Achieving regio- and stereo-control in the fluorination of aziridines under acidic conditions

Abstract

We developed an efficient fluorination protocol that converts easily accessible aziridines into β-fluoroamines, which are important motifs in biologically active molecules. In contrast with traditional fluorination approaches, DMPU-HF has shown both higher reactivity and regioselectivity and good functional group tolerance; thus, a wide scope of β-fluoroamines can now be accessed conveniently. The stereochemical behavior of ring opening depends on the substitution pattern of the aziridine substrates.

HBr–DMPU: The First Aprotic Organic Solution of Hydrogen Bromide

“…However, the excess reactivity of HBr toward ethers and esters excludes ethereal and ester solvents. Inspired by the concept of hydrogen bond basicity (p K BHX ) that was first systematically summarized by Laurence, [20] we previously succeeded in a new formulation of hydrogen fluoride, HF–DMPU, [21] which exhibits a higher reactivity than its predecessors [22] in a wide scope of transformations. We hypothesized that DMPU could effectively form hydrogen bond complexes with HBr.…”

Switchable Regioselectivity in the Opening of Aziridine by Fluoride: DFT Calculation and Synthesis of Fluorinated Piperidines

“…However, the issue of regioselectivity is a roadblock to realize this strategy. Many different methods have been developed for the ring opening of aziridine and aziridinium by fluoride, However, most of the methods focus on the reactivity, and very few investigated the regioselectivity …”

Bromofluorination of unsaturated compounds using DMPU/HF as a fluorinating reagent

“…We also demonstrated the synthetic utility and effectiveness of DMPU/HF in some nucleophilic fluorination reactions: the gold-catalyzed hydrofluorination of alkynes [13], fluoro-Prins cyclization reactions [14] and ring-opening fluorination of aziridines [15]. DMPU/HF exhibited high reactivity and selectivity compared with the other aforementioned HF-based reagents.…”