Stereoselective Synthesis of Densely Functionalized Pyrrolidin-2-ones by a Conjugate Addition/Nitro-Mannich/Lactamization Reaction

摘要

Copper-catalyzed conjugate addition of diorganonzinc reagents to nitroacrylate 1 followed by a subsequentnnitro-Mannich reaction and in situ lactamization leads to annefficient one-pot synthesis of 1,3,5-trisubstituted 4-nitropyrrolidin-n2-ones (5). The versatility of the reaction isnshown for a wide range of N-p-(methoxy)phenyl protectednaldimines 3 derived from alkyl, aryl, and heteroaryl aldehydes.nThe densely functionalized pyrrolidin-2-ones 5 are isolated asnsingle diastereoisomers (40 examples, 33−84% yield). An enantioselective copper-catalyzed conjugate addition of diethylzinc lednto highly crystalline products that could be recrystallized to enantiopurity in high yield. A range of successful chemoselectiventransformations were investigated, which widens the applicability of the pyrrolidn-2-ones as stereochemically pure building blocksnfor further organic synthesis.