Fig. 2.

N-heterocycle scope of (A) Mn(CF₃-PDP) 1 methylene C–H oxidation and (B) Mn(PDP) 2 tertiary C–H oxidations with and without HBF4 nitrogen protonation. (C) Aliphatic C–H oxidation of drugs and drug derivatives with and without HBF₄ nitrogen protonation. Isolated yields are an average of two to three experiments, major isolated site of oxidation is highlighted in yellow, and recovered starting material (RSM) is given in parentheses. Experimental pK_aH reported in water (see SI Appendix for references). Blue boxes with numbers indicate frequency of N-heterocycles in FDA approved drugs according to ref. 1. ClAcOH, chloroacetic acid. NPhth, phthalimide. General methylene oxidation with HBF₄ was done using Method A at -36 °C unless otherwise noted. General methylene oxidation without HBF₄ was done using Method B unless otherwise noted. ^aNitrogen was HBF₄•OEt₂ protected as described in Materials and Methods. ^bMethod A at 0 °C. ^cModified Method D [2.5 mol% Mn(CF₃-PDP) 1, 7.5 equiv. ClAcOH, 5 equiv. H₂O₂] at -36 °C. ^dWith 20% di-oxidation. ^eModified Method D [2.5 mol% Mn(CF₃-PDP) 1, 7.5 equiv. ClAcOH, 5 equiv. H₂O₂] at 0 °C. ^fMethod C [2 x 5 mol% Mn(CF₃-PDP) 1] at 0 °C. ^gRatios are statistically corrected. ^hMethod C [3 x 5 mol% Mn(CF₃-PDP) 1] at 0 °C. ⁱMethod D. ^jMethod A at -36 °C. ^kMethod B with Mn(PDP) 2. ^lMethod A with Mn(PDP) 2. ^m3 x 5 mol% Fe(PDP), iterative addition protocol (ref. 21). ⁿMethod C [2 x 5 mol% Mn(PDP) 2] at -36 °C. ^oMethod B. ^pMethod C [3 x 5 mol% Mn(CF₃-PDP) 1] at -36 °C.