Rhodium(II) catalysed three-component coupling: a novel reaction of in situ generated iodonium ylides

Article abstract of DOI:10.1016/j.tetlet.2007.11.021

Cyclic ethers are cleaved in the presence of nitromethane, a base, a hypervalent iodine compound and a Rh(II) catalyst to give nitromethoxy acetates in up to 71% isolated yields. The reaction is a three-component coupling of an ether with a nitromethane d

Full text of DOI:10.1016/j.tetlet.2007.11.021

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 57–61
Rhodium(II) catalysed three-component coupling:
a novel reaction of in situ generated iodonium ylides
Hanne Therese Bonge and Tore Hansen*
University of Oslo, Department of Chemistry, Sem Sælands vei 26, 0315 Oslo, Norway
Received 25 September 2007; revised 2 November 2007; accepted 2 November 2007
Available online 7 November 2007
Abstract—Cyclic ethers are cleaved in the presence of nitromethane, a base, a hypervalent iodine compound and a Rh(II) catalyst to
give nitromethoxy acetates in up to 71% isolated yields. The reaction is a three-component coupling of an ether with a nitromethane
derived carbenoid and a carboxylate group originating from the hypervalent iodine compound.
Ó 2007 Elsevier Ltd. All rights reserved.
Iodonium ylides are a class of hypervalent iodine com-
pounds that can be used as precursors to metal carbe-
noids.1–6 Iodonium ylides are prepared from an active
methylene compound and a hypervalent iodine precur-
sor, and they have gained interest as synthetic equiva-
lents to diazo compounds.7 Traditionally, they have
been prepared from active methylene compounds with
two electron-withdrawing groups, due to the higher
stability of the corresponding ylides.5 In the studies
and utilisation of in situ generated iodonium ylides,
focus has so far been mainly on cyclopropanation reac-
tions.1–4,6,8–11 Single reports of C–H insertion11 and a
rearrangement through intramolecular generation of
an oxonium ylide12 have also been published.
and a rhodium catalyst, afforded 4-(nitromethoxy)butyl
acetate 1 (Scheme 1).
We started investigating this unprecedented three-com-
ponent coupling reaction by doing a broad screening,
exploring the effects of different bases and catalysts on
the reaction (Table 1). In these experiments, PhI(OAc)2
(1.0 equiv), THF (10.0 equiv), a base, a rhodium(II)
catalyst and a large excess of nitromethane (neat) were
added simultaneously and the reaction allowed to stir
at room temperature for 3 h. All reagents were used as
received. We found that the yield of 1 was highly depen-
dent on the choice of base, with potassium fluoride and
potassium acetate giving the best yields. Furthermore, in
all the reactions, independent of base, 1 was the main
product. The acetate group in 1 must originate from
bis(acetoxy)iodobenzene since PhI(OAc)2 was the only
source of acetate available in the reaction mixture when
non-acetate bases were used. To the best of our
knowledge, this is the first example of an iodonium ylide
reaction where the carboxylate ligand on PhI(OAc)2
participates as a reactant and is incorporated in the
product.
The reaction of a carbene or carbenoid with an ether can
have different outcomes. The area has not yet been thoro-
ughly studied, but in addition to C–H insertion and
various rearrangements,13 there are descriptions of both
ether polymerisation14,15 and ether cleavage by photoly-
sis,16 as well as examples of Rh(II) catalysed ether cleav-
age employing an alkylideneiodonium salt.17 We
recently described a method for cyclopropanation with
an in situ generated iodonium ylide flanked with only
one electron-withdrawing group.18 We now report how
this iodonium ylide, prepared from nitromethane, may
also be utilised in a novel reaction with cyclic ethers.
O
PhI(OAc)2
O
We discovered that treatment of THF with nitro-
methane, bis(acetoxy)iodobenzene (PhI(OAc)2), a base,
CH3NO2
Rh(II)
Base
O
O
NO2
1
*
Corresponding author. Tel.: +47 22855386; fax: +47 22855441;
e-mail: torehans@kjemi.uio.no
Scheme 1.
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.11.021

58
H. T. Bonge, T. Hansen / Tetrahedron Letters 49 (2008) 57–61
Table 1. Initial screening
results seemed to be more reproducible at 30 °C than
at room temperature. A reaction time of 3 h, as chosen
to begin with, proved to be sufficient. Increasing the
reaction time to 7, 15 or 24 h had no effect on yields.
A reaction time of 1 h gave a 66% yield of 1, compared
to 75% after 3 h. Rigorously dry conditions did not
increase yields, whereas 0.3 equiv of added water pre-
vented completely the reaction. We originally believed
that 2 equiv of base was necessary. It did, however,
become apparent that the reaction was in fact catalytic
with regards to base, and as little as 0.6 equiv of potas-
sium fluoride was sufficient to obtain high a yield of 1
(Table 3, entry 2). Since both nitromethane and THF
are inexpensive and readily available, both were initially
used in a rather large excess. Experiments showed that
the amounts of THF and nitromethane could be
decreased to 5 equiv and 10 equiv, respectively, without
significant effect on the yields (Table 3, entries 6–8). The
amounts of all three reagents could not be reduced
simultaneously without lowering the yield (Table 3,
entry 12). To reduce the equivalents of THF and nitro-
methane, the amount of potassium fluoride had to be at
least 1.0 equiv.
Entry Catalyst
Catalyst Base
loading
(mol %)
Equiv
Yield
of base of 1a (%)
1
2
3
Rh2(esp)2
Rh2(esp)2
Rh2(esp)2
2.5
2.5
2.5
KF
1.0
1.0
1.0
2.2
75
69
32
55
43
26
0
42
34
33
12
10
KOAc
NaOAc
KF
4
5
6
7
Rh2(OOct)4 2.5
Rh2(OOct)4 2.5
Rh2(OOct)4 2.5
Rh2(OOct)4 2.5
Na2CO3 2.2
K2CO3
MgO
2.2
2.2
2.2
2.2
2.2
2.2
2.2
8
9
10
11
12
Rh2(OAc)2
Rh2(OAc)2
Rh2(OAc)2
Rh2(OAc)2
Rh2(OAc)2
10
10
10
10
10
KF
K3PO4
K2CO3
CsF
CsCO3
a Measured by internal standard (1,3,5-trimethoxy benzene) in 1H
NMR analysis of crude reaction mixture.
It was clear from the initial screening that the ligands on
the dirhodium core of the catalyst had a substantial
effect on the outcome of the reaction. Hence, the effect
of different catalysts and catalyst loadings was systemati-
cally examined (Table 2). Potassium fluoride was chosen
as the base for these and the following optimisation
experiments. Whereas Pd(OAc)2 and Cu(acac)2 failed
to catalyse the formation of 1 (entries 12 and 13), all
the Rh(II) catalysts tested provided 1. Ether cleavage
did not occur in the absence of catalyst. The bridged
catalyst Rh2(esp)2 was the catalyst of choice in the
previously described cyclopropanation reaction with
nitromethane.18 Once again, this catalyst proved the
most efficient, allowing for a rather low catalyst loading
while still giving good yields (entries 1–4). Reducing the
catalyst loading to only 1 mol % still gave a yield of 64%
(entry 4).
Having established a satisfactory set of reaction condi-
tions, we then proceeded to investigate the effect of other
hypervalent iodine compounds. The experiments were
performed at 30 °C, using a catalyst loading of
2.5 mol % and reagent amounts as shown in Table 3,
entry 8. PhI(OPiv)2 gave a 57% yield of 4-(nitro-
methoxy)butyl pivalate, the analogous product to 1.
This result confirmed that the carboxylate group in the
product originated from the hypervalent iodonium
source. With PhI(TFA)2 as the hypervalent iodine
compound, no formation of the TFA-derivative of 1
was observed. Iodosylbenzene, having no carboxylate
substituent on iodine, gave a complex product mixture.
These factors having been established, we started
investigating the effects of other parameters on the reac-
tion. Initially, all experiments were performed at room
temperature. However, more satisfactory results were
obtained when the temperature was increased to 30 °C.
The reaction showed a slight temperature dependence;
To examine the scope of the three-component coupling
reaction, a number of cyclic ethers were exposed to the
same reaction conditions as described for the previous
experiments. Table 4 shows the results from this exami-
nation, in which no steps were taken to optimise the
reaction conditions for the substrates in entries 2–10.
Table 2. Effect of catalyst and catalyst loading
Table 3. Effect of varying the amounts of reagents
Entry Catalyst
Catalyst loading (mol %) Yield of 1a (%)
Entry
KF
(equiv)
THF
(equiv)
MeNO2
(equiv)
Yield of
1a (%)
1
2
3
Rh2(esp)2
Rh2(esp)2
Rh2(esp)2
Rh2(esp)2
10
5
2.5
1
71
74
75
64
63
55
55
31
57
42
11
0
1
2
3
4
5
6
7
8
9
0.5
0.6
0.8
1.0
1.5
1.0
1.0
1.0
1.0
1.0
1.0
0.6
10
10
10
10
10
5
10
5
3
18.6
18.6
18.6
18.6
18.6
18.6
10
10
10
10
5
67
76
76
75
78
71
73
71
58
33
67
59
4
5
6
7
Rh2(OOct)4 10
Rh2(OOct)4
Rh2(OOct)4 2.5
5
8
9
Rh2(OOct)4
Rh2TMA4
1
10
10
11
12
13
Rh2(OAc)2 10
Rh2TFA4
Pd(OAc)2
Cu(acac)2
10
10
10
10
11
12
1
5
5
0
10
a Measured by internal standard (1,3,5-trimethoxy benzene) in 1H
NMR analysis of crude reaction mixture.
a Measured by internal standard (1,3,5-trimethoxy benzene) in 1H
NMR analysis of crude reaction mixture.

H. T. Bonge, T. Hansen / Tetrahedron Letters 49 (2008) 57–61
59
Table 4. Scope of different substrates
Entry
Substrate
Product(s)
Yielda (%)
71
O
OAc
1
O2N
O2N
O2N
O
O
O
O
2
3
55
45b
32
28
23
9
OAc
OAc
O2N
O
OAc
O
OAc
O
4
O
NO2
O
O2N
O2N
5
O
OAc
O
OAc
6
O
O
O
O
O
O
OAc
7
O2N
O2N
—
O
8
7
OAc
O
9
0
O
O
10
—
0
a Isolated yield after flash chromatography.
b 1.6:1 ratio favouring the product of attack by AcOÀ at C-2.
The best isolated yield, 71%, was obtained with THF.
The other substrates gave low to moderate yields. No
general trend emerged regarding what types of ethers
are more easily cleaved in the reaction. 2-Methyl tetra-
hydrofuran (Table 4, entry 3) gave the two products of
attack at the 2- and 5-position in a ratio of 1.6:1, favour-
ing the product from attack at C-2. The substrate 2,5-
dihydrofuran, having a double bond, represented an
opportunity to investigate whether ether cleavage or
cyclopropanation was the preferred reaction. Even
though the reaction conditions were not very different
from the conditions we previously used in the cycloprop-
anation of olefins with nitromethane,18 the reaction
resulted in the product of ether cleavage (Table 4, entry
5) and no cyclopropane was observed. The reaction was
also tested on THP (Table 4, entry 2) to explore the
effect of changing the ring size. THP gave the analogous
product to THF in 55% yield. Two compounds failed to
undergo a three-component coupling. Neither 2-MeO-
tetrahydrofuran nor 2,3-di-hydrobenzofuran gave any
analogous products to the rest of the series.
Scheme 2 shows two probable mechanistic pathways for
the cleavage of THF with nitromethane and PhI(OAc)2.

60
H. T. Bonge, T. Hansen / Tetrahedron Letters 49 (2008) 57–61
NO2
NO2
O2N
O
O
O
NO2
PhI(OAc)2
Base
I
AcO-
Path A
RhLn
O
CH3NO2
RhLn
O
H+
Path B
H+
NO2
O2N
O
O
O
AcO-
O
Scheme 2. A plausible reaction mechanism.
Initial formation of an iodonium ylide from nitro-
methane and PhI(OAc)2 is followed by Rh(II) catalysed
generation of the analogous ethereal oxonium ylide.
Attack on the oxonium ylide, or on the corresponding
protonated oxonium ion, by an acetate group then
results in ring opening. Considering the weak nucleo-
philic nature of AcOÀ and the presence of KF, compet-
ing attack by FÀ instead of the acetate ion might have
been anticipated. However, the product from such a
reaction was not detected.
generated through ring opening by another molecule of
trimethylene oxide, generating a new oxonium ylide or
ion that was subsequently attacked by acetate. The
formation of product 5 may be explained by a formal
Nef reaction of product 4. The formation of products
4 and 5 may be due to the higher ring strain of trimeth-
ylene oxide compared to THF, making the ring opening
of the trimethylene oxonium ylide or ion favourable
enough to allow nucleophilic attack and cleavage by
other ether molecules.
When oxetane was used as the ether substrate (Table 4,
entry 8), three products were isolated and characterised
(Scheme 3). Product 3 is the analogous product to the
rest of the series, formed by ring opening of the oxonium
ylide or oxonium ion by acetate. Product 4 was possibly
In summary, we have developed a novel procedure for
cleavage of a range of cyclic ethers, employing nitro-
methane and a hypervalent iodine compound. The reac-
tion is a three-component reaction, coupling an ether
with a nitromethane derived carbenoid and an acetate
group originating from the hypervalent iodine com-
pound. This represents the first example where an
in situ generated iodonium ylide reacts intermolecularly
to generate a cyclic oxonium ylide. Further studies to
broaden the scope of the reaction will be reported in
due course.
O
O
O
5 (3%)
O
O
O2N
O
Acknowledgments
Financial support by the Department of Chemistry,
University of Oslo and the Norwegian Research Council
is gratefully acknowledged. We thank Alpharma,
Degussa and H. Lundebeck A/S for donation of a
HPLC column and chemicals.
O
O
O
3 (7%)
NO2
2
O
O
O
Supplementary data
4 (13%)
Scheme 3. Products isolated after flash chromatography.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2007.11.021.
O
NO2

H. T. Bonge, T. Hansen / Tetrahedron Letters 49 (2008) 57–61
61
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