Lepidiline-Derived Imidazole-2(3H)-Thiones: (3+2)-Cycloadditions vs. Nucleophilic Additions in Reactions with Fluorinated Nitrile Imines

Two series of imidazole-2(3<i>H</i>)-thiones inspired by naturally occurring lepidiline alkaloids, bearing either one or two benzyl-type substituents located at the N(1)/N(3) atoms, respectively, were prepared and examined in reactions with in situ generated <i>C</i>-trifluoromethyl-<i>N</i>-aryl nitrile imines. <i>N</i>,<i>N</i>-Dibenzylated imidazole-2-thiones served exclusively as C=S dipolarophiles to afford hitherto unknown CF₃-functionalized spiro [1,3,4-thiadiazole-5,2'-imidazole] derivatives formed through the (3+2)-cycloaddition pathway. In contrast, the enolizable <i>N</i>-monobenzylated imidazole-2-thiones provided acyclic products, i.e., hydrazonothioates, resulting from nucleophilic addition of the respective en(thio)late onto the <i>C</i>-termini of the 1,3-dipole. The presented results extend the scope of both fluorinated products available via trapping of the in situ generated CF₃-nitrile imines as well as synthetic analogues of lepidilines. In addition, spectroscopic analysis of the obtained products and the known related systems revealed ¹³C NMR chemical shifts attributed to the <i>C</i>-(CF₃) atom as useful probes to differentiate the open-chain hydrazonothioates (δ = 112-120), 2,2-diaryl/dialkyl-2,3-dihydro-1,3,4-thiadiazoles (δ = 130-145), and more strained spiro-1,3,4-thiadiazole derivatives (δ = 166-170) reported herein.