While olefin amination with aminium radical cations is a classical method for C-N bond formation, catalytic variants that utilize simple 2° amine precursors remain largely undeveloped. Herein we report a new visible-light photoredox protocol for the intramolecular anti-Markovnikov hydroamination of aryl olefins that proceeds through catalytically generated aminium radical intermediates. Mechanistic studies are consistent with a process involving amine oxidation via electron transfer, turnover-limiting C-N bond formation, and a second electron transfer step to reduce a carbon-centered radical, rendering the overall process redox-neutral. A range of structurally diverse N-aryl heterocycles can be prepared in good to excellent yields under conditions significantly milder than those required by conventional aminium-based protocols.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/ja5056774 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Magic Blue-Initiated S2-Type Ring Opening of Activated Aziridines: Friedel-Crafts-Type Alkylation of Electron-Rich Arenes/Heteroarenes.
J Org Chem
August 2024
Department of Chemistry, Indian Institute of Technology, Kanpur 208016, India.
A transition metal-free, atom-economical, and highly stereospecific synthetic approach to Friedel-Crafts-type alkylation of arenes/heteroarenes has been developed. The protocol involves the catalytic aminium radical-cation salt (Magic Blue)-initiated S2-type nucleophilic ring opening of activated aziridines with arenes/heteroarenes to give the corresponding 2,2-diarylethylamines up to 99% yield and 85% ee (for nonracemic aziridines) in a very short reaction time. Moreover, on reaction with 1,3-dimethylindole and benzofuran, aziridines undergo domino-ring-opening cyclization (DROC) to give the various biologically significant heterocyclic scaffolds in moderate to good yields.
View Article and Find Full Text PDFOrganic Synthesis Away from Equilibrium: Contrathermodynamic Transformations Enabled by Excited-State Electron Transfer.
Acc Chem Res
July 2024
Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States.
ConspectusChemists have long been inspired by biological photosynthesis, wherein a series of excited-state electron transfer (ET) events facilitate the conversion of low energy starting materials such as HO and CO into higher energy products in the form of carbohydrates and O. While this model for utilizing light-driven charge transfer to drive catalytic reactions thermodynamically "uphill" has been extensively adapted for small molecule activation, molecular machines, photoswitches, and solar fuel chemistry, its application in organic synthesis has been less systematically developed. However, the potential benefits of these approaches are significant, both in enabling transformations that cannot be readily achieved using conventional thermal chemistry and in accessing distinct selectivity regimes that are uniquely enabled by excited-state mechanisms.
View Article and Find Full Text PDFPhotoenzymatic Asymmetric Hydroamination for Chiral Alkyl Amine Synthesis.
J Am Chem Soc
April 2024
DOE Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
Chiral alkyl amines are common structural motifs in pharmaceuticals, natural products, synthetic intermediates, and bioactive molecules. An attractive method to prepare these molecules is the asymmetric radical hydroamination; however, this approach has not been explored with dialkyl amine-derived nitrogen-centered radicals since designing a catalytic system to generate the aminium radical cation, to suppress deleterious side reactions such as α-deprotonation and H atom abstraction, and to facilitate enantioselective hydrogen atom transfer is a formidable task. Herein, we describe the application of photoenzymatic catalysis to generate and harness the aminium radical cation for asymmetric intermolecular hydroamination.
View Article and Find Full Text PDFCatalytic Aminium Radical-Cation Salt (Magic Blue)-Initiated S2-Type Nucleophilic Ring-Opening Transformations of Aziridines.
J Org Chem
February 2024
Department of Chemistry, Indian Institute of Technology, Kanpur 208016, India.
A simple and atom economic protocol for the construction of C-X/C-C bonds via catalytic aminium radical-cation salt (Magic Blue)-initiated S2-type nucleophilic ring-opening transformations of racemic and nonracemic aziridines with different hetero and carbon nucleophiles to afford various amino ethers, thioethers, and amines in up to 99% yield, and with perfect enantiospecificity for some substrates but reduced ee with others (for nonracemic aziridines), is developed. This aminium radical-cation salt-initiated, S2-type nucleophilic ring-opening strategy, along with various cyclization protocols, is employed to synthesize various biologically significant compounds.
View Article and Find Full Text PDFGround State Generation and Cyclization of Aminium Radicals in the Formation of Tetrahydroquinolines.
Org Lett
February 2024
Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom.
This paper reports the first examples of ground state radical-mediated intramolecular C-H amination to afford 1-methyl-1,2,3,4-tetrahydroquinolines from -2,4-dinitrophenoxy derivatives of arylpropylamines. Whereas the photoactivation of -2,4-dinitrophenoxyamines for intermolecular reactions has been established, ground state chemistry provides the desired cyclization products in moderate to excellent yields using Ru(bpy)Cl (42-95% yields) under acidic conditions under an air atmosphere.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!