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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Synergistic Palladium/Copper‐Catalyzed 1,4‐Difunctionalization of 1,3‐Dienes for Stereodivergent Construction of 1,5‐Nonadjacent Stereocenters

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(21)

Published: March 21, 2024

Abstract The construction of two distal stereocenters through a single catalytic process is great interest in organic synthesis. While there are some successful reports regarding stereodivergent preparation 1,3‐ or 1,4‐stereocenters, the more challenged 1,5‐nonadjacent have never been achieved fashion. Herein we describe synergistic palladium/copper catalysis for 1,4‐difunctionalization reactions 1,3‐dienes, providing access to quaternary stereocenters. Because each catalysts separately controlled one newly formed stereocenters, synthesis all four diastereomers products could readily be simply by choosing an appropriate combination chiral catalysts. Experimental and computational studies supported mechanism involving Heck/Tsuji–Trost cascade reaction, origins stereoselectivity were elucidated.

Language: Английский

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Stereodivergent Construction of 1,5/1,7‐Nonadjacent Tetrasubstituted Stereocenters Enabled by Pd/Cu‐Cocatalyzed Asymmetric Heck Cascade Reaction

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(35)

Published: May 16, 2024

Abstract The construction of chiral motifs containing nonadjacent stereocenters in an enantio‐ and diastereoselective manner has long been a challenging task synthetic chemistry, especially with respect to their stereodivergent synthesis. Herein, we describe protocol that enables the 1,5/1,7‐nonadjacent tetrasubstituted through Pd/Cu‐cocatalyzed Heck cascade reaction. Notably, C=C bond relay strategy involving shift π‐allyl palladium intermediate was successfully applied asymmetric 1,7‐nonadjacent stereocenters. current method allows for efficient preparation molecules bearing two privileged scaffolds, oxindoles non‐natural α‐amino acids, good functional group tolerance. full complement four stereoisomers products could be readily accessed by simple combination metal catalysts different enantiomers.

Language: Английский

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Stereodivergent Construction of 3,3′-Disubstituted Oxindoles via One-Pot Sequential Allylation/Alkylation and Its Application to the Total Synthesis of Trigolute B and D

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

The absolute and relative configurations of bioactive chiral molecules are typically relevant to their biological properties. It is thus highly important desirable construct all possible stereoisomers a lead candidate or given natural compound. Synergistic dual catalysis has been recognized as reliable synthetic strategy for variety predictable stereodivergent transformations. Despite the impressive progress made in this field, carbon-carbon bond-formation reactions involving stabilized nucleophiles remain elusive. Herein, we report an iridium- magnesium-catalyzed one-pot sequential allylic alkylation/nucleophilic alkylation cascade process synthesis four 3,3'-disubstituted oxindoles through three-component reaction. A diverse array products readily prepared with high functional group compatibility good yields excellent diastereo- enantioselectivities. Subsequently, total spirooxindole alkaloid trigolutes B D accomplished concise unified route using same set starting materials.

Language: Английский

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Iron- and Organo-Catalyzed Borrowing Hydrogen for the Stereoselective Construction of Tetrahydropyrans

Organic Letters, Journal Year: 2024, Volume and Issue: 26(27), P. 5788 - 5793

Published: June 27, 2024

Stereocontrolled oxa-Michael additions are challenging, given the high reversibility of process, which ultimately leads to racemization newly formed stereocenters. When iron-catalyzed borrowing hydrogen from allylic alcohols was combined with a stereocontrolled organocatalytic addition, wide array chiral tetrahydropyrans were efficiently prepared. The reaction could be performed in diastereoselective manner pre-existing stereocenters or enantioselectively achiral substrates. key success reactivity iron complex, selective for alcohol dehydrogenation and irreversibly led final product.

Language: Английский

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Copper/ruthenium relay catalysis enables 1,6-double chiral inductions with stereodivergence

Chemical Science, Journal Year: 2024, Volume and Issue: 15(26), P. 10135 - 10145

Published: Jan. 1, 2024

A stereodivergent synthesis of chiral ζ-hydroxy amino esters containing 1,6-stereocenters and a unique β,γ-unsaturation was developed through asymmetric Cu/Ru relay catalysis to conduct the borrowing hydrogenation/1,6-Michael addition protocol.

Language: Английский

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Asymmetric Relay Catalysis Enables Unreactive Allylic Alcohols to Participate in 1,3-Dipolar Cycloaddition of Azomethine Ylides

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

Current synthetic transformations occur readily with starting materials that possess both innate reactivity and steric accessibility or functional-group-oriented reactivity. However, achieving reactions inactive feedstock substrates remains significantly challenging normally requires cumbersome prior functional group manipulations. Herein, we report an unprecedented example of catalytic asymmetric 1,3-dipolar cycloaddition azomethine ylides nonactivated alkenes enabled by copper/ruthenium relay catalysis. Key to the success is temporary activation strategy initiated oxidative dehydrogenation inert allylic alcohols into electron-demanding reversed highly reactive enones, which triggers ensuing Cu-catalyzed followed reductive hydrogenation deliver functionalized chiral pyrrolidines construction two C-C bonds four well-defined stereogenic centers in atom-/step-economical redox-neutral manner. This method features mild reaction conditions, operational simplicity, broad substrate scope also characterized formal dynamic kinetic resolution. Mechanistic studies control experiments supported a typical borrowing-hydrogen cascade orthogonally merged revealed superiority reliability catalysis are controlled release but unstable enones impede undesired polymerization. It should be noted up stereoisomers otherwise inaccessible cyclobutanes could prepared through concise late-stage elaborations.

Language: Английский

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Iron/Rhodium Bimetallic Lewis Acid/Transition Metal Relay Catalysis for Alkynylation/Cyclotrimerization Sequential Reactions Toward Isoindolinone Derivatives from N,O-Cyclic Acetals

Catalysts, Journal Year: 2025, Volume and Issue: 15(2), P. 151 - 151

Published: Feb. 6, 2025

A novel sequential one-pot bimetallic catalytic system combining Fe(III)-catalyzed alkynylation and a Rh(I)-catalyzed [2+2+2] reaction was successfully developed. The σ-Lewis acid properties of iron (III) the π-Lewis rhodium (I) catalysts were unified in an unprecedented intermolecular alkynylation/cyclotrimerization process. Using this unique Fe/Rh relay system, variety benzo pyrridinoisoindolinone derivatives obtained under mild conditions from easily available N-(propargyl) hydroxy aminals, as simplest N-acyliminium ion precursors, several alkynes.

Language: Английский

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Manganese(I)-Catalyzed Enantioselective Formal Anti-Markovnikov Hydroalkoxylation of Racemic Allylic Alcohols: A Borrowing Hydrogen Access

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

An enantioselective manganese(I)-catalyzed formal anti-Markovnikov hydroalkoxylation of racemic allylic alcohols has been developed using a chiral N6-type macrocyclic ligand, affording wide range γ-alkoxypropyl in high isolated yields with excellent enantioselectivities. The synthetic utility this protocol was further proven by gram-scale synthesis γ-alkoxypropanol 3n and derivatization 3a to drug molecule, (S)-dapoxetine, for the treatment premature ejaculation erectile dysfunction. Mechanistic studies support that reaction proceeds via hydrogen-borrowing cascade pathway.

Language: Английский

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α,α-Difluorinated Allylsulfones: gem-Difluoroethylenyl Reagents for Synthesis of Fluorinated Chiral α-Quaternary Amino Acids

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

Among numerous fluorine-containing molecules, chiral gem-difluoroethylenes (C═CF2) exhibited unique properties in agrochemicals, pharmaceuticals, and materials science. However, the general synthetic methods were limited to functionalization/defluorination of trifluoromethylalkenes. Here, we disclose a new type difluoroethylenyl reagent, α,α-difluoro allylsulfones, which allows highly enantioselective Cu-catalyzed desulfonylative SN2′ substitution with benzylideneamino esters. This protocol presents novel strategy for construction diversified α-quaternary amino acid derivatives containing gem-difluoroethylene moiety excellent results (up 86% yield, generally 90–98% ee). The ease synthesis applications this protocol, transformations products revealed potential utility chemistry.

Language: Английский

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