Catalyst-Free sp3C-H Acyloxylation: Regioselective Synthesis of 1-Acyloxy Derivatives of the Natural Product Tanshinone IIA.
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 sp3C-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.
CAS Key Laboratory of Receptor Research, Synthetic Organic & Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, People's Republic of China.|University of Chinese Academy of Sciences , Beijing 100049, People's Republic of China.
Chunyong
C
Ding
CAS Key Laboratory of Receptor Research, Synthetic Organic & Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, People's Republic of China.|ShanghaiTech University , Shanghai 20120, People's Republic of China.
Jie
J
Li
CAS Key Laboratory of Receptor Research, Synthetic Organic & Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, People's Republic of China.|University of Chinese Academy of Sciences , Beijing 100049, People's Republic of China.
Mingkun
M
Jiao
CAS Key Laboratory of Receptor Research, Synthetic Organic & Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, People's Republic of China.|ShanghaiTech University , Shanghai 20120, People's Republic of China.|University of Chinese Academy of Sciences , Beijing 100049, People's Republic of China.
Ao
A
Zhang
D045784:Abietanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D013237:Stereoisomerism
D045784:Abietanes; D004365:Drugs, Chinese Herbal; C021751:tanshinone