Effect of Fluorinated Alcohols on the Reactivity and Selectivity of the Oxoiron(V) Intermediates in C(sp ³ )–H Oxidations

In recent years, β-fluorinated alcohols have been increasingly utilized as reaction solvents in a variety of direct hydroxylations of aliphatic C–H bonds, catalyzed by bioinspired Fe-, Mn-, Ni-, and Pd-based catalysts. However, direct experimental data related to the effect of fluorinated alcohols on the reactivity of the key high-valent metal-oxo intermediates have been lacking. Herein, such data are presented, witnessing the promoting effect of 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) on the intrinsic reactivity of the low-spin intermediate [(PDP Me2OMe )Fe V =O(OCOCH 3 )](OTf) 2 ( 1a ) toward methylcyclopentane (mcp) and cis- 1,2-dimethylcyclohexane (dmch) (PDP X -substituted N, N ′-bis(pyridin-2-ylmethyl)-( S, S )-2,2′-bipyrrolidine). This effect is pronounced in the presence of HFIP. In contrast, for the high-spin intermediate [(PDP NMe2 )Fe V =O(OCOCH 3 )](OTf) 2 ( 2a ), such a promoting effect of fluorinated alcohols was not revealed. The conversion of mcp and dmch in the corresponding systems 1 /H 2 O 2 /AA and 2 /H 2 O 2 /AA in HFIP or TFE increases if compared with CH 3 CN, with the selectivity for tertiary (3°) C–H sites simultaneously decreasing at the expense of more significant engagement of secondary C–H sites into the oxidation. A detailed DFT-based computational study suggests that the reactivity enhancement upon the addition of fluorinated alcohols is due to hydrogen bonding between the fluorinated alcohol and the perferryl active species, which reduces the potential barrier for H abstraction.