Abstract
The pyridine-enabled cross dehydrogenative coupling of sp2 C-H bonds of polyfluoroarenes and unactivated sp3 C-H bonds of amides was achieved via a copper-promoted process with good functional group compatibility. This reaction showed great site-selectivity by favoring the sp2 C-H bonds ortho to two fluoro atoms of arenes and the sp3 C-H bonds of α-methyl groups over those of the α-methylene, β- or γ-methyl groups of the aliphatic amides. Mechanistic studies revealed that sp3 C-H bond cleavage is an irreversible but not the rate-determining step, and the sp2 C-H functionalization of arenes appears precedent to the sp3 C-H functionalization of amides in this process.
Highlights
View Article OnlinePyridine-enabled copper-promoted cross dehydrogenative coupling of C(sp2)–H and unactivated C(sp3)–H bonds†
Transition metal-promoted direct functionalization of unactivated C–H bonds is a highly valuable approach for the selective construction of C–C bonds, and considerable efforts have been devoted into this research area over the past couple of decades.[1]
We have examined and report here the copper-promoted cross dehydrogenative coupling of aliphatic amides[9] and poly uoroarenes[10] (Scheme 1b), which provides an efficient access to alkyl-substituted per uoroarenes, an important structural motif in pharmaceuticals and agrochemicals.[11]
Summary
Pyridine-enabled copper-promoted cross dehydrogenative coupling of C(sp2)–H and unactivated C(sp3)–H bonds†. The pyridine-enabled cross dehydrogenative coupling of sp[2] C–H bonds of polyfluoroarenes and unactivated sp[3] C–H bonds of amides was achieved via a copper-promoted process with good functional group compatibility. This reaction showed great site-selectivity by favoring the sp[2] C–H bonds ortho to two fluoro atoms of arenes and the sp[3] C–H bonds of a-methyl groups over those of the amethylene, b- or g-methyl groups of the aliphatic amides. Mechanistic studies revealed that sp[3] C–H bond cleavage is an irreversible but not the rate-determining step, and the sp[2] C–H functionalization of arenes appears precedent to the sp[3] C–H functionalization of amides in this process
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