Oxygen Migration–Defluorination Strategy Enables the Aminocarbonylation of Enaminones with o-Aminobenzamides and CF₂Br₂

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Фев. 24, 2025

The development of different concept approaches and user-friendly carbonyl surrogates for aminocarbonylation is highly desirable. Herein, we report the photocatalytic enaminones with easily available o-aminobenzamides CF2Br2 through an oxygen migration-defluorination strategy. reaction features switchable transformation construction carbamoyl-substituted enol products allows expedient synthesis fully substituted maleimides under mild conditions.

Язык: Английский

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Triftosylhydrazone in Single-Atom Skeletal Editing

Accounts of Chemical Research, Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

ConspectusIn the past decade, single-atom skeletal editing, which involves precise insertion, deletion, or exchange of single atoms in core skeleton a molecule, has emerged as promising synthetic strategy for rapid construction diversification complex molecules without laborious de novo processes. Among them, carbene-initiated editing is particularly appealing due to ready availability and diverse reactivities carbene species. The initial endeavors modify heteroarenes through carbon-atom insertion could date back 1881, when Ciamician Denstedt described conversion pyrroles pyridines by trapping haloform-derived free carbene. Despite its potential value, general applicability this one-carbon seen limited progress poor yields harsh reaction conditions. Significant advances via were achieved only 3 years Levin, Ball, Xu, Song, Glorius, others. hallmark these approaches facile halocyclopropanation followed regioselective ring opening facilitated expulsion halide ion. Consequently, specially designed α-halocarbene precursors, such haloform derivatives, α-halodiazoacetates, chlorodiazirines, α-chlorodiazo oxime esters, can be employed achieve Ciamician–Denstedt-type editing. This not limits types functional groups installed on expansion products but also prevents their widespread adoption, especially late-stage contexts. enduring quest develop environmentally friendly versatile superior group compatibility, application diversifications investigation mechanistic insights into carbon reactions remain fundamental objective.In our over 5 years, we have developed o-trifluoromethylbenzenesulfonylhydrazones (named Triftosylhydrazones) operationally safe easily decomposable diazo surrogates explored various challenging catalytic transfer reactions. Recently, put great efforts expanding scope unlocking triftosylhydrazones precursors Since 2018, realized range acyclic 1,3-dicarbonyls with silver carbenes access 1,4-dicarbonyls, proceeding cyclopropanation/ring-opening process. Inspired results, recently demonstrated series transition-metal-catalyzed highly selective medicinally interesting like pyrroles, indoles, 1,2-diazoles carbenic insertion. We then strained three-membered nitrogen- oxygen-containing heterocycles single-carbon atoms. In Account, present an overview achievements heterocycles, organized based three situ-generated key intermediates, cyclopropane, N-ylide, O-ylide from focus scopes, features, applications. hope that Account will provide valuable contribute development new methodologies both chemistry fields.

Язык: Английский

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N‐Heterocycle‐Editing to Access Fused‐BN‐Heterocycles via Ring‐Opening/C−H Borylation/Reductive C−B Bond Formation

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(10)

Опубликована: Янв. 10, 2024

Skeletal editing of N-heterocycles has recently received considerable attention, and the introduction boron atom into heterocycles often results in positive property changes. However, direct enlargement through insertion is rarely reported literature. Here, we report a N-heterocyclic reaction combination C-H borylation, accessing fused-BN-heterocycles. The synthetic potential this chemistry was demonstrated by substrate scope late-stage diversification products.

Язык: Английский

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Controllable Skeletal and Peripheral Editing of Pyrroles with Vinylcarbenes

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(24)

Опубликована: Апрель 10, 2024

Abstract The skeletal editing of azaarenes through insertion, deletion, or swapping single atoms has recently gained considerable momentum in chemical synthesis. Here, we describe a practical strategy using vinylcarbenes situ generated from trifluoromethyl vinyl N ‐triftosylhydrazones, leading to the first dearomative pyrroles carbon‐atom insertion. Furthermore, depending on used catalyst and substrate, three types peripheral reactions are also disclosed: α‐ γ‐selective C−H [3+2] cycloaddition. These controllable molecular provide powerful platform for accessing medicinally relevant CF 3 ‐containing ‐heterocyclic frameworks, such as 2,5‐dihydropyridines, piperidines, azabicyclo[3.3.0]octadienes, allylated readily available pyrroles. Mechanistic insights experiments density functional theory (DFT) calculations shed light origin substrate‐ catalyst‐controlled chemo‐ regioselectivity well reaction mechanism.

Язык: Английский

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Toward the Generation of 2-Amino-3-Formyl Difunctionalized Chromones via Pd-Enabled Rearrangement Strategy

ACS Catalysis, Год журнала: 2023, Номер 13(19), С. 12692 - 12699

Опубликована: Сен. 14, 2023

Accomplished herein is a rearrangement strategy for the highly efficient assembly of synthetically cumbersome while medicinally significant 2-amino-3-formyl chromones via palladium-catalyzed ring-opening, rearrangement, and cyclization process. Such sequence enables formation one C(sp2)–O bond C(sp2)–C(sp2) bond, reconstruction benzo-γ-pyrone moiety in single operation, thus producing difunctionalized chromone-incorporated derivatives. The reaction proceeds shorter time (30 min 3-iodochromones most cases) atom- step-economical manner. synthetic application current protocol further demonstrated by late-stage modification pharmaceuticals their intermediates, gram-scale reactions, transformations functional groups, as well synthesis bioactive molecules drugs. Mechanistic studies indicate that nucleophilic ring-opening process moiety, phenoxy anion intermediate, an intramolecular might be involved present system.

Язык: Английский

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Dearomative Insertion of Fluoroalkyl Carbenes into Azoles Leading to Fluoroalkyl Heterocycles with a Quaternary Center

Angewandte Chemie International Edition, Год журнала: 2023, Номер 63(1)

Опубликована: Ноя. 15, 2023

Abstract The skeletal ring expansion of heteroarenes through carbene insertion is gaining popularity in synthetic chemistry. Efficient strategies for heterocyclic to access heterocycles containing a fluoroalkyl quaternary carbon center are highly desirable because their broad applications medicinal Herein, we report general strategy the dearomative one‐carbon azoles using N ‐triftosylhydrazones as precursors, resulting ring‐expanded excellent yields with good functional‐group compatibility. generality this methodology late‐stage diversification pharmaceutically interesting bioactive molecules and versatile transformations products has been demonstrated.

Язык: Английский

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One‐Carbon Ring Expansion of Indoles and Pyrroles: A Straightforward Access to 3‐Fluorinated Quinolines and Pyridines

Angewandte Chemie International Edition, Год журнала: 2023, Номер 63(5)

Опубликована: Дек. 12, 2023

Abstract 3‐Fluorinated quinolines and pyridines are prevalent pharmacophores, yet their synthesis is often challenging. Herein, we demonstrate that dibromofluoromethane as bromofluorocarbene source enables the one‐carbon ring expansion of readily available indoles pyrroles to structurally diverse 3‐fluorinated pyridines. This straightforward protocol requires only a short reaction time ten minutes can be performed under air atmosphere. Preliminary investigations reveal this strategy also applied other valuable azines by using different 1,1‐dibromoalkanes bromocarbene sources.

Язык: Английский

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Silver‐Catalyzed Dearomative Skeletal Editing of Indazoles by Donor Carbene Insertion

Chemistry - A European Journal, Год журнала: 2024, Номер 30(16)

Опубликована: Янв. 11, 2024

Abstract Given the prevalence of heterocyclic scaffolds in drug‐related molecules, converting these highly modular into structural diversified and dearomatized analogs is an ideal strategy for improving their physicochemical pharmacokinetic properties. Here, we described efficient method silver carbene‐mediated dearomative N−N bond cleavage leading to skeletal hopping between indazole 1,2‐dihydroquinazoline via a selective single‐carbon insertion procedure. Using this methodology, series dihydroquinazoline analogues with diarylmethylene‐substituted quaternary carbon centers were constructed excellent yields good functional group compatibility, which was further illustrated by late‐stage diversification important pharmaceutically active ingredients. DFT calculations indicated that catalyst not only induces formation carbene, but also activates diazahexatriene intermediate, plays crucial role C−N bond.

Язык: Английский

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Pd‐Catalyzed Synthesis of Aryl Esters Involving Difluorocarbene Transfer Carbonylation

European Journal of Organic Chemistry, Год журнала: 2024, Номер 27(10)

Опубликована: Фев. 14, 2024

Abstract A Pd‐catalyzed three‐component intermolecular reaction between aryl halides, ClCF 2 COONa and phenols is developed. series of benzoates were synthesized in up to 84 % yield via difluorocarbene transfer carbonylation. It devoted acquiring the targeted products by construction new C−C, C=O C−O bonds a one‐pot, one‐step process. The feature this method includes use readily available starting materials, showing outstanding resistance spatial obstruction simple operation procedure with mild conditions. Therefore, makes methodology useful alternative other schemes typically used for synthesis esters.

Язык: Английский

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Asymmetric one-carbon ring expansion of diverse N-heterocycles via copper-catalyzed diyne cyclization

Science Advances, Год журнала: 2024, Номер 10(41)

Опубликована: Окт. 9, 2024

One-carbon ring expansion reaction of N-heterocycles has gained particular attention in the past decade because this method allows for conversion readily available into potentially useful complex ring-expanded N-heterocycles, which are inaccessible by traditional methods. However, catalytic asymmetric variant been rarely reported to date. Herein, we disclose an enantioselective one-carbon through chiral copper-catalyzed diyne cyclization, leading practical, atom-economic and divergent assembly array valuable bearing a quaternary stereocenter generally good excellent yields with enantioselectivities (up >99% ee). This protocol represents first example based on alkynes.

Язык: Английский

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