Iron-catalyzed carbonylation-peroxidation of alkenes with aldehydes and hydroperoxides

Article abstract of DOI:10.1021/ja204226n

A three-component reaction of alkenes, aldehydes, and hydroperoxides catalyzed by FeCl₂ to β-peroxy ketones has been achieved. This three-component reaction can be also applied to the synthesis of α-carbonyl epoxides, through either a stepwise base-induced epoxidation of the separated β-peroxy ketone products or a one-pot process by simply adding base to the reaction mixture after the completion of the three-component reaction.

Full text of DOI:10.1021/ja204226n

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pubs.acs.org/JACS
Iron-Catalyzed Carbonylation-Peroxidation of Alkenes with
Aldehydes and Hydroperoxides
Weiping Liu, Yuanming Li, Kaisheng Liu, and Zhiping Li*
Department of Chemistry, Renmin University of China, Beijing 100872, China
S Supporting Information
b
Scheme 1. Catalytic
ABSTRACT: A three-component reaction of alkenes,
CarbonylationꢀPeroxidationꢀEpoxidation
aldehydes, and hydroperoxides catalyzed by FeCl2 to
β-peroxy ketones has been achieved. This three-component
reaction can be also applied to the synthesis of R-carbonyl
epoxides, through either a stepwise base-induced epoxida-
tion of the separated β-peroxy ketone products or a one-pot
process by simply adding base to the reaction mixture after
the completion of the three-component reaction.
Table 1. Optimization of the Reaction Conditionsa
ifunctionalization of alkenes is a class of significant synthetic
D
reactions that allow for the buildup of molecular complexity
in a single procedure. Dihydroxylation1 and Palladium-catalyzed
oxidative difunctionalization of alkenes2 demonstrated its high
impacts on synthetic chemistry.3 Carbonylation of alkenes4 has
been developed as one of powerful methods for synthesis of
carbonyl compounds, including large-scale commodity products
and versatile chemical intermediates. However, difunctionaliza-
tion of alkenes to introduce a carbonyl group and another
different functional group such as alcohol, amine, and peroxide
is still a distinct challenge.4,5 Herein, we wish to disclose a novel
iron-catalyzed, three-component carbonylationꢀperoxidation
reaction of alkene, aldehyde, and hydroperoxide to afford β-peroxy
ketones (Scheme 1). This iron-catalyzed, three-component
reaction can be also applied to the synthesis of R-carbonyl
epoxide through either a stepwise base-induced epoxidation of
the separated β-peroxy ketone products or a one-pot process by
simply adding base to the reaction mixture after the completion
of three-component reaction.
2a
3a
catalyst
solvent
yield
4a (%)b
entry
(equiv)
(equiv)
(2.5 mol %)
(3.0 mL)
1
1
3
3
3
4
5
5
5
5
5
5
5
5
5
5
5
3
3
2
1
3
3
3
3
3
3
3
3
3
3
3
3
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl3
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DCEc
PhMec
DMSOc
H2Oc
13
53
37
15
71
91
67
55
15
38
66
63
79
<5
<5
41
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
The application of readily available and nontoxic iron
catalysts instead of expensive and sensitive catalysts is highly
attractive for chemical synthesis.6 Recently, great progress has
been made in exploring iron-catalyzed CꢀH transformation.7
Our group and others successfully employed a Fe(II or III)/
peroxide catalytic system for CꢀC bond formation.8,9
Inspired by these, we challenged ourselves to see whether
difunctionalization of alkenes with a carbonyl group and
another group, such as alkoxyl and peroxyl group, could be
also reached.
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
FeCl3 6H2O
3
FeBr2
Fe(OAc)2
Fe(acac)2
-
a Conditions: 1a (0.5 mmol), 85 °C, 1 h, under N2. b Reported yields
were based on 1a and determined by 1H NMR using an internal
standard. c 100 °C.
The reaction of styrene 1a, benzaldehyde 2a, and tert-butyl
hydroperoxide 3a was chosen as a model to investigate our
tentative idea (Table 1).10 To our delight, a 91% yield of the
desired carbonylationꢀperoxidation product 4a was achieved in
the presence of 5 equiv of2a and 3 equiv of 3a using FeCl2 as catalyst
(entry 6). The efficiency of this transformation was dramatically
affected by the choice of solvents and iron catalysts (entries 7ꢀ15). It
should be noted that 4a was indeed formed without a catalyst, albeit
in a low yield (entry 16). The regioselectivity of this transformation
was confirmed by the condensation of 4a with 2,4-dinitrophenyl
hydrazine 5 (eq 1). X-ray diffraction analysis revealed that carbonyl
Received: May 8, 2011
Published: June 20, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/ja204226n J. Am. Chem. Soc. 2011, 133, 10756–10759
|

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Table 2. The Representative Results for the Carbonyla-
the reactions of R,β-unsaturated ketones with hydroperoxides
under base conditions.12 Mechanistically, β-peroxy ketone is a key
intermediate in these reactions. With our established three-
component protocol, epoxidation of 4 was investigated subse-
quently. After brief screening of base, it was found that 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) efficiently catalyzed
the epoxidation of 4 to furnish the corresponding epoxides 8
(Table 3).13 Delightfully, we found that the R-carbonyl ep-
oxides could be prepared by a one-pot process based on the
established carbonylationꢀperoxidationꢀepoxidation meth-
odologies (Scheme 2). The desired epoxides were efficiently
obtained from the three-component reactions of alkene, alde-
hyde, and hydroperoxde.
tionꢀPeroxidation Reactiona,b
In an attempt to rationalize the possible pathways for this
exclusively regioselective carbonylationꢀperoxidation trans-
formation, alkenyl aldehyde 9 was synthesized and subjected
to the standard reaction conditions (eq 3). Intramolecular
carbonylation-peroxidation product 10 was obtained.
Although this intramolecular transformation turned out to
be less efficient compared with the intermolecular cases,
importantly, the expected products derived from styrene 1a
1
were not detected by H NMR analysis (eq 3). This result
indicates that the reaction undergoes carbonylation followed
by peroxidation. Furthermore, TEMPO-adduct aldehayde 11
was isolated quantitatively when TEMPO was introduced to
the reaction, while the formation of 4a was completely
suppressed (eq 4). This result provided good evidence that
(1) acyl radical was formed under the standard conditions;
(2) cationic pathway is unlikely involved in this reaction.14
In addition, the reactions of tert-butyl peroxybenzote with
styrene did not provide the expected carbonylationꢀperoxidation
product under the standard reaction conditions. Therefore, the
possibility of tert-butyl peroxybenzote generated in situ as a possible
intermediate could be excluded for this transormation.15
a Conditions: 1 (0.5 mmol), 2 (2.5 mmol), 3 (1.5 mmol), MeCN
(3.0 mL), under N2. b Reported yields were based on 1 and determined
1
by H NMR using an internal standard; isolated yields were given in
parentheses. c 2 h. d β-Hydroxy ketone 4e0 was also obtained in 25% yield.
group attached to the β-carbon of styrene (see Supporting In-
formation).
The scopes of the substrates were investigated under the
optimized reaction conditions (Table 2). R-Substituted styrenes
afforded the desired products, 4b and 4c, in excellent yields.
2-Vinylnaphthalene, 4-vinylpridine, and 1,3-butadiene led to the
corresponding products in moderate yields. Gratifyingly, aliphatic
aldehydes were successfully applied to this transform under the
standard conditions. In most cases, the carbonylationꢀperoxidation
products were obtained in synthetically useful yields. Interestingly,
the decarbonylation product 7instead of the desired carbonylationꢀ
peroxidation product was obtained quantitatively when pivaldehyde
2r was applied under the standard conditions (eq 2). This result
indicated that decarbonylation competes with carbonylation kineti-
cally depended on the nature of substituent of aldehydes.11
On the basis of the above results and literature reports,16
a
tentative reaction mechanism for iron-catalyzed carbonyla-
tionꢀperoxidation of alkenes is given in Scheme 3. Alkyloxy
and alkylperoxy radicals are generated from a serious of steps,
including steps (a) and (b), by iron catalyst. Subsequently,
hydrogen abstraction by oxyl radicals, such as tert-butoxyl radical,
gives acyl radical (step c). The radical addition followed by
radical coupling17 leads to the final product (steps d and e).
However, further studies are needed to disclose the exact
mechanistic details of this transformation.
In summary, we have demonstrated a novel and practical
protocol of iron-catalyzed carbonylationꢀperoxidation of alkenes.
β-Peroxy ketones were selectively and efficiently constructed by
the three-component reaction of alkenes, aldehydes, and hydro-
peroxides. The three-component reaction was further applied
to the synthesis of R-carbonyl epoxides. Further studies on the
Epoxidation of alkenes is an important chemical process in
synthetic chemistry. R-Carbonyl epoxides could be synthesized by
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Table 3. DBU-Catalyzed Epoxidation Reactionsa,b
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
zhipingli@ruc.edu.cn
’ ACKNOWLEDGMENT
Financial support by the National Science Foundation of
China (20832002 and 21072223), the Fundamental Research
Funds for the Central Universities, and the Research Funds of
Renmin University of China (10XNL017). We thank Profs.
Zhenfeng Xi and Zhi-Xiang Yu in Peking University for helpful
discussions.
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