Total Syntheses of (±)-Gephyrotoxin and (±)-Perhydrogephyrotoxin

• Published in: Bulletin of the Chemical Society of Japan Vol. 88; no. 4; pp. 522 - 537
• Main Authors: Shirokane, Kenji, Tanaka, Yuya, Yoritate, Makoto, Takayama, Nobuaki, Sato, Takaaki, Chida, Noritaka
• Format: Journal Article
• Language: English
• Published: TOKYO The Chemical Society of Japan 2015; Chemical Soc Japan; Chemical Society of Japan
• Subjects: Aldehydes; Allyl compounds; Chemical reactions; Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Redox reactions; Science & Technology; Strategy; Synthesis; Transformations; ORGANOMETALLIC REAGENTS; DIRECT TRANSFORMATION; SECONDARY AMIDES; ALPHA-ACETOXY ETHERS; TERTIARY AMIDES; FORMAL TOTAL-SYNTHESIS; REDUCTIVE ALKYLATION; STEREOSELECTIVE-SYNTHESIS; AMIDE BOND FORMATION; NUCLEOPHILIC-ADDITION
• ISSN: 0009-2673; 1348-0634
• DOI: 10.1246/bcsj.20140398

This article describes the full details of our total syntheses of gephyrotoxin and perhydrogephyrotoxin. Our central strategy toward the total synthesis is based on the use of an N-methoxy group as a reactivity control element. The N-methoxyamide group enabled unique transformations, involving i) the direct coupling reaction of the N-methoxyamide with an aldehyde, and ii) the amide-selective reductive allylation. These reactions were never accomplished without the assistance of the N-methoxy group. The amide-selective reductive allylation of the N-methoxyamide was especially practical, and excluded a number of extra steps including protecting group manipulations and redox reactions in the total syntheses.