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

Abstract

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 Lambda-[Fe(CF3SO3)(2)((S,S,R)-MCPP)] (Lambda-1P), Delta-[Fe(CF3SO3)(2)((R,R,R)-MCPP)] (Delta-1P), Lambda-[Fe(CF3SO3)(2)((S,S,R)-BPBPP)] (Lambda-2P), and Delta-[Fe(CF3SO3)(2)((R,R,R)-BPBPP)] (Delta-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 (Lambda or Delta). X-ray diffraction analysis shows that in Lambda-1P and Lambda-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 Lambda-[Fe(CF3SO3)(2)((S,S)-MCP)] (Lambda-1), Lambda-[Fe(CF3SO3)(2)((S,S)-BPBP)] (Lambda-2), Delta-[Fe(CF3SO3)(2)((R,R)-BPBP)] (Delta-2), Lambda-[Fe(CH3CN)(2)((S,S)-BPBP)] (SbF6)(2) (Lambda-2SbF(6)), and Delta-[Fe(CH3CN)(2)((R,R)-BPBP)](SbF6)(2) (Delta-2SbF(6)), which lack the steric bulk introduced by the pinene rings. Cavity-containing complexes Lambda-1P and Lambda-2P exhibit enhanced activity in comparison with Delta-1P, Delta-2P, Lambda-1, Lambda-2, and Lambda-2SbF(6). The regioselectivity exhibited by catalysts Lambda-1P, Lambda-2P, Delta-1P, and Delta-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 Lambda-2 and Lambda-2SbF(6)