Regioselective Oxidation of Nonactivated Alkyl C–H Groups Using Highly Structured Non-Heme Iron Catalysts

Selective oxidation of alkyl C–H groups constitutes
one of the highest challenges in organic synthesis. In this work,
we show that mononuclear iron coordination complexes Λ-[Fe­(CF3SO3)2((S,S,R)-MCPP)] (Λ-1P), Δ-[Fe­(CF3SO3)2((R,R,R)-MCPP)] (Δ-1P), Λ-[Fe­(CF3SO3)2((S,S,R)-BPBPP)] (Λ-2P), and Δ-[Fe­(CF3SO3)2((R,R,R)-BPBPP)] (Δ-2P) catalyze the
fast, efficient, and selective oxidation of nonactivated alkyl C–H
groups employing H2O2 as terminal oxidant. These
complexes are based on tetradentate N-based ligands and contain iron
centers embedded in highly structured coordination sites defined by
two bulky 4,5-pinenopyridine donor ligands, a chiral diamine ligand
backbone, and chirality at the metal (Λ or Δ). X-ray diffraction
analysis shows that in Λ-1P and Λ-2P the pinene rings create cavity-like structures that isolate the iron
site. The efficiency and regioselectivity in catalytic C–H
oxidation reactions of these structurally rich complexes has been
compared with those of Λ-[Fe­(CF3SO3)2((S,S)-MCP)] (Λ-1), Λ-[Fe­(CF3SO3)2((S,S)-BPBP)] (Λ-2), Δ-[Fe­(CF3SO3)2((R,R)-BPBP)] (Δ-2), Λ-[Fe­(CH3CN)2((S,S)-BPBP)]­(SbF6)2 (Λ-2SbF6), and Δ-[Fe­(CH3CN)2((R,R)-BPBP)]­(SbF6)2 (Δ-2SbF6), which lack the steric
bulk introduced by the pinene rings. Cavity-containing complexes Λ-1P and Λ-2P exhibit enhanced activity
in comparison with Δ-1P, Δ-2P, Λ-1, Λ-2, and Λ-2SbF6. The regioselectivity exhibited by catalysts Λ-1P, Λ-2P, Δ-1P, and Δ-2P in the C–H oxidation of simple organic molecules can be predicted on the basis of the innate properties of
the distinct C–H groups of the substrate. However, in specific
complex organic molecules where oxidation of multiple C–H sites
is competitive, the highly elaborate structure of the catalysts allows modulation of C–H regioselectivity between the oxidation of
tertiary and secondary C–H groups and also among multiple methylene
sites, providing oxidation products in synthetically valuable yields.
These selectivities complement those accomplished with structurally
simpler oxidants, including non-heme iron catalysts Λ-2 and Λ-2SbF6.