Abstract
An oxidative sequence for the conversion of oxindoles to structurally distinct heterocyclic scaffolds and aniline derivatives is disclosed by the combination of a copper-catalyzed C-H peroxidation and subsequent base-mediated fragmentation reaction. In contrast to classic enzymatic (i.e., kynurenine pathway) and biomimetic methods (i.e., Witkop-Winterfeldt oxidation) for oxidative indole cleavage, this protocol allows for the incorporation of external nucleophiles. The new transformation displays broad functional group tolerance and is applicable to tryptophan derivatives, opening potential new avenues for postsynthetic modification of polypeptides, bioconjugation, and unnatural amino acid synthesis.
| Original language | English |
|---|---|
| Pages (from-to) | 988-991 |
| Number of pages | 4 |
| Journal | Organic Letters |
| Volume | 19 |
| Issue number | 5 |
| DOIs | |
| State | Published - 3 Mar 2017 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2017 American Chemical Society.
Funding
This work was supported by the NSF under the CCI Center for Selective C−H Functionalization (CHE-1205646). We thank DAAD (postdoctoral fellowship to H.F.T.K.), NSERC (graduate scholarship to A.F.G.G.), NSF (predoctoral research fellowship to D.C.D., No. DGE-1144469), the Gordon and Betty Moore Foundation, Amgen, Abbott, Boehringer Ingelheim, and Caltech for financial support. Larry Henling (Caltech) is acknowledged for X-ray analysis, and Dr. Robert Craig and Dr. Guillaume Lapointe (both Caltech) are thanked for helpful discussions.
| Funders | Funder number |
|---|---|
| National Science Foundation | 1205646, CHE-1205646 |
| Gordon and Betty Moore Foundation | |
| Abbott Laboratories | |
| Amgen | |
| Boehringer Ingelheim | |
| Natural Sciences and Engineering Research Council of Canada | DGE-1144469 |
| Deutscher Akademischer Austauschdienst |