Incorporation of Axial Chirality into Phosphino-Imidazoline Ligands for Enantioselective Catalysis

Abstract

A complementary strategy for ligand tuning that enables controlling ligand conformation is described here. The concept is demonstrated with new ligands that are employed in the catalytic enantioselective preparation of the highly important C2-aminoalkyl five-membered heterocycle motif. The alkynylation/cyclization sequence developed here is convergent, highly modular, and allows for a complementary scope to the heteroarylation of imines. This new ligand platform should offer new possibilities for expanding the use of PHIM-type ligands in a large variety of new transformations.

Gold‐Catalyzed Transformations of Propargyl Alcohols and Propargyl Amines

“…In 2017, Aponick and co‐workers applied this method to the enantioselective preparation of 2‐aminoalkyl heterocyclic building blocks . The authors used an axially chiral phosphino‐imidazoline ligand (StackPhim) to achieve an enantioselective Cu‐catalyzed A 3 ‐coupling, affording enantioenriched propargylic amine 61 .…”

Lactone Synthesis by Enantioselective Orthogonal Tandem Catalysis

“…With the goal of developing a method to couple these alkyne reactivities in an efficient one‐pot transformation, it was recognized that both reaction and ligand selection would be crucial, and although chiral ligands are most commonly used for enantioselectivity, they can also efficiently control other types of selectivity . Studies from our laboratory have been directed at using heterocyclic chiral biaryl ligands in enantioselective transformations and we postulated that our Stack ligands might also control other types of selectivity. We recently reported conjugate addition to Meldrum's acid derivatives in water, and we decided that this would be a suitable reaction platform from which to build a subsequent catalytic transformation to form the six‐membered lactone 7 .…”

The Asymmetric A3(Aldehyde–Alkyne–Amine) Coupling: Highly Enantioselective Access to Propargylamines

“…Following the same strategy, new P,N-ligands L23 and L24 (StackPhim) were prepared by the same group in 2017 [66]. The two diastereomeric phosphines could be readily separated by simple column chromatography without a resolution process.…”