Mechanochemical assisted chemoselective and stereoselective hydrogen-bonding catalyzed addition of dithiomalonates to enones

Dithiomalonates proved to be active nucleophiles in the stereoselective additions to chalcones, dienones, and en-ynones affording the desired Michael adducts with good to high yields and enantioselectivities. In contrast, the analogous dibenzyl malonate remained inactive. Bifunctional Cinchona-based squaramides secured the effective chirality transfer and the selectivity towards Michael adducts of various bisthiomalonates following the soft enolization approach. The thioester’s nature impacted the reactivity and stability of the reactants or products. While the reactions performed in solution led to the products, the required time along with byproducts formation such as thio-Michael adducts, limiting the applicability of reactive dithioesters. On the contrary, reactions performed under solvent-free, ball milling conditions furnished adducts up to six times faster, with subtly or no byproduct generation. Therefore, the mechanochemical approach revealed to be an effective tool for supporting the hardly effective reactions under standard solution conditions. Detailed KS-DFT studies supported the experimental observations shedding more light on the intricate active nucleophile formation, and different chemical reaction pathways, as well as indicating the crucial transitions state governing the observed stereoselectivities