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

ConspectusContradictory to the first intuitive impression that forging putatively flat aromatic rings evades stereoisomerism, a striking variety of atropisomeric compounds are conceivable by formation arenes, offering captivating avenues for catalyst-controlled stereoselective strategies. Since assembled products contain one or several rotationally restricted single bonds characterized especially well defined molecular architectures, they distinctly suitable numerous pertinent applications. In view fascinating arene-forming aldol condensation pathways taking place in polyketide biosynthesis (cyclases/aromatases (CYC/ARO)), versatile small-molecule-catalyzed reaction appeared as an exceptionally appealing synthetic means prepare various unexplored our efforts presented herein. initial studies, use secondary amine organocatalysts provided excellent selectivities condensations broad range products, such biaryls and amides. further analogy biosynthesis, it was also formed catalytic cascade reactions. The small-molecule catalysts thereby enabled us transfer this concept conversion unnatural noncanonical substrates, thus giving access atropisomers with particular value versatility reactions activation modes strategy individually control stereogenic axes, similar methodologies developed controlling stereocenter configurations. By iterative building block additions combined form rings, stereodivergent catalyst–substrate-matched -mismatched were obtained. Besides amines, cinchona-alkaloid-based quaternary ammonium salts proved be highly efficient overcoming severe substrate bias. obtained multiaxis systems, all biaryl suitably rotation even at high temperatures, spatially defined. helical structure is therefore excellently suited applications.While previous methods distinguish two stereoisomers each unit, catalyst beyond realms dualistic stereoisomerism remained unexplored. selective preparation O?ki their sixfold stereogenicity Rh-catalyzed [2 + 2 2] cyclotrimerizations, out six possible resulting from bond shown catalytically addressable. Catalyst over higher-order interconnects conformational analysis catalysis offers explore uncharted stereochemical space creating unprecedented motifs.