Scientists crack 80-year-old chemical puzzle to transform medicine making

Researchers at the University of St Andrews, in collaboration with the University of Bath, have solved an 80-year-old chemical puzzle involving the [1,2]-Wittig rearrangement, a reaction historically considered too unpredictable to control for selective synthesis. This rearrangement, which reorganizes atoms within a molecule, is crucial because it affects the chirality—or "handedness"—of molecules, a property vital in pharmaceuticals where one chiral form can be therapeutic while the other may cause side effects. By combining laboratory experiments with advanced quantum chemistry calculations, the team discovered that the reaction proceeds through a two-step cascade: an initial catalyst-driven asymmetric rearrangement that sets the molecule’s chirality, followed by a previously unrecognized molecular reshuffle that preserves this chirality rather than scrambling it. This breakthrough fundamentally shifts the understanding of stereochemistry in rearrangement reactions and opens new avenues for designing selective chemical processes. The ability to reliably control the chirality in the [1,2]-Wittig rearr