UK chemists have assembled three molecular building blocks into a complex organic molecule using a catalytic mixture of iridium and palladium. 

Ronald Grigg and colleagues at the University of Leeds, Johnson Matthey and Pfizer, have designed a cascade of reactions which occur sequentially, in one-pot, in the presence of a bimetallic catalyst. 

All in all, the cascade reactions form three C-C bonds, one tetrasubstituted carbon centre, one spirocyclic ring and one di- or tri-substituted exocyclic alkene. 

The first step, the functionalisation of alcohols with 1,3-dimethylbarbituric acid, is catalysed by iridium. The alcohol acts as an alkylating agent and a new C-C bond is formed. If the starting material is benzylic alcohol with iodine at the ortho position, this intermediate reacts with an allene to form a spirocyclic ring with an exocyclic di- or tri-substituted double bond. Palladium catalyses these steps of the synthesis - the palladium reaction involves allene insertion to the arylpalladium iodide species to generate a pi-allyl intermediate which after intramolecular cyclisation forms a spirocyclic barbituric acid derivative.

'Key factors in the robust design of catalytic multicomponent processes employing two or more metals is the relative reactivity rates of both the metal catalysts and the various substrates,' said Grigg. 

In the future, the researchers hope to use relative rate data to design processes with high atom economic core organic reactions (e.g. aldol, Michael addition, etc.) and, as a consequence, generate expanded cascades of yet higher complexity.

Alison Stoddart