A divergent strategy for synthesis of the tetrahydroisoquinoline alkaloids renieramycin G and a lemonomycin analog

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• 作者：Philip Magnus ; ^{p.magnus@mail.utexas.edu} ; Kenneth S. Matthews
• 关键词：Tetrahydroisoquinoline alkaloids ; Lemonomycin ; Renieramycin ; N-Acyl iminium ion cyclization ; Ionic hydrogenation ; Isoquinoline synthesis ; Diastereoselective reprotonation
• 刊名：Tetrahedron
• 出版年：2012
• 出版时间：5 August, 2012
• 年：2012
• 卷：68
• 期：31
• 页码：6343-6360
• 全文大小：1181 K

文摘

A divergent synthesis to the tetrahydroisoquinoline alkaloids (¡À)-renieramycin G and (¡À)-lemonomycinone amide is reported. A strategy was developed that allowed access to both the diazabicyclo[3.3.1]nonane and diazabicyclo[3.2.1]octane ring systems of the respective targets from a common advanced?intermediate. The high diastereoselectivity observed throughout the synthesis is controlled by the first stereocenter formed from alkylation of an unactivated isoquinoline. Key findings include the synthesis of isoquinolines under palladium-free Larock conditions, diastereoselective ionic hydrogenation conditions to set the 1,3-cis-tetrahydroisoquinoline architecture, a highly diastereoselective reprotonation, and a thiophilic Lewis acid-catalyzed 5-endo-trig N-acyl iminium ion silyl enol ether cyclization. This divergent approach to the tetrahydroisoquinoline alkaloids offers an alternative strategy to further structural diversity in this family of natural products.