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The synthesis of small heterocycles under neat mechanochemical conditions is of great interest in the field of drug design because most of the commercially available drugs contain at least one heterocyclic unit. The sodium borohydride (NaBH4) promoted reductive cyclization to fused dihydrofuran under grinding technique is one of the compendium additions for the clean future. The development of chemoselective reduction under silica‐gel supported conditions represents significant progress in organic synthesis, offering a versatile and efficient method for selective reduction of specific functional groups within complex molecules. Synthesis of isoindole derivatives from the chemoselective reduce product via a sustainable short synthetic pathway is another significant process of our newly developed protocol. Finally, antileishmanial investigations of our synthesized compounds establish a soft bridge between biology and chemistry. [ABSTRACT FROM AUTHOR]