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A highly atroposelective synthesis of nonbiaryl N-C atropisomers was achieved via direct aminations of 1,3-benzenediamines with azodicarboxylates enabled by chiral phosphoric acid catalysis. A series of N-substituents, benzene-substituents and azodicarboxylates were well tolerated, generating N-C atropisomers with high configurational stability. The facile derivatizations and utilizations of the chiral products as novel chiral organocatalysts demonstrate the value of these reactions.
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http://dx.doi.org/10.1039/d0cc02368j | DOI Listing |
Beilstein J Org Chem
August 2025
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
pH-Responsive molecular switches and motors are a class of organic molecules whose three-dimensional structure can be changed by acid-base stimuli. To date, pH-responsive molecular switches have been developed using various functional groups, but further advances require expanding the range of pH-responsive systems and discovering new molecular architectures. Here, we investigate the pH-responsive behavior of -disubstituted benzamidine, which generates atropisomers and / isomers.
View Article and Find Full Text PDFJ Am Chem Soc
July 2025
College of Chemistry, Zhengzhou University, Zhengzhou, Henan 450001, China.
Catalyst-guided divergent synthesis marks a paradigm shift in organic synthesis, offering transformative potential to access structurally diverse molecules. By leveraging symmetric enolates as programmable synthons, we established a catalyst-guided atroposelective - and -acylation for the switchable divergent synthesis of N-C and N-N axially chiral pyridones. The outstanding enantio- and regiocontrol (- vs -acylation) originated from the development of new chiral 4-pyrrolidinopyridine (PPY) derivatives and PPY--oxides as orthogonal acyl-transfer catalysts.
View Article and Find Full Text PDFOrg Lett
April 2025
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Here we present an enantioselective intramolecular hydroamination reaction of -aminophenyl-1,3-enynes via cooperative catalysis of Pd(0) and chiral phosphoric acid. This approach enables the efficient construction of N-N/C-N axially stereogenic indoles with broad skeletal diversity and high levels of enantioselectivity in a completely atom-economic manner. Mechanistic studies indicate that a protonation of the alkyne moiety via Pd(0) π-Lewis base activation is favored, and the chiral phosphate counteranion plays a crucial role in controlling the atroposelectivity in the ring-closure step.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
September 2024
College of Chemistry, Zhengzhou University, Zhengzhou, Henan, 450001, China.
A symmetric anion mediated dynamic kinetic asymmetric Knoevenagel reaction was established as a general and efficient method for accessing both N-C and N-N atropisomers. The resulting highly enantio-pure pyridine-2,6(1H,3H)-diones exhibit diverse structures and functional groups. The key to excellent regio- and remote enantiocontrol could be owed to the hydrogen bond between the enolate anion and triflamide block of the organocatalyst.
View Article and Find Full Text PDFAcc Chem Res
September 2023
College of Chemistry and Chemical Engineering, Qingdao University, Qingdao 266071, China.
ConspectusAtropisomers bearing a rotation-restricted axis are common structural units in natural products, chiral ligands, and drugs; thus, the prevalence of asymmetric synthesis has increased in recent decades. Research into atropisomers featuring an N-containing axis (N-X atropisomers) remains in its infancy compared with the well-developed C-C atropisomer analogue. Notably, N-X atropisomers could offer divergent scaffolds, which are extremely important in bioactive molecules.
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