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

Abstract

Abstract 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.