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

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• 作者：James C. Anderson ; Lisa R. Horsfall ; Andreas S. Kalogirou ; Matthew R. Mills ; Gregory J. Stepney ; Graham J. Tizzard
• 刊名：The Journal of Organic Chemistry
• 出版年：2012
• 出版时间：July 20, 2012
• 年：2012
• 卷：77
• 期：14
• 页码：6186-6198
• 全文大小：483K
• 年卷期：v.77,no.14(July 20, 2012)
• ISSN：1520-6904

文摘

Copper-catalyzed conjugate addition of diorgano zinc reagents to nitroacrylate 1 followed by a subsequent nitro-Mannich reaction and in situ lactamization leads to an efficient one-pot synthesis of 1,3,5-trisubstituted 4-nitropyrrolidin-2-ones (5). The versatility of the reaction is shown for a wide range of N-p-(methoxy)phenyl protected aldimines 3 derived from alkyl, aryl, and heteroaryl aldehydes. The densely functionalized pyrrolidin-2-ones 5 are isolated as single diastereoisomers (40 examples, 33鈥?4% yield). An enantioselective copper-catalyzed conjugate addition of diethylzinc led to highly crystalline products that could be recrystallized to enantiopurity in high yield. A range of successful chemoselective transformations were investigated, which widens the applicability of the pyrrolidn-2-ones as stereochemically pure building blocks for further organic synthesis.