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Total Synthesis of Verruculogen and Fumitremorgin A Enabled by Ligand-Controlled C–H Borylation

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journal contribution
posted on 19.08.2015 by Yu Feng, Dane Holte, Jochen Zoller, Shigenobu Umemiya, Leah R. Simke, Phil S. Baran
Verruculogen and fumitre­morgin A are bioactive alkaloids that contain a unique eight-membered endo­peroxide. Although related natural products such as fumitre­morgins B and C have been previously synthesized, we report the first synthesis of the more complex, endo­peroxide-containing members of this family. A concise route to verruc­ulogen and fumitre­morgin A relied not only on a hydroperoxide/indole hemiaminal cyclization, but also on the ability to access the seemingly simple starting material, 6-methoxy­tryptophan. An iridium-catalyzed C–H borylation/Chan–Lam procedure guided by an N-TIPS group enabled the conversion of a tryptophan derivative into a 6-methoxy­tryptophan derivative, proving to be a general way to functionalize the C6 position of an N,C3-disubstituted indole for the synthesis of indole-containing natural products and pharmaceuticals.