Thermal and catalytic transylidations between halonium ylides and synthesis and reaction of stable aliphatic chloronium ylides

Article abstract of DOI:10.1021/ja074624h

Intermolecular transylidation between halonium ylides under thermal and catalytic (rhodium(II) acetate) conditions, which makes it possible to synthesize a hitherto unknown kind of aliphatic chloronium ylides as well as a variety of bromonium and iodonium

Full text of DOI:10.1021/ja074624h

Published on Web 01/25/2008
Thermal and Catalytic Transylidations between Halonium Ylides and
Synthesis and Reaction of Stable Aliphatic Chloronium Ylides
Masahito Ochiai,* Norihiro Tada, Takuya Okada, Atushi Sota, and Kazunori Miyamoto
Graduate School of Pharmaceutical Sciences, UniVersity of Tokushima, 1-78 Shomachi, Tokushima 770-8505, Japan
Received July 16, 2007; E-mail: mochiai@ph.tokushima-u.ac.jp
Scheme 1
Iodonium ylides serve as excellent progenitors for generation of
singlet carbenes1 because of the hyper-leaving group ability of aryl-
λ3-iodanyl groups.2 Under thermal, catalytic, or photochemical
conditions, they transfer the alkylidene groups to a wide range of
heteroatom nucleophiles involving nitrogen heterocycles, phos-
phines, arsines, sulfides, sulfoxides, and selenides, providing a
useful preparative method for pyridinium, phosphonium, and
sulfonium ylides, etc.3 In spite of the surging interest and activity
in ylide chemistry, the transylidation between halonium ylides, in
Table 1. Transylidation of Bromonium 1 to Iodonium Ylides 2a
which carbenes generated from halonium ylides are captured by
temp
C)
time
(h)
yieldb
(%)
alkyl and aryl halides, remains unknown except for an intramo-
lecular transylidation of iodonium ylides.4 Intermediate formation
of labile alkyliodonium ylides via ylide transfer of aryliodonium
ylides has been proposed but with no evidence.5,6
entry
1
ArI
additivec
(
°
2
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
1a PhI
1b PhI
1b PhI
1b PhI
1b PhI
1b p-MeOC6H4I
1b p-MeOC6H4I
1b p-MeC6H4I
1b p-FC6H4I
1b p-ClC6H4I
1b p-BrC6H4I
1b p-CF3C6H4I
1c PhI
1b PhI
1b PhI
1b PhI
1b PhI
1b p-MeC6H4I
1b p-FC6H4I
1b p-CF3C6H4I
160
130
140
150
160
160
140
160
160
160
160
160
160
40
40
40
40
40
40
40
1
1
1
1
1
1
1
1
1
1
1
1
1
5
5
5
5
5
5
5
2a
2a
2a
2a
2a
2b
2b
2c
2d
2e
2f
2g
2h
2a
2a
2a
2a
32(36)d
(56)d
(76)d
(76)
87(89)
46
70
89
79
78
We report herein, for the first time, unambiguous experimental
evidence for the intermolecular transylidation between halonium
ylides under thermal and catalytic conditions, which makes it
possible to synthesize a hitherto unknown kind of aliphatic
chloronium ylides 3 as well as a variety of bromonium and
iodonium ylides 1 and 2. Very interestingly, compared to the
bromonium and iodonium ylides 1a and 2a, the chloronium ylide
3a serves as a much better progenitor for generation of carbenes
(or carbenoids) and efficiently undergoes cyclopropanation of
olefins such as cyclooctadiene under uncatalyzed thermal conditions.
Heating a 0.1 M solution of bromonium ylide 1b,7 prepared from
p-trifluoromethylphenyl(difluoro)-λ3-bromane by the ligand ex-
change with bis(trifluoromethylsulfonyl)methane, in iodobenzene
at 160 °C for 1 h resulted in the smooth intermolecular transylidation
yielding the iodonium ylide 2a (Ar ) Ph, Rfn ) CF3) in 87% yield
after purification by silica gel column chromatography (Scheme 1
and Table 1, entry 5). Even at 130 °C, the ylide transfer to the
iodide takes place, but the rate considerably slows down. In a
marked contrast, use of the iodonium ylide 2g with the p-CF3 group
instead of the bromonium ylide 1b did not show any evidence for
carbene transfer to iodobenzene under the conditions, and the ylide
2g was recovered quantitatively. This is the first firmly established
example indicating that the intermolecular transylidation between
halonium ylides takes place.
Iodonium ylides 2b-g with electron-donating (MeO, Me) and
-withdrawing substituents (CF3, F, Cl, Br) were prepared in good
to high yields. Highly nucleophilic p-methoxyiodobenzene under-
goes more efficiently the carbene capture at a lower temperature
(140 °C) compared to our standard conditions (Table 1, entries 6
and 7).
In the bromonium to iodonium ylide exchange, rhodium(II)
acetate was found to be the catalyst of choice for carbenoid
capture by iodobenzenes: thus, addition of a catalytic amount
(5 mol %) of Rh2(OAc)4 dramatically decreased the reaction
temperature, and high yields of iodonium ylides 2 were obtained
at 40 °C for 5 h (Table 1, entries 17-20). Traditional copper
catalysts Cu(acac)2 and CuI required longer reaction times, except
for CuCN.
65
89
71
CuI
Cu(acac)2
CuCN
Rh2(OAc)2
Rh2(OAc)2
Rh2(OAc)2
Rh2(OAc)2
(10)d
(63)d
(93)d
94(100)
2c 100
2d
2g
99
96
a Conditions: ylide 1 (0.1 M), Ar. b Isolated yields. Numbers in
parentheses are 1H NMR yields. c Metal catalyst (5 mol %). d Recovered
ylides 1: 8, 34, 3, 89, 18, and 3% for entries 1-3 and 14-16.
The relative rates of this thermal transylidation for a series of
substituted iodobenzenes with p-Me, p-Cl, and p-CF3 groups were
measured at 140 °C for 3 h by competitive reactions, in which a
mixture of each 40-fold excess of two competing substrates was
used (Scheme S1). A control experiment showed that, in the
competitive ylide transfer of the bromonium ylide 1b to PhI and
p-CF3C6H4I, ratios of the products 2a and 2g were nearly constant
for the samples taken at intervals through several half-lives (Figure
S1). Furthermore, transylidations between the iodonium ylides 2a
and 2c (or 2g) were found to be negligibly small under the
conditions (Schemes S2 and S3). Electron-releasing p-Me group
increases the relative rate krel of the carbene transfer: 1.33
(p-MeC6H4I); 1.0 (PhI); 0.82 (p-ClC6H4I); 0.52 (p-CF3C6H4I).
Hammett plot showed a good correlation of the relative rate factors
with σp constants and gave the reaction constant F ) -0.54 (r )
0.99). A larger negative F value of -0.91 (r ) 1.0) was evaluated
in the Rh(II)-catalyzed carbenoid transfer reaction at 40 °C for 1 h
(Figure S2).8 The fact that the rate of uncatalyzed decomposition
of the ylide 1b is independent of the concentrations of iodide (PhI)
9
2118
J. AM. CHEM. SOC. 2008, 130, 2118-2119
10.1021/ja074624h CCC: $40.75 © 2008 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Transylidation between Bromonium Ylides 1a
Scheme 3
temp
C)
time
(h)
yieldb
(%)
entry
ArBr
(
°
1
Scheme 4
1
2c,d
3
PhBr
PhBr
130
40
4
5
1
1
1
1
5
1
2
1
1a
1a
1d
1e
1f
48(48)e
6(7)e
p-MeOC6H4Br
o-MeOC6H4Br
p-MeC6H4Br
p-MeC6H4Br
3,5-Me2C6H3Br
p-FC6H4Br
150
150
150
150
130
130
130
130
55(64)e
47(58)e
60(66)
(0)
4
5
6c
7
1f
1g
1h
1h
1i
44(51)e
(2)
8
9c
10c
p-FC6H4Br
p-ClC6H4Br
65(72)e
44(43)e
ylide 1b, however, increased the yield of the chloronium ylide 3d
to 15% (Scheme 3).
a Conditions: ylide 1b (0.1 M), air. b Isolated yields. Numbers in
parentheses are 1H NMR yields. c Under Ar. d Rh2(OAc)2 (5 mol %).
e Recovered ylide 1b: 7, 53, 5, 15, 3, 19, and 42% for entries 1-4, 7, 9,
and 10.
Cyclopropanation of olefins with iodonium ylides usually
requires use of a transition metal catalyst such as Rh(II) or Cu to
generate reactive metallocarbene intermediates.3a,10 In fact, the
attempted reaction of cyclooctadiene with iodonium ylide 2a
recovered it unchanged under uncatalyzed thermal conditions
(100 °C, 24 h, Scheme 4). Use of the bromonium ylide 1a afforded
the cyclopropane 4 but in a low yield (12%), whereas the thermal
reaction of the chloronium ylide 3a with cyclooctadiene took place
smoothly, probably via generation of reactive carbene, and produced
4 in 72% yield. A greater leaving group ability of the λ3-chloranyl
and λ3-bromanyl groups compared to that of the λ3-iodanyl group
seems to be responsible for the observed differences in reactivity
between these halonium ylides.11
Scheme 2
is not compatible with a carbenoid mechanism, which involves a
rate-limiting nucleophilic attack of iodobenzene on the ylidic carbon
atom of 1b (Figure S3). A small negative F value for the uncatalyzed
thermal transylidations of bromonium 1b to iodonium ylides 2
would probably suggest generation of a reactive carbene :C(SO2-
CF3)2, being electrophilic in nature, as well as an early transition
state for carbene transfer.
Intermolecular transylidation between bromonium ylides 1 takes
place smoothly under thermal conditions; thus, heating a solution
of the ylide 1b in bromobenzene at 130 °C for 4 h in the air afforded
the bromonium ylide 1a in 48% yield, whereas Rh(II)-catalyzed
conditions gave poor results (Table 2, entries 1 and 2). A variety
of substituted bromonium ylides 1d-i were prepared in 44-65%
yields. It is noted that the transylidation to electron-rich p-MeC6H4-
Br occurs readily in the air but not under Ar, while interestingly,
the reverse was found for that to electron-deficient p-FC6H4Br
(compare entries 5, 6, 8, and 9).
In 1954, a transient formation of a highly labile chloronium ylide
was suggested in the thermal decomposition of ethyl diazoacetate
in benzal chloride.9 Stable aromatic chloronium ylides, in which
the ylide carbanions were stabilized through aromatization in
heterocyclic rings, have been prepared by the thermolysis of
diazodicyanoimidazole in chlorobenzene;6a however, no stable and
well-established aliphatic chloronium ylides are known. We are very
pleased to find that chlorobenzenes also serve as acceptor molecules
in these alkylidene transfer reactions of the bromonium ylide 1b,
yielding aliphatic chloronium ylides 3 (Scheme 2); thus, under
thermal conditions, chlorobenzene gave the chloronium ylide 3a
in 24% yield after purification by silica gel preparative TLC.
Chloronium ylides 3b and 3c with electron-donating groups (p-
Me and p-MeO) on the aromatic ring were also prepared in 19-
25% yields, but the attempted alkylidene transfer to chlorobenzene
with an electron-withdrawing p-CF3 group, yielding the ylide 3d,
was found to be fruitless. Use of the more reactive chloronium
ylide 3a in the transylidation reaction instead of the bromonium
In conclusion, thermal and metal-catalyzed transylidation of
halonium ylides provides us a tool for the synthesis of a variety of
halonium ylides, including the aliphatic chloronium ylide, which
serves as a nice progenitor for generation of carbenes (or car-
benoids).
Supporting Information Available: Experimental details, Schemes
S1-S3, and Figures S1-S3. This material is available free of charge
via the Internet at http://pubs.acs.org.
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