Atroposelective catalysis.

Atropisomeric compounds-stereoisomers that arise from the restricted rotation about a single bond-have attracted widespread attention in recent years due to their immense potential for applications in a variety of fields, including medicinal chemistry, catalysis and molecular nanoscience. This increased interest led to the invention of new molecular motors, the incorporation of atropisomers into drug discovery programmes and a wide range of novel atroposelective reactions, including those that simultaneously control multiple stereogenic axes. A diverse set of synthetic methodologies, which can be grouped into desymmetrizations, (dynamic) kinetic resolutions, cross-coupling reactions and de novo ring formations, is available for the catalyst-controlled stereoselective synthesis of various atropisomer classes.

Diastereodivergent Catalysis.

Alongside enantioselective catalysis, synthetic chemists are often confronted by the challenge of achieving catalyst control over the relative configuration to stereodivergently access desired diastereomers. Typically, these approaches iteratively or simultaneously control multiple stereogenic units for which dual catalytic methods comprising sequential, relay, and synergistic catalysis emerged as particularly efficient strategies. In this Perspective, the benefits and challenges of catalyst-controlled diastereodivergence in the construction of carbon stereocenters are discussed on the basis of illustrative examples.

Catalyst Control over Threefold Stereogenicity: Selective Synthesis of Atropisomeric Sulfones with Stereogenic C-S Axes.

Catalyst control over higher-order stereogenicity addresses significantly extended stereochemical space, but selective methods to govern threefold stereogenic units remained elusive. Herein, we report the stereoselective synthesis of threefold stereogenic triptycyl sulfones with atropisomerism arising from a C(sp )-S bond. An oxidation of a stereodynamic thioether controlled by a chiral phosphoric acid catalyst allowed selective access to enantioenriched triptycyl sulfoxides.

Photocatalytic deracemisation of cobalt(III) complexes with fourfold stereogenicity.

The deracemisation of fourfold stereogenic cobalt(III) diketonates with a chiral photocatalyst is described. With only 0.5 mol% menthyl Ru(bpy) photocatalyst, an enantiomeric enrichment of up to 88 : 12 e.

Catalyst-Controlled Stereoselective Barton-Kellogg Olefination.

Overcrowded alkenes are expeditiously prepared by the versatile Barton-Kellogg olefination and have remarkable applications as functional molecules owing to their unique stereochemical features. The induced stereodynamics thereby enable the controlled motion of molecular switches and motors, while the high configurational stability prevents undesired isomeric scrambling. Bistricyclic aromatic enes are prototypical overcrowded alkenes with outstanding stereochemical properties, but their stereocontrolled preparation was thus far only feasible in stereospecific reactions and with chiral auxiliaries.

Catalyst Control over Twofold and Higher-Order Stereogenicity by Atroposelective Arene Formation.

Contradictory to the first intuitive impression that forging putatively flat aromatic rings evades stereoisomerism, a striking variety of atropisomeric compounds are conceivable by the formation of arenes, offering captivating avenues for catalyst-controlled stereoselective strategies. Since the assembled atropisomeric products that contain one or several rotationally restricted single bonds are characterized by especially well defined molecular architectures, they are distinctly suitable for numerous pertinent applications. In view of the fascinating arene-forming aldol condensation pathways taking place in polyketide biosynthesis (cyclases/aromatases (CYC/ARO)), the versatile small-molecule-catalyzed aldol reaction appeared as an exceptionally appealing synthetic means to prepare various unexplored atropisomeric compounds in our efforts presented herein.

Tandem Acid/Pd-Catalyzed Reductive Rearrangement of Glycol Derivatives.

Herein, we describe the acid/Pd-tandem-catalyzed transformation of glycol derivatives into terminal formic esters. Mechanistic investigations show that the substrate undergoes rearrangement to an aldehyde under [1,2] hydrogen migration and cleavage of an oxygen-based leaving group. The leaving group is trapped as its formic ester, and the aldehyde is reduced and subsequently esterified to a formate.