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This article describes the first enantioselective synthesis of the Tasmanian marine alkaloid (+)-cylindricine B. The concise construction of the compound hinged on dearomative retrosynthetic logic combined with a tactical advance in the generation of congested, cyclic, alpha-tertiary amine centers. The scope of this key coupling reaction was explored in addition to providing a synthetic application for Cu-catalyzed enantioselective dearomatization of N-acyl-pyridiniums. The synthesis proceeds in five or six steps from commercially available starting materials.
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Dearomative Access to (−)-Thebaine and Derivatives
A synthesis of the natural product thebaine is reported in eight steps from commercially available starting materials, hinging on the dearomatization and coupling of simple aromatic starting materials. This provides divergent access to two unnatural opioid derivatives and is aimed at the long-term development of synthetic opioid analogs of the “wonderdrug” Naloxone. Additionally, a formal enantioselective synthesis of all reported targets is disclosed that leverages a catalytic asymmetric dearomatization via anion-pairing catalysis.
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- Award ID(s):
- 2154662
- PAR ID:
- 10552028
- Publisher / Repository:
- American Chemical Society
- Date Published:
- Journal Name:
- Organic Letters
- Volume:
- 25
- Issue:
- 47
- ISSN:
- 1523-7060
- Page Range / eLocation ID:
- 8424 to 8428
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1021/acs.orglett.3c03270
