The introduction of two oxygen atoms across an alkene
is conceptually the mostdirect route toR-diketones but has
remained largely unexplored, and stoichiometric quan-
tities of oxidant are typically required.7 These reactions
generate large amounts of waste, which leads to envir-
onmental and economic issues associated with recy-
cling or removal of the reduction byproducts. For the
synthesis of complex, functionalized R-diketones, the
tandem alkene dihydroxylationꢀoxidation procedure
has proved most popular with respect to functional
group tolerance and mild reaction conditions.8 Khan et
al., in their pioneering work, reported a Ru-catalyzed
conversion of vicinal dihaloalkenes to R-diketones
using NaIO4.9 In this communication, we describe the
first catalytic oxidation of alkenes to R-diketones in
moderate to excellent yields.
Table 1. Optimization of Reaction Conditionsa
entry
catalyst
cocatalyst oxidant
solvent
yieldb
1
2
3
4
5
6
7
8
9
Ru(cymene)Cl2
Ru(cymene)Cl2
Ru(cymene)Cl2
Ru(cymene)Cl2
Ru(cymene)Cl2
Ru(cymene)Cl2
Ru(cymene)Cl2
Ru(cymene)Cl2
Ru(cymene)Cl2
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
TBHP toluene/MeCN/H2O 91%
TBHP toluene/H2O
TBHP MeCN/H2O
TBHP toluene/MeCN
TBHP DCE/H2O
47%
79%
83%
17%
23%
N.D.c
27%
23%
N.D.c
TBHP DME/H2O
TBHP DMSO/H2O
TBHP CH3NO2/H2O
TBHP Dioxane/H2O
TBHP iPrOH/H2O
10 Ru(cymene)Cl2
11
ꢀ
TBHP toluene/MeCN/H2O N.D.c
12 [Ru(cymene)Cl2]2 Bu4NCl TBHP toluene/MeCN/H2O N.D.c
13 [Ru(cymene)Cl2]2 Bu4NBr TBHP toluene/MeCN/H2O N.D.c
(6) (a) Zhu, Z.; Espenson, J. H. J. Org. Chem. 1995, 60, 7728–7732.
(b) Dayan, S.; Ben-David, I.; Rozen, S. J. Org. Chem. 2000, 65, 8816–
8818. (c) Murray, R. W.; Singh, M. J. Org. Chem. 1993, 58, 5076–5080.
(d) Wolfe, S.; Ingold, C. F. J. Am. Chem. Soc. 1983, 105, 7755–7757. (e)
Wan, Z.; Jones, C. D.; Mitchell, D.; Pu, J. Y.; Zhang, T. Y. J. Org. Chem.
2006, 71, 826–828. (f) Yusubov, M. S.; Zholobova, G. A.; Vasilevsky,
S. F.; Tretyakov, E. V.; Knight, D. W. Tetrahedron 2002, 58, 1607–1610.
(g) Giraud, A.; Provot, O.; Peyrat, J.-F.; Alami, M.; Brion, J.-D.
Tetrahedron 2006, 62, 7667–7673. (h) Mousset, C.; Provot, O.; Hamze,
A.; Bignon, J.; Brion, J.-D.; Alami, M. Tetrahedron 2008, 64, 4287–4294.
(i) Yusybov, M. S.; Filimonov, V. D. Synthesis 1991, 131–132. (j) Zhang,
C.; Jiao, N. J. Am. Chem. Soc. 2010, 132, 28–29. (k) Niu, M.; Fu, H.;
Jiang, Y.; Zhao, Y. Synthesis 2008, 2879–2882. (l) Tan, K. J.; Wille, U.
Chem. Commun. 2008, 6239–6241. (m) Ren, W.; Xia, Y.; Ji, S.-J.; Zhang,
Y.; Wan, X.; Zhao, J. Org. Lett. 2009, 11, 1841–1844. (n) Che, C.-M.;
Yu, W.-Y.; Chan, P.-M.; Cheng, W.-C.; Peng, S.-M.; Lau, K.-C.; Li, W.-
K. J. Am. Chem. Soc. 2000, 122, 11380–11392. (o) Al-Rashid, Z. F.;
Johnson, W. L.; Hsung, R. P.; Wei, Y.; Yao, P.-Y.; Liu, R.; Zhao, K. J.
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Yanase, T.; Maegawa, T.; Monguchi, Y.; Sajiki, H. Adv. Synth. Catal.
2010, 352, 1630–1634.
14 PdCl2
Bu4NI
Bu4NI
TBHP toluene/MeCN/H2O N.D.c
TBHP toluene/MeCN/H2O N.D.c
15 Pd(OAc)2
16 [Ru(cymene)Cl2]2 Bu4NI
17 [Ru(cymene)Cl2]2 Bu4NI
18 [Ru(cymene)Cl2]2 Bu4NI
19 [Ru(cymene)Cl2]2 Bu4NI
20 [Ru(cymene)Cl2]2 Bu4NI
O2
toluene/MeCN/H2O N.D.c
NaClO toluene/MeCN/H2O N.D.c
oxone toluene/MeCN/H2O N.D.c
(tBuO)2 toluene/MeCN/H2O N.D.c
H2O2
TBHP toluene/MeCN/H2
toluene/MeCN/H2O N.D.c
21 RuCl3
Bu4NI
86%
22 [Ru(benzene)Cl2]2 Bu4NI
23 [Ru(cymene)Cl2]2 Bu4NI
24 [Ru(cymene)Cl2]2 Bu4NI
TBHP toluene/MeCN/H2O 88%
TBHP toluene/MeCN/H2O 83%d
TBHP toluene/MeCN/H2O N.D.e
a 0.5 mmol of 1a, 0.005 mmol (1 mol %) of [Ru(cymene)Cl2]2,
0.15 mmol (30 mol %) of Bu4NI, and 3.6 equiv of TBHP in toluene/
MeCN/H2O at room temperature unless otherwise noted. b Isolated
yield. c Not detected. d 100 mmol of 1a. e 1,2-Diphenylethyne was used as
substrate.
(7) (a) Clayton, M. D.; Marcinow, Z.; Rabideau, P. W. Tetrahedron
ꢁ
Several groups have reported Ru-catalyzed oxo-functio-
nalizations of alkenes, such as epoxidation,10dihydroxy-
lation,11 ketohydroxylation,12 and oxidative cleavage.13
This suggested that controlling selectivity could be a big
challenge. (E)-1,2-Diphenylethene (1a) was selected as
a model substrate to establish the reaction conditions.
Through optimizing the reaction conditions, we determined
that 1 mol % [Ru(cymene)Cl2]2/30 mol % Bu4NI/3.6 equiv
of t-BuOOH (70% in aqueous solution) in toluene/MeCN/
H2O at room temperature for 1 h furnished the desired
oxidation product benzil 2a (Table 1, entry 1) in excellent
yield (91%). The transformation proceeded with high
selectivity, and only trace amounts of benzaldehyde (<5%)
were observed. Gratifyingly, the reaction was little affected
by atmospheric moisture and could, therefore, be per-
formed under air.
The influence of catalyst, cocatalyst, oxidant, and sol-
vent on the efficiency of this alkene oxidation is shown in
Table 1. Noproduct 2awas obtainedinthe absence of a Ru
catalyst (entry 11). When other Ru precursors, such as
RuCl3 and [Ru(benzene)Cl2]2, were used as catalysts,
comparable yields were achieved (entries 21 and 22).
Switching the catalyst to PdCl2 or Pd(OAc)2 did not
provide the desired product 2a (entry 14 and 15). Solvent
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