Selective ortho-C–H Activation in Arenes without Functional Groups

Abstract

Aromatic C–H activation in alkylarenes is a key step for the synthesis of functionalized organic molecules from simple hydrocarbon precursors. Known examples of such C–H activations often yield mixtures of products resulting from activation of the least hindered C–H bonds. Here we report highly selective ortho -C–H activation in alkylarenes by simple iridium complexes. We demonstrate that the capacity of the alkyl substituent to override the typical preference of metal-mediated C–H activation for the least hindered aromatic C–H bonds results from transient insertion of iridium into the benzylic C–H bond. This enables fast iridium insertion into the ortho -C–H bond, followed by regeneration of the benzylic C–H bond by reductive elimination. Bulkier alkyl substituents increase the ortho selectivity. The described chemistry represents a conceptually new alternative to existing approaches for aromatic C–H bond activation.

Mechanism of Pd/Senphos-Catalyzed trans-Hydroboration of 1,3-Enynes: Experimental and Computational Evidence in Support of the Unusual Outer-Sphere Oxidative Addition Pathway

“…The present calculation formally identifies the Pd-enyne π-complex as the resting state of the catalyst with the caveat that the outer-sphere oxidative addition adduct Int 1 can, within reasonable computational error range, be considered as the resting state as well. , With a predicted energy difference of less than 1.0 kcal/mol between the π-complex and Int 1, it is possible that the equilibrium, and as a consequence the resting state, may be influenced by reaction stoichiometry (e.g., concentration of H-B(cat)) under the reaction conditions. The rate-limiting transition state TS 3 involves the hydride abstraction step by the borane shuttle and is 17.7 kcal/mol above the resting state.…”

Allosteric control of olefin isomerization kinetics via remote metal binding and its mechanochemical analysis

“…All calculations were performed with Gaussian 16.C in vacuum; the Berny algorithm was applied to locate stationary points and tight convergence criteria and ultrafine integration grids were used in optimizations and frequency calculations. Reactant conformers of the macrocycles were generated and optimized as previously described 18 , except for the used model chemistry (B3LYP/def2SVP); we previously demonstrated that the def2SVP basis set leads to faster convergence of geometry optimizations of complexes of heavy transition metals and yields kinetic barriers for reactions of such complexes in better agreement with experiment than LANL2DZ 52 . Free energies of individual conformers were sums of the single-point electronic energy calculated at the (u)BMK/def2SVP level and the corresponding thermodynamic corrections calculated statistically-mechanically with all frequencies <500 cm −1 replaced with 500 cm −1 to avoid artifactually large contributions of vibrations to Δ G ǂ 53 .…”

Relay Copper-Catalyzed Synthesis of Imidazo[1,5-a]pyridine Scaffolds from Phenylalanine and Halohydrocarbon

“…Over past decades, traditional-metal-catalyzed C–H functionalization has been demonstrated as a powerful strategy for the conversion of organic molecules, − providing an efficient pathway for synthesizing Im5Py compounds. For instance, Zhu developed a strategy utilizing Cu­(II) and Fe­(III) cocatalysts to access Im5Py derivatives via intramolecular C­(sp 2 )–H amination, while Adimurthy reported on the construction of Im5Py derivatives through a copper-catalyzed cascade denitrogenative transannulation reaction of pyridotriazoles (Figure B). , Despite these significant achievements, compounds of this kind still remain a challenge and offer room for the development of practical strategies.…”