TADDOL-Based Phosphane-Phosphite Ligands in Enantioselective Cu-Catalyzed Grignard 1,4-Additions Followed by Mannich-Type Alkylations

Copper(I) complexes of TADDOL-based phosphanephosphite ligands catalyze enantioselective conjugate additions of various Grignard reagents to cyclic enones. Through trapping of the resulting chiral magnesium enolates with N-benzylidene-4-methylbenzenesulfonamide (as an imine) in one-pot procedures, the corresponding Mannich products (i.e., beta-aminocarbonyl compounds) were obtained in good yields and high enantiomeric purities, although with only low diastereoselectivities

Enantioselective One-Pot Conjugate Addition of Grignard Reagents to Cyclic Enones Followed by Amidomethylation

Enantioselective conjugate addition of Grignard reagents to enones, catalyzed by Cu-Taniaphos or Josiphos complex, affords chiral enolates. Ensuing one-pot Mannich reaction with TiCl₄-generated imine leads to aminocarbonyl compounds with benzyloxycarbonyl-protected nitrogen. Both diastereomers of these compounds are isolated in moderate yields but high enantiomeric purities (up to er 97.5:2.5)