WORKPLAN
Workpackage 1
WP1 Domino organocatalysis
WP LEADER UNIBO
Objectives
Design new organocatalysts based on ferrocene, pyrrolidine and modified pyrrolydine, binaphtyl and exploring their behaviour in organocatalytic model reactions. Use the prepared catalysts for organocatalytic Domino reactions with nitroderivatives and preparing cyclohexene derivatives. Test the better catalyst in new this new domino reactions. Preparing key intermediates for the synthesis of oseltamivir through organocatalytic domino reactions. Studying the cyclization of the derivatives.
Description of work
The work will involve standard organic synthetic techniques by a single postdoctoral co-worker working in the different groups. The workpackage 1 is divided by different task, studied and exploited by different groups compound.
Task 1: Model reactions and preparation of 3 and 4. The work plan will start with the study of model reactions with the synthesis of key intermediates. This will give immediately information to all partners for the other synthesis of other derivatives.
Task 2. Ferrocene organocatalysis. At the same time, new ferrocene compounds 9-11 will be prepared and tested in model reaction. Ferrocene derivatives combine planar chirality with stereocenters, and the action of acidic group inserting in the ferrocene framework can give new interesting and never prepared organic catalyst.
Task 3: Preparation of organocatalyst based on pyrrolydine. Pyrrolidine 18-27 will be prepared and tested in the model domino reactions, taking advantage of the dissemination of knowledge within the consortium.
Task 4: Preparation of new organocatalyst based on binaphtalene. Chiral bynapthyl containing amines, 28-35 will be also prepared and tested in the model reactions. The preparation of the key intermediate for the oseltamivir synthesis will be the focus of the next WP. With the most successful Domino reaction advanced intermediates for the oseltamivir synthesis will be obtained, and after will be studied the synthetic step for the transformation of these intermediate in oseltamivir (see Scheme 5). As alternative and valid approach that will be explored, in WP1, we have considered a different synthetic strategy: The asymmetric synthesis of Neuraminidase inhibitors will be prepared though a stepwise approach, as is defined in Scheme 6.
Task 5. Synthesis through a two step approach. This alternative approach consider to use organocatalytic reaction for preparing open intermediate and the cyclize them to the desired advanced cyclohexene derivatives with classical organic reaction or by the use of organocatalytic routes.
Deliverables
Three reports (D1, D2, D3), at month 12, will be provided detailing all compounds prepared, their activity in the standard reactions and in the new domino reactions, details of the journal publications realised and planned from workpackages. Another two reports will be available at month 20 and 24 (D4, D5). Aspect of this deliverable will be presented in the public domain via the web interface and the scientific part of the project symposia (D16)