Cobalt-catalyzed enantioselective C–H/N–H annulation of aryl sulfonamides with allenes or alkynes: facile access to C–N axially chiral sultams

Chemical Science, Journal Year: 2023, Volume and Issue: 14(26), P. 7291 - 7303

Published: Jan. 1, 2023

Herein we report a cobalt-catalyzed enantioselective C-H/N-H annulation of aryl sulfonamides with allenes and alkynes, using either chemical or electrochemical oxidation. By O2 as the oxidant, proceeds efficiently low catalyst/ligand loading 5 mol% tolerates wide range allenes, including 2,3-butadienoate, allenylphosphonate, phenylallene, resulting in C-N axially chiral sultams high enantio-, regio-, position selectivities. The alkynes also exhibits excellent enantiocontrol (up to >99% ee) variety functional sulfonamides, internal terminal alkynes. Furthermore, oxidative is achieved simple undivided cell, demonstrating versatility robustness cobalt/Salox system. gram-scale synthesis asymmetric catalysis further highlight practical utility this method.

Language: Английский

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Data-driven design of new chiral carboxylic acid for construction of indoles with C-central and C–N axial chirality via cobalt catalysis

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 31, 2023

Challenging enantio- and diastereoselective cobalt-catalyzed C-H alkylation has been realized by an innovative data-driven knowledge transfer strategy. Harnessing the statistics of a related transformation as source, designed machine learning (ML) model took advantage delta enabled accurate extrapolative enantioselectivity predictions. Powered model, virtual screening broad scope 360 chiral carboxylic acids led to discovery new catalyst featuring intriguing furyl moiety. Further experiments verified that predicted acid can achieve excellent stereochemical control for target alkylation, which supported expedient synthesis large library substituted indoles with C-central C-N axial chirality. The reported approach provides powerful data engine accelerate molecular catalysis harnessing hidden value available structure-performance statistics.

Language: Английский

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Cobalt(III)-catalyzed asymmetric ring-opening of 7-oxabenzonorbornadienes via indole C–H functionalization

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 25, 2023

Abstract Asymmetric ring-opening of 7-oxabenzonorbornadienes is achieved via Co-catalyzed indole C–H functionalization. The utilization chiral Co-catalyst consisting a binaphthyl-derived trisubstituted cyclopentadienyl ligand resulted in high yields (up to 99%) and excellent enantioselectivity (>99% ee) for the target products with tolerance diverse functional groups. Opposite diastereoselectivities are obtained or Cp*CoI 2 CO. Combined experimental computational studies suggest β -oxygen elimination being selectivity-determining step reaction. Meanwhile, reactions 7-azabenzonorbornadiene could also be executed diastereodivergent manner.

Language: Английский

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Ni- and Pd-Catalyzed Enantioselective 1,2-Dicarbofunctionalization of Alkenes

Synthesis, Journal Year: 2023, Volume and Issue: 56(01), P. 1 - 15

Published: June 12, 2023

Abstract Catalytic enantioselective 1,2-dicarbofunctionalization (1,2-DCF) of alkenes is a powerful transformation growing importance in organic synthesis for constructing chiral building blocks, bioactive molecules, and agrochemicals. Both two- three-component context, this family reactions generates densely functionalized, structurally complex products single step. Across several distinct mechanistic pathways at play these transformations with nickel or palladium catalysts, stereocontrol can be obtained through tailored ligands. In Review we discuss the various strategies, mechanisms, catalysts that have been applied to achieve enantioinduction alkene 1,2-DCF. 1 Introduction 2 Two-Component Enantioselective 1,2-DCF via Migratory Insertion 3 Radical Capture 4 Three-Component 5 6 Miscellaneous Mechanisms 7 Conclusion

Language: Английский

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Enantioselective C–H bond functionalization under Co(iii)-catalysis

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(25), P. 3354 - 3369

Published: Jan. 1, 2024

Enantioselective C–H functionalization relies on 4d and 5d metals, but with their depletion, sustainable alternatives using 3d metals are crucial.

Language: Английский

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Enantioselective Synthesis of Indole-Fused Polycycles Bearing Four Consecutive Stereocenters via Rhodium Catalysis

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Indole-fused polycycles are common in natural products and bioactive molecules, yet their concise efficient synthesis remains challenging, especially for compounds with multiple stereocenters. Herein, we report the application of a chiral CpxRhIII catalyst enantioselective C–H activation/[4+2] annulation indoles bicyclic alkenes. This catalytic system exhibits high enantioselectivity broad functional group tolerance operates under benign conditions. The scope this methodology encompasses variety substrates, delivering novel polycyclic four consecutive stereocenters bridged ring good to excellent yields remarkable enantioselectivities (≤1:99 er). approach facilitates structurally diverse molecules that retain integrity while introducing chirality. More importantly, 3ab significantly inhibited proliferation CESS Kasumin-1 cells IC50 values 0.76 0.28 μM, respectively. In addition, has been demonstrated as an effective agent promoting apoptosis cells.

Language: Английский

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Parametrization of κ²-N,O-Oxazoline Preligands for Enantioselective Cobaltaelectro-Catalyzed C–H Activations

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 4450 - 4459

Published: Feb. 28, 2025

Enantioselective electrocatalyzed C–H activations have emerged as a transformative platform for the assembly of value-added chiral organic molecules. Despite recent progress, construction multiple C(sp3)-stereogenic centers via C(sp3)–C(sp3) bond formation has thus far proven to be elusive. In contrast, we herein report an annulative activation strategy, generating Fsp3-rich molecules with high levels diastereo- and enantioselectivity. κ2-N,O-oxazoline preligands were effectively employed in enantioselective cobalt(III)-catalyzed reactions. Using DFT-derived descriptors regression statistical modeling, performed parametrization study on modularity preligands. The resulted model describing ligands' selectivity characterized by key steric, electronic, interaction behaviors.

Language: Английский

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C–H bond activation and sequential addition to two different coupling partners: a versatile approach to molecular complexity

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(15), P. 6738 - 6756

Published: Jan. 1, 2022

Sequential multicomponent C–H bond addition is a powerful approach for the rapid, modular generation of molecular complexity in single reaction.

Language: Английский

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Rhodium(III)-Catalyzed Enantioselective C–H Activation/Annulation of Ferrocenecarboxamides with Internal Alkynes

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(5), P. 3083 - 3093

Published: Feb. 21, 2022

Efficient synthesis of planar chiral ferrocene-fused heterocyclic molecules is challenging in asymmetric synthesis. Herein, we report an enantioselective C–H activation/annulation ferrocenecarboxamides with internal alkynes promoted by CpRh(III) catalysis. Trisubstituted Cp-derived Rh complexes are found to be enabling catalysts, which lead a broad substrate scope good functional group compatibility. Planar pyridone products obtained high yields (up 90%) excellent enantioselectivity 99% ee). Combined experimental and computational studies support the proposed reaction mechanism.

Language: Английский

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Three-Component Coupling of Arenes, Ethylene, and Alkynes Catalyzed by a Cationic Bis(phosphine) Cobalt Complex: Intercepting Metallacyclopentenes for C–H Functionalization

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(10), P. 4530 - 4540

Published: March 4, 2022

A cobalt-catalyzed intermolecular three-component coupling of arenes, ethylene, and alkynes was developed using the well-defined air-stable cationic bis(phosphine) cobalt(I) complex, [(dcype)Co(η6-C7H8)][BArF4] (dcype = 1,2-bis(dicyclohexylphosphino)ethane; BArF4 B[(3,5-(CF3)2)C6H3]4), as precatalyst. All three components were required for turnover formation ortho-homoallylated arene products. range directing groups including amide, ketone, 2-pyridyl substituents on promoted reaction. The method exhibited broad functional group tolerance allowing late-stage functionalization two drug molecules, fenofibrate haloperidol. series control reactions, deuterium labeling studies, resting state analysis, well synthesis substrate- product-bound η6-arene complexes supported a pathway involving C(sp2)–H activation from cobalt(III) metallacycle.

Language: Английский

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