Sulfonimidamides by Sequential Mechanochemical Chlorinations and Aminations of Sulfinamides

Steven Terhorst, Tim Jansen, Tim Langletz and Carsten Bolm*

*RWTH Aachen University, Institute of Organic Chemistry, Landoltweg 1, D-52074 Aachen, Germany, Email: carsten.bolmoc.rwth-aachen.de

S. Terhorst, T. Jansen, T. Langletz, C. Bolm, Org. Lett., 2022, 24, 4109-4113.

DOI: 10.1021/acs.orglett.2c01099

see article for more reactions

Abstract

A one-pot, two-step mechanochemical synthesis of sulfonimidamides requires neither a solvent nor inert conditions. In a mixer mill, sulfinamides are rapidly converted to sulfonimidoyl chlorides by oxidative chlorination with N-chlorosuccinimide (NCS). Subsequent substitutions with amines provides a wide range of diversely substituted sulfonimidamides.

see article for more examples

General procedures for the synthesis of sulfonimidamides

Sulfinamide (0.15 mmol, 1 equiv) was placed in a ZrO₂ mixer mill jar (12 mL) along with 8 ZrO₂ balls (3 mm) and N-chlorosuccinimide (22.0 mg, 0.165 mmol, 1.1 equiv) unless noted differently. The reaction vessel was closed and installed in the mixer mill. The frequency was set to 25 Hz and the time to 15 minutes. After completion, the jar was opened and the sulfonimidoyl chloride used without further purification except for products 4al and 4am. For the purification of these products, a dry silica plug (1 cm) was prepared. The reaction mixture was dissolved in DCM (approximately 20 mL) and dried on silica under reduced pressure. Silica-Plug filtration using 2% EtOAc in pentane as the eluent afforded the sulfonimidoyl chloride.

An amine (0.3 mmol, 2.0 equiv) was added to the sulfonimidoyl chloride, the jar was closed and the mixture was milled in a mixer mill for 1 h at 25 Hz. The reaction mixture was dissolved in DCM and washed with water (3 × 20 mL). The organic phase was separated, combined, dried over Na₂SO₄ and concentrated by reduced pressure. The crude mixture was separated by column chromatography (2-20% EtOAc in pentane) to obtain the corresponding product.

Key Words

sulfonimidamides, NCS, mechanochemistry

ID: J54-Y2022