Intermediate Control: Unlocking Hitherto Unknown Reactivity and Selectivity in N-Conjugated Allenes and Alkynes

Accounts of Chemical Research, Год журнала: 2025, Номер 58(2), С. 281 - 298

Опубликована: Янв. 3, 2025

ConspectusControlling selectivity through manipulation of reaction intermediates remains one the most enduring challenges in organic chemistry, providing novel solutions for selective C-C π-bond functionalization. This approach, guided by activation principles, provides an effective method functional group installation, enabling direct synthesis molecules that are inaccessible conventional pathways. In particular, functionalization N-conjugated allenes and alkynes has emerged as a promising research focus, driven advances controlling reactive strategies. this regard, our group, alongside others, established some new approaches have suitable platform functionalized enamides. Account reviews recent developments field, highlighting modes reactivity selectivity, atom-economical functionalizations, strategies regio- stereocontrol, while mechanistic insights into related transformations.Our study is systematically organized two sections based on substrate type chronological progression. first section, we establish allenamide-derived intermediates, both allenamide-alkyne (AA) cross-coupling few electrophile-promoted hydrofunctionalization reactions. The unprecedented Pd-catalyzed achieved neighboring chelation, with phosphine ligand selection outcome. parallel, functionalizations─including haloalkynylation, hydrooxycarbonylation, hydrodifluoroalkylation, intermolecular hydroamination─are strategic electrophiles or their precursors.Additionally, findings demonstrate how ynamides' toward nucleophiles, controlled activator modulation, expands scope accessible transformations. Key include: (1) chemoselective [2 + 2 2] annulation efficient trapping N-arylated nitrilium ynamides, (2) divergent C-H indole-derived vinylogous ynamides metal via intramolecular hydroarylation, (3) bromoalkynylation-enabled migration 1,3-alkynyl shift.The final section explores N-electron polarization 1,3-enynes enables chemoselectivity metal-free inter- couplings indole substrates. Our modulating conjugation within enyne skeleton─through linear cross conjugation─can pathways control product selectivity.This aims to stimulate broader intermediate-controlled activated π-systems. Future directions include advanced design, strategies, deeper studies enable rational development.

Язык: Английский

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The Merger of Halogen Atom Transfer (XAT) and Energy Transfer Catalysis (EnT) for the Modular 1,2-Iminylalkylation of Diazenes

Organic Letters, Год журнала: 2023, Номер 25(38), С. 7009 - 7013

Опубликована: Сен. 14, 2023

The 1,2-iminylalkylation of diazenes using alkyl iodides in combination with an O-benzoyl oxime is reported. In this transformation, acted as a radical precursor and XAT mediator. addition to common iodides, other such iodomethane, iodomethane-d3, trifluoroiodomethane, ethyl difluoroiodoacetate, iodoalkanes containing unprotected hydroxyl amide groups can also serve C-radical precursors the electrophilic acceptors.

Язык: Английский

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Modular Room Temperature Synthesis of Sulfoximidoyl Amidines Enabled by Pd-Catalyzed Cascade Aza-Claisen Rearrangement Strategy

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Reported herein is a concise synthesis of sulfoximidoyl amidines enabled by Pd-catalyzed cascade aza-Claisen rearrangement and nucleophilic reaction at room temperature. Free NH-sulfoximines N-allylynamides were employed as the modular building blocks to produce expected sulfoximine amidine derivatives in highly chemoselective models 100% atom efficiency. A broad range functional groups well tolerated under these gentle conditions give desired products generally good excellent yields.

Язык: Английский

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HFIP-Mediated, Regio-, and Stereoselective Hydrosulfenylation of Ynamides: A Versatile Strategy to Access Ketene N,S-Acetals

Organic & Biomolecular Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Herein, we report an HFIP-mediated, versatile, sustainable, atom-economical, and regio- stereoselective hydro-functionalization of ynamides with various S-nucleophiles (1 equiv.) such as thiols, thiocarboxylic acids, carbamates, xanthates, O,O-diethyl S-hydrogen phosphorothioate to access a wide variety stereodefined trisubstituted ketene N,S-acetals under mild conditions. This protocol requires only HFIP, which plays multiple roles, acting Brønsted acid protonate the ynamide regioselectively at beta carbon generate reactive keteniminium intermediate, stabilizing intermediate solvent through H-bonding. After nucleophilic attack S-nucleophile on deprotonation, HFIP is regenerated in most cases can be easily recovered recycled, revealing high sustainability protocol. Remarkably, all reactions are highly efficient furnish excellent yields many pure products were obtained just by washing crude reaction mixture pentane. Significantly, green chemistry metrics found excellent.

Язык: Английский

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Chiral Phosphoric Acid-Catalyzed Kinetic Resolution of Tertiary Alcohol-Tethered Ynamides via Controllable Hydroalkoxylation

ACS Catalysis, Год журнала: 2025, Номер unknown, С. 2424 - 2433

Опубликована: Янв. 27, 2025

Язык: Английский

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TMSOTf/TfOH-Promoted [4 + 2] Annulation of Ynamides with 2-Aminoarylnitriles To Construct 2,4-Diaminoquinolines

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 9, 2025

An effective strategy to synthesize 2,4-diaminoquinoline compounds has been efficaciously developed via a TMSOTf/TfOH-promoted [4 + 2] annulation of ynamides with 2-aminoarylnitriles. Compared the reported transition-metal catalysts, this metal-free promotion system presented remarkable advancement, enabling facile and regiospecific assembly frameworks wide functional group compatibility moderate excellent yields.

Язык: Английский

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Nitrogen-Based Organofluorine Functional Molecules: Synthesis and Applications

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Апрель 22, 2025

Fluorine and nitrogen form a successful partnership in organic synthesis, medicinal chemistry, material sciences. Although fluorine-nitrogen chemistry has long rich history, this field received increasing interest made remarkable progress over the past two decades, driven by recent advancements transition metal organocatalysis photochemistry. This review, emphasizing contributions from 2015 to 2023, aims update state of art synthesis applications nitrogen-based organofluorine functional molecules chemistry. In dedicated sections, we first focus on fluorine-containing reagents organized according type groups attached nitrogen, including N-F, N-RF, N-SRF, N-ORF. review also covers nitrogen-linked building blocks, catalysts, pharmaceuticals, agrochemicals, underlining these components' broad applicability growing importance modern

Язык: Английский

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Catalytic intermolecular hydrofunctionalizations of ynamides

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(8), С. 2351 - 2374

Опубликована: Янв. 1, 2024

This review carefully summarizes the advances achieved in catalytic hydrofunctionalization of ynamides and is categorized by bond formation type including C−C, C−X, C−O, C−N, C−S, C−P, C−Si, C−Ge bonds.

Язык: Английский

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TMSOTf-Catalyzed [4 + 2] Annulation of Ynamides and β-(2-Aminophenyl)-α,β-ynones for the Synthesis 2-Aminoquinolines

Organic Letters, Год журнала: 2024, Номер 26(17), С. 3503 - 3508

Опубликована: Апрель 25, 2024

A metal-free TMSOTf-catalyzed [4 + 2] annulation of ynamides with β-(2-aminophenyl)-α,β-ynones enables the regiospecific and facile assembly 2-aminoquinoline frameworks. The catalyst TMSOTf presented a remarkable advancement compared to previously reported transition-metal catalysts. wide range 3-aryl/alkyl-substituted 2-aminoquinolines were generated in moderate excellent yields due mild conditions.

Язык: Английский

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Synthetic Strategy for Unsymmetrical α-Fluoro-α′-aryl Ketones

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

α-Fluoro-α′-aryl ketones are crucial in pharmaceuticals and agrochemicals. However, synthesizing unsymmetrical α-fluoro-α′-aryl poses regioselective challenges. This study presents a one-pot aryl-oxy-fluorination method for such fluoro-aryl ketones. Using ynamide, aryl boronic acid, F-source under Pd-catalysis, this efficiently produces wide range of valuable with potential applications. Through combination control experiments DFT studies, we proposed reaction mechanism involving situ acetic acid formation.

Язык: Английский

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