Credit: © 2008 ACS

Enzymes are made up of large numbers of amino acids — the overwhelming majority of which are chiral. The ability of these proteins to influence the stereochemical outcome of reactions they catalyse, however, originates not directly from this string of left- or right-handed building blocks, but rather from their well-defined three-dimensional structures. In an attempt to mimic such behaviour in a synthetic system, Jon Parquette and co-workers1 from Ohio State University have now shown that stereocentres at the periphery of a dendrimer can direct the substituents on a single bond at its centre to adopt a fixed conformation.

The central building block of the dendrimer is a biphenyl group that resembles the binaphthyl structure ubiquitous in asymmetric catalysis — here, however, the energy barrier to rotation about the biaryl bond is relatively low, and the two aromatic rings can rotate relative to one another. The arms of the dendrimer — dendrons — are diamide groups that, because of hydrogen bonding, can fold into two possible helical conformations. The helicity of the diamide unit can direct the conformation of the biphenyl group, but, in the absence of any further functionalization, the dendrimer would exist as a mixture of structures — with all the possible conformations present. When simple chiral groups with defined stereochemistry are added to the dendrons, a single helicity in the diamide unit is preferred, and the chiral information is thus relayed to the central scaffold of the dendrimer.

To show that this relay process is effective, Parquette and colleagues used the dendrimer as a ligand in an asymmetric hydrogenation reaction. Control experiments on a similar system with a conformationally fixed scaffold at the centre of the dendrimer eliminated the possibility that the stereochemical induction comes directly from the chiral substituents at the outside edge of the structure.