Enantioselective Nickel-Electrocatalyzed Reductive Propargylic Carboxylation with CO₂

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(21), P. 14864 - 14874

Published: May 16, 2024

The exploitation of carbon dioxide (CO2) as a sustainable, plentiful, and harmless C1 source for the catalytic synthesis enantioenriched carboxylic acids has long been acknowledged pivotal task in synthetic chemistry. Herein, we present current-driven nickel-catalyzed reductive carboxylation reaction with CO2 fixation, facilitating formation C(sp3)–C(sp2) bonds by circumventing handling moisture-sensitive organometallic reagents. This electroreductive protocol serves practical platform, paving way propargylic (up to 98% enantiomeric excess) from racemic carbonates CO2. efficacy this transformation is exemplified its successful utilization asymmetric total (S)-arundic acid, (R)-PIA, (S)-chizhine D, (S)-cochlearin G, (S,S)-alexidine, thereby underscoring potential electrosynthesis achieve complex molecular architectures sustainably.

Language: Английский

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Photoredox/Cr-catalyzed enantioselective radical-polar crossover transformation via C-H functionalization

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 4, 2025

Asymmetric multicomponent reactions that aim to control multiple chiral centers with high selectivity in a single step remain an on-gonging challenge. The realm of enantioselective radical-polar crossover transformation achieved through C-H Functionalization has yet be fully explored. Herein, we present successful description photoredox/Cr-catalyzed three-component (hetero)arylalkylation 1,3-dienes functionalization. A diverse array homoallylic alcohols could obtained good excellent yields, accompanied by outstanding enantioselectivity. asymmetric build two simultaneously and demonstrates broad substrate tolerance, accommodating various drug-derived aldehydes, (hetero)aromatics, 1,3-diene derivatives. Preliminary mechanistic studies indicate the involvement radical intermediate, allylic chromium species reacting aliphatic aromatic aldehydes Zimmerman–Traxler transition states enabled dual photoredox catalysis. ongoing Here, authors photoredox- chromium-catalyzed

Language: Английский

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Asymmetric 1,4-functionalization of 1,3-enynes via dual photoredox and chromium catalysis

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 26, 2022

Abstract The merger of photoredox and transition-metal catalysis has evolved as a robust platform in organic synthesis over the past decade. stereoselective 1,4-functionalization 1,3-enynes, prevalent synthon synthetic chemistry, could afford valuable chiral allene derivatives. However, tremendous efforts have been focused on ionic reaction pathway. radical-involved asymmetric 1,3-enynes remains prominent challenge. Herein, we describe three-component 1,4-dialkylation via dual chromium to provide allenols. This method features readily available starting materials, broad substrate scope, good functional group compatibility, high regioselectivity, simultaneous control axial central chiralities. Mechanistic studies suggest that this proceeds through redox-neutral

Language: Английский

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Merging Carbonyl Addition with Photocatalysis

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(8), P. 1135 - 1147

Published: March 31, 2022

The carbonyl group stands as a fundamental scaffold and plays ubiquitous role in synthetically important chemical reactions both academic industrial contexts. Venerable transformations, including the aldol reaction, Grignard Wittig Nozaki-Hiyama-Kishi constitute vast empowering synthetic arsenal. Notwithstanding, two-electron mechanisms inherently confine breadth of accessible reactivity topological patterns.Fostered by rapid development photoredox catalysis, combing well-entrenched addition radicals can harness several unique increasingly sustainable transformations. In particular, unusual carbon-carbon carbon-heteroatom disconnections, which are out reach chemistry, be conceived. To meet this end, novel strategy toward utilization simple compounds intermolecular radical acceptors was developed. reaction is enabled visible-light photoredox-initiated hole catalysis. situ Brønsted acid activation moiety prevents β-scission from occurring. Furthermore, regioselective alkyl obviates use metals, ligands, or additives, thus offering high degree atom economy under mild conditions. On basis same concept work Schindler co-workers, carbonyl-olefin cross-metathesis, induced visible light, has also been achieved, leveraging Prins-elimination sequence.Recently, dual chromium catalysis developed us Kanai, complementary approach to revered reaction. Leveraging intertwined synergy between light metal, radical-to-polar crossover transformations eminent molecular motifs have Reactions such redox-neutral allylation aldehydes alkylation harvest power enable catalytic metal. Overall, exquisite levels diastereoselectivity enforced via highly compact transition states. Other examples, dialkylation 1,3-dienes propargylation portray versatile combination multicomponent coupling endeavors. Highly valuable motifs, commonly occur complex drug natural product architectures, now accessed single operational step. Going beyond addition, seminal contributions Fagnoni MacMillan preconized photocatalytic HAT-based acyl formation key aldehyde valorization strategy. Our articulated concept, carboxy hydrogen abstractors regio- chemoselective alkynylation trifluoromethylthiolation.This Account, narrative our others' at interface radical-based photochemistry, aims provide core guiding foundations disruptive developments. We envisage that extending crossovers manifolds, taming less-activated carbonyls, processes, merging electron steps with energy-transfer events will propel breakthroughs near future.

Language: Английский

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Metal-Catalyzed Enantioconvergent Transformations

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(20), P. 11817 - 11893

Published: Oct. 4, 2023

Enantioconvergent catalysis has expanded asymmetric synthesis to new methodologies able convert racemic compounds into a single enantiomer. This review covers recent advances in transition-metal-catalyzed transformations, such as radical-based cross-coupling of alkyl electrophiles with nucleophiles or alkylmetals and reductive two mainly under Ni/bis(oxazoline) catalysis. C–H functionalization can be performed an enantioconvergent manner. Hydroalkylation alkenes, allenes, acetylenes is alternative reactions. Hydrogen autotransfer been applied amination alcohols C–C bond forming reactions (Guerbet reaction). Other metal-catalyzed involve addition allylic systems carbonyl compounds, propargylation phenols, 3-bromooxindoles, allenylation allenolates propargyl bromides, hydroxylation 1,3-dicarbonyl compounds.

Language: Английский

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Enantio‐ and Diastereoselective Synthesis of Chiral Tetrasubstituted α‐Amino Allenoates Bearing a Vicinal All‐Carbon Quaternary Stereocenter with Dual‐Copper‐Catalysis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(31)

Published: June 1, 2023

The skeletons of chiral tetrasubstituted allenes bearing a vicinal all-carbon quaternary stereocenter are importance but still challenging to synthesize. Herein, we report enantio- and diastereoselective γ-additions 1-alkynyl ketimines with dual-copper-catalysis under mild conditions, affording α-amino allenoates in high yields (up 99 % yield) excellent enantioselectivities ee) diastereoselectivities >20 : 1 dr). Importantly, the stereodivergent synthesis products was realized by asymmetric γ-addition reaction Grignard reagent promoted epimerization. Moreover, dual-copper-catalyzed reactions were smoothly applied gram-scale adopted introduce allenyl moieties into bioactive molecules. Mechanistic experiments density functional theory (DFT) calculations demonstrated that catalyzed double copper catalysts.

Language: Английский

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Asymmetric α-allylic allenylation of β-ketocarbonyls and aldehydes by synergistic Pd/chiral primary amine catalysis

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 22, 2023

We herein describe an asymmetric α-allylic allenylation of β-ketocarbonyls and aldehydes with 1,3-enynes. A synergistic chiral primary amine/Pd catalyst was identified to facilitate the utilization 1,3-enynes as atom-economic achiral allene precursors. The catalysis enables construction all-carbon quaternary centers-tethered allenes bearing non-adjacent 1,3-axial central stereogenic centers in high level diastereo- enantio-selectivity. By switching configurations ligands aminocatalysts, diastereodivergence can be achieved any four diastereoisomers accessed enantio- selectivity.

Language: Английский

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A Radical Approach for Asymmetric α-C–H Addition of N-Sulfonyl Benzylamines to Aldehydes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(8), P. 5316 - 5323

Published: Feb. 16, 2024

Efficient synthesis of enantioenriched amines is great importance due to their significant synthetic and biological applications. Photoredox-mediated asymmetric α-amino C(sp3)–H functionalization offers an atom-economical sustainable approach access chiral amines. However, the development analogous reactions in its early stages, generally affording with a single stereocenter. Herein, we present novel synergistic triple-catalysis for α-C–H addition readily available N-sulfonyl aldehydes under mild conditions. This method allows efficient diverse array valuable β-amino alcohols bearing vicinal stereocenters. Unlike previous reports, our protocol employs radical using earth-abundant Cr catalysis. Quinuclidine plays dual role by facilitating highly selective hydrogen-atom transfer generate radicals promoting dissociation Cr–O bond, which crucial overall catalytic cycle as evidenced control, NMR, DFT experiments. Preliminary mechanistic studies, including trapping, nonlinear effect, Stern–Volmer plot, kinetic isotope Hammett offer insights into reaction pathway.

Language: Английский

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Electrocatalytic Asymmetric Nozaki–Hiyama–Kishi Decarboxylative Coupling: Scope, Applications, and Mechanism

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(7), P. 4872 - 4882

Published: Feb. 7, 2024

The first general enantioselective alkyl-Nozaki-Hiyama-Kishi (NHK) coupling reactions are disclosed herein by employing a Cr-electrocatalytic decarboxylative approach. Using easily accessible aliphatic carboxylic acids (via redox-active esters) as alkyl nucleophile synthons, in combination with aldehydes and enabling additives, chiral secondary alcohols produced good yield high enantioselectivity under mild reductive electrolysis. This reaction, which cannot be mimicked using stoichiometric metal or organic reductants, tolerates broad range of functional groups is successfully applied to dramatically simplify the synthesis multiple medicinally relevant structures natural products. Mechanistic studies revealed that this asymmetric e-NHK reaction was enabled catalytic tetrakis(dimethylamino)ethylene, acts key mediator mediate electroreduction Cr

Language: Английский

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Recent advances in the metal-catalyzed asymmetric synthesis of chiral allenes

Organic Chemistry Frontiers, Journal Year: 2022, Volume and Issue: 9(18), P. 5053 - 5073

Published: Jan. 1, 2022

Recent advances in the metal-catalyzed asymmetric synthesis of chiral allenes are summarized. This review is categorized based on starting material, including alkynes, racemic allenes, and conjugated dienes.

Language: Английский

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