Scalable Enantioselective Total Synthesis of (−)‐Goniomitine

• Published in: Angewandte Chemie International Edition Vol. 58; no. 4; pp. 1174 - 1177
• Main Authors: Bin, Huai‐Yu, Wang, Ke, Yang, Dan, Yang, Xiao‐Hui, Xie, Jian‐Hua, Zhou, Qi‐Lin
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 21.01.2019; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: asymmetric synthesis; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Enantiomers; goniomitine; Hydrogenation; indole alkaloids; Iridium; natural products; Oxidation; Physical Sciences; Science & Technology; total synthesis; indole alkaloids; natural products; NATURAL-PRODUCT; asymmetric synthesis; CYCLIZATIONS; goniomitine; (+/-)-GONIOMITINE; total synthesis; ASYMMETRIC HYDROGENATION; CHIRAL IRIDIUM CATALYSTS; SIMPLE INDOLE ALKALOIDS
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201812822

A scalable enantioselective total synthesis of (−)‐goniomitine has been developed by using an iridium‐catalyzed asymmetric hydrogenation of an exocyclic enone ester to control the configuration of the molecule. The synthesis begins from commercially available starting materials, and proceeds through an integrated asymmetric ketone hydrogenation, Johnson–Claisen rearrangement, and one‐pot oxidation/deprotection/cyclization process. With this highly efficient and scalable strategy, (−)‐goniomitine was synthesized in eleven steps with 27 % overall yield, and formal enantioselective syntheses of (+)‐1,2‐dehydroaspidospermidine, (+)‐aspidospermidine, and (+)‐vincadifformine were also achieved. Going, going, goniomitine: A scalable enantioselective synthetic strategy featuring an iridium‐catalyzed asymmetric hydrogenation of an exocyclic enone ester for the total synthesis of (−)‐goniomitine and formal syntheses of (+)‐1,2‐dehydroaspidospermidine, (+)‐aspidospermidine, and (+)‐vincadifformine is reported.