Synergistic Dual Catalysis in Stereodivergent Synthesis

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(6), P. 3812 - 3844

Published: Feb. 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.

Language: Английский

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

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(7)

Published: Dec. 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.

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 access to non-natural α-amino acids via enantio- and Z / E -selective catalysis

Science, Journal Year: 2024, Volume and Issue: 385(6712), P. 972 - 979

Published: Aug. 29, 2024

The precise control of

Language: Английский

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Enantioselective Tsuji‐Trost α‐Fluoroallylation of Amino Acid Esters with Gem‐Difluorinated Cyclopropanes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(23)

Published: Feb. 27, 2024

A novel enantioselective Tsuji-Trost-type cross coupling reaction between gem-difluorinated cyclopropanes and N-unprotected amino acid esters enabled by synergistic Pd/Ni/chiral aldehyde catalysis is presented herein. This transformation streamlined the diversity-oriented synthesis (DOS) of optically active α-quaternary α-amino bearing a linear 2-fluoroallylic motif, which served as an appealing platform for construction other valuable enantioenriched compounds. The key intermediates were confirmed HRMS detection, while DFT calculations revealed that excellent enantioselectivity was attributed to stabilizing non-covalent interactions Pd(II)-π-fluoroallyl species Ni(II)-Schiff base complex.

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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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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Enantioselective Synthesis of Axially Chiral Alkylidenecycloalkanes via Copper-Catalyzed Functionalization of Acyl Allenols

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 2351 - 2358

Published: Jan. 24, 2025

Language: Английский

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