Enantiomer-Selective Carbamoylation of Racemic α-Hydroxy γ-Lactones with Chiral CuII Catalysts: An Example of a Highly Active Lewis Acid Catalyzed Reaction

Enantiomer‐selective carbamoylation of racemic α‐hydroxy γ‐lactones with half equivalents of isocyanates in the presence of chiral CuII catalysts was studied. Among a series of catalyst bearing chiral bis(oxazoline) (box) and pyridine(bisoxazoline) ligands, [Cu(tBu‐box)]X2 [X=OSO2CF3 (3 a), SbF6 (3 b)] showed the highest enantioselectivity in the reaction of pantolactone (1 a). Use of n‐C3H7NCO, a small alkyl isocyanate, in CH2Cl2 solution was important to achieve a high level of enantiomer selection. The tBu‐box‐CuII catalyst efficiently differentiated two enantiomers of β‐substituted α‐hydroxy γ‐lactones under the optimized reaction conditions, resulting in a stereoselectivity factor (s=kfast/kslow) of up to 209. Furthermore, this catalyst is highly active, so that the carbamoylation can be conducted with a substrate‐to‐catalyst molar ratio of 2000–3000. A catalytic cycle of this reaction is also proposed. Higher activity, better selectivity: The tBu‐box‐CuII complex performs high catalytic activity and enantiomer selectivity in the carbamoylation of racemic α‐hydroxy γ‐lactones. The reaction is conducted with a substrate‐to‐catalyst molar ratio of 2000–3000 to achieve a stereoselectivity factor (s=kfast/kslow) of up to 209.