Aqueous single step synthesis and structural characterization of allylated, propargylated, and benzylated 3-substituted 3-aminooxindoles

Article abstract of DOI:10.1080/00397911.2017.1348524

Efficient zinc-mediated allylation, propargylation, and benzylation of isatin-derived imines were undertaken for the synthesis of 3-substituted 3-aminooxindoles with ≈80% yield. Such alternative approach has efficiently avoided the use of catalysts, sever

Full text of DOI:10.1080/00397911.2017.1348524

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Aqueous Single Step Synthesis and Structural
Characterization of Allylated, Propargylated, and
Benzylated 3-Substituted 3-Aminooxindoles
Sameer A. Karpe, Man Singh & L. Raju Chowhan
To cite this article: Sameer A. Karpe, Man Singh & L. Raju Chowhan (2017): Aqueous Single Step
Synthesis and Structural Characterization of Allylated, Propargylated, and Benzylated 3-Substituted
3-Aminooxindoles, Synthetic Communications, DOI: 10.1080/00397911.2017.1348524
To link to this article: http://dx.doi.org/10.1080/00397911.2017.1348524
View supplementary material
Accepted author version posted online: 10
Jul 2017.
Submit your article to this journal
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20
Download by: [University of Bath]
Date: 11 July 2017, At: 13:27

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Aqueous Single Step Synthesis and Structural Characterization of Allylated,
Propargylated, and Benzylated 3-Substituted 3-Aminooxindoles
Sameer A. Karpe1, Man Singh1, L. Raju Chowhan1
1School of Chemical Sciences, Central University of Gujarat, Gandhinagar, Gujarat, India
Corresponding author Man Singh E-mail: skarpe.karpe@gmail.com
The authors declare no competing financial interest.
Abstract
Efficient zinc-mediated allylation, propargylation, and benzylation of isatin derived
imines were undertaken for the synthesis of 3-substituted 3-aminooxindoles with ≈ 80%
yield. Such alternative approach has efficiently avoided the use of catalysts, severe
reaction conditions, multistep procedures, and reaction additives. For exploring and
materializing the synthetic utility, different allyl, propargyl, and benzyl bromides were
used for generalizing the synthetic route. The structure of the synthesized compounds
was established and confirmed by 1H NMR, 13C NMR, FTIR, and mass spectroscopic
techniques.
1

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Graphical Abstract
KEYWORDS: Barbier-type reaction; allylation; propargylation; benzylation; 3-
substituted 3-aminooxindoles
1.
INTRODUCTION
Synthetic chemist always gets fascinated for developing simpler and greener strategies
for synthesizing chemical compounds found in nature because of their interesting
biological properties.[1] In this regard, functionalized organic molecules are used as
synthetic building blocks, for example, many times the oxindoles are utilized for the
synthesis of natural products and complex molecules.[2] Interestingly, among these
oxindoles, the 3-substituted 3-aminooxindoles are found in many pharmaceutically active
compounds and natural products. Specifically, the 3-substituted 3-aminooxindole
2

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
skeleton is a core structure of compound 1 to 8 (Fig. 1), out of which compound 1 is a
potent gastrin/cholecystokinin-B receptor antagonist AG-041R.[3] The compound 2 acts
as an orally active non-peptide vasopressin VIb receptor antagonist SSR-149415.[4] The
compound 3 serves as an HIV protease inhibitor,[5] while compound 4 is an anti-malarial
agent.[6] The compound 5 is a CRTH2 antagonist,[7] while compound 6 exhibits[8]
inhibitory properties against Mycobacterium tuberculosis protein tyrosine phosphatase B.
The compound 7 and 8 exhibits anti-tumor[9] and analgesic[10] activities respectively.
Because of this pharmaceutical importance, chemists are putting their sincere efforts in
exploring and developing novel strategies for the synthesis of 3-substituted 3-
aminooxindoles with higher yield.[11] The nature and pattern of substitution at the C-3
position of 2-oxindole ring is the crucial factor for generating diverse biological
activities.[12] It is also reported that few natural products and pharmaceuticals contain the
2-oxindole ring having a free N-H.[13]
To date, various methods have been reported for their synthesis.[14] Among them, Alcaide
et al.[15] have reported allylation and propargylation reactions of imino-isatins mediated
by In and Zn in aqueous media to form quaternary 3-amino-2-oxindoles. Zhou et al.[16]
have described Sakurai-Hosomi allylation of isatin ketimines catalyzed by
Hg(ClO4)2·3H2O and Hg(OTf)2 using allyltrimethylsilane. By using N-tert-butanesulfinyl
ketimines as a substrate, Chen et al.[17] have reported an asymmetric approach for the
synthesis of chiral tetrasubstituted 3-aminooxindoles at room temperature. However, in
all these methods either costly metal or catalyst or additive was added. Such
complications have been resolved to some extent by our present approach, where we are
3