A Concise Total Synthesis of (−)‐Berkelic Acid

• Published in: Angewandte Chemie International Edition Vol. 60; no. 10; pp. 5141 - 5146
• Main Authors: Cheng, Hong‐Gang, Yang, Zhenjie, Chen, Ruiming, Cao, Liming, Tong, Wen‐Yan, Wei, Qiang, Wang, Qingqing, Wu, Chenggui, Qu, Shuanglin, Zhou, Qianghui
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 01.03.2021; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Catellani reaction; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; natural products; Physical Sciences; reductive coupling; Science & Technology; spiro-compounds; total synthesis; FORMAL SYNTHESIS; Catellani reaction; reductive coupling; KETONE FORMATION; TETRACYCLIC CORE; SPIROKETAL; ALKYL-HALIDES; CHAIN; natural products; TERTIARY ALKYL; spiro-compounds; COUPLING REACTIONS; BERKELIC ACID; ASSIGNMENT; total synthesis
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202014660

Reported here is a concise total synthesis of (−)‐berkelic acid in eight linear steps. This synthesis features a Catellani reaction/oxa‐Michael cascade for the construction of the isochroman scaffold, a one‐pot deprotection/spiroacetalization operation for the formation of the tetracyclic core structure, and a late‐stage Ni‐catalyzed reductive coupling for the introduction of the lateral chain. Notably, four stereocenters are established from a single existing chiral center with excellent stereocontrol during the deprotection/spiroacetalization process. Stereocontrol of the intriguing deprotection/spiroacetalization process is supported by DFT calculations. A concise total synthesis of (−)‐berkelic acid in eight linear steps was developed. This synthesis features a Catellani reaction/oxa‐Michael cascade for the construction of the isochroman scaffold, a one‐pot deprotection/spiroacetalization operation for the formation of tetracyclic core structure, and a late‐stage Ni‐catalyzed reductive coupling for the introduction of the lateral chain.