Selective C–H halogenation over hydroxylation bynon-heme iron(IV)-oxo

摘要

Non-heme iron based halogenase enzymes promote selective halogenation of the sp3-C–H bond throughiron(IV)-oxo-halide active species. During halogenation, competitive hydroxylation can be preventedcompletely in enzymatic systems. However, synthetic iron(IV)-oxo-halide intermediates often result ina mixture of halogenation and hydroxylation products. In this report, we have developed a new syntheticstrategy by employing non-heme iron based complexes for selective sp3-C–H halogenation byoverriding hydroxylation. A room temperature stable, iron(IV)-oxo complex, [Fe(2PyN2Q)(O)]2+ wasdirected for hydrogen atom abstraction (HAA) from aliphatic substrates and the iron(II)-halide[FeII(2PyN2Q)(X)]+ (X, halogen) was exploited in conjunction to deliver the halogen atom to the ensuingcarbon centered radical. Despite iron(IV)-oxo being an effective promoter of hydroxylation of aliphaticsubstrates, the perfect interplay of HAA and halogen atom transfer in this work leads to the halogenationproduct selectively by diverting the hydroxylation pathway. Experimental studies outline the mechanisticdetails of the iron(IV)-oxo mediated halogenation reactions. A kinetic isotope study between PhCH3 andC6D5CD3 showed a value of 13.5 that supports the initial HAA step as the RDS during halogenation.Successful implementation of this new strategy led to the establishment of a functional mimic of nonheme halogenase enzymes with an excellent selectivity for halogenation over hydroxylation. Detailedtheoretical studies based on density functional methods reveal how the small difference in the liganddesign leads to a large difference in the electronic structure of the [Fe(2PyN2Q)(O)]2+ species. Bothexperimental and computational studies suggest that the halide rebound process of the cage escapedradical with iron(III)-halide is energetically favorable compared to iron(III)-hydroxide and it brings inselective formation of halogenation products over hydroxylation.