Highly Diastereoselective Cascade [5+1] Double Michael Reaction, a Route for The Synthesis of Spiro Thio-Oxindoles

Abstract

The first diastereoselective synthesis of spiro-thiooxindole is reported via Michael reaction between thiooxindoles and divinyl ketones. The reaction was conducted without any catalyst or additive under green conditions, i.e., ethanol as the solvent and room temperature. This study showed the art of governing regioselectivity in which novel spiro frameworks were generated in high yields. In addition to simple and column chromatography-free purification, the high diastereoselectivity makes this protocol very robust. The regio- and stereo- selectivity of the reaction has been discussed in light of the theoretical calculations, and molecular docking has been performed on the reaction products. Our method presents the first synthesis of cis-spiro thiooxindoles, which can be used to generate cis-spiro oxindoles. According to our docking studies, the latter demonstrates higher binding affinities towards the LdUMPS than corresponding trans-spiro oxindoles and may be utilized to develop new hit compounds for leishmaniasis treatment.