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

AbstractIn 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 K2SO4 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.