Why Conventional Design Rules for C–H Activation Fail for Open-Shell Transition-Metal Catalysts

The design of selective and active
C–H activation catalysts
for direct methane-to-methanol conversion is challenging. Bioinspired
complexes that form high-valent metal–oxo intermediates capable
of hydrogen abstraction and rebound hydroxylation are promising candidates.
This promise has made them a target for computational high-throughput
screening, typically simplified through the use of linear free energy
relationships (LFERs). However, their mid-row transition-metal centers
have numerous accessible spin and oxidation states that increase the
combinatorial scale of design efforts. Here, we carry out a computational
design screen of over 2500 mid-row 3d transition-metal complexes with
four metals in numerous spin and oxidation states. We demonstrate
the importance of spin/oxidation state in dictating design principles,
limiting the generalization of strategies derived for widely studied
high-spin Fe­(II) catalysts to other metals or spin/oxidation states.
Combined assessment of the effect of ligand-field tuning on reaction
step energetics and on the identity of the ground state allows us
to propose refined design strategies for spin-allowed methane-to-methanol
catalysis. We observe weak coupling of energetics and design principles
between reaction steps (e.g., oxo formation vs methanol release),
meaning that LFERs do not generalize across our larger catalyst set.
To rationalize relative reactivity in known catalysts, we instead
compute independent reaction energies and propose strategies for further
improvements in catalyst design.