Palladium-Catalyzed Ligand-Controlled Switchable Hetero-(5 + 3)/Enantioselective [2σ+2σ] Cycloadditions of Bicyclobutanes with Vinyl Oxiranes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(29), P. 19621 - 19628

Published: May 13, 2024

For nearly 60 years, significant research efforts have been focused on developing strategies for the cycloaddition of bicyclobutanes (BCBs). However, higher-order and catalytic asymmetric BCBs long-standing formidable challenges. Here, we report Pd-catalyzed ligand-controlled, tunable cycloadditions divergent synthesis bridged bicyclic frameworks. The dppb ligand facilitates formal (5+3) vinyl oxiranes, yielding valuable eight-membered ethers with scaffolds in 100% regioselectivity. Cy-DPEphos promotes selective hetero-[2σ+2σ] to access pharmacologically important 2-oxabicyclo[3.1.1]heptane (O-BCHeps). Furthermore, corresponding O-BCHeps 94–99% ee has achieved using chiral (S)-DTBM-Segphos, representing first cross-dimerization two strained rings. obtained are promising bioisosteres ortho-substituted benzenes.

Language: Английский

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Catalytic Asymmetric Synthesis of Sulfinamides via Cu-Catalyzed Asymmetric Addition of Aryl Boroxines to Sulfinylamines

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(26), P. 17580 - 17586

Published: June 20, 2024

The application of sulfinamides has been witnessed in medicinal and agrochemistry with employment asymmetric transformations. However, methods for their catalytic synthesis have rarely explored. Herein, the enantioselective addition aryl boroxines to sulfinylamines via Cu catalyst newly developed Xuphos ligand were reported. A series chiral can be readily accessed one step. This protocol enables stereospecific transformation sulfonimidoyl fluorides, sulfonimidamides, sulfonimidate esters. DFT calculations revealed reaction pathway, migratory insertion is enantio-determining noncovalent interaction between oxygen atom C-H bonds crucial enantioselectivity control.

Language: Английский

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Design and Application of New Pyridine-Derived Chiral Ligands in Asymmetric Catalysis

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(6), P. 957 - 970

Published: March 6, 2024

ConspectusThe innovation of chiral ligands has been crucial for the asymmetric synthesis functional molecules, as demonstrated by several types widely applied "privileged" ligands. In this context, pyridine-derived ligands, far some oldest and most utilized in catalysis, have attracted considerable research interest past half-century. However, development broadly applicable pyridine units (CPUs) plagued intertwining challenges, thus delaying advancements many reactions.This Account aims to summarize recent progress new CPU-containing focusing on a rationally designed, modular, tunable CPU developed our laboratory. A significant problem thwarting conventional designs is paradox between broad reactivity stereoselectivity; that is, while enhanced stereoselectivity may be achieved introducing elements close N atom, concomitant increase local steric hindrance often limits catalytic activity scope. Our newly features rigid [6-5-3] fused-ring framework spirocyclic ketal side wall. The well-defined three-dimensional structure minimizes (inner layer) tunes peripheral environment (outer remote substituents, securing stereoselectivity. Different chelating were readily assembled using structural module, with applications mechanistically diverse transition-metal-catalyzed reactions. Thus, series 2,2′-bipyridine successfully employed general, efficient, highly enantioselective nickel-catalyzed intermolecular reductive addition, Ullmann coupling ortho-chlorinated aryl aldehydes, carboxylation benzylic (pseudo)halides CO2. Notably, these exhibited superior reactions compared common N-based iridium-catalyzed C–H borylation was N,B-bidentate ligand. Furthermore, challenging, additive-free, broad-scope transfer hydrogenative direct amination half-sandwich iridium catalyst supported N,C-bidentate excellent performance high stereoselectivity, which, when combined experimental computational mechanistic investigations, "double-layer control" design concept.Considering described herein should inspire creation novel catalysts drive

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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Catalyst Control over S(IV)-stereogenicity via Carbene-derived Sulfinyl Azolium Intermediates

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(36), P. 25350 - 25360

Published: Sept. 2, 2024

Stereoselective synthesis utilizing small-molecule catalysts, particularly N-heterocyclic carbene (NHC), has facilitated swift access to enantioenriched molecules through diverse activation modes and NHC-bound reactive intermediates. While carbonyl derivatives, imines, "activated" alkenes have been extensively investigated, the exploration of heteroatom-centered analogues intermediates long neglected, despite significant potential for novel chemical transformations they offer once recognized. Herein, we disclose a carbene-catalyzed new mode by generating unique sulfinyl azolium from nucleophilic addition in situ-generated mixed sulfinic anhydride Combined experimental computational mechanistic investigations pinpoint chiral NHC-catalyzed formation intermediate as enantio-determining step. The "S"-based imparts high efficiency catalytic construction sulfur-stereogenic compounds, giving rise sulfinate esters with yields enantioselectivities under mild conditions. Notably, distinct most enantioselective focusing on "C" central products, our study realizes carbene-catalyst control over "S" stereocenters via direct asymmetric S-O bond first time. Furthermore, these sulfinyl-containing products could serve versatile synthetic platforms

Language: Английский

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Enantioselective Synthesis of Hydrindanes via Palladium-Catalyzed Asymmetric Desymmetrization of Cyclohexadiene Derivatives

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

We herein disclose a strategy for the asymmetric desymmetrization of cyclohexadiene derivatives via palladium-catalyzed Heck and tandem Heck/Tsuji-Trost allylic alkoxylation reaction. By employing DCE as solvent, we obtained variety chiral hydrindanes containing an all-carbon quaternary carbon center tertiary in good yields with excellent enantioselectivities. With alcohols valuable one stereocenter two centers were constructed high level enantioinduction.

Language: Английский

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Amino Turbo Chirality and Its Asymmetric Control

Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

A series of new targets containing 3 chiral elements central, orientational, and turbo chirality have been designed synthesized asymmetrically. The absolute configurations conformations these types were concurrently controlled by using sulfonimine auxiliary unambiguously determined x-ray diffraction analysis. These include alpha unnatural amino acid derivatives, which may play an important role for drug design, discovery, development. Three propellers framework are covalently connected to a C(sp

Language: Английский

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Construction of axially chiral molecules enabled by photoinduced enantioselective reactions

Chemical Science, Journal Year: 2024, Volume and Issue: 15(32), P. 12636 - 12643

Published: Jan. 1, 2024

Axially chiral molecular scaffolds are widely found in pharmaceutical molecules, functionalized materials, and ligands. The synthesis of these compounds has garnered considerable interest from both academia industry. construction such enabled by transition metal catalysis organocatalysis under thermodynamic conditions, been extensively studied well-reviewed. In recent years, photoinduced enantioselective reactions have emerged as powerful methods for the catalytic axial chirality. this review, we provide an overview various synthetic strategies chirality, with a specific focus on reaction design mechanisms. Additionally, discuss limitations current highlight future directions field.

Language: Английский

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Novel Sulfinamide-Based Chiral Ligand Promoted Chiral Diarylmethanol Preparation via exo-Directed Asymmetric C–H Alkynylation under Mild Conditions

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 2540 - 2549

Published: Jan. 28, 2025

Language: Английский

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Transfer Learning-Enabled Ligand Prediction for Ni-Catalyzed Atroposelective Suzuki–Miyaura Cross-Coupling Based on Mechanistic Similarity: Leveraging Pd Knowledge for Ni Discovery

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

The rational design of novel molecular catalysts often confronts challenges due to complex structure–performance relationships. Emerging data-driven approaches provide revolutionary solutions, yet the application machine learning new catalyst development inevitably faces a low-data regime with limited effective modelings available. In this study, we present transfer strategy facilitate knowledge from well-documented Pd catalysis novel, underexplored Ni system. By synergistically modeling extensive data Ni/Sadphos data, our approach accurately predicted Sadphos ligands, enabling first atroposelective Ni-catalyzed Suzuki–Miyaura cross-coupling reaction. synthetic utility learning-predicted ligand was further demonstrated in its broad scope, gram-scale synthesis, and precise control dual axial chiralities ternaphthalene through sequential coupling under catalysis. Additionally, density functional theory calculations were employed reveal reaction mechanism stereochemical model catalyst, validating proposed mechanistic connection between Pd. This work demonstrates how models can effectively leverage connectivity, applying relationship literature predict catalysts, providing for few-shot perspective.

Language: Английский

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