Modular synthesis of 3,3-disubstituted oxindoles from nitrones and acrylic acids.

We developed a modular synthesis for 3,3-disubstituted oxindoles, utilising readily accessible nitrones and acrylic acids. This approach facilitates the preparation of a diverse array of oxindoles through the variation of the starting materials. We demonstrated the applicability of this method through a gram-scale reaction and a synthesis of esermethole.

Asymmetric Total Synthesis of Fasicularin by Chiral N-Alkoxyamide Strategy.

The asymmetric total synthesis of fasicularin is reported. The key to success is the use of a chiral N-alkoxyamide to control both reactivity and stereoselectivity. This functional group enables the aza-spirocyclization and the reductive Strecker reaction, which cannot be realized with an ordinary amide.

Chemoselective reductive nucleophilic addition to tertiary amides, secondary amides, and N-methoxyamides.

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 carbonyl centers is a challenge because classical methods require harsh reaction conditions to overcome the poor electrophilicity of the amide carbonyl group. We have successfully developed a reductive nucleophilic addition of mild nucleophiles to tertiary amides, secondary amides, and N-methoxyamides that uses the Schwartz reagent [Cp2 ZrHCl].

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.