916582-47-3Relevant academic research and scientific papers
Total synthesis of (±)-gephyrotoxin by amide-selective reductive nucleophilic addition
Shirokane, Kenji,Wada, Takamasa,Yoritate, Makoto,Minamikawa, Ryo,Takayama, Nobuaki,Sato, Takaaki,Chida, Noritaka
supporting information, p. 512 - 516 (2014/01/23)
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. Aim for selectivity: A chemoselective approach that utilizes N-methoxyamides has been developed for the total synthesis of (±)-gephyrotoxin. The N-methoxy group enabled the direct coupling of the amide with an aldehyde and amide-selective reductive allylation in the presence of a more electrophilic methyl ester, which resulted in the most concise and efficient total synthesis of (±)-gephyrotoxin described to date.
Chemoselective reductive nucleophilic addition to tertiary amides, secondary amides, and N-methoxyamides
Nakajima, Minami,Oda, Yukiko,Wada, Takamasa,Minamikawa, Ryo,Shirokane, Kenji,Sato, Takaaki,Chida, Noritaka
supporting information, p. 17565 - 17571 (2015/02/19)
As the complexity of targeted molecules increases in modern organic synthesis, chemoselectivity is recognized as an important factor in the development of new methodologies. Chemoselective nucleophilic addition to amide car-bonyl centers is a challenge because classical methods require harsh reaction conditions to overcome the poor elec-trophilicity of the amide carbonyl group. We have successfully developed a reductive nucleophilic addition of mild nu-cleophiles to tertiary amides, secondary amides, and N-methoxyamides that uses the Schwartz reagent [Cp2ZrHCl]. The reaction took place in a highly chemoselective fashion in the presence of a variety of sensitive functional groups, such as methyl esters, which conventionally require protection prior to nucleophilic addition. The reaction will be applicable to the concise synthesis of complex natural alkaloids from readily available amide groups.
