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1,2,6-Thiadiazine 1-Oxides: Unsaturated Three-Dimensional S,N-Heterocycles from Sulfonimidamides

Jan-Hendrik Sch÷bel, Marco Thomas Passia, Nadja Anna Wolter, Rakesh Puttreddy, Kari Rissanen and Carsten Bolm*

*Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany, Email:

J.-H. Sch÷bel, M. T. Passia, N. A. Wolter, R. Puttreddy, K. Rissanen, C. Bolm, Org. Lett., 2020, 22, 2702-2706.

DOI: 10.1021/acs.orglett.0c00666

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An aza-Michael-addition/cyclization/condensation reaction sequence starting from sulfonimidamides and propargyl ketones provides 1,2,6-thiadiazine 1-oxides. These three-dimensional S,N-heterocycles have been further functionalized by standard cross-coupling reactions, selective bromination of the heterocyclic ring, and conversion into a β-hydroxy substituted derivative.

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General procedure for the syntheses of 1,2,6-thiadiazine 1-oxides

An oven-dried Schlenk tube equipped with magnetic stirring bar and septum was charged with the sulfonimidamide (1.0 equiv), molecular sieves 4 ┼ (5.0 mg / 0.1 mmol) and cesium carbonate (2.1 equiv). The Schlenk tube was evacuated in high vacuum and backfilled with argon. This process was repeated three times. Anhydrous dimethyl sulfoxide (1.0 mL / 0.1 mmol) was added via syringe and the resulting suspension was stirred for 15 min at room temperature. A solution of the propargyl ketone (1.5 equiv) in anhydrous dimethyl sulfoxide (1.0 mL / 0.1 mmol) was added dropwise via syringe, and the reaction mixture was stirred for 3 h at room temperature. After completion of the reaction, saturated aqueous sodium hydrogen carbonate solution (5 mL / 0.1 mmol) was added. The crude mixture was extracted with dichloromethane (3 x 10 mL / 0.1 mmol). The combined organic layers were dried over anhydrous magnesium sulfate and the solvents were removed under reduced pressure by a rotary evaporator. Purification by flash column chromatography using n-pentane/ethyl acetate as gradient elution (see each case for details) afforded the desired 1,2,6-thiadiazine 1-oxide.

Key Words

N-Heterocycles, S-Heterocycles

ID: J54-Y2020