Single catalyst gives two products from racemic mixture

Chemists in the US have demonstrated a remarkable reaction in which a single catalyst can transform a racemic mixture - molecules identical in every way except for their chirality - into two distinct enantiomerically pure products. The finding is significant because it describes a new catalytic system to steer reactions towards producing specific ’enantiopure’ products - something that is crucial in many organic syntheses where chirality of reactants and products is vital.

Bin Wu, Jon R. Parquette and TV RajanBabu of Ohio State University took a racemic mixture of aziridines, which contain a strained three-membered ring, and reacted it with an azide in the presence of a catalyst based on two yttrium centres held within an organic framework.

Instead of obtaining a racemic mixture of products, as would ordinarily happen, two distinct products were obtained with the strained ring of each enantiomer of the aziridine being attacked in a subtly different way: the yttrium catalyst accelerated the ring opening of aliphatic aziridines by trimethylsilylazide, inducing nucleophilic attack at the primary position of one enantiomer and at the secondary position of the other.  The two products were themselves nearly enantiopure - essentially only one chiral form of each product was formed.

There are a number of ways of carrying out so-called asymmetric catalysis to obtain one chiral product in favour of another. A technique called kinetic resolution, for example, uses a catalyst that preferentially accelerates the reaction of one enantiomer, leaving behind the slow-reacting one. Even when the difference in rates of reactions of the two enantiomers is very high, only a maximum of 50 per cent yield is thus possible. Simultaneously accelerating the reaction rates of both enantiomers to produce different enantiopure products is extremely rare. In some cases, these products can be further converted into a single, enantiopure intermediate.  

Varinder Aggarwal, an organic chemist at the University of Bristol in the UK, says that the work is important. ’It is a remarkable reaction with great utility, as the racemic aziridines are easy to prepare but the enantioenriched products are not. Furthermore, this work has the potential to open up a whole new platform of research.’

’This is mainly a proof of concept in executing these reactions with a bimetallic catalyst,’ says RajanBabu. ’I am certain it is only a matter of time before we engineer other catalysts with different scaffolding around the metal centres to carry out other reactions of this nature.’

The precise way by which the catalyst distinguishes between the two substrates is not yet clear. ’It could be that the catalyst holds the different substrates in a specific orientation so that only one carbon is accessible to nucleophilic attack in the complex,’ says Parquette. ’But at this stage that is speculation.’

Simon Hadlington