Iron-Catalyzed Acyloxyalkylation of Styrenes Using Hypervalent Iodine Reagents

Article abstract of DOI:10.1021/acs.orglett.7b00923

Iron-catalyzed acyloxyalkylation of styrene derivatives using hypervalent iodine reagents was achieved. The acyloxyalkylation reaction proceeded using various types of styrenes and hypervalent iodine reagents. The acyloxyalkylated products were obtained in moderate to good yields without loss of the functional groups. The reaction proceeded via the formation of radical species derived from hypervalent iodine reagents by decarboxylation.

Full text of DOI:10.1021/acs.orglett.7b00923

Letter
pubs.acs.org/OrgLett
Iron-Catalyzed Acyloxyalkylation of Styrenes Using Hypervalent
Iodine Reagents
Zijia Wang,† Motomu Kanai,‡ and Yoichiro Kuninobu*,†,§
†Institute for Materials Chemistry and Engineering, Kyushu University, 6-1 Kasugakoen, Kasuga-shi, Fukuoka 816-8580, Japan
‡Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
§CREST, Japan Science and Technology Agency (JST), 6-1 Kasugakoen, Kasuga-shi, Fukuoka 816-8580, Japan
S
* Supporting Information
ABSTRACT: Iron-catalyzed acyloxyalkylation of styrene derivatives using
hypervalent iodine reagents was achieved. The acyloxyalkylation reaction
proceeded using various types of styrenes and hypervalent iodine reagents.
The acyloxyalkylated products were obtained in moderate to good yields without
loss of the functional groups. The reaction proceeded via the formation of radical
species derived from hypervalent iodine reagents by decarboxylation.
n recent decades, complexes and salts of second- and third-
I
row transition metals, such as palladium, ruthenium,
rhodium, and iridium, have emerged as powerful catalysts.1
The utilization of these metals as catalysts, however, is limited
by their relatively high cost and toxicity. On the other hand,
iron is the most abundant transition metal in the geosphere,
and iron catalysts have recently received much attention in
synthetic organic chemistry.2
Transition-metal-catalyzed difunctionalization of alkenes is
an important topic because the reactions can introduce two
new functional groups in only one step to efficiently construct
highly functionalized structures of pharmaceuticals and natural
products.3−6 Acyloxyalkylation of alkenes remains challenging;
however, examples are quite rare.7,8 Combined osmium-
promoted Sharpless epoxidation and successive alkylation of
the formed epoxides are a well-known traditional oxyalkylation
of alkenes, but the osmium catalyst is highly toxic and the
epoxidation and successive alkylation require two steps, features
that do not meet the current requirements of organic reactions.
Buchwald and co-workers recently realized a rapid synthesis of
enantiomerically enriched lactones by copper-catalyzed enan-
tioselective radical oxyalkylation of alkenes (Figure 1a, upper
row).9 Zhu and co-workers achieved copper(II)-catalyzed
oxyalkylation of alkenes with alkylnitriles (Figure 1a, lower
row).10 Wang and co-workers recently reported the first
example of a rhenium-catalyzed oxyalkylation of styrenes with
hypervalent iodine reagents,11 which act as both an oxidant and
alkylation reagent in the difunctionalization of styrenes (Figure
1b, upper row), but visible light irradiation is required for many
hypervalent iodine reagents.
Figure 1. Transition-metal-catalyzed radical acyloxyalkylation of
alkenes.
substrates (Table 1). The desired reaction did not proceed in
the presence of catalytic amounts of Fe(CO)3(cot) and
phenanthroline (L1) (entry 1). Acyloxyalkylated product 3aa,
however, was obtained using L2 or L3 as a ligand (entries 2 and
3). The desired product 3aa was not formed by introducing
electoron-withdrawing or -donating groups on the phenyl
groups of the phenanthroline derivatives (entries 4 and 5).
We successfully replaced the rhenium catalyst in this reaction
with an iron catalyst (Figure 1b, lower row). Iron-catalyzed
acyloxyalkylation is economical and environmentally benign,
and the reaction requires no visible light irradiation.
We optimized the reaction conditions using 1-(tert-butyl)-4-
Received: March 28, 2017
vinylbenzene (1a) and iodobenzene diacetate (2a) as model
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b00923
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Organic Letters
Letter
Table 1. Optimization of Reaction Conditions of Alkene
Acyloxyalkylation
Scheme 1. Reactions between Several Styrenes 1 and
(Diacetoxyiodo)benzene (2a)
a
a
a
Reaction conditions: 1 (0.250 mmol, 1.0 equiv), 2a (0.3250 mmol,
1.3 equiv), Fe(CO)3(cot) (0.0500 mmol, 10 mol %), L10 (0.0500
mmol, 10 mol %), CH3CN (1.0 mL), 70 °C, 12 h.
benzyl-, and α-phenylstyrenes 1l−1p. Five-membered hetero-
aromatic compounds with a vinyl group, 1q and 1r, also
provided the corresponding oxtalkylated products 3qa and 3ra
in 66% and 51% yields, respectively.
Next, we investigated several hypervalent iodine reagents
(Scheme 2). In all entries, no visible light irradiation was
necessary to produce radical species from the hypervalent
iodine reagents. Hypervalent iodine reagents 2b−2d bearing
primary, secondary, and tertiary alkyl groups produced the
corresponding acyloxyalkylated products 3bb−3bd in 63%−
82% yields. In a previous study by Wang, no results of the use
of any hypervalent iodine reagents containing functional groups
were reported (Figure 1b, lower row).7 We therefore
investigated hypervalent iodine reagents 2e−2j bearing func-
tional groups, such as trifluoromethyl and carbonyl groups as
well as chlorine, bromine, and iodine atoms. As a result, the
corresponding acyloxyalkylated products 3be−3bj were
obtained in moderate to good yields without loss of the
functional groups. The desired products 3bk and 3bl were also
obtained using hypervalent iodine reagents 2k and 2l bearing 4-
chlorophenyl and 4-methylbenzyl groups.
To elucidate the reaction mechanism, we conducted a
reaction in the presence of 1.0 equiv of 2,2,6,6-tetramethyl-
piperidine 1-oxyl (TEMPO) as a radical scavenger. As a result,
the acyloxyalkylation reaction did not proceed at all. This result
indicated that the acyloxyalkylation reaction proceeded via a
radical pathway. The proposed mechanism for the iron-
catalyzed acyloxyalkylation of styrene derivatives using hyper-
valent iodine reagents is shown in Scheme 3, based on the
a
Reaction conditions: 1a (0.250 mmol, 1.0 equiv), 2a (0.325 mmol,
1.3 equiv), iron catalyst (0.0500 mmol, 10 mol %), ligand (0.0500
mmol, 10 mol %), CH3CN (1.0 mL), 70 °C, 12 h. cot =
b
cyclooctatetraene. Yield determined by 1H NMR using 1,1,2,2-
c
tetrachloroethane as an internal standard. Isolated yield.
Phenanthrolines L6−L9 with substituents at the 2- and 9-
positions promoted the desired reaction (entries 6−9). 2,9-
Dimethyl-4,7-diphenyl-1,10-phenanthroline (L10) afforded the
best result, and 3aa was obtained in 53% yield (entry 10). The
desired product 3aa was not formed using 9,10-phenanthrene-
dione (L11) or 4,7-di(tert-butyl)bipyridine (L12) as a ligand
(entries 11 and 12). Acyloxyalkylated product 3aa was also
obtained in 50% yield using Fe(OAc)2 as a catalyst (entry 13).
Other iron complexes and salts gave 3aa in lower yields.12
The substrate scope of styrenes was investigated next
(Scheme 1). Styrene derivatives 1b and 1c gave target products
3ba and 3ca. α-Methylstyrenes 1d−1k also produced the
desired products 1da−1ka in moderate to good yields without
loss of the functional groups. The corresponding acyloxyalky-
lated products 3la−3pa were also afforded using α-butyl-, α-
B
DOI: 10.1021/acs.orglett.7b00923
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Organic Letters
Letter
iodobenzene; (4) addition of C to styrene derivative 1 to
give benzyl radical D; (5) oxidation of D by [Fe]n+1 to form
benzyl cation E; and (6) addition of the carbozylate to E to
produce the desired product 3.
Scheme 2. Reactions between Styrene 1b and
(Diacyloxyiodo)benzene 2
a
The desired product 3aa was also obtained even in gram
scale (Scheme 4). Treatment of 1.71 g of 1a with 2a in the
presence of catalytic amounts of Fe(CO)3(cot) and L4 gave
1.15 g of 3aa in 46% yield.
Scheme 4. Gram-Scale Reaction
In summary, we successfully developed an iron-catalyzed
acyloxyalkylation of styrene derivatives using hypervalent iodine
reagents. The choice of phenanthroline ligands was important
to promote the reaction. In a similar previously reported
rhenium-catalyzed reaction, visible light irradiation was
necessary for many hypervalent iodine reagents. The present
reaction, however, required no irradiation. The reaction
proceeded in moderate to good yields, even in gram scale,
using a variety of styrenes and hypervalent iodine reagents
without loss of the functional groups. Compared with the
rhenium-catalyzed reaction, the scope of hypervalent iodine
reagents with functional groups was expanded. We hope that
the present result will provide useful insight into synthetic
organic chemistry using iron catalysts.
ASSOCIATED CONTENT
* Supporting Information
■
S
a
Reaction conditions: 1b (0.250 mmol, 1.0 equiv), 2 (0.325 mmol, 1.3
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b00923.
equiv), Fe(CO)3(cot) (0.0500 mmol, 10 mol %), L10 (0.0500 mmol,
10 mol %), CH3CN (1.0 mL), 70 °C, 12 h.
Experimental procedures and compound characterization
data of all new compounds (PDF)
Scheme 3. Proposed Reaction Mechanism
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: kuninobu@cm.kyushu-u.ac.jp.
ORCID
Motomu Kanai: 0000-0003-1977-7648
Yoichiro Kuninobu: 0000-0002-8679-9487
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was partially supported by CREST from JST and
Grant-in-Aid for Scientific Research (B) from the Ministry of
Education, Culture, Sports, Science, and Technology of Japan.
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(12) Fe(0) powder, 41%; [FeCp*(CO)2]2, 30%; Fe(acac)2, 38%;
Fe(OTf)2, 0%; Fe(ClO4)2, 12%; FeS, 34%; FeF2, 24%; FeCl2, 19%;
FeBr2, 25%; Fe3O4, 0%; Fe(OEt)3, 26%; Fe(OTf)3, 0%.
D
DOI: 10.1021/acs.orglett.7b00923
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