Final Activity Report Summary - BIFCINCAT (Bifunctional Cinchona Alkaloid Derived Organocatalysts and Their Reactions)
We have demonstrated the use of bifunctional base and acid organic catalysts for the stereoselective construction of Michael adducts of nitro olefins and pro-nucleophiles derived from amides. In the first project area the Michael adducts were found to undergo synthetically relevant cascade reactions with imine electrophiles leading to highly substituted piperidinone products in high enantiomeric and diastereomeric excess. The reaction cascade was broad in scope, efficient and easy to perform.
In the second project area, the Michael addition was used as a key step in the shortest total synthesis of Nakadomarin A reported to date. The key nucleophile in the reaction was developed from pyrroglutamic acid in 5 steps and reacted with a highly substituted nitro olefin. The adduct was formed in high diastereomeric excess and on scale. A subsequent nitro Mannich casdade gave the core of the natural product. Further manipulations, including the development of a new iminim trap sequence by partial reduction of lactams was developed.
During the course of the work new chiral sulfonic acid catalysts were developed and tested in some catalytic asymmetric transformations.
In the second project area, the Michael addition was used as a key step in the shortest total synthesis of Nakadomarin A reported to date. The key nucleophile in the reaction was developed from pyrroglutamic acid in 5 steps and reacted with a highly substituted nitro olefin. The adduct was formed in high diastereomeric excess and on scale. A subsequent nitro Mannich casdade gave the core of the natural product. Further manipulations, including the development of a new iminim trap sequence by partial reduction of lactams was developed.
During the course of the work new chiral sulfonic acid catalysts were developed and tested in some catalytic asymmetric transformations.