We report herein an organocatalytic asymmetric protocol for the construction of tetrasubstituted carbon stereocenters bearing three heteroatoms. The reaction proceeded via the enantioselective intramolecular cyclization reaction of vinylidene -quinone methide (VQM) with imidates to form pentacyclic heterocycles. The formed tetrasubstituted carbon center was stable under a high temperature and the conditions for further transformations.
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http://dx.doi.org/10.1021/acs.orglett.2c01842 | DOI Listing |
Commun Chem
March 2025
Department of Chemistry, Loker Hydrocarbon Research Institute, University of Southern California, 837 Bloom Walk, Los Angeles, CA, 90089-1661, USA.
Carbon-heteroatom bonds are of great importance due to their prevalence in pharmaceuticals, agrochemicals, materials, and natural products. Despite the effective use of metal-catalyzed cross-coupling reactions between sp-hybridized organohalides and soft heteroatomic nucleophiles for carbon-heteroatom bond formation, the use of sp-hybridized organohalides remain limited and the coupling with thiols remains elusive. Here, we report the coupling of sp-hybridized benzyl or tertiary halides with soft thiol nucleophiles catalyzed by iron and extend the utility to alcohol and amine nucleophiles.
View Article and Find Full Text PDFOrg Lett
February 2025
Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226031, UP, India.
Reported here is a catalytic redox-neutral geminal dual C-H functionalization of oxindoles with two distinct aromatics using anilines. The reaction proceeded through a pluripotent tetra-substituted alkene intermediate via an extended resonance stabilized carbocation. It furnished wide chemical space around oxindoles with the generation of all carbon quaternary centers (>35 examples) in good to excellent yields.
View Article and Find Full Text PDFJ Org Chem
February 2025
Department of Chemistry, Indian Institute of Technology Indore, Simrol, Indore 453552, Madhya Pradesh, India.
An efficient CsCO-promoted and copper(I)-catalyzed double cyclization of -nitrochalcones with vinyl malononitriles for the access to a variety of tri- and tetra-substituted acridones and their fused derivatives with a value-added CN group has been developed for the first time. This one-pot operation proceeds through a Michael-cyclization-aromatization, followed by regioselective -amination via nucleophilic aromatic substitution (SAr) reaction, resulting in two C═C bonds and a C-N bond for acridone ring synthesis. This economic strategy based on 100% carbon atoms ensures the successive formation of two rings in a one-pot operation, good to high yields, a wide range of substrates, and good tolerance of functionalities.
View Article and Find Full Text PDFJ Am Chem Soc
February 2025
Hefei National Research Center for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei 230026, China.
Asymmetric radical transformations (ARTs) are vital for constructing chiral drugs and materials, while the highly reactive nature of radicals often imposes a challenge in selectivity control of these processes. Inspired by the principles of enzyme-cofactor cooperation to enhance stereochemical induction in enantioselective radical transformations, we developed an enantioselective asymmetric radical azidation cooperative organo- and transition metal catalysis. This approach enables the efficient synthesis of heavily functionalized tertiary azides from readily available aldehydes.
View Article and Find Full Text PDFOrg Lett
February 2025
CNRS, INSA Rouen Normandie, Univ Rouen Normandie, Normandie Univ, CARMeN UMR 6064, INC3M FR 3038, F-76000 Rouen, France.
The α-3-(1,2,4-triazine)-α-cyanoacetate derivatives exhibit a unique and well-defined dearomatized structure undergoing efficient organocatalytic aromatization-alkylation sequences with Michael acceptors in order to construct an all-carbon tetrasubstituted stereocenter with high ee values. These new players in the field of enantioselective catalytic benzylic C-H functionalization afford versatile molecular platforms toward the construction of valuable 3D-heterocycles.
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