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

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(47), P. 24941 - 24949

Published: Sept. 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.

Language: Английский

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

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(4), P. 1971 - 1985

Published: Jan. 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.

Language: Английский

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Recent Progress of Diatomic Catalysts: General Design Fundamentals and Diversified Catalytic Applications

Small, Journal Year: 2022, Volume and Issue: 18(46)

Published: Sept. 23, 2022

Abstract In recent years, some experiments and theoretical work have pointed out that diatomic catalysts not only retain the advantages of monoatomic catalysts, but also introduce a variety interactions, which exceed limit catalytic performance can be applied to many fields. Here, interaction between adjacent metal atoms in is elaborated: synergistic effect, spacing enhancement effect (geometric effect), electronic effect. With regard classification characterization various new are classified into four categories: heteronuclear/homonuclear, with/without carbon carriers, their measures introduced explained detail. aspect preparation widely used atomic layer deposition method, metal–organic framework derivative simple ball milling method introduced, with emphasis on formation mechanism catalysts. Finally, effective control strategies key applications electrocatalysis, photocatalysis, thermal catalysis, other fields given.

Language: Английский

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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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Catalytic Asymmetric Hydroalkoxylation and Formal Hydration and Hydroaminoxylation of Conjugated Dienes

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(7), P. 3915 - 3925

Published: Feb. 10, 2023

The straightforward construction of stereogenic centers bearing unprotected functional groups, as in nature, has been a persistent pursuit synthetic chemistry. Abundant applications free enantioenriched allyl alcohol and hydroxylamine motifs have made the asymmetric hydration hydroaminoxylation conjugated dienes from water hydroxylamine, respectively, intriguing efficient routes that have, however, unachievable thus far. A fundamental challenge is failure to realize transition-metal-catalyzed enantioselective C–O bond constructions via hydrofunctionalization dienes. Here, we perform comprehensive study toward stereoselective formal by synthesizing set new P,N-ligands identifying an aryl-derived oxime surrogate for both hydroxylamine. Asymmetric hydroalkoxylation with also elucidated. Furthermore, versatile derivatizations following provide indirect but concise hydrophenoxylation, hydrofluoroalkoxylation, hydrocarboxylation unreported Finally, ligand-to-ligand hydrogen transfer process proposed based on results preliminary mechanistic experiments.

Language: Английский

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Asymmetric transformations enabled by synergistic dual transition-metal catalysis

Chem Catalysis, Journal Year: 2022, Volume and Issue: 3(1), P. 100455 - 100455

Published: Nov. 17, 2022

Language: Английский

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Ni-Catalyzed Enantioselective Hydrofunctionalizations of 1,3-Dienes

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(24), P. 15638 - 15647

Published: Dec. 6, 2022

Ni-catalyzed enantioselective hydrofunctionalizations of conjugated dienes are particularly demanding reactions to devise because they require not only addressing the inherent challenges associated with development an transformation but also overcoming all other aspects selective catalysis (chemoselectivity, regioselectivity, diastereoselectivity, etc.). However, value-added nature chiral allylic and homoallylic derivatives obtained by these methods, lack efficient alternatives, use earth-abundant first-row transition metal have led renewed interest over past decade. In this Perspective, we give overview developments in field, from original findings (often dating back last century) most recent contributions. Emphasis is placed on hydrofunctionalization agent (C(sp), C(sp2), C(sp3), N, P, or O).

Language: Английский

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Recent Advances in Nonprecious Metal Catalysis

Organic Process Research & Development, Journal Year: 2023, Volume and Issue: 27(3), P. 423 - 447

Published: Feb. 17, 2023

Nonprecious-metal-catalyzed alternatives to powerful precious metal transformations are of increasing interest in academia and the pharmaceutical industry due lower cost, better sustainability, toxicity. With continual growth broad field nonprecious catalysis (NPMC), we have chosen highlight selected articles published from March June 2022 which intended examples NPMC that feel may be especially relevant development. We aim inspire academic industrial innovation through discussion herein.

Language: Английский

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Chiral Aldehyde Catalysis-Enabled Asymmetric α-Functionalization of Activated Primary Amines

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(5), P. 776 - 794

Published: Feb. 21, 2024

ConspectusThe development of catalytic activation modes provides a reliable and effective platform for designing new enantioselective reactions preparing chiral molecules with diverse structures. Chiral aldehyde catalysis is an attractive concept in asymmetric catalysis, which utilizes catalyst to promote the hydroamination allylic amines, α-functionalization primary or transamination α-keto esters. Typically, aldehyde-catalyzed amines efficient straightforward method synthesis α-functionalized does not require any additional protection deprotection manipulations amine group. However, achieving stereoselective transformations high efficiency enantioselectivity by this strategy has remained intractable challenge.This Account summarizes our endeavors application catalysis. Using as catalyst, we reported α-C alkylation 2-aminomalonate 3-indolylmethanol 2014, represents first activated amine. Subsequently, several axially catalysts were continuously prepared using BINOL starting material, their applications explored. On one hand, they used organocatalysts realize various α-amino acid esters, such 1,4-addition toward conjugated enones/α,β-unsaturated diesters cyclic 1-azadienes well α-arylation/allylation benzylation corresponding halohydrocarbons. Notably, taking advantage difference distribution sites between two catalysts, disclosed diastereodivergent 1,6-conjugated addition Mannich reactions. other potential cooperative transition metal also been demonstrated. Enabled combination aldehyde, palladium complex, Lewis acid, α-allylation amino esters allyl alcohol was established. Moreover, ternary system successfully 1,3-dienes, allenes, allenylic 1,3-disubstituted arylmethanol cascade Heck-alkylation reaction. The nickel complex allows α-propargylation propargylic excellent enantioselectivities. These provide large library optically active acids. With those key building blocks, formal multiple natural products biologically significant unnatural accomplished. This includes stereodivergent pyrrolizidine alkaloid NP25302 product (

Language: Английский

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Direct access to spirocycles by Pd/WingPhos-catalyzed enantioselective cycloaddition of 1,3-enynes

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 27, 2021

Abstract Spirocycles play an important role in drug discovery and development. The direct, catalytic, enantioselective synthesis of spirocycles from readily available starting materials atom economic manner remains a highly sought-after task organic synthesis. Herein, Pd-hydride-catalyzed cycloaddition method for the spirocyclic compounds directly two classes commonly materials, 1,3-enynes cyclic carbon−hydrogen (C−H) bonds, is reported. reactions employ chiral Pd/WingPhos catalyst to both suppress formation bis-allenyl by-products control stereoselectivity. 1,3-Enynes are used as dielectrophilic four-carbon units reactions, which also enables enyne substrate-directed enantioselectivity switch with good levels stereocontrol. present spirocycle tolerates broad range functional groups 1,3-enyne substrates, including alcohols, esters, nitriles, halides, olefins. A variety diverse nucleophiles, pharmaceutically heterocycles carbocycles, can be flexibly incorporated spiro scaffolds.

Language: Английский

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