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Reaction Mechanisms

Tying up topological chirality

Chemists develop new method to synthesize and separate chiral catenanes

by Laura Howes
April 11, 2019 | A version of this story appeared in Volume 97, Issue 15


Proposed reaction scheme for producing topological enantiomers.
Credit: Chem
Adding a stereogenic center to catenane rings before interlocking them gives two possible products that differ in the relative orientation of the rings, illustrated by the arrows.

Linked molecules have long captured chemists’ imaginations, and their synthesis even won researchers the 2016 Nobel Prize in Chemistry. But while these molecules are often discussed in terms of molecular motors and switches, Steve Goldup’s lab at the University of Southampton is more interested in understanding how to make them. Now, his team has developed a method for synthesizing and separating topologically chiral catenanes, enabling investigations of the exotic molecules’ properties (Chem 2019, DOI: 10.1016/j.chempr.2019.03.008).

“The work is a major step forward,” says Nicholas Evans of Lancaster University. He says it’s the first demonstration of enantiopure samples of topologically chiral catenanes on a preparative scale.

Topological chirality refers to a higher-level spatial orientation in these molecules. On their own, the catenane loops are not chiral. When they are interlinked, their chirality depends on their orientations relative to each other. The only way the chirality could be flipped would be to open a ring and reform it in the other direction.

The synthetic trick is to create a precursor with a chiral auxiliary on one end before linking it round another loop in a copper-catalyzed reaction. Researchers use the chiral auxiliary to direct the stereochemical outcome and separate the two resulting molecules with flash chromatography. Finally, they remove the auxiliaries to produce pure enantiomers.

Interlocked compounds with chiral substituents have been used for asymmetric catalysis. Goldup hopes to find similar uses for topologically chiral molecules. “We don’t know what the benefits of topological chirality might be in catalysis because no one’s ever been able to study it,” Goldup says. “This is a newly available stereogenic unit. Let’s find out what we can do with it.”



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