Catalyst-Free sp3 C–H Acyloxylation: Regioselective Synthesis of 1‑Acyloxy Derivatives of the Natural Product Tanshinone IIA

• Published in: Journal of natural products (Washington, D.C.) Vol. 79; no. 10; pp. 2514 - 2520
• Main Authors: Ding, Chunyong, Li, Jie, Jiao, Mingkun, Zhang, Ao
• Format: Journal Article
• Language: English
• Published: American Chemical Society and American Society of Pharmacognosy 28.10.2016
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.6b00370

Tanshinone IIA is a valuable bioactive natural product isolated from the well-known Chinese herb Danshen. Structural manipulation of the A-ring of tanshinone IIA is rather limited. In this study, a substrate tautomerization-induced catalyst-free benzylic sp3 C–H acyloxylation approach is reported that allows the direct introduction of various acyloxy groups at the A-ring benzylic methylene of various tanshinone IIA substrates, thus avoiding the use of expensive transition metal catalysts and the production of harmful byproducts. This approach features a unique acid-induced reversible enolization/oxa-conjugate addition process followed by oxidation to exclusively give a series of diverse 1-acyloxylated derivatives under simple conditions in a regioselective manner. Compared with the literature procedures, this protocol demonstrates a higher efficiency, a more robust functional-group tolerance, atom economy, and lower cost.