Chalcogen bond-guided conformational isomerization enables catalytic dynamic kinetic resolution of sulfoxides

Conformational isomerization of organic molecules can be guided by noncovalent interactions. Here, the authors report the synthesis of chiral sulfoxides catalyzed by N-heterocyclic carbenes; intramolecular chalcogen bonding interactions are key for conformational locking. Conformational isomerization can be guided by weak interactions such as chalcogen bonding (ChB) interactions. Here we report a catalytic strategy for asymmetric access to chiral sulfoxides by employing conformational isomerization and chalcogen bonding interactions. The reaction involves a sulfoxide bearing two aldehyde moieties as the substrate that, according to structural analysis and DFT calculations, exists as a racemic mixture due to the presence of an intramolecular chalcogen bond. This chalcogen bond formed between aldehyde (oxygen atom) and sulfoxide (sulfur atom), induces a conformational locking effect, thus making the symmetric sulfoxide as a racemate. In the presence of N-heterocyclic carbene (NHC) as catalyst, the aldehyde moiety activated by the chalcogen bond selectively reacts with an alcohol to afford the corresponding chiral sulfoxide products with excellent optical purities. This reaction involves a dynamic kinetic resolution (DKR) process enabled by conformational locking and facile isomerization by chalcogen bonding interactions.

Automated summary

The authors report a synthetic method for the asymmetric synthesis of chiral sulfoxides using intramolecular chalcogen bonding interactions. The reaction involves conformational locking and facile isomerization enabled by chalcogen bonding interactions, leading to the formation of chiral sulfoxide products with excellent optical purities.