Copper-Catalyzed Direct Cycloaddition of Imidazoles and Alkenes to Trifluoromethylated Tricyclic Imidazoles

Abstract

We reported herein a copper-catalyzed trifluoromethylarylated cycloaddition of imidazoles and olefins using CF3SO2Cl as the radical source to synthesize highly functionalized tricyclic imidazoles. This procedure exhibits a wide range of substrate scope with 25%–93% isolated yields (36 examples). Mechanistic studies were carried out to support a free trifluoromethyl radical pathway.

Photoinduced Trifluoromethylation with CF3Br as a Trifluoromethyl Source: Synthesis of α-CF3-Substituted Ketones

“…Specifically, radical trifluoromethylation has recently received considerable attention along with the rapid development of mild methods to generate trifluoromethyl radical species. 3 Diverse trifluoromethylation reagents including Togni reagents, 4 Umemoto reagents, 5 Ruppert–Prakash reagents (Me 3 SiCF 3 ), 6 Langlois reagent (CF 3 SO 2 Na), 7 CF 3 SO 2 Cl, 8 CF 3 I, 9 and CF 3 Br 10 have been developed as radical trifluoromethyl sources successively. Among these reagents, CF 3 Br is the only one that combines the advantages of low cost and high atom economy.…”

Cu‐Catalyzed C−H Perfluoroalkylation/Cyclization of Unactivated Alkenes: Synthesis of Perfluoroalkylated Tricyclimidazoles

“…Up to now, there are only few reports on the preparation of functionalized polycyclic benzimidazoles by direct radical cascade cyclization of imidazole and olefins. In 2021, Li's group reported a copper‐catalyzed trifluoromethylated cycloaddition of N ‐alkenoxyl/‐alkenyl imidazoles with alkenes [16a] . In the same year, Li's group investigated a visible light promoted difluoroalkylated cascade reaction of imidazoles and alkenes for the synthesis of functionalized polycyclic imidazoles (Scheme 1b) [16b] .…”

Visible Light Promotes Cascade Trifluoromethylation/Cyclization, Leading to Trifluoromethylated Polycyclic Quinazolinones, Benzimidazoles and Indoles

“…This transformation provides a facile way to construct polycyclic aza -heterocycles, which are usually found in various pharmaceutical compounds ( Scheme 2 ). Moreover, this approach features a low-cost trifluoromethyl source and wide substrate tolerance compared with other methods [ 42 , 43 , 44 , 45 , 46 , 47 , 48 ].…”

“…The following supporting information can be downloaded at: , Experimental details and characterization data for products 3a – 3x , 5a, 5b, 5e – 5h and 7a − 7j [ 42 , 46 , 47 , 49 , 50 , 51 ].…”