molecules Article Synthesis of 2-Mercapto-(2-Oxoindolin-3- Ylidene)Acetonitriles from 3-(4-Chloro-5H -1,2,3- Dithiazol-5-Ylidene)Indolin-2-ones Boris Letribot 1 ,Régis Delatouche 1 , Hervé Rouillard 1 , Antoine Bonnet 1 , Jean-René Chérouvrier 1 , Lisianne Domon 1 , Thierry Besson 2 ID and Valérie Thiéry 1, * ID 1 University of La Rochelle, UMR CNRS 7266 LIENSs, 17000 La Rochelle, France; boris.letribot@gmail.com (B.L.); regis.delatouche@gmail.com (R.D.); herve.rouillard@hotmail.com (H.R.); antoine.bonnet@univ-lr.fr (A.B.); jean-rene.cherouvrier@univ-lr.fr (J.-R.C.); lisianne.domon@univ-lr.fr (L.D.) 2 Normandie University, UNIROUEN, INSA Rouen, CNRS, COBRA UMR 6014, 76000 Rouen, France; thierry.besson@univ-rouen.fr * Correspondence: valerie.thiery@univ-lr.fr; Tel.: +33-5-46-45-82-76 Received: 23 May 2018; Accepted: 6 June 2018; Published: 8 June 2018   Abstract: Alkylidene oxindoles are important functional moieties and building blocks in pharmaceutical and synthetic chemistry. Our interest in biologically active compounds focused our studies on the synthesis of novel oxindoles, bearing on the exocyclic double bond at the C8, CN, and S groups. Extending the potential applications of Appel’s salt, we developed a new synthetic approach by investigating the reactions of C5-substituted 2-oxindoles with 4,5-dichloro-1,2,3-dithiazolium chloride (Appel’s salt) to give original (Z)-3-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)indolin-2-one derivatives, and new 2-mercapto-(2-oxoindolin-3-ylidene)acetonitriles via a dithiazole ring-opening reaction. The work described in this article represents further applications of Appel’s salt in the conception of novel heterocyclic rings, in an effort to access original bioactive compounds. Fifteen new compounds were prepared and fully characterized. Keywords: 1,2,3-dithiazole; Appel’s salt; 3-alkenyl-2-oxindole 1. Introduction 3-Alkenyl-2-oxindoles are an important class of heterocyclic compounds which are well established in the field of pharmaceutical chemistry, and they possess a large range of pharmacological activities [1–6]. For example, oxindole derivatives recently emerged as privileged scaffolds in the modulation of adenosine monophosphate-activated protein kinase (AMPK) [7], and 2-oxindole-based hydrazides are potent cytotoxic agents with apoptotic induction properties [8]. Substituted oxindoles are also very interesting building blocks for their role as starting materials toward more complex oxindole-based structures such as spirooxindoles [9,10]. Original piperidinoyl spirooxindoles can be obtained in very high yields and with excellent enantioselectivities via the hetero-Diels–Alder reaction between 2-aza-3-silyloxy-butadienes and alkylidene oxindoles [11]. It was also reported that donor or acceptor substituents at the ethylenic C8 carbon atom of isatylidenes constitutes an exceptional push–pull example, in which the electronic behavior of a fixed substituent on a double bond may be reversed by the electronic nature of the substituent at the opposite side of that double bond [12]. Palladium-catalyzed asymmetric allylic amination of racemic butadiene monoxide with oxindole derivatives was successfully developed using a chiral phosphoramidite–olefin hybrid ligand [13]. Conventional synthetic routes to 3-alkenyl-oxindoles (aldol condensation of unsubstituted oxindoles or Wittig reactions on isatins) exhibit poor selectivity [14,15]. During the last decade, original synthetic routes based on intramolecular metallocatalyzed cyclizations leading to the formation of the Molecules 2018, 23, 1390; doi:10.3390/molecules23061390 www.mdpi.com/journal/molecules