来源：市场资讯
（来源：康龙化成）
Versatile Synthesis of Cyclopentenones via Skeletal Editing of Phenols
Mohammad Sodoor,∥ Jacob D. Hart,∥ Anna Wen Qing Koh, Sriyansh Nigam, Chin Yee Ho, Gabriel Chun Yi Ng, Hoi-Yeung Li, and Phillip S. Grant*
a, Division of Chemistry and Biological Chemistry, School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637371, Singapore. b, Nanyang Biologics, Singapore 119962, Singapor. c, School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
Recommended by Depei Meng _ MC4
KEY WORDS: Skeletal Editing, photo chemistry,oxidative dearomatization(反应类型), C(sp2)─C(sp3)(成键类型), cyclopentenones (产物),phenols (原料)
ABSTRACT: Cyclopentenones feature prominently in synthetic and medicinal chemistry because of their ability to act as covalent warheads and their versatility as synthetic intermediates. Yet, skeletal editing methods to access cyclopentenones are not well developed, making scaffold hopping at late stage unworkable. Here, we present a versatile approach to 2-cyclopentenones via the p- and o-carbon deletion of phenols. Deletion is achieved through a combination of oxidative dearomatization, photorearrangement, and tandem decarboxylation/alkene positional isomerization. Through a slight adaptation, this platform also allowed the ring contraction of guaiacols to access 2-(methoxycarbonyl)-2-cyclopentenones. We applied this methodology to the skeletal editing of a range of phenols, including natural products, and conducted a detailed mechanistic study. Cyclopentenones accessed by this method were tested for cytotoxicity against a panel of cancer cell lines, leading to the identification of a novel anticancer hit compound with a probable covalent mechanism of action.
(A) Cyclopentenones are important bioactive scaffolds. (B) Synthesis of cyclopentenones by skeletal editing. (C) This work.
Substrate scope of ortho-carbon deletion
Substrate scope of para-carbon deletion
Substrate scope of guaiacol ring contraction
Summary and Comments
In summary, Prof. Phillip S. Grant’s group present an approach to the para- and ortho carbon deletion of phenols, providing access to cyclopentenones. Ring contraction is first achieved by oxidative dearomatization and photorearrangement, which affords mixtures of (methoxycarbonyl)-substituted cyclopentenones. These mixtures are converged via tandem decarboxylation and alkene positional isomerization under acidic conditions. The authors applied this method to the C atom deletion of a range of phenols, including natural products, and conducted a detailed mechanistic study of the photochemical processes involved.
新加坡南洋理工大学Phillip Grant教授团队结合氧化脱芳构化和光重排等过程，成功实现酚类化合物邻/对位碳原子选择性删除，获得对应的环戊烯酮。该方法首先通过氧化脱芳构化和光重排实现缩环，得到不同位点（甲氧基羰基）取代的环戊烯酮混合物。这些混合物在酸性条件下经串联脱羧和烯烃位置异构化实现收敛，得到单一的环戊烯酮产物。该方法可应用于多种酚类化合物（包括天然产物）的碳原子消除。同时，作者也对其光化学过程开展了详细机理研究。
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