Tetrahedron Letters
Iron-catalyzed alkoxycarbonylation–peroxidation
of alkenes with carbazates and T-Hydro
Zhenzhen Zong a, Shenglin Lu a, Wenxiao Wang a, Zhiping Li a,b,
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a Department of Chemistry, Renmin University of China, Beijing 100872, China
b State Key Laboratory of Heavy Oil Processing, China University of Petroleum, Beijing 102249, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Iron-catalyzed alkoxycarbonylation–peroxidation of alkenes with carbazates and T-Hydro was devel-
oped. A variety of b-ester peroxides were synthesized efficiently and selectively in a single step starting
from readily available starting materials.
Received 10 September 2015
Revised 12 October 2015
Accepted 15 October 2015
Available online 23 October 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Iron catalysis
Alkoxycarbonylation
Peroxidation
Difunctionalization
Peroxidation is a fundamental methodology to introduce a per-
oxy (–OO–) group into organic molecules, which are receiving con-
siderable attention in pharmaceutical industries, biochemistry, and
synthetic chemistry. A number of peroxidation reactions have been
developed.1 Autoxidation is widely used to prepare various cyclic
peroxides and hydroperoxides under O2 or air.2 Kharasch oxidation
also presents an efficient method to synthesize the mixed perox-
ides using transition metal and hydroperoxides.3 Besides, the addi-
tion of peroxy radicals to alkenes and the nucleophilic substitution
of hydroperoxides with electrophiles are complementary strate-
gies to synthesize the peroxides.4 Nevertheless, the selectivity
and efficiency of the peroxidation are still great challenges. There-
fore, new peroxidation methods are highly desirable and valuable.
Difunctionalization of alkenes has attracted much attention
because of its rapid introduction of two functional groups across
a C–C double bond in a single operation.5 Recently, difunctionaliza-
tion of alkenes with a peroxy and another functional group is
becoming an attractive strategy for the preparation of organic per-
oxides (Scheme 1). In 2010, Taniguchi group disclosed an alkoxy-
carbonylation–hydroperoxidation of alkenes by aerobic oxidation
of hydrazines, in which the OOH group was easily decomposed
to a OH group (Eq. 1).6 Later, Taniguchi,7 Heinrich,8 and Leow9
groups revealed the method could be also applied to introduce aryl
and hydroperoxy group to alkenes selectively (Eq. 1). In 2011, we
demonstrated an acylation–peroxidation reaction, where a stable
tert-butyl peroxy group could be selectively introduced instead of
a frangible hydroperoxy group (Eq. 2).10 In 2014, Klussmann group
reported a carbo-peroxidation of alkenes using ketones and TBHP
(tert-butyl hydroperoxide; Eq. 3).11 In 2015, Loh12 and Wan13
groups successfully applied alcohols and diazo compounds as alkyl
groups to realize the alkylation–peroxidation of alkenes14 (Eqs. 4
and 5). Herein, we would like to report an iron-catalyzed15
alkoxycarbonylation–peroxidation reaction of alkenes with
carbazates and T-Hydro (70% TBHP in water; Eq. 6).
To determine the best reaction conditions, methyl carbazate 1a
and benzyl methacrylate 2a were chosen as model substrates
(Table 1). A 78% yield of the desired peroxide 3a was obtained by
the reaction of 1a, 2a, and T-Hydro with iron phthalocyanine
([Fe(Pc)]) as catalyst in CH2Cl2 (entry 1). However, other tested iron
salts showed no catalytic activity (entries 2–4). Interestingly, the
desired product 3a was obtained in 33% yield at 50 °C in the
presence of FeCl2Á4H2O (entry 5). These results indicated that
the Pc ligand of [Fe(Pc)] might enhance the reducibility of iron cat-
alyst and the methoxycarbonyl radical could be generated from
methyl carbazate 1a at 0 °C accordingly.6–9 CuCl2 led to 3a in 24%
yield (entry 6), while 3a was not detected using CoCl2 and MnCl2
(entries 7 and 8). Screening reaction conditions identified CH2Cl2
as a better solvent (entries 9–12). The yields of 3a were substan-
tially reduced by decreasing the amount of 1a and T-Hydro (entries
13 and 14). It should be noted that 3a was not obtained in the
absence of catalyst (entry 15).
Subsequently, the scope of the substrates was investigated
under the optimized reaction conditions (Table 2). To our delight,
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0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.