Enantioselective Construction of Quaternary Stereocenters via A Chiral Spiro Phosphoric Acid-Assisted Formal Gold Carbene gem-Dialkylation Reaction

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(28), P. 19261 - 19270

Published: July 1, 2024

Enantioselective construction of all-carbon quaternary stereocenters has attracted much attention over the past few decades. A variety catalytic asymmetric methods have been disclosed based on use presynthesized complex reagents that impart congested steric hindrance to reaction center, which generally produce chiral molecules through forming one C-C bond. The readily available could build two bonds same carbonic center with concomitant assembly remains challenging. Herein, we disclose a alkyne multifunctionalization using gold and spiro phosphoric acid (SPA) for synergistic catalysis. In this method, accessible internal alkynes served as key carbene precursors, followed by

Language: Английский

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Enantioselective Palladium‐Catalyzed Directed Migratory Allylation of Remote Dienes

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(34)

Published: June 30, 2023

Chain walking has been an efficient route to realize the functionalization of inert C(sp3 )-H bonds, but this strategy is limited mono-olefin migration and functionalization. Herein, we demonstrate feasibility tandem directed simultaneous migrations remote olefins stereoselective allylation for first time. The adoption palladium hydride catalysis secondary amine morpholine as solvent critical achieving high substrate compatibility stereochemical control with method. protocol also applicable three vicinal bonds thus construct continuous stereocenters along a propylidene moiety via short synthetic process. Preliminary mechanistic experiments corroborated design dienes.

Language: Английский

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Stereodivergent Conjugate Addition between Iminium and α-Azaaryl α-Fluoroenolate Intermediates by Synergistic Amine and Lewis Acid Catalysis

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(20), P. 13838 - 13845

Published: Oct. 12, 2023

Despite advances in the field of asymmetric catalysis, synthesis complete sets stereoisomers multistereogenic molecules, particularly those incorporating a fluorine atom, remains challenging task. We report, herein, stereodivergent method for tertiary alkyl fluorides vicinal stereogenic pairs through conjugate addition α-fluoro azaaryl acetamides to α,β-unsaturated aldehydes catalyzed by combination two chiral catalysts: copper Lewis acid and an amine. This process occurs synergistic catalytic cycle which reaction between situ-generated iminium α-azaaryl α-fluoroenolate intermediates constructs carbon–carbon bond, furnishing array 4-fluorinated 1,5-aldehyde amides with high stereocontrol. By simply varying combinations catalyst enantiomers, all four products are selectively accessible. Moreover, can be further derivatized into other enantioenriched fluorinated some contain stereocenters within three contiguous stereocenters.

Language: Английский

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Recent advances in Stereoselective Construction of Fluorinated Quaternary Carbon Centers from Fluorinated Compounds

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: 22(23), P. 4592 - 4612

Published: Jan. 1, 2024

Synthesis of fluorinated quaternary carbon centers by a series asymmetric alkylation, arylation, Mannich, Michael addition, aldol, and allylation reactions.

Language: Английский

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Chemodivergent Tandem Hydroalkylation and Hydroalkenoxylation of Conjugated Enynes

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(13), P. 9742 - 9751

Published: June 14, 2024

Due to the instability and weak O-nucleophilicity of enol, carbonyl compounds prefer function as C-nucleophiles instead O-nucleophiles in extensively studied transition metal-catalyzed hydrofunctionalizations unsaturated bonds. The corresponding hydroalkenoxylation reaction has thus long been unexplored. Here, we describe a chemodivergent protocol for challenging reactions. Dictated by Pd catalyst bearing different ligands, both 5-exo-trig 6-endo-trig processes are demonstrated be feasible between 1,3-enynes ketoesters, polysubstituted hydrofurans hydropyrans achieved good yields excellent chemoselectivities. In addition, enantioselective is also explored under an Rh moderate efficiency but with high stereoselectivities. Mechanistic studies corroborate designed tandem hydroalkylation uncover that ligand-to-ligand hydrogen transfer process might involved turnover-limiting step hydroalkenoxylation.

Language: Английский

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Asymmetric formal sp2-hydrocarbonations of dienes and alkynes via palladium hydride catalysis

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 9, 2023

Abstract Transition metal-catalyzed asymmetric hydrofunctionalizations of unsaturated bonds via π-ƞ 3 substitution have emerged as a reliable method to construct stereogenic centers, and mainly rely on the use heteroatom-based or carbon nucleophiles bearing acidic C-H bonds. In comparison, sp 2 are generally not under consideration because enormous challenges in cleaving corresponding inert Here, we report protocol achieve formal hydrocarbonations, including hydroalkenylation, hydroallenylation hydroketenimination both 1,3-dienes alkynes hydroalkylation Wittig reaction cascade. A series unachievable motifs hydrofunctionalizations, such di-, tri- tetra-substituted alkenes, allenes, tri-substituted ketenimines allyl skeletons all facilely constructed high regio-, diastereo- enantioselectivities with this cascade design. Stereodivergent synthesis four stereoisomers 1,4-diene stereocenter Z/E-controllable olefin unit highlights power present protocol. An interesting mechanistic feature is revealed that alkyne actually undergoes hydrocarbonation formation conjugated diene intermediate, different from conventional viewpoint hydrofunctionalization only involves allene species.

Language: Английский

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Transition Metal-Catalyzed Asymmetric Migratory Allylic C—H Functionalization of Remote Dienes

Chinese Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 45(2), P. 592 - 592

Published: Jan. 1, 2025

Language: Английский

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Palladium(0) and Brønsted Acid Co‐catalyzed Enantioselective Hydro‐Cyclization of 2,4‐Dienyl Hydrazones and Oximes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(44)

Published: Aug. 6, 2024

Abstract The transition metal‐catalyzed asymmetric hydro‐functionalization of 1,3‐dienes has been well explored, but most reactions focus on electron‐neutral substrates in an intermolecular manner. Here we first demonstrate that readily available 2,4‐dienyl hydrazones and oximes can be efficiently utilized the hydro‐cyclization reaction under co‐catalysis a Brønsted acid chiral palladium complex, furnishing multifunctional dihydropyrazones dihydroisoxazoles, respectively. Diverse substitution patterns for both types electron‐deficient diene compounds are tolerated, corresponding heterocycles were generally constructed with moderate to excellent enantioselectivity, which elaborated access products higher molecular complexity diversity. Control experiments density functional theory calculations support α‐regioselective protonation dienyl by concurrent π‐Lewis base activation Pd 0 complex is energetically favoured formation active π‐allylpalladium intermediates, outer‐sphere allylic amination or etherification mode adopted deliver observed cyclized enantioselectively.

Language: Английский

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Copper-Catalyzed Regioselective 1,4-Sulfonyl Indolylation of 1,3-Dienes with Sulfonyl Chloride and Indoles

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

Published: Feb. 22, 2025

A copper-based catalytic system has been described to enable the efficient 1,4-sulfonylindolylation of 1,3-dienes with sulfonyl chloride and indoles. This protocol offers a practical method for synthesis allylsulfone-containing indole derivatives broad range compatible functionalities excellent chemo- regioselectivities. Mechanistic studies suggest that copper catalyst plays dual role initiating radicals prompting coupling in this conjugated diene-selective 1,4-difunctionalization strategy.

Language: Английский

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Palladium‐Catalyzed Enantioselective Migratory Hydroamidocarbonylation of Amide‐Linked Alkenes to Access Chiral α‐Alkyl Succinimides

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: July 15, 2024

A Pd-catalyzed asymmetric isomerization-hydroamidocarbonylation of amide-containing alkenes was developed, affording a variety chiral α-alkyl succinimides in moderate to good yields with high enantioselectivities. The key success introducing bulky 1-adamentyl P-substitution and 2,3,5,6-tetramethoxyphenyl group into the rigid P-chirogenic bisphosphine ligand create stronger steric hinderance deeper catalytic pocket. By this approach, regio- or stereo-convergent synthesis enantiomeric from mixture olefin isomers achieved.

Language: Английский

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