Design principles of the use of alkynes in radical cascades

Nature Reviews Chemistry, Journal Year: 2023, Volume and Issue: 7(6), P. 405 - 423

Published: March 28, 2023

Language: Английский

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Palladium (II)‐Catalyzed C−H Activation with Bifunctional Ligands: From Curiosity to Industrialization

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(19)

Published: Feb. 29, 2024

Abstract In 2001, our curiosity to understand the stereochemistry of C−H metalation with Pd prompted first studies in Pd(II)‐catalyzed asymmetric activation (RSC Research appointment: 020 7451 2545, Grant: RG 36873, Dec. 2002). We identified four central challenges: 1. poor reactivity simple salts native substrates; 2. few strategies control site selectivity for remote bonds; 3. lack chiral catalysts achieve enantioselectivity via metalation, and 4. low practicality due limited coupling partner scope use specialized oxidants. These challenges necessitated new catalyst reaction development. For , we developed approaches enhance substrate–catalyst affinity together novel bifunctional ligands which participate accelerate cleavage step. site‐selectivity introduced concept systematically modulating distance geometry between a directing template, catalyst, substrate selectively access bonds. devised predictable stereomodels catalyst‐controlled enantioselective based on participation ligands. Finally, have varied catalytic manifolds Pd(II) accommodate diverse partners while employing practical oxidants such as peroxides. advances culminated numerous reactions, setting stage broad industrial applications.

Language: Английский

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Remote site-selective arene C–H functionalization enabled by N-heterocyclic carbene organocatalysis

Nature Catalysis, Journal Year: 2024, Volume and Issue: 7(8), P. 900 - 911

Published: July 11, 2024

Language: Английский

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Late-stage meta-C–H alkylation of pharmaceuticals to modulate biological properties and expedite molecular optimisation in a single step

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 18, 2024

Catalysed C-H activation has emerged as a transformative platform for molecular synthesis and provides new opportunities in drug discovery by late-stage functionalisation (LSF) of complex molecules. Notably, small aliphatic motifs have gained significant interest medicinal chemistry their beneficial properties applications sp

Language: Английский

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Pd-catalyzed regioselective activation of C(sp²)–H and C(sp³)–H bonds

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Differentiating between two highly similar C-H bonds in a given molecule remains fundamental challenge synthetic organic chemistry. Directing group assisted strategies for the functionalisation of proximal has been known last few decades. However, distal bond is strenuous and requires distinctly specialised techniques. In this review, we summarise advancement Pd-catalysed C(sp

Language: Английский

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Photo‐Induced Ruthenium‐Catalyzed Double Remote C(sp²)−H / C(sp³)−H Functionalizations by Radical Relay

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(32)

Published: May 9, 2022

Distal C(sp2 )-H and C(sp3 functionalizations have recently emerged as step-economical tools for molecular synthesis. However, while the )-C(sp3 ) construction is of fundamental importance, its formation through double remote )-H/C(sp3 activation has proven elusive. By merging ruthenium-catalyzed meta-C(sp2 functionalization with an aliphatic hydrogen atom transfer (HAT) process, we, herein, describe catalyzed twofold via photo-induced ruthenium-mediated radical relay. Thus, arene bonds alkane were activated by a single catalyst in operation. This process was accomplished at room temperature visible light-notably without exogenous photocatalysts. Experimental computational theory studies uncovered manifold comprising ortho-C-H activation, single-electron-transfer (SET), 1,n-HAT (n=5-7) σ-activation means ruthenium(II) catalyst.

Language: Английский

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Functionalized Cycloolefin Ligand as a Solution to Ortho-Constraint in the Catellani-Type Reaction

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(8), P. 4871 - 4881

Published: Feb. 16, 2023

The Catellani reaction, i.e., the Pd/norbornene (NBE) catalysis, has been evolved into a versatile approach to multisubstituted arenes via ortho-functionalization/ipso-termination process of haloarene. Despite significant advances over past 25 years, this reaction still suffered from an intrinsic limitation in substitution pattern haloarene, referred as "ortho-constraint". When ortho substituent is absent, substrate often fails undergo effective mono ortho-functionalization process, and either ortho-difunctionalization products or NBE-embedded byproducts predominate. To tackle challenge, structurally modified NBEs (smNBEs) have developed, which were proved for ortho-aminative, -acylative, -arylative reactions ortho-unsubstituted haloarenes. However, strategy incompetent solving ortho-constraint with ortho-alkylation, date there lacks general solution challenging but synthetically useful transformation. Recently, our group developed Pd/olefin unstrained cycloolefin ligand served covalent catalytic module enable ortho-alkylative without NBE. In work, we show that chemistry could afford new reaction. A functionalized bearing amide internal base was designed, allowed iodoarenes suffering before. Mechanistic study revealed capable both accelerating C-H activation inhibiting side reactions, accounts its superior performance. present work showcased uniqueness catalysis well power rational design metal catalysis.

Language: Английский

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Biocatalytic control of site-selectivity and chain length-selectivity in radical amino acid halogenases

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(12)

Published: March 13, 2023

Biocatalytic C-H activation has the potential to merge enzymatic and synthetic strategies for bond formation. FeII/αKG-dependent halogenases are particularly distinguished their ability both control selective as well direct group transfer of a bound anion along reaction axis separate from oxygen rebound, enabling development new transformations. In this context, we elucidate basis selectivity enzymes that perform halogenation yield 4-Cl-lysine (BesD), 5-Cl-lysine (HalB), 4-Cl-ornithine (HalD), allowing us probe how site-selectivity chain length achieved. We now report crystal structure HalB HalD, revealing key role substrate-binding lid in positioning substrate C4 vs C5 chlorination recognition lysine ornithine. Targeted engineering further demonstrates these selectivities can be altered or switched, showcasing develop biocatalytic applications.

Language: Английский

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Close‐Shell Reductive Elimination versus Open‐Shell Radical Coupling for Site‐Selective Ruthenium‐Catalyzed C−H Activations by Computation and Experiments

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(22)

Published: Feb. 27, 2023

Ruthenium-catalyzed σ-bond activation-assisted meta-C-H functionalization has emerged as a useful tool to forge distal C-C bonds. However, given the limited number of mechanistic studies, clear understanding origin site-selectivity and complete reaction pattern is not available. Here, we present systematic computational studies on ruthenium-catalyzed C-H with primary, secondary, tertiary alkyl bromides aryl bromides. The scission formation were carefully examined. Monocyclometalated ruthenium(II) complexes identified active species, which then underwent inner-sphere single electron transfer (ISET) activate organic results from competition between close-shell reductive elimination open-shell radical coupling. Based this understanding, multilinear regression model was built predict site-selectivity, further validated by experiments.

Language: Английский

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Late‐Stage C−H Activation of Drug (Derivative) Molecules with Pd(ll) Catalysis

Chemistry - A European Journal, Journal Year: 2023, Volume and Issue: 29(71)

Published: Oct. 17, 2023

Abstract This review comprehensively analyses representative examples of Pd(II)‐catalyzed late‐stage C−H activation reactions and demonstrates their efficacy in converting bonds at multiple positions within drug (derivative) molecules into diverse functional groups. These transformative hold immense potential medicinal chemistry, enabling the efficient selective functionalization specific sites molecules, thereby enhancing pharmacological activity expanding scope candidates. Although notable articles have focused on drug‐like using transition‐metal catalysts, reviews specifically focusing Pd(II) catalysts are required owing to prominence as most widely utilized metal for ability introduce a myriad groups bonds. The utilization Pd‐catalyzed methodologies impressive success introducing various groups, such cyano (CN), fluorine (F), chlorine (Cl), aromatic rings, olefin, alkyl, alkyne, hydroxyl with high regioselectivity functional‐group tolerance. breakthroughs serve invaluable tools discovery development, offering strategic options optimize candidates drive exploration innovative therapeutic solutions.

Language: Английский

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