Regio‐ and Enantioselective Iridium‐Catalyzed N‐Allylation of Indoles and Related Azoles with Racemic Branched Alkyl‐Substituted Allylic Acetates

Kim, Seung Wook; Schempp, Tabitha T.; Zbieg, Jason R.; Stivala, Craig E.; Krische, Michael J.

doi:10.1002/ange.201902799

Cited by 14 publications

(4 citation statements)

References 109 publications

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“…In addition to aryl bromides, vinyl bromides were incorporated as well in this reaction, leading to structually diverse chiral Nallyl indoles 4a-4f in 35-60% yields with 73-95% ee values. Remarkably, this modular alkenylation complements previously established metal-catalyzed indole N-allylations in that di-and trisubstituted allylic products bearing aryl and alkyl groups are readily accessed 27,29,31,70,71 .…”

Section: Reaction Scopementioning

confidence: 67%

Enantioselective synthesis of N-alkylindoles enabled by nickel-catalyzed C-C coupling

Ren

Zhou

et al. 2022

Nat Commun

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Enantioenriched N-alkylindole compounds, in which nitrogen is bound to a stereogenic sp3 carbon, are an important entity of target molecules in the fields of biological, medicinal, and organic chemistry. Despite considerable efforts aimed at inventing methods for stereoselective indole functionalization, straightforward access to a diverse range of chiral N-alkylindoles in an intermolecular catalytic fashion from readily available indole substrates remains an ongoing challenge. In sharp contrast to existing C–N bond-forming strategies, here, we describe a modular nickel-catalyzed C–C coupling protocol that couples a broad array of N-indolyl-substituted alkenes with aryl/alkenyl/alkynyl bromides to produce chiral N-alkylindole adducts in single regioisomeric form, in up to 91% yield and 97% ee. The process is amenable to proceed under mild conditions and exhibit broad scope and high functional group compatibility. Utility is highlighted through late-stage functionalization of natural products and drug molecules, preparation of chiral building blocks.

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Section: Reaction Scopementioning

confidence: 67%

Enantioselective synthesis of N-alkylindoles enabled by nickel-catalyzed C-C coupling

Ren

Zhou

et al. 2022

Nat Commun

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“…In recent years, some transition-metal-catalyzed N-alkylation of indoles were performed . Ru, Rh, Pd, Ir, Pt, and Cu were demonstrated to catalyze the reaction. For example, Trost et al and Hartwig et al.…”

Section: Introductionmentioning

confidence: 99%

Palladium-Catalyzed Reaction of Indolines with Dihydropyrroles: Access to N-Alkylated Indoles

Jiang,

Wang

2024

J. Org. Chem.

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Palladium-catalyzed reaction of indolines with 1-acyl-2,3-dihydro-1H-pyrroles or 1-acyl-2,5-dihydro-1H-pyrroles in air produces N-alkylated indoles. A combination of Pd(CH 3 CN) 2 Cl 2 and dppf effectively catalyzes the reaction of 1-acyl-2,3dihydro-1H-pyrroles, and the combination of Pd(CH 3 CN) 2 Cl 2 and dcypf is more effective for the reaction of 1-acyl-2,5-dihydro-1Hpyrroles. The method has a wide scope of substrates and shows good compatibility of functional groups.

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“…[2] Consistent with the innate reactivity of indoles,i ntermolecular asymmetric allylation of the C3position of indole is aw ell-established process. [3] Thea nalogous N1-allylation is relatively less well-explored, although there exist various innovative methods for this recently developed by the groups of Hartwig, [4] You, [5] Krische [6] and others. [7] To the best of our knowledge,there are no methods capable of directly allylating indole at the C2-position in an enantioselective,i ntermolecular fashion.…”

Section: Introductionmentioning

confidence: 99%

Iridium‐Catalyzed Enantioselective Intermolecular Indole C2‐Allylation

et al. 2020

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The enantioselective intermolecular C2-allylation of 3-substituted indoles is reported for the first time.This directing group-free approach relies on ac hiral Ir-(P,o lefin) complex and Mg(ClO 4 ) 2 Lewis acid catalyst system to promote allylic substitution, providing the C2-allylated products in typically high yields (40-99 %) and enantioselectivities (83-99 %e e) with excellent regiocontrol. Experimental studies and DFT calculations suggest that the reaction proceeds via direct C2allylation, rather than C3-allylation followed by in situ migration. Steric congestion at the indole-C3 position and improved p-p stackingi nteractions have been identified as major contributors to the C2-selectivity. Scheme 1. Intermolecular indole C2-allylation.

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Regio‐ and Enantioselective Iridium‐Catalyzed N‐Allylation of Indoles and Related Azoles with Racemic Branched Alkyl‐Substituted Allylic Acetates

Cited by 14 publications

References 109 publications

Enantioselective synthesis of N-alkylindoles enabled by nickel-catalyzed C-C coupling

Enantioselective synthesis of N-alkylindoles enabled by nickel-catalyzed C-C coupling

Palladium-Catalyzed Reaction of Indolines with Dihydropyrroles: Access to N-Alkylated Indoles

Iridium‐Catalyzed Enantioselective Intermolecular Indole C2‐Allylation

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