title: Literature Survey and Further Studies on the 3-Alkylation of N-Unprotected 3-Monosubstituted Oxindoles. Practical Synthesis of N-Unprotected 3,3-Disubstituted Oxindoles and Subsequent Transformations on the Aromatic Ring.
abstract: The paper provides a comprehensive review of the base-catalysed C3-alkylation of N-unprotected-3-monosubstituted oxindoles. Based on a few, non-systematic studies described in the literature using butyllithium as the deprotonating agent, an optimized method has now been elaborated, via the corresponding lithium salt, for the selective C3-alkylation of this family of compounds. The optimal excess of butyllithium and alkylating agent, and the role of the halogen atom in the latter (alkyl bromides vs. iodides) were also studied. The alkylation protocol has also been extended to some derivatives substituted at the aromatic ring. Finally, various substituents were introduced into the aromatic ring of the N-unprotected 3,3-dialkyloxindoles obtained by this optimized method.
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, P.O.B. 91, 1521 Budapest, Hungary. ekokai@mail.bme.hu.|Directorate of Drug Substance Development, Egis Pharmaceuticals PLC., P.O.B. 100, 1475 Budapest, Hungary. ekokai@mail.bme.hu.|Department of Materials Technology, GAMF Faculty of Engineering and Computer Science, Pallasz Athéné University, P.O.B. 700, 6001 Kecskemét, Hungary. ekokai@mail.bme.hu.
authors.forename: Eszter
authors.initials: E
authors.lastname: Kókai
authors.affiliation: Directorate of Drug Substance Development, Egis Pharmaceuticals PLC., P.O.B. 100, 1475 Budapest, Hungary. simig.gyula@egis.hu.
authors.forename: Gyula
authors.initials: G
authors.lastname: Simig
authors.affiliation: Directorate of Drug Substance Development, Egis Pharmaceuticals PLC., P.O.B. 100, 1475 Budapest, Hungary. volk.balazs@egis.hu.
authors.forename: Balázs
authors.initials: B
authors.lastname: Volk
mesh_terms: D000478:Alkylation; D002384:Catalysis; D006219:Halogens / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D000078183:Oxindoles; D011522:Protons; D013237:Stereoisomerism
chemical_list: D006219:Halogens; D007211:Indoles; D009942:Organometallic Compounds; D000078183:Oxindoles; D011522:Protons; C046771:butyllithium; C022960:2-oxindole
keywords: alkylation; lithiation; oxidation; oxindole; regioselectivity