In-Flow Generation of Thionyl Fluoride (SOF) Enables the Rapid and Efficient Synthesis of Acyl Fluorides from Carboxylic Acids.

Herein, we report an approach for generating thionyl fluoride (SOF) from the commodity chemicals thionyl chloride (SOCl) and potassium fluoride (KF). The methodology relies on a microfluidic device that can efficiently produce and dose this toxic gaseous reagent under extremely mild and safe conditions. Subsequently, the in situ-generated thionyl fluoride is reacted with an array of structurally and electronically differing carboxylic acids, leading to the direct and efficient synthesis of highly sought-after acyl fluorides.

A unified flow strategy for the preparation and use of trifluoromethyl-heteroatom anions.

The trifluoromethyl group (CF) is a key functionality in pharmaceutical and agrochemical development, greatly enhancing the efficacy and properties of resulting compounds. However, attaching the CF group to heteroatoms such as sulfur, oxygen, and nitrogen poses challenges because of the lack of general synthetic methods and reliance on bespoke reagents. Here, we present a modular flow platform that streamlines the synthesis of heteroatom-CF motifs.

Electrophilic Reagents for the Direct Incorporation of Uncommon SCFCFH and SCFCF Motifs.

The introduction of fluoroalkylthioether groups has attracted the attention of the drug-discovery community given the special physicochemical and pharmacokinetic features they confer to bioactive compounds, yet these are often limited to standard SCF and SCFH moieties. Herein, two saccharin-based electrophilic reagents have been disclosed for the incorporation of uncommon SCFCFH and SCFCF motifs. Their reactivity performance, multigram-scale preparation, and divergent derivatization have been thoroughly investigated with a variety of nucleophiles, including natural products and pharmaceuticals.

Enantioselective Synthesis of Aminodiols by Sequential Rhodium-Catalysed Oxyamination/Kinetic Resolution: Expanding the Substrate Scope of Amidine-Based Catalysis.

Regio- and stereoselective oxyamination of dienes through a tandem rhodium-catalysed aziridination-nucleophilic opening affords racemic oxazolidinone derivatives, which undergo a kinetic resolution acylation process with amidine-based catalysts (ABCs) to achieve s values of up to 117. This protocol was applied to the enantioselective synthesis of sphingosine.