The trading of space for time under weakly activated catalysis: expeditious synthesis of β-NH2 alcohols via a direct ammonolysis of epoxides with ammonia

Abstract

The direct synthesis of β-NH₂ alcohols via flexible ammonolysis of epoxides is still a challenging and unresolved problem. Herein, we present a strategy of “trading space for time under weakly activated catalysis” and “shielding the reactivity of the product”, and thereby developed a novel single-step ammonolysis reaction of epoxides with ammonia. A stoichiometric amount of HCO₂NH₄ as an additive plays a dual role in the global activation of substrates and in completely suppressing the side reaction of excessive alkylation. A broad scope of substrates including terpene- and steroid-derived epoxides cleanly afforded the target β-NH₂ alcohols in good to excellent yields under easily adjustable mild conditions. Furthermore, this synthetic protocol is metal-free and eco-friendly and could be used for the gram-scale synthesis of biologically active β-NH₂ alcohols that could be converted to diverse functionalized molecules with ease.