Organocatalytic C–H Bond Arylation of Aldehydes to Bis-heteroaryl Ketones

Abstract

An organocatalytic aldehyde C-H bond arylation process for the synthesis of complex heteroaryl ketones has been developed. By exploiting the inherent electrophilicity of diaryliodonium salts, we have found that a commercial N-heterocyclic carbene catalyst promotes the union of heteroaryl aldehydes and these heteroaromatic electrophile equivalents in good yields. This straightforward catalytic protocol offers access to ketones bearing a diverse array of arene and heteroarene substituents that can subsequently be converted into molecules displaying structural motifs commonly found in medicinal agents.

Catalytic kinetic resolution of a dynamic racemate: highly stereoselective β-lactone formation by N-heterocyclic carbene catalysis

“…50–61 These unique Lewis bases have been used to generate acyl anion, 62–76 homoenolate, 77–94 and enolate equivalents, 41,95–105 as well as promote hydroacylation 106–111 and an exciting variety of non– Umpolung processes. 112–115 These carbene-catalyzed processes have been used to access numerous challenging compound classes with high levels of diastereo- and enantioselectivities.…”

One‐Pot Synthesis and Applications of N‐Heteroaryl Iodonium Salts

“…Aryl(uracyl)iodonium salts[15] have recently been applied in the preparation of heteroaryl ketones using an N-heterocyclic carbene (NHC) catalyst [16]. While chemoselective, the cost of N , N -dimethyluracil makes this dummy group less attractive in standard reactions [17].…”

C–H Bond Activation for Arylations

“…With Organocatalysts Gaunt's group [75] in 2013 reported an organocatalytic C-H bond arylation of aldehydes with diaryliodonium salts using commercial NHC (N-heterocyclic carbene) catalysts ( Figure 4.39). This methodology affords a diverse range of aromatic ketones, of particular interest in medicinal chemistry.…”