Recent Strategies in the Nucleophilic Dearomatization of Pyridines, Quinolines, and Isoquinolines

Chemical Reviews, Год журнала: 2024, Номер 124(3), С. 1122 - 1246

Опубликована: Янв. 2, 2024

Dearomatization reactions have become fundamental chemical transformations in organic synthesis since they allow for the generation of three-dimensional complexity from two-dimensional precursors, bridging arene feedstocks with alicyclic structures. When those processes are applied to pyridines, quinolines, and isoquinolines, partially or fully saturated nitrogen heterocycles formed, which among most significant structural components pharmaceuticals natural products. The inherent challenge lies low reactivity heteroaromatic substrates, makes dearomatization process thermodynamically unfavorable. Usually, connecting event irreversible formation a strong C–C, C–H, C–heteroatom bond compensates energy required disrupt aromaticity. This aromaticity breakup normally results 1,2- 1,4-functionalization heterocycle. Moreover, combination these subsequent tandem stepwise protocols allows multiple heterocycle functionalizations, giving access complex molecular skeletons. aim this review, covers period 2016 2022, is update state art nucleophilic dearomatizations showing extraordinary ability dearomative methodology indicating their limitations future trends.

Язык: Английский

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Recent Advances in the Reaction of MBH Carbonates: Scope and Mechanism

Asian Journal of Organic Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Июнь 27, 2024

Abstract In recent years, Morita‐Baylis‐Hillman (MBH) carbonates have been extensively used in domino reactions for the synthesis of novel cyclic and acyclic compounds. This review highlights progress made last decade a series compounds from an uncyclized reaction or annulation MBH carbonates, which demonstrates that excellent reactivity high research value as representative substrates organic synthesis. We hope summary understanding can inspire chemists to apply these design more efficient reactions, will be beneficial drug chemistry.

Язык: Английский

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Merging Organocatalysis with 1,2-Boronate Rearrangement: A Lewis Base-Catalyzed Asymmetric Multicomponent Reaction

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(40), С. 27305 - 27311

Опубликована: Сен. 24, 2024

Catalytic asymmetric multicomponent 1,2-boronate rearrangements provide a practical approach for synthesizing highly valuable enantioenriched boronic esters. When applied to alkenyl or heteroaryl boronates, these reactions have relied mainly on transition-metal catalysis. Herein, we present an organocatalytic, Lewis base-catalyzed rearrangement, involving indoles, esters, and Morita-Baylis-Hillman carbonates, leading enantioenriched, substituted indole indoline derivatives. Using cinchona alkaloid-based catalysts, high selectivity has been achieved, enabling expansion of the chemical space around pharmaceutically relevant

Язык: Английский

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Highly Regioselective Synthesis of N‐β‐trifluoromethyl 2‐pyridones via anti‐Markovnikov Hydroamination of α‐(trifluoromethyl)styrenes with 2‐pyridones

Chemistry - An Asian Journal, Год журнала: 2023, Номер 18(10)

Опубликована: Апрель 8, 2023

Abstract A novel and facile method for the synthesis of N ‐β‐CF 3 ‐substituted 2‐pyridones via hydroamination α‐(trifluoromethyl)styrenes with was described. The reaction proceeded smoothly at room temperature, affording a variety ‐(β‐trifluoromethyl‐β‐arylethyl)pyridin‐2(1 H )‐ones in moderate to good yields excellent ‐regioselectivity.

Язык: Английский

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Direct Enantioselective Allylic Alkylation of α-Amino Esters to Quaternary Glutamates via Strategic Pyridoxal Catalyst Design

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

Опубликована: Апрель 24, 2025

The difficulty for N-unprotected α-substituted glycinates as α-C nucleophiles originates from both competing N nucleophilic interference and steric hindrance of the α substituent, which makes direct asymmetric alkylation with Morita-Baylis-Hillman (MBH) adducts especially challenging. Given wide utilization α-quaternary chiral glutamic acid derivatives in therapeutic studies, we took advantage biomimetic carbonyl catalysis to achieve their efficient synthesis. A bifunctional centrally pyridoxal, featured an expanded catalytic cavity reduced around aldehyde group, was designed synthesized. In this work, describe novel pyridoxal enabled MBH acetates. broad range multiple modifications were produced high reactivity excellent stereocontrol.

Язык: Английский

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Synthesis of β‐Amino Acid Derivatives via Enantioselective Lewis Base Catalyzed N‐Allylation of Halogenated Amides with Morita‐Baylis‐Hillman Carbonates

Chemistry - A European Journal, Год журнала: 2023, Номер 30(14)

Опубликована: Дек. 20, 2023

Abstract Trifluoro‐ and trichloroacetamides serving as pronucleophiles undergo enantioselective Lewis base catalyzed N ‐allylation with Morita‐Baylis‐Hillman carbonates to produce enantioenriched β‐amino acid derivatives. The reactions proceed a kinetic resolution give the allylation products remaining in good yields high enantioselectivity. obtained are amenable diastereoselective derivatization library of spiro‐isoxazoline lactams.

Язык: Английский

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Difluorocarbene enabled ester insertion/1,4-acyl rearrangement of 2-acetoxylpyridines: Modular access to gem-difluoromethylenated 2-pyridones

Tetrahedron Letters, Год журнала: 2023, Номер 119, С. 154413 - 154413

Опубликована: Фев. 21, 2023

Язык: Английский

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Rhodium-Catalyzed Selective Nucleophilic Cyclization/Cross-Coupling of Two ortho-Alkynylanilines Bearing Differential N-Substituents

Organic Letters, Год журнала: 2023, Номер 25(31), С. 5890 - 5895

Опубликована: Авг. 2, 2023

Herein, we reported an effective selective nucleophilic cyclization/cross-coupling cascade reaction of N-tosyl ortho-alkynylanilines and N-acyl using Rh(COD)2BF4/tBuXantPhos as a catalyst. The present protocol features excellent chemo- regioselectivity, high atom-economy, broad range substrates. mechanism studies indicated that the key to success this is powerful capacity rhodium catalyst recognize N-substituent group in cyclization alkyne insertion.

Язык: Английский

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Alternative Reactions to Friedel-crafts Acylation on Highly Activated Substrates

Current Organic Chemistry, Год журнала: 2024, Номер 28(13), С. 1006 - 1022

Опубликована: Май 15, 2024

Abstract: Friedel-crafts acylation (FCAcyl) is the most widespread method used to prepare aryl ketones and aldehydes. However, depending on type of group attached benzene, their derivatives influence electronic characteristics structural orientations compounds during acylation; thus, groups are very important for success reaction. The existence strong electron-donating groups, such as polyhydroxy/ polyalkoxyphenols anilines aromatic ring, makes this reaction difficult. To overcome these problems with aim obtaining from benzene compounds, appropriate methodologies were described. Therefore, review consists showing importance applicability Houben-Hoesch Sugasawa reactions alternatives polyhydroxy/polyalkoxyphenols anilines, respectively. main advances in original also use an alternative renowned should be taken into consideration synthetic tool because there possibility reducing steps, consequent improvement yield, addition optimizing performance.

Язык: Английский

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2‐Hydroxypyridines as N‐ and O‐Nucleophiles in Organic Synthesis

European Journal of Organic Chemistry, Год журнала: 2023, Номер 27(2)

Опубликована: Ноя. 6, 2023

Abstract 2‐Hydroxypyridines have emerged as versatile nucleophiles in organic synthesis. The N ‐ and O ‐functionalization of 2‐hydroxypyridines affords straightforward practical methods for the construction ‐substituted 2‐pyridones 2‐hydroxypyridines, which are important structural motifs numerous natural products, pharmaceuticals biologically active compounds. Nonetheless, competition between presents an inevitable formidable challenge. In past few decades, chemoselective and/or has received extensive attention from synthetic community, resulting development elegant effective strategies to address this chemoselectivity. This review provides a summary recent advancements realm transition‐metal organo‐catalyzed, well visible‐light promoted functionalization including ‐alkylation, ‐allylation, ‐arylation, ‐alkenylation, ‐alkenylation.

Язык: Английский

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