Total Synthesis of (+)-Aloperine. Use of a Nitrogen-Bound Silicon Tether in an Intramolecular Diels-Alder Reaction

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• 作者：Arthur D. Brosius ; Larry E. Overman ; and Lothar Schwink
• 刊名：Journal of the American Chemical Society
• 出版年：1999
• 出版时间：February 3, 1999
• 年：1999
• 卷：121
• 期：4
• 页码：700 - 709
• 全文大小：434K
• 年卷期：v.121,no.4(February 3, 1999)
• ISSN：1520-5126

文摘

Enantioselective total syntheses of aloperine (1), N-methylaloperine (2), and N-allylaloperine (3)are reported. The central element of the synthetic strategy is an intramolecular Diels-Alder reaction in whichthe cycloaddends are tethered by a N-silylamine linkage. The total synthesis of 1 proceeds from commerciallyavailable 3-hydroxypiperidine hydrochloride (54) and (R)-pipecolinic acid (35) by way of nine isolated andpurified intermediates. The synthesis is sufficiently efficient that gram quantities of (+)-aloperine (1) can bereadily prepared. Early exploratory studies also introduced a convenient method for tethering cycloadditionpartners with a sulfonamide unit to realize the intramolecular Diels-Alder cycloaddition of a vinylsulfonamide: 45 46.