Multicomponent Synthesis of 3-Thiazolines Using a Modified Asinger-Type Reaction

Vincent R.A.M. Reinartz, Jordy M. Saya, Darya Hadavi, Jules Harings, Romano V. A. Orrù

The classical Asinger reaction is a four-component process combining sulfur, ammonia, and oxo compounds to access 3-thiazolines, but its efficiency can be hampered by in situ ammonia-derived imine formation. We report a one-pot, two-step modification using preformed trimethylsilyl-imines to efficiently yield the desired 3-thiazolines. This method tolerates a wide range of aromatic aldehydes and α-halocarbonyl compounds under microwave irradiation. Benzothiazole-3-thiazoline products undergo bond isomerization to 2-thiazolines in HFIP under elevated microwave conditions, facilitating the synthesis of (±)-firefly luciferin and related derivatives.