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

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.