Synthesis of Substituted 1,2,3,4-Tetrahydro-1-thiacarbazole and Spiro[pyrrolidinone-3,3′-indolinones] through a Common Intermediate Obtained by Condensation of Indolin-2-one, (Aryl)aldehydes, and Meldrum's Acid

Abstract

Trimolecular adducts resulting from condensation between indolin‐2‐one (or indoline‐2‐thione), (aryl)aldehydes, and Meldrum’s acid are useful intermediates for the synthesis of either 1,2,3,4‐tetrahydro‐1‐thiacarbazoles or spiro[pyrrolidino‐3,3′‐oxindoles] related to the natural product horsfiline. These latter compounds were obtained in a three‐step procedure characterized by acyl azide formation, Curtius rearrangement, and subsequent thermal spiro cyclization. The relative stereochemistry of the spiro derivatives was determined by comparison of NOESY data and calculated conformational analyses. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Utilisation of 1,3‐Dicarbonyl Derivatives in Multicomponent Reactions

“…Among them, enamines have been extensively studied. As examples, condensation of indole,167 or more recently indolin‐2‐one,168 with Meldrum’s acid and various aldehydes resulted in the one‐pot syntheses of ethyl indolylpropionates and of spiro[pyrrolidine‐3,3′‐indolinones], respectively, in a so‐called Yonemitsu condensation. Extending this three‐component reaction to 2‐substituted indoles, Sati and co‐workers recently reported an easy access to functionalised tetrahydrocarbazoles 169.…”

Indole based multicomponent reactions towards functionalized heterocycles

“…A successful application of the previous domino process on 72 allowed the isolation of functionalized spiro-oxindole derivatives 73. 41 It is important to note that the spiro-oxindole core is present in various alkaloids, for example horsfiline or spirotyprostatines, of biological interest. Toward combinatorial utilisation, the reversibility of this process was also studied by using benzaldehyde and 4-fluorobenzaldehyde combined with mass spectral analytical methods.…”

(E)‐3‐X‐indoline‐2‐ones as potent and selective inhibitors against different receptor tyrosine kinase (RTKs) in solution vs gas phase, at DFT

“…Nucleophilic displacement of 2‐halo substituents on indoles has been used for the preparation of tyrosine kinase inhibitors, and their diselena‐analogs . Moreover, there are an increasing number of experimental investigations on sulfur‐containing indoles as ( E )‐3‐X‐indoline‐2‐ones in the [4 + 2] cycloadditions, displaying their interesting electrophilicity, nucleophilicity, and structural features and potent biological activity profiles (Scheme ) …”