Manganese catalysts for C-H activation: an experimental/theoretical study identifies the stereoelectronic factor that controls the switch between hydroxylation and desaturation pathways

Abstract

We describe competitive C-H bond activation chemistry of two types, desaturation and hydroxylation, using synthetic manganese catalysts with several substrates. 9,10-Dihydrophenanthrene (DHP) gives the highest desaturation activity, the final products being phenanthrene (P1) and phenanthrene 9,10-oxide (P3), the latter being thought to arise from epoxidation of some of the phenanthrene. The hydroxylase pathway also occurs as suggested by the presence of the dione product, phenanthrene-9,10-dione (P2), thought to arise from further oxidation of hydroxylation intermediate 9-hydroxy-9,10-dihydrophenanthrene. The experimental work together with the density functional theory (DFT) calculations shows that the postulated Mn oxo active species, [Mn(O)(tpp)(Cl)] (tpp = tetraphenylporphyrin), can promote the oxidation of dihydrophenanthrene by either desaturation or hydroxylation pathways. The calculations show that these two competing reactions have a common initial step, radical H abstraction from one of the DHP sp(3) C-H bonds. The resulting Mn hydroxo intermediate is capable of promoting not only OH rebound (hydroxylation) but also a second H abstraction adjacent to the first (desaturation). Like the active Mn(V)=O species, this Mn(IV)-OH species also has radical character on oxygen and can thus give H abstraction. Both steps have very low and therefore very similar energy barriers, leading to a product mixture. Since the radical character of the catalyst is located on the oxygen p orbital perpendicular to the Mn(IV)-OH plane, the orientation of the organic radical with respect to this plane determines which reaction, desaturation or hydroxylation, will occur. Stereoelectronic factors such as the rotational orientation of the OH group in the enzyme active site are thus likely to constitute the switch between hydroxylase and desaturase behavior.

Figure 1

Potential energy profiles, in kcal mol⁻¹, for the first H abstraction (above) and OH rebound (below) steps. The dashed and solid lines stand for the triplet and quintet pathways, respectively.

Figure 2

Optimized geometries of the Q-2 (left) and Q-3 (right) intermediates.

Figure 3

Rotation of the Mn-OH bond in the presence of the MHP^• radical. For each θ orientation of the OH group all other structural parameters are optimized. Q-2, Q-3 and Q-6 are the first H abstraction product, OH rebound reactant and desaturation product, respectively.

Figure 4

Desaturation pathway. The potential energies, in parentheses, are given in kcal mol⁻¹.

Figure 5

Possible reaction pathways in the catalytic oxidation of DHP.

Figure 6

SOMO orbitals of intermediate Q-2. Spin density is plotted in Figure 7.

Figure 7

Spin density of Q-2. The excess of alpha and beta spin densities are represented in blue and green, respectively. Local spin densities are given in parenthesis.

Scheme 1

Reaction mechanisms postulated for hydroxylation and desaturation.

Scheme 2

Postulated hydroxylation-desaturation switches: 1) formation of a carbocation and 2) orientation of the radical.

Scheme 3

Catalytic oxidation of DHP.

Scheme 4

Desaturation reaction with various substrates: 1) 1,3-cyclohexadiene, 2) 1,4-cyclohexadiene, 3) indoline, 4) N-methyl indoline and 5) [a,e]-dibenzohexamethyleneimine.