Photocatalytic Three-Component Reductive Coupling Synthesis of gem-Difluorohomoallyl Secondary Amines

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

gem-Difluorohomoallyl amines, an important class of gem-difluoroalkenes, are prevalent moieties in many bioactive compounds. However, limited methods suitable for the synthesis this type compound containing secondary amines. Here, we display a photocatalytic multicomponent protocol gem-difluoroalkenes which makes use readily available materials: arylamines, alkyl aldehydes, and α-trifluoromethyl alkenes. Moreover, ketones amines also substrates. Preliminary mechanistic experiments indicate that key α-amino radical was involved, generated from reduction situ-formed imines (or iminium ions) by reduced photocatalyst. Subsequent addition to alkenes β-F elimination deliver desired products.

Language: Английский

---

Accessing Fluorinated Tertiary Homoallylamines via Photocatalytic Defluorinative Aminoalkylation of Fluoroalkyl-Substituted Alkenes

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(11), P. 8252 - 8260

Published: May 13, 2024

Due to their appealing physiological attributes, tertiary aliphatic amines are pervasive in a myriad of biologically active molecules. In particular, featuring homoallylic substituents serve as versatile synthetic building blocks. Therefore, there is growing demand for the development practical and modular methods rapid assembly sp3-rich complex from readily accessible chemical feedstock. Here, we disclose multicomponent, reductive photocatalytic protocol that merges secondary alkylamines, carbonyl compounds, fluoroalkyl-substituted alkenes, yielding fluorinated homoallylamines. This defluorinative aminoalkylation involves addition alkyl-substituted α-amino radicals, generated reduction situ-generated iminium ions by photocatalyst, alkenes subsequent fluoride elimination, reliably furnishing gem-difluoroalkene monofluoroalkene motifs not easily through alternative methods. Utility method was demonstrated its broad functional group compatibility, derivatization synthesis drug analogues.

Language: Английский

---

Visible light-promoted defluorinative alkylation/arylation of α-trifluoromethyl alkenes with thianthrenium salts

Green Chemistry, Journal Year: 2024, Volume and Issue: 26(17), P. 9371 - 9377

Published: Jan. 1, 2024

Defluorinative alkylation and arylation between thianthrenium salts α-trifluoromethyl alkene to afford gem -difluoroolefins by easily recycling thianthrene under visible light irradiation free of metal photocatalyst.

Language: Английский

---

Photocatalyzed 1,3-Bromodifluoroallylation of [1.1.1]Propellane with α-Trifluoromethylalkenes and KBr Salts

Organic Letters, Journal Year: 2024, Volume and Issue: 26(32), P. 6889 - 6893

Published: Aug. 6, 2024

Herein we unveil a visible-light-driven transition-metal-free 1,3-bromodifluoroallylation of [1.1.1]propellane. This reactivity is harnessed through organophotocatalysis, providing practical synthetic pathways to 1-brominated-3-

Language: Английский

---

Nucleophilic addition of bulk chemicals with imines using N-functionalized hydroxylamine reagents as precursors

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

C–C and C–X bond forming reactions are essential tools in organic synthesis, constantly revolutionizing human life. Among the key methods for constructing new chemical bonds nucleophilic addition involving imines. However, inherent challenges synthesizing storing imines have stimulated interest designing stable precursors, which generates situ during reaction. This approach offers a promising alternative to traditional strategies holds significant potential future applications. Here we report direct general of with cost-effective feedstocks easily accessible nucleophiles, specifically utilizing N‑functionalized hydroxylamine reagents as bench-stable precursors. methodology streamlines synthesis various products, such amino acid derivatives, through wide range reaction types, including C–C, C–N, C–O, C–S constructions. Mechanistic studies DFT calculations provide insights into plausible mechanism that supports in-situ imine formation. The stimulate precursors can generate Here, authors N functionalized

Language: Английский

---

Organophotoredox-Driven Three-Component Synthesis of β-Trifluoromethyl β-Amino Ketones

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

In this work, we present a photoredox three-component reaction that enables the synthesis of medicinally relevant β-trifluoromethyl β-amino ketones from N-trifluoroethylhydroxylamine derivative, styrenes and DMSO. Remarkably, fluoromethyl, difluoromethyl pentafluoroethyl analogues are also accessed using same conditions. The mechanistic investigations, including radical trapping experiments, cyclic voltammetry, Stern-Volmer quenching studies isotope labelling experiments support photoinduced radical/polar crossover Kornblum-type oxidation mechanisms. Finally, applicability organic skeletons is showcased by notable derivatization reactions.

Language: Английский

---

Visible-Light-Mediated Radical α-C(sp³)─H gem-Difluoroallylation of Amides with Trifluoromethyl Alkenes via Halogen Atom Transfer and 1,5-Hydrogen Atom Transfer

Organic Letters, Journal Year: 2025, Volume and Issue: 27(10), P. 2377 - 2382

Published: March 5, 2025

Direct gem-difluoroallylation at the α-carbonyl position is a challenging process by conventional methods. Herein we report photocatalytic radical α-C(sp3)─H of amides with trifluoromethyl alkenes to access target compounds good yields and functional group tolerance. The mild effective conditions allow gem-difluoroalkene motifs as carbonyl bioisosteres incorporated concisely some complex molecules, including gemfibrozil estrone derivatives, presenting great potential for late-stage functionalization drugs, natural products, bioactive intermediates. Mechanistic investigations suggest pathway combining XAT 1,5-HAT.

Language: Английский

---

Nitrogen-Based Organofluorine Functional Molecules: Synthesis and Applications

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: April 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

Language: Английский

---

Visible-Light-Driven Tandem Cyclization of o-Hydroxyaryl Enaminones: Access to 3-(α-Arylsulfonamido)trifluoroethyl Chromones

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

A visible-light-driven intermolecular tandem α-amidotrifluoroethylation/cyclization of enaminones using a previously unreported N-trifluoroethylaminopyridinium salt was achieved in the absence transition metal catalysts or bases. Notable features this synthetic method include mild conditions, high selectivity, excellent functional group compatibility, and satisfactory yields. Preliminary mechanistic studies indicate that reaction proceeds via radical pathway, involving an situ generated N-trifluoroethyl radical, followed by 1,2-H shift.

Language: Английский

---

Visible-Light-Mediated Addition Reactions of Sulfur-Containing Reagents with α-Trifluoromethyl Alkenes

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Herein, we described the addition reactions of sulfur-containing reagents (sodium sulfinates, dithiosulfonates) with α-trifluoromethyl alkenes under visible light. A series trifluoromethyl sulfonates were synthesized via visible-light-induced radical reaction sodium sulfinates and to obtain protons from solvent. dithiosulfonated derivatives bifunctionalization dithiosulfonates.This strategy has advantages mild conditions, good substrate universality high yield up 99% yield.

Language: Английский

---