Total Synthesis of (±)-Gephyrotoxin by Amide-Selective Reductive Nucleophilic Addition

A chemoselective approach for the total synthesis of (±)‐gephyrotoxin has been developed. The key to success was the utilization of N‐methoxyamides, which enabled the direct coupling of the amide with an aldehyde and selective reductive nucleophilic addition to the amide in the presence of a variety of sensitive and electrophilic functional groups, such as a methyl ester. This chemoselective approach minimized the use of protecting‐group manipulations and redox reactions, which resulted in the most concise and efficient total synthesis of (±)‐gephyrotoxin described to date. Selektivität als Ziel: Eine chemoselektive Methode unter Verwendung von N‐Methoxyamiden wurde zur Totalsynthese von (±)‐Gephyrotoxin entwickelt. Die N‐Methoxy‐Gruppe ermöglichte die direkte Kupplung des Amids mit einem Aldehyd sowie die Amid‐selektive reduktive Allylierung in der Anwesenheit eines elektrophileren Methylesters, was zu der bislang kürzesten und effizientesten Totalsynthese von (±)‐Gephyrotoxin führte.