Distal meta-alkenylation of formal amines enabled by catalytic use of hydrogen-bonding anionic ligands

Abstract

•Distal C–H activation mediated by non-covalent interactions •Catalytic amount of anionic ligand induces H-bonding interaction with amides •H bonding enables Pd-catalyzed distal meta-activation •Amines with variable linker lengths are susceptible to this protocol Regioselective and site-selective functionalization of distal C–H bonds has remained a significant challenge over the last decades. Although covalently attached directing groups have been designed to help solve this puzzle, their profound impact on step economy significantly hinders the protocol’s applicability. Weak non-covalent interactions have been developed to overcome this, but they have mainly been explored with Ir catalysis. Herein, we aim to execute a Pd-catalyzed meta-selective C–H functionalization of simple amines by harnessing weak non-covalent interactions between an anionic ligand and neutral substrate. A catalytic amount of organic salt acts as a suitable ligand for efficient meta-selective C–H olefination. Experimental and computational studies suggest that site selectivity is governed by the key H-bonding interaction between an anionic donating ligand and neutral motifs. The protocol can be further extended to amines with variable linker lengths, outlining the versatility and applicability of our methodology, while utilizing only a catalytic amount of directing ligand for the transformation. Regioselective and site-selective functionalization of distal C–H bonds has remained a significant challenge over the last decades. Although covalently attached directing groups have been designed to help solve this puzzle, their profound impact on step economy significantly hinders the protocol’s applicability. Weak non-covalent interactions have been developed to overcome this, but they have mainly been explored with Ir catalysis. Herein, we aim to execute a Pd-catalyzed meta-selective C–H functionalization of simple amines by harnessing weak non-covalent interactions between an anionic ligand and neutral substrate. A catalytic amount of organic salt acts as a suitable ligand for efficient meta-selective C–H olefination. Experimental and computational studies suggest that site selectivity is governed by the key H-bonding interaction between an anionic donating ligand and neutral motifs. The protocol can be further extended to amines with variable linker lengths, outlining the versatility and applicability of our methodology, while utilizing only a catalytic amount of directing ligand for the transformation. Charge-controlled Pd catalysis enables the meta-C–H activation and olefination of arenesMondal et al.ChemJanuary 24, 2023In Briefvan Gemmeren and co-workers report a method that enables the meta-selective olefination of arenes on the basis of a charge-controlled Pd-catalyzed C–H activation. The method relies on charge-charge and charge-dipole interactions to achieve unconventional regioselectivities. Mechanistic investigations support this novel means of controlling regioselectivity in Pd-catalyzed C–H activation. A broad scope of functionalized benzyl ammonium products can be accessed, and these are shown to be valuable linchpins for further functionalization toward densely functionalized arenes with challenging substitution patterns. Full-Text PDF Open Access