Synergistic Pd/Cu-Catalyzed 1,5-Double Chiral Inductions

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 9241 - 9251

Published: March 19, 2024

Much attention has been focused on the catalytic asymmetric creation of single chiral centers or two adjacent stereocenters. However, construction nonadjacent stereocenters is significant importance but challenging because lack remote induction models. Herein, based a C═C bond relay strategy, we report synergistic Pd/Cu-catalyzed 1,5-double model. All four stereoisomers target products bearing 1,5-nonadjacent involving both allenyl axial and central chirality could be obtained divergently by simply changing combination catalysts with different configurations. Control experiments DFT calculations reveal novel mechanism 1,5-oxidative addition, contra-thermodynamic η3-allyl palladium shift, conjugate nucleophilic substitution, which play crucial roles in control reactivity, regio-, enantio-, diastereoselectivity. It expected that this strategy may provide general protocol for synthesis structural motifs distant

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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Palladium-Catalyzed Allylic Alkylation Reactions of Nucleophilic Allenones: Asymmetric Allylic Alkylation, Z/E Divergent Allylic Alkylation, and [5 + 2] Annulation

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(13), P. 9940 - 9954

Published: June 19, 2024

Metal-catalyzed allenylic substitution reactions where allenes serve as electrophilic precursors have been recognized a rapid way for novel allene construction. On the contrary, chemistry in which act nucleophiles has far less investigated, especially powerful platform such metal-catalyzed allylic alkylation reactions. We herein describe two unprecedented palladium-catalyzed of an nucleophile. In first reaction, using vinyloxazolidinones allyl precursor, asymmetric allylation trisubstituted allenones worked well to prepare array axially chiral tetrasubstituted allenes. Mechanistic studies and density functional theory (DFT) calculations indicated that weak hydrogen-bonding interaction between acidic C(sp2)–H allenone nitrogen anion π-azaallyl-Pd species is key success stereocontrol. This reaction revealed intriguing reactivity nucleophilic time. second with use allenylethylene carbonates π-oxyallyl-Pd precursors, presented unique under different conditions provide divergent synthetic access (E)- (Z)-allenyl diene products. Interestingly, subsequent sequential intramolecular cyclization/isomerization (Z)-product delivered dihydrooxepine derivatives [5 + 2] annulation

Language: Английский

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Nickel-Catalyzed Asymmetric Propargylation for the Synthesis of Axially Chiral 1,3-Disubstituted Allenes

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(46), P. 21022 - 21029

Published: Nov. 10, 2022

The general enantioselective catalytic synthesis of axially chiral 1,3-disubstituted allenes from readily available racemic propargylic alcohol derivatives remains a long-standing challenge in organic synthesis. Here we report an efficient nickel-catalyzed asymmetric substitution reaction/Myers rearrangement carbonates that furnishes series enantioenriched using newly designed N-sulfonylhydrazone reagents as diazo surrogates. This reaction proved to be remarkably with regard substrate scope, affording diverse range allenic compounds good yields excellent enantioselectivities. Additionally, applications this powerful strategy for the methyl (S)-8-hydroxyocta-5,6-dienoate, (S)-laballenic acid, (S)-phlomic and (S)-Δ9,10-pentacosadiene are described, further highlighting broad potential these new discovery novel reactions.

Language: Английский

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Three-Component Approach to Densely Functionalized Trifluoromethyl Allenols by Asymmetric Organocatalysis

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(18), P. 10001 - 10006

Published: April 26, 2023

We have developed a new three-component catalytic coupling reaction of alkynyl boronates, diazomethanes, and aliphatic/aromatic ketones in the presence BINOL derivatives. The proceeds with remarkably high enantio- diastereoselectivity (up to three contiguous stereocenters) affording tertiary CF3-allenols single operational step. under mild, neutral, metal-free conditions, which leads level functional group tolerance.

Language: Английский

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Alkyl amines and ethers as traceless hydride donors in [1,5]-hydride transfer cascade reactions

Organic & Biomolecular Chemistry, Journal Year: 2023, Volume and Issue: 21(4), P. 700 - 714

Published: Jan. 1, 2023

The use of alkyl amines and ethers as traceless hydride donors in [1,5]-hydride transfer cascade reactions has been reviewed herein.

Language: Английский

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DeepSA: a deep-learning driven predictor of compound synthesis accessibility

Journal of Cheminformatics, Journal Year: 2023, Volume and Issue: 15(1)

Published: Nov. 2, 2023

With the continuous development of artificial intelligence technology, more and computational models for generating new molecules are being developed. However, we often confronted with question whether these compounds easy or difficult to synthesize, which refers synthetic accessibility compounds. In this study, a deep learning based model called DeepSA, was proposed predict synthesis compounds, provides useful tool choose molecules. DeepSA is chemical language that developed by training on dataset 3,593,053 using various natural processing (NLP) algorithms, offering advantages over state-of-the-art methods having much higher area under receiver operating characteristic curve (AUROC), i.e., 89.6%, in discriminating those synthesize. This helps users select less expensive synthesis, reducing time cost required drug discovery development. Interestingly, comparison Graph Attention-based method shows SMILES alone can also efficiently visualize extract compound's informative features. available online below web server ( https://bailab.siais.shanghaitech.edu.cn/services/deepsa/ ) our group, code at https://github.com/Shihang-Wang-58/DeepSA .

Language: Английский

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Assembly of Diverse Allenes via Activator-Free Palladium-Catalyzed Regioselective γ-Arylation of Propargylamines with Boronic Acids

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

Published: Feb. 7, 2025

Controlling the reaction selectivity to achieve a precision synthesis is constant concern for chemists. Here, we report palladium-catalyzed deaminative coupling of propargylamines with arylboronic acids generate allene skeletons. Importantly, this approach allows regioselective γ-arylation unactivated propargyl tertiary amines access various allenes in absence amino-activating reagents. We present wide range and boronic demonstrate synthetic application target products construct valuable compounds.

Language: Английский

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“Cesium Effect”-Mediated/Controlled Divergent Synthesis via Synergistic Pd/Cu-Catalyzed Cascade Reactions

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 8390 - 8402

Published: May 5, 2025

Language: Английский

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