Fig. 1.

C(sp³)–H oxidation in the presence of N-heterocyclic functionality. (A) Saturated carbocycles are bioisosteres of aryl fragments and can improve the potency and solubility of N-heterocyclic drugs. (B) In contrast to carbocycles, aryl fragments in N-heterocyclic drugs are rapidly diversified. (C) Multistep syntheses are often required to introduce oxygen functionality onto carbocycles in N-heterocyclic drugs. (D) 5 to 9 step de novo syntheses were required to access aliphatic metabolites of the antipsychotic drug blonanserin. (E) Previously reported methylene C–H oxidation methods demonstrate limited heterocycle scope and structural diversity in comparison to pharmaceutical chemical space. ^aThese catalysts can be found in references.