Strategic Advances in Sequential C-Arylations of Heteroarenes

Abstract

Sequence-specific C-arylation strategies have important applications in medicinal and material research. These strategies allow C–C bond formations in a regioselective manner to synthesize large molecular libraries for studying structure–activity profiles. The past decade has seen the development of single C–C bond forming reactions using various transition-metal catalysts, cryogenic metalation strategies, and metal-free methods. Sequential arylations of heterocycles allow for the formation of multiaryl derivatives and are a preferred choice over de novo synthetic routes. This perspective sheds light on recent strategic advances to develop various sequential synthetic routes for the multiarylation of heteroarenes. This perspective addresses many challenges in optimizing sequential routes with respect to catalysts, reaction parameters, and various strategies adopted to obtain diversely arylated products.

The Synthesis and Photophysical Properties of Weakly Coupled Diketopyrrolopyrroles

“…Interestingly, the synthesis of DPP 13 from DPP 14 and 8 via Suzuki coupling led to the formation of dye 13 in 1% yield only. Therefore, we resorted to direct arylation, which had recently become a major tool in the synthesis of dyes [ 84 , 85 ] (including DPPs) [ 86 , 87 , 88 ], and heterocyclic PAHs [ 89 ]. Gratifyingly, DPP 12 underwent smooth reaction with compound 7 under the reaction conditions developed by Doucet and co-workers [ 90 ], to afford the desired DPP 13 in 33% yield ( Scheme 3 , Figure S7 ).…”

Visible light-driven C–H arylation of heteroarenes with aryl diazonium salts in water catalyzed by a Z-scheme CuInS2/K-C3N4 heterojunction

“…4 Traditionally, arylated heteroarenes are prepared by the Suzuki reaction using aromatic halides and aryl organoboron reagents as starting materials. 5,6 These methods are very effective and widely used in academia and industry. However, they produce stoichiometric halides or boric acid and/or use noble metal catalysts.…”

Recent Advances in Transition-Metal-Free Late-Stage C-H and N-H Arylation of Heteroarenes Using Diaryliodonium Salts

“…Late-stage diversification strategies that are based on heteroaromatic frameworks that contain multiple reactive sites are challenging and attractive for use in drug discovery [ 1 , 2 , 3 ]. Because small changes can have a huge impact on bioactive profile, this approach offers unique opportunities for the generation of new drug-like analogs of lead structures without extra synthetic steps or resorting to de novo synthesis [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”

“…In addition, mechanism investigations with radical scavengers suggested a mechanism not related to a single electron-transfer process. Based on Olofsson’s study on the metal-free N -arylation of amides, the authors proposed two pathways such as [ 1 , 2 ]-rearrangement as a normal ligand coupling and [ 2 , 3 ]-rearrangement from two possible T-shaped intermediates in equilibrium [ 95 ].…”