Copper-Catalyzed Regioselective sp<sup>3</sup> C–H Azidation of Alkyl Substituents of Indoles and Tetrahydrocarbazoles

Huang, Liwu; Xun, Xudong; Zhao, Man; Xue, Jianzhong; Li, Guofeng; Liu, Hong

doi:10.1021/acs.joc.9b01742

Cited by 20 publications

(16 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a fourth manifold, the mechanism could occur by a pathway analogous to iron-catalyzed oxidation reactions through an iron-oxo species. , In this case, reaction of a C( sp 3 )–H bond with an iron-nitride or iron-nitrene complex could occur. Subsequent transfer of azide from 1 or an iron-azide complex would form the C( sp 3 )–N bond. ,, …”

Section: Results and Discussionmentioning

confidence: 99%

“…Subsequent transfer of azide from 1 or an ironazide complex would form the C(sp 3 )−N bond. 29,33,46 Finally, a fifth mechanism could occur by a hybrid of the previous four. In one such hybrid, oxidation of iron(II) by 1 would form an electrophilic iron(III)-azide complex.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…The data in section 3 showed that homolysis of the N−I bond of 1 at 50 °C generates azidyl and λ 2 -iodanyl radicals, one or both of which could abstract a hydrogen atom from a C(sp 3 )−H bond (Figure 8 and Figure 9). Both λ 2 - iodanyl and azidyl radicals have been proposed in prior literature to undergo site-selective abstraction of tertiary C(sp 3 )−H bonds, 24,46,61,64 a site-selectivity that matches that observed in the azidation reaction; therefore, the identity of the radical species that abstracts the hydrogen atom from the C(sp 3 )−H bond in the azidation reaction was investigated.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Mechanistic Investigation of the Iron-Catalyzed Azidation of Alkyl C(sp³)–H Bonds with Zhdankin’s λ³-Azidoiodane

et al. 2021

View full text Add to dashboard Cite

An in-depth study of the mechanism of the azidation of C(sp 3)–H bonds with Zhdankin’s λ3-azidoiodane reagent catalyzed by iron(II)(pybox) complexes is reported. Previously, it was shown that tertiary and benzylic C(sp 3)–H bonds of a range of complex molecules underwent highly site-selective azidation by reaction with a λ3-azidoiodane reagent and an iron(II)(pybox) catalyst under mild conditions. However, the mechanism of this reaction was unclear. Here, a series of mechanistic experiments are presented that reveal critical features responsible for the high selectivity and broad scope of this reaction. These experiments demonstrate the ability of the λ3-azidoiodane reagent to undergo I–N bond homolysis under mild conditions to form λ2-iodanyl and azidyl radicals that undergo highly site-selective and rate-limiting abstraction of a hydrogen atom from the substrate. The resultant alkyl radical then combines rapidly with a resting state iron(III)-azide complex, which is generated by the reaction of the λ3-azidoiodane with the iron(II)(pybox) complex, to form the C(sp 3)–N3 bond. This mechanism is supported by the independent synthesis of well-defined iron complexes characterized by cyclic voltammetry, X-ray diffraction, and EPR spectroscopy, and by the reaction of the iron complexes with alkanes and the λ3-azidoiodane. Reaction monitoring and kinetic studies further reveal an unusual effect of the catalyst on the rate of formation of product and consumption of reactants and suggest a blueprint for the development of new processes leading to late-stage functionalization of C(sp 3)–H bonds.

show abstract

Section: Results and Discussionmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mechanistic Investigation of the Iron-Catalyzed Azidation of Alkyl C(sp³)–H Bonds with Zhdankin’s λ³-Azidoiodane

et al. 2021

View full text Add to dashboard Cite

show abstract

“…However, the commonly used azidation reagent failed to give the azidation product (Scheme 67d). 271 3,3-Difunctionalized oxindoles are the core structures of many natural products and drugs. In the context of the synthesis of 3-substituted 3-azido-2-oxindoles, the Gade group in 2013 reported the first direct and enantioselective C−H azidation of oxindoles 267 using Fe catalyst prepared from Fe(CO 2 Et) 2 with the 1,3-bis(1,3-oxazolin-2-ylmethylene)isoindoline ligand (boxmi, 268) in situ.…”

Section: Azidation Of Benzylic/heterobenzylic C−h Bondsmentioning

confidence: 99%

New Strategies for the Synthesis of Aliphatic Azides

2021

View full text Add to dashboard Cite

Aliphatic azides are a versatile class of compounds found in a variety of biologically active pharmaceuticals. These compounds are also recognized as useful precursors for the synthesis of a range of nitrogen-based scaffolds of therapeutic drugs, biologically active compounds, and functional materials. In light of the growing importance of aliphatic azides in both chemical and biological sciences, a vast array of synthetic strategies for the preparation of structurally diverse aliphatic azides have been developed over the past decades. However, to date, this topic has not been the subject of a dedicated review. This review aims to provide a concise overview of modern synthetic strategies to access aliphatic azides that have emerged since 2010. The discussed azidation reactions include (a) azidation of C–C multiple bonds, (b) azidation of C–H bonds, (c) the direct transformation of vinyl azides into other aliphatic azides, and (d) miscellaneous reactions to access aliphatic azides. We critically discuss the synthetic outcomes and the generality and uniqueness of the different mechanistic rationale of each of the selected reactions. The challenges and potential opportunities of the topic are outlined.

show abstract

“…Hong and co-workers developed a copper-mediated protocol for the regioselective sp 3 C-H azidation of alkyl substituents of indoles (Scheme 23). 51 A wide variety of 2,3-alkyl indoles 67 accomplished the azidation products 69 under easy and mild reaction conditions in the presence of azidoiodinane reagent 68. They also extended the reaction to tetrahydrocarbazoles and obtained the corresponding a-azide tetrahydrocarbazoles in good yields.…”

Section: C-n Bond Formationmentioning

confidence: 99%

Progress and prospects in copper-catalyzed C–H functionalization

et al. 2020

View full text Add to dashboard Cite

show abstract

Copper-Catalyzed Regioselective sp³ C–H Azidation of Alkyl Substituents of Indoles and Tetrahydrocarbazoles

Cited by 20 publications

References 54 publications

Mechanistic Investigation of the Iron-Catalyzed Azidation of Alkyl C(sp³)–H Bonds with Zhdankin’s λ³-Azidoiodane

Mechanistic Investigation of the Iron-Catalyzed Azidation of Alkyl C(sp³)–H Bonds with Zhdankin’s λ³-Azidoiodane

New Strategies for the Synthesis of Aliphatic Azides

Progress and prospects in copper-catalyzed C–H functionalization

Contact Info

Product

Resources

About

Copper-Catalyzed Regioselective sp3 C–H Azidation of Alkyl Substituents of Indoles and Tetrahydrocarbazoles

Cited by 20 publications

References 54 publications

Mechanistic Investigation of the Iron-Catalyzed Azidation of Alkyl C(sp3)–H Bonds with Zhdankin’s λ3-Azidoiodane

Mechanistic Investigation of the Iron-Catalyzed Azidation of Alkyl C(sp3)–H Bonds with Zhdankin’s λ3-Azidoiodane

New Strategies for the Synthesis of Aliphatic Azides

Progress and prospects in copper-catalyzed C–H functionalization

Contact Info

Product

Resources

About

Copper-Catalyzed Regioselective sp³ C–H Azidation of Alkyl Substituents of Indoles and Tetrahydrocarbazoles

Mechanistic Investigation of the Iron-Catalyzed Azidation of Alkyl C(sp³)–H Bonds with Zhdankin’s λ³-Azidoiodane

Mechanistic Investigation of the Iron-Catalyzed Azidation of Alkyl C(sp³)–H Bonds with Zhdankin’s λ³-Azidoiodane