Enantioselective Michael addition of diethyl malonate to nitroolefins with bifunctional 2-aminodmap/urea organocatalyst

Bakırcı Çetinkaya, İrem
The enantioselective organocatalytic Michael addition reaction has gained increased attention as an asymmetric synthesis strategy for C-C bond formation. In this regard, (1R,2R)-trans-1,2-cyclohexanediamine derived C1 symmetrical 2-aminoDMAP has been synthesized in our group. The remaining primary amine was modified with 1-isothiocyanato-(3,5)-bis(trifluoromethyl) benzene 3,5-Bis (trifluoromethyl) phenyl isothiocyanate and 3,5-bis(trifluoromethyl) phenyl isocyanate to afford bifunctional 2-aminoDMAP/thiourea and 2-aminoDMAP/urea organocatalysts. The efficieny of organocatalyst has been tested in Michael addition of diethyl malonate to trans-β-nitrostyrene by screening the parameters such as catalyst loading amount, concentration, solvent and temperature. The best condition was found as 5 mol% catalyst loading at room temperature in toluene and the target GABA precursor was synthesized for 4 h in 94% ee. With the optimized reaction condition in hand, the scope of enantioselective organocatalytic conjugate addition was examined further by varying trans-β-nitroolefins. Most of the conjugate addition products were obtained in high to excellent yields (65-95%) and selectivities (80-99% ee).