Highly Diastereoselective [3 + 2] Cycloaddition of Aziridines with Difluorinated Silyl Enol Ethers: Divergent Synthesis of 4,4-Difluoropyrrolidines and 4-Fluoropyrroles

Organic Letters, Год журнала: 2024, Номер 26(3), С. 751 - 756

Опубликована: Янв. 12, 2024

A highly diastereoselective [3 + 2] cycloaddition of aziridines with difluorinated silyl enol ethers has been developed. This approach provides a facile methodology for functionalized gem-difluorinated pyrrolidines in good to excellent yields functional group tolerance. one-pot, two-step synthesis structurally interesting fluorinated pyrroles also developed through cycloaddition/aromatization/desulfonation sequence. Moreover, readily available substrates, mild reaction conditions, and easy scale-up show practical advantages.

Язык: Английский

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Synthesis of Fluorinated Pyrrolo[2,1-a]isoquinolines through Decarboxylative/Dehydrofluorinative [3 + 2] Cycloaddition Aromatization of Isoquinolinium N-Ylides with Difluoroenoxysilanes

Organic Letters, Год журнала: 2023, Номер 25(26), С. 4908 - 4912

Опубликована: Июнь 23, 2023

A decarboxylative/dehydrofluorinative formal [3 + 2] cycloaddition aromatization of isoquinolinium N-ylides with difluoroenoxysilanes has been developed. This methodology provides a facile and straightforward synthetic pathway to afford highly functionalized fluorinated pyrrolo[2,1-a]isoquinolines in good excellent yields under mild conditions. Moreover, gram-scale derivatization experiments for the late-stage functionalization drug molecules have also demonstrated.

Язык: Английский

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Multicomponent Dearomative Difluoroalkylation of Isoquinolines with Difluorinated Silyl Enol Ethers: Divergent Synthesis of gem-Difluorinated Heterocycles

Organic Letters, Год журнала: 2023, Номер 25(28), С. 5366 - 5371

Опубликована: Июль 11, 2023

A multicomponent dearomative difluoroalkylation of isoquinolines has been developed with difluorinated silyl enol ethers serving as poor nucleophiles without an additional transition-metal or organic catalyst. The sequential oxidative rearomatization under different alkaline conditions provides a controllable formal C-H and difluoromethylation method for peroxide metal oxidant. series including pharmaceutical, phenanthridine, quinolines, were suitable substrates to construct gem-difluorinated heterocycles. inexpensive starting materials, mild reaction conditions, simple operation also show practical environmentally benign advantages.

Язык: Английский

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Hexafluoroisopropanol (HFIP)-Promoted Hydrodifluoroalkylation of Furans and Vinyl Ethers Using Difluorinated Silyl Enol Ethers for the Synthesis of gem-Difluorinated Ethers

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

Опубликована: Фев. 18, 2025

A hexafluoroisopropanol (HFIP)-promoted hydrodifluoroalkylation of furans and vinyl ethers with difluorinated silyl enol has been developed. Because the inherent electron richer nature poor nucleophilicity ethers, employment simple as substrates for nucleophilic dearomatization without a metal or stoichiometric chemical oxidizing reagent is challenging, especially considering rearomatization driving force ring fragmentation furan system. This protocol exploits formation oxocarbenium intermediate from using HFIP proton source to allow addition which provides an efficient synthetic strategy install gem-difluorinated group into heterocycles.

Язык: Английский

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(3+2) Annulation of Donor–Acceptor Cyclopropanes with Difluoroenoxysilanes: Syntheses of gem-Difluorocyclopentenes via α,α-Difluoroketone Scaffolds

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

Опубликована: Март 27, 2025

Herein, we present an acid- and base-mediated approach for ring opening of donor-acceptor cyclopropanes (DACs) followed by (3+2) annulation, yielding biologically relevant gem-difluorinated cyclopentenes via α,α-difluoroketone scaffolds. Fluorinated rings are essential building blocks in drug discovery materials research. This methodology has a broad substrate scope, is scalable, provides practical synthetic route to obtain value-added fluorinated compounds.

Язык: Английский

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Synthesis of gem-Difluoro-3,4-dihydro-2H-pyrans via a TfOH-Catalyzed [4 + 2] Annulation of Difluoroenoxysilanes with α-Cyano Chalcones

Organic Letters, Год журнала: 2024, Номер 26(7), С. 1447 - 1451

Опубликована: Фев. 14, 2024

Difluoroenoxysilane, a commonly used difluoroallylating reagent, has attracted considerable attention in recent years. However, its application the annulation reaction for construction of fluorinated heterocyclic compounds remains relatively limited. Presented here is Brønsted acid-catalyzed efficient formal [4 + 2] difluoroenoxysilanes with α-cyano chalcones. The developed protocol demonstrates tolerance to various substituents under mild conditions, providing reliable approach construct gem-difluoro-3,4-dihydro-2H-pyrans good excellent yields high diastereoselectivities.

Язык: Английский

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HFIP-Promoted Divergent Cycloadditions of Difluoroenoxysilanes with 2-Indolylmethanols: Synthesis of Fluoro 2H-Pyrano[3,4-b]indoles and gem-Difluoro Cyclopenta[b]indoles

Organic Letters, Год журнала: 2024, Номер 26(22), С. 4610 - 4615

Опубликована: Май 23, 2024

An oxa-6π-electrocyclization of difluoroenoxysilanes with diaryl 2-indolylmethanols has been developed. In addition, a rarely reported C3-nucleophilic [3+2] cycloaddition dialkyl disclosed. This divergent approach affording readily available as three-atom and C2 synthons provides rapid access to fluoro 2

Язык: Английский

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Difluoroenoxysilane: Expanding Allenamide Hydrodifluoroalkylation for Diverse Carbon Frameworks

Organic Letters, Год журнала: 2024, Номер 26(27), С. 5676 - 5681

Опубликована: Июнь 26, 2024

This study presents an effective route to access functionalizable fluorinated enamides characterized by their high regiospecificity around the allenamide. Synthetic applications of resulting difluorocarbonyl-bearing enamide products were pursued through straightforward synthetic transformations prepare unknown functionalized valuable halogenated O-heterocycles and C5 skeletons. Experimental mechanistic studies showed that hydrodifluoroalkylation occurs via a hidden Brønsted acid activation, thereby establishing new electrophilic activation mode for allenamide conjugated iminium intermediate.

Язык: Английский

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DMSO-Promoted Difluoroalkylation of Organophosphonium Salts with Difluoroenol Silyl Ethers

Organic Letters, Год журнала: 2022, Номер 24(30), С. 5557 - 5561

Опубликована: Июль 22, 2022

An efficient method for the synthesis of β,β-di(hetero)aryl-α,α-difluorinated ketones using readily available organophosphonium salts and difluoroenol silyl ethers has been developed. This mild reaction features a good functional group tolerance, scaled-up synthesis, synthetic simplicity. By taking advantage DMSO as less-toxic promoter solvent difluoroalkylation C–P bond functionalization, use transition-metal catalysts sensitive additives could be avoided.

Язык: Английский

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1,6‐Addition Reactions of Difluoroenol Silyl Ethers with Benzoquinones and Quinonediimines To Access Difluorooxymethyl and Difluoroaminomethyl Compounds

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(24), С. 4550 - 4555

Опубликована: Ноя. 14, 2023

Abstract The etherification and amination of difluoroenol silyl ethers with benzoquinones quinonediimines were achieved by using hexafluoroisopropanol (HFIP) as the solvent. This 1,6‐addition reaction could construct difluorooxymethyl difluoroaminomethyl compounds under metal‐free conditions. It is preliminarily speculated that took place through a single electron transfer (SET) process.

Язык: Английский

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