Copper‐Catalyzed C−H Difluoroalkylation of Coumarins with Fluoroalkyl Bromides

Abstract

An efficient method for the copper-catalyzed selective CÀ H difluoroalkylation of coumarins and with low cost and readily available ethyl bromodifluoroacetate and N-phenyl bromodifluoroacetamide has been reported. This reaction exhibits good functional group tolerance with respect to coumarins and difluoroalkylation reagents, and several redox-sensitive sub-strates have been successfully CÀ H difluoroalkylated in good to high yield. This design could further expand the scope to other heteroarenes, including furan, benzofuran, pyrrole, pyridinone, chromenone, indole, and quinolinone. A mechanism involving copper-catalyzed in-situ generation of fluoroalkyl radical is proposed.

Direct Perfluoroalkylation of C−H Bonds in (Hetero)arenes

“…[106] Finally, the Rao group recently reported another coppercatalyzed system for the difluoroalkylation of coumarins as well as other heterocycles. [107] Using copper iodide as the copper source, 1,10-phenanthroline as the ligand in the presence of dipotassium phosphate in acetonitrile at 110 °C, they were able to successfully functionalize a series of coumarins with ethyl bromodifluoroacetate and N-benzyl-bromodifluoroacetamide as difluoroalkylating agents. Ethoxycarbonyldifluoromethylation of other heterocycles such as furan, benzofuran and N-methylindole was also viable and afforded the corresponding products in good to very good yields (Scheme 41).…”

Base/B2pin2-Mediated Iodofluoroalkylation of Alkynes and Alkenes

“…Obviously, the reaction was quenched in the presence of butylated hydroxytoluene (BHT), and the expected trapped product 3ao was isolated in 20% yield. 17 All that matters is that intermediate 3ao is derived from a secondary carbon radical which was trapped by BHT and detected by 1 H and 13 C NMR spectroscopy, GC-MS and HRMS. Next, upon using radical clock substrate 3ap, the ring-opened product 3ar was isolated in 28% yield, instead of product 3aq.…”

Copper‐Catalyzed Direct Perfluoroalkylation of Heteroarenes

“…If both strategies have been implemented to design efficient processes for the directed [9] and innate [10] perfluoroalkylation of C−H bonds in (hetero)arenes, main limitations still remain with regards to the scope of these processes, the nature of the (hetero)arenes that can be perfluoroalkylated as well as the fluorinated chains that can be introduced and the reagents utilized. With respect to the innate perfluoroalkylations reported to date, if Minisci‐type perfluoroalkylations of electron‐deficient heteroarenes have been extensively investigated, the radical species being generated by oxidative techniques, [10d] transition metal catalysis, [10b,g,i,j,l,n] photoredox catalysis [10c,e,f,h,k,p] or by electrochemistry, [10m,o] a general method enabling the direct perfluoroalkylation of a broad range of electron‐rich heteroarenes is still to be reported and would be of high significance in terms of synthetic chemistry.…”