Enantio‐ and Diastereodivergent Synthesis of Spirocycles through Dual‐Metal‐Catalyzed [3+2] Annulation of 2‐Vinyloxiranes with Nucleophilic Dipoles

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(47), С. 24941 - 24949

Опубликована: Сен. 17, 2021

The development of efficient and straightforward methods for obtaining all optically active isomers structurally rigid spirocycles from readily available starting materials is great value in drug discovery chiral ligand development. However, the stereodivergent synthesis bearing multiple stereocenters remains an unsolved challenge owing to steric hindrance ring strain. Herein, we report enantio- diastereodivergent through dual-metal-catalyzed [3+2] annulation oxy π-allyl metallic dipoles with less commonly employed nucleophilic (imino esters). A series spiro compounds a pyrroline olefin were easily synthesized manner (up 19:1 dr, >99 % ee), which showed promise as new type N-olefin ligand. Preliminary mechanistic studies also carried out understand process this bimetallic catalysis.

Язык: Английский

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Ni-Catalyzed Ligand-Controlled Regiodivergent Reductive Dicarbofunctionalization of Alkenes

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(27), С. 10282 - 10291

Опубликована: Июнь 24, 2021

Transition-metal-catalyzed dicarbofunctionalization of alkenes involving intramolecular Heck cyclization followed by intermolecular cross-coupling has emerged as a powerful engine for building heterocycles with sterically congested quaternary carbon centers. However, only exo-cyclization/cross-coupling products can be obtained; endo-selective cyclization/cross-coupling not been reported yet and still poses formidable challenge. We herein report the first example catalyst-controlled regiodivergent synthesis five- six-membered benzo-fused lactams bearing all-carbon Using chiral Pyrox- or Phox-type bidentate ligand, 5-exo cyclization/cross-couplings proceed favorably to produce indole-2-ones in good yields excellent regioselectivity enantioselectivities (up 98% ee). When C6-carboxylic acid-modified 2,2′-bipyridine was used 3,4-dihydroquinolin-2-ones were obtained through 6-endo-selective processes. This transformation is modular tolerant variety functional groups. The ligand rather than substrate structures precisely dictates pattern. Moreover, synthetic value this protocol demonstrated preparation biologically relevant molecules structural scaffolds.

Язык: Английский

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Diboron(4)‐Catalyzed Remote [3+2] Cycloaddition of Cyclopropanes via Dearomative/Rearomative Radical Transmission through Pyridine

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(52)

Опубликована: Ноя. 8, 2022

Abstract Ring structures such as pyridine, cyclopentane or their combinations are important motifs in bioactive molecules. In contrast to previous cycloaddition reactions that necessitated a directly bonded initiating functional group, this work demonstrated novel through‐(hetero)arene radical transmission concept for selective activation of remote bond. An efficient, metal‐free and atom‐economical [3+2] between 4‐pyridinyl cyclopropanes alkenes alkynes has been developed modular synthesis pyridine‐substituted cyclopentanes, cyclopentenes bicyclo[2.1.1]hexanes difficult access using known methods. This complexity‐building reaction was catalyzed by very simple inexpensive diboron(4) compound took place via dearomative/rearomative processes. The substrate scope broad more than 100 new compounds were prepared generally high yields. Mechanistic experiments density function theory (DFT) investigation supported relay catalytic cycle involving alkylidene dihydropyridine intermediates boronyl transfer.

Язык: Английский

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Photoinduced Regiodivergent and Enantioselective Cross-Coupling of Glycine Derivatives with Hydrocarbon Feedstocks

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Regiodivergent asymmetric synthesis represents a transformative strategy for the efficient generation of structurally diverse chiral products from single set starting materials, significantly enriching their enantiomeric composition. However, design radical-mediated regiodivergent and enantioselective reactions that can accommodate wide range functional groups substrates has posed significant challenges. The obstacles primarily lie in switching regioselectivity achieving high enantiodiscrimination, especially when dealing with high-energy intermediates. To address these issues, we have developed new catalytic system integrates photoinduced hydrogen atom transfer (HAT) copper catalysis, involving fine-tuning ligands, additives, other reaction parameters. facilitates cross-couplings between N-aryl glycine ester/amide derivatives abundant hydrocarbon feedstocks through strong C(sp3)–H bond activation. This approach allows controlled stereoselective formation C(sp3)–C(sp3) C(sp3)–N bonds, yielding rich variety C- or N-alkylated esters amides commendable yields (up to 92% yield), exclusive regioselectivities (typically >20:1 rr), enantioselectivities 96% ee). Our methodology not only provides promising avenue incorporation alkyl functionalities onto specific sites biologically molecules but also offers practical while simultaneously induction within photochemical reactions.

Язык: Английский

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Access to 5,6-Spirocycles Bearing Three Contiguous Stereocenters via Pd-Catalyzed Stereoselective [4 + 2] Cycloaddition of Azadienes

Organic Letters, Год журнала: 2021, Номер 23(8), С. 2884 - 2889

Опубликована: Март 26, 2021

We present herein a highly diastereo- and enantioselective Pd-catalyzed [4 + 2] cycloaddition of benzofuran-derived azadienes with vinyl benzoxazinanones, which represents rare stereoselective this class fused as two-atom synthon. The use phosphoramidite ligand bearing chiral secondary amine simple biphenyl backbone proved to be the key construct novel spirocyclic tetrahydroquinoline scaffold containing three contiguous stereocenters single diastereomer in high enantioselectivity.

Язык: Английский

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Recent advances in Pd-catalyzed asymmetric cyclization reactions

Chemical Society Reviews, Год журнала: 2023, Номер 53(2), С. 883 - 971

Опубликована: Дек. 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.

Язык: Английский

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Divergent Enantioselective Access to Diverse Chiral Compounds from Bicyclo[1.1.0]butanes and α,β-Unsaturated Ketones under Catalyst Control

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Сен. 30, 2024

Achieving structural and stereogenic diversity from the same starting materials remains a fundamental challenge in organic synthesis, requiring precise control over selectivity. Here, we report divergent catalytic methods that selectively yield either cycloaddition or addition/elimination products bicyclo[1.1.0]butanes α,β-unsaturated ketones. By employing chiral Lewis acid Brønsted catalysts, achieved excellent regio-, diastereo-, enantioselectivity across all three distinct transformations, affording diverse array of synthetically valuable bicyclo[2.1.1]hexanes cyclobutenes. The outcomes are controlled by differential activation substrates specific catalyst with reaction conditions dictating pathway This strategy demonstrates power catalysis creating molecular complexity diversity, offering tool for synthesis enantioenriched building blocks.

Язык: Английский

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Synthesis of Chiral Endocyclic Allenes and Alkynes via Pd-Catalyzed Asymmetric Higher-Order Dipolar Cycloaddition

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Сен. 18, 2024

A Pd-catalyzed asymmetric higher-order dipolar cycloaddition between allenyl carbonates and azadienes is achieved by exploiting novel alkylidene-π-allyl-Pd dipoles. This research provides a modular platform for the synthesis of challenging chiral endocyclic allenes bearing medium-sized heterocyclic motif centrally stereocenter in good yields with high enantio- diastereoselectivities (29 examples, up to 97% yield, 97:3 er >19:1 dr). Experimental computational studies elucidate possible reaction mechanism observed stereochemical results. Based on mechanistic understanding, new π-propargyl-Pd dipole was designed further extend success higher order strategy 10-membered alkynes from propargyl (13 98% yield 94.5:5.5 er).

Язык: Английский

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Asymmetric Synthesis of 2,2‐Difluorotetrahydrofurans through Palladium‐Catalyzed Formal [3+2] Cycloaddition

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(44), С. 23641 - 23645

Опубликована: Сен. 8, 2021

The asymmetric synthesis of 2,2-difluorinated tetrahydrofurans was accomplished via enantioselective formal [3+2] cycloaddition catalyzed by palladium. reaction between gem-difluoroalkenes and racemic vinyl epoxides or vinylethylene carbonates resulted in the formation enantioenriched 2,2-difluorotetrahydrofurans with an enantioselectivity up to 98 %. Notably, used readily available (R)-BINAP as ligand at a low loading yielded wide variety difluorinated products moderate high yields. Both chiral diastereomers could be obtained single sequence.

Язык: Английский

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Recent applications of vinylethylene carbonates in Pd-catalyzed allylic substitution and annulation reactions: Synthesis of multifunctional allylic and cyclic structural motifs

Coordination Chemistry Reviews, Год журнала: 2022, Номер 462, С. 214526 - 214526

Опубликована: Март 30, 2022

Язык: Английский

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