Applications of Thermal Activation, Ball‐milling and Aqueous Medium in Stereoselective Michael Addition of Nitromethane to Enynones Catalyzed by Chiral Squaramides

Stereoselective addition of nitromethane to conjugated en‐ynones was performed through the application of chiral squaramides. Three non‐classical approaches to promote the addition reaction were tested, including activation of the nucleophile by inorganic base in a biphasic aqueous system, thermal activation, and ball‐milling. Hydrogen‐bonding catalysis was effective in all these methods, providing 1,4‐addition products in high yields and stereoselectivities of up to 98% requiring 1–5 mol% of Cinchona alkaloid squaramide.