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

• DOI: 10.1002/ange.201308905
• Publication Date: 2013-11-29T09:26:58Z
• Authors: Kenji Shirokane; Takamasa Wada; Makoto Yoritate; Ryo Minamikawa; Nobuaki Takayama; Takaaki Sato; Noritaka Chida
• Keywords: Mesylates; Molecular Structure; Stereoisomerism; Amides; 01 natural sciences; Catalysis; 0104 chemical sciences; Alkaloids; Trialkyltin Compounds; Oxidation-Reduction; Scandium

AbstractA 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.