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Remote steric control for undirected <i>meta</i> -selective C–H activation of arenes

Ramadoss Boobalan, Yushu Jin, Sobi Asako, Laurean Ilies

2022Science138 citationsDOIOpen Access PDF

Abstract

Regioselective functionalization of arenes remains a challenging problem in organic synthesis. Steric interactions are often used to block sites adjacent to a given substituent, but they do not distinguish the remaining remote sites. We report a strategy based on remote steric control, whereby a roof-like ligand protects the distant para site in addition to the ortho sites, and thereby enables selective activation of meta carbon-hydrogen (C–H) bonds in the absence of ortho or para substituents. We demonstrate this concept for iridium-catalyzed meta -selective borylation of various monosubstituted arenes, including complex drug molecules. This strategy has the potential to expand the toolbox of C–H bond functionalization to previously nondifferentiable reaction sites.

Topics & Concepts

Steric effectsBorylationChemistryRegioselectivitySurface modificationSubstituentLigand (biochemistry)Combinatorial chemistryIridiumHydrogen bondStereochemistryMoleculeCatalysisArylOrganic chemistryReceptorAlkylBiochemistryPhysical chemistryCatalytic C–H Functionalization MethodsCatalytic Cross-Coupling ReactionsOrganoboron and organosilicon chemistry
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