Secondary alicyclic amines are converted to their corresponding ring-fused imidazoles in a simple procedure consisting of oxidative imine formation followed by a van Leusen reaction. Amines with an existing α-substituent undergo regioselective ring-fusion at the α'-position. This method was utilized in a synthesis of fadrozole.
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http://dx.doi.org/10.1055/a-2022-1511 | DOI Listing |
Org Lett
December 2024
Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, West Bengal, India.
Amines are essential due to their structural diversity and biological significance. Introducing the valuable bicyclopentane (BCP) moiety at the α-position of amines offers a promising strategy for developing novel bioactive compounds. This study outlines a divergent synthesis approach to generate α-amino-functionalized bicyclopentyl iodides and methylene cyclobutanols under mild and environmentally sustainable conditions.
View Article and Find Full Text PDFChem Commun (Camb)
September 2024
Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur-741246, West Bengal, India.
The functionalization of α-C(sp)-H bonds in amines has become a focal point of contemporary research. Here, we report a new approach utilizing photocatalysis α-C(sp)-H bond functionalization in alicyclic and aliphatic secondary amines facilitated by intramolecular 1,5-hydrogen atom transfer (HAT). This finding unlocks a sustainable method for rapidly constructing complex heterocyclics cross-dehydrogenative C-C coupling of protected amines and nitrogen-containing heterocycles.
View Article and Find Full Text PDFOrg Lett
July 2024
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, Florida 32611, United States.
Unprotected alicyclic amines undergo α-C-H bond phosphonylation via a two-stage one-pot process involving the oxidation of amine-derived lithium amides with simple ketone oxidants, generating transient imines which are then captured with phosphites or phosphine oxides. Amines with an existing α-substituent undergo regioselective α'-phosphonylation. Amine α-arylation and α'-phosphonylation can be combined, generating a difunctionalized product in a single operation.
View Article and Find Full Text PDFOrganometallics
April 2023
Department of Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, Michigan 48109, United States.
This communication describes the Pd-catalyzed C(sp)-H functionalization of a tropane derivative to generate products with functionalization at two (β/γ) or three (β/γ/β) different sites on the alicyclic amine core. These reactions proceed via an initial dehydrogenation to generate an alkene product that can react further to form a Pd(I) alkene-bridged dimer. Functionalization of this dimer affords β/γ/β-functionalized allylic arylation and allylic acetoxylation products.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
February 2024
Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, 333 Cassell Drive, Baltimore, Maryland 21224, United States.
Currently, there are no FDA-approved medications for the treatment of psychostimulant use disorders (PSUD). We have previously discovered "atypical" dopamine transporter (DAT) inhibitors that do not display psychostimulant-like behaviors and may be useful as medications to treat PSUD. Lead candidates (e.
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