Organocatalytic Asymmetric Synthesis of 2,3-Dihydro-4H-imidazol-4-ones via Cyclocondensation of N-Silyl Iminoesters

Chiral 2,3-dihydro-4H-imidazol-4-ones are key motifs in both synthetic and biological chemistry. However, their accessibility is classically limited to optical resolution of enantioenriched products. Herein, we report the catalytic asymmetric synthesis of these 4-imidazolones via the cyclocondensation of N-silyl iminoesters and N-unprotected ketimines using a chiral phosphoric acid catalyst. The enantioselective reaction has a broad substrate tolerance and maintains high yields and enantioselectivities (up to 99%, 99% ee). Furthermore, the enantioselective dimerization of N-silyl iminoesters to afford various chiral imidazolones was performed in the same catalytic system (up to 95%, 99% ee). The obtained products were easily converted into significant chiral heterocyclic molecules such as imidazoles, imidazolidines, and nitrones. Experimental results and density functional theory (DFT) calculations revealed a plausible reaction mechanism and the origin of the asymmetric induction.