RESUMEN
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.
RESUMEN
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. In addition, use of the chiral alkoxy group establishes two consecutive stereocenters in the aza-spirocyclization through remote stereocontrol.
RESUMEN
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]. 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.
Asunto(s)
Alcaloides/síntesis química , Amidas/síntesis química , Aminas/química , Compuestos Organometálicos/química , Compuestos Organometálicos/síntesis química , Alcaloides/química , Amidas/química , Fenómenos Químicos , Ésteres , Estructura Molecular , EstereoisomerismoRESUMEN
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.