Accessing elusive enantiopure dihydrobenzimidazoles via organocatalytic [4+2] cycloaddition reactions

Documented herein is an unprecedented example of organocatalytic eliminative [4+2] formal cycloaddition reaction between novel imidazole-based alkylidene malononitriles 1, functioning as ε-activatable o-quinodimethane (oQDM) diene precursors, and diverse enals 2 functioning as organocatalytically activatable dienophiles. A series of N-protected dihydrobenzimidazoles of type 3 was efficiently obtained in one step with excellent enantioselectivities.1 Different challenging issues had to be faced in this endeavour, including the non-facile, remote γ-deprotonation/temporary dearomatization2 of the highly stable 5-methyl-imidazole-4-carbaldehyde precursors, and cohabitation of the basic/nucleophilic imidazole ring with the amine organocatalyst. Finely merging the traceless-malononitrile activation strategy3 with the chiral iminium ion LUMO-lowering activation modality turned out to be a good option, successfully consigning the designed products upon careful optimization of the experimental conditions.