C2-symmetrical bis(camphorsulfonamides) as chiral ligands for enantioselective addition of diethylzinc to benzaldehyde

Purpose of the research was to determine the activity of chiral bis(sulfonamide) ligands derived from camphor in the addition of diethylzinc to benzaldehyde. Chiral bis(ketosulfonamides) and bis(hydroxysulfonamides), have been synthesized in a reaction of diamines with camphorsulfonic acid chloride. Their activity in a reaction of asymmetric addition of dialkylzinc to benzaldehyde in a presence of titanium(IV) tetraisopropoxide was determined. The bis(ketosulfonamide) ligands reveal low enantioselectivity, with the ee% not exceeding 12%. The bis(hydroxysulfonamides) reveal much higher asymmetric induction in the investigated ZnEt2 addition. The best enantiomeric excess (62%) has been observed for bis(hydroxysulfonamide) obtained from 1,3-diaminepropane. The yields of the reaction obtained after 18 h are 92–96%. Crystal structures have been solved for bis(ketosulfonamide) ligands obtained from diamines based on C2 to C4 chain. The (2R) configuration in the rings systems of bis(hydroxysulfonamide) containing the C3 bridge was also determined by the crystal structure analysis. The sulfonamides have been characterized by IR, 1H and 13C NMR.

Graphical abstractActivity of chiral bis(ketosulfonamides) and bis(hydroxysulfonamides) ligands derived from camphor was determined in the addition of diethylzinc to benzaldehyde in a presence of titanium(IV) isopropoxide. The bis(ketosulfonamide) ligands reveal low enantioselectivity (ee% < 12%). The bis(hydroxysulfonamides) reveal much higher asymmetric induction. The best enantiomeric excess (62%) has been observed for bis(hydroxysulfonamide) obtained from 1,3-diaminepropane. Crystal structures have been determined for bis(ketosulfonamide) ligands and bis(hydroxysulfonamide) containing the C3 bridge. Figure optionsDownload full-size imageDownload as PowerPoint slide