Asymmetric Three-Component Radical Cascade Reactions Enabled by Synergistic Photoredox/Brønsted Acid Catalysis: Access to α-Amino Acid Derivatives DOI Creative Commons
Chao Che,

Yi‐Nan Lu,

Ting Fang

et al.

ACS Central Science, Journal Year: 2024, Volume and Issue: 11(1), P. 36 - 45

Published: Aug. 16, 2024

Multicomponent reactions (MCRs), highly sought-after methods to produce atom-, step-, and energy-economic organic syntheses, have been developed extensively. However, catalytic asymmetric MCRs, especially those involving radical species, remain largely unexplored owing the difficulty in stereoselectively regulating extraordinarily high reactivity of open-shell species. Herein, we report a conceptually novel three-component cascade reaction readily accessible glycine esters, α-bromo carbonyl compounds 2-vinylcyclopropyl ketones via synergistic photoredox/Brønsted acid catalysis, which three sequential C–C (σ/π/σ) bond-forming events occurred through addition/ring-opening/radical–radical coupling protocol, affording an array valuable enantioenriched unnatural α-amino derivatives bearing two contiguous stereogenic centers alkene moiety moderate good yield with diastereoselectivity, excellent enantioselectivity E-dominated geometry under mild conditions. The relay process, unique proton-coupled electron transfer (PCET)-promoted radical–radical coupling, is supported by mechanistic investigations quantum mechanics calculations should garner broad interest further inspire development multicomponent reactions.

Language: Английский

Synergistic Dual Catalysis in Stereodivergent Synthesis DOI
Liang Wei, Cong Fu,

Zuo-Fei Wang

et al.

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

Citations

31
Synergistic Pd/Cu-Catalyzed 1,5-Double Chiral Inductions DOI
Jiacheng Zhang, Yicong Luo, Zheng En

et al.

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

Citations

19
Asymmetric α-allylic allenylation of β-ketocarbonyls and aldehydes by synergistic Pd/chiral primary amine catalysis DOI Creative Commons

Chang You,

Mingying Shi,

Xueling Mi

et al.

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

Citations

26
Iridium-Catalyzed Enantioselective Transfer Hydrogenation of 1,1-Dialkylethenes with Ethanol: Scope and Mechanism DOI
Qian Lu, Yu Cui, Lan Gan

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(5), P. 3427 - 3437

Published: Jan. 20, 2024

Despite half a century's advance in the field of transition-metal-catalyzed asymmetric alkene hydrogenation, enantioselective hydrogenation purely alkyl-substituted 1,1-dialkylethenes has remained an unmet challenge. Herein, we describe chiral PCNOx-pincer iridium complex for transfer this class with ethanol, furnishing all-alkyl-substituted tertiary stereocenters. High levels enantioselectivity can be achieved reactions substrates secondary/primary and primary/primary alkyl combinations. The catalyst is further applied to redox isomerization disubstituted alkenols, producing stereocenter remote resulting carbonyl group. Mechanistic studies reveal dihydride species, (PCNOx)Ir(H)2, as catalytically active intermediate, which decay dimeric species (κ3-PCNOx)IrH(μ-H)2IrH(κ2-PCNOx) via ligand-remetalation pathway. deactivation under conditions H2 much faster than that EtOH, explains why (PCNOx)Ir effective but ineffective hydrogenation. suppression di-to-trisubstituted by regioselective 1,2-insertion partly responsible success system, underscoring critical role played pincer ligand 1,1-dialkylethenes. Moreover, computational elucidate significant influence London dispersion interaction between substrate on control, illustrated complete reversal stereochemistry through cyclohexyl-to-cyclopropyl group substitution substrates.

Language: Английский

Citations

11
Enantioselective Tsuji‐Trost α‐Fluoroallylation of Amino Acid Esters with Gem‐Difluorinated Cyclopropanes DOI
Zheng Su,

Binhong Tan,

Hui He

et al.

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

Citations

11
Diastereodivergent Catalysis DOI Creative Commons
Daniel Moser,

Tanno A. Schmidt,

Christof Sparr

et al.

JACS Au, Journal Year: 2023, Volume and Issue: 3(10), P. 2612 - 2630

Published: Sept. 26, 2023

Alongside enantioselective catalysis, synthetic chemists are often confronted by the challenge of achieving catalyst control over relative configuration to stereodivergently access desired diastereomers. Typically, these approaches iteratively or simultaneously multiple stereogenic units for which dual catalytic methods comprising sequential, relay, and synergistic catalysis emerged as particularly efficient strategies. In this Perspective, benefits challenges catalyst-controlled diastereodivergence in construction carbon stereocenters discussed on basis illustrative examples. The concepts then transferred diastereodivergent atropisomeric systems with twofold higher-order stereogenicity well E- Z-configured alkenes.

Language: Английский

Citations

21
Enantio- and diastereodivergent synthesis of fused indolizines enabled by synergistic Cu/Ir catalysis DOI Creative Commons

Bing‐Ke Zhu,

Hui Xu,

Lu Xiao

et al.

Chemical Science, Journal Year: 2023, Volume and Issue: 14(15), P. 4134 - 4142

Published: Jan. 1, 2023

Highly selective assembly of 2,3-fused indolizines was achieved via a cascade allylation/Friedel–Crafts type reaction with Cu/Ir catalysis. This protocol furnishes stereodivergent synthesis chiral bearing three stereogenic centers excellent results.

Language: Английский

Citations

19
Synergistic catalysis for stereocontrol of prochiral nucleophiles in palladium-catalyzed asymmetric allylic substitution DOI
Xi Wang,

Youbin Peng,

Ling Zhao

et al.

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(8), P. 2238 - 2255

Published: July 20, 2023

Language: Английский

Citations

18
Bimetallic Ru/Ru‐Catalyzed Asymmetric One‐Pot Sequential Hydrogenations for the Stereodivergent Synthesis of Chiral Lactones DOI Creative Commons

Jingli He,

Zhaodi Li,

Ruhui Li

et al.

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

Citations

8
Copper-catalyzed asymmetric allylic substitution of racemic/meso substrates DOI Creative Commons
Jun Li, Junrong Huang, Yan Wang

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(22), P. 8280 - 8294

Published: Jan. 1, 2024

The synthesis of enantiomerically pure compounds is a pivotal subject in the field chemistry, with enantioselective catalysis currently standing as primary approach for delivering specific enantiomers. Among these strategies, Cu-catalyzed asymmetric allylic substitution (AAS) significant and irreplaceable, especially when it comes to use non-stabilized nucleophiles (pK > 25). Although AAS prochiral substrates has also been widely developed, methodologies involving racemic/meso are highly desirable, undergo dynamic processes give single enantiomer products. Inspired by pioneering work Alexakis, Feringa Gennari groups, continuously employed deracemization desymmetrization enriched In this review, we mainly focus on developments over past two decades, providing an explicit outline ligands employed, scope nucleophiles, underlying their practical applications.

Language: Английский

Citations

6