BIFCINCAT · Bi-functional Cinchona Alkaloid derived Organocatalysts and their reactions
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2006-10-18 → 2008-10-17
- EU contribution
- €159,614
- Participants
- 1
- Scheme
- EIF
Lines connect the coordinator with its partners.
Results in brief
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.
Data: CORDIS, © European Union
Project objective
Bifunctional catalysts operate in a similar fashion to enzymes by simultaneously activating both substrate and reagent and promoting a reaction where the stereochemical outcome is controlled.As both substrate and reagent are simultaneously activated, many new types of stereoselective reaction are waiting to be discovered.In this proposal, we introduce a new family of asymmetric bifunctional organocatalysts, which benefit from a strong Lewis basic site and a strong hydrogen donor group coupled to a rigid chiral scaffold originating from a cinchona alkaloid backbone.Such catalysts should be capable of not only promoting highly enantioselective reactions of acidic pro-nucleophiles (such as malonate esters) to reactive Michael acceptors (such as nitro olefins), but have the power to promote reactions between less reactive reagents (such as to alpha, beta-unsaturated ketones, esters, imides).If this is the case, then the implications of the chemistry for the synthesis of important enantioenriched building block s for the synthesis of natural products and drug compounds is phenomenal. The chemistry proposed is built on solid and exciting preliminary results.Unlike traditional metal ion catalysed reactions, the attraction of reactions catalysed by bifunctional org anocatalystsis in the technical simplicity of performing, monitoring, sampling and working-up the reactions to give the desired products.Glove box techniques are not required, variables associated with the metal ions (counterions, impurities, toxicity, disposal) are not introduced and moisture or oxygen sensitivity is not an issue.These benefits allow for rapid identification and optimization of the catalysts in the reactions and bode well for the use of the reactions in the pharmaceutical and related industries and academia alike.
Original text from CORDIS.
Participants
- UNIVERSITY OF MANCHESTER · MANCHESTERCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union