A Catalytic Oxidative Quinone Heterofunctionalization Method: Synthesis of Strongylophorine‐26

• Published in: Angewandte Chemie International Edition Vol. 57; no. 31; pp. 9805 - 9809
• Main Authors: Yu, Wanwan, Hjerrild, Per, Jacobsen, Kristian M., Tobiesen, Henriette N., Clemmensen, Line, Poulsen, Thomas B.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 26-07-2018
• Edition: International ed. in English
• Subjects: Catalysis; Catalysts; Chemical synthesis; cobalt; Cytotoxicity; Natural products; Nucleophiles; oxidation; Quinones; Reoxidation; terpenoids; oxidation; natural products; cobalt; quinones; terpenoids
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201805580

The preparation of heteroatom‐substituted p‐quinones is ideally performed by direct addition of a nucleophile followed by in situ reoxidation. Albeit an appealing strategy, the reactivity of the p‐quinone moiety is not easily tamed and no broadly applicable method for heteroatom functionalization exists. Shown herein is that Co(OAc)2 and Mn(OAc)3⋅2 H2O act as powerful catalysts for oxidative p‐quinone functionalization with a collection of O, N, and S nucleophiles, using oxygen as the terminal oxidant. Preliminary mechanistic observations and the first synthesis of the cytotoxic natural product strongylophorine‐26 is presented.
Sine qua non: Heteroatom‐functionalized p‐quinones are important within the chemical sciences and recurring elements of bioactive natural products. A powerful catalytic method employing transition‐metal salts and molecular oxygen as the terminal oxidant, for direct coupling of p‐quinones to O, N, and S nucleophiles, is reported. The value of the method is demonstrated by the first preparation of the terpenoid strongylophorine‐26.