Synergistic Dual Catalysis in Stereodivergent Synthesis

ACS Catalysis, Год журнала: 2024, Номер 14(6), С. 3812 - 3844

Опубликована: Фев. 23, 2024

Chiral skeletons with multiple stereogenic centers widely reside in nature and drugs, their relative absolute configuration often determine physiological or pharmacological properties. Stereodivergent synthesis of chiral molecules is not only great significance, but also highly challenging since the formation one diastereomers inherently preferred most asymmetric reactions. dual catalysis, introduced 2013 by Carreira group, perfectly catered to all requirements for full stereoselectivity control given reactions two catalysts are utilized a synergistic way act independently, has now been arguably efficient strategy realize stereodivergent synthesis. This comprehensive review presents an overview development enabled catalysis past ten years, providing readers fundamental attributes as well ability, scope, mechanism, limitations this strategy.

Язык: Английский

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

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(13), С. 9241 - 9251

Опубликована: Март 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

Язык: Английский

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Copper/Ruthenium Relay Catalysis for Stereodivergent Access to δ‐Hydroxy α‐Amino Acids and Small Peptides

Angewandte Chemie International Edition, Год журнала: 2023, Номер 63(7)

Опубликована: Дек. 29, 2023

Abstract An atom‐ and step‐economical redox‐neutral cascade reaction enabled by asymmetric bimetallic relay catalysis merging a ruthenium‐catalyzed borrowing‐hydrogen with copper‐catalyzed Michael addition has been realized. A variety of highly functionalized 2‐amino‐5‐hydroxyvaleric acid esters or peptides bearing 1,4‐non‐adjacent stereogenic centers have prepared in high yields excellent enantio‐ diastereoselectivity. Judicious selection rational modification the Ru catalysts careful tuning conditions played pivotal role stereoselectivity control as well attenuating undesired α‐epimerization, thus enabling full complement all four stereoisomers that were otherwise inaccessible previous work. Concise stereodivergent synthesis key intermediates for biologically important chiral molecules further showcases synthetic utility this methodology.

Язык: 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, Год журнала: 2024, Номер 63(21)

Опубликована: Март 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.

Язык: Английский

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Ligand-Controlled, Nickel-Catalyzed Stereodivergent Construction of 1,3-Nonadjacent Stereocenters

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(22), С. 15453 - 15463

Опубликована: Май 25, 2024

In contrast to the asymmetric synthesis of molecules with a single stereocenter or 1,2-adjacent stereocenters, simultaneous construction acyclic 1,3-nonadjacent stereocenters via catalyst in an enantioselective and diastereoselective manner remains formidable challenge. Here, we demonstrate diastereodivergent through Ni-catalyzed reductive cyclization/cross-coupling alkene-tethered aryl bromides α-bromoamides, which represents major remaining stereochemical challenge cyclization/difunctionalization alkenes. Using Ming-Phos as ligand, diverse set oxindoles containing were obtained high levels enantio- diastereoselectivity. Mechanistic experiments density functional theory calculations indicate that magnesium salt plays key role controlling Furthermore, another complementary stereoisomeric products constructed from same starting materials using Ph-Phox ligand.

Язык: 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, Год журнала: 2024, Номер 63(35)

Опубликована: Май 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.

Язык: 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, Год журнала: 2025, Номер unknown

Опубликована: Янв. 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.

Язык: Английский

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Modular access to chiral bridged piperidine-γ-butyrolactones via catalytic asymmetric allylation/aza-Prins cyclization/lactonization sequences

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 2, 2024

Abstract Chiral functionalized piperidine and lactone heterocycles are widely spread in natural products drug candidates with promising pharmacological properties. However, there remains no general asymmetric methodologies that enable rapid assemble both critical biologically important units into one three-dimensional chiral molecule. Herein, we describe a straightforward relay strategy for the construction of enantioenriched bridged piperidine-γ-butyrolactone skeletons incorporating three skipped stereocenters via allylic alkylation aza -Prins cyclization/lactonization sequences. The excellent enantioselectivity control allylation simplest precursor is enabled by synergistic Cu/Ir-catalyzed protocol; success can be attributed to pivotal role ester substituent, which acts as preferential intramolecular nucleophile terminate intermediacy piperid-4-yl cation species. resulting bridged-heterocyclic show impressive preliminary biological activities against panel cancer cell lines.

Язык: Английский

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Bimetallic Ru/Ru‐Catalyzed Asymmetric One‐Pot Sequential Hydrogenations for the Stereodivergent Synthesis of Chiral Lactones

Advanced Science, Год журнала: 2024, Номер 11(23)

Опубликована: Март 21, 2024

Abstract Asymmetric sequential hydrogenations of α ‐methylene γ ‐ or δ ‐keto carboxylic acids are established in one‐pot using a bimetallic Ru/Ru catalyst system, achieving the stereodivergent synthesis all four stereoisomers both chiral and ‐lactones with two non‐vicinal carbon stereocenters high yields (up to 99%) excellent stereoselectivities >99% ee >20:1 dr). The compatibility Ru systems is investigated detail, it found that basicity reaction system plays key role hydrogenation processes. protocol can be performed on gram‐scale low loading 11000 S/C) resulting products allow for many transformations, particularly several intermediates useful preparation drugs natural products.

Язык: Английский

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Structurally divergent enantioselective synthesis of benzofuran fused azocine derivatives and spiro-cyclopentanone benzofurans enabled by sequential catalysis

Chemical Science, Год журнала: 2023, Номер 14(39), С. 10768 - 10776

Опубликована: Янв. 1, 2023

An important objective in organic synthesis and medicinal chemistry is the capacity to access structurally varied complex molecules rapidly affordably from easily available starting materials. Herein, a protocol for divergent of benzofuran fused azocine derivatives spiro-cyclopentanone benzofurans has been developed via chiral bifunctional urea catalyzed reaction between aurone-derived α,β-unsaturated imine ynone followed by switchable annulation reactions Lewis base catalysts (DBU PPh3) with concomitant epimerization. The skeletally diversified products were formed high yields diastereo- enantioselectivities. Computational analysis DFT accurate DLPNO-CCSD(T) employed gain deeper insights into mechanistic intricacies investigate role skeletal diversity.

Язык: Английский

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