Aerobic synthesis of N-sulfonylamidines mediated by N-heterocyclic carbene copper(I) catalysts

A new catalytic strategy for the one-pot synthesis of N-sulfonylamidines is described. The cationic copper(I) complexes were found to be highly active and efficient under mild conditions in air and in the absence of solvent. A copper acetylide is proposed as key intermediate in this transformation.


General Information
Solvents and reagents were used as received without further purification. Azides were synthesised according to reported procedures. 1

General catalytic procedure
A vial was charged with [Cu(Triaz)2]BF4 (4.5 mg, 1 mol %), the alkyne (0.5 mmol), the azide (0.6 mmol), and the amine (0.6 mmol). The reaction was stirred neat for the appropriate amount of time. Dichloromethane (2 mL) and a saturated aqueous solution of ammonium chloride (3 mL) were added and the reaction mixture stirred during 30 minutes. The aqueous layer was extracted with dichloromethane (3 × 10 mL). The combined organic layers were dried over MgSO4, filtered and the solvent was removed under vacuum. The crude product was purified by flash column chromatography or by recrystallization. The reported yields are the average of two reactions.

Entry
Catalyst Solvent Conversion (%) a, b

Stoichiometric reaction 2: tosyl azide and diisopropylamine
A vial was charged, in air, with tosyl azide (92 µL, 0.6 mmol) and diisopropylamine (85 µL, 0.6 mmol). The reaction mixture was stirred at room temperature for 24 hours under solvent-free conditions. Then, D-chloroform was added to the reaction mixture, which was analysed by 1 H-NMR spectroscopy. Only starting materials were observed.  A small amount of the sulfonyl triazole was observed as well as diisopropylamine and tosyl azide.
THF was then removed under vacuum and D-chloroform was added to the reaction mixture, which was analysed by 1 H-NMR spectroscopy. Only starting materials were observed.