New research from the University of Bath and the University of St Andrews, published in Nature Chemistry, has discovered the key to unlocking an 80-year-old chemical puzzle, which could have important ramifications for fine chemical processes like those involved in the manufacture of medicines.

Chiral molecules are asymmetric or non-superimposable on their mirror image – each side is different, existing in “right hand” and “left hand” forms. Often only one of these “handed” forms has the desired chemical or biological activity, while the other may have unwanted side effects.

Using a combination of lab experiments and quantum chemistry calculations, researchers have now discovered a new way to control the handedness of a notoriously difficult chemical process, known as the ‘[1,2]-Wittig rearrangement’ that will impact on how scientists design selective chemical reactions.

First discovered over 80 years ago, this process selectively reorganises atoms within a molecule but was traditionally considered too unpredictable to control, making it almost impossible to use.

However, the research team from St Andrews and Bath discovered that a catalyst first steers the molecule through an initial asymmetric rearrangement that sets its ‘handedness’, that is followed by a previously unrecognised molecular reshuffle that maintains molecular chirality.

This breakthrough will pave the way for faster, cleaner, and more selective ways to make complex molecules of a single handedness — with applications ranging from new drugs to advanced materials.

The research is published in Nature Chemistry.

Lead author of the paper, Professor Andrew Smith from the University of St Andrews, said: “This discovery represents a fundamental shift in how we understand and control stereochemistry in rearrangement reactions.”

Co-lead Dr Matthew Grayson from the University of Bath’s Department of Chemistry and Institute of Sustainability and Climate Change, added: “Our findings open the door to new asymmetric transformations based on mechanistic pathways that chemists previously dismissed as inaccessible.”