Recent advances in Rh(i)-catalyzed enantioselective C–H functionalization

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(7), P. 3457 - 3484

Published: Jan. 1, 2024

Chiral carbon-carbon (C-C) and carbon-heteroatom (C-X) bonds are pervasive very essential in natural products, bioactive molecules, functional materials, their catalytic construction has emerged as one of the hottest research fields synthetic organic chemistry. The last decade witnessed vigorous progress Rh(I)-catalyzed asymmetric C-H functionalization a complement to Rh(II) Rh(III) catalysis. This review aims provide most comprehensive up-to-date summary covering recent advances activation for functionalization. In addition development diverse reactions, chiral ligand design mechanistic investigation (inner-sphere mechanism, outer-sphere 1,4-Rh migration) will also be highlighted.

Language: Английский

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Low Coordination State Rh^I‐Complex as High Performance Catalyst for Asymmetric Intramolecular Cyclopropanation: Construction ofpenta‐Substituted Cyclopropanes

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(10)

Published: Jan. 5, 2023

A simple, broad-scope rhodium(I)/chiral diene catalytic system for challenging asymmetric intramolecular cyclopropanation of various tri-substituted allylic diazoacetates was successfully developed. The low coordination state RhI -complex exhibits an extraordinarily high degree tolerance to the variation in extent substitution allyl double bond, thus allowing efficient construction a wide range penta-substituted, fused-ring cyclopropanes bearing three contiguous stereogenic centers, including two quaternary carbon stereocenters, highly enantioselective manner with ease at catalyst loading as 0.1 mol %. stereoinduction mode this -carbene-directed investigated by DFT calculations, indicating that π-π stacking interactions between aromatic rings chiral ligand and diazo substrate play key role control reaction enantioselectivity.

Language: Английский

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Asymmetric Cyclopropanation of Primary N-Vinylamides via Carbene Transfer Catalyzed by Cationic Rh(I)/Diene Complexes: An Unexpected Outer-Sphere Mechanism

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(12), P. 9385 - 9396

Published: June 6, 2024

A highly enantioselective intermolecular [2 + 1] cycloaddition of primary N-vinylamides with carbene intermediates was developed by taking advantage cationic rhodium(I)/diene catalysis under mild conditions at room temperature. This cyclopropanation method facilitates rapid access to enantioenriched cyclopropylamides, an important motif in drug discovery, generally good yields and high stereoselectivities (>20:1 dr, up 99% ee). approach employs a rhodium(I) catalyst form pre-equilibrium complex enamide substrate. Kinetic experiments comprehensive density functional theory (DFT) calculations were performed elucidate the reaction mechanism. The kinetic data DFT results support existence resting-state between two substrates. computational studies show that involves interesting, unexpected outer-sphere mechanistic pathway involving sole Rh(I) catalytic cycle major product reveal diazo decomposition step is rate-determining step.

Language: Английский

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Conformational Locking Induced Enantioselective Diarylcarbene Insertion into B−H and O−H Bonds Using a Cationic Rh(I)/Diene Catalyst

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(45)

Published: July 18, 2024

Abstract Transition‐metal‐catalyzed enantioselective transformations of aryl/aryl carbene are inherently challenging due to the difficulty in distinguishing between two arene rings reaction process thus remain largely less explored. The few successful examples reported so far, without exception, have all been catalyzed by Rh(II)‐complexes. Herein, we describe our development a novel cationic Rh(I)/chiral diene catalytic system capable efficient B−H and O−H insertions with diaryl diazomethanes, allowing access broad range gem ‐diarylmethine boranes ethers good yields high enantioselectivities. Notably, previously unattainable asymmetric diarylcarbene insertion into bond was achieved for first time. A remarkable feature this newly designed Rh(I)/diene catalyst bearing ortho ‐amidophenyl substitutents is that it can distinguish through stereochemically selective control π–π stacking interactions. DFT calculations indicate rotation‐restricted conformation complex played an important role highly transformations. This work provides interesting unprecedented stereocontrol mode metal

Language: Английский

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A combined experimental and computational study reveals a crossover between conventional cross-coupling and carbene insertion pathways in a Pd catalyzed C(sp²)–H insertion

Chemical Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Computational (DFT and DLPNO-CCSD(T)) calculations along with experimental tools (deuterium labelling, kinetic studies using VTNA, ESI-HRMS UV) are used to probe the mechanism of a Pd(ii)-catalyzed enantioselective carbene insertion into C(sp2)-H indole. Using deuterium labelling studies, we demonstrate intermediacy metal-hydride species, which contrasts mechanistic routes for other transition metals (Rh, Fe, Au, Cu, etc.). Our VTNA study reveals order be one in both diazo indole, microkinetic modelling aligns well computationally predicted mechanism. The is further supported by detection most stable intermediate catalytic cycle ESI-HRMS. An investigation origin stereoselectivity DLPNO-CCSD(T) presents new paradigm, wherein stereocontrol arises during formation Pd itself as opposed proton transfer steps found all metal catalysts.

Language: Английский

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A Unified Strategy for the Synthesis of Diverse Bicyclo[2.2.2]octadiene Ligands

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

Published: April 19, 2025

A new approach for the enantioselective synthesis of various bicyclo[2.2.2]octadiene ligands has been developed, which features a chiral oxazaborolidinium-catalyzed asymmetric Diels-Alder reaction to construct bicyclo[2.2.2]octane framework. The pivotal ketone 12 served as common intermediate that was finally transformed into desired C1- and C2-symmetric dienes. This work provides an alternative method reported diene would be beneficial exploration potentials this type versatile ligand in transformations.

Language: Английский

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Carbenoid Reactions Promoted by Solids: From Lewis to Brønsted Catalysts

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

Published: April 23, 2025

ConspectusDiazocarbonyl compounds have become essential tools in organic synthesis, due to their ability situ generate reactive carbenes and be inserted a variety of otherwise stable bonds, such as C-H, C-C, H-O, so on. However, soluble metal salt or complex catalyst is generally required selectively activate couple the carbene, metals employed far are expensive (Rh, Au, Ag, Cu) often unrecoverable. It noteworthy that price ligands can make cheaper (i.e., other ligand-free noble catalysts. In realm modern sustainable chemistry, most these methodologies now unacceptable must adapted, simple strategies for include carbene photoactivation use recoverable solid Unfortunately, despite research field insertion reactions has extended more than 50 years, examples with catalysts still minor, efficient only been reported last two decades.This Account shows journey faced by our group eight years find challenging reactions, employing diazocarbonyl precursors. We will contextualize results those previous The discovery 2017 quasi-linear Pd4 cluster stabilized within metal-organic framework (MOF) was able catalyze Büchner spurred design supported clusters reactions. Pd4-MOF could reused 20 times batch implemented flow process. Following this, catalytic solids, including Au Ag metals, not same MOF but also on oxides zeolites supports, showed good activity were reusable.Our temporarily finishes 2024 when "blank" experiments dealuminated zeolite surprisingly revealed this acid, without any metal, easily activates compound catalyzes thus providing cheap, commercially available, reusable Overall, rapid progress solid-catalyzed activation, formation, achieved during moving from difficult prepare based acid zeolites, pointing confined Brønsted acids study near future.

Language: Английский

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Catalyst-free electro-photochemical insertion reactions of carbene anion radicals by convergent paired electrolysis

Cell Reports Physical Science, Journal Year: 2024, Volume and Issue: 5(5), P. 101944 - 101944

Published: May 1, 2024

Paired electrolysis is an energy-efficient electrochemical reaction where both anodic and cathodic electron flow directly induces product formation with maximum faradaic efficiency. Herein we report a metal-free convergent pair electro-photochemical strategy to generate radical cation anion that resulted in the N-alkylation of various N-heterocycles, amines, sulfonamides. The also facilitated site-selective CH-alkylation benzo fused morpholine, indolines, OH- SH- alkylation phenols thiophenols aryl diazo esters. Mild condition such as 5 mA constant current W blue LED were sufficient complete within 2 h. Late-stage APIs sulfadiazines privileged scaffolds like sulfonamides diazepanes have been achieved successfully. This paired photo-electrolysis establishes new way achieve important reactions better productivity shorter time over existing strategies.

Language: Английский

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D₄-Symmetric Dirhodium Tetrakis(binaphthylphosphate) Catalysts for Enantioselective Functionalization of Unactivated C–H Bonds

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(28), P. 19460 - 19473

Published: July 3, 2024

Dirhodium tetrakis(2,2′-binaphthylphosphate) catalysts were successfully developed for asymmetric C–H functionalization with trichloroethyl aryldiazoacetates as the carbene precursors. The 2,2′-binaphthylphosphate (BNP) ligands modified by introduction of aryl and/or chloro functionality at 4,4′,6,6′ positions. As BNP are C2-symmetric, resulting dirhodium complexes expected to be D4-symmetric, but X-ray crystallographic and computational studies revealed this is not always case because internal T-shaped CH−π aryl–aryl interactions between ligands. optimum catalyst Rh2(S-megaBNP)4, 3,5-di(tert-butyl)phenyl substituents 4,4′ positions 6,6′ This adopts a D4-symmetric arrangement ideally suited site-selective unactivated tertiary sites high levels enantioselectivity, outperforming best tetracarboxylate reaction. standard reactions conducted loading 1 mol % lower loadings can used if desired, illustrated in cyclohexane 91% ee 0.0025 (29,400 turnover numbers). These further illustrate effectiveness donor/acceptor carbenes intermolecular expand toolbox available catalyst-controlled functionalization.

Language: Английский

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Enantioselective Si−H Insertion of Arylvinyldiazoesters Promoted by Rhodium(I)/Diene Complexes

Advanced Synthesis & Catalysis, Journal Year: 2024, Volume and Issue: 366(11), P. 2514 - 2518

Published: April 12, 2024

Abstract An enantioselective Si−H insertion between α‐arylvinyldiazoesters and silanes has been developed by employing rhodium(I)/chiral diene complex as the catalyst. This protocol offers a catalytic asymmetric approach to various chiral containing α‐arylvinyl functionality at room temperature with good enantiocontrol (89–99% ee). Transformation of resulting enantiomerically enriched α‐arylvinyl‐α‐silyl esters led variety other valuable building blocks. The deuterium kinetic isotope effect experiments revealed rhodium(I)‐mediated concerted mechanism.

Language: Английский

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