Solving a Mystery with Classical and Dual Photoredox Catalysis: Application of Nickel in the Synthesis of Ergot Alkaloids.
Jan Brauer, Rainer Wiechert, Anika Hahn, Till Opatz
Organic letters May 24, 2024 DOI: 10.1021/acs.orglett.4c01291 via PubMed
Summary
AI-generated from the abstractA new synthetic route to the ergot alkaloid lysergene and a formal total synthesis of LSD avoids palladium, using two nickel-catalyzed steps instead. A key intermediate previously reported by Hendrickson et al. in 2004 could not be reproduced with matching spectral data, raising doubts about their original route. However, the authors successfully leveraged this elusive intermediate to complete their own synthesis.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Keywords | Catalysis Chemical_synthesis Pharmaceutical_research Medicinal_compounds Sustainable_chemistry |
| Citations | 5 |
| Key finding | A palladium-free synthesis of lysergene and a formal total synthesis of LSD was achieved using two nickel-catalyzed steps, despite the inability to reproduce a key intermediate from a prior report. |
Abstract
A short synthesis of the ergot alkaloid lysergene and a formal total synthesis of lysergic acid diethylamide (LSD) under the avoidance of palladium and including two nickel-catalyzed steps instead have been developed. A key intermediate of this approach has already been reported by Hendrickson et al. in 2004 (Hendrickson, J.B. et al. Org. Lett. 2004, 6, 3-5), yet the spectral data do not match, adding to doubts about the course of their route. While the final steps of the Hendrickson synthesis could not be reproduced, we were able to leverage the elusive intermediate.