Preparation of new bis(oxazoline) ligand bearing non-covalent interaction sites and an application in the highly asymmetric Diels–Alder reaction

New asymmetric bis(oxazoline) (Box) ligand bearing amide group at the oxazoline 4-position, (S,S)-2,2′-methylenebis(4-tert-butylcarbamoyl-2-oxazoline) (1S), was designed and synthesized for selective catalytic reaction. The crystal structure of the ternary copper complex, consisting of 1S and N-benzoyl-N-phenyl-hydroxylamine, demonstrated interligand interactions, such as hydrogen bonding and CH-π interaction. Catalytic performance of the copper complex with 1S was investigated for an asymmetric Diels–Alder reaction using benzylidene-2-acetylpyridine and 1,3-cyclohexadiene (CHD). The reaction product was enantio-pure endo-(pyridin-2-yl)(3-phenylbicyclo[2,2,2]oct-5-ene-2-yl)methanone (BPCD), of which crystal structure was analyzed by the X-ray method. No stereo- and enantio-isomer of BPCD was detected by chiral HPLC analysis. Introduction of hydrogen bonding site into 1S can promote the Diels–Alder reaction even though using poor reactive CHD. Without 1S, this reaction did not give any product. Addition of 2-propanol to this reaction system inhibited the formation of BPCD, indicating that the designed interligand interaction sites, especially hydrogen bonding, play an important role for catalytic performance.