Discovery of Bifunctional Thiourea/Secondary-Amine Organocatalysts for the Highly Stereoselective Nitro-Mannich Reaction of α-Substituted Nitroacetates

The readily accessible bifunctional thiourea/secondary-amine organocatalysts for the highly stereoselective Nitro-Mannich reaction of simple esters of α-substituted nitroacids and N-Boc imines were reported. The enantioselectivity of the isomer is found to increase and the N-H group plays a crucial role in the catalytic transition state other than acting as Brønsted base. Good enantioselectivity could be obtained catalyzed by urea-secondary amine and the enantiomeric excess (ee) value is found to decrease in the absence of 4Å molecular sieves. In case of methyl 2-nitropropanoiate, excellent diastereo- and enantioselectivities are observed for aryl imines nearing diverse electron-withdrawing or donating substitutions. The nitro-Mannich products resulting from α-phenyl nitroacetate and N-Boc benzaldimine, are found to be labile at ambient temperature due to its crowded structure.