesting reactions, which are different from traditional NHC-catalyzed ionic processes, offering otherwise inaccessible activation modes. These discoveries have opened a door to NHC organocatalysis for the manipulation of radical reactions. Due to its obvious potential in synthetic organic chemistry, it is timely to provide a perspective on this emerging field.

Automated summary

Radical/radical cross-coupling reactions are efficient and direct methods for constructing chemical bonds. The widespread application of persistent radical effect (PRE) has been limited by the fact that the known types of transient radicals far outnumber the known types of persistent radicals. Recent research has focused on developing efficient cross-coupling reactions between transient radicals, and transition-metal catalysis has been successfully used to prolong radical lifetimes, enabling their utilization in formal radical/radical cross-couplings.