A novel and catalyst-free aqueous mediated multicomponent domino reaction (MCR) capable of affording medicinally important spiro[indole-3,4′-pyrazolo[3,4-e][1,4]thiazepines] under sonication in excellent yield and in shorter time is reported. This new protocol provides a new seven-membered ring system selectively instead of the expected five-membered ring system or other possible isomers. The structure and relative stereochemistry of spiro products was established by single crystal X-ray analysis of a representative compound and spectroscopic techniques. In comparison to conventional synthesis, the advantages of this method are that it is catalyst-free, has an easy workup and uses water as the solvent which is considered to be relatively environmentally benign, and this work offers a new way to create molecular complexity with maximum simplicity. The representative compounds were screened for their ability to inhibit the enzyme α-amylase.