Convenient One-Pot Synthesis of Spirooxindole Derivatives Containing a 1,3,4-Thiadiazine Scaffold

Heterocycles containing the spirooxindole scaffold has been found to display antitumor, antimicrobial, antifungal and antimalarial activities. Moreover, the spirooxindole motif is a core structure of various natural products, such as spirotryprostatin, strychnofoline and cyclopiamine. Molecules containing the 1,3,4-thiadiazineskeleton are frequently found in biologically activecompounds that display excellent antifungal, antimicrobial, antiinflammatory, cardiovascular, anti-HIV, antidiabetic and antidepressant activities. Generally, 1,3,4-thiadiazine derivatives are preparedthrough cyclocondensation of amino thiols with bifunctionalreagents such as α-halo ketones [1].On the other hand,various methods have been reported in the literature for the synthesis of spirooxindoles [2], but the synthesis ofmolecules containing both spirooxindole and 1,3,4-thiadiazinemoieties has not been reported. In a continuation of our efforts toward the synthesis ofspirooxindole derivatives [3], we report the One-Pot threecomponentreaction of isatin derivatives1, 2-aryl-2-oxoethylthiocyanates 2, and hydrazonoyl chlorides 3 in thepresence of Et3N in refluxing EtOAc to afford the corresponding4′H-spiro[indole-3,5′-[1,3,4]thiadiazin]-2(1H)-ones 4 in high yield (figure 1).