Radical C(sp3)–H functionalization and cross-coupling reactions

Protocol for chemo- and regioselective C(sp3)–H activation using a heterogeneous copper powder-catalyzed reaction

“…Thus, for the non-directed C(sp 3 )−H bond activation, choosing weaker C(sp 3 )−H bonds (e.g., benzyl, allyl etc.) over unbiased strong alkyl C(sp 3 )−H bonds have been more fruitful ( Feng et al., 2012 ; Golden et al., 2022 ; Liu et al., 2013 , 2020 ; Lu et al., 2017 ; Manna et al., 2020 ; Nandi and Jana, 2022 ; Rout et al., 2014 ; Suh et al., 2020 ; Vasilopoulos et al., 2017 ).…”

Electrophoto-catalytic decoupled radical relay enables highly efficient and enantioselective benzylic C-H functionalization

“…Enzyme catalysis, e.g., P450, represents one of the most efficient strategies for this target, wherein hydrogen atom abstraction from C-H substrate to metal-oxo active center contributes to the sp 3 C-H bonds activation and a radical rebound pathway is typically responsible for the bond formation [10][11][12] . To diversify the functionalities incorporated, numerous catalytic systems based on hydrogen atom transfer (HAT) and radical functionalization have been established for the sp 3 C-H bond functionalization [13][14][15] . Despite the advances, the asymmetric version is still of great challenge due to the extreme difficulty in enantio-control of radical functionalization.…”

Copper-Catalyzed C(sp3)–H Methylation via Radical Relay

“…Building upon the Kharasch–Sosnovsky reaction, − we have developed various C–H functionalization protocols that convert sp 3 C–H bonds to C–N and C–O bonds employing amides, anilides, , and acyl-protected phenols that result in β-diketiminate-stabilized [Cu II ]-FG intermediates in radical relay catalysis (Figure a). Recently, we have shown that copper­(II) complexes with Cu–C bonds also function in this radical relay protocol.…”

“…C­(sp 3 )–H methylation can occur via copper-catalyzed radical relay employing t BuOO t Bu as oxidant similar to other C–H functionalization reactions that form C–N, C–O, and C–C bonds (Figure ). − In contrast to other protocols that involve relatively stable [Cu II ]-FG intermediates, experimental and computational studies suggest that [Cu II ]-Me generates the Me • radical capable of H atom abstraction of sp 3 C–H substrates R-H to form radicals R • . At the same time, Me • radicals generated may compete with R • for capture by [Cu II ]-Me ( 3 ) to form [Cu]­(Me)­(R) intermediates (R = Me, alkyl) that undergo facile reductive elimination which can lead to nonproductive methyl group usage (R = Me).…”