Nickel‐Catalyzed Defluorinative Asymmetric Cyclization of Fluoroalkyl‐Substituted 1,6‐Enynes for the Synthesis of Seletracetam

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(46)

Опубликована: Сен. 23, 2022

Abstract The introduction of fluorine‐containing groups into organic molecules can significantly affect their physical and chemical properties has long been used as an effective strategy for drug discovery development. Consequently, the development catalytic asymmetric methods synthesis heterocycles is highly desirable sought after. Herein, we describe a nickel‐catalyzed defluorinative cyclization fluoroalkyl‐substituted 1,6‐enynes, providing expedient access to synthetically attractive 4‐fluorovinyl‐substituted 2‐pyrrolidones in good yields with remarkable high levels chemo‐, regio‐, enantioselectivities (90–99 % ee,>35 examples). This protocol features readily available starting materials excellent functional group compatibility, exhibits complementary regioselectivity. utility this was demonstrated enantioselective antiepileptic Seletracetam.

Язык: Английский

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Enantioselective Metal-Catalyzed Reductive Coupling of Alkynes with Carbonyl Compounds and Imines: Convergent Construction of Allylic Alcohols and Amines

ACS Catalysis, Год журнала: 2022, Номер 12(14), С. 8164 - 8174

Опубликована: Июнь 23, 2022

The use of alkynes as vinylmetal pronucleophiles in intermolecular enantioselective metal-catalyzed carbonyl and imine reductive couplings to form allylic alcohols amines is surveyed. Related hydrogen auto-transfer processes, wherein or serve dually reductants proelectrophiles, also are cataloged, applications target-oriented synthesis. These processes represent an emerging alternative the stoichiometric reagents Nozaki-Hiyama-Kishi (NHK) reactions alkenylation.

Язык: Английский

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Enantioselective Cobalt-Catalyzed Hydroboration of Fluoroalkyl-Substituted Alkenes to Access Chiral Fluoroalkylboronates

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(33), С. 15333 - 15338

Опубликована: Авг. 11, 2022

Selective defluoroborylation and asymmetric hydroboration reactions of fluoroalkyl-substituted terminal alkenes with pinacolborane (HBpin) have been developed cobalt catalysts generated from Co(acac)2 bisphosphine ligands. A variety undergo this enantioselective hydroboration, affording the corresponding chiral alkylboronates containing stereogenic carbon centers high enantioselectivity (up to 98% ee). This provides a versatile foundation for synthesis organofluorine compounds centers.

Язык: Английский

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Bulky P-stereogenic ligands. A success story in asymmetric catalysis

Coordination Chemistry Reviews, Год журнала: 2023, Номер 489, С. 215192 - 215192

Опубликована: Май 9, 2023

Since the development of BisP* ligand by Imamoto, P-stereogenic phosphines bearing a bulky tert-butyl group and smaller alkyl have demonstrated extraordinary proficiency in wide range asymmetric processes. Over time, this class ligands has brought about introduction more rigid backbones, three-hindered quadrant concept, substitution adamantyl. The methyl fragment also been introduced phosphino-oxazoline-type ligands, chemists industrial sector contributed to evolution reporting first successful Buchwald-type monophosphines for coupling reactions. present review covers synthesis applications that developed since advent late 1990s, with special emphasis on successfully applied catalysis.

Язык: Английский

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Cobalt‐Catalyzed Enantioselective Reductive α‐Chloro‐Carbonyl Addition of Ketimine to Construct the β‐Tertiary Amino Acid Analogues

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(25)

Опубликована: Янв. 22, 2024

β-Tertiary amino acid derivatives constitute one of the most frequently occurring units in natural products and bioactive molecules. However, efficient asymmetric synthesis this motif still remains a significant challenge. Herein, we disclose cobalt-catalyzed enantioselective reductive addition reaction ketimine using α-chloro carbonyl compound as radical precursor, providing expedient access to diverse array enantioenriched β-quaternary analogues. This protocol exhibits outstanding enantioselectivity broad substrate scope with excellent functional group tolerance. Preliminary mechanism studies rule out possibility Reformatsky-type confirm involvement species stereoselective process. The synthetic utility has been demonstrated through rapid assembly iterative oligopeptide, showcasing its versatile platform for late-stage modification drug candidates.

Язык: Английский

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Recent Advances in Cyclization Reactions of 1,6‐Enynes

Advanced Synthesis & Catalysis, Год журнала: 2024, Номер 366(6), С. 1220 - 1268

Опубликована: Янв. 22, 2024

Abstract Elaborated molecular architectures, specifically those bearing one or more carbon stereocenters, stand as an important class of carbocyclic and heterocyclic frameworks because they are frequently occurring core structures in numerous natural products biologically active pharmaceutical molecules. Over the past few decades, development versatile synthetic approaches via cascade cyclization reactions 1,6‐enynes for construction a series fused spiro compounds has been focus great deal research initiatives. These synthesis strategies peculiarly fascinating context assembly wide array molecules, products, agrochemicals, functional materials. In this review, recent developments transformations with diverse coupling reagents summarized since 2018, which could be divided into five categories: 1) Introduction; 2) Transition metal catalyzed 1,6‐enynes; 3) Metal‐free 4) Visible‐light‐induced 5) Electrocatalytic 1,6‐enynes.

Язык: Английский

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Nickel-catalyzed switchable arylative/endo-cyclization of 1,6-enynes

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 4, 2024

Abstract Carbo- and heterocycles are frequently used as crucial scaffolds in natural products, fine chemicals, biologically pharmaceutically active compounds. Transition-metal-catalyzed cyclization of 1,6-enynes has emerged a powerful strategy for constructing functionalized carbo- heterocycles. Despite significant progress, the regioselectivity alkyne functionalization is entirely substrate-dependent. And only exo -cyclization/cross-coupling products can be obtained, while endo -selective cyclization/cross-coupling remains elusive still poses formidable challenge. In this study, we disclose nickel-catalyzed switchable arylation/cyclization which nature ligand dictates arylation, electrophilic trapping reagents determine selectivity mode. Specifically, using commercially available 1,10-phenanthroline facilitates trans -arylation/cyclization to obtain seven-membered ring 2-naphthyl-substituted bisbox promotes cis access six-membered products. Diastereoselective cyclizations have also been developed synthesis enantioenriched piperidines azepanes, core structural elements pharmaceuticals possessing important biological activities. Furthermore, experimental density functional theory studies reveal that arylation process controlled by steric hindrance ligand; reaction mechanism involves -cyclization followed Dowd-Beckwith-type expansion form

Язык: Английский

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Cobalt‐Catalyzed Enantioselective Hydroboration/Cyclization of 1,7‐Enynes: Asymmetric Synthesis of Chiral Quinolinones Containing Quaternary Stereogenic Centers

Angewandte Chemie International Edition, Год журнала: 2019, Номер 58(26), С. 8882 - 8886

Опубликована: Апрель 15, 2019

An asymmetric cobalt-catalyzed hydroboration/cyclization of 1,7-enynes to synthesize chiral six-membered N-heterocyclic compounds was developed. A variety aniline-tethered react with pinacolborane afford the corresponding boryl-functionalized quinoline derivatives in high yields enantioselectivity. This cyclization 1,7-enyens provides a general approach access series containing quaternary stereocenters.

Язык: Английский

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Cobalt-Catalyzed Regiodivergent Stereoselective Hydroboration of 1,3-Diynes To Access Boryl-Functionalized Enynes

ACS Catalysis, Год журнала: 2019, Номер 9(11), С. 10109 - 10114

Опубликована: Окт. 3, 2019

We report a regiodivergent and stereoselective hydroboration of 1,3-diynes with pinacolborane (HBpin) in the presence cobalt catalysts generated situ from bench-stable Co(acac)2 bisphosphine ligands. These were activated by reactions HBpin. A range unsymmetrical symmetrical reacted smoothly HBpin Co(acac)2/xantphos to selectively afford enynylboronate products boron addition internal carbon 1,3-diyne unit. However, these Co(acac)2/dppf form external show good functional group compatibility can be readily scaled up gram-scales without using drybox. Deuterium-labeling experiments suggest cis-addition less-hindered triple bond 1,3-diynes. Furthermore, comparison regioselectivity between cobalt-catalyzed hydrosilylation same substrate suggests that Co(acac)2/xantphos-catalyzed regioselective proceeds through cobalt-hydride intermediate while Co(acac)2/dppf-catalyzed proceed boryl intermediate.

Язык: Английский

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Enantioselective Cobalt‐Catalyzed Intermolecular Hydroacylation of 1,6‐Enynes

Angewandte Chemie International Edition, Год журнала: 2020, Номер 59(38), С. 16409 - 16413

Опубликована: Июнь 11, 2020

Abstract We report a cobalt‐catalyzed hydroacylation of 1,6‐enynes with exogenous aldehydes in domino sequence to construct enantioenriched ketones. The products were obtained good yields excellent regio‐, diastereo‐, and enantioselectivity. Furthermore, the chiral served as valuable precursors access complex spirocyclic scaffolds three contiguous stereocenters. asymmetric process exhibited no C−H crossover KIE, thus indicating that bond cleavage was not involved turnover‐limiting step.

Язык: Английский

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