Enantioselective Total Synthesis of (−)-Himalensine A via a Palladium and 4-Hydroxyproline Co-catalyzed Desymmetrization of Vinyl-bromide-tethered Cyclohexanones

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(9), P. 5422 - 5430

Published: Feb. 23, 2023

Herein, we describe the convergent enantioselective total synthesis of himalensine A in 18 steps, enabled by a highly enantio- and diastereoselective construction morphan core via palladium/hydroxy proline co-catalyzed desymmetrization vinyl-bromide-tethered cyclohexanones. The reaction pathway was illuminated density functional theory calculations, which support an intramolecular Heck situ-generated enamine intermediate, where exquisite enantioselectivity arises from carboxylate coordination to vinyl palladium species rate- enantio-determining carbopalladation steps. tolerates diverse N-derivatives, all-carbon quaternary centers, trisubstituted olefins, providing access molecular scaffolds found range complex natural products. Following large-scale preparation key substrate installation β-substituted enone moiety, rapid achieved using strategy based on amide coupling/Michael addition/allylation/ring-closing metathesis sequence allowed introduction three five rings only synthetic steps (after telescoping). Moreover, our provides new known tetracyclic late-stage intermediate that has been used previously many Daphniphyllum alkaloids.

Language: Английский

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Palladium‐Catalyzed Enantioselective C–H Arylations and Alkenylations of 2‐Aminobiaryls with Atmospheric Air as the Sole Oxidant

Angewandte Chemie International Edition, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Optically active 2-aminobiaryls are valuable chiral frameworks with broad applications in catalysis, synthetic chemistry, and materials science. Here, we present a simple practical methodology for their asymmetric synthesis via enantioselective palladium catalyzed C-H arylations or alkenylations of racemic precursors. The utilizes kinetic resolution strategy, producing two highly enantioenriched axially molecules: the C-C coupling product unreacted starting material. Notably, have established reaction conditions that enable situ regeneration Pd(II) catalyst using atmospheric air as sole oxidant. Finally, showcase utility this approach by preparing several derivatives relevant to field catalysis.

Language: Английский

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Palladium‐Catalyzed Enantioselective C–H Arylations and Alkenylations of 2‐Aminobiaryls with Atmospheric Air as the Sole Oxidant

Angewandte Chemie, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Abstract Optically active 2‐aminobiaryls are valuable chiral frameworks with broad applications in catalysis, synthetic chemistry, and materials science. Here, we present a simple practical methodology for their asymmetric synthesis via enantioselective palladium catalyzed C−H arylations or alkenylations of racemic precursors. The utilizes kinetic resolution strategy, producing two highly enantioenriched axially molecules: the C−C coupling product unreacted starting material. Notably, have established reaction conditions that enable situ regeneration Pd(II) catalyst using atmospheric air as sole oxidant. Finally, showcase utility this approach by preparing several derivatives relevant to field catalysis.

Language: Английский

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Enantioselective Synthesis of 1-Dihydrobenzazepines through Rh₂(II)-Catalyzed Cycloisomerization of 1,6-Enyne

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

The 1-dihydrobenzazepine skeleton has emerged as a privileged structural motif in bioactive molecules. However, due to lack of asymmetric methodology, access chiral 1-dihydrobenzazepines remained limited. Herein, we report the first intermolecular cycloisomerization benzo-fused enynes for synthesis via dirhodium catalysis. This methodology features high efficiency (up 98% yield), enantioselectivity 99% ee), and broad scope nucleophiles, including oxygen nucleophiles (alcohols, phenols, carboxylic acids) carbon (silyl enol ethers). Theoretical experimental mechanistic studies reveal that reaction pathway encompasses an cycloisomerization, which gives rise carbene containing donor–acceptor (D-A) cyclopropane moiety, followed by ring-opening process stereoselective nucleophilic attack external on cyclopropyl ring. Control experiments demonstrate pivotal role terminal group capped alkynyl substrates achieving good efficiency.

Language: Английский

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Axially Chiral 2-Hydroxybiaryls by Palladium-Catalyzed Enantioselective C–H Activation

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(21), P. 13994 - 13999

Published: Oct. 16, 2023

This article describes the discovery and development of a palladium-catalyzed asymmetric C–H olefination 2-hydroxybiaryls. The strategy allows direct assembly optically active, axially chiral 2-substituted-2′-hydroxybiaryls from readily available precursors demonstrates that native hydroxy unit substrates can work as an efficient directing group for activation. represents substantial advantage over other approaches require preinstallation metal coordinating units. simplicity approach versatility products allow practical synthesis broad variety active binaphthyl derivatives.

Language: Английский

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Novel Sulfinamide-Based Chiral Ligand Promoted Chiral Diarylmethanol Preparation via exo-Directed Asymmetric C–H Alkynylation under Mild Conditions

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 2540 - 2549

Published: Jan. 28, 2025

Language: Английский

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Chiral Osmium(II)/Salox Species Enabled Enantioselective γ‐C(sp³)−H Amidation: Integrated Experimental and Computational Validation For the Ligand Design and Reaction Development

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(20)

Published: March 19, 2024

Abstract Herein, multiple types of chiral Os(II) complexes have been designed to address the appealing yet challenging asymmetric C(sp 3 )−H functionalization, among which Os(II)/Salox species is found be most efficient for precise stereocontrol in realizing amidation. As exemplified by enantioenriched pyrrolidinone synthesis, such tailored catalyst efficiently enables an intramolecular site‐/enantioselective amidation γ‐position dioxazolone substrates, benzyl, propargyl and allyl groups bearing various substituted forms are well compatible, affording corresponding γ‐lactam products with good er values (up 99 : 1) diverse functionality (>35 examples). The unique performance advantage developed system terms catalytic energy profile induction has further clarified integrated experimental computational studies.

Language: Английский

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A palladium catalyzed asymmetric desymmetrization approach to enantioenriched 1,3-disubstituted isoindolines

Chemical Science, Journal Year: 2023, Volume and Issue: 14(40), P. 11267 - 11272

Published: Jan. 1, 2023

Herein, we report the first palladium/MPAA catalyzed enantioselective C-H activation/[4 + 1] annulation of diarylmethyltriflamide and olefins to construct chiral cis-1,3-disubstituted isoindoline derivatives. The use a readily accessible mono-N-protected amino acid as ligand improves efficiency enantioselectivity catalytic transformation. developed method provides access both enantiomers product using either d or l-phenylalanine derivative facilitating synthesis optically active 1,3-disubstituted

Language: Английский

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Secondary Cationic Interaction Driven Substrate Ligand Affinity for Pd(II)-Catalyzed Enantioselective C-H Activation of Ferrocenyl Amines

Published: April 12, 2024

Secondary amines as a directing group for C-H activation have limitations they are prone to undergo oxidation, allylic deamination, and β-hydride elimination. The fundamental challenge observed here is the competition between desired versus vulnerable β-C-H bond of secondary amine when substrate ligand affinity not strong enough. Herein, potential axially chiral NOBINAc revealed on accelerating enantioselective Pd(II)-catalyzed process ferrocenyl amines. Further, interaction cesium cation with sulfonate plays an impressive role in mitigating threat elimination via enhanced affinity. This approach resulted intermolecular annulation allenes, leading ferrocene fused tetrahydropyridines up 70% yields 98% ee.

Language: Английский

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Secondary Cationic Interaction Driven Substrate Ligand Affinity for Pd(II)-Catalyzed Enantioselective C-H Activation of Ferrocenyl Amines

Published: July 29, 2024

Secondary amines as a directing group for C-H activation have limitations they are prone to undergo oxidation, allylic deamination, and β-hydride elimination. The fundamental challenge observed here is the competition between desired versus vulnerable β-C-H bond of secondary amine when substrate ligand affinity not strong enough. Herein, potential axially chiral NOBINAc revealed accelerate enantioselective PdII-catalyzed process ferrocenyl amines. Further, interaction cesium cation with sulfonate plays an impressive role in mitigating threat elimination via enhanced affinity. This approach resulted activation, intermolecular annulation, alkenylation allenes activated olefines, leading ferrocene fused tetrahydropyridines alkenylated up 70% yields 99:1 er.

Language: Английский

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