Design, Preparation, and Implementation of an Imidazole-Based Chiral Biaryl P,N-Ligand for Asymmetric Catalysis

Abstract

A new strategy for increasing the barrier to rotation in biaryls has been developed that allows for the incorporation of 5-membered aromatic heterocycles into chiral atropisomers. Using this concept, an imidazole-based biaryl P,N-ligand has been designed and prepared as a single enantiomer. This ligand performs exceptionally well in the enantioselective A(3)-coupling, demonstrating the potential of this new design element.

Chromatographic resolution of atropisomers for toxicity and biotransformation studies in pharmaceutical research

“…The atropisomers are separated with the U-shape significant of a partial conversion of atrops in each other. One published article has discussed in regarding of the influence of -interactions on the energy barrier as well as the influence of pentafluoro group that will elevate this energy and will "stabilize" the compound toward one atropisomer [16].…”

Lactone Synthesis by Enantioselective Orthogonal Tandem Catalysis

“…[23] Studies from our laboratory have been directed at using heterocyclic chiral biaryl ligands in enantioselective transformations [24][25][26][27][28][29] and we postulated that our Stack ligands might also control other types of selectivity. [23] Studies from our laboratory have been directed at using heterocyclic chiral biaryl ligands in enantioselective transformations [24][25][26][27][28][29] and we postulated that our Stack ligands might also control other types of selectivity.…”

“…With the goal of developing am ethod 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,t hey can also efficiently control other types of selectivity. [23] Studies from our laboratory have been directed at using heterocyclic chiral biaryl ligands in enantioselective transformations [24][25][26][27][28][29] and we postulated that our Stack ligands might also control other types of selectivity. We recently reported conjugate addition to Meldrumsa cid derivatives in water, [30] and we decided that this would be asuitable reaction platform from which to build asubsequent catalytic transformation to form the six-membered lactone 7.…”

Enantioselective Copper‐Catalyzed Quinoline Alkynylation

“…As part of al igand development program exploring the use of StackPhos (9), [13] we became interested in the question of how to catalytically install alkynes at the quinoline C2 with stereocontrol, thus envisioning an ew synthetic approach to martinellic acid (1). [2,14] P, Nligands such as QUINAP (7)and PINAP (8)h ave been reported for copper-catalyzed alkyne addition reactions.I nterestingly,w hile Taylor and Schreiber reported the use of 7 in the enantioselective addition to isolated dihydroisoquinolinium salts, [15] satisfactory results were not obtained in the related reaction of the fully aromatic quinolines.…”

“…[17] These ligands share ac ommon structural motif,m ore specifically,t he biaryl system always consists of two six-membered aromatics that provide similar binding modes,w hich may be suboptimal in certain reactions. [17e] Encouraged by our success with StackPhos, [13] an axially chiral imidazole-based P, Nligand, we decided to investigate quinoline addition reactions as the electron-rich five-membered biaryl ring system with different dihedral and bite angles may help overcome this limitation.…”