Ni-Catalyzed Direct Reductive Amidation via C–O Bond Cleavage

A novel Ni-catalyzed reductive amidation of C­(sp²)–O and C­(sp³)–O electrophiles with isocyanates is described. This umpolung reaction allows for an unconventional preparation of benzamides using simple starting materials and easy-to-handle Ni catalysts

Ni-Catalyzed Direct Carboxylation of Benzyl Halides with CO₂

A novel Ni-catalyzed carboxylation of benzyl halides with CO₂ has been developed. The described carboxylation reaction proceeds under mild conditions (atmospheric CO₂ pressure) at room temperature. Unlike other routes for similar means, our method does not require well-defined and sensitive organometallic reagents and thus is a user-friendly and operationally simple protocol for assembling phenylacetic acids

Ni-Catalyzed Direct Carboxylation of Benzyl Halides with CO₂

A novel Ni-catalyzed carboxylation of benzyl halides with CO₂ has been developed. The described carboxylation reaction proceeds under mild conditions (atmospheric CO₂ pressure) at room temperature. Unlike other routes for similar means, our method does not require well-defined and sensitive organometallic reagents and thus is a user-friendly and operationally simple protocol for assembling phenylacetic acids

Ni-Catalyzed Carboxylation of C(sp²)– and C(sp³)–O Bonds with CO₂

In recent years a significant progress has been made for the carboxylation of aryl and benzyl halides with CO₂, becoming convenient alternatives to the use of stoichiometric amounts of well-defined metal species. Still, however, most of these processes require the use of pyrophoric and air-sensitive reagents and the current methods are mostly restricted to organic halides. Therefore, the discovery of a mild, operationally simple alternate carboxylation that occurs with a wide substrate scope employing readily available coupling partners will be highly desirable. Herein, we report a new protocol that deals with the development of a synergistic activation of CO₂ and a rather challenging activation of inert C­(sp²)–O and C­(sp³)–O bonds derived from simple and cheap alcohols, a previously unrecognized opportunity in this field. This unprecedented carboxylation event is characterized by its simplicity, mild reaction conditions, remarkable selectivity pattern and an excellent chemoselectivity profile using air-, moisture-insensitive and easy-to-handle nickel precatalysts. Our results render our method a powerful alternative, practicality and novelty aside, to commonly used organic halides as counterparts in carboxylation protocols. Furthermore, this study shows, for the first time, that traceless directing groups allow for the reductive coupling of substrates without extended π-systems, a typical requisite in many C–O bond-cleavage reactions. Taking into consideration the limited knowledge in catalytic carboxylative reductive events, and the prospective impact of providing a new tool for accessing valuable carboxylic acids, we believe this work opens up new vistas and allows new tactics in reductive coupling events

Selective C(sp²)–H Halogenation of “Click” 4‑Aryl-1,2,3-triazoles

Selective bromination reactions of “click compounds” are described. Electron-neutral and electron-deficient arenes selectively undergo unprecedented Pd-catalyzed C–H <i>ortho</i>-halogenations assisted by simple triazoles as modular directing groups, whereas electron-rich arenes are regioselectively halogenated following an electrophilic aromatic substitution reaction pathway. These C–H halogenation procedures exhibit a wide group tolerance, complement existing bromination procedures, and represent versatile synthetic tools of utmost importance for the late-stage diversification of “click compounds”. The characterization of a triazole-containing palladacycle and density functional theory studies supported the mechanism proposal

Co-Catalyzed C(sp³)–H Oxidative Coupling of Glycine and Peptide Derivatives

Cobalt-catalyzed selective α-alkylation and α-heteroarylation processes of α-amino esters and peptide derivatives are described. These cross-dehydrogenative reactions occur under mild conditions and allow for the rapid assembly of structurally diverse α-amino carbonyl compounds. Unlike enolate chemistry, these methods are distinguished by their site-specificity, occur without racemization of the existing chiral centers, and exhibit total selectivity for aryl glycine motifs over other amino acid units, hence providing ample opportunities for peptide modifications

Selective C(sp²)–H Halogenation of “Click” 4‑Aryl-1,2,3-triazoles

Selective bromination reactions of “click compounds” are described. Electron-neutral and electron-deficient arenes selectively undergo unprecedented Pd-catalyzed C–H <i>ortho</i>-halogenations assisted by simple triazoles as modular directing groups, whereas electron-rich arenes are regioselectively halogenated following an electrophilic aromatic substitution reaction pathway. These C–H halogenation procedures exhibit a wide group tolerance, complement existing bromination procedures, and represent versatile synthetic tools of utmost importance for the late-stage diversification of “click compounds”. The characterization of a triazole-containing palladacycle and density functional theory studies supported the mechanism proposal

Triazole-Directed Pd-Catalyzed C(sp²)–H Oxygenation of Arenes and Alkenes

Selective Pd-catalyzed C­(sp²)–H oxygenation of 4-substituted 1,2,3-triazoles is described. Unlike previous metal-catalyzed C–H functionalization events, which preferentially occur at the activated heterocyclic C–H bond, the regioselective oxygenation of the arene/alkene moiety is now achieved featuring the unconventional role of a simple triazole scaffold as a modular and selective directing group