Copper-Catalyzed Late-Stage Benzylic C(sp3)–H Trifluoromethylation

Benzylic C−H acylation by cooperative NHC and photoredox catalysis

“…Benzylic C–H bonds occur in many bioactive compounds and ~25% of the top-selling 200 pharmaceuticals contain this structural motif 5 , 6 . Great efforts have been devoted to functionalize such C–H bonds and benzylic C–C 7 – 11 , C–N 12 – 14 , C–O 15 – 18 , and C–F bond 19 , 20 formation among others 21 , 22 have been realized. However, direct benzylic C–H bond acylation is not well explored.…”

Trifluoromethylation of Alkyl Radicals: Breakthrough and Challenges†

“…To our delight, with CuCN as the catalyst, (bpy)Zn(CF 3 ) 2 as the CF 3 source, NFSI ( N ‐fluorobis(benzenesulfonyl)imide) as the oxidant, along with Zn(OAc) 2 and Zn(OTf) 2 as additives, the reaction of a variety of alkylarenes ( 4 ) proceeded at room temperature, furnishing the benzylic C–H trifluoromethylation products ( 5 ) in satisfactory yields (Scheme 5). [ 5 ] The protocol exhibited wide functional group compatibility, enabling late‐stage modification of a number of drug molecules or complex natural products. The proposed mechanism is also depicted in Scheme 5.…”

Recent Advances in Copper-Catalyzed Radical C–H Bond Activation Using N–F Reagents

“…The regioselective benzylic Csp 3 -H trifluoromethylation was successfully implemented in high efficiency under mild conditions (Scheme 10). 19 Scheme 9 Cross-dehydrogenative coupling of heteroaromatics with simple alkanes and ethers nitrile as the source of nitrogen (Scheme 11). 20 Importantly, this reaction also allowed the C-H bond amination of a variety of hydrocarbons, such as cyclohexane or cyclooctane, without the need for installation of a directing group.…”