Recent advances in Pd-catalyzed asymmetric cyclization reactions

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 53(2), P. 883 - 971

Published: Dec. 18, 2023

This review aims to collect advancements in enantioselective palladium-catalyzed cyclization reactions over the past eleven years, and it is organized into thirteen sections depending on different types of transformations involved.

Language: Английский

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Sadphos as Adaptive Ligands in Asymmetric Palladium Catalysis

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 31, 2024

ConspectusPalladium catalysis, as one of the most important strategies in asymmetric synthesis, has continuously attracted attention organic chemists. With development chiral ligands, increasingly challenging reactions and substantial progress catalysis are being realized.Since 2014, we have focused on exploiting a series sulfinamide phosphine ligands called "Sadphos," including Ming-Phos, Xu-Phos, Xiao-Phos, Xiang-Phos, TY-Phos, PC-Phos, GF-Phos, WJ-Phos. These can be easily prepared two to four steps using commercial materials. new types shown remarkable performance transition-metal-catalyzed reactions, especially Pd-catalyzed transformations. X-ray diffraction analysis, mechanistic studies, density functional theory calculations revealed that Sadphos coordinate with Pd0 PdII species Pd0/P, Pd0/P,S, or PdII/P,O modes.This Account summarizes our recent efforts toward palladium-catalyzed enantioselective ligands. were found privileged very crucial promote by increasing reactivity enantioselectivity. Ming-Phos is an effective ligand coupling intramolecular Heck providing highly trisubstituted allenes, axially anilides, gem-diarylmethine silanes, disubstituted dihydroisoquinolinones. Incorporation electron-rich cyclohexyl group moiety afforded which showed unique effect transformations, reductive Heck, dearomative Mizoroki–Heck, tandem Heck/Suzuki coupling, carboiodination, carboamination, cross-coupling reactions. Using similar strategy, synthesized more electron–rich TY-Phos Xiang-Phos bearing t-butyl 1-adamantyl at P atoms, respectively. Regarding stereoelectronic features, these characteristic best choice satisfy requirements fluoroarylation gem-difluoroalkenes, intermolecular α-arylation aldehydes, carboetherification alkenyl oximes, carboheterofunctionalization 2,3-dihydrofurans. Compared aforementioned attractive features high nucleophilicity originating from CH2PPh2 ortho-substituent side aryl ring, presumably responsible for its efficiency. The Pd/Xiao-Phos catalyst system shows good secondary oxides, affording P-stereogenic products multiple molecular skeletons. modification basic backbone introducing xanthene skeleton motivated us design synthesize monophosphines, named PC-Phos GF-Phos. various arylation sulfenate anions, denitrogenative cyclization benzotriazoles, dearomatization indoles. practicability GF-Phos was validated three-component N-tosylhydrazones, halides, terminal alkynes, well N-tosylhydrazones vinyl iodides pendent amines. In addition, ferrocene-derived WJ-Phos employed Suzuki–Miyaura reaction, biaryl monophosphine oxides excellent enantiomeric excesses.

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 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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Recent Advances in Palladium‐Catalyzed Asymmetric Heck/Tsuji–Trost Reactions of 1,n‐Dienes

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(26)

Published: Feb. 13, 2024

Abstract Transition–metal catalyzed tandem asymmetric reactions were powerful tools to access various chiral compounds. Many strategies have been developed for the coupling of 1,n‐dienes with aryl halides via a Heck/Tsuji–Trost process. However, control regio‐ and stereo‐chemistry remains challenging task. This minireview details recent advances in field by palladium complex, which opened new opportunities expanded our understanding this area research years.

Language: Английский

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Pd-Catalyzed Enantioselective Three-Component Carboamination of 1,3-Cyclohexadiene

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(31), P. 21231 - 21238

Published: July 29, 2024

Asymmetric Pd-catalyzed three-component carboamination reactions of dienes to construct chiral cyclohexenylamines, which are great importance in many fields chemistry, have remained largely unexplored. Here, we demonstrate a highly enantio- and regioselective Pd/Ming-Phos-catalyzed 1,3-cyclohexadiene with readily available aryl iodides anilines for facile access diverse valuable cyclohexenylamines. The process shows excellent functional group tolerance, easy scalability, mild conditions. Moreover, mechanistic studies suggest that this reaction has first-order dependence on the concentration palladium catalyst aniline.

Language: Английский

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Pd-Catalyzed Asymmetric Aza-Heck Cyclization/Sonogashira Reaction of Alkene-Tethered Oxime Esters and Alkynes

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(7), P. 5305 - 5313

Published: March 26, 2024

Over the past few decades, Narasaka–Heck-type difunctionalization of tethered alkenes has emerged as a powerful strategy to produce heterocyclic scaffolds. However, asymmetric synthesis rarely been explored. Herein, we report robust palladium-catalyzed enantioselective Narasaka–Heck cyclization–Sonogashira reaction alkene-tethered oxime esters and terminal alkynes. By employing new Ming-Phos ligand, obtain high yields pyrrolines with quaternary stereocenter enantioselectivities under mild conditions. Density functional theory (DFT) study reveals weak interaction between aromatic ring substrate fragment naphthyl group in which probably accounts for stereoselectivity.

Language: Английский

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Enantioselective Aminosilylation of Alkenes by Palladium/Ming‐Phos‐Catalyzed Tandem Narasaka–Heck/Silylation Reaction

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 5, 2024

A Pd-catalyzed enantioselective aminosilylation of alkenes via tandem Aza-Heck/silylation reaction under Pd/Sadphos catalysis is disclosed. wide array oxime esters and silicon reagents are tolerated, furnishing the chiral pyrrolines bearing one quaternary or two contiguous stereocenters in good yield with high enantioselectivity. Not only terminal but also tri-substituented internal successfully participate reaction, delivering vicinal complete diastereoselectivity DFT study conducted to probe pathway origin enantioselectivity, which revealed that stereoinduction arises from weak interaction between aromatic ring substrate fragment naphthyl group ligand.

Language: Английский

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Enantioselective Heck/Tsuji−Trost reaction of flexible vinylic halides with 1,3-dienes

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 22, 2025

Abstract The enantioselective domino Heck/cross-coupling has emerged as a powerful tool in modern chemical synthesis for decades. Despite significant progress relative rigid skeleton substrates, the implementation of asymmetric cascades highly flexible haloalkene substrates remains challenging and long-standing goal. Here we report an efficient Heck/Tsuji−Trost reaction vinylic halides with 1,3-dienes enabled by palladium catalysis. Specifically, Heck insertion stereodetermining step to form ƞ 3 allyl complex situ trapping nucleophiles enable Heck/etherification formal (4 + 2) cycloaddition manner. Engineering Sadphos bearing androgynous non-C 2 -symmetric chiral sulfinamide phosphine ligands are vital component achieving excellent catalytic reactivity enantioselectivity. This strategy offers general, modular divergent platform rapidly upgrading feedstock dienes various value-added molecules is expected inspire development other Heck/cross-couplings.

Language: Английский

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SadPhos Library: A Comprehensive Resource for Exploring Chiral Ligand Chemical Space

Chemistry - An Asian Journal, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Abstract Traditionally, the discovery of ligands for organic reactions has relied heavily on intuition and experience chemists, leading to a trial‐and‐error process that is both time‐consuming inherently biased. The rise data science now offers more systematic efficient approach exploring chemical spaces, moving beyond heuristic constraints conventional ligand design enabling data‐driven, predictive method. In this study, we introduce “SadPhos Library”, comprehensive collection 890 reported chiral sulfinamide phosphine ligands, use physical descriptors systematically map their space. By examining small dataset known active demonstrate how SadPhos library can help identify key properties associated with performance thus streamline optimization. Furthermore, employing dimensionality reduction clustering techniques, pinpoint representative subset facilitates targeted exploration diverse landscape.

Language: Английский

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