We report a deoxygenative amidation reaction of alcohols with carbamoyl chlorides to afford amides through nickel-photoredox dual catalysis. Good to excellent yields can be obtained even for diverse complex sugar and steroid derivatives. The reaction is scalable, and the synthetic utility of the reaction was demonstrated by the homologation of alcohols to deliver several important γ-amino alcohols and a synthetically challenging bioactive compound intermediate.
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http://dx.doi.org/10.1021/acs.orglett.4c00519 | DOI Listing |
Nat Commun
January 2025
Flow Chemistry Group, Van't Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam, Amsterdam, The Netherlands.
Secondary amines are vital functional groups in pharmaceuticals, agrochemicals, and natural products, necessitating efficient synthetic methods. Traditional approaches, including N-monoalkylation and reductive amination, suffer from limitations such as poor chemoselectivity and complexity. Herein, we present a streamlined deoxygenative photochemical alkylation of secondary amides, enabling the efficient synthesis of α-branched secondary amines.
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January 2025
State Key Laboratory of Organometallic Chemistry and Shanghai Hongkong Joint Laboratory in Chemical Synthesis, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032 (China).
Singly occupied molecular orbital (SOMO) activation of in situ generated enamines has achieved great success in (asymmetric) α-functionalization of carbonyl compounds. However, examples on the use of this activation mode in the transformations of other functional groups are rare, and the combination of SOMO activation with transition metal catalysis is still less explored. In the area of deoxygenative functionalization of amides, intermediates such as iminium ions and enamines were often generated in situ to result in the formation of α-functionalized amines.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
The simple and efficient conversion of carboxylic acids into structurally diverse organic molecules is highly desirable in chemical synthesis. This review covers recent developments in photocatalytic methodology for late-stage transformations of complex carboxylic acids and their derivatives enabled by radical decarboxylation and deoxygenation, highlighting some representative and significant contributions in this field. These advancements are categorized based on the reactivity patterns exhibited by the carboxylic acids.
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December 2024
School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003, Jiangsu, P. R. China.
A protocol of amide-to-amine transformation that is convenient, mild, and easy to perform is a long-sought goal from the viewpoint of catalysis. Herein, we have utilized easily accessible W(CO)(NCMe) as a precatalyst for the deoxygenative reduction of 1°, 2° and 3° amides under mild conditions. Mechanism studies unraveled that the generated is potentially a vital species in activating C═O of amides by providing the H-bonding network during the catalytic cycle.
View Article and Find Full Text PDFChem Commun (Camb)
September 2024
Department of Chemistry, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, 110016, India.
A metal-free strategy has been developed for the α-arylation of carboxylic acids, secondary amides, and esters employing arenes as key reagents. This process entails the Lewis-acid catalyzed reductive Friedel-Crafts alkylation of arenes utilizing α-ketoacids, facilitated by silane in HFIP solvent. The transformation exhibits exceptional functional group tolerance, enabling late-stage functionalization of natural products.
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