Metal-Free Synthesis of 3,3-Difluoro-2-Oxindoles

doi:10.11944/j.issn.1000-0518.2016.11.160035

Chinese Journal of Applied Chemistry ›› 2016, Vol. 33 ›› Issue (11): 1279-1283.DOI: 10.11944/j.issn.1000-0518.2016.11.160035

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Metal-Free Synthesis of 3,3-Difluoro-2-Oxindoles

MAI Wenpeng(),YANG Liu,LYU Mingxiu,WANG Yanwei,CAO Yi,LU Kui()

School of Materials and Chemical Engineering,He'nan Institute of Engineering,Zhengzhou 450006,China

Received:2016-01-21 Accepted:2016-04-07 Published:2016-11-01 Online:2016-11-01
Contact: MAI Wenpeng,LU Kui
Supported by:
Supported by the National Natural Science Foundation of China(No.2172046, No.21302042)

Abstract

Abstract:

A novel method for the synthesis of 3,3-difluoro-2-oxindoles was developed. 2-Bromo-2,2-difluoro-N-phenylacetamide was prepared from neat simple aromatic amines with ethyl bromodifluoroacetate. Reflux of the product in CH₃CN with CH₃I for 24 h gave 2-bromo-2,2-difluoro-N-methyl-N-phenylacetamide in 75%~90% yields. In the presence of 3.0 chemometric number sodium formaldehyde sulfoxylate, this key intermediate undergoes intramolecular radical cyclization in aqueous solution(N,N-dimethylformamide/H₂O) and affords the final product 3,3-difluoro-1-methylindolin-2-ones in 53%~72% yields. This method can be performed in aqueous solution from commercially available and affordable starting materials without any metal catalysts. It shows potential in industrial production of 3,3-difluoro-2-oxindoles.

Key words: acetanilide, sodium formaldehyde sulfoxylate, difluoro-methylindolin-one, metal-free

MAI Wenpeng, YANG Liu, LYU Mingxiu, WANG Yanwei, CAO Yi, LU Kui. Metal-Free Synthesis of 3,3-Difluoro-2-Oxindoles[J]. Chinese Journal of Applied Chemistry, 2016, 33(11): 1279-1283.

References

[1]	Schlosser M.CF3-Bearing Aromatic and Heterocyclic Building Blocks[J]. Angew Chem Int Ed,2006,45(33):5432-5446.
[2]	Müller K,Faeh C,Diederich F.Fluorine in Pharmaceuticals:Looking Beyond Intuition[J]. Science,2007,317:1881-1886.
[3]	Hangan D. Understanding Organofluorine Chemistry.An Introduction to C—F the Bond[J]. Chem Soc Rev,2008,37(2):308-319.
[4]	Badillo J J,Hanhan N V,Franz A K.Enantioselective Synthesis of Substituted Oxindoles and Spirooxindoles with Applications in Drug Discovery[J]. Curr Opin Drug Discovery Dev,2010,13(6):758-776.
[5]	Li Y M,Sun M,Wang H L,et al.Direct Annulations Toward Phosphorylated Oxindoles:Silver Catalyzed Carbon-Phosphorus Functionalization of Alkenes[J]. Angew Chem Int Ed,2013,52(14):3972-3976.
[6]	Wei W T,Zhou M B,Fan J H,et al.Synthesis of Oxindoles by Iron-Catalyzed Oxidative 1,2-Alkylarylation of Activated Alkenes with an Aryl C(sp2)H Bond and a C(sp3)H Bond Adjacent to a Heteroatom[J]. Angew Chem Int Ed,2013,52(13):3638-3641.
[7]	Matcha K,Narayan R,Antonchick A P.Metal-Free Radical Azidoarylation of Alkenes:Rapid Access to Oxindoles by Cascade C—N and C—C Bond-Forming Reactions[J]. Angew Chem Int Ed,2013,52(31):7985-7989.
[8]	Xie J,Xu P,Li H,et al.A Room Temperature Decarboxylation/C—H Functionalization Cascade by Visible-light Photoredox Catalysis[J]. Chem Commun,2013,49(50):5672-5674.
[9]	Meng Y,Guo L N,Wang H,et al.Metal-free Oxidative Hydroxyalkylarylation of Activated Alkenes by Direct sp3 C—H Functionalization of Alcohols[J]. Chem Commun,2013,49(68):7540-7542.
[10]	Zhou M B,Wang C Y,Song R J,et al.Oxidative 1,2-Difunctionalization of Activated Alkenes with Benzylic C(sp3)—H Bonds and Aryl C(sp2)-H Bonds[J]. Chem Commun,2013,49(88):10370-10372.
[11]	Zhu J,Zhang W,Zhang L J,et al.Copper-Mediated Fluoroalkylation Reactions with Iododifluoroacetamides:Controlling the Selectivity Among Cross-Coupling Intramolecular Cyclization and Homocoupling Reactions[J]. J Org Chem,2010,75(16):5505-5512.
[12]	Shi S L,Buchwald S L.Palladium-Catalyzed Intramolecular C—H Difluoroalkylation:Synthesis of Substituted 3,3-Difluoro-2-Oxindoles[J]. Angew Chem Int Ed,2015,54(5):1646-1650.
[13]	Mai W P,Sun B,Qian G S,et al.Metal-free Trifluoroethylation of Activated Alkenes:Rapid Access to Construct Fluorinated 3,3-Disubstituted 2-Oxindoles[J]. Tetrahedron,2015,71(44):8416-8423.
[14]	Huang B N,Liu J T.A Facile Method for the Perfluoroalkylation of Pyridine Its Derivatives[J]. Tetrahedron Lett,1990,31(19):2711-2712.

Metal-Free Synthesis of 3,3-Difluoro-2-Oxindoles

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