Mechanochemical approaches in an organic synthesis have received increased interest because of their wide applications in green methodologies. Ball milling has been fruitfully utilized in the synthesis of various (elemental) organic scaffolds, including common drugs or drug candidates. However, the utilization of ball milling in asymmetric organic synthesis has not been adequately investigated. Thus, the aim of this review is to highlight the attractive features of the applications of mechanochemistry via ball milling in asymmetric organic syntheses in order to attract the attention of a wider section of the synthesis community.

1-Butane sulfonic acid-3-methylimidazolium tosylate, [BSMIM]OTs, is found to be a remarkable catalyst for the tandem cyclization of 4-hydroxycoumarin with chalcones for the syntheses of pyrano[3,2-c]coumarins under solvent-free conditions. The developed protocol is applicable for the construction of biologically important pyranocoumarins from easily accessible chalcones having various substituents. This reaction possibly proceeds through Michael addition followed by cyclization. The feasibility of catalyst recycling is also demonstrated. This method produces only water as the byproduct and represents a green synthetic protocol. The catalytic reaction proceeded very smoothly under solvent-free conditions and showed high regioselectivity. Clean reaction, non-chromatographic purification technique, easily accessible reactants, and metal and solvent-free and environmentally friendly reaction conditions are the notable advantages of this procedure. In addition, this method shows lower E-factors.

An environmentally benign nano CuO catalyzed “on-water” strategy has been developed for one-pot synthesis of isoindolo[2,1-a]quinazolines by a three-component coupling of isatoic anhydride, 2-carboxybenzaldehyde and amines in high yields. Aryl, heteroaryl and alkyl amines reacted very well under the present reaction conditions. Water plays a major role to accelerate this transformation through hydrogen bond mediated ‘electrophile–nucleophile dual activation’. The catalyst can be reused several times without significant loss of catalytic activity. The present method produces no waste, and represents a green synthetic protocol.