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

Molecules

Eszter Kókai¹  Gyula Simig²  Balázs Volk² 

[1]Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, P.O.B. 91, 1521 Budapest, Hungary

[2]Directorate of Drug Substance Development, Egis Pharmaceuticals PLC., P.O.B. 100, 1475 Budapest, Hungary

关键词: oxindole;    alkylation;    lithiation;    regioselectivity;    oxidation;   

DOI  :  10.3390/molecules22010024

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown