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A site‐selective C(3)/C(4)‐alkylation of N‐pyridylisoquinolones is achieved by employing C−C bond activation of cyclopropanols under Ru(II)‐catalyzed/Cu(II)‐mediated conditions. The regioisomeric ratios of the products follow directly from the electronic nature of the cyclopropanols and isoquinolones used, with electron‐withdrawing groups yielding predominantly the C(3)‐alkylated products, whereas the electron‐donating groups primarily generate the C(4)‐alkylated isomers. Density functional theory calculations and detailed mechanistic investigations suggest the simultaneous existence of the singlet and triplet pathways for the C(3)‐ and C(4)‐product formation. Further transformations of the products evolve the utility of the methodology thereby yielding scaffolds of synthetic relevance. [ABSTRACT FROM AUTHOR]

We report a detailed experimental and theoretical analysis of through‐space arene activation with halogens, tetrazoles and achiral esters and amides. Contrary to previously assumed direct activation through σ‐complex stabilization, our results suggest that these reactions proceed by a relay mechanism wherein the lone pair‐containing activators form exothermic π‐complexes with electrophilic nitronium ion before transferring it to the probe ring through low barrier transition states. Noncovalent interactions (NCI) plots and Quantum Theory of Atoms in Molecules (QTAIM) analyses depict favorable interactions between the Lewis base (LB) and the nitronium ion in the precomplexes and the transition states, suggesting directing group participation throughout the mechanism. The regioselectivity of substitution also comports with a relay mechanism. In all, these data pave the way for an alternate platform of electrophilic aromatic substitution (EAS) reactions. [ABSTRACT FROM AUTHOR]

Gold‐catalyzed dehydro‐Diels‐Alder reactions of ynamide derivatives allow efficient access to a variety of N‐containing aromatic heterocycles. A dual gold catalysis mechanism was postulated for transformations involving the formation of C−C bonds by reaction between a terminal alkyne and an enynamide fragment. In this article, complete experimental and computational investigations into the mechanism of such a transformation are reported. Support for a dual gold catalysis was found and it was shown that the concerted or stepwise nature of the cyclization event depends on the substitution of the ynamide moiety. The reaction was found to proceed in three stages: 1) formation of a σ,π‐digold complex from the terminal alkyne, 2) cyclization to produce a gem‐diaurated aryl complex, and 3) catalyst transfer to free the product and regenerate the σ,π‐digold complex. [ABSTRACT FROM AUTHOR]