Metal-Catalyst-Free One-Pot Aqueous Synthesis of trans-1,2-Diols from Electron-Deficient α,β-Unsaturated Amides via Epoxidation Using Oxone as a Dual Role Reagent

Abstract

In organic synthesis, incorporating two functional groups into the carbon-carbon double bond of α,β-unsaturated amides is challenging due to the electron-deficient nature of the olefin moiety. Although a few examples of dihydroxylation of α,β-unsaturated amides have been demonstrated, producing cis-1,2-diols using either highly toxic OsO₄ or other specialized metal reagents in organic solvents, they are limited to several specific amides. We describe herein a general and one-pot direct synthesis of trans-1,2-diols from electron-deficient α,β-unsaturated amides through dihydroxylation using oxone as a dual-role reagent in water. This reaction does not require any metal catalyst and produces non-hazardous and nontoxic K₂ SO₄ as the sole byproduct. Moreover, epoxidation products could also be selectively formed by adjusting the reaction conditions. By the strategy, the intermediates of Mcl-1 inhibitor and antiallergic bioactive molecule can be synthesized in one pot. The gram-scale synthesis of trans-1,2-diol which is isolated and purified by recrystallization further shows the potential applications of this new reaction in organic synthesis.

Keywords: dihydroxylation; dual role; epoxides; one-pot; ring-opening.