H‐Bond Donor‐Directed Switch of Diastereoselectivity in the Enantioselective Intramolecular Aza‐Henry Reaction of Ketimines

• Published in: Chemistry : a European journal Vol. 30; no. 63; pp. e202402488 - n/a
• Main Authors: Tian, Jun‐Song, Yi‐Gong, Wu, Zhong‐Wei, Yu, Jin‐Sheng, Zhou, Jian
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 12.11.2024
• Subjects: Adducts; Ammonium; Ammonium salts; Aniline; Diastereodivergent; Enantiomers; Functionalization of C=N bond; Imines; Ketoesters; Phase transfer catalysis; Phosphoramide; Quaternary ammonium salts; Stereoselectivity; Tetrahydroquinoline; Phase transfer catalysis; Diastereodivergent; Phosphoramide; Functionalization of C=N bond; Tetrahydroquinoline
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202402488

We report an H‐bond donor controlled diastereoselective switchable intramolecular aza‐Henry reaction of ketimines derived from α‐ketoesters and 2‐(2‐nitroethyl)anilines, allowing facile access to chiral tetrahydroquinolines bearing an aza‐quaternary carbon stereocenter, which are privileged scaffold for medicinal researches. While newly developed cinchona alkaloid derived phosphoramide‐bearing quaternary ammonium salt C2 selectively give cis‐adducts in up to 20 : 1 dr and 99 % ee, the corresponding urea‐bearing analogue C8 preferentially give trans‐adducts in up to 20 : 1 dr and 99 % ee. An unprecedented highly enantioselective diastereodivergent intramolecular aza‐Henry reaction of ketimines derived from α‐ketoesters and 2‐(2‐nitroethyl)anilines by using newly developed bifunctional PTC catalyst C2 or C8 featuring a phosphoramide or urea as the H‐bond donor has been developed, providing facile access both cis and trans diastereomers of chiral tetrahydroquinolines featuring adjacent tetrasubstituted‐tertiary stereocenters in good to excellent stereoselectivity