Diamine-Tethered Bis(thiourea) Organocatalyst for Asymmetric Henry Reaction

We have developed a novel multifunctional C2-symmetric biphenyl-based diamine-tethered
bis­(thiourea) organocatalyst,
which was tested in the asymmetric Henry reaction. Under thoroughly
optimized conditions, the catalyst provided exceptionally high yields
and excellent enantioselectivities especially for electron-deficient
aromatic and heterocyclic substrates. Due to a high affinity of the
catalyst to silica gel, a simple chromatography-free nitroaldol isolation
procedure was feasible. Preliminary kinetic and spectroscopic experiments
were performed in order to complete the mechanistic picture of the
organocatalyzed nitroaldolization process. Finally, the developed
synthetic strategy was successfully applied to the catalytic enantioselective
syntheses of enantiopure (S)-econazole and (R)-mirabegron a late-stage intermediate.