Elimination Reaction Cooks Up Chiral Allenes

One chemist’s trash can be another’s treasure. Take the β-hydride elimination, which chemists are trained to suppress during transition-metal-mediated bond formations. A team at the University of Texas, San Antonio, has turned that thinking around and is now using β-hydride elimination to make chiral allenes (J. Am. Chem. Soc., DOI: 10.1021/ja401606e). These compounds, which have two consecutive double bonds in a carbon chain, appear in some liquid crystals and an anti­ulcer drug. But the drug is a mixture of two isomers because pure chiral allenes are hard to make. A handful of research groups are bucking convention and treating β-hydride eliminations as reactions in their own right, says Doug E. Frantz, who led the research. But his lab’s transformation is the first example of an asymmetric version of the reaction. Ian T. Crouch and Robynne K. Neff developed chiral phosphite ligands to carry out the chemistry, which so far works best when starting with (E)-enol triflates. Those reagents are expensive to make, Frantz says, and his team is looking for ways around them. They plan to use the reaction to make libraries of allenes for Eli Lilly & Co.’s Open Innovation Drug Discovery program. They’re also partnering with chemical reagent supplier Sigma-Aldrich to make the phosphite ligands available for everyone.