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Carbon-centred stereochemistry can be made intrinsically dynamic Now in Nature Chemistry → Congrats team Chemistry at York #MolMatYork and Durham Chemistry, Aisha N. Bismillah 🍉 Toby Johnson Dr Burhan Hussein Andrew Turley Promeet Saha Video Dr Anna Tanczos
94,869 просмотров • 3 лет назад •via X (Twitter)
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Carbon atoms with 4 different groups attached can exist in 2 mirror-image forms (enantiomers) Unlike other common stereogenic motifs, these sp3-C centres can't spontaneously flip between enantiomers without first breaking bonds. The sp3-C inversion barrier is too high

We used the fluxional Cope rearrangement of barbaralanes to make dynamically chiral molecules. They flip ∼1 million times a second We needed a substitution pattern that breaks the front-to-back mirror plane (σv″) but keeps a mirror plane at the Cope transition state (σv′)

The dynamic cages adapt to nearby stereochemical information. Covalently attaching a fixed stereocentre breaks the degeneracy of the rearrangement, i.e. favours either the R- or S-cage @TobyJohnson144 made these Mosher's esters

Low-temperature solution NMR spectra match up with solid-state NMR of a single crystal, confirming that the cage stereochemistry is being biased by the tether in solution

found that adding a dienophile stops the dynamic enantiomerisation of the cage by [2+2+2] cycloaddition. Reversing the cycloaddition restarts the fluxional rearrangement

We realised that the adaptive sp3-C chirality of the cage could be linked to the stereochemistry of coordinated metal ions, so we made phosphoramidite derivatives

The phosphoramidite acts as a bidentate P,olefin ligand for Pd. Now, during the Cope rearrangement the Pd 'walks' along the side of the cage while remaining coordinated. It flips dynamically between A and C stereochemistry in the process

found that a similar cationic Ru complex adapts to the presence of chiral counterions The inital 50:50 mixture of (R,C)- and (S,A)-complexes gradually shifts towards one enantiomer after adding TRISPHAT or BORBIN

We took advantage of this phenomenon in enantioselective ion-pair catalysis Paired with achiral or racemic P,olefin ligands, the chiral phosphoric acid BDHP gives negligible ee. But our fluxional ligand can adapt to the chiral counterion formed in situ, performing better

@NatureChemistry @ChemistryatYork @DurhamChemistry @ANBismillah @TobyJohnson144 @b_a_hussein @_AndrewTurley @PromeetSaha @SciCommStudios Congrats!


