Enantioselective Catalytic Asymmetric A3 Coupling with Phosphino-Imidazoline Ligands

A practical
application of the UCD-PHIM ligand in the copper-catalyzed
asymmetric A3 coupling is reported for aromatic, alkenylic, and alkynylic
aldehydes under mild reaction conditions, low catalytic loading, and
at ambient temperature. A broad range of aldehydes, secondary amines
with a cheaper ethyne equivalent, 2-methyl-3-butyn-2-ol, was explored
and enantioselectivities of up to 99% ee were obtained. The importance
of (i) axial chirality and central chirality, (ii) imidazoline moiety
over oxazoline moiety, and (iii) phosphine unit is investigated for
A3 coupling by synthesizing and testing a series of related ligands
to UCD-PHIM.