Straightforward syntheses of hypervalent iodine(III) reagents mediated by selectfluor

Article abstract of DOI:10.1021/ol051446t

(Chemical Equation Presented) Use of Selectfluor allows hypervalent iodine(III) species such as aryl iodine(III) difluoride, diacetate, and di(trifluoroacetate) and Koser's salt to be easily prepared. Aryl iodine(III) difluoride and diacetate can be synthesized from the corresponding arene and elemental iodine in one-pot procedures.

Full text of DOI:10.1021/ol051446t

ORGANIC
LETTERS
2005
Vol. 7, No. 18
3961-3964
Straightforward Syntheses of
Hypervalent Iodine(III) Reagents
Mediated by Selectfluor
Chengfeng Ye, Brendan Twamley, and Jean’ne M. Shreeve*
Department of Chemistry, UniVersity of Idaho, Moscow, Idaho 83844-2343
jshreeVe@uidaho.edu
Received June 22, 2005
ABSTRACT
Use of Selectfluor allows hypervalent iodine(III) species such as aryl iodine(III) difluoride, diacetate, and di(trifluoroacetate) and Koser’s salt
to be easily prepared. Aryl iodine(III) difluoride and diacetate can be synthesized from the corresponding arene and elemental iodine in
one-pot procedures.
The incorporation of fluorine into molecules results in
dramatic changes in their physical, chemical, and biological
properties.1 Constantly expanding commercial products rang-
ing from anticancer agents to agrochemicals to lubricants
for spaceships to toothpaste contain C-F bonds. Among the
dozens of fluorinating reagents, Selectfluor (1) continues to
be one of the most powerful tools of choice as “tamed
fluorine.” In less than two years, 1 has been the subject of
three major reviews.2 Although 1 is most often employed as
an extremely effective electrophilic fluorinating reagent, it
also plays an important role as mediator or catalyst in organic
syntheses. For example, Stavber and Zupan demonstrated
that 1 was the effective mediator for direct iodination of
arenes and ketones using iodine with 1 where only one-half
equivalent each of I2 and 1 was necessary for this task.3 On
the other hand, due to the very useful oxidizing properties
of hypervalent iodine(III), exemplified by iodine(III) di-
fluoride and diacetate and Koser’s salt, it has attracted
surging interest in organic synthesis.4 Although aryl iodine-
(III) difluoride has been considered for use as a fluorinating
reagent, this application was usually limited by its synthesis
and storage difficulties. Previously, the iodine(III) difluoride
compounds were prepared by one-step procedures that
involved elemental fluorine (at -100 °C),5 SF4,6 XeF2,7 or
an electrochemical process,8 as well as some recently
improved routes involving multiple-step protocols (Scheme
1).9
(4) (a) Zhdankin, V. V.; Stang, P. J. Chem. ReV. 2002, 102, 2523-2584.
(b) Wirth, T. HyperValent Iodine Chemistry: Modern DeVelopments in
Organic Synthesis; Springer-Verlag: Berlin, 2003. (c) Moriarty, R. M. J.
Org. Chem. 2005, 70, 2893-2903. (d) Wirth, T. Angew. Chem., Int. Ed.
2005, 44, 3656-3665.
(5) Naumann, D.; Ruther, G. J. Fluorine Chem. 1980, 15, 213-222.
(6) Lyalin, V. V.; Orda, V. V.; Alekseeva, L. A. Zh. Org. Khim. 1970,
6, 329-332. CAN 72, 110915.
(7) (a) Zupan, M.; Pollak, A. Chem. Commun. 1975, 715-716. (b) Zupan,
M. Collect. Czech. Chem. Commun. 1977, 42, 266-274.
(8) Hara, S.; Hatakeyama, T.; Chen, S. Q.; Ishi-I, K.; Yoshida, M.;
Sawaguchi, M.; Fukuhara, T.; Yoneda, N. J. Fluorine Chem. 1998, 87, 185-
192.
(9) (a) Sawaguchi, M.; Ayuba, S.; Hara, S. Synthesis 2002, 1802-1803.
(b) Motherwell, W. B.; Greaney, M. F.; Edmunds, J. J.; Steed, J. W. J.
Chem. Soc. Perkin Trans. 1 2002, 2816-2826. (c) Hara, S.; Yoshida, M.;
Fukuhara, T.; Yoneda, N. Chem. Commun. 1998, 965-986. (d) Yoneda,
N. J. Fluorine Chem. 2004, 125, 7-17. (e) Arrica, M. A.; Wirth, T. Eur.
J. Org. Chem. 2005, 395-403.
(1) (a) Olah, G. A.; Chambers, R. D.; Prakash, G. K. S. Synthetic Fluorine
Chemistry; John Wiley: New York, 1992. (b) Hudlicky, M.; Pavlath, A.
E.; Chemistry of Organic Fluorine Compounds II; American Chemical
Society: Washington, DC, 1995. (c) Chambers, R. D. Fluorine in Organic
Chemistry; Blackwell Publishing: Oxford, 2004.
(2) (a) Singh, R. P.; Shreeve, J. M. Acc. Chem. Res. 2004, 37, 31-44.
(b) Nyffeler, P. T.; Duron, S. G.; Burkart, M. D.; Vincent, S. P.; Wong,
C.-H. Angew. Chem., Int. Ed. 2004, 44, 192-212. (c) Stavber, S.; Zupan,
M. Acta Chim. SloV. 2005, 52, 13-26.
(3) (a) Zupan, M.; Iskra, J.; Stavber, S. Tetrahedron Lett. 1997, 38, 6305-
6306. (b) Stavber, S.; Kralj, P.; Zupan, M. Synlett 2002, 598-600. (c)
Stavber, S.; Kralj, P.; Zupan, M. Synthesis 2002, 1513-1518. (d) Stavber,
S.; Jereb, M.; Zupan, M. Chem. Commun. 2002, 488-489.
10.1021/ol051446t CCC: $30.25
© 2005 American Chemical Society
Published on Web 08/05/2005

Scheme 1
Scheme 3
Herein, we report a facile and straightforward synthesis
of hypervalent iodine(III) reagents using Selectfluor.
Selectfluor (1), Accufluor NFPY (2), and MEC-31 (3) are
very common electrophilic reagents of choice, but there are
no reports on the reactions of such fluorinating reagents with
aryl iodides10 (Scheme 2).
Table 1, good regioselectivity and yields were achieved for
Table 1. One-Pot Synthesis of Aryl-IF2 or -I(OAc)2 from
Arenea
Scheme 2
As a matter of fact, the reaction of 2 equiv of Selectfluor
(1) with iodobenzene or 4-iodotoluene led to the facile and
quantitative syntheses of hypervalent aryl iodine difluorides
(4a, 4b) as determined by NMR spectra in CD3CN. The
isolated yield, however, can be low (ca. 30%) due to the
intrinsic instability of iodine(III) difluoride compounds. This
can be greatly improved by the addition of trace amounts of
Et3N‚3HF before workup, as the presence of HF may
stabilize the aryl iodine(III) difluoride. Excess quantities of
Selectfluor did not lead to fluorination of the phenyl ring.
The reactions of other fluorinating reagents under the same
conditions, e.g., Accufluor NFPY and MEC-31, with io-
doarenes did not produce hypervalent iodine difluoride
compounds.
When CH3CN/AcOH or CH3CN/trifluoroacetic acid (TFA)
was used as a solvent, the corresponding aryl iodine(III)
diacetate or di(trifluoroacetate) was the sole product. More-
over, when the solvent of CH3CN/AcOH contains another
equivalent of TsOH‚H2O, the products of Koser’s salt (7a,
7b) precipitated from the solution in good yield and high
purity (Scheme 3).
a For 4, solvent ) CH3CN. For 5, solvent ) CH3CN (AcOH). b Impure.
mono-, di-, and tri-substituted benzenes.
It is noteworthy that this is the first report of straightfor-
ward synthesis of hypervalent iodine(III) difluoride and
diacetate from arene and elemental iodine, while the previous
methods start from the corresponding iodoarene. Further-
more, this method is fairly mild and easy to handle; no
special precautions or equipment were needed.
Iodine(III) compounds have been widely used as oxidants
or catalysts for organic transformations. For the ease of the
recycling of iodoarene, polymers7,11 or ionic liquid-sup-
ported12 hypervalent iodine(III) reagents continue to be of
On the basis of Stavber and Zupan’s endeavor devoted to
the syntheses of iodoarenes mediated by 1,3 we found that
when the stoichiometry of 1 used in the reaction was
increased to 2.5 equiv, the aryl-IF2 or -I(OAc)2 could be
easily obtained under the given conditions. As shown in
(11) Tohma, H.; Takizawa, S.; Maegawa, T.; Kita, Y. Angew. Chem.,
Int. Ed. 2000, 39, 1306-1308.
(12) (a) Qian, W.; Jin, E.; bao, W.; Zhang, Y. Angew. Chem., Int. Ed.
2004, 43, 2-5. (b) Handy, S. T.; Okello, M. J. Org. Chem. 2005, 70, 2874-
2877.
(10) (a) Lal, G. S. J. Org. Chem. 1993, 58, 2791-2796. (b) Syvret, R.
G.; Butt, K. M.; Nguyen, T. P.; Bulleck, V. L.; Rieth, R. D. J. Org. Chem.
2002, 67, 4487-4493.
3962
Org. Lett., Vol. 7, No. 18, 2005

considerable interest. Our protocol also proceeds smoothly
for direct synthesis of polymer-supported iodine(III) diac-
etate, with nearly one-third of the phenyl rings of the
copolymer being loaded with I(OAc)2 based on elemental
analysis.13
Solid-State Structures of 4b, 4f. There are only three
reported single-crystal structures of hypervalent RIF2 species.
Compound 4b is the most common aryl-IF2 reagent, and the
original report of its structure indicated that the I-F bond
lengths were quite different (2.1 and 1.5 Å).14 As the material
is easily crystallized, we reinvestigated this structure as well
as the structure of 4f. A thermal ellipsoid plot of 4b is shown
in Figure 1a. This compound crystallizes in an orthorhombic
arene carbon atom and two intermolecular I‚‚‚F interactions
(I1‚‚‚F1i, 3.050(3), I1‚‚‚F2ii, 3.101(3) Å, and I2‚‚‚F3i, 3.253-
(3), I2‚‚‚F4ii, 2.895(3) Å; i ) 1/2 - x, y, -1/2 + z, ii ) 1/2
- x, y, 1/2 + z). The structure of 4f,18 Figure 1b, has less
symmetry (triclinic, P-1), and has four crystallographically
independent molecules in the asymmetric unit. The I-F bond
lengths and angles are similar to those in 4b (I-F av )
2.019, 1.991 Å; F-I-F ) 172.5-174.4°); however, the
iodine atoms are now only four coordinate with a distorted
square planar geometry. There is only one intermolecular
I‚‚‚F interaction (I‚‚‚F ) 2.856(3), 2.829(3), 2.989(3), and
3.026(3) Å) per molecule. In both 4b and 4f, the most notable
feature is the I‚‚‚F supramolecular synthon. The I‚‚‚F
interaction is short and in 4b, together with some extra I‚‚
‚F interactions (I1-F3iii, 3.389(3) Å; iii ) x, y, -1 + z)
and CH‚‚‚F close contacts, generates an interesting zigzag
double-chain motif (Figure 2a). In 4f, the synthon is localized
Figure 1. Thermal ellipsoid plot (30%) of (a) 4b and (b) 4f.
Hydrogen atoms have been removed for clarity. Only one confor-
mation of the disordered methyl group is shown in 4f.
Figure 2. (a) Zigzag double-chain synthon formed via I‚‚‚F
intermolecular interactions in 4b. (b) Chair conformation ring
synthon in 4f. Hydrogen atoms and some labeling omitted for
clarity.
system, with two crystallographically independent molecules
in the asymmetric unit.15 The I-F bond lengths are ap-
proximately equal (2.025(3), 1.995(3) Å and 2.023(3), 1.992-
(3) Å to each independent iodine atom). These bond lengths
are very similar to those in C6F5IF2 (2.029, 1.954 Å)16 and
CF3IF2 (1.982(2) Å),17 which clearly demonstrates that the
structure of 4b is not unusual as previously thought. The
F-I-F array is not linear (171.0 and 174.4°) and is a result
of the large space requirements of the lone pairs and
intermolecular interactions (vide infra). This angle is less
acute than that in CF3IF2 (164.5°) but similar to those in
C6F5IF2 (171.6, 170.5°). The bonded fluorine atoms are
apical, and the distorted equatorial plane consists of the ipso
and forms an unusual eight-membered chair I-F ring (Figure
2b). There are weak CH‚‚‚F contacts (ca. 2.45 Å) between
these localized synthons and adjacent synthons.
Reaction Behavior of PhIF2 vs Selectfluor. We also
explored the reaction properties of iodobenzene difluoride
prepared in situ (coded as [PhIF2]) rather than the isolated
pure compound (PhIF2), using 1,1-diphenylethene as a model
substrate. Under the conditions outlined in Scheme 4, a
rearranged ketone was the major product when aqueous HF
(50%), Et3N‚3HF, or pyridinium polyhydrogen fluoride
(PPHF)19 was employed as a catalyst for [PhIF2] (conditions
a). The typical rearranged product, 1,1-difluoro-1,2-diphe-
nylethane,7 was only observed when PhIF2/PPHF was used
(conditions c), indicating that the side-product of Selectfluor,
which would be present when PhIF2 is not purified, may
interfere with the rearrangement reaction. In sharp contrast,
(13) ACROS, Polystyrene: 2% divinylbenzene copolymer beads, 200-
400 mesh. A 0.1 g amount of this copolymer was treated with I2 (1 mmol)
and Selectfluor (5 mmol) in acetonitrile for 24 h, filtered, and washed with
acetic acid and acetonitrile, 0.19 g. Elemental analysis: C, 50.44; H, 4.62;
I, 24.46. Nearly one-third of the phenyl rings were loaded with -I(OAc)2
based on iodine content.
(14) Wilkinson, J. A. Chem. ReV. 1992, 92, 505-519.
(15) Crystal data for 4b: C7H7F2I, MW ) 256.03, orthorhombic, Pca2-
(1), T ) 87(2) K, Bruker SMART APEX, Mo KR, λ ) 0.71073 Å, a )
17.9460(7) Å, b ) 11.4823(5) Å, c ) 7.3257(3) Å, V ) 1509.54(11) Å3,
Z ) 8, size 0.33 × 0.12 × 0.06 mm3, Fcalcd ) 2.253 Mg/m3, µ ) 4.196
(18) Crystal data for 4f: C12H17F2I, MW ) 326.16, triclinic, space group
P-1, T ) 87(2) K, Bruker SMART APEX, Mo KR, λ ) 0.71073 Å, a )
11.5263(7) Å, b ) 12.7649(8) Å, c ) 17.7467(11) Å, R ) 76.027 (1)°, â
) 81.454 (1)°, γ ) 88.146 (1)°, V ) 2505.7(3) Å3, Z ) 8, size ) 0.42 ×
0.24 × 0.11 mm3, Fcalcd ) 1.729 Mg/m3, µ ) 2.548 mm-1, reflections
collected/unique 38 176/9078, R(int) ) 0.0319, R1 ) 0.0485, wR2 ) 0.1269
(I > 2σI); GOF ) 1.032.
mm-1, reflections collected/unique 23 053/2737, R(int) ) 0.0291, R1
0.0228, wR2 ) 0.0568 (I > 2σI), GOF ) 1.057.
)
(16) Bailly, F.; Barthen, P.; Breuer, W.; Frohn, H.-J.; Giesen, M.; Helber,
J.; Henkel, G.; Priwitzer, A. Z. Anorg. Allg. Chem. 2002, 626, 1406-1413.
(17) Minkwitz, R.; Berkei, M. Inorg. Chem. 1998, 37, 5247-5250.
(19) Reddy, V. P.; Alleti, R.; Perambuduru, M. K.; Welz-Biermann, U.;
Buchholz, H.; Prakash, G. K. S. Chem. Commun. 2005, 654-656.
Org. Lett., Vol. 7, No. 18, 2005
3963

iodinated ketone (11)21 was identified. Expansion of this
method to other olefins is underway.
Scheme 4
Mechanism Considerations. There are two plausible
intermediates for aryl iodine(III) diacetate from reaction of
1 and iodoarene: (i) peroxyacetic acid formed in situ by
reaction of 1 and AcOH or (ii) aryl iodine(III) difluoride.
Under the same conditions, no Baeyer-Villiger products
were detected by GC-MS for the diphenyl ketone, which
indicates that peroxyacetic acid was not produced in situ.
However, when treated with acetic acid, mesityl-IF2 was
quickly converted quantitatively into its diacetate. This result
suggests that aryl-IF2 may be the effective intermediate.
When elemental iodine is used for the direct formation of
aryl iodine(III) diacetate (conditions in Table 1), I(OAc)3
may also be an intermediate besides aryl-IF2. Actually, I2
could slowly be consumed just in the presence of 3 equiv of
1 in CH3CN/AcOH. However, in our hands, reaction of
22
Scheme 5
I(OAc)3 only with electron-rich arene was able to afford
the corresponding aryl-I(OAc)2 (5f, 5g) in good yield; for
5c-e, yields were very low. In addition, considering that
the formation of I(OAc)3 mediated by Selectfluor is a slow
process, the aryl iodine(III) difluoride rather than I(OAc)3
may be the intermediate in this case.
In conclusion, use of Selectfluor allows hypervalent iodine-
(III) species such as aryl iodine difluoride, diacetate, and
di(trifluoroacetate) and Koser’s salt to be easily prepared,
and the former two iodine(III) reagents can be prepared from
the corresponding arene and I2 in one-pot procedures.
Acknowledgment. The authors acknowledge the financial
support of the AFOSR, (Grant F49620-03-1-0209), the NSF
(Grant CHE0315275), and the ONR (Grant N00014-02-1-
0600).
Selectfluor (in the absence of any iodine(III) moiety) gives
the Vic-difluorinated compound (conditions b). In other
words, 1 equiv of iodobenzene changes the reaction behavior
of Selectfluor.
Supporting Information Available: Experimental sec-
1
tion and characterization data, H NMR spectra for all
Interestingly, when 1,1-diphenylethene was directly treated
with Selectfluor and I2 in acetonitrile (conditions d) without
addition of arene to produce aryl-IF2, the desired rearranged
gem-difluorinated species can readily form. Thus, the tedious
procedure of recycling of iodoarene under conditions c and
compounds, as well as CIF files for crystal structures 4b,
4f. This material is available free of charge via the Internet
at http://pubs.acs.org.
OL051446T
20
preparation of XeF2 were circumvented. Moreover, when
(21) Futami, Y.; Nishino, H.; Kurosawa, K. Bull. Chem. Soc. Jpn. 1989,
62, 3182-3186.
(22) I(OAc)3 is extremely sensitive to moisure and was prepared as
described by: Birchall, T.; Frampton, C. S.; Kapoor, P. Inorg. Chem. 1989,
28, 636-639.
the solvent contained acetic acid (conditions e), the product
became very complex, in which 39% of the rearranged
(20) Patrick, T. B.; Qian, S. Org. Lett. 2000, 2, 3359-3360.
3964
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