New Binaphthyl-Proline-Based Chiral Ligands Bearing Imidazoline Groups: Design, Synthesis, and Their Application in Enantioselective Conjugate Addition of 4-Hydroxycoumarin and Related Nucleophiles to β,γ-Unsaturated α-Ketoesters

Abstract

This paper describes the design and application of new binaphthyl-proline-based chiral ligands bearing imidazoline functional groups. These chiral ligands incorporate the advantages of both the binaphthyl and proline skeletons, they are featured with regulatable electronic and steric properties for the imidazoline functional groups, and form chiral complexes with different metal salts such as cuprous acetate. In the presence of an appropriate amount of a chiral catalyst, enantioselective conjugate addition of 4-hydroxycoumarin or related nucleophiles to different β,γ-unsaturated α-ketoesters proceeded readily, giving the desired products in high yield (up to 99%) and excellent enantiomeric excess (up to 99%).

Cu(II)‐Catalyzed Enantioselective Aza‐Friedel‐Crafts Reaction of 1‐Naphthols and Electron‐Rich Phenols with Isatin‐Derived Ketimines

“…In the case of C11 , nitrogen atom of the proline moieties adopted ( S )‐configuration (denoted as C11 ‐N( S ), Scheme 4). [18] This is also in agreement with our previous X‐ray diffraction result on the similar imidazoline‐containing chiral ligand [17] …”

“…Studies showed that in the presence of appropriate amount of in situ prepared chiral catalyst, enantioselective addition of 4-hydroxycourmarins to β,γ-unsaturated α-ketoesters proceeded readily, giving the desired products in up to 99 % yield and up to 99 % ee. [17] To further extend the application scope of these chiral ligands, we decided to test them in enantioselective Friedel-Crafts alkylation of naphthols and phenols with isatin-derived N-Boc ketimines as a continuation of our program in the preparation of biologically interesting chiral molecules.…”

“…[18] This is also in agreement with our previous X-ray diffraction result on the similar imidazoline-containing chiral ligand. [17] When the chiral ligand was allowed to be mixed with metal salts such as Cu(OTf) 2 , two forms of copper complexes, namely, C11-N(R)-Cu(OTf) 2 ( 7 In the presence of a suitable base such as piperidine, complex 8 was formed and acted as the catalyst of the reaction. The substrate coordinated to the central metal in a bidentate manner, with either the nitrogen atom or the oxygen atom cisto the imidazoline moiety.…”

“…In this type of chiral ligands, the steric feature could be altered by the use of substituents R 3 /R 4 with different sizes, and the electronic property could be fine‐tuned by introducing different substituents R 2 to sp 3 nitrogen atom of the imidazoline moiety. Studies showed that in the presence of appropriate amount of in situ prepared chiral catalyst, enantioselective addition of 4‐hydroxycourmarins to β,γ‐unsaturated α‐ketoesters proceeded readily, giving the desired products in up to 99 % yield and up to 99 % ee [17] …”

“…Preparation of chiral ligands C1-C11: chiral ligands C1-C11 were prepared based on previous report. [17] Chiral ligands C1-C8 were known compounds. Characterization of chiral ligands C9-C11 were given here.…”