Total Synthesis of Daphenylline via Diels–Alder Cycloaddition and Rhodium-Catalyzed C–H Alkynylation
Daphenylline, a structurally intricate <i>Daphniphyllum</i> alkaloid, poses a formidable synthetic challenge due to its highly fused hexacyclic [6.6.5.7.6.5] framework and multiple stereocenters. Herein, we report an efficient total synthesis of daphenylline in 12 steps from known starting materials, featuring a key intramolecular Diels-Alder reaction, oxidative aromatization, Rh-catalyzed C-H alkynylation, and aldol condensation. Our approach leverages a carbonyl-directed C-H functionalization strategy to achieve regioselective alkynylation within a complex pentacyclic framework without the need for strongly coordinating directing groups.
Authors
- Xingang Xie (ORCID: https://orcid.org/0000-0002-0707-1229)
- Aohang Liu
- Huaxuan Zhang (ORCID: https://orcid.org/0000-0003-1675-3480)
- Gaoyuan Zhao (ORCID: https://orcid.org/0000-0003-4838-865X)
- Wei Chen (ORCID: https://orcid.org/0000-0002-1131-3585)
- Pengfei Yu (ORCID: https://orcid.org/0009-0001-4331-5403)
- Huilin Li (ORCID: https://orcid.org/0000-0001-8088-6718)
- Jinwei Huang
- Xuegong She (ORCID: https://orcid.org/0000-0002-3002-2433)
Institutions
- Lanzhou University (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-06-30
- DOI
- https://doi.org/10.1021/acs.orglett.5c02227
- Citations
- 1
- Primary Topic
- Catalytic C–H Functionalization Methods
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- Lanzhou University
- National Natural Science Foundation of China
- Science and Technology Program of Gansu Province