New chiral thiols and C2-symmetrical disulfides of Cinchona alkaloids: ligands for the asymmetric Henry reaction catalyzed by Cu II complexes

Abstract

Seven Cinchona alkaloids were reacted with thioacetic acid and Bu 3P/diethyl diazadicarboxylate in THF at 0–25 °C to give the corresponding thiolacetates with complete inversion of configuration at the substitution center. The thus obtained chiral thiolesters were converted into thiols and these compounds were oxidized to the respective disulfides of C 2-symmetry. Both C-9 thioles and disulfides were tested as chiral ligands in the Cu-catalyzed asymmetric Henry reaction. When the thiol derivatives of an 8,9- like configuration were applied in the reaction of benzaldehyde and nitromethane, the obtained nitroaldol was of the same absolute configuration as the catalyst and the observed enantioselectivity was up to 83% ee. These ligands gave higher ees than the corresponding thioethers, disulfides, and thioles of 8,9- unlike configuration. The results obtained are in agreement with the proposed transition-state model involving nucleophilic attack of a deprotonated nitromethane directed preferably at one side of the O-complexed benzaldehyde.