Enantio- and Diastereodivergent Construction of 1,3-Nonadjacent Stereocenters Bearing Axial and Central Chirality through Synergistic Pd/Cu Catalysis

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(32), С. 12622 - 12632

Опубликована: Авг. 5, 2021

In contrast to the widely explored methods for asymmetric synthesis of molecules bearing a single stereocenter or adjacent stereocenters, concurrent construction 1,3-stereogenic centers in an enantio- and diastereoselective manner remains challenge, especially acyclic systems. Herein, we report diastereodivergent 1,3-nonadjacent stereocenters allenyl axial central chirality through synergistic Pd/Cu-catalyzed dynamic kinetic allenylation with racemic allenylic esters. The protocol is suitable wide range substrates including challenging esters less sterically bulky substituents provided chiral products high levels diastereoselectivities (up >20:1 dr >99% ee). Furthermore, several representative transformations involving axial-to-central transfer were conducted, affording useful structural motifs containing nonadjacent manner.

Язык: Английский

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Bimetallic Catalysis in Stereodivergent Synthesis

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(45)

Опубликована: Авг. 2, 2022

Abstract Bimetallic catalysis has emerged as an efficient strategy for the development of new chemical reactions. Importantly, this also provides a simple and powerful platform stereodivergent synthesis, whereby all possible stereoisomers products bearing two stereocenters can be easily prepared from same set starting materials. In Minireview, allylic substitution, propargylic hydrofunctionalization, annulation based on bimetallic been summarized. It is expected that more catalytic systems will developed applied synthesis valuable molecules.

Язык: Английский

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Enantio‐ and Diastereodivergent Synthesis of Spirocycles through Dual‐Metal‐Catalyzed [3+2] Annulation of 2‐Vinyloxiranes with Nucleophilic Dipoles

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(47), С. 24941 - 24949

Опубликована: Сен. 17, 2021

The development of efficient and straightforward methods for obtaining all optically active isomers structurally rigid spirocycles from readily available starting materials is great value in drug discovery chiral ligand development. However, the stereodivergent synthesis bearing multiple stereocenters remains an unsolved challenge owing to steric hindrance ring strain. Herein, we report enantio- diastereodivergent through dual-metal-catalyzed [3+2] annulation oxy π-allyl metallic dipoles with less commonly employed nucleophilic (imino esters). A series spiro compounds a pyrroline olefin were easily synthesized manner (up 19:1 dr, >99 % ee), which showed promise as new type N-olefin ligand. Preliminary mechanistic studies also carried out understand process this bimetallic catalysis.

Язык: Английский

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Dispersion and Steric Effects on Enantio-/Diastereoselectivities in Synergistic Dual Transition-Metal Catalysis

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(4), С. 1971 - 1985

Опубликована: Янв. 20, 2022

Comprehensive computational studies were carried out to explore the mechanisms of enantioselective Cu/Pd and stereodivergent Cu/Ir dual-catalytic syntheses α,α-disubstituted α-amino acids (α-AAs). A chiral copper azomethine ylide undergoes facile α-allylation with racemic π-allylpalladium species or stereopure π-allyliridium complex stereoconvergently stereodivergently furnish single/double stereocenters, respectively. Stereoselectivity at α-center is controlled by facial selectivity respect prochiral nucleophile. Despite apparently similar transition-state assemblies, models distortion/interaction analyses disclose versatile modes stereoinduction wherein can face-selectively intercept metal−π-allyl intermediates utilizing attractive dispersion interactions and/or sterically caused distortions. Generation β-stereocenter in system relies on a stereospecifically generated allyliridium electronically branched-to-linear selectivity, while dual yields linear monochiral product due steric factors π–π stacking interactions. The demonstrate molecular level how ligand-encoded information transferred α-/β-sites resulting α-AAs mode regio-/stereoselection altered differences transition-metal-stabilized coupling partners. To facilitate stereoselective catalysis, suite analytical tools extract controlling for asymmetric induction demonstrated.

Язык: Английский

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Stereodivergent total synthesis of rocaglaol initiated by synergistic dual-metal-catalyzed asymmetric allylation of benzofuran-3(2H)-one

Chem, Год журнала: 2022, Номер 8(7), С. 2011 - 2022

Опубликована: Май 2, 2022

Язык: Английский

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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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Dual Catalysis in Organic Synthesis: Current Challenges and New Trends

European Journal of Organic Chemistry, Год журнала: 2022, Номер 26(1)

Опубликована: Дек. 9, 2022

Abstract Dual catalysis is one of the most powerful strategies for development chemical reactions in organic synthesis. This strategy can be divided into cooperative catalysis, relay and sequential according to actual mode operation communication between catalysts. In recent years, such has been applied a large number studies since it advantages of: 1) increasing reactivity enabling challenging transformations; 2) offering way controlling stereoselectivity asymmetric reactions, which traditional catalytic systems; 3) catalyze stereodivergent synthesis molecules bearing or more stereocenters from same starting materials. Perspective, intends introduce reader EurJOC special collection on Catalysis , aims summarize different categories dual demonstrate their benefits constructing new bonds selective manner. Finally, current challenges trends will also presented.

Язык: Английский

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Asymmetric transformations enabled by synergistic dual transition-metal catalysis

Chem Catalysis, Год журнала: 2022, Номер 3(1), С. 100455 - 100455

Опубликована: Ноя. 17, 2022

Язык: Английский

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Cooperative Catalyst‐Enabled Regio‐ and Stereodivergent Synthesis of α‐Quaternary α‐Amino Acids via Asymmetric Allylic Alkylation of Aldimine Esters with Racemic Allylic Alcohols

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(46)

Опубликована: Сен. 26, 2022

We describe cooperative bimetallic catalysis that enables regio-/stereodivergent asymmetric α-allylations of aldimine esters. By employing Et3 B as the key activator, racemic allylic alcohols can be directly ionized to form Pd or Ir-π-allyl species in presence achiral chiral Ir complexes, respectively. The less more substituted termini metal-π-allyl are amenable nucleophilic attack by Cu-azomethine ylide, formation which is simultaneously facilitated B, affording α-quaternary α-amino acids with high regioselectivity and excellent stereoselectivity. use readily available electrophilic precursors represents an improvement from environmental atom/step economy perspective. Computational mechanistic studies reveal crucial role additive origins stereo- regioselectivities analyzing steric effects, dispersion interactions, frontier orbital population.

Язык: Английский

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