Non‐biological catalysts following the governing principles of enzymes are attractive systems to disclose unprecedented reactivities. Most of those existing catalysts feature an adaptable molecular recognition site for substrate binding that are prone to undergo conformational selection pathways. Herein, we present a non‐biological catalyst that is able to bind substrates via the induced fit model according to in‐depth computational calculations. The system, which is constituted by an inflexible substrate‐recognition site derived from a zinc‐porphyrin in the second coordination sphere, features destabilization of ground states as well as stabilization of transition states for the relevant iridium‐catalyzed C−H bond borylation of pyridine. In addition, this catalyst appears to be most suited to tightly bind the transition state rather than the substrate. Besides these features, which are reminiscent of the action modes of enzymes, new elementary catalytic steps (i. e. C−B bond formation and catalyst regeneration) have been disclosed owing to the unique distortions encountered in the different intermediates and transition states.
Selective
iridium-catalyzed C–H bond borylations of unbiased
or directing-group-free substrates typically occur under long reaction
times and mild temperatures in order to avoid unselective processes
including catalyst deactivation. Herein, we describe a supramolecular
approach that enables the C–H bond borylation of challenging
pyiridines and imidazoles in very short reaction times (up to 2 h)
with a negligible incubation period for catalyst activation. The catalyst
is based on a highly rigid zinc–porphyrin substrate-recognition
site in the secondary coordination sphere and a triazolopyridine chelating
fragment attached to the first coordination sphere at iridium. The
borylation occurs at the C–H bond from the substrate located
at four chemical bonds apart from the molecular recognition site with
the selectivity being exclusively imposed by the distance between
the active site and the molecular recognition site regardless of the
nature of the N,N-chelating fragment
coordinating to iridium as further supported by density functional
theory (DFT) calculations. Additional studies (control experiments,
nuclear magnetic resonance, and single-crystal X-ray diffraction)
unraveled key catalyst deactivation pathways in which up to three
different partners (water, methoxide ligands from the iridium precursor,
and the triazolopyridine fragment) compete with the N-heterocycle
substrate for binding to the molecular recognition site of the supramolecular
catalyst. This fundamental understanding made possible the identification
of a supramolecular catalyst featuring a 4-methyl substitution pattern
in the first coordination sphere at iridium that provides a suitable
balance of steric and electronic effects in both primary and secondary
coordination spheres, thereby bypassing the manifold catalyst deactivation
pathways. DFT calculations further indicated the importance of noncovalent
interactions beyond the molecular recognition site on the stabilization
of the different intermediates and transition sates.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.