Methylene C-H bonds are among the most difficult chemical bonds to selectively functionalize because of their abundance in organic structures and inertness to most chemical reagents. Their selective oxidations in biosynthetic pathways underscore the power of such reactions for streamlining the synthesis of molecules with complex oxygenation patterns. We report that an iron catalyst can achieve methylene C-H bond oxidations in diverse natural-product settings with predictable and high chemo-, site-, and even diastereoselectivities. Electronic, steric, and stereoelectronic factors, which individually promote selectivity with this catalyst, are demonstrated to be powerful control elements when operating in combination in complex molecules. This small-molecule catalyst displays site selectivities complementary to those attained through enzymatic catalysis.
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