Axial chirality

About: Axial chirality is a research topic. Over the lifetime, 1230 publications have been published within this topic receiving 26867 citations.

Atroposelective Synthesis of Axially Chiral Biaryl Compounds

Abstract: A rotationally hindered and thus stereogenic biaryl axis is the structurally and stereochemically decisive element of a steadily growing number of natural products, chiral auxiliaries, and catalysts. Thus, it is not surprising that significant advances have been made in the asymmetric synthesis of axially chiral biaryl compounds over the past decade. In addition to the classic approach (direct stereoselective aryl-aryl coupling), innovative concepts have been developed in which the asymmetric information is introduced into a preformed, but achiral-that is, symmetric or configurationally labile-biaryl compound, or in which an aryl--C single bond is stereoselectively transformed into an axis. This Review classifies these strategies according to their underlying concepts and critically evaluates their scope and limitations with reference to selected model reactions and applications. Furthermore, the preconditions required for the existence of axial chirality in biaryl compounds are discussed.

Recent advances and new concepts for the synthesis of axially stereoenriched biaryls

Abstract: Axial chirality is a key feature of many important organic molecules, such as biologically active compounds, stereogenic ligands and optically pure materials. Significant efforts in the field of the atropisomeric synthesis of biaryls have hence been undertaken over the past decade. Several major improvements of the already known methods to build up such chiral backbones (e.g. oxidative couplings and stereoselective Suzuki–Miyaura arylations) have been achieved and, in parallel, novel concepts have emerged enabling unprecedented synthetic routes toward molecules of this kind. These outstanding steps further unlocked the door to the preparation of previously difficult-to-access precursors of privileged ligands like BINOL, BINAM, QUINAP and many other molecules of interest.

Assessing Atropisomer Axial Chirality in Drug Discovery and Development

Abstract: Assessing Atropisomer Axial Chirality in Drug Discovery and Development Steven R. LaPlante,* Lee D. Fader, Keith R. Fandrick, Daniel R. Fandrick, Oliver Hucke, Ray Kemper, Stephen P. F. Miller, and Paul J. Edwards* Department of Chemistry, Boehringer Ingelheim (Canada) Ltd., 2100 Cunard Street, Laval, Quebec, H7S 2G5, Canada Chemical Development, Non-Clinical Drug Safety, Boehringer Ingelheim Pharmaceutical Inc., 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States Office of New Drug Quality Assessment, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Building 22, Room 1446, Silver Spring, Maryland 20993, United States

Chiral monodentate phosphine ligand MOP for transition-metal-catalyzed asymmetric reactions.

Abstract: Chiral monophosphines, whose chirality is due to biaryl axial chirality, have been prepared from enantiomerically pure 2, 2'-dihydroxy-1,1'-binaphthyl and demonstrated to be highly efficient chiral ligands for transition-metal-catalyzed organic transformations, especially for reactions where chelating bisphosphine ligands cannot be used. The high efficiency is observed in palladium-catalyzed asymmetric hydrosilylation of a wide variety of olefins such as alkyl-substituted terminal olefins and in asymmetric reactions via pi-allylpalladium intermediates represented by asymmetric reduction of allylic esters with formic acid.

Dynamic Kinetic Resolution of Biaryl Atropisomers via Peptide-Catalyzed Asymmetric Bromination

Abstract: Despite the widespread use of axially chiral, or atropisomeric, biaryl ligands in modern synthesis and the occurrence of numerous natural products exhibiting axial chirality, few catalytic methods have emerged for the direct asymmetric preparation of this compound class. Here, we present a tripeptide-derived small-molecule catalyst for the dynamic kinetic resolution of racemic biaryl substrates. The reaction proceeds via an atropisomer-selective electrophilic aromatic substitution reaction using simple bromination reagents. The result is an enantioselective synthesis that delivers chiral nonracemic biaryl compounds with excellent optical purity and good isolated chemical yields (in most cases a >95:5 enantiomer ratio and isolated yields of 65 to 87%). A mechanistic model is advanced that accounts for the basis of selectivity observed.