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

Abstract

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.

Chalcogen bonding catalysis

“…The activation energy difference for the process, between the two conformers, was found to be 8.06 kcal mol −1 providing the rationale behind the DKR process (Scheme 29). 47…”

Asymmetric Synthesis of S(IV) and S(VI) Stereogenic Centers

“…The Chi and Zheng group recently reported DKR of sulfoxides catalyzed using a chiral N -heterocyclic carbene ( Scheme 28 ). 77 The X-ray structure of the substrate suggested an intramolecular chalcogen bond (ChB) between the oxygen atom of the aldehyde and the sulfur atom of the sulfoxide. The ChB-induced conformational locking effect resulted in a racemic sulfoxide and through facile conformational isomerization enabled the efficient DKR.…”

Bidentate Ligand Driven Intramolecularly Te…O Bonded Organotellurium Cations from Synthesis, Stability to Catalysis

“…Consequently, cationic organotelluriums with decreased electron density show increased Lewis acidity and enhanced catalytic efficiency. [11] Organotelluriums have also the potential for biological activities such as the decomposition of peroxides, as radical chain-breaking antioxidants, as antitumor and antileishmanial agents. [12,13] Further organotelluriums are used in dyes, [14] and materials.…”

“…[7–10] The ability of the non‐bonding interaction is increased with the positive charge on the chalcogen center. Consequently, cationic organotelluriums with decreased electron density show increased Lewis acidity and enhanced catalytic efficiency [11] . Organotelluriums have also the potential for biological activities such as the decomposition of peroxides, as radical chain‐breaking antioxidants, as antitumor and antileishmanial agents [12,13] .…”