Catalytic Enantioselective Sulfur Alkylation of Sulfenamides for the Asymmetric Synthesis of Sulfoximines

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(39), P. 17808 - 17814

Published: Sept. 26, 2022

Sulfoximines are increasingly incorporated in agrochemicals and pharmaceuticals, with the two enantiomers of chiral sulfoximines often having profoundly different binding interactions biomolecules. Therefore, their application to drug discovery development requires challenging preparation single rather than racemic mixtures. Here, we report a general fundamentally new asymmetric synthesis sulfoximines. The first S-alkylation sulfenamides, which readily accessible sulfur compounds one carbon nitrogen substituent, represents key step. A broad scope for was achieved by rhodium-catalyzed coupling diazo under mild conditions. When rhodium catalyst utilized loadings as low 0.1 mol %, products were obtained high yields enantiomeric ratios up 98:2 at newly generated center. efficiently converted variety complete retention stereochemistry. utility this approach further demonstrated complex sulfoximine agrochemical.

Language: Английский

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Transition-metal-catalyzed atroposelective synthesis of axially chiral styrenes

Chemical Communications, Journal Year: 2023, Volume and Issue: 59(85), P. 12669 - 12684

Published: Jan. 1, 2023

Recent advances in the asymmetric synthesis of axially chiral styrenes catalyzed by transition metals were summarized.

Language: Английский

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Electrooxidative Rhodium(III)/Chiral Carboxylic Acid‐Catalyzed Enantioselective C−H Annulation of Sulfoximines with Alkynes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(15)

Published: Jan. 30, 2024

Abstract The combination of achiral Cp*Rh(III) with chiral carboxylic acids (CCAs) represents an efficient catalytic system in transition metal‐catalyzed enantioselective C−H activation. However, this hybrid catalysis is limited to redox‐neutral activation reactions and the adopt oxidative remains elusive pose a significant challenge. Herein, we describe development electrochemical Cp*Rh(III)‐catalyzed annulation sulfoximines alkynes enabled by acid (CCA) operationally friendly undivided cell at room temperature. A broad range enantioenriched 1,2‐benzothiazines are obtained high yields excellent enantioselectivities (up 99 % yield 98 : 2 er). practicality method demonstrated scale‐up reaction batch reactor external circulation. crucial intermediate isolated, characterized, transformed, providing rational support for Rh(III)/Rh(I) electrocatalytic cycle.

Language: Английский

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Cobalt(III)-Catalyzed Enantioselective C–H Functionalization: Ligand Innovation and Reaction Development

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

ConspectusIn contrast to precious transition metals, such as palladium and rhodium, the development of novel chiral ligands for enantioselective C-H functionalizations catalyzed by earth-abundant, cost-effective, environmentally friendly 3d metals poses substantial challenges, primarily due variable oxidation states, intricate coordination patterns, limited mechanistic insights. In this Account, we summarize our research endeavors in three types Co(III) catalysis: pseudotetrahedral achiral Cp*Co(III)/chiral carbonyl acid (CCA) catalysis, situ-generated octahedral cobalt(III) via cobalt/salicyloxazoline (Salox) Co(II)/chiral phosphoric (CPA) cooperative achieved through strategic ligand design. Our initial objective was achieve functionalization Cp*Co(III) catalysts with external ligands, aiming circumvent laborious preparation CpxCo(III) complexes. To end, developed several CCA incorporating non-covalent interactions (NCIs) a crucial design element. Next, address limitations associated lengthy synthesis Cp-ligated complexes difficulties modification, explored concept situ generation catalysis using commercially available cobalt(II) salts tailor-made ligands. This exploration led two innovative catalytic systems, namely, Co(II)/Salox Co(II)/CCA sequential catalysis. The emerged versatile strategy, demonstrating excellent enantioselectivities across range asymmetric reactions construct various molecules central, axial, planar, inherent chirality. facile single step, along ease further enhances versatility applicability approach. Moreover, successfully applied cobalt/Salox electro- photochemical-catalyzed functionalization, electrons or oxygen traceless oxidant, thereby eliminating need stoichiometric chemical oxidants. Through studies reaction developments, elucidated detailed structure-enantioselectivity relationships which are expected inform future endeavors. Finally, Co(II)/CPA enabled spiro-γ-lactams olefination/asymmetric [4 + 1] spirocyclization. Mechanistically, establishment stereochemistry occurs during cyclization where CPA serves both neutral Brønsted acid, stereoinduction independent cleavage step. We anticipate that insights advancements Account will inspire innovations drive progress metal-catalyzed reactions.

Language: Английский

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Ru(II)/Chiral Carboxylic Acid-Catalyzed Asymmetric [4 + 3] Annulation of Sulfoximines with α,β-Unsaturated Ketones

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(22), P. 13876 - 13883

Published: Oct. 27, 2022

Sulfur-stereogenic containing benzo-fused heterocycles have gained much attention in drug discovery. However, the asymmetric synthesis of these chiral molecules with structural diversity is very challenging. Herein, we report benzothiadiazine-1-oxides a seven-membered ring via achiral Ru(II)-catalyzed [4 + 3] annulation sulfoximines α,β-unsaturated ketones assisted by carboxylic acid (CCA). A broad range benzothiadiazepine-1-oxides bearing various functional groups could be prepared up to 90% yield >99% ee, expanding chemical space sulfoximines. Notably, oxidative cleavage double bonds products gave N-benzoyl C–S axis.

Language: Английский

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Enantioselective Synthesis of 1,2‐Benzothiazine 1‐Imines via Ru^II/Chiral Carboxylic Acid‐Catalyzed C−H Alkylation/Cyclization

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(29)

Published: May 17, 2023

Sulfondiimines are diaza-analogues of sulfones with a chiral sulfur center. Compared to and sulfoximines, their synthesis transformations have so far been studied lesser extent. Here, we report the enantioselective 1,2-benzothiazine 1-imines, i.e., cyclic sulfondiimine derivatives from sulfondiimines sulfoxonium ylides via C-H alkylation/cyclization reactions. The combination [Ru(p-cymene)Cl2 ]2 newly developed spiro carboxylic acid is key achieving high enantioselectivity.

Language: Английский

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Pd-catalyzed asymmetric Larock reaction for the atroposelective synthesis of N─N chiral indoles

Science Advances, Journal Year: 2024, Volume and Issue: 10(19)

Published: May 10, 2024

Atropisomeric indoles defined by a N─N axis are an important class of heterocycles in synthetic and medicinal chemistry material sciences. However, they remain heavily underexplored due to limited methods challenging stereocontrol over the short bonds. Here, we report highly atroposelective access axially chiral via asymmetric Larock reaction. This protocol leveraged powerful role phosphoramidite ligand attenuate common dissociation original reaction, forming with excellent functional group tolerance high enantioselectivity palladium-catalyzed intermolecular annulation between readily available o -iodoaniline alkynes. The multifunctionality prepared allowed diverse post-coupling transformations, affording broad array functionalized indoles. Experimental computational studies have been conducted explore reaction mechanism, elucidating enantio-determining rate-limiting steps.

Language: Английский

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Synthesis of Chiral Sulfoximines via Iridium‐Catalyzed Regio‐ and Enantioselective C−H Borylation: A Remarkable Sidearm Effect of Ligand

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(6)

Published: Dec. 13, 2022

Transition metal-catalyzed enantioselective C-H activation of prochiral sulfoximines for non-annulated products remains a formidable challenge. We herein report iridium-catalyzed borylation N-silyl diaryl using well-designed chiral bidentate boryl ligand with bulky side arm. This method is capable accommodating broad range substrates under mild reaction conditions, affording vast array high enantioselectivities. also demonstrated the synthetic utility on preparative-scale diverse downstream transformations, including synthesis version bioactive molecules. Computational studies showed that arm confers regio- and enantioselectivity through steric effect.

Language: Английский

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Recent Advances in the Synthesis of Cyclic Sulfoximines via C–H Bond Activation

Molecules, Journal Year: 2023, Volume and Issue: 28(3), P. 1367 - 1367

Published: Feb. 1, 2023

Sulfoximines, a ubiquitous class of structural motifs, are widely present in bioactive molecules and functional materials that have received considerable attention from modern organic chemistry, pharmaceutical industries, science. Sulfoximines proved to be an effective directing group for C-H functionalization which was investigated the synthesis cyclic sulfoximines. Within last decade, great progress has been achieved Thus, this review highlights recent advances sulfoximines via activation strategy is classified based on substrate types.

Language: Английский

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Rhodium-catalyzed atroposelective access to trisubstituted olefinsviaC–H bond olefination of diverse arenes

Chemical Science, Journal Year: 2023, Volume and Issue: 14(29), P. 7999 - 8005

Published: Jan. 1, 2023

The atroposelective synthesis of axially chiral acyclic olefins remains a daunting challenge due to their relatively lower racemization barriers, especially for trisubstituted ones. In this work, C-H olefination has been realized open-chain via activation two classes (hetero)arenes in the coupling with sterically hindered alkynes. employment phenyl N-methoxycarbamates as arene reagents afforded phenol-tethered olefins, carbamate being traceless directing group. N-methoxy-2-indolylcarboxamides corresponding olefin by circumventing redox-neutral [4 + 2] annulation. reactions proceeded excellent Z/E selectivity, chemoselectivity, regioselectivity, and enantioselectivity both hydroarylation systems.

Language: Английский

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