Convenient syntheses of fluorous aryl iodides and hypervalent iodine compounds: ArI(L)n reagents that are recoverable by simple liquid/liquid biphase workups, and applications in oxidations of hydroquinones

Article abstract of DOI:10.1002/chem.200390034

Iodinations of the ortho, meta, and para fluorous arenes (R_f8CH₂CH₂ CH₂)₂C₆H₄ (R_f8=(CF₂)₇CF₃) with I₂/H₅IO₆ in AcOH/H₂SO₄/H₂O give 3,4-(R_f8CH₂CH₂ CH₂)₂C₆H₃I (5) and the analogous 2,4- (6) and 2,5- (7) isomers, respectively. Spectroscopic yields are > 90%, but 5 and 7 must be separated by chromatography from by-products (yields isolated: 70%, 97%, 61%). Reaction of 1,3,5-(R_f8CH₂CH₂ CH₂)₃C₆H₃ with PhI(OAc)₂/I₂ gives 2,4,6-(R_f8CH₂CH₂ CH₂)₃C₆H₂I (8) on multigram scales in 97% yield. The CF₃C₆F₁₁/toluene partition coefficients of 5-8 (24°C: 69.5:30.5 (5), 74.7:25.3 (6), 73.9:26.1 (7), 98.0:2.0 (8)) are lower than those of the precursors, but CF₃C₆F₁₁/MeOH gives higher values (97.0:3.0 (5), 98.6:1.4 (6), 98.0:2.0 (7), > 99.3: < 0.3 (8)). Reactions of 5-8 with excess NaBO₃ in AcOH yield the corresponding ArI(OAc)₂ species 9-12 (9, 85% as a 90:10 9/5 mixture; 10, 97%; 11, 95%; 12, 93% as a 95:5 12/8 mixture). These rapidly oxidize 1,4-hydroquinones in MeOH. Subsequent additions of CF₃C₆F₁₁ give liquid biphase systems. Solvent removal from the CF₃C₆F₁₁ phases gives 5-8 in > 99-98% yields, and solvent removal from the MeOH phases gives the quinone products, normally in > 99-95% yields. The recovered compounds 5-8 are easily reoxidized to 9-12 and used again.

Full text of DOI:10.1002/chem.200390034

FULL PAPER
Convenient Syntheses of Fluorous Aryl Iodides and Hypervalent Iodine
Compounds: ArI(L) Reagents That Are Recoverable by Simple Liquid/
n
Liquid Biphase Workups, and Applications in Oxidations of Hydroquinones
Christian Rocaboy and John A. Gladysz*[a]
Abstract: Iodinations of the ortho,
meta, and para fluorous arenes (R CH -
toluene partition coefficients of 5 ±8
(248C: 69.5:30.5 (5), 74.7:25.3 (6),
73.9:26.1 (7), 98.0:2.0 (8)) are lower
than those of the precursors, but
CF C F /MeOH gives higher values
85% as a 90:10 9/5 mixture; 10, 97%; 11,
95%; 12, 93% as a 95:5 12/8 mixture).
These rapidly oxidize 1,4-hydroquinones
in MeOH. Subsequent additions of
CF C F give liquid biphase systems.
f8
2
CH CH ) C H (R ˆ (CF ) CF ) with
2
2
2
6
4
f8
2
7
3
I /H IO in AcOH/H SO /H Ogive 3,4-
2
5
6
2
4
2
(
R CH CH CH ) C H I (5) and the
f8 2 2 2 2 6 3
3
6
11
3
6
11
analogous 2,4- (6) and 2,5- (7) isomers,
respectively. Spectroscopic yields are
(97.0:3.0 (5), 98.6:1.4 (6), 98.0:2.0 (7),
>99.3: < 0.3 (8)). Reactions of 5 ± 8 with
Solvent removal from the CF C F
3 6 11
phases gives 5 ± 8 in >99 ± 98% yields,
and solvent removal from the MeOH
phases gives the quinone products, nor-
mally in >99 ± 95% yields. The recov-
ered compounds 5 ± 8 are easily reoxi-
dized to 9 ± 12 and used again.
>
90%, but 5 and 7 must be separated
by chromatography from by-products
yields isolated: 70%, 97%, 61%). Re-
excess NaBO in AcOH yield the corre-
3
sponding ArI(OAc) species 9 ± 12 (9,
2
(
action of 1,3,5-(R CH CH CH ) C H
f8
2
2
2
3
6
3
Keywords: fluorine
¥ hypervalent
with
PhI(OAc) /I
gives
2,4,6-
2
2
iodine ¥ oxidations ¥ quinones ¥
recycling
(
R CH CH CH ) C H I (8) on multi-
f8 2 2 2 3 6 2
gram scales in 97% yield. The CF C F /
3
6
11
site from the electronegative Rfn groups.[5ꢀ More recently,
many such compounds have been found to exhibit little or no
solubility in organic solvents at room temperature, but
significant solubility at elevated temperatures. Thus, reactions
can be conducted under homogeneous conditions at the high-
temperature limit, and the fluorous material recovered by a
simple solid/liquid phase separation at the low-temperature
limit.[ This variant renders a fluorous solvent unnecessary.
Aryl iodides are extremely versatile synthetic organic
Introduction
Over the past eight years, many new compounds with high
affinities for perfluoroalkane and perfluorodialkyl ether
™fluorous∫) solvents have been synthesized.
[1±3ꢀ
(
This has
been prompted by the development of ™fluorous biphase
chemistry∫,[ which as most frequently implemented exploits
the markedly temperature-dependent miscibilities of organic
and fluorous solvents. At room temperature, most combina-
tions give two phases.[ However, with moderate heating, one
phase is obtained. Reactions can be conducted under
homogeneous conditions at the high-temperature limit.
Organic products and fluorous catalysts or by-products can
be separated under liquid/liquid biphase conditions at the
low-temperature limit.
1ꢀ
6, 7ꢀ
4ꢀ
[8ꢀ
building blocks. They are also precursors to a variety of
exceedingly useful and extensively applied hypervalent iodine
reagents.[
9±14ꢀ
Unfortunately, the latter produce a stoichiomet-
ric amount of an aryl iodide or similar waste product. These
have seldom been recycled, apparently for lack of a conven-
ient protocol. This represents a distinct disadvantage from the
standpoint of ™green∫ chemistry, which is playing an increas-
ingly important role in process design.[ Over the last few
years, several immobilization strategies have been described,
as further detailed below.[ All of these feature polystyrene
or silica supports, and the intrinsic advantages and disadvan-
tages associated with insoluble reagents and heterogeneous
reaction conditions.
High fluorous phase affinities are achieved by appending
sufficient numbers of ™pony tails∫ of the formula
15ꢀ
(
(
CH ) (CF ) CF , herein abbreviated as (CH ) R . The
2 m 2 nÀ1 3 2 m fn
16ꢀ
CH2)m or ™spacer∫ segment partially insulates the reactive
[
aꢀ Prof. Dr. J. A. Gladysz, Dr. C. Rocaboy
Institut f¸r Organische Chemie
We thought that fluorous aryl iodide species that could be
utilized under homogeneous conditions and recovered as
described above would provide valuable complements to
these methodologies. Interestingly, no aryl iodides with high
Friedrich-Alexander-Universit‰t Erlangen-N¸rnberg
Henkestrasse 42, 91054 Erlangen (Germany)
Fax (‡49)-9131-8526865
E-mail: gladysz@organik.uni-erlangen.de
88
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Chem. Eur. J. 2003, 9, No. 1

8
8±95
[17ꢀ
fluorous phase affinities have so far been reported. We and
several other groups[ have described simple fluorous aryl
bromides such as p-BrC H (CH ) R (m/n ˆ 2/6, 2/8, 3/8),
Table 1. Summary of relevant partition coefficients (248C).
18ꢀ
Analyte
CF
3
C
6
F
3 6
11:toluene CF C F11:MeOH
6
4
2
m
fn
[aꢀ
R
f8CH
2
CH
2
CH
CH
2
C
6
H
5
49.5:50.5
and used these as precursors to a variety of other fluorous
molecules. However, compounds that contain only one pony
[aꢀ
1
2
3
4
1,2-(Rf8CH
2
2
CH
2
)
2
C
6
H
4
4
91.2:8.8
90.7:9.3[
aꢀ
1,3-(R CH CH CH ) C H
f8
2
2
2
2
6
tail per aromatic[
4, 18, 20ꢀ
or heteroaromatic
[20, 21ꢀ
ring exhibit
1,4-(R CH CH CH ) C H
91.1:8.9[aꢀ
f8
2
2
2
2
6
4
[
aꢀ
1,3,5-(Rf8CH
2
CH
2
CH
2
)
3
C
6
H
3
> 99.7: < 0.3
73.7:26.3[
low fluorous phase affinities.
aꢀ
1
1
,2-(Rf6CH
,2-(Rf10CH
2
CH
CH
2
CH
CH
2
)
2
C
6
H
4
As shown in Scheme 1, we have found that benzenoid
di- and trialdehydes undergo efficient Wittig reactions
with the ylide derived from the phosphonium salt
[aꢀ
2
2
2
)
2
C
6
H
4
97.4:2.6
69.5:30.5[bꢀ
97.0:3.0[bꢀ
5
6
7
8
3,4-(R CH CH CH ) C H I
f8
2
2
2
2
2
2
2
2
2
2
2
2
6
6
6
3
3
3
74.7:25.3[
bꢀ
98.6:1.4
[bꢀ
2,4-(Rf8CH
2,5-(Rf8CH
2,4,6-(Rf8CH CH CH ) C H I
2 2 2 3 6 2
CH
CH
CH
CH
)
)
C
C
H
H
I
I
[
bꢀ
[bꢀ
73.9:26.1
98.0:2.0[
50.7:49.3
93.5:6.5[
98.0:2.0
bꢀ
[bꢀ
> 99.7: < 0.3
[
aꢀ
R
R
f8CH
f8CHˆCH
2
CH
2
2
CH I
cꢀ
Rf8
Rf8
2
H
O
[aꢀ See reference [19ꢀ. [bꢀ This work. [cꢀ See reference [20ꢀ.
n
n
n
(a)
(b)
Results
n = 1, 2, 3; Rf8 = (CF2)7CF3
Fluorous aryl iodides: As shown in Scheme 2, the doubly
pony-tailed fluorous arenes (R CH CH CH ) C H (1, 1,2-; 2,
‡
À
Scheme 1. Syntheses of fluorous arenes. a) [Ph
3 2 2 2 3
PCH CH Rf8ꢀ I , K CO ,
f8
2
2
2
2
6
4
p-dioxane/H O , 9 58 C; b) 10% Pd/C, 1 atm H , EtOH/CF C H .
2
2
3 6 5
1,3-; 3, 1,4-) were iodinated by using a standard procedure
involving periodic acid (H IO ) and iodine in a mixture of
5
6
aqueous acetic and sulfuric acid.[ Reactions were highly
regioselective. Nonetheless, in most cases small quantities of
alternative isomers or diiodides formed (<10%), as assayed
8ꢀ
‡
À [19ꢀ
[
Ph PCH CH R ꢀ I . Subsequent hydrogenation leads to
3 2 2 f8
fluorous benzene derivatives with two to three pony tails and
three methylene spacers. As summarized in Table 1, these
exhibit CF C F /toluene partition coefficients of about 91:9
for two pony tails, and >99: < 1 for three pony tails. We
therefore set out to attempt the iodination of these fluorous
arenes, to elaborate the resulting aryl iodides to fluorous
hypervalent iodine compounds, to apply the later in oxidation
reactions, and to efficiently recover and reuse the fluorous by-
products. The successful realization of all of these objectives is
described below.
1
by H NMR spectra of the crude reaction mixtures. For
example, the ortho-substituted arene 1 gave the iodide 3,4-
(R CH CH CH ) C H I (5) as the major product (>90%), as
3
6 11
f8
2
2
2
2
6
3
1
evidenced by the H NMR coupling pattern of the aromatic
protons. However, signals consistent with the 2,3-regioisomer
(5'), the only other possible monoiodide, could also be
detected (see Experimental Section). Other signals were
consistent with one of the diiodide by-products shown in
Scheme 2 (A, A'). Iodide 5 could be isolated in pure form in
Rf8(CH2)3
Rf8(CH2)3
Rf8(CH2)3
Rf8(CH2)3
c)
a), 85 °C
70% Rf8(CH2)3
I
85%
90:10, 9:5)
Rf8(CH2)3
I(OAc)2
(
1
5
9
(
CH2)3Rf8
(CH2)3Rf8
I
2 3 f8
(CH ) R
a), 75 °C
97% Rf8(CH2)3
c)
Rf8(CH2)3
Rf8(CH2)3
97%
Rf8(CH2)3
R (CH )
I(OAc)2
2
3
6
7
10
I
I(OAc)2
2 3 f8
(CH ) R
a), 90 °C
61% Rf8(CH2)3
c)
(CH2)3Rf8
(CH2)3Rf8 95%
f8
2 3
11
(
CH2)3Rf8
CH2)3Rf8
(CH2)3Rf8
(CH2)3Rf8
I(OAc)2
(CH2)3Rf8
b), 60 °C
c)
Rf8(CH2)3
Rf8(CH2)3
I
Rf8(CH2)3
9
7%
93%
95:5, 12:8)
(
(
(CH2)3Rf8
4
8
12
Rf8(CH2)3
Rf8(CH2)3
I
Rf8(CH2)3
Rf8(CH2)3
Rf8(CH2)3
Rf8(CH2)3
I
5'
I
A
A'
I
I
Scheme 2. Syntheses of fluorous iodoarenes and (diacetoxyiodo)arenes. a) I
2
, H
5
6 2 4 2 2 2 3 2
IO , AcOH/H SO /H O ; b) I, PhI(OAc) , AcOEt; c) NaBO ¥ H O,
AcOH, 658C.
Chem. Eur. J. 2003, 9, No. 1
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89

J. A. Gladysz and C. Rocaboy
FULL PAPER
70% yield, but a rather tedious column chromatography was
C H I(OAc) (9 ± 12) formed in high yields. The reactions
6
5-n
2
necessary.
of 6 and 7 required only 5 ± 7 h, and simple aqueous workups
gave 10 and 11 as analytically pure yellowish and white solids
in 95 ± 97% yields.
For some reason, the oxidations of 5 and 8 to 9 and 12 could
only be taken to 90 ± 95% completion. Longer reaction times
ultimately gave lower conversions, suggesting some type of
reductive decomposition pathway. Commercial peracetic acid
(39% in acetic acid) gave little or no reaction with 8 under a
variety of conditions (30 equivalents; acetic acid, 658C or 2:1
In contrast, the meta-substituted arene 2 gave only a single
iodide, 2,4-(R CH CH CH ) C H I (6), the structure of which
followed from the six distinct aryl C NMR signals. It could
easily be isolated in 97% yield, and no by-products were
observed. The para-substituted arene 3 can give only one
monoiodide, 2,5-(R CH CH CH ) C H I (7), and spectro-
scopic yields were >90%. However, H NMR signals
consistent with a diiodide by-product were also detected.
These could also be removed chromatographically, although
again at some sacrifice with respect to the final yield (61%).
When iodinations of the triply pony-tailed fluorous arene
f8
2
2
2
2
6
3
1
3
f8
2
2
2
2
6
3
1
v/v CHCl /acetic acid, 408C). Accordingly, 9 could only be
3
isolated in 85% yield as an oily mixture of 9 and 5 (ca. 90:10).
Similarly, 12 was isolated as a white solid in 93% yield as a
mixture of 12 and 8 (ca. 95:5). Attempted crystallization from
hexanes or CHCl3 (À208C) did not remove residual 8.
However, analytically pure 12 could be isolated on small
scales by filtration through Celite with acetic acid. This
exploits the extremely low solubility of 8 in acetic acid at room
temperature.
1
,3,5-(R CH CH CH ) C H (4) were attempted under
f8
2
2
2
3
6
3
similar
conditions,
the
expected
product
2,4,6-
(
R CH CH CH ) C H I (8) was usually obtained. However,
f8 2 2 2 3 6 2
the degree of conversion was not very reproducible. There-
fore, an alternative protocol involving (diacetoxyiodo)ben-
zene (PhI(OAc) ) and iodine in ethyl acetate was evaluat-
2
[
8, 22ꢀ
ed.
As shown in Scheme 2, this gave 8 in high yields on
The (diacetoxyiodo)arenes 9 ± 12 exhibited good solubil-
ities in common fluorous and organic solvents such as
CF C F , CF C F , CF C H , hexane,diethyl ether, THF,
multigram scales. Surprisingly, this recipe gave inferior results
when applied to 1 ± 3.
3
6
11
3
6
5
3
6
5
The fluorous aryl iodides 5 ± 8, and all other new com-
pounds below, were characterized by microanalysis and H
and 13C NMR spectroscopy. Each was rather low-melting (ca.
7, 65, 91, and 808C), and differential scanning calorimetry
DSC) showed no other phase transitions. At room temper-
CH Cl , CHCl , and acetone. They were also slightly soluble
2 2 3
1
in EtOH, MeOH, and acetic acid. Each was stable in air at
room temperature for weeks, and no special care was required
for handling. The structural assignments were supported by
the NMR, IR, and microanalytical data. For example, IR
3
(
ature, 5 ± 8 were soluble in fluorinated solvents such as
spectra showed a diagnostic band for the acetoxy group ( nÄ ˆ
À1
CF C F and CF C H , and many organic solvents with
1648 ± 1652 cm
(CˆO)). Since 9 ± 12 were not volatile
3
6
11
3
6
5
moderate polarities (pentane, hexanes, toluene, diethyl ether,
THF, CH Cl , CHCl ). They were sparingly soluble in
enough for GC analyses, no partition coefficients were
determined. However, they are expected to be more polar
and less fluorophilic than the aryl iodides 5 ± 8.
2
2
3
acetone, even less soluble in EtOH and acetonitrile, and
nearly insoluble in MeOH and acetic acid. Iodide 7, which has
two pony tails in a para relationship, was the least soluble in
Hydroquinone oxidations and fluorous aryl iodide recycling:
Applications for the preceding compounds were sought. Both
(diacetoxyiodo)benzene and its trifluoroacetoxy analogue are
[19ꢀ
the series, analogous to the trend with 1 ± 3.
The CF C F /toluene partition coefficients of 5 ± 8 were
3
6 11
determined by GC as detailed in the Experimental Section.
These reflect relative as opposed to absolute solubilities, and
are summarized in Table 1. For reasons apparent below,
measurements were also made with a second solvent system,
CF C F /MeOH. Trends are analyzed in the Discussion
frequently used for the oxidation of hydroquinones to
quinones, and related transformations.[
9, 10, 26ꢀ
However, the
phenyl iodide coproduct is normally discarded. Accordingly,
analogous reactions with 9 ± 12 were investigated. Three
hydroquinones–1,4-hydroquinone (13a), 2,3,5-trimethyl-1,4-
hydroquinone (13b), and 2,6-di(tert-butyl)-1,4-hydroquinone
3
6 11
section.
(
13c)–were selected for study, as summarized in Table 2.
The hydroquinones 13a ± c were dissolved in MeOH at
Fluorous (diacetoxyiodo)arenes: Hypervalent iodine com-
pounds of the formula ArI(O CR) are easily prepared by
oxidations of aryl iodides. One convenient procedure utilizes
room temperature and treated either with 1.0 equivalent of 10
or 11, or 1.2 equivalents of 9 or 12. The slight excesses of 9 and
12 were intended to compensate for the residual aryl iodide.
Despite the modest solubilities of 9 ± 12 in MeOH, the
heterogeneous mixture rapidly turned yellow, diagnostic of
the quinones 14a ± c. However, white solids remained,
consistent with the low solubilities of the aryl iodide
coproducts 5 ± 8. After 2 ± 3 h, the fluorous solvent CF C F
11
2
2
the inexpensive reagent sodium perborate (NaBO ) in acetic
3
acid.[
23±25ꢀ
Although mechanistic questions remain, it has been
suggested that this oxidation involves peracetic acid, gener-
ated in situ.[ Thus, reactions are typically conducted at 408C
or less to minimize any independent thermal decomposition
of the peracid, and further reactions of products. However,
the fluorous aryl iodides 5 ± 8 were insoluble under these
conditions, and no reactions occurred in mixed acetic acid/
25ꢀ
3
6
was added to give MeOH/CF C F liquid/liquid biphase
3
6 11
systems. These steps are represented graphically in Scheme 3.
The lower fluorous layer was colorless, and from the
partition coefficients in Table 1 was presumed to contain
nearly all of the aryl iodides 5 ± 8. The upper organic layer was
yellow, and from the partition coefficients of other polar
organic molecules[ was presumed to contain all of the
CHCl solvent systems.
3
Interestingly, the aryl iodides 5 ± 8 were soluble in acetic
acid at 658C. Hence, 658C acetic acid solutions of 5 ± 8 were
treated with excesses of NaBO ¥ H O. As shown in Scheme 2,
3
2
4ꢀ
the expected (diacetoxyiodo)arenes (R CH CH CH ) -
f8
2
2
2 n
90
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Fluorous Aryl Iodides
88±95
Scheme 3. Schematic diagram of reaction conditions for Table 2.
reproducible effect, it may in some way be connected to the
lower solubility of this series of compounds noted above.
Table 2. Oxidations of hydroquinones 13 to benzoquinones 14.
(Rf8(CH2)3)n
f8 2 3 n
(R (CH ) )
I(OAc)2
I
9
-12
5-8
MeOH, RT
- 2 AcOH)
Discussion
+
+
(
R1
R2
R1
R1
R2
R1
Syntheses and physical properties of fluorous ArI(L) com-
n
HO
OH
O
O
pounds: Scheme 2 shows that fluorous aryl iodides with high
fluorous phase affinities can be prepared in good to excellent
yields from the corresponding fluorous arenes. Overall, only
three straightforward steps from commercially available
benzenoid aldehydes are required (Scheme 1 and 2). Two of
the new iodides, 6 and 8, are easily obtained in pure form on
multigram scales. However, as emphasized previously,[
the most important consideration in the synthesis of fluorous
molecules is not the number of steps but the ease of
purification and/or avoidance of by-products. The other new
iodides, 5 and 7, are difficult to separate from what should be
trivial amounts of isomers or diiodides.
1
2
a R = R = H
1
2
b R = R = Me
1
2
13a-c
c R = tBu, R = H
14a-c
Entry ArI(OAc)
2
Hydroquinone Quinone (%)[aꢀ Aryl iodide (%)[aꢀ
1
2
3
4
5
6
7
9[
bꢀ
13a
13a
13a
13b14b
13b14b
13c
14a (95)
14a (98)
14a (98)
(100)
(65)
14c (96)
14c (95)
5 (98)
6 (100)
6 (99)
6 (100)
7 (98)
6 (100)
8 (100)
[
[
[
[
[
[
cꢀ
10
10
10
11
10
12
6b, 17, 28ꢀ
c,dꢀ
cꢀ
cꢀ
[eꢀ
cꢀ
bꢀ
13c
[
[
[
aꢀ Yields of isolated materials pure by 1H NMR (>95%) spectroscopy.
bꢀ 1.2 equiv; yield of recovered aryl iodide based upon this quantity.
cꢀ 1.0 equiv. [dꢀ The reaction was conducted with 10 that had been
regenerated from 6 from the reaction in entry 2. [eꢀ 65:35 14b/11 mixture,
as assayed by H NMR spectroscopy.
Analogous mixtures with methyl or ethyl in place of the
R CH CH CH moieties would not present extraordinary
f8
2
2
2
1
separation challenges. In our view, the pony tails bring about a
leveling effect∫ with regard to the polarity properties
™
commonly exploited in chromatographic purifications. Fur-
thermore, since all by-products have the same spatial relation-
ship of pony tails, chromatography on fluorous silica gel[
would not be effective either. Another handicap is that
fluorous molecules are intrinsically less prone to crystallize. In
related efforts, we have made repeated attempts to efficiently
convert the arene R CH CH CH C H to the singly pony-
quinones 14a ± c. The phases were separated and rinsed, and
solvents were removed under reduced pressure. As shown in
Table 2, this gave the quinones 14a ± c in (with a single
exception) >99 ± 95% yields, and the aryl iodides 5 ± 8 in
29ꢀ
>
99-98% yields (based upon the amount of 9 ± 12 employed).
1
No by-products or impurities were detected by H NMR
spectroscopy.
f8
2
2
2
6
5
[
30, 31ꢀ
tailed para-substituted iodide 4-R CH CH CH C H I.
f8
2
2
2
6
4
The easiest doubly pony-tailed (diacetoxyiodo)arene to
obtain in analytically pure form, 10, was used with each of the
hydroquinones 13a ± c (entries 2, 4, 6 in Table 2). The aryl
iodide recovered in entry 2, 6, was reoxidized to 10 as in
Scheme 2. This sample was directly used in a second oxidation
of 13a, at the original loading and with comparable results
However, we have been unable to devise a user-friendly
separation from the ortho isomer and/or unreacted arene.
Under the conditions in Scheme 2, a 72:28 para/ortho mixture
forms, and four preparative columns are needed to obtain a
34% yield of pure material.[
The oxidations of 5 ± 8 to (diacetoxyiodo)arenes 8 ± 12
(Scheme 2) can be effected in high yields with cheap, readily
available materials. Although two products, 8 and 12, are for
some reason always obtained with small amounts of starting
aryl iodide, this is of no consequence with respect to most
subsequent chemistry, such as the applications in Table 2. It is
31, 32ꢀ
(
1
Table 2, entry 3). The (diacetoxyiodo)arenes 9 (Table 2, entry
) and 12 (Table 2, entry 7) appear similarly effective,
although here the slight excesses employed must be kept in
mind. Only 11 gave an incomplete oxidation of hydroquinone
to quinone. Although we have no simple explanation for this
Chem. Eur. J. 2003, 9, No. 1
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91

J. A. Gladysz and C. Rocaboy
FULL PAPER
also likely that the isomers or diiodides that accompany the
formation of 5 and 7 could be ™carried along∫ with no negative
effect. However, the ease of purification of 6 and 8 renders the
corresponding (diacetoxyiodo)arenes 10 and 12 the most
attractive candidates for further study and use. The latter has
the advantage of a higher fluorous phase affinity. While 8 ± 12
represent the first hypervalent iodine compounds with
fluorous aryl moieties, there is an extensive literature of such
species with fluorous alkyl moieties.[9, 33ꢀ These also represent
attractive candidates for recyclable oxidizing agents.
use of fluorous solvents. As noted in the introduction, solid/
liquid phase separations involving insoluble or thermomor-
phic fluorous species are attracting increasing attention.[
Given that 5 ± 8 have very low solubilities in the reaction
solvent, MeOH, a solid/liquid phase separation at the stage of
the middle panel in Scheme 3 would recover a high fraction of
the aryl iodide. However, due to the obvious need for very
high efficiencies in recycling, we believe that this approach
would be best evaluated with analogs with longer perfluor-
oalkyl groups. These always confer lower solubilities,[ and
based upon trends noted above, the Rf10 analogue of 7 would
constitute a particularly attractive candidate.
Nonetheless, liquid/liquid biphase protocols are preferred
for many types of applications. A possible second-generation
improvement would be to extend the preceding chemistry to
hypervalent iodine compounds derived from fluorous carbox-
ylic acids. Many [bis(trifluoroacetoxy)iodoꢀarenes have been
6, 7ꢀ
34ꢀ
Interestingly, the oxidation protocol in Scheme 2 fails when
applied to perfluoroalkyl-substituted aryl iodides,[ illustrat-
ing the importance of the insulating (CH ) spacer units in 5 ±
23ꢀ
2
3
8
. However, the triply pony-tailed fluorous triarylphosphine
P(p-C H CH CH CH R ) remains less basic than PPh , as
6
4
2
2
2
f8
3
3
assayed by the IR nCO value of an iridium adduct.[ Hence,
the inductive effect of the perfluoralkyl segment can be
transmitted through many connecting atoms.[ We suggest
that the basicities of 5 ± 8 are decreased by a comparable
amount relative to phenyl iodide. This would also render 9 ±
17ꢀ
5ꢀ
previously applied in oxidations. Furthermore, such
a
(R CH CH CH ) C H I(O CR ) species would generate
f8
2
2
2
n
6
5-n
2
fn' 2
its ™own fluorous liquid phase∫ by virtue of the two
equivalents of the fluorous carboxylic acid HO CR liber-
12 slightly stronger oxidants than (diacetoxyiodo)benzene.
2
fn
Table 1 shows that when an iodide substituent is added to a
ated. It might also be possible to directly regenerate the
(R CH CH CH ) C H I(O CR ) species by the simple
fluorous arene, the fluorous phase affinity decreases. This is
an expected consequence of the increased polarity and
polarizability.[ In fact, an aliphatic iodo group has an effect
very similar to that of a phenyl group, as evidenced by the
CF C F /toluene partition coefficients of R CH CH CH I
f8
2
2
2
n
6
5-n
2
fn' 2
addition of NaBO or another suitable oxidant.
3
4ꢀ
Another important question is how the protocols in Table 2
and Scheme 3 compare with those involving other recoverable
hypervalent iodine reagents. Examples of the insoluble,
polymer-supported species noted in the introduction are
3
6
11
f8
2
2
2
and R CH CH CH C H (ca. 50:50). Related fluorohydro-
f8
2
2
2
6
5
[
20ꢀ
[16ꢀ
carbons, such as R CH ˆ CH , give higher values (ca. 94:6).
depicted in Scheme 4. In general, these systems also give
f8
2
Thus, in a CF C F /toluene biphase system, the doubly pony-
both high yields and reactivities. Excellent results with regard
to recovery, reoxidation, and reuse have been reported in
most cases. However, there are also shortcomings, as can be
found with any recycling method.
3
6
11
tailed iodides 5 ± 7 would give significant leaching (ca. 70 ±
5:30 ± 25). The two with ortho pony tails (6,7) have slightly
higher partition coefficients, and it would be of interest to
know the value for the 2,6 isomer.
7
Importantly, the triply pony-tailed iodide 8 maintains a high
CF C F /toluene partition coefficient (98:2). Furthermore,
when toluene is replaced by the much more polar solvent
MeOH, the partition coefficients of 5 ± 8 increase dramati-
cally. Now the doubly pony-tailed iodides show excellent
retention (ca. 98:2), and no leaching of 8 can be detected
H
3
6
11
PS
N
n
PS
I(OAc)2
PS
I(O CCF )
2
3 2
O
I(OAc)2
B16a-d
C16d
D16e (n = 0,1)
(
<0.3%). This is a logical consequence of the higher polarity
O
+
PS
O
of MeOH, and the low absolute solubility of 5 ± 8 in MeOH.
Longer perfluoroalkyl groups also increase partition coeffi-
cients, as illustrated by 1,2-(R CH CH CH ) C H in Table 1.
Hence, the Rf10 homologs of 5 ± 8 would exhibit still higher
PS
I(OH)(OTs)
PS
IC CR
O
_
OTs
I
f10
2
2
2
2
6
4
HO
O
E16f
F16f
G16h
fluorophilicities.
HO
O
I
H
O
SiO2
Oxidations of hydroquinones; fluorous liquid/liquid biphase
recycling: The simplicity and effectiveness of the hydro-
quinone oxidations in Table 2 and Scheme 3, and the ease of
separation of the quinone product and fluorous aryl iodide
coproduct, hardly need to be emphasized. The reactivities of
N
O
O
O
H16g
Scheme 4. Other recyclable hypervalent iodine reagents.
[26ꢀ
9
± 12 are comparable to those of (diacetoxyiodo)benzene
[27ꢀ
and related (diacetoxyiodo)heteroarenes. It is noteworthy
that a fluorous solvent is not required during the reaction.
Rather, liquid/liquid biphase conditions are used only for
product isolation and coproduct recycling.
Those that have been noted for such polymer-supported
reagents include nonlinear kinetic behavior, unequal distri-
bution and/or access of active sites to the reaction media,
solvation problems associated with the nature of the support,
reactivity differences associated with subtle variations in
polymer backbones, altered stereoselectivities, ease of mon-
In this regard, there is a cost incentive to develop recycling
strategies for fluorous catalysts and reagents that avoid the
92
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Chem. Eur. J. 2003, 9, No. 1

Fluorous Aryl Iodides
88±95
itoring as compared to homogeneous systems, and synthetic
difficulties in transferring standard organic reactions to the
solid phase.[ For example, reagent B in Scheme 4 was
12 h at 858C. Sublimed I
2
was periodically redissolved by swirling the flask.
The mixture was allowed to cool to room temperature, and was extracted
with CH Cl (50 mL). Saturated aqueous Na was added to the purple
2 2 3
S O
35ꢀ
2
2
extract with vigorous stirring (50 mL), and the mixture became colorless.
The aqueous phase was extracted again with CH Cl (30 mL), and the
combined organic phases were dried (MgSO ). The solvent was removed by
4
prepared by the iodination of polystyrene with I /I O /
2
2
5
2
2
[14a,bꢀ
H SO .
Thus, regioisomers and diiodinated arenes can
2
4
rotary evaporation to give a slightly colored oil. A series of preparative
silica gel columns (3 ± 6 depending upon scale; pentane elution) gave 5 as a
colorless oil that solidified upon standing (1.726 g, 1.535 mmol, 70%). M. p.
be expected, analogously to the crude reaction mixtures in
Scheme 2.
To be even-handed, various shortcomings have also been
noted for fluorous methodologies. These include fluorous
solvent cost, fluorous solvent leaching, and environmental
persistence.[4ꢀ Accordingly, we view the value of this work–
which has resulted in the first aryl iodides that are easily
recoverable under liquid/liquid biphase conditions–as lying
in the expansion of the portfolio of recovery methods. The
protocols represented in Scheme 4 are complementary to
those in Table 2 and Scheme 3, and the specific application
will often dictate the optimal approach. In any event, the
chemical community now has a much broader palette of
strategies to choose from.
3
78C (capillary), 35.98C (DSC); elemental analysis (%) calcd for
C H F I: C 29.91, H 1.34; found: C 29.68, H 1.30; NMR (CDCl ):
2
8
15 34
3
2
3
1
H NMR: d ˆ 1.84 ± 1.92 (m; 2CH
2
CH
2
CF
2
), 2.09 ± 2.18 (m; 2CH
2
CF
6
H
),
),
3
3
2.64, 2.66 (2t, JH,H ˆ 8 Hz; 2ArCH
2
), 6.91 (d, JH,H ˆ 8 Hz; 1H of C
4
3
4
7
1
3
.51 (d, JH,H ˆ 2 Hz; 1H of C
6
H
3
), 7.52 ppm (dd, JH,H ˆ 8 Hz, JH,H ˆ 2 Hz;
1
3
1
H of C
6
H
3
); C{ H} NMR (partial): d ˆ 21.9, 22.1 (2s; 2CH
2
CH
2 2
CF ),
2
[37ꢀ
0.7, 30.8 (2t,
131.4, 136.1, 138.4, 138.5, 141.4 ppm (6s; C
the following minor H signals were also present (see text and Scheme 2):
J
C,F ˆ 22 Hz; 2CH
2
CF ), 31.7, 31.8 (2s; 2ArCH ), 92.1,
2
2
6
H
3
). Prior to chromatography,
1
1
3
3
5
1
1
': H NMR: d ˆ 2.74, 2.86 (2t, JH,H ˆ 8 Hz; 2ArCH
2
), 6.87 (t, JH,H ˆ 8 Hz;
4
3
H of C
H of C
6
H
3
), 7.14 (d, JH,H ˆ 2 Hz; 1H of C
6
H
3
), 7.74 ppm (d, JH,H ˆ 8 Hz;
1
6
H
3
); A or A' (tentative assignment): H NMR ˆ d ˆ 2.60 (t,
3
JH,H ˆ 8 Hz; 2ArCH ), 7.66 ppm (s; C H ).[38ꢀ
2
6
2
2
,4-(Rf8CH
2
CH
2
CH
2
)
2
C
CH
6
H
3
I (6): The procedure for 5 was repeated at 758C
19ꢀ
with 1,3-(Rf8CH
.500 mmol), H
0.20 mL), and water (1.00 mL). An identical workup (only one preparative
column required) gave 6 as a colorless oil that solidified upon standing
0.844 g, 0.750 mmol, 97%). M. p. 658C (capillary), 66.18C (DSC);
2
CH
2
2
)
2
C
6
H
4
(2;[ 0.772 g, 0.773 mmol), I
2
(0.647 g,
2
(
5
IO
6
(0.660 g, 2.895 mmol), acetic acid (5.00 mL), H
2
SO
4
Conclusion
(
elemental analysis (%) calcd for C28
15
H F34I: C 29.91, H 1.34; found: C
This study has described efficient syntheses of the first series
of fluorous aryl iodides (5 ± 8) and hypervalent iodine com-
pounds (9 ± 12). The former constitute exceedingly useful
synthons for other fluorous compounds, and the latter
represent forerunners of what should be a wide variety of
synthetically useful and easily recoverable iodine-containing
fluorous reagents. The applicability of 9 ± 12 to the oxidation
of hydroquinones has been demonstrated, and workups under
fluorous biphase conditions give very high yields of quinones
1
3
2
8
0.30, H 1.45; H NMR (CDCl
3
): d ˆ 1.86 ± 1.99 (m; 2CH
2
CH
2
CF
2
), 2.01 ±
3
3
.18 (m; 2CH
2
CF
2
), 2.63, 2.79 (2t, JH,H ˆ 8 Hz; 2ArCH
2
), 6.73 (dd, JH,H
ˆ
4
4
Hz, JH,H ˆ 2 Hz; 1H of C
6
H
3
), 7.00 (d, JH,H ˆ 2 Hz; 1H of C
6 3
H ), 7.23 ppm
3
13
1
(d, J ˆ 8 Hz; 1H of C H ); C{ H} NMR (partial): d ˆ 20.9, 21.8 (2s;
H,H
6
3
2
2CH
2
2
CH ), 34.5, 39.8 (2s;
), 97.7,[ 128.7, 129.7, 140.1, 141.5, 143.8 ppm (6s; C
ArCH H ).
2 6 3
2
CF
2
), 30.3, 30.4 (2t,
J
C,F ˆ 22 Hz; 2CH
2
CF
2
37ꢀ
2
,5-(Rf8CH
2
CH
2
CH
CH
IO
2.40 mL), and water (16 mL). After 24 h, more H
2
)
2
C
6
H
3
I (7): The procedure for 5 was repeated at 908C
(3;[
19ꢀ
6.47 g, 6.48 mmol),
I
(6.71 g,
SO
6
(2.95 g, 12.94 mmol)
with 1,4-(Rf8CH
5.92 mmol), H
2
2
CH
2
)
2
C
6
H
4
2
2
(
5
6
(5.91 g, 25.92 mmol), acetic acid (80 mL), H
IO
2
4
5
(
organic phase), and fluorous aryl iodides (fluorous phase)
was added, and the mixture was stirred an additional 24 h at 908C. An
identical workup gave 7 as a white solid (4.42 g, 3.93 mmol, 61%). M. p.
that can be efficiently recycled. There are also tantalizing
possibilities for other recovery strategies, and the continued
development of this area of fluorous chemistry can be
confidently predicted.
9
C
18C (capillary), 89.68C (DSC); elemental analysis (%) calcd for
1
28
H
15
F
34I: C 29.91, H 1.34; found: C 29.91, H 1.76; H NMR (CDCl
3
):
d ˆ 1.86 ± 1.96 (m; 2CH
2
CH
2
CF
2
3
), 2.01 ± 2.23 (m; 2CH
2
CF
), 7.13 (d, JH,H
); C{ H} NMR (partial): d ˆ
2
), 2.64, 2.79 (2t,
3
3
J
H,H ˆ 8 Hz; 2ArCH
2
), 7.11 (d, JH,H ˆ 8 Hz; 1H of C
6
H
3
ˆ
1
3
1
8
Hz; 1H of C
6 3 6 3
H ), 7.68 ppm (s; 1H of C H
2
2
3
1.0, 21.9 (2s; 2CH
2
CH
2
CF
2
37ꢀ
), 30.4, 30.5 (2t, JC,F ˆ 22 Hz; 2CH
2 2
CF ), 34.0,
9.5 (2s, 2ArCH
2
), 100.8,[ 128.8, 129.5, 139.7, 141.1, 141.6 ppm (6s; C
6
H
3
).
1
Experimental Section
Prior to chromatography, minor H signals tentatively assigned to a
3
diiodide were also present (see text): d ˆ 2.73 (t,
J
H,H ˆ 8 Hz; 2ArCH
2
),
General: All reactions were conducted under N
were treated as follows: THF, diethyl ether, toluene, hexanes, distilled from
Na/benzophenone; MeOH, distilled from Mg; CF (Aldrich),
CF 5; CDCl
(2 Â Oakwood or ABCR), distilled from P
ꢀacetone (Cambridge Isotope or Aldrich), other ™reagent grade∫
solvents, H IO , PhI(OAc) , NaBO ¥ H
2
unless noted. Chemicals
7.64 ppm (s; C ).
6 2
H
2
1
4
(
,4,6-(Rf8CH CH CH
,3,5-(Rf8CH CH CH
.025 mmol), PhI(OAc)
15 mL), sealed with a septum, covered totally with aluminum foil, and
2
2
2
)
3
C
6
H
2
I (8): A round-bottom flask was charged with
C
6
H
5
[19ꢀ
3
)
C
H
(4;
1.957 g, 1.341 mmol),
I
2
(1.042 g,
2
2
2
3
6
3
3
C
6
F
11, CF
3
C
6
F
5
2
O
3
,
(1.296 g, 4.025 mmol), and ethyl acetate
2
[
D
6
5
6
2
3
2
O(3 Â Oakwood or Aldrich), 1,4-
immersed in an oil bath at 608C. The mixture was stirred for 24 h, allowed
to cool to room temperature, and poured onto a saturated aqueous solution
hydroquinone, 2,3,5-trimethyl-1,4-hydroquinone, 2,6-di(tert-butyl)-1,4-hy-
droquinone (3 Â Acros), used as received. NMR spectra were recorded on
of Na
2 Â 25 mL) into the aqueous phase. The mixture was vigorously stirred
until colorless. The organic phase was separated and dried (MgSO ).
2 2 3
S O (50 mL). The reaction flask was rinsed twice with diethyl ether
standard Jeol or Bruker 400 MHz FT spectrometers at ambient probe
(
1
temperatures and referenced as follows: H, residual internal CHCl
3
(d ˆ
4
1
3
7.27 ppm) or [D
5
ꢀacetone (d ˆ 2.05 ppm); C, internal CDCl
3
(d ˆ
Solvent was removed by rotary evaporation to give a yellowish oil. Most of
the phenyl iodide coproduct was removed by oil pump vacuum, leaving a
yellowish solid. Column chromatography (silica gel, hexanes elution) gave
7
7.2 ppm) or [D
6
ꢀacetone (d ˆ 29.6 ppm). IR spectra were measured on
an ASI React-IR spectrometer. Gas chromatography was conducted on a
ThermoQuest Trace GC 2000 instrument. DSC data were recorded with a
Mettler-Toledo DSC821 instrument and treated by standard methods.
Elemental analyses were conducted with a Carlo Erba EA1110 instrument.
8
as a white solid (2.056 g, 1.297 mmol, 97%). M. p. 808C (capillary),
[
36ꢀ
8
3.18C (DSC); elemental analysis (%) calcd for C39
H
20
F
51I: C 29.56, H 1.27;
1
found: C 29.87, H 1.41; H NMR (CDCl
3
/CF
3
C
6
F
5
, 9:1 v/v): d ˆ 1.92 ± 2.16
3
3
3
1
8
(
,4-(Rf8CH
,2-(Rf8CH
.814 mmol), H
0.60 mL), and water (4 mL). The sample was stirred for 18 h at 858C.
Then H IO (1.005 g, 4.409 mmol) was added and the sample stirred for
2
CH
2
CH
CH
IO
2
)
2
C
6
H
3
I (5): A round-bottom flask was charged with
(m; 3CH
2ArCH ), 6.90 ppm (s;
CH CF ), 21.8 (s; CH
C,F ˆ 22 Hz; 2CH CF
2
CH
2
CF
2
), 2.66 (t,
J
H,H ˆ 8 Hz; ArCH
2
), 2.88 (t,
J
H,H ˆ 8 Hz,
(1;[
19ꢀ
2.200 g, 2.203 mmol),
I
(2.237 g,
SO
C
H
CH
); C{ H} NMR (partial): d ˆ 21.0 (s;
13
1
2
CH
2
2
)
2
C
6
H
4
2
2
6
2
2
5
6
(2.010 g, 8.814 mmol), acetic acid (20 mL), H
2
4
2CH
2
2
2
2
2
CF
2
), 30.3 (t, JC,F ˆ 22 Hz; CH
2
CF
2
), 30.5
2
[37ꢀ
(t,
J
2
2
), 34.3 (s; ArCH
).
2 2
), 41.3 (s; 2ArCH ), 104.3,
5
6
127.9, 141.3, 145.2 ppm (4s; C
6
H
2
Chem. Eur. J. 2003, 9, No. 1
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/03/0901-0093 $ 20.00+.50/0
93

J. A. Gladysz and C. Rocaboy
FULL PAPER
1
3
(
,4-(Rf8CH
0.270 g, 0.240 mmol) and acetic acid (4.00 mL) and placed in a 658C oil
bath. The mixture was stirred to dissolve 5, and NaBO ¥ H O(0.239 g,
.401 mmol) was added portionwise over the course of 0.5 h. The flask was
sealed with a septum and the mixture stirred under nitrogen (5 h; TLC
showed the disappearance of 5). Water (25 mL) and CHCl (25 mL) were
added. The organic phase was removed and the aqueous solution again
extracted with CHCl
(2 Â 25 mL). The combined organic extracts were
dried (MgSO ). The solvent was removed by rotary evaporation and further
2
CH
2
CH
2
)
2
C
6
H
3
I(OAc)
2
(9): A Schlenk flask was charged with 5
1,4-Benzoquinone (14a): H NMR ([D
6
ꢀacetone): d ˆ 6.83 ppm (s; 4CHˆ);
1
3
1
C{ H} NMR: d ˆ 151.1 (s; 4CHˆ), 188.1 ppm (s; 2CˆO); IR (thin film):
À1
nÄ ˆ 1645 cm (CˆO).
3
2
2
,3,5-Trimethyl-1,4-benzoquinone (14b): 1H NMR ([D
[27ꢀ
2
6
ꢀacetone):
d ˆ
4
4
1.95 (d,
J
H,H ˆ 1.6 Hz; CH
3
), 1.99 (s; 2CH
3
), 6.58 ppm (q,
J
H,H ˆ 1.6 Hz;
13
1
3
CH ); C{ H} NMR: d ˆ 11.9, 12.2, 15.7 (3s; 3CH
ˆ
3
), 133.5 (s; CH ), 141.1,
ˆ
1
1
41.3, 146.0 (3s; 3CCH
3
), 187.7, 188.1 ppm (2s, 2C O); IR (thin film): nÄ ˆ
ˆ
À1
3
645 cm (C ˆ O).
4
1
ꢀacetone):[27ꢀ d ˆ
2
,6-Di(tert-butyl)-1,4-benzoquinone (14c): H NMR ([D
6
dried under oil pump vacuum to give 9 as a light brown oil (0.282 g,
0
1
3
1
1.26 (s; 6CH
3
), 6.47 (s; 2CHˆ); C{ H} NMR ˆ 29.0 (s; 6CH
3
), 34.9 (s;
1
.227 mmol, 85%) that contained ca. 10% residual 5 (see text). H NMR
2
C(CH
3
)
3
), 134.0 (s; 2CHˆ), 154.5 (s; 2CC(CH
3
)
3
), 188.8 ppm (s; 2CˆO);
(
J
CDCl
3
): d ˆ 1.94 ± 2.21 (m; 2CH
2
CH
2
CF
2
), 2.00 (s; 2CH
3
), 2.79, 2.80 (2t,
À1
IR (thin film): nÄ ˆ 1645 cm (CˆO).
3
3
H,H ˆ 8 Hz; 2ArCH
2
), 7.30 (d, JH,H ˆ 8 Hz; 1H of C
6 3
H ), 7.90 (s; 1H of
3
13
1
Partition coefficients: The following is representative. A 10 mL vial was
charged with 5 (0.0156 g, 0.0138 mmol), CF 11 (2.000 mL), and MeOH
C
2
2
C
6
H
3
), 7.91 ppm (d, JH,H ˆ 8 Hz; 1H of C
6
H
3
); C{ H} NMR (partial): d ˆ
2
3 6
C F
0.4 (s; 2CH
3
), 21.7, 21.9 (2s, 2CH
2
CH
2
CF
2
), 30.7, 30.9 (2t, JC,F ˆ 22 Hz,
), 119.8,[ 131.8, 133.5, 135.7, 142.1, 143.3 (6s;
37ꢀ
(2.000 mL), fitted with a mininert valve, vigorously shaken (2 min), and
immersed (cap-level) in an oil bath at 358C. After 12 h, the bath was
removed. After 12 ± 24 h, a 0.500 mL aliquot of each layer was added to
0.250 mL of a standard 0.0244m solution of eicosane in hexane. The
samples were diluted with ether and GC analysis (average of 7 ± 8
injections) showed that 0.00325 mmol of 5 was in the CF C F11 aliquot
3 6
and 0.000101 mmol in the MeOH aliquot (97.0:3.0; a 2.000/0.500 scale
factor gives a total mass recovery of 0.0150 g, 97%).
CH CF ), 32.0 (s; 2ArCH
2
2
2
À1
H
3
), 176.6 ppm (s, 2CˆO); IR (thin film): nÄ ˆ 1648 cm (CˆO).
6
2
0
,4-(Rf8CH I(OAc)
2
CH
2
CH
2
)
2
C
6
H
3
2
(10): Compound
6
(0.265 g,
.235 mmol), NaBO ¥ H O(0.235 g, 2.357 mmol), and acetic acid
3 2
(
4.00 mL) were combined in a procedure analogous to that given for 9. A
similar workup gave 10 as a yellowish solid (0.283 g, 0.227 mmol, 97%).
M. p. 68 ± 698C (capillary), 67.58C (DSC); elemental analysis (%) calcd for
C
1
32
H
21
F
34IO
4
: C 30.94, H 1.70; found: C 30.74, H 1.84; H NMR (CDCl
3
):
ˆ
3
d ˆ 1.92 ± 2.19 (m; 2CH
2
CH
2
CF
2
), 1.98 (s; 2CH
3
), 2.79, 3.07 (2t,
J
H,H
3
4
8
Hz; 2ArCH
H,H ˆ 2 Hz; 1H of C
2
), 7.15 (dd, JH,H ˆ 8 Hz, JH,H ˆ 2 Hz; 1H of C
6
H
H
3
), 7.31 (d,
4
3
13
1
J
6
H
3
), 8.17 ppm (d, JH,H ˆ 8 Hz; 1H of C
6
3
); C{ H}
Acknowledgement
NMR (partial): d ˆ 20.2 (s; 2CH
3
), 21.6, 21.8 (2s; 2CH
2
CH
2
2
CF ), 30.4, 30.5
2
[37ꢀ
(
1
2t, JC,F ˆ 22 Hz; 2CH
2
CF
2
), 35.0, 38.4 (2s; 2ArCH
2
), 125.1, 129.6, 130.1,
We thank the Deutsche Forschungsgemeinschaft (DFG; GL 301/3 ± 1) for
support, and Dr. Drew Rutherford for some exploratory iodination
reactions. This work was conducted as part of a Ph. D. thesis defended in
the Department of Chemistry at the University of Utah.
38.6, 143.2, 146.6 (6s; C
648 cm (CˆO).
6
H
3
), 176.9 ppm (s; 2CˆO); IR (thin film): nÄ ˆ
À1
1
2
,5-(Rf8CH I(OAc)
2
CH
2
CH
2
)
2
C
6
H
3
2
(11): Compound
7
(0.208 g,
0
.185 mmol), NaBO ¥ H O(0.369 g, 3.70 mmol), and acetic acid
3 2
(
8.00 mL) were combined in a procedure analogous to that given for 9. A
similar workup gave 11 as a white solid (0.218 g, 0.175 mmol, 95%). M. p.
[1ꢀ I. T. Horv a¬ th, Acc. Chem. Res. 1998, 31, 641.
1
C
02 ± 1048C (capillary), 102.78C (DSC); elemental analysis (%) calcd for
[2ꢀ a) E. de Wolf, G. van Koten, B.-J. Deelman, Chem. Soc. Rev. 1999, 28,
37; b) M. Cavazzini, F. Montanari, G. Pozzi, S. Quici, J. Fluorine Chem.
1999, 94, 183; c) E. G. Hope, A. M. Stuart, J. Fluorine Chem. 1999,
100, 75; d) J. Yoshida, K. Itami, Chem. Rev. 2002, 102, 3693.
[3ꢀ J. A. Gladysz, D. P. Curran, Tetrahedron 2002, 58, 3823, and following
papers in this special issue devoted to ™fluorous chemistry∫.
1
32
H
21
F
34IO
4
: C 30.94, H 1.70; found: C 30.70, H 1.81; H NMR (CDCl
3
):
ˆ
3
d ˆ 1.84 ± 2.19 (m; 2CH
2
3
CH
2
CF
2
), 2.00 (s, 2CH
3
), 2.80, 3.06 (2t,
J
H,H
4
8
Hz; 2ArCH
of C ), 8.07 (s; 1H of C
1.7, 21.8 (2s; 2CH CH CF
8.1 (2s; 2ArCH
2
), 7.43 (d, JH,H ˆ 8 Hz; 1H of C
6
H
3
), 7.46 (d, JH,H ˆ 8 Hz; 1H
1
3
1
6
H
3
6
H
3
); C{ H} NMR (partial): d ˆ 20.2 (s; 2CH
3
),
2
2
3
2
2
2
37ꢀ
), 30.3, 30.5 (2t, JC,F ˆ 22 Hz; 2CH
2 2
CF ), 34.3,
[
2
), 127.1, 130.1, 133.1, 137.8, 140.7, 142.3 (6s, C
6
H
3
), 176.6
[4ꢀ Survey of practical considerations and underlying physical principles:
L. P. Barthel-Rosa, J. A. Gladysz, Coord. Chem. Rev. 1999, 190 ± 192,
À1
(
s; 2CˆO); IR (thin film): nÄ ˆ 1652 cm (CˆO).
5
87.
2
,4,6-(Rf8CH
2
CH
2
CH
2
)
3
C
6
H
2
I(OAc)
2
(12): Compound
8
(1.70 g,
[
5ꢀ H. Jiao, S. Le Stang, T. So o¬ s, R. Meier, P. Rademacher, K. Kowski, L.
1.075 mmol), NaBO
3
¥ H
2
O(2.14 g, 21.5 mmol), and acetic acid
Jafarpour, J.-B. Hamard, S. P. Nolan, J. A. Gladysz, J. Am. Chem. Soc.
(
35.00 mL) were combined in a procedure analogous to that given for 9.
2
002, 124, 1516.
6ꢀ a) M. Wende, R. Meier, J. A. Gladysz, J. Am. Chem. Soc. 2001, 123,
1490; b) see also C. Rocaboy, J. A. Gladysz, Org. Lett. 2002, 4, 1993.
7ꢀ a) K. Ishihara, S. Kondo, H. Yamamoto, Synlett 2001, 9, 1371; b) J.
Xiang, A. Orita, J. Otera, Adv. Synth. Catal. 2002, 344, 84.
8ꢀ E. B. Merkushev, Synthesis 1988, 923.
A similar workup gave 12 as a white solid (1.79 g, 1.05 mmol, 93%) that
contained about 5% residual 8 (see text). To obtain an analytical sample,
about 0.200 g was placed at the top of a 10 Â 2 cm Celite column, which was
eluted with acetic acid. The initial fractions contained pure 12. M. p. 89 ±
9
C
[
[
1
08C (capillary), 88.58C (DSC); elemental analysis (%) calcd for
[
[
1
43
H
26
F
51IO
4
: C 30.33, H 1.54; found: C 30.33, H 1.88; H NMR (CDCl
3
):
9ꢀ a) P. J. Stang, V. V. Zhdankin, Chem. Rev. 1996, 96, 1123; b) V. V.
Zhdankin, P. J. Stang, Chem. Rev. 2002, 102, 2523.
3
d ˆ 1.94 (s; 2CH
3
3
), 1.94 ± 2.21 (m; 3CH
2
CH
), 7.20 ppm (s; C
), 21.1 (s, CH CH CF ), 21.8 (s; 2CH
CF ), 34.8 (s; ArCH ), 40.0 (s; 2ArCH
2
CF
2
), 2.79 (t,
J
H,H ˆ 8 Hz;
1
ArCH
2
), 3.14 (t, JH,H ˆ 8 Hz; 2ArCH
2
6 2
H
); 13C{ H} NMR
[
10ꢀ a) A. Varvoglis, Hypervalent Iodine in Organic Synthesis, Academic
Press: San Diego, CA, 1997; b) A. Varvoglis, Tetrahedron 1997, 53,
(
3
partial): d ˆ 20.1 (s; 2CH
3
2
2
2
2
CH
2
CF
2
),
),
2
0.5 (t,
J
C,F ˆ 22 Hz; 3CH
2
2
2
2
1
179; c) A. Varvoglis, S. Spyroudis, Synlett 1998, 3, 221.
11ꢀ T. Wirth, Angew. Chem. 2001, 113, 2889; Angew. Chem. Int. Ed. 2001,
0, 2812.
[
37ꢀ
1
28.4, 131.1, 144.6, 146.4 (4s; C
6
H
2
), 176.7 ppm (s; 2CˆO); IR (thin film):
[
À1
nÄ ˆ 1648 cm (CˆO).
4
Oxidations of hydroquinones: A Schlenk flask was charged with hydro-
quinones 13a ± c (Table 2; 0.243 ± 0.608 mmol) and (diacetoxyiodo)arenes
[12ꢀ a) K. C. Nicolaou, P. S. Baran, Y.-L. Zhong, K. Sugita, J. Am. Chem.
Soc. 2002, 124, 2212; b) K. C. Nicolaou, K. Sugita, P. S. Baran, Y.-L.
Zhong, J. Am. Chem. Soc. 2002, 124, 2221; c) K. C. Nicolaou, P. S.
Baran, Y.-L. Zhong, S. Barleunga, K. W. Hunt, R. Kranich, J. Vega, J.
Am. Chem. Soc. 2002, 124, 2233; d) K. C. Nicolaou, T. Montagnon,
P. S. Baran, Y.-L. Zhong, J. Am. Chem. Soc. 2002, 124, 2245; e) K. C.
Nicolaou, T. Montagnon, P. S. Baran, Angew. Chem. Int. Ed. 2002, 41,
993; Angew. Chem. 2002, 114, 1035; f) K. C. Nicolaou, D. L. F. Gray, T.
Montagnon, S. T. Harrison, Angew. Chem. Int. Ed. 2002, 41, 996;
Angew. Chem. 2002, 114, 1038; g) K. C. Nicolaou, T. Montagnon, P. S.
Baran, Angew. Chem. Int. Ed. 2002, 41, 1386; Angew. Chem. 2002, 114,
1444.
9
± 12 (10 and 11, 1.0:1.0 mol ratio; 9 and 12, 1.0:1.2 mol ratio). Freshly
distilled MeOH (5.00 ± 8.00 mL) was added with stirring. The suspension
quickly turned light yellow. After 2 ± 3 h, CF 11 (5.00 ± 10.00 mL) was
3
6
C F
added, giving a liquid/liquid biphase system with all species dissolved. The
upper yellow MeOH phase was carefully removed via syringe, and the
fluorous phase extracted with MeOH (2 Â 2.00 mL). The combined MeOH
3 6
solutions were extracted with CF C F11 (2.00 mL). The solvents were
3 6 11
removed from the combined MeOH solutions and combined CF C F
solutions by rotary evaporation to give the quinones 14a ± c and aryl
1
iodides 5 ± 8 that were pure by H NMR spectroscopy (>95%). Yields are
summarized in Table 2, and additional data are as follows.
[13ꢀ H. Morales-Rojas, R. A. Moss, Chem. Rev. 2002, 102, 2497.
94
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/03/0901-0094 $ 20.00+.50/0
Chem. Eur. J. 2003, 9, No. 1

Fluorous Aryl Iodides
88±95
[
14ꢀ Additional lead references: a) D. Macikenas, E. Skrypczak-Jankun,
J. D. Protasiewicz, J. Am. Chem. Soc. 1999, 121, 7164; b) M. Ochiai, Y.
Kitagawa, N. Takayma, Y. Takaoka, M. Shiro, J. Am. Chem. Soc. 1999,
[23ꢀ A. McKillop, D. Kemp, Tetrahedron 1989, 45, 3299.
[24ꢀ M. Ochiai, K. Oshima, T. Ito, Y. Masaki, M. Shiro, Tetrahedron Lett.
1991, 32, 1327.
1
21, 9233.
15ꢀ M. Poliakoff, J. M. Fitzpatrick, T. R.Farren, P. T. Anastas, Science
002, 297, 807, and references therein.
[25ꢀ a) A. McKillop, W. R. Sanderson, Tetrahedron 1995, 51, 6145; b) C.
Karunakaran, P. N. Palanisamy, J. Mol. Cat. A 2001, 172, 9.
[26ꢀ A. Pelter, S. Elgendy, Tetrahedron Lett. 1988, 29, 677.
[27ꢀ H. Togo, T. Nabana, K. Yamaguchi, J. Org. Chem. 2000, 65, 8391.
[28ꢀ C. Rocaboy, Gladysz, J. A. New J. Chem. 2003, 27, in press.
[29ꢀ D. P. Curran, Synlett 2001, 1488.
[
[
2
16ꢀ a) H. Togo, G. Hogami, M. Yokoyama, Synlett 1998, 534; b) S. V. Ley,
A. W. Thomas, H. Finch, J. Chem. Soc. Perkin Trans. 1 1999, 669; c) H.
Tohma, S. Takizawa, T. Maegawa, Y. Kita, Angew. Chem. Int. Ed.
2
000, 39, 1306; Angew. Chem. 2000, 112, 1362; d) H. Tohma, H.
[30ꢀ D. Rutherford, B. Bennett, unpublished results, University of Utah.
[31ꢀ S. Le Stang, unpublished results, Universit‰t Erlangen-N¸rnberg.
[32ꢀ This simple compound remains an ongoing synthetic challenge.
Routes based upon a Wittig reaction of 4-iodobenzaldehyde (analo-
gous to Scheme 1) are complicated by competing carbon ± iodine bond
Morioka, S. Takizawa, M. Arisawa, Y. Kita, Tetrahedron 2001, 57, 345;
e) S. Ficht, M. M¸lbaier, A. Giannis, Tetrahedron 2001, 57, 4863; f) X.
Huang, Q. Zhu, Tetrahedron Lett. 2001, 42, 6373; g) M. M¸lbaier, A.
Giannis, Angew. Chem. Int. Ed. 2001, 40, 4393; Angew. Chem. 2001,
1
13, 4530; h) G. Sorg, A. Mengel, G. Jung, J. Rademann, Angew.
hydrogenolysis under all CˆC hydrogenation conditions (homoge-
neous and heterogeneous) evaluated to date.[
30, 31ꢀ
No practical way
Chem. Int. Ed. 2001, 40, 4395; Angew. Chem. 2001, 113, 4533.
17ꢀ T. So o¬ s, B. L. Bennett, D. Rutherford, L. P. Barthel-Rosa, J. A
Gladysz,. Organometallics 2001, 20, 3079.
[
[
has been found to separate the resulting mixture of
4-Rf8CH CH CH I and Rf8CH CH CH . The same mixture
2
2
2
C
6
H
4
2
2
2 6 5
C H
18ꢀ a) S. Kainz, D. Koch, W. Baumann, W. Leitner, Angew. Chem. Int. Ed.
is also obtained upon treatment of the diazonium cation [4-
‡
1
997, 36, 1628; Angew. Chem. 1997, 109, 1699; b) B. Betzemeier, P.
Knochel, Angew. Chem. Int. Ed. 1997, 36, 2623; Angew. Chem. 1997,
09, 2736; c) P. Bhattacharyya, D. Gudmunsen, E. G. Hope, R. D. W.
Kemmitt, D. R. Paige, A. M. Stuart, J. Chem. Soc. Perkin Trans. 1 1997,
R
f8CH
2
CH
2
CH
2
C
6
H
4
N
2
ꢀ
with KI. Some lead references that relate
to these side reactions: a) N. Faucher, Y. Ambroise, J.-C. Cintrat, E.
Doris, F. Pillon, B. Rousseau, J. Org. Chem. 2002, 67, 932; b) R. Kumar,
P. R. Singh, Tetrahedron Lett. 1972, 13, 613.
1
3609; d) S. Kainz, Z. Luo, D. P. Curran, W. Leitner, Synthesis 1998,
1425; e) S. Schneider, W. Bannwarth, Angew. Chem. Int. Ed. 2000, 39,
4142; Angew. Chem. 2000, 112, 4293; f) B. Richter, E. de Wolf, G.
[33ꢀ T. Umemoto, Chem. Rev. 1996, 96, 1757.
[34ꢀ L. J. Alvey, D. Rutherford, J. J. J. Juliette, J. A. Gladysz, J. Org. Chem.
1998, 63, 6302.
van Koten, B.-J. Deelman, J. Org. Chem. 2000, 65, 3885; g) D. R. Palo,
C. Erkey, Organometallics 2000, 19, 81; h) Q. Zhang, Z. Luo, D. P.
Curran, J. Org. Chem. 2000, 65, 8866; i) S. Darses, M. Pucheault, J.-P.
Gen e√ t, Eur. J. Inorg. Chem. 2001, 1121; j) W. Chen, L. Xu, J. Xiao,
Tetrahedron Lett. 2001, 42, 4275.
[35ꢀ a) T. J. Dickerson, N. N. Reed, K. D. Janda, Chem. Rev. 2002, 102,
3325; b) C. M. Baldino, J. Comb. Chem. 2000, 2, 89.
[36ꢀ H. K. Cammenga, M. Epple, Angew. Chem. Int. Ed. 1995, 34, 1171;
Angew. Chem. 1995, 107, 1284.
[37ꢀ This signal is assigned as the C-I resonance.
[38ꢀ This chemical shift agrees well with that reported for an analogue of
A: A. Zweig, K. R. Huffman, G. W. Nachtigall J. Org. Chem. 1977, 42,
4049.
[
19ꢀ C. Rocaboy, D. Rutherford, B. L. Bennett, J. A. Gladysz, J. Phys. Org.
Chem. 2000, 13, 596.
20ꢀ L. E. Kiss, I. Kˆvesdi, J. R a¬ bai, J. Fluorine Chem. 2001, 108, 95.
21ꢀ C. Rocaboy, F. Hampel, J. A. Gladysz, J. Org. Chem. 2002, 67, 6863.
22ꢀ H. Togo, G. Nogami, M. Yokoyama, Synlett 1998, 534.
[
[
[
Received: August 28, 2002 [F4375ꢀ
Chem. Eur. J. 2003, 9, No. 1
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/03/0901-0095 $ 20.00+.50/0
95