Metal-free, organocatalytic syn diacetoxylation of alkenes

Article abstract of DOI:10.1021/ol301311e

A novel method for the organocatalytic syn diacetoxylation of alkenes has been developed using aryl iodides as efficient catalysts. A broad range of substrates, including electron-rich as well as electron-deficient alkenes, are smoothly transformed by the new procedure, furnishing the desired products in good to excellent yields with high diastereoselectivity (up to >19:1 dr).

Full text of DOI:10.1021/ol301311e

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Metal-Free, Organocatalytic Syn
Diacetoxylation of Alkenes
Wenhe Zhong, Shan Liu, Jun Yang, Xiangbao Meng,* and Zhongjun Li*
The State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical
Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, P.R. China
xbmeng@bjmu.edu.cn; zjli@bjmu.edu.cn
Received May 11, 2012
ABSTRACT
A novel method for the organocatalytic syn diacetoxylation of alkenes has been developed using aryl iodides as efficient catalysts. A broad range
of substrates, including electron-rich as well as electron-deficient alkenes, are smoothly transformed by the new procedure, furnishing the
desired products in good to excellent yields with high diastereoselectivity (up to >19:1 dr).
Metal-catalyzed dioxygenation of alkenes has emerged
as one of the most powerful methods for the preparation of
valuable syn-1,2-diols.1 Among them, OsO4-catalyzed syn
dihydroxylation of alkenes along with its asymmetric
version developed by Sharpless et al., has been elegantly
demonstrated and widely used in organic synthesis.2
Because of the high cost and toxicity of Os complexes,
other alternative metal catalysts such as ruthenium,3
manganese,4 iron,5 and palladium6 have been applied to
syn dioxygenation of alkenes (Scheme 1). However, most
of the metal catalysts are costly and toxic to some degree,
which limits their applications on an industrial scale.
Therefore, the development of metal-free alkene syn
dioxygenation procedures represents an attractive area of
research. Herein, to the best of our knowledge,7 we report
the first organocatalytic syn diacetoxylation of alkenes by
using aryl iodide as catalyst,8 which was in situ oxidized to
generate hypervalent iodine(III) species in the presence of
peroxide.
Scheme 1. Catalytic Syn Dioxygenation of Alkenes
(1) Bataille, C. J. R.; Donohoe, T. J. Chem. Soc. Rev. 2011, 40, 114.
(2) (a) VanRheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett.
1976, 17, 1973. (b) Schroder, M. Chem. Rev. 1980, 80, 187. (c) Jacobsen,
E. N.; Marko, I.; Mungall, W. S.; Schroeder, G.; Sharpless, K. B. J. Am.
Chem. Soc. 1988, 110, 1968. (d) Finn, M. G.; Sharpless, K. B. J. Am.
Chem. Soc. 1991, 113, 113. (e) Kolb, H. C.; Van Nieuwenhze, M. S.;
Sharpless, K. B. Chem. Rev. 1994, 94, 2483. (f) Salvador, J. A. R.;
Silvestre, S. M.; Moreira, V. M. Curr. Org. Chem. 2008, 12, 492.
(3) Selected examples for ruthenium catalysis: (a) Ho, C.-M.; Yu,
W.-Y.; Che, C.-M. Angew. Chem., Int. Ed. 2004, 43, 3303. (b) Plietker,
B.; Niggemann, A.; Pollrich, A. Org. Biomol. Chem. 2004, 2, 1116.
(c) Yip, W.-P.; Yu, W.-Y.; Zhu, N.; Che, C.-M. J. Am. Chem. Soc. 2005,
127, 14239. (d) Yip, W.-P.; Ho, C.-M.; Zhu, N.; Lau, T.-C.; Che, C.-M.
Chem.;Asian J. 2008, 3, 70. (e) Plietker, B.; Neisius, N. M. J. Org.
Chem. 2008, 73, 3218.
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R.; De Vos, D. E.; Alsters, P. L.; Feringa, B. L. Tetrahedron Lett. 2002,
43, 2619. (b) de Boer, J. W.; Brinksma, J.; Browne, W. R.; Meetsma, A.;
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7990. (c) Chow, T. W.-S.; Liu, Y.; Che, C.-M. Chem. Commun. 2011,
11204.
Although the metal-free dioxygenation of alkenes re-
mains a fascinating objective, only a few methods have
beendescribed. In2005, Sudalai and co-workersdeveloped
r
10.1021/ol301311e
XXXX American Chemical Society

a catalytic version of the WoodwardÀPrevost reaction
employing LiBr as the catalyst, and the syn dioxygenation
products were obtained with high diastereoselectivities
in the presence of NaIO4 at a high temperature.9 Quite
recently, Tomkinson et al. reported an effective alkene syn
dihydroxylation with malonoyl peroxides, and most
of the products were obtained with excellent stereo-
selectivity.8,10a In recent years, there has been an increasing
interest in the area of oxidative transformations mediated
by hypervalent iodine reagents, owing to their good oxi-
dizing properties and availability.11 As one impor-
tant application, hypervalent iodine reagent mediated
alkene dioxygenation has been well developed recently.12
However, stoichiometric use of hypervalent iodine leads to
equimolecular amounts of aryl iodides as a waste and is
mostly castigated by synthetic chemists. To address this
issue, development of aryl iodide-based organocatalytic
transformations has attracted much attention.11b,13 In
these reactions, aryl iodides are oxidized to hypervalent
compounds, which then undergo oxidative reactions and
release the aryl iodides to achieve a catalytic pathway. We
envisioned that by employing an aryl iodide as a catalyst in
the presence of an oxidant we might be able to realize a
novel organocatalytic syn dioxygenation procedure for
alkenes.
iodobenzene (0.1 equiv) in the presence of H2O2 with
BF3 OEt2 as additive at room temperature, a good yield
3
of the dioxygenated product was obtained, though in low
diastereoselectivity (Table 1, entry 1). We inferred that the
anti products, arose from oxidation of the substrate by
peroxy compounds in two steps: epoxidation followed by a
ring-opening process.14 Further increasing of the loading
of iodobenzene did not provide significant improvement in
product yield and stereoselectivity. To our delight, oxida-
tion was achieved in good yield as well as diastereoselec-
tivity when the substrate was delivered slowly via syringe
pump over 12 h (Table 1, entry 3). Moreover, detailed
studies showed that employing TfOH12c as the additive
was more efficient than BF3 OEt212d,e under these circum-
3
stances (see the Supporting Information). Subsequently,
a series of aryl iodides bearing electron-withdrawing
(Table 1, entries 5 and 6) or electron-donating (Table 1,
entries 7À9) substituents were investigated, and the results
indicated that iodomesitylene served as the most efficient
catalyst for this transformation. The main reason for the
enhanced reactivity of iodomesitylene is attributed to this
aryl iodide with electron-donating groups being more
easily oxidized to form the reactive hypervalent iodine(III)
species, suppressing the unfavorable side reactions accord-
ingly. Furthermore, lower catalyst loading also furnished
the desired products in good yield, albeit with decreased
diastereoselectivities (Table 1, entries 11 and 12).
With this in mind, we began our studies with indene
as a model substrate. When indene was reacted with
(5) (a) Suzuki, K.; Oldenburg, P. D.; Que, L., Jr. Angew. Chem., Int.
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Ed. 2008, 47, 1887. (b) Companye, A.; Gomez, L.; Fontrodona, X.;
Table 1. Optimization of Aryl Iodide Catalyzed Indene Diace-
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Ribas, X.; Costas, M. Chem.;Eur. J. 2008, 14, 5727. (c) Bruijnincx,
P. C. A.; Buurmans, I. L. C.; Gosiewska, S.; Moelands, M. A. H.; Lutz,
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M.; Rajaraman, G. Angew. Chem., Int. Ed. 2007, 46, 8067. (e) Chow,
T. W.-S.; W, E. L.-M.; Guo, Z.; Liu, Y.; Huang, J.-S.; Che, C.-M. J. Am.
Chem. Soc. 2010, 132, 13229. (f) Oldenburg, P. D.; Feng, Y.; Pryjomska-
Ray, I.; Ness, D.; Que, L., Jr. J. Am. Chem. Soc. 2010, 132, 17713.
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2962. (b) Wang, A.; Jiang, H.; Chen, H. J. Am. Chem. Soc. 2009, 131,
3846. (c) Wang, W.; Wang, F.; Shi, M. Organometallics 2010, 29, 928.
(d) Park, C. P.; Lee, J. H.; Yoo, K. S.; Jung, K. W. Org. Lett. 2010, 12,
2450. (e) Zhu, M.-K.; Zhao, J.-F.; Loh, T.-P. J. Am. Chem. Soc. 2010,
132, 6284. (f) Wang, A.; Jiang, H. J. Org. Chem. 2010, 75, 2321.
(7) Santi et al. developed a novel olefin dihydroxylation catalyzed by
diphenyl diselenide, but the diastereoselectivity was dependent on the
substrate: Santoro, S.; Santi, C.; Sabatini, M.; Testaferri, L.; Tiecco, M.
Adv. Synth. Catal. 2008, 350, 2881.
(8) Schwarz, M.; Reiser, O. Angew. Chem., Int. Ed. 2011, 50, 10495.
(9) Emmanuvel, L.; Ali Shaikh, T. M.; Sudalai, A. Org. Lett. 2005, 7,
5071.
(10) Peroxide mediated dihydroxylation of alkenes: (a) Griffith,
J. C.; Jones, K. M.; Picon, S.; Rawling, M. J.; Kariuki, B. M.; Campbell,
M.; Tomkinson, N. C. O. J. Am. Chem. Soc. 2010, 132, 14409. (b) Yuan,
C.; Axelrod, A.; Varela, M.; Danysh, L.; Siegel, D. Tetrahedron Lett.
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2012, 77, 921.
entry
catalyst (mol %)
PhI (10)
additive (mol %) yieldb (%)
drc
1
2
3d
4
BF3 OEt2 (10)
71
73
78
82
78
81
84
85
84
90
84
79
62
48
3.7:1
3.8:1
10:1
12.5:1
10:1
5.3:1
12.5:1
6.7:1
14:1
14:1
9:1
3
PhI (20)
BF3 OEt2 (10)
3
PhI (20)
BF3 OEt2 (10)
3
PhI (20)
TfOH (2)
TfOH (2)
TfOH (2)
TfOH (2)
TfOH (2)
5
4-IC6H4I (20)
4-ClC6H4I (20)
4-MeC6H4I (20)
4-MeOC6H4I (20)
6
7
8
9
2,4,6-Me3C6H2I (20) TfOH (2)
2,4,6-Me3C6H2I (20) TfOH (5)
2,4,6-Me3C6H2I (15) TfOH (5)
2,4,6-Me3C6H2I (10) TfOH (5)
10
11
12
13
14
6:1
e
TfOH (5)
e
2:1
(11) Recent reviews, see: (a) Wirth, T. Angew. Chem., Int. Ed. 2005,
44, 3656. (b) Richardson, R. D.; Wirth, T. Angew. Chem., Int. Ed. 2006,
45, 4402. (c) Ochiai, M. Chem. Rec. 2007, 7, 12. (d) Zhdankin, V. V.;
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Eur. J. Org. Chem. 2008, 4229. (f) Dohi, T.; Kita, Y. Chem. Commun.
2009, 2073. (g) Uyanik, M.; Ishihara, K. Chem. Commun. 2009, 2086.
2,4,6-Me3C6H2I (20)
3.3:1
a 1.0 mmol scale of 1a, 3.0 equiv of H2O2 (30%), 1.3 mL of Ac2O, 2.0
mL of AcOH, rt; then 3.0 mL of pyridine and 0.7 mL of Ac2O, rt.
b Isolated yield. c Determined by 1HNMR integration (syn/anti).
d Entries 3À14: 1a was added via syringe pump over 12 h. e Not added.
ꢀ
(h) Pouysegu, L.; Deffieux, D.; Quideau, S. Tetrahedron 2010, 66, 2235.
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With the optimized conditions identified, we next ex-
plored the generality of this new procedure. As shown
in Scheme 2, a variety of terminal alkenes, including
B
Org. Lett., Vol. XX, No. XX, XXXX

alkyl-substituted and aryl-substituted derivatives were ef-
ficiently elaborated to the corresponding products in good
to excellent yield, merely catalyzed by iodomesitylene and
H2O2 at ambient temperature. During the preparation of
our manuscript, Gade et al.15a developed a triflic acid
catalyzed diacetoxylation of alkenes in the presence of
peroxyacids.15 m-Chloroperbenzoic acid (m-CPBA) was
necessary to improve the reaction efficiency in some cases,
and the diacetoxylation of internal alkenes was usually
obtained with low diastereoselectivity. In our procedure,
all of the substrates were smoothly functionalized by using
environmentally benign H2O2 as oxidant. In order to further
investigate the stereoselectivity of this procedure, a series of
internal alkenes were subjected to the standard conditions.
Significantly, most of the internal alkenes were compa-
tible with this methodology and afforded the diacetoxyla-
tion products in moderate to excellent yield as well as
Scheme 3. Oganocatalytic Syn Diacetoxylation of Internal
Olefinsa
Scheme 2. Organocatalytic Diacetoxylation of Terminal Alkenesa
a Standard conditions, see Table 1, entry 10.
b Isolated yield.
c Determined by 1H NMR integration.
d 0.2 equiv of PhI was used.
e 2eÀi: 0.2 equiv of 4-MeC6H4I; substrate was added over 24 h.
f 2jÀn: 4-MeC6H4I (0.1 equiv), BF3 OEt2 (3.0 equiv), m-CPBA (1.2À1.4
3
equiv) was added in two batches, rt.
diastereoselectivity (summarized in Scheme 3), which re-
presents an unprecedented oganocatalytic alkene syn di-
oxygenation. When cinnamyl benzyl ether was exposed
to the standard procedure, a 45% yield of product
was obtained (Scheme 3, 2e). Gratifyingly, the use of
4-MeC6H4I as catalyst gave rise to a 63% yield.
We reasoned that the low efficiency of iodomesitylene in
thiscase might beduetostericpreferencefor linear internal
alkenes. Reactions of other cinnamyl alcohol derivatives
catalyzed by 4-MeC6H4I furnished the desired products in
moderate to good yield and excellent diastereoselectivity
(Scheme 3, 2fÀh). However, attempts to perform the
reaction with trans-methyl cinnamate resulted in trace
amounts of product, and the majority of starting material
recovered. Continuous efforts focused on searching for
alternative oxidants, such as oxone, peracetic acid and
tert-butyl hydroperoxide, but were unsuccessful. Finally,
we found that 0.1 equiv of 4-MeC6H4I smoothly catalyzed
a Standard conditions, see Table 1, entry 10; then 0.7 mL Ac2O, rt,
overnight.
b Yield of isolated product.
c 4fÀj: Substrate was added over 24 h, and 0.1 equiv of TfOH was used.
d Syn/anti.
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Chenede, A. Angew. Chem., Int. Ed. 2009, 48, 4605. (h) Uyanik, M.;
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Org. Lett., Vol. XX, No. XX, XXXX
C

Scheme 4. Multigram Scale Syn Diacetoxylation of Methyl
Cinnamate
Scheme 6. Proposed Mechanism for Aryl Iodide Catalyzed
Alkene Syn Dioxygenation
Scheme 5. Control Experiment
or BF3 OEt212d,e and undergoes electrophilic addition to
3
alkenes to yield intermediate B, providing the syn diace-
tates through a Woodward pathway (B to F). We found
that electron-deficient alkenes (R,β-unsaturated esters)
were tolerated with the oxidants, and most of the starting
material was recovered in the absence of aryl iodide
catalyst, in accord with the result that excellent diastereos-
electivities were obtained without the slow addition pro-
cedure (Table 3, 2jÀn).
In summary, the first metal-free organocatalytic alkene
syn diacetoxylation procedure has been developed through
use of readily available aryl iodides as catalysts. A broad
range of alkenes, electron-rich as well as electron-poor,
were found to be well-tolerated, and the reactions could be
carried out at room temperature. The procedure can also
be applied on multigram scale to deliver the desired
products in excellent yield as well as diastereoselectivity.
Considering the mild conditions and environmental benig-
nity, we anticipate that this new methodology may repre-
sent a valuable alternative to the existing metal-catalyzed
methods.
the dioxygenation of trans-methyl cinnamate applying
m-CPBA as oxidant without slow addition of substrate,
giving up to 98% yield and up to >19:1 (syn/anti) selec-
tivity (Scheme 3, 2j). Subsequent exploration of other
methylcinnamate derivatives alsoprovided excellent yields
as well as diastereoselectivities (Scheme 3, 2kÀn). Notably,
a 5.00 g scale of reaction could be conducted, further
demonstrating the synthetic practicality of this new proce-
dure (Scheme 4).
When trans-methyl 2,3-epoxy-3-phenylpropanoate (1o)
was subjected to the conditions, in the presence or absence
of aryl iodide (Scheme 5), the diacetate products were
obtained with low diastereoselectivities, indicating that
an oxirane intermediate may not be involved in the selec-
tive syn dioxygenation process. A plausible mechanism is
proposed in Scheme 6 which accords with the results
mentioned above. As electron-rich alkenes tend to engage
in epoxidation14 in the presence of peroxide, leading to the
poor stereoselective products (G), slow addition allows the
substrate to be oxidized by the in situ generated hyper-
valent iodine(III) species (A) that is activated by TfOH12c
Acknowledgment. This work was supported by grants
from the National Natural Science Foundation of China
(NSFC No. 21072017, 20732001) and the National Basic
Research Program of China (Grant No. 2012CB822100).
Supporting Information Available. All experimental
procedures and data for compounds. This material is
available free of charge via the Internet at http://pubs.
acs.org.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX