Construction of 3,4-Dihydroquinolone Derivatives through Pd-Catalyzed [4+2] Cycloaddition of Vinyl Benzoxazinanones with α‑Alkylidene Succinimides

• Published in: Journal of organic chemistry Vol. 89; no. 5; pp. 3279 - 3291
• Main Authors: Yu, Ting-Ting, Huang, Peng-Ting, Chen, Ben-Hong, Zhong, Ya-Jun, Han, Bo, Peng, Cheng, Zhan, Gu, Huang, Wei, Zhao, Qian
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.03.2024; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; BENZYLIDENE SUCCINIMIDES; ASYMMETRIC CONSTRUCTION; PALLADIUM; MELODINUS; NITROGEN-HETEROCYCLES; TANDEM; CYCLIZATION REACTIONS; 1,3-DIPOLAR CYCLOADDITION; BIOLOGICAL-ACTIVITY; STEREOSELECTIVE-SYNTHESIS
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.3c02728

The construction of 3,4-dihydroquinolone derivatives has attracted a considerable amount of attention due to their extensive applications in medicinal chemistry. In this study, we present the Pd-catalyzed [4+2] cycloaddition of vinyl benzoxazinanones with α-alkylidene succinimides for the efficient synthesis of 3,4-dihydroquinolones. This approach presents numerous advantages, including the ready availability of starting materials, mild reaction conditions without the use of additional bases, and a wide range of substrates. In particular, all of the desired products can be easily afforded in high yields (≤99%) and excellent diastereoselectivities (>20:1). The practicality and reliability of this strategy were demonstrated by the successful scale-up synthesis and subsequent straightforward synthetic transformations.