Asymmetric Total Syntheses of Di‐ and Sesquiterpenoids by Catalytic C−C Activation of Cyclopentanones

• Published in: Angewandte Chemie Vol. 132; no. 20; pp. 7922 - 7930
• Main Authors: Hou, Si‐Hua, Prichina, Adriana Y., Zhang, Mengxi, Dong, Guangbin
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 11.05.2020
• Subjects: Activation; Aglycones; Amination; Asymmetrische Synthesen; C-H-Aktivierung; Chemistry; Direct conversion; Diterpenes; Enantiomers; Natural products; Phosphoric acid; Regioselectivity; Rhodium; Sesquiterpenoids; Substrates; Terpenoide; Totalsynthesen
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201915821

To show the synthetic utility of the catalytic C−C activation of less strained substrates, described here are the collective and concise syntheses of the natural products (−)‐microthecaline A, (−)‐leubehanol, (+)‐pseudopteroxazole, (+)‐seco‐pseudopteroxazole, pseudopterosin A–F and G—J aglycones, and (+)‐heritonin. The key step in these syntheses involve a Rh‐catalyzed C−C/C−H activation cascade of 3‐arylcyclopentanones, which provides a rapid and enantioselective route to access the polysubstituted tetrahydronaphthalene cores presented in these natural products. Other important features include 1) the direct C−H amination of the tetralone substrate in the synthesis of (−)‐microthecaline A, 2) the use of phosphoric acid to enhance efficiency and regioselectivity for problematic cyclopentanone substrates in the C−C activation reactions, and 3) the direct conversion of serrulatane into amphilectane diterpenes by an allylic cyclodehydrogenation coupling. Zur Demonstration des Nutzens der Rh‐katalysierten C‐C/C‐H‐Aktivierungskaskade von 3‐Arylcyclopentanonen für die Synthese werden die kollektiven knappen und asymmetrischen, vier‐ bis neunstufigen Synthesen folgender Terpenoide beschrieben: (−)‐Microthecalin A, (−)‐Leubehanol, (+)‐Pseudopteroxazol, (+)‐seco‐Pseudopteroxazol, Pseudopterosin‐A–F‐ und Pseudopterosin‐G–J‐Aglycone sowie (+)‐Heritonin.