This report details the development of a masked N-centered radical strategy that harvests the energy of light to drive the conversion of cyclopropylimines to 1-aminonorbornanes. This process employs the N-centered radical character of a photoexcited imine to facilitate the homolytic fragmentation of the cyclopropane ring and the subsequent radical cyclization sequence that forms two new C-C bonds en route to the norbornane core. Achieving bond-forming reactivity as a function of the N-centered radical character of an excited state Schiff base is unique, requiring only violet light in this instance. This methodology operates in continuous flow, enhancing the potential to translate beyond the academic sector. The operational simplicity of this photochemical process and the structural novelty of the (hetero)aryl-fused 1-aminonorbornane products are anticipated to provide a valuable addition to discovery efforts in pharmaceutical and agrochemical industries.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917850 | PMC |
| http://dx.doi.org/10.1002/anie.201909492 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Shifting Lithium Amide Reactivity to the Radical Domain: Regioselective Radical C-H Functionalization of 3-Iodooxetane for the Synthesis of 1,5-Dioxaspiro[2.3]hexanes.
Angew Chem Int Ed Engl
January 2025
University of Bari: Universita degli Studi di Bari Aldo Moro, Dept. of Pharmacy - Drug Sciences, via E. Orabona 4, 70125, Bari, ITALY.
Strained spiro-heterocycles (SSH) have gained significant attention within the medicinal chemistry community as promising (sp3)-rich bioisosteres for their aromatic and non-spirocyclic counterparts. We herein report access to an unprecedented spiro-heterocycle - 1,5-dioxaspiro[2.3]hexane.
View Article and Find Full Text PDFAminoalkylation of Alkenes Enabled by Triple Radical Sorting.
J Am Chem Soc
January 2025
Merck Center for Catalysis at Princeton University, Princeton, New Jersey 08544, United States.
The direct synthesis of C(sp)-rich architectures is a driving force for innovation in synthetic organic chemistry. Such scaffolds impart beneficial properties onto drug molecules that correlate with greater clinical success. Consequently, there is a strong impetus to develop new methods by which to access sp-rich molecules from commercial feedstocks, such as alkenes.
View Article and Find Full Text PDFDiverse N-Oxidation of Primary Aromatic Amines Controlled by Engineered P450 Peroxizyme Variants Facilitated by Dual-Functional Small Molecule.
Adv Sci (Weinh)
December 2024
Key Laboratory of Photoelectric Conversion and Utilization of Solar Energy, Qingdao New Energy Shandong Laboratory, CAS Key Laboratory of Biofuels, Shandong Provincial Key Laboratory of Synthetic Biology, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, China.
Amine oxidation is an important organic reaction for the production of high-value N-containing compounds. However, it is still challenging to control the reactivity of active N-centered radicals to selectively access N-oxidation products. Herein, this study reports the engineering of cytochrome P450BM3 into multifunctional N-oxidizing enzymes with the assistance of dual-functional small molecules (DFSM) to selectively produce N-oxygenation (i.
View Article and Find Full Text PDFConverting macrocycle lactams into bicyclic lactams is proposed as an additional way to further increase the metabolic stability of peptide-based drugs. Unfortunately, the synthesis of bicyclic lactams has to start almost from scratch. This study explores the Hofmann-Löffler-Freytag (HLF) reaction mechanism and products as a potential late-stage functionalisation strategy for facile conversion of macrocyclic to bicyclic ring.
View Article and Find Full Text PDF-Carbazolyl π-Radical and Its Antiaromatic Nitrenium Ion: A Threshold Photoelectron Spectroscopic Study.
J Phys Chem A
November 2024
Laboratory for Synchrotron Radiation and Femtochemistry, Paul Scherrer Institut (PSI), Villigen CH-5232, Switzerland.
Understanding the structure and properties of heterocyclic radicals and their cations is crucial for elucidating reaction mechanisms as they serve as versatile synthetic intermediates. In this work, the -carbazolyl radical was generated via pyrolysis and characterized using photoion mass-selected threshold photoelectron spectroscopy coupled with tunable vacuum-ultraviolet synchrotron radiation. The -centered radical is classified as a π-radical (B), with the unpaired electron found to be delocalized over the central five-membered ring of the carbazole.
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!