Radical NHC Catalysis

Abstract

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.

Visible light-mediated NHC and photoredox co-catalyzed 1,2-sulfonylacylation of allenesviaacyl and allyl radical cross-coupling

“…N-heterocyclic carbenes (NHCs) 9 could stabilize acyl radicals 10 and open a new avenue for single-electron-transfer (SET)-mediated radical acylation chemistry. 11 Since the pioneering works of Studer 12 and Ohmiya, 13 a elegant progress has been achieved in NHC-involved cross-couplings of ketyl radicals with O-centered radicals, 12 alkyl radicals, 13–18 and highly active allene radicals 19 by employing aldehydes or derivatives of carboxylic acid (Scheme 1b). The attachment of NHCs could modulate the stability of transient acyl radicals to persistent ones, which may offer the opportunity for radical acylation of allyl radicals.…”

Carbene-catalyzed kinetic resolution of bispirooxindoles: selective lactam amidation and access to challenging chiral scaffolds

“…1a). 5–17 However, current KR studies are primarily addressing racemic substrates having each just one chiral center, owing to the operational constraints of constructing substrates with multiple chiral centers and enriching optically pure multichiral compounds, 18 and there have been very few reports on KR utilizing inactive groups distant from the chiral atoms. 19,20…”

Diastereoselective Radical Aminoacylation of Olefins through N-Heterocyclic Carbene Catalysis

“…N-Heterocyclic carbenes (NHCs) are well-known as nucleophilic organocatalysts for the umpolung of aldehydes via Breslow intermediates . Moving from traditional ionic chemistry logic to a radical approach, recent electrochemical and methodological studies , revealed that the reduction potential of deprotonated Breslow intermediate A was sufficiently negative to perform single electron transfer (SET) with various single electron acceptors, such as TEMPO, nitro compounds, – and polyhalides , (Figure C). Pioneering studies from Ohmiya’s group reported NHC-catalyzed radical decarboxylative coupling of aldehydes with redox-active esters, allowing for the rapid assembly of functionalized ketones .…”