Credit: © 2009 NPG

In the design of new synthetic organic reactions, those that can create multiple carbon–carbon bonds and stereocentres in the same reaction are of great interest. Such rapid generation of molecular complexity from simple precursors is useful in building the types of structure widely found in biologically active natural products and drug molecules.

Now, Gregory Fu and co-workers from the Massachusetts Institute of Technology have reported1 a phosphine-catalysed reaction that forms two rings, three contiguous stereocentres and an E-alkene isomer double bond from a linear substrate. Conjugate addition of the phosphine catalyst to an ynone first generates a zwitterionic enolate. A second conjugate addition of this enolate to a pendant α, β-unsaturated ester generates a second enolate and forms the first ring and two stereocentres. This second enolate reacts with the original ketone to close the second ring and elimination of the phosphine generates the alkene. The reaction has been used to generate several examples of 5,5-fused-ring systems and, so far, two examples of a 6,5-fused-ring system — structures that are found in several natural products.

Fu and co-workers now hope to develop an enantioselective version of their reaction and the initial results are promising. Despite the phosphine being a relatively long way from the carbon–carbon bonds that are formed, a first attempt using a chiral phosphine resulted in a 60% enantiomeric excess without any further optimization of the reaction conditions.