Recent advances in transition metal-catalyzed N-atom transfer reactions of azides

Transition metal-catalyzed N-atom transfer reactions of azides provide efficient ways to construct new carbon–nitrogen and sulfur–nitrogen bonds. These reactions are inherently green: no additive besides catalyst is needed to form the nitrenoid reactive intermediate, and the by-product of the reaction is environmentally benign N2 gas. As such, azides can be useful precursors for transition metal-catalyzed N-atom transfer to sulfides, olefins and C–H bonds. These methods offer competitive selectivities and comparable substrate scope as alternative processes to generate metal nitrenoids

Efficient Synthesis of 3<i>H</i>‑Indoles Enabled by the Lead-Mediated α‑Arylation of β‑Ketoesters or γ‑Lactams Using Aryl Azides

The development of a lead-mediated α-arylation reaction between aryl azides and β-ketoesters or γ-lactams that facilitates the formation of 3<i>H</i>-indoles is disclosed. Twenty-five examples are included which demonstrate the generality of this reaction to access aryl azides bearing tetrasubstituted <i>o</i>-alkyl substituents. When paired with a Staudinger reduction, this reaction streamlines the synthesis of functionalized 3<i>H</i>-indoles

Rh₂(II)-Catalyzed Ester Migration to Afford 3<i>H</i>‑Indoles from Trisubstituted Styryl Azides

Rh₂(II)-Complexes trigger the formation of 3<i>H</i>-indoles from <i>ortho</i>-alkenyl substituted aryl azides. This reaction occurs through a 4π-electron-5-atom electrocyclization of the rhodium <i>N</i>-aryl nitrene followed by a [1,2]-migration to afford only 3<i>H</i>-indoles. The selectivity of the migration is dependent on the identity of the β-styryl substituent

Iron-Catalyzed Reductive Cyclization of <i>o</i>‑Nitrostyrenes Using Phenylsilane as the Terminal Reductant

Using microscale high-throughput experimentation, an efficient, earth-abundant iron phenanthroline complex was discovered to catalyze the reductive cyclization of <i>ortho</i>-nitrostyrenes into indoles via nitrosoarene reactive intermediates. This method requires only 1 mol % of Fe­(OAc)₂ and 1 mol % of 4,7-(MeO)₂phen and uses phenylsilane as a convenient terminal reductant. The scope and limitations of the method were illustrated with 21 examples, and an investigation into the kinetics of the reaction revealed first-order behavior in catalyst and silane and zero-order behavior with respect to nitrostyrene

Rh₂(II)-Catalyzed Intramolecular Aliphatic C–H Bond Amination Reactions Using Aryl Azides as the N-Atom Source

Rhodium­(II) dicarboxylate complexes were discovered to catalyze the intramolecular amination of unactivated primary, secondary, or tertiary aliphatic C–H bonds using aryl azides as the N-atom precursor. While a strong electron-withdrawing group on the nitrogen atom is typically required to achieve this reaction, we found that both electron-rich and electron-poor aryl azides are efficient sources for the metal nitrene reactive intermediate

Iron(II) Bromide-Catalyzed Intramolecular C–H Bond Amination [1,2]-Shift Tandem Reactions of Aryl Azides

Iron­(II) bromide catalyzes the transformation of <i>ortho</i>-substituted aryl azides into 2,3-disubstituted indoles through a tandem ethereal C–H bond amination [1,2]-shift reaction. The preference for the 1,2-shift component of the tandem reaction was established to be Me < 1° < 2° < Ph

Rh₂(II)-Catalyzed Selective Aminomethylene Migration from Styryl Azides

Rh₂(II)-Carboxylate complexes were discovered to promote the selective migration of aminomethylenes in β,β-disubstituted styryl azides to form 2,3-disubstituted indoles. Mechanistic data are also presented that suggest that the migration occurs stepwise before diffusion of the iminium ion

Rh₂(II)-Catalyzed Selective Aminomethylene Migration from Styryl Azides

Rh₂(II)-Carboxylate complexes were discovered to promote the selective migration of aminomethylenes in β,β-disubstituted styryl azides to form 2,3-disubstituted indoles. Mechanistic data are also presented that suggest that the migration occurs stepwise before diffusion of the iminium ion

Iron(II) Bromide-Catalyzed Intramolecular C–H Bond Amination [1,2]-Shift Tandem Reactions of Aryl Azides

Iron­(II) bromide catalyzes the transformation of <i>ortho</i>-substituted aryl azides into 2,3-disubstituted indoles through a tandem ethereal C–H bond amination [1,2]-shift reaction. The preference for the 1,2-shift component of the tandem reaction was established to be Me < 1° < 2° < Ph

Development of a Suzuki Cross-Coupling Reaction between 2‑Azidoarylboronic Pinacolate Esters and Vinyl Triflates To Enable the Synthesis of [2,3]-Fused Indole Heterocycles

The scope and limitations of a Suzuki reaction between 2-azidoarylboronic acid pinacolate esters and vinyl triflates are reported. This cross-coupling reaction enables the regioselective synthesis of indoles after a subsequent Rh^II₂-catalyzed sp²-C–H bond amination reaction