New developments in asymmetric organocatalysis

• Research unit: COST
• Project number: C11.0080

Key words (English)

Chemistry; Organic Synthesis; Asymmetry; Organocatalysis; green chemistry

Research programs (English)

COST-Action CM0905 - Organocatalysis - ORCA

Short description (English)

The last decade saw an amazing new interest in organocatalysis. Our group was among the pioneers in Switzerland to work in this field. Our project focuses on 3 aspects of asymmetric conjugate addition. 1. The design of new organocatalyst. Based on structure-activity relationship, and DFT calculations, we shall focus on fluorinated pyrrolidine-type catalyst. 2. New Michael acceptors. After focusing on the functional group (carbonyl, sulfone, phosphonate), we are interested in the 1,4 versus 1,6 regioselectivity of polyene or enyne type Michael acceptors. 3. New nucleophiles. In contrast to enamine catalysis, imminium activation allows non-carbonyl nucleophiles to be used. We shall focus on sulfones and phosphonate nucleophiles, as nitro and carbonyl donnors have already been overstudied. 4. Multicatalytic cascade reactions, where a metal catalyst is involved, as well as an organocatalyst, in one-pot reactions.

Partners and International Organizations (English)

BE; CZ; EE; FI; FR; DE; EL; HU; IE; IT; LV; NL; NO; PT; RO; SI; ES; SE; TR; UK

Abstract (English)

The aim of this COST network is to find new reactions and selectivities with organocatalysts. These catalysts consist of small organic molecules that act as very small artificial enzymes. Such an approach combines the efficiency of enzymes without all the ecological aspects related to transition-metal catalysis. As such, organocatalysis is the “greenest” way to do organic synthesis. Our group has concentrated its efforts on several aspects: 1. New more efficient and selective organocatalysts 2. New original electrophiles, such as nitrodienes and dienic sulfones 3. New nucleophilic partners, such as Angelica lactone, that can provide all-carbon quaternary stereogenic centers 4. Cascade reactions where two or more reactions are done in the same pot. The new organocatalysts are based on various aminals of prolinal and its derivatives. Thus, we have recently described the effect of fluorine on the organocatalyst backbone and studied the conformational changes it provides. Concerning dienic systems, we have now extended this chemistry to diesters, with the same success as for sulfones. New electrophiles have successfully been tested, such as ethylenic keto-amides and keto-esters. As for new nucleophilic partners, we have studied the behaviour of diketones and keto-cyanides, which provide new polycyclic compounds with high stereo- and enantioselectivity. We have also started new studies with diaminocarbene organocatalysts (N-Heterocyclic Carbenes, NHC) to also get polycyclic compounds with high stereo- and enantioselectivity Finally, we have investigated chiral phosphoric acid derivatives, in new transposition reactions. The results are excellent on the semi-pinacol rearrangement, and provide fluorinated and other halogenated products, useful in medicinal chemistry.

References in databases (English)

Swiss Database: COST-DB of the State Secretariat for Education and Research Hallwylstrasse 4 CH-3003 Berne, Switzerland Tel. [phone] Swiss Project-Number: C11.0080