ORGANIC
LETTERS
2013
Vol. 15, No. 6
1162–1165
Oxygen Insertion of o‑Quinone under
Catalytic Hydrogenation Conditions
Da-Li Zhang,† Li-Yan Zhou,‡ Jun-Min Quan,‡ Wei Zhang,† Lian-Quan Gu,†
Zhi-Shu Huang,† and Lin-Kun An*,†
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China,
and Laboratory of Chemical Genomics, Shenzhen Graduate School of Peking University,
Shenzhen 518055, China
Received November 7, 2012
ABSTRACT
An oxygen-insertion reaction that transforms an o-quinone and a conjugated R-diketone substrate into an anhydride product or derivative under
catalytic hydrogenation conditions is reported. The experiments and computations indicate that the oxygen insertion proceeds via a radical
mechanism mediated by an acetoxyl radical.
Chemo- and regioselective oxygen insertion into a CꢀC
bond represents a versatile synthetic strategy of great value
in organic chemistry, which includes BaeyerꢀVilliger oxi-
dation,1 photooxidation,2 ozonolysis,3 and so on. All of
these methods generally occur under oxidants, such as
peracids in BaeyerꢀVilliger oxidations, singlet oxygen in
photooxidation, and ozone in ozonolysis. However, these
methods with common oxidants have several disadvantages.
For example, peracids used in BaeyerꢀVilliger oxidation are
costly, intrinsically unstable, toxic, and environmentally
unfriendly,4 while photooxidation and ozonolysis exhibit
low reaction selectivity and yield for targeted products. Here
we report an oxygen-insertion oxidation that transforms an
o-quinone and a conjugated R-diketone substrate into an
anhydride product or derivative under catalytic hydrogena-
tion conditions.
Tanshinone anhydride-type derivatives are a kind of
minor chemical component of Salvia miltiorrhiza Bunge,
a well-known traditional Chinese medicinal herb.5 Their
syntheses have attracted our efforts due to their potential
biological activity. During our study, we surprisingly
found that the anhydride-type product 2 of cryptotanshi-
none (1) was obtained under the Pd/C catalytic hydrogena-
tion conditions (Table 1). Compound 2 was characterized by
HRMS, 1D NMR,5a and 2D NMR spectra and finally
confirmed by X-ray single crystal analysis (SFigure 2). The
reaction in ethanol gave the oxygen-insertion product 2 and
its alcoholytic product S1 (Supporting Information) in 83%
total oxygen-insertion yield (Table 1, entry 4). To our best
knowledge, this represents the first case of oxygen insertion
into a CꢀC bond under catalytic hydrogenation conditions,
† Sun Yat-sen University.
‡ Shenzhen Graduate School of Peking University.
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r
10.1021/ol400164e
Published on Web 03/01/2013
2013 American Chemical Society