Stereodivergent Synthesis of Allenes with α,β‐Adjacent Central Chiralities Empowered by Synergistic Pd/Cu Catalysis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(9)

Published: Jan. 3, 2023

The stereodivergent synthesis of allene compounds bearing α,β-adjacent central chiralities has been realized via the Pd/Cu-catalyzed dynamic kinetic asymmetric alkylation racemic allenylic esters. matched reactivity bimetallic catalytic system enables challenging reaction aryl-substituted acetates with sterically crowded aldimine esters smoothly under mild conditions. Various chiral non-natural amino acids a terminal allenyl group are easily synthesized in high yields and excellent diastereo- enantioselectivities (up to >20 : 1 dr, >99 % ee). Importantly, all four stereoisomers product can be readily accessed by switching configurations two metal catalysts. Furthermore, easy interconversion between uncommon η3 -butadienyl palladium intermediate featuring weak C=C/Pd coordination bond stable Csp2 -Pd is beneficial for transformation process (DyKAT).

Language: Английский

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Stereodivergent Construction of Csp³−Csp³Bonds Bearing Vicinal Stereocenters by Synergistic Palladium and Phase‐Transfer Catalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(2)

Published: Nov. 16, 2022

Abstract Synergistic catalysis has emerged as one of the most powerful tools for stereodivergent formation Csp 3 −Csp bonds bearing vicinal stereocenters. Despite many successes that have been achieved in this field, coupling reactions involving stabilized nucleophiles remain challenging because competing single‐catalysis pathway. Herein, we report a synergistic palladium/phase‐transfer catalyst system enables diastereodivergent 1,3‐dienes with nucleophile oxindoles. Both syn and anti products, quaternary tertiary stereocenters, could be selectively produced good yields high enantio‐ diastereoselectivities. Non‐covalent activation via chiral ion pair biphasic is crucial success factor achieving diastereodivergence.

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

Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)

Published: March 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.

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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Nickel/Copper‐Cocatalyzed Asymmetric Benzylation of Aldimine Esters for the Enantioselective Synthesis of α‐Quaternary Amino Acids

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(23)

Published: March 23, 2022

The first asymmetric Ni/Cu cocatalyzed benzylation of aldimine esters is reported. A series benzyl-substituted α-quaternary amino acids could be synthesized in high yield and with levels enantioselectivity (up to 90 % 99 ee). experimental theoretical calculation results suggested that the strong electrophilicity η3 -benzylnickel intermediate crucial for reactivity, enabling reaction under base-free conditions. Furthermore, this method has been applied synthesis cell adhesion inhibitor BIRT-377 analogues, key NK1 receptor antagonist PD154075 CCK-B CI-988.

Language: Английский

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Enantioselective Three‐Component Photochemical 1,4‐Bisalkylation of 1,3‐Butadiene with Pd/Cu Catalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(40)

Published: June 27, 2022

Catalysis by excited-state palladium has emerged as an active area of research, but controlling the enantioselectivity remains a challenge. Herein, we report use synergistic Pd/Cu catalysis to accomplish first three-component photochemical 1,4-bisalkylation reactions 1,3-butadiene. Consequently, α-amino acid esters bearing quaternary stereocenters were expeditiously synthesized from three simple starting materials: alkyl bromide, butadiene, and aldimine ester. Experimental computational investigation reaction mechanism confirmed radical pathway involving species. The stereochemistry is mainly controlled chiral Cu catalyst.

Language: Английский

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Stereodivergent dehydrative allylation of β-keto esters using a Ru/Pd synergistic catalyst

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

Published: Oct. 12, 2022

Abstract α-Alkylation of a β-keto ester is frequently used reaction for carbon–carbon bond formation. However, extension to stereoselective remains significant challenge, because the product easily racemizes under acidic or basic conditions. Here, we report hybrid system consisting Pd and Ru complexes that catalyzes asymmetric dehydrative condensation between cinnamyl-type allylic alcohols esters. α-Non-substituted can be allylated afford an α-mono-substituted with high regio-, diastereo-, enantioselectivity. No epimerization occurs owing nearly neutral conditions, which achieved by rapid proton transfer from Pd-enolate formation π-allyl complex Four diastereomers synthesized on demand changing stereochemistry complex. Eight stereoisomers three adjacent stereogenic centers employing diastereoselective reduction ketone in products. The formal synthesis (+)-pancratistatin demonstrates utility reaction.

Language: Английский

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Desymmetrization of Geminal Difluoromethylenes using a Palladium/Copper/Lithium Ternary System for the Stereodivergent Synthesis of Fluorinated Amino Acids

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(47)

Published: Oct. 10, 2023

Fluorinated amino acids and related peptides/proteins have been found widespread applications in pharmaceutical agricultural compounds. However, strategies for introducing a C-F bond into an enantioselective manner are still limited no such asymmetric catalysis strategy has reported. Herein, we successfully developed Pd/Cu/Li ternary system stereodivergent synthesis of chiral fluorinated acids. This method involves sequential desymmetrization geminal difluoromethylenes allylic substitution with acid Schiff bases via Pd/Li Pd/Cu dual activation, respectively. A series non-natural bearing allylic/benzylic fluorine motif easily synthesized high yields excellent regio-, diastereo-, enantioselectivities (up to >20 : 1 dr >99 % ee). density functional theory (DFT) study revealed the F-Cu interaction substrate Cu catalyst significantly influence stereoselectivity.

Language: Английский

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