Iron-catalyzed oxidative addition of alkoxycarbonyl radicals to alkenes with carbazates and air

Article abstract of DOI:10.1002/anie.201005574

Clean and simple: Alkoxycarbonyl radicals generated from carbazates by iron catalysis in air underwent addition to a variety of alkenes to give the corresponding β-hydroxyesters (see scheme). The simple experimental procedure for this transformation has the added advantage that the reagents are environmentally friendly. R¹,R²=alkyl, alkynyl, aryl, CO₂Et; [Fe(Pc)]=iron phthalocyanine. Copyright

Full text of DOI:10.1002/anie.201005574

Communications
DOI: 10.1002/anie.201005574
Radical Reactions
Iron-Catalyzed Oxidative Addition of Alkoxycarbonyl Radicals to
Alkenes with Carbazates and Air**
Tsuyoshi Taniguchi,* Yuki Sugiura, Hisaaki Zaimoku, and Hiroyuki Ishibashi
À
Carbonylation reactions are powerful tools for C C bond
formation in synthetic chemistry.[1] In this area, carbonyl
radicals, such as acyl, alkoxycarbonyl, and carbamoyl radicals,
are useful reactive intermediates because they enable the
direct introduction of a carbonyl moiety, such as ketone, ester,
or amide group, into organic compounds by addition to a
multiple bond.[2] Many methods for the generation of acyl
radicals and reactions of acyl radicals have been reported.[3]
Reactions of carbamoyl radicals are relatively well-known,[4]
but examples of reactions of alkoxycarbonyl radicals are
limited.[5] In general, alkoxycarbonyl and carbamoyl radicals
are generated from the corresponding selenides and xan-
thates by treatment with a combination of Bu3SnH and an
initiator and photoirradiation [Scheme 1, Eq. (1)].[4,5] How-
ever, these methods have the disadvantage that they require
the use of toxic reagents and special equipment.
air [Scheme 1, Eq. (2)]. Recently, iron has received attention
as a low-toxic and inexpensive substitute for rare metals, such
as palladium.[8] Many iron-catalyzed reactions, such as the
À
oxidation of olefins or C H bonds and carbon–carbon or
carbon–heteroatom coupling reactions, have been devel-
oped.[9]
To determine the best reaction conditions, we chose a-
methylstyrene (1) and methyl carbazate (2a) as model
substrates. The treatment of
a mixture of 1 and 2a
(2.2 equiv) with FeCl3 (10 mol%) in THF at reflux in air
gave b-hydroxyester 3a in 36% yield (Table 1, entry 1).[10,11]
Table 1: Optimization of the reaction conditions.
Entry
Catalyst
2a [equiv]
Atmosphere
t [h]
Yield [%][a]
1
2
3
4
5
6
FeCl3
2.2
2.2
2.2
1.2
3.0
2.2
2.2
2.2
air
air
air
air
air
O2
air
air
100
48
44
18.5
43
6
36
4
Fe(NO3)3
[Fe(Pc)]
[Fe(Pc)]
[Fe(Pc)]
[Fe(Pc)]
[Fe(Pc)]
none
82
40
84
45
71
n.r.[c]
7[b]
8
48
48
[a] Yield of the isolated product. [b] The reaction was carried out with
5 mol% of [Fe(Pc)]. [c] No reaction.
Scheme 1. Methods for the generation of alkoxycarbonyl radicals.
It is known that radical species are generated from
hydrazine compounds through the formation of diazenes in
the presence of oxidants, such as oxygen and transition
metals.[6] A number of radical reactions based on the
oxidation of hydrazines have been reported.[7] Herein, we
report an iron-catalyzed intermolecular oxidative addition of
alkoxycarbonyl radicals derived from carbazates to alkenes in
A reaction with Fe(NO3)3 as the catalyst gave only a trace
amount of 2a (Table 1, entry 2). When iron phthalocyanine
([Fe(Pc)]; 10 mol%) was used in air, product 3a was obtained
in excellent yield (Table 1, entry 3). The use of a minimum
amount of 2a (1.2 equiv) led to significantly lower yield of 3a
(Table 1, entry 4), whereas no improvement in yield was
observed with 3.0 equivalents of 2a (Table 1, entry 5). The
reaction time under a pure O2 atmosphere instead of air was
shorter, but the yield of 3a was decreased (Table 1, entry 6).
The use of half the amount of the catalyst slightly prolonged
the reaction time, but the yield of 3a was still good (Table 1,
entry 7). In the absence of an iron catalyst, no reaction was
observed (Table 1, entry 8).
[*] Dr. T. Taniguchi, Y. Sugiura, H. Zaimoku, Prof. Dr. H. Ishibashi
School of Pharmaceutical Sciences
Institute of Medical, Pharmaceutical and Health Sciences
Kanazawa University, Kakuma-machi, Kanazawa 920-1192 (Japan)
Fax: (+81)76-234-4439
Next, we examined the reaction of a-methylstyrene (1)
with various carbazates in the presence of the catalyst
[Fe(Pc)] (Table 2). The reactions of various carbazates and
1 gave b-hydroxyesters 3a–e in moderate and good yields
(Table 2, entries 1–5). However, tert-butyl carbazate (2 f) and
benzyl carbazate (2g) were converted into products 3 f and 3g
E-mail: tsuyoshi@p.kanazawa-u.ac.jp
[**] This research was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science,
and Technology of Japan.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201005574.
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Chemie
Table 2: Radical reactions of various carbazates.
Entry
2
t [h]
Yield [%][a]
1
2
3
4
5
6
7
a (R=Me)
b (R=Et)
44
28
50
100
45
38
82
64
57
47
64
7
c (R=iPr)
d (R=Ph)
e (R=CH2CCl3)
f (R=tBu)
g (R=Bn)
33
3
[a] Yield of the isolated product.
in very low yields as a result of the decomposition of these
carbazates (Table 2, entries 6 and 7).[12]
The FeCl3-catalyzed reaction of ethyl carbazate (2b)
proceeded readily to give b-hydroxyester 3b in better yield
than that observed for the equivalent reaction of methyl
carbazate (2a; Scheme 2 and Table 1, entry 1). Recently,
Scheme 3. Plausible mechanism.
release of molecular nitrogen.[6,14,15] The addition of radical 9
to alkene 1 and subsequent trapping of the resultant radical
intermediate 10 by molecular oxygen then affords the peroxy
radical 11, which reacts with an FeII species to give the iron
À
complex 12. Finally, the O O bond of 12 undergoes cleavage
to generate the alkoxy radical 13, followed by hydrogen
abstraction from carbazate 2a or diazene 7 to give b-
hydroxyester 3a;[16] intermediate 6 or 8 might be generated
along with an FeIII species in this step. When 2a was treated
with a stoichiometric amount of 2,2,6,6-tetramethyl-1-piper-
idine-1-oxyl (TEMPO) in the presence of [Fe(Pc)] and air,
compound 14 was obtained in good yield (Scheme 4). This
result supports the generation of methoxycarbonyl radical 9
in this reaction.[17]
Scheme 2. Reaction of ethyl carbazate (2b) and 1 in the presence of
FeCl3.
Buchwald and Bolm reported that a trace amount of copper
as a contaminant of FeCl3 plays the role of a catalyst in some
iron-catalyzed reactions.[13] Therefore, we also examined the
reaction with highly purified FeCl3 (> 99.99%). When 1 was
treated with ethyl carbazate (2b) in the presence of FeCl3 of
greater than 99.99% purity instead of the standard FeCl3
reagent (> 97%), no change in the yield of b-hydroxyester 3b
was observed (Scheme 2). This result clearly indicates that the
present reaction is catalyzed by iron.
A plausible mechanism for the reaction is shown in
Scheme 3. The reaction may be initiated by single-electron
transfer between methyl carbazate (2a) and an FeIII species
generated in the presence of oxygen to give the cation radical
5. Deprotonation of the cation radical 5 generates the radical
intermediate 6, and the subsequent process involving the
single-electron oxidation of 6 by an FeIII species and
deprotonation gives diazene 7. Diazene 7 undergoes oxida-
tion by a similar pathway (or hydrogen abstraction by the
alkoxy radical 13) to give the radical intermediate 8, from
which the methoxycarbonyl radical 9 is formed with the
Scheme 4. Reaction of methyl carbazate (2a) and TEMPO.
Finally, we investigated the generality of this iron-
catalyzed radical reaction of alkenes with methyl carbazate
(2a; Table 3). 2-Aryl propenes 1a–d bearing methoxy, nitro,
and halogen substituents on the aromatic ring or a naphthyl
group provided the corresponding b-hydroxyesters 4a–d in
good yields (Table 3, entries 1–4). The reaction of styrene
(1e) gave b-hydroxyester 4e together with an equal amount
of the b-ketoester 4e’ produced by the oxidation of 4e
(Table 3, entry 5). Alkenes 1 f–h, with a similar electronic
structure to that of styrene, were also converted into the
corresponding b-hydroxyesters 4 f–h (Table 3, entries 6–8).
The reaction of enyne 1i proceeded smoothly to give b-
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Communications
Table 3: Radical reactions of various alkenes.
cleavage of the cyclobutane following the addition of the
alkoxycarbonyl radical gave ester 4m’ along with b-hydroxy-
ester 4m (Table 1, entry 13).
In summary, we have developed a method for the
formation of alkoxycarbonyl radicals from carbazates with
iron catalysts and air. The present iron-catalyzed reaction of
alkoxycarbonyl radicals has several advantages: 1) many
carbazate precursors of alkoxycarbonyl radicals are stable
solids and are readily available; 2) the reaction is environ-
mentally friendly, since the iron catalyst has low toxicity and is
inexpensive, molecular oxygen is used as an oxidant, and the
group eliminated from the radical precursors is molecular
nitrogen; and 3) the experimental procedure is very simple
and safe. Further studies directed toward the application of
iron-catalyzed radical reactions to various substrates are
currently under way in our laboratory.
Entry
1
t
[h]
4
Yield
[%][a]
1
2
3
4
Ar=4-MeOC6H4
Ar=4-NO2C6H4
Ar=4-BrC6H4
Ar=b-C10H7
a
b
c
22
28
25
24
67
61
81
72
d
42
37
5
e
35
Experimental Section
General procedure: A mixture of the alkene (0.5 mmol), methyl
carbazate (99.1 mg, 1.1 mmol), and [Fe(Pc)] (28.4 mg, 0.05 mmol) in
THF (2.5 mL) was heated at 658C in air. After removal of the solvent
under reduced pressure, the residue was purified by silica-gel
chromatography (hexane/EtOAc). Caution: The corresponding per-
oxide is known to be generated from THF in the presence of oxygen.
Although we have never detected peroxides in this reaction,
appropriate caution should always be paid when the reaction is
carried out a large scale.
6
7
f
24
24
62
71
g
8
9
h
i
33
27
72
73
Received: September 6, 2010
Published online: December 1, 2010
Keywords: carbazates · iron catalysis · oxygenation ·
.
radical reactions · synthetic methods
10[b]
11[b]
12
j
47
46
26
57
38
73
k
l
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21
24
13[b]
m
47
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1j and 1k, the use of an increased amount of 2a led to the
formation of the corresponding b-hydroxyesters 4j and 4k in
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Chemie
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˘
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À1
À
(BDE) of THF (C H bond) is approximately 90 kcalmol
,
;
À1
À
whereas that of ethyl carbazate (N H bond) is 82 kcalmol
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