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DOI: 10.1055/a-1948-3335
A Seven-Step Total Synthesis of (–)-Thebaine
We thank the National Natural Science Foundation of China (Grant No. 22250410258) and the Ministry of Science and Technology of the People's Republic of China for financial support.
This paper is dedicated to Professor Cristina Nevado, University of Zürich, in recognition of her receipt of the 2021 Dr. Margaret Faul Women in Chemistry Award
Abstract
The morphinan alkaloid (–)-thebaine is an industrially important chemical intermediate deployed in the semi-synthesis of various opioid medicines. Here, a seven-step total synthesis of this natural product is reported from simple, commercially available starting materials. The pivotal aryl allyl ether substrate, which is obtained through successive Suzuki-Miyaura cross-coupling and Mitsunobu substitution reactions, was engaged in a double-Heck cyclization sequence. The tetracyclic product of these processes was subjected to a photochemical hydroamination reaction that generated a N-Boc piperidine derivative embodying the full pentacyclic morphinan framework. Over a further three simple steps, this last compound was converted into (–)-thebaine.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1948-3335.
- Supporting Information
Publication History
Received: 05 August 2022
Accepted: 21 September 2022
Accepted Manuscript online:
21 September 2022
Article published online:
08 November 2022
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