Formal Ir-Catalyzed Ligand-Enabled Ortho and Meta Borylation of Aromatic Aldehydes via in Situ-Generated Imines

The ligand-enabled development of ortho and meta C–H borylation of aromatic aldehydes is reported. It was envisaged that while ortho borylation could be achieved using <i>tert</i>-butylamine as the traceless protecting/directing group, meta borylation proceeds via an electrostatic interaction and a secondary interaction between the ligand of the catalyst and the substrate. These ligand–substrate electrostatic interactions and secondary B–N interactions provide an unprecedented controlling factor for meta-selective C–H activation/borylation

Rh-Catalyzed Transannulation of <i>N</i>-Tosyl-1,2,3-Triazoles with Terminal Alkynes

The first transannulation of 1,2,3-triazoles with terminal alkynes into pyrroles is reported. The reaction proceeds in the presence of a Rh2(oct)4/AgOCOCF3 binary catalyst system providing a straightforward approach to 1,2,4-trisubstituted pyrroles in good to excellent yields

Silanol: A Traceless Directing Group for Pd-Catalyzed <i>o</i>-Alkenylation of Phenols

A silanol-directed, Pd(II)-catalyzed C–H alkenylation of phenols is reported. This work features silanol, as a novel traceless directing group, and a directed o-C–H alkenylation of phenols. This new method allows for efficient synthesis of diverse alkenylated phenols, including an estrone derivative

Double-Fold Ortho and Remote C–H Bond Activation/Borylation of BINOL: A Unified Strategy for Arylation of BINOL

A double-fold ortho and remote C–H borylation of BINOL is described. The proposed mechanisms involved electrostatically and sterically directed ortho and remote C–H activation processes, respectively. While B2eg2 (eg = ethylene glycolate) directs the C–H activation at ortho positions, a combination of HBpin and B2pin2 activates remote C–H bonds. The strategy was combined with Suzuki arylation as a one-pot protocol for the rapid synthesis of BINOL derivatives with retention of chirality

Synthesis of Catechols from Phenols via Pd-Catalyzed Silanol-Directed C–H Oxygenation

A silanol-directed, Pd-catalyzed C–H oxygenation of phenols into catechols is presented. This method is highly site selective and general, as it allows for oxygenation of not only electron-neutral but also electron-poor phenols. This method operates via a silanol-directed acetoxylation, followed by a subsequent acid-catalyzed cyclization reaction into a cyclic silicon-protected catechol. A routine desilylation of the silacyle with TBAF uncovers the catechol product

Fused Tetrazoles as Azide Surrogates in Click Reaction: Efficient Synthesis of N-Heterocycle-Substituted 1,2,3-Triazoles

It has been shown that various pyrido-, quinolino-, pyrazino-, and quinoxalinotetrazoles can be used efficiently as azide components in Cu-catalyzed click reaction with alkynes. This method allows for efficient synthesis of a wide variety of N-heterocyclic derivatives of 1,2,3-triazoles

Ir-Catalyzed Intramolecular Transannulation/C(sp²)–H Amination of 1,2,3,4-Tetrazoles by Electrocyclization

An efficient strategy for the intramolecular denitrogenative transannulation/C­(sp²)–H amination of 1,2,3,4-tetrazoles bearing C8-substituted arenes, heteroarenes, and alkenes is described. The process involves the generation of the metal–nitrene intermediate from tetrazole by the combination of [Cp*IrCl₂]₂ and AgSbF₆. It has been shown that the reaction proceeds via an unprecedented electrocyclization process. The method has been successfully applied for the synthesis of a diverse array of α-carbolines and 7-azaindoles

Iron-Catalyzed Intermolecular C–N Cross-Coupling Reactions via Radical Activation Mechanism

A concept for intermolecular C–N cross-coupling amination has been discovered using tetrazoles and aromatic and aliphatic azides with boronic acids under iron-catalyzed conditions. The amination follows an unprecedented metalloradical activation mechanism that is different from traditional metal-catalyzed C–N cross-coupling reactions. The scope of the reaction has been demonstrated by the employment of a large number of tetrazoles, azides, and boronic acids. Moreover, several late-stage aminations and a short synthesis of a drug candidate have been showcased for further synthetic utility. Collectively, this iron-catalyzed C–N cross-coupling should have wide applications in the context of medicinal chemistry, drug discovery, and pharmaceutical industries

Iron-Catalyzed Intermolecular Amination of Benzylic C(sp³)–H Bonds

A catalytic system for intermolecular benzylic C(sp3)–H amination is developed utilizing 1,2,3,4-tetrazole as a nitrene precursor via iron catalysis. This method enables direct installation of 2-aminopyridine into the benzylic and heterobenzylic position. The method selectively aminates 2° benzylic C(sp3)–H bond over the 3° and 1° benzylic C(sp3)–H bonds. Experimental studies reveal that the C(sp3)–H amination undergoes via the formation of a benzylic radical intermediate. This study reports the discovery of new method for 2-pyridine substituted benzylamine synthesis using inexpensive, biocompatible base metal catalysis that should have wide application in the context of medicinal chemistry and drug discovery

C–H Borylation Catalysts that Distinguish Between Similarly Sized Substituents Like Fluorine and Hydrogen

By modifying ligand steric and electronic profiles it is possible to C–H borylate ortho or meta to substituents in aromatic and heteroaromatic compounds, where steric differences between accessible C–H sites are small. Dramatic effects on selectivities between reactions using B2pin2 or 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (HBpin) are described for the first time. Judicious ligand and borane combinations give highly regioselective C–H borylations on substrates where typical borylation protocols afford poor selectivities