Calcium catalyzed enantioselective intramolecular alkene hydroamination with chiral C2-symmetric bis-amide ligands

Abstract

The chiral building block (R)-(+)-2,2′-diamino-1,1′-binaphthyl, (R)-BINAM, which is often used as backbone in privileged enantioselective catalysts, was converted to a series of N-substituted proligands ^R1-H₂ (R = CH₂tBu, C(H)Ph₂, PPh₂, dibenzosuberane, 8-quinoline). After double deprotonation with strong Mg or Ca bases, a series of alkaline earth (Ae) metal catalysts ^R1-Ae·(THF)_n was obtained. Crystal structures of these C₂-symmetric catalysts have been analyzed by quadrant models which show that the ligands with C(H)Ph₂, dibenzosuberane and 8-quinoline substituents should give the best steric discrimination for the enantioselective intramolecular alkene hydroamination (IAH) of the aminoalkenes H₂CCHCH₂CR′₂CH₂NH₂ (CR′₂ = CPh₂, CCy or CMe₂). The dianionic ^R1²⁻ ligand in ^R1–Ae·(THF)_n functions as reagent that deprotonates the aminoalkene substrate, while the monoanionic (^R1-H)⁻ ligand formed in this reaction functions as a chiral spectator ligand that controls the enantioselectivity of the ring closure reaction. Depending on the substituent R in the BINAM ligand, full cyclization of aminoalkenes to chiral pyrrolidine products as fast as 5 minutes was observed. Product analysis furnished enantioselectivities up to 57% ee, which marks the highest enantioselectivity reported for Ca catalyzed IAH. Higher selectivities are impeded by double protonation of the ^R1²⁻ ligand leading to complete loss of chiral information in the catalytically active species.