An Endo‐Selective Epoxide‐Opening Cascade for the Fast Assembly of the Polycyclic Core Structure of Marine Ladder Polyethers

• Published in: Angewandte Chemie International Edition Vol. 59; no. 42; pp. 18473 - 18478
• Main Authors: Li, Feng‐Xing, Ren, Shu‐Jian, Li, Pei‐Fang, Yang, Peng, Qu, Jin
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 12.10.2020
• Edition: International ed. in English
• Subjects: Alcohols; brevenal; Butanol; Chemical reactions; Chemical synthesis; cyclization cascades; epoxide-opening reactions; fluorinated alcohol; marine polyethers; Polyethers; epoxide-opening reactions; cyclization cascades; fluorinated alcohol; brevenal; marine polyethers
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202007980

The rapid synthesis of marine ladder polyethers from polyepoxide precursors (in analogy with the biosynthetic pathway hypothesized by Nakanishi) is hampered by the fact that the exo‐selective epoxide‐opening cyclization cascade that gives THF‐type polyethers is preferred over the endo‐selective cascade that gives the desired products. We found that perfluoro‐tert‐butanol (PFTB) cooperating with 1‐ethyl‐3‐methylimidazolium tetrafluoroborate ([EMIM]BF4) can promote endo‐selective epoxide‐opening cyclization reactions of trisubstituted epoxy alcohols. Starting from readily accessible homochiral polyepoxy alcohols with a methyl group at all the endo‐cyclization sites, we were able to construct polyethers up to five consecutive fused 6‐, 7‐, and/or 8‐membered rings in one step. Notably, molecules with the 7/7/6/6 and 7/7/6/7/6 polyether frameworks of hemibrevetoxin B and brevenal, respectively, could be synthesized in 40 % and 17 % chemical yields. Starting from readily accessible homochiral polyepoxy alcohols with a methyl group at all endo‐cyclization sites, polyethers of up to five consecutive fused 6‐, 7‐, and/or 8‐membered rings were constructed in one step. Notably, marine ladder polyethers hemibrevetoxin B and brevenal with 7/7/6/6 and 7/7/6/7/6 polyether frameworks, respectively, could be synthesized with the corresponding 40 % and 17 % chemical yields.