‘Dynamic bonds’ reshape the rules of aromaticity and chirality


New discoveries in ‘dynamic bonds’ could reshape our fundamental understanding of key chemical concepts, including aromaticity and chirality. A team at the University of York in the UK has synthesised a polycyclic molecule whose aromaticity can be switched on and off, as well as a carbon cage where chiral carbon atoms interconvert without breaking bonds at the stereocentre. This ‘subverts our view of carbon-based molecules as fixed objects’, according to lead author Paul McGonigal. In the future, these new concepts could one day underpin ‘new applications for dynamic molecular materials’.

The researchers started by studying fluxional molecules.1 In these species, different functional groups interchange positions but, depending on the velocity of the process and the timescales of the observations, they may appear identical. An example is the extremely fast interconversion between cyclohexane chair and boat conformations. In an attempt to control and condition the interconversion rates of a range of fluxional molecules, researchers at York started overcrowding the structures with bulky and highly crowded systems. ‘We were lucky to observe both phenomena while exploring the effects of bond strain in fluxional molecules,’ explains McGonigal. Previously, the team had used this strategy to create unusual luminescence in strained structures, such as molecular rotors. Now, the results demonstrate dynamism is more common in organic molecules than previously thought.

Breaking aromaticity

The concept of aromaticity has mesmerised chemists for centuries. The new work shows aromaticity can be turned on and off, practically on demand, just by adding increasingly bulky groups around an aromatic ring – a tropylium cation. Previously, these rearrangements required external energy inputs. The bulky groups around the tropylium twist the molecule beyond its limits – eventually the contorted conformation ruptures aromaticity and forces a rearrangement of the seven-membered ring into a fused cyclopentane–cyclobutene – a bycycloheptane – non-aromatic structure dubbed ‘Dewar tropylium’.

‘It’s most interesting seeing that an aromatic tropylium cation rearranges to a bycyclic homo-antiaromatic [species],’ says Judy Wu, an expert in aromaticity based at the University of Houston in the US. ‘Typically, antiaromatic structures are experimentally difficult to capture.’ Antiaromatic molecules, unless somehow trapped or stabilised, tend to have very short lives. ‘They quickly escape from being antiaromatic,’ explains Wu. ‘However, here steric crowding largely limits and directs the path for [the] rearrangement, and a homo-antiaromatic carbocation is formed.’ According to the authors, this happens because the bulky groups around the tropylium have a propeller-like structure that locks the two different positions. This creates an extremely high energetic penalty for recovering aromaticity. ‘As far as I know, the only known example of a tropylium cation converting into an [antiaromatic] cation happens by photochemical rearrangement – light supplies the needed energy.’

‘We actually predicted the structures that would work, using DFT computational calculations and simulating different groups and positions,’ says McGonigal. The simulations suggested that steric bulk has a stronger influence than electronic effects, and phenanthrene rings surrounding the tropylium ring offered the perfect balance. Nevertheless, the rearrangement is still a speedy, dynamic process. ‘We could follow it using low-temperature nuclear magnetic resonance, [and] separately synthesising the molecules to study their properties,’ adds McGonigal.

In future studies, the team plans to expand the possibilities beyond tropylium as ‘it’s not the most frequently encountered functional group with aromaticity’, says McGonigal. Applying the findings to benzene rings remains a huge challenge – as well as carefully controlling the rearrangement, maybe through switchable steric groups. ‘Switching aromaticity on and off could have applications in the reactivity of metal sandwich complexes and self-assembled systems,’ he adds.

Controlling chirality

In another paper, the team describe a controlled interconversion between the enantiomers of chiral carbon centres without breaking carbon–carbon bonds at the stereocentre.2 They suspect the effect was unexplored because ‘it requires a carefully engineered cage-like structure, and it’s extremely quick and difficult to prove’, according to first author Aisha Bismillah. ‘It’s faster than the “ring flipping” in cyclohexane chairs,’ she adds. Although the spontaneous interconversion of enantiomers is common in sp3 nitrogen centres, this effect is extraordinary in sp3 carbons. ‘There’s other examples in intramolecular processes that include transesterification reactions and rotaxane shuttling … but it’s still quite unique. We isolated a single self-contained small molecule that fully enantiomerises,’ adds Bismillah.

‘Because of the rapid interconversion between enantiomers, chemists had probably previously assumed [this effect] wasn’t useful or interesting,’ says Matthew Fuchter, an expert in chiral systems at Imperial College London, UK. This discovery, he argues, poses interesting questions about the definitions of chirality, and ‘how we select molecules to study’. Chirality emerges from the existence of two non-superimposable mirror images of a given molecular structure. ‘Conventionally, we only tend to consider the chirality of molecules if the pair of enantiomers can be isolated, separated and studied,’ says Fuchter. And, in this case, fluxional molecules change configurations through very low barrier processes, which are extremely quick. In the discovered ‘dynamic carbon cages’, the shifts of structure in carbon–carbon double bonds rapidly interconvert the stereochemistry of the chiral carbons in the cage.

To study the different enantiomers, researchers used low temperature NMR and functionalisation strategies that ‘locked’ the chiral systems through auxiliaries and cycloadditions. The reactions yield diastereomers, which facilitate full characterisation. Additionally, this shows how minimal amounts of chiral information causes a cascade of events, setting the chiral configuration of several adjacent centres. ‘The dynamic nature of this framework becomes most relevant when coupled with other systems, [it’s] a way to communicate chiral information from remote sites to functional sites,’ including catalytic centres, explains Fuchter.

‘The chiral cage adapts, and this configuration triggers the transmission of stereochemical information,’ says Bismillah. ‘Such “sergeant and soldiers” systems, where small additions amplify chiral information, have many applications in chiral gels and polymers, as well as catalysis,’ she adds. Fuchter thinks that, while the level of asymmetric induction observed for catalysis in this study is weaker than state-of-the-art solutions with conventional chiral ligands, ‘the way of transmitting chiral information to the metal centre, and the associated mechanisms for interconversion [are] really interesting’, he says. Fuchter adds that this needs further exploration.

‘Our dynamic carbon cages hop back and forth between their mirror image structures millions of times a second, seeing them adapt to match changes in their environment is truly remarkable,’ says Bismillah. In the future, she adds, ‘we want to study the interactions between our chiral systems and biomolecules, to interrogate biochemical mechanisms and uncover their influence in drugs, for example’.

Bonds, aromaticity and chirality are fundamental chemistry concepts. ‘Many of their underlying principles were developed hundreds of years ago,’ says McGonigal, who’s ‘extremely satisfied’ at having challenged the idea that carbon–carbon bonds are fixed and immovable. ‘We’ve demonstrated that carbon-based molecules can be much more dynamic than previously thought.’