Asymmetric Conjugate Addition of 3‐Hydroxychromen‐4‐Ones to Electron‐Deficient Olefins Catalyzed by Recyclable C2‐Symmetric Squaramide

• Published in: Advanced synthesis & catalysis Vol. 364; no. 2; pp. 426 - 439
• Main Authors: Kovalevsky, Ruslan A., Kucherenko, Alexander S., Korlyukov, Alexander A., Zlotin, Sergei G.
• Format: Journal Article
• Language: English
• Published: Heidelberg Wiley Subscription Services, Inc 18.01.2022
• Subjects: Alkenes; Asymmetry; bioactive compounds; C2-symmetric squaramides; Catalysts; Chemical synthesis; chromones; conjugated addition; Enantiomers; Esterification; flavonoids; green chemistry; organocatalysis; Reaction products; Single crystals
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.202101019

The readily scalable asymmetric synthesis of the chiral chromone derivatives functionalized at position 2 via electrophilic enantioselective olefination of the chromone core with nitroolefins and ß,γ‐unsaturated α‐ketoesters in the presence of simple C2‐symmetric tertiary amine‐squaramide catalyst was developed. The reaction products were obtained in 80–99% yield with 89–99% ee in 95% EtOH. The absolute configurations of the synthesized chromone derivatives were unambiguously established by transformation of compound (R)‐3 aa to known methyl (R)‐β‐nitro‐α‐phenylpropionate and by the single crystal XRD analysis of compounds (R,S)‐5 aa and (R,S)‐5 ab. Catalyst V poorly soluble in common organic solvents could be easily separated from the reaction mixture and reused up to 10 catalytic cycles. Catalytic hydrogenation and esterification reactions of the synthesized compounds were carried out to demonstrate synthetic potential of the developed procedure.