New ways of making molecules

3 Apr 2017. NUS chemists have developed a molecular transformation process for producing biologically useful compounds for pharmaceutical products.

The pharmaceutical and chemical industries are constantly looking for easier ways to make valuable and more complex molecules. Researchers have found a new way to transform allenoates, a chemical compound, into useful molecules. The new method is able to produce selective products in large quantities. This reduces wastage and is a more efficient process.

Molecular symmetry is a fundamental concept in chemistry that can elucidate a molecule’s physical and chemical properties. What if a molecule “loses the symmetry”? It becomes a chiral compound that is very important in modern drug preparation. Such novel molecular transformations are called desymmetrisation reactions.

Recently, Prof LU Yixin and his research team from the Department of Chemistry, NUS have devised a transformative chemical process for allenoates to undergo intramolecular Rauhut–Currier reactions to desymmetrise cyclohexadienones. The Rauhut–Currier reaction is a simple and efficient method for creating molecules with carbon-carbon bonds in organic synthesis. Such reactions involving allenoates are rare. This new reaction is able to produce bicyclic lactones in high yields and excellent stereo-selectivity, using the amine catalyst, β-ICD. During the desymmetrisation process, the team also discovered that if a mixture of γ-substituted allenoate stereoisomers is used, only one form of the product is obtained. The discovery of this process opens a new avenue to produce stereochemically enriched allenes through synthetic chemical reactions.

This work not only documents the new reactivity of allenoates for intramolecular Rauhut–Currier reactions, it also provides a new approach toward synthesis of synthetically versatile bicyclic lactone and allene derivatives. This provides the pharmaceutical and chemical industries with new ways of creating valuable molecules.

Figure shows the desymmetrisation of cyclohexadienones via an intramolecular process. (a) and (b) are two competing pathways. (Right) Catalyst for the desymmetrisation reactions, β-ICD.

Reference

Yao WJ; Dou XW; Wen S; Wu JE; Vittal JJ; Lu YX*, “Enantioselective desymmetrization of cyclohexadienones via an intramolecular Rauhut-Currier reaction of allenoates” NATURE COMMUNICATIONS Volume: 7 Article Number: 13024 DOI: 10.1038/ncomms13024 Published: 2016.