Synthesis of CF3-Containing 2-Imidazolines and Imidazoles via a Iodide-Promoted [3+2] Cyclization Reaction

We report herein a general and effective system achieving cyclization of beta-trifluoromethyl enones with amidines in the presence of 1,3-diiodo-5,5-dimethylhydantoin (DIH), which affords a range of trifluoromethylated 2-imidazolines in synthetically useful yields with good diastereoselectivities (up to 95% yield, up to 98:2 dr) and good functional group tolerance. Furthermore, the one-pot synthesis of trifluoromethylated imidazoles via sequential cyclization and oxidation is demonstrated. More significantly, the reaction mechanism was verified by ESI-MS studies of possible intermediates, and a reasonable reaction mechanism was proposed.

Automated summary

We report a general and effective system for the cyclization of beta-trifluoromethyl enones with amidines using 1,3-diiodo-5,5-dimethylhydantoin (DIH) as a catalyst. This reaction provides a range of trifluoromethylated 2-imidazolines in high yields and good diastereoselectivities, with good tolerance towards functional groups. Additionally, a one-pot synthesis of trifluoromethylated imidazoles via sequential cyclization and oxidation is demonstrated. The reaction mechanism is verified by ESI-MS studies, confirming a reasonable proposed mechanism.