Access to the Cinnoline Scaffold via Rhodium-Catalyzed Intermolecular Cyclization under Mild Conditions

Herein, we report Rh­(III)-catalyzed, <i>N</i>-amino (hydrazine)-directed C–H functionalization with α-diazo-β-ketoesters for access to the cinnoline scaffold. A diverse set of nondiscriminating conditions obtained for a highly efficient test transformation prompted use of a substrate-replacement technique for an in-depth search of experimental parameter space and pinpointing of the optimized conditions. A successive C–H activation/C–C coupling/intramolecular dehydration mechanistic sequence is proposed. The ability to perform gram-scale synthesis proves the synthetic utility of this simple, yet efficient, method

Visible Light-Activatable Oxidase Mimic of 9‑Mesityl-10-Methylacridinium Ion for Colorimetric Detection of Biothiols and Logic Operations

In this work, 9-mesityl-10-methylacridinium ion (Acr⁺-Mes) is found to act as an effective photocatalyst mimicking the function of oxidase. Upon visible light illumination, the excited Acr⁺-Mes is able to exhibit superior enzymatic catalytic activity for small molecular substrates as well as protein biomacromolecule (cytochrome c). The experiment results demonstrate that the Acr⁺-Mes oxidase mimic shows higher affinity to 3,3′,5,5′-tetramethylbenzidine (TMB) than natural horseradish peroxidase or the reported molecule oxidase mimic. The reaction mechanism is ascribed to the strong oxidation property of the long-lived electron-transfer state (Acr^•-Mes^•+) and the electron transfer from Acr^•-Mes radical to dissolved oxygen to generate superoxide radicals, which can easily oxidize various substrates. On the basis of these observations, the light-activatable Acr⁺-Mes with an oxidase-like activity as the probe is utilized for cost-effective, sensitive, and highly selective colorimetric detection of two biothiols (L-cysteine and L-glutathione). The lowest detectable concentrations of L-Cys and L-GSH is 100 nM, which is lower than that of most of the reported methods for biothiols. Beyond this, we construct a series of visual molecular logic gates (AND, INH, and NOR) using the oxidase mimic-involved reaction systems

A Versatile, Traceless C–H Activation-Based Approach for the Synthesis of Heterocycles

A versatile, traceless C–H activation-based approach for the synthesis of diversified heterocycles is reported. Rh­(III)-catalyzed, <i>N</i>-amino-directed C–H alkenylation generates either olefination products or indoles (in situ annulation) in an atom- and step-economic manner at room temperature. The remarkable reactivity endowed by this directing group enables scale-up of the reaction to a 10 g scale at a very low catalyst loading (0.01 mol %/0.1 mol %). Ex situ annulation of olefination product provides entry into an array of heterocycles

Access to the Cinnoline Scaffold via Rhodium-Catalyzed Intermolecular Cyclization under Mild Conditions

Herein, we report Rh­(III)-catalyzed, <i>N</i>-amino (hydrazine)-directed C–H functionalization with α-diazo-β-ketoesters for access to the cinnoline scaffold. A diverse set of nondiscriminating conditions obtained for a highly efficient test transformation prompted use of a substrate-replacement technique for an in-depth search of experimental parameter space and pinpointing of the optimized conditions. A successive C–H activation/C–C coupling/intramolecular dehydration mechanistic sequence is proposed. The ability to perform gram-scale synthesis proves the synthetic utility of this simple, yet efficient, method

Co(III)-Catalyzed, Internal and Terminal Alkyne-Compatible Synthesis of Indoles

A Co­(III)-catalyzed, internal and terminal alkyne-compatible indole synthesis protocol is reported herein. The <i>N</i>-amino (hydrazine) group imparts distinct, diverse reactivity patterns for directed C–H functionalization/cyclization reactions. Notable synthetic features include regioselectivity for a <i>meta</i>-substituted arylhydrazine, regioselectivity for a chain-branched terminal alkyne, formal incorporation of an acetylenic unit through C2-desilylation on a C2-silylated indole derivative, formal inversion of regioselectivity through consecutive C3-derivatization and C2-desilylation processes, and formal bond migration for a linear-chain terminal alkyne

Co(III)-Catalyzed, Internal and Terminal Alkyne-Compatible Synthesis of Indoles

A Co­(III)-catalyzed, internal and terminal alkyne-compatible indole synthesis protocol is reported herein. The <i>N</i>-amino (hydrazine) group imparts distinct, diverse reactivity patterns for directed C–H functionalization/cyclization reactions. Notable synthetic features include regioselectivity for a <i>meta</i>-substituted arylhydrazine, regioselectivity for a chain-branched terminal alkyne, formal incorporation of an acetylenic unit through C2-desilylation on a C2-silylated indole derivative, formal inversion of regioselectivity through consecutive C3-derivatization and C2-desilylation processes, and formal bond migration for a linear-chain terminal alkyne

Bidentate Directing-Enabled, Traceless Heterocycle Synthesis: Cobalt-Catalyzed Access to Isoquinolines

Traceless heterocycle synthesis based on transition-metal-catalyzed C–H functionalization is synthetically appealing but has been realized only in monodentate directing systems. Bidentate directing systems allow for the achievement of high catalytic reactivity without the need for a high-cost privileged ligand. The first bidentate directing-enabled, traceless heterocycle synthesis is demonstrated in the cobalt-catalyzed synthesis of isoquinolines via 2-hydrazinylpyridine-directed C–H coupling/cyclization with alkynes. Convenient directing group installation through a ubiquitously present ketone group allows synthetic elaboration for complex molecules

Bidentate Directing-Enabled, Traceless Heterocycle Synthesis: Cobalt-Catalyzed Access to Isoquinolines

Traceless heterocycle synthesis based on transition-metal-catalyzed C–H functionalization is synthetically appealing but has been realized only in monodentate directing systems. Bidentate directing systems allow for the achievement of high catalytic reactivity without the need for a high-cost privileged ligand. The first bidentate directing-enabled, traceless heterocycle synthesis is demonstrated in the cobalt-catalyzed synthesis of isoquinolines via 2-hydrazinylpyridine-directed C–H coupling/cyclization with alkynes. Convenient directing group installation through a ubiquitously present ketone group allows synthetic elaboration for complex molecules

Bidentate Directing-Enabled, Traceless Heterocycle Synthesis: Cobalt-Catalyzed Access to Isoquinolines

Traceless heterocycle synthesis based on transition-metal-catalyzed C–H functionalization is synthetically appealing but has been realized only in monodentate directing systems. Bidentate directing systems allow for the achievement of high catalytic reactivity without the need for a high-cost privileged ligand. The first bidentate directing-enabled, traceless heterocycle synthesis is demonstrated in the cobalt-catalyzed synthesis of isoquinolines via 2-hydrazinylpyridine-directed C–H coupling/cyclization with alkynes. Convenient directing group installation through a ubiquitously present ketone group allows synthetic elaboration for complex molecules

Bidentate Directing-Enabled, Traceless Heterocycle Synthesis: Cobalt-Catalyzed Access to Isoquinolines

Traceless heterocycle synthesis based on transition-metal-catalyzed C–H functionalization is synthetically appealing but has been realized only in monodentate directing systems. Bidentate directing systems allow for the achievement of high catalytic reactivity without the need for a high-cost privileged ligand. The first bidentate directing-enabled, traceless heterocycle synthesis is demonstrated in the cobalt-catalyzed synthesis of isoquinolines via 2-hydrazinylpyridine-directed C–H coupling/cyclization with alkynes. Convenient directing group installation through a ubiquitously present ketone group allows synthetic elaboration for complex molecules