Regioselective oxidation of nonactivated alkyl C-H groups using highly structured non-heme iron catalysts

摘要

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(CF_3SO_3) _2((S,S,R)-MCPP)] (Λ-1P), Δ-[Fe(CF_3SO_3)_2((R,R,R)-MCPP)] (Δ-1P), Λ-[Fe(CF_3SO_3)_2((S,S,R)-BPBPP)] (Λ-2P), and Δ-[Fe(CF_3SO_3)_2((R,R,R)-BPBPP)] (Δ-2P) catalyze the fast, efficient, and selective oxidation of nonactivated alkyl C-H groups employing H_2O_2 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(CF_3SO_3)_2((S,S)-MCP)] (Λ-1), Λ-[Fe(CF_3SO_3)_2((S,S)-BPBP)] (Λ-2), Δ-[Fe(CF_3SO_3)_2((R,R)-BPBP)] (Δ-2), Λ-[Fe(CH_3CN)_2((S,S)-BPBP)](SbF_6)_2 (Λ-2SbF_6), and Δ-[Fe(CH_3CN)_2((R,R)-BPBP)](SbF_6)_2 (Δ-2SbF_6), 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-2SbF_6.