Diastereodivergent Desymmetric Annulation to Access Spirooxindoles: Chemical Probes for Mitosis

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(7), P. 4199 - 4207

Published: Feb. 13, 2023

Spirooxindoles have emerged as promising architectures for engineering biologically active compounds. The diastereodivergent construction of unique scaffolds this type with full control continuous chiral centers including an all-carbon quaternary stereogenic center is yet to be developed. Here, we report unprecedented desymmetric [3 + 3] annulation oxabicyclic alkenes enals enabled by N-heterocyclic carbene (NHC)/Rh cooperative catalysis, leading a series enantiomerically enriched spirooxindole lactones excellent enantioselectivities (up >99% ee) and diastereoselectivities >95:5 dr). combined catalyst system comprises rhodium complex that controls the configuration at electrophilic carbon NHC nucleophilic oxindole-containing carbon; thus, four stereoisomers products can readily obtained simply switching configurations two catalysts. Transformations spirooxindoles delivered synthetically useful Importantly, those arrested mammalian cells in mitosis exhibited potent antiproliferative activities against HeLa cells. Significantly, both absolute relative exert prominent effects on bioactivities, underscoring great importance catalytic asymmetric synthesis beyond creating tools exploration structure–activity relationships.

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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Cobalt-Catalyzed Domino Transformations via Enantioselective C–H Activation/Nucleophilic [3 + 2] Annulation toward Chiral Bridged Bicycles

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(22), P. 15576 - 15586

Published: May 16, 2024

Selective synthesis of chiral bridged (hetero)bicyclic scaffolds via asymmetric C–H activation constitutes substantial challenges due to the multiple reactivities strained bicyclic structures. Herein, we develop domino transformations through an unprecedented cobalt-catalyzed enantioselective activation/nucleophilic [3 + 2] annulation with symmetrical alkenes. The methods offer straightforward access a wide range molecules bearing [2.2.1]-bridged cores four and five consecutive stereocenters in single step. Two elaborate salicyloxazoline (Salox) ligands were synthesized based on rational design mechanistic understanding. well-defined pockets generated from coordination around trivalent cobalt catalyst direct orientation alkenes, leading excellent enantioselectivity.

Language: Английский

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Decarboxylative Alkylation of Morita–Baylis–Hillman Acetates with Aliphatic Acids via Photochemical Iron-Mediated Ligand-to-Metal Charge Transfer

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Carboxylic acids are bench-stable and readily available chemical feedstocks that function as optimal fundamental synthetic platforms for the construction of C(sp3)–C(sp3) bonds via decarboxylation processes. We present a novel practical protocol decarboxylative alkylation Morita–Baylis–Hillman acetates with various carboxylic photoinduced iron-mediated ligand-to-metal charge transfer (LMCT) process under redox-neutral conditions. This method exhibits remarkable tolerance to wide array acids, including primary, secondary, tertiary obviating requirement preactivated radical precursors. The preliminary mechanistic analyses indicate pathway is involved in this catalytic transformation.

Language: Английский

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Enantioselective C–H annulations enabled by either nickel- or cobalt-electrocatalysed C–H activation for catalyst-controlled chemodivergence

Nature Catalysis, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

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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Transition‐Metal‐Catalyzed Transformations Involving the Heck Reaction

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(15), P. 2436 - 2466

Published: June 12, 2023

Abstract Elaborated molecular architectures including complex carbocycles, heterocycles, and polycyclic structures represent an important class of organic compounds because they are ubiquitous structural units in a broad variety biologically pharmacologically relevant natural products, medicinal molecules, functional materials. A major challenge modern synthetic methodology is the development strategically efficient selective construction these from readily available starting Transition‐metal‐catalyzed transformations involving Heck reaction as pivotal step have afforded powerful approach for accessing sophisticated skeletons set easy‐to handle materials, thus highlighting its potential significance streamlining drug discovery process. Over past few decades, significant effort has been devoted to derivatives versatile routes, number direct strategies reported. In this review, latest advances transition‐metal‐catalyzed critical summarized, which could be divided into six categories: 1) Heck/Sonogashira tandem reaction; 2) Heck/Suzuki 3) Heck/Heck 4) Heck/Hiyama 5) Heck/Cacchi 6) Heck/C−H bond functionalization reaction.

Language: Английский

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Copper-catalyzed asymmetric allylic substitution of racemic/meso substrates

Chemical Science, Journal Year: 2024, Volume and Issue: 15(22), P. 8280 - 8294

Published: Jan. 1, 2024

The synthesis of enantiomerically pure compounds is a pivotal subject in the field chemistry, with enantioselective catalysis currently standing as primary approach for delivering specific enantiomers. Among these strategies, Cu-catalyzed asymmetric allylic substitution (AAS) significant and irreplaceable, especially when it comes to use non-stabilized nucleophiles (pK > 25). Although AAS prochiral substrates has also been widely developed, methodologies involving racemic/meso are highly desirable, undergo dynamic processes give single enantiomer products. Inspired by pioneering work Alexakis, Feringa Gennari groups, continuously employed deracemization desymmetrization enriched In this review, we mainly focus on developments over past two decades, providing an explicit outline ligands employed, scope nucleophiles, underlying their practical applications.

Language: Английский

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A synergistic Rh(I)/organoboron-catalysed site-selective carbohydrate functionalization that involves multiple stereocontrol

Nature Chemistry, Journal Year: 2022, Volume and Issue: 15(3), P. 424 - 435

Published: Dec. 30, 2022

Abstract Site-selective functionalization is a core synthetic strategy that has broad implications in organic synthesis. Particularly, exploiting chiral catalysis to control site selectivity complex carbohydrate functionalizations emerged as leading method unravel unprecedented routes into biologically relevant glycosides. However, robust catalytic systems available overcome multiple facets of stereoselectivity challenges this end still remain scarce. Here we report synergistic Rh(I)- and organoboron-catalysed protocol, which enables access synthetically challenging but arylnaphthalene Our depicts the employment Rh(I) site-selective showcases utility boronic acid compatible co-catalyst. Crucial success our judicious choice suitable organoboron catalyst. We also determine exquisite aspects stereocontrol, including enantio-, diastereo-, regio- anomeric dynamic kinetic resolution, are concomitantly operative.

Language: Английский

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Transition‐Metal‐Catalyzed Directing Group Assisted (Hetero)aryl C−H Functionalization: Construction of C−C/C‐Heteroatom Bonds

The Chemical Record, Journal Year: 2021, Volume and Issue: 21(12), P. 3758 - 3778

Published: June 23, 2021

Abstract Transition‐metal‐catalyzed C−H functionalization is one of the fascinating scientific fronts in organic synthesis for formation conjugated arenes and has emerged as a benchmark to revolutionize synthetic enterprise since past decades. In this realm, chelation‐guided bonds using an exogenous directing group received considerable attention recently expedient regioselective construction C−C C‐heteroatom efficient sustainable alternative. This article outlines our contribution towards wide variety transformations that have been achieved by directed through fine tuning catalytic systems.

Language: Английский

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