Synthesis, structure, and chemoselective reactivity of N-(2-iodylphenyl) acylamides: Hypervalent iodine reagents bearing a pseudo-six-membered ring.scaffold

Article abstract of DOI:10.1002/anie.200502707

A pseudo-benziodoxazine structure with intramolecular secondary I...O bonding, as shown by X-ray analysis, is seen in a series of N-(2-iodylphenyl) acylamides prepared from 2-iodoaniline (see scheme). These compounds contain a six-membered pseudocyclic scaffold about an iodine(v) center and are able to oxidize either alcohols or sulfides, with the reactivity depending largely on the substitution pattern on the amide group adjacent to the iodyl moiety. (Chemical Equation Presented).

Full text of DOI:10.1002/anie.200502707

Angewandte
Chemie
Synthetic Methods
The low solubility of 2, which restricts its practical
application, arises from strong intermolecular secondary
I···O, hydrogen-bonding, and p-stacking interactions
observed for IBX in the solid state.[4] Several research
groups have tried to overcome this preparative limitation by
performing oxidation at elevated temperatures,[5a] using an
ionic liquid and water as a reaction medium,[5b] or function-
alizing the IBX aromatic core.[5c] Also, a number of solid-
supported reagents in which the IBX scaffold is linked to a
polymer have been reported.[6] Another fruitful approach
coined by Protasiewicz, Wirth, and co-workers[7a–e] involves
the incorporation of an ortho-substituent into l5- and l3-
iodanes (e.g., sulfone 3 and benzyl ether 4), thus resulting in
intramolecular secondary bonding interactions. This ortho-
stabilization leads to a partial disruption of the polymeric
network, and consequently enhances solubility. More
recently, investigations from our group have resulted in a
series of stable and soluble IBX analogs: IBX amides 5a,[7f]
IBX esters 5b,[7g] as well as IBX sulfonamides 6a and IBX
sulfonate esters 6b.[7h] A planar pseudo-benziodoxole moiety
that arises from the intramolecular nonbonding iodine–
oxygen interaction is a key structural feature present in this
series of compounds, as shown by X-ray crystallographic
analysis. The readily available hypervalent iodine reagents 5–
6 possess reactivity similar to IBX and DMP and have proved
to be useful oxidizing reagents towards alcohols[8a] and
sulfides.[8b] The synthesis of polymer-supported IBX esters
and amides has been reported as well.[8c]
We report herein the elaboration of the ortho-stabilization
concept with regard to l5-iodanes. Our initial aim was to
furnish an aryl iodyl species with a pseudo-six-membered ring
unit such that the iodine(v) atom and ortho-sustituent donor
atom were located in the 1,6-position. To obtain the required
scaffold, we decided on an amide group as the ortho sustitu-
ent. Indeed, changing the aryl amide function in the
substituted IBX amide to an aryl carbamoyl group yields N-
(2-iodylphenyl)acylamides 7 with the required pseudo-ben-
ziodoxazine structure (Scheme 2). Assuming that an isosteric
switch will not substantially change the molecular electronic
parameters of the system when carried out, one can expect 7
to be close to the IBX amides in oxidative properties.
Furthermore, the ortho-amide group offers a large variety
of structural modifications, which may allow control over the
reactivity profile of the title compounds.
DOI: 10.1002/anie.200502707
Synthesis, Structure, and Chemoselective
Reactivity of N-(2-Iodylphenyl)acylamides:
Hypervalent Iodine Reagents Bearing a Pseudo-
Six-Membered Ring Scaffold**
Uladzimir Ladziata, Alexey Y. Koposov, Ka Y. Lo,
Jeff Willging, Victor N. Nemykin,*and
Viktor V. Zhdankin*
During the past decade, hypervalent iodine compounds have
gained significant attention as mild, selective, and environ-
mentally benign reagents in synthetic organic chemistry.[1,2]
The oxidation of sensitive and complex alcohols[2a,b] and
amines,[2c] the cyclization of anilides,[2d] the introduction of
a,b unsaturation into carbonyl compounds,[2e] and the aroma-
tization of tetrahydronaphthalene-1,4-diones[2f] are among
elegant synthetic transformations effected by organic io-
dine(v) compounds (l5-iodanes). However, the major
reagents used for these unique protocols, Dess–Martin
periodinane (DMP, 1)[2a] and its precursor 1-hydroxy-1,2-
benziodoxol-3-(1H)-one (IBX, 2; see Scheme 1,[2b] suffer
from a number of drawbacks, namely, DMP is highly sensitive
towards moisture[3a] and unstable to prolonged storage,
whereas IBX is explosive under impact or on heating to
> 2008C,[3b] is nonrecyclable, and has limited solubility in
most organic solvents except dimethyl sulfoxide (DMSO).
A set of sixteen pseudo-benziodoxazines 14–17 was
prepared to investigate the influence of the structure of the
ortho sustituent on the oxidative activity of the target N-(2-
iodylphenyl)acylamides and to explore the chemistry of these
novel reagents (Scheme 2). Synthesis of 14–17 was performed
by acylation of the commercially available 2-iodoaniline (8)
with a range of acyl chlorides. Subsequent treatment of the
obtained amides 9a–e and 10 with NaH in dry THF, followed
by alkylation with MeI and BnBr in the case of 9a–e, led to
pyrrolidinone 13 and substituted amides 11a–e and 12a–e.
Oxidation of iodoarenes 11–13 with 3,3-dimethyldioxirane
afforded 14–17 in good yields. All the products were isolated
in the form of stable, white solids.[9]
Scheme 1. Cyclic and pseudocyclic hypervalent iodine reagents.
[*]U. Ladziata, A. Y. Koposov, K. Y. Lo, J. Willging,
Prof. Dr. V. N. Nemykin, Prof. Dr. V. V. Zhdankin
Department of Chemistry
University of Minnesota Duluth
Duluth, MN 55812 (USA)
Fax: (+1)218-726-7394
E-mail: vnemykin@d.umn.edu
vzhdanki@d.umn.edu
[**]This work was supported by a research grant from the National
Science Foundation (CHE 0353541) and by a NSF-MRI award
(CHE 0416157).
Compounds 14–17 were identified by spectroscopic and
ESI-mass-spectrometric analysis; single-crystal X-ray analysis
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2005, 44, 7127 –7131
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7127

Communications
hypervalent iodine center and the carbonyl
oxygen atom. Indeed, the rotation of the C(6)-
C(11)-N(5)-C(13) fragment to a zero-degree
torsion angle results in a I(1)···O(4) distance of
=
1.86 Š, which is typical for the I O bond, and
therefore a planar geometry in the case of 15e
cannot be achieved. Another important feature
of the crystal structure of 15e is an unusual
arrangement of the 3D polymeric network. As
with the previously reported IBX analogues,[7a–h]
molecules of 15e form infinite polymeric chains
in the bis-m-oxo motif. This structure, however,
differs from those observed earlier in two ways:
First, the I(1)···O’’(2) and I(1)···O’(3) distances
are unusually different, with the latter close to the
intramolecular I(1)···O(4) distance, whereas the
former is close to the sum of the iodine and
oxygen van der Waals radii (Figure 1). Second,
the observed polymeric chain is spiral shaped
along the principal c axis, whereas in previously
reported IBX analogs such polymer motifs were
close to a linear geometry. Overall, the formation
of a six-membered pseudocycle in 15e leads to
several unique features in the solid-state struc-
ture.
Scheme 2. Preparation of target aryl iodyl derivatives 14a–e, 15a–e, 16a–e, and 17. a) RCOCl
(1.0 equiv), Et3N (1.1 equiv), THF, 08C!RT, 30 min; b) 1. NaH (1.1 equiv), THF, 08C, 30 min;
2. MeI (1.3 equiv), THF, 08C!RT, 3 h; (c) 1. NaH (1.1 equiv), THF, 08C, 30 min; 2. BnBr
(1.3 equiv), THF, 08C!RT, 3 h; d) NaH (1.1 equiv), THF, 08C!RT, 3 h; e) 3,3-dimethyldioxir-
ane (3.0 equiv, 0.1m in acetone), CH2Cl2, 08C!RT, 3 h. Cy=cyclohexyl.
The solubility of 14–17 varies appreciably
depending on the nature of the substituents.
Specifically, 14a–d and pyrrolidinone 17 have
very limited solubilities in polar organic solvents,
was also used in the case of 15e. IR spectra of all compounds
such as dichloromethane, 1,2-dichloroethane (DCE), and
acetonitrile. In contrast, 15a–e and especially 16 exhibit
showed a strong absorption for I O at 760–780 cmꢀ1. With a
=
few exceptions (amides 14e, 15c–e, 16e, and 17), the expected
carbonyl absorption appeared as two strong bands: the first
[10]
band at 1640–1675 cmꢀ1 (characteristic amide C O stretch)
=
[10]
and the second at 1600–1620 cmꢀ1 (C N Ar stretch).
= ꢀ
Compounds 14e and 15c–e showed a single band at 1600–
1620 cmꢀ1, whereas 16e and 17 were characterized by a sole
band at 1643 cmꢀ1. 1H NMR analysis indicated practically no
downfield shift for the proton ortho to the iodine atom
relative to iodo derivatives 9–13. In the 13C NMR spectra of
ꢀ
iodyl arenes 14a–e and 17, the signal for C IO2 was observed
at approximately d = 133 ppm, whereas for amides 15–16 this
signal emerged at d = 142 ppm. The ESI-HRMS spectra of
14–17 demonstrated strong peaks that correspond to dimers
[2M+Na]+, as well as weaker [M+Na]+ peaks. These data will
be rationalized later during the discussion of the reactivity
profile of compounds 7.
Single crystals of 15e of X-ray-diffraction quality were
obtained by slow evaporation from a methanol solution.[11] As
anticipated, the structure of 15e exhibits a strong I(1)···O(4)
intramolecular interaction which affords the pseudo-benzio-
doxazine ring (Figure 1). The observed I(1)···O(4) distance of
2.647 Š is a typical for Iv pseudocyclic moieties.[7a–h] The
resulting pseudo-benziodoxazine scaffold is not planar and a
torsion angle of 41.338 was observed for the C(6)-C(11)-N(5)-
C(13) fragment. This observation is rather intriguing because
all known five-membered pseudocyclic iodine(v)-containing
compounds have a planar geometry. Such a dramatic differ-
ence can be explained by the steric interaction between the
Figure 1. CAMERON drawing of a polymeric chain in the solid-state
structure of 15e at the 30% probability level (hydrogen atoms are
omitted for clarity, Ar=2-C6H4NMeCOtBu). Selected distances [Š]and
angles [8]: I(1)–O(2) 1.791, I(1)–O(3) 1.832, I(1)···O’’(2) 3.226,
I(1)···O’(3) 2.627, I(1)–C(6) 2.115, I(1)···O(4) 2.647, N(5)–C(13) 1.349,
O(4)–C(13) 1.225, O(2)-I(1)-O(3) 103.88, O(2)-I(1)-C(6) 99.01, O(3)-
I(1)-C(6) 94.38, O(2)-I(1)···O(4) 166.31, C(6)-C(11)-N(5)-C(13) 41.33.
7128
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Angewandte
Chemie
Table 1: Oxidative activity of 14–17 towards benzyl alcohol and methyl
para-tolyl sulfide.
excellent solubility in polar organic solvents, for example, the
solubilities of 15d, 15e, and 16e in CH2Cl2 are 0.97, 0.12, and
1.4m, respectively. The plausible reason for the low solubility
of 14 is the formation of intermolecular hydrogen bonds
through amide hydrogen atoms which cause extra reinforce-
ment of the polymeric network. In the case of 17, the low
solubility could be explained by the presence of a compact
pyrrolidinone ring which offers minor steric demand and,
thus, causes no disruption of the polymeric structure.
The oxidation activity of 14–17 was evaluated by studying
the oxidation of benzyl alcohol and methyl para-tolyl sulfide.
Preliminary reactivity investigations with 16d (reagent/sub-
strate = 1:2) showed that these oxidations proceed quantita-
tively at reflux within 1.5 hours and with MeCN or DCE as
the optimal reaction solvents. Reaction at reflux is essential
for fast conversions; for example, full conversion requires 36–
48 hours at room temperature in DCE as the solvent. To
compare reactivity, 14–17 were reacted under uniform con-
ditions (the results are presented in Table 1).
The experimental results show that the oxidative activity
of 14–17 depends on the nature of the ortho-substituent to a
significant extent. On examination of the oxidative ability of
14–17, a clear pattern emerges: First, unsubstituted amides 14,
with the exception of pivalamide 14e, exhibit virtually no
oxidative activity. This fact appears to arise from the
negligible solubility of these compounds in MeCN. Com-
pound 14e renders moderate solubility and, hence, oxidizes
benzyl alcohol. Interestingly, amide 14e is not reactive
towards methyl para-tolyl sulfide. Furthermore, series 15,
with 15d displaying the optimal activity, also demonstrates
similar selective oxidative behavior. In series 16, the selectiv-
ity vanishes and both benzyl alcohol and methyl para-tolyl
sulfide were oxidized effectively. In
Entry
Reagent[a]
Conversion[b] in
reaction (1) [%]
Conversion[c] in
reaction (2) [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
14a
14b
14c
14d
14e
15a
15b
15c
15d
15e
16a
16b
16c
16d
16e
17
0
0
2
0
0
0
0
0
9
6
0
0
3
36
32
70
22
72
39
19
68
36
66
79
0
0
95
81
31
64
96
8
15d
77[d]
89[d]
[a]The ratio of BnOH and para-Tol SMe to reagents 14–17 was 2:1.
[b]Determined by GCMS; benzaldehyde and the respective iodoarenes 9
and 11–13 were the only reaction products detected. [c]Determined by
GCMS; methyl para-tolyl sulfoxide and the respective iodoarenes 9 and
11–13 were the only reaction products detected. [d]Reaction was
performed in the presence of TsOH (10 mol%).
both sets of compounds, the acet-
amide derivatives (15a and 16a)
display
considerable
reactivity
towards methyl para-tolyl sulfide.
Finally, 17 does not oxidize alcohols,
but reacts slowly with the sulfide
functionality.
The character of such a struc-
ture–activity relationship can be
explained by examination of the
equilibrium between amide 7 and
benziodoxazine 18 (Scheme 3). The
cyclic form 18 apparently has
decreased electrophilic reactivity
because of its zwitterionic structure
with the negative charge on the iodyl
moiety and is, thus, not able to react
with sulfides to form either inter-
mediates 19 or 20. On the other
hand, the iodyl moiety in benziodox-
azine 18 is possibly basic enough to
abstract a proton from an alcohol to
yield the protonated cyclic form 21.
Subsequent attack by an alkoxide
leads to alkoxyiodane 23, which
undergoes decomposition to form
Scheme 3. Proposed mechanistic rationale for the reactivity of pseudo-benziodoxazines 14–17 towards
alcohols and sulfides. I effect=inductive effect.
Angew. Chem. Int. Ed. 2005, 44, 7127 –7131
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7129

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an aldehyde according to the conventional mechanism.[3a] In
1.0 equiv) led to upfield signals for C NRCO and C IO2,
ꢀ
ꢀ
=
contrast, the open form 7 is more electrophilic and reacts
unselectively with both the alcohol and sulfide groups. We can
speculate that 14e and 15c–e, which are selective towards
alcohol oxidation, have 18 as the major form in solution. The
cyclic form 18 of 14e and 15c–e is possibly stabilized by the
electron-donating effect of the R1 group and especially the R2
group through the decrease in the positive charge on the
nitrogen atom (see 24). In 15a,b, the Me and nPr substituents
offer less stabilization, and minor amounts of the open form 7
is present in solution. Hence, partial oxidation of the sulfur
atom is observed in 15a,b. For series 16, the cyclic form 18 is
highly disfavored because of steric reasons (Scheme 3; see
25), and no selectivity is observed. Compound 17 possesses
lowered reactivity because of low solubility, and it is
exclusively reactive towards the sulfide group. This behavior
could be explained by the fact that the formation of
benziodoxazine 26 is also highly disfavored because of the
formation of a double bond at the bridgehead of a bicyclic
system.
whereas the upfield signal for C O vanished, thus putatively
yielding the mesylate species similar to the open form 7
(Figure 2). Indeed, no selectivity was observed when oxida-
tions were carried out with 15d in the presence of a catalytic
amount of TsOH (Ts = para-toluenesulfonyl; Table 1,
entry 17). Conceivably, the formation of electrophilic species
22, which is close to 7 in reactivity, is responsible for such a
major change in the oxidative behavior. The 13C NMR spectra
of 15e and 16e correspond to the cyclic and open forms of
15a, respectively (Figure 2). The latter spectroscopic data
match the reactivity profile of 15e and 16e perfectly but
contradict the X-ray data obtained for 15e. This data can be
rationalized by the supposition that the zwitterionic cyclic
form 18 exists only in solution, in which charge separation is
stabilized by polar solvent molecules, and thus could not be
observed in the solid state.
To validate the chemoselective reactivity of 15d, the
oxidation reactions of thioalcohols 26 and 28 were studied
(Scheme 4). However, when 0.5 equivalents of oxidant in
DCE at reflux were used, considerable amounts (approxi-
mately 30% by GCMS) of the respective sulfoxides were
formed along with the main products 27 and 29. Probably, the
The proposed mechanism is supported by experimental
and spectral data. In their IR spectra, 14e and 15c–e showed a
single band at 1600–1620 cmꢀ1, which is a typical C N Ar
= ꢀ
stretch. Compounds 16e and 17 were characterized by a single
band at 1643 cmꢀ1, thus indicating an amide carbonyl
function. All other compounds showed carbonyl absorptions
in both of these regions. The 13C NMR spectra of 15a in
=
ꢀ
[D6]DMSO revealed pairs of close signals for C O, C
ꢀ
NRCO, and C IO2 (Figure 2). We assume that this phenom-
enon results from the coexistence of forms 7 and 18 in
solution. The same type of spectrum is observed for 15b and
16a–d in [D6]DMSO and CD3CN (but not in CD3OD).
Addition of MsOH (Ms = methanesulfonyl; approximately
Scheme 4. Site-selective oxidation of thioalcohols 26 and 28. a) 15d
(1.0 equiv), MeSEt (1.0 equiv), DCE, reflux, 2.5 h.
Figure 2. 13C NMR spectra (d=136–180 ppm) of iodylarenes 15a, 15a+MsOH (1.0 equiv), 15e, and 16e in [D6]DMSO.
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Angewandte
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[6] a) M. Mülbaier, A. Giannis, Angew. Chem. 2001, 113, 4530;
initially formed alkoxyiodane 23 can oxidize the sulfur atom
to yield the sulfoxide functionality. To avoid this complica-
tion, MeSEt (1.0 equiv) was added to the reaction mixture
and the quantity of 15d was increased to 1.0 equivalent. This
alteration in the protocol afforded target aldehydes 27 and 29
(sole oxidation products of 26 and 28 as determined by
GCMS) in good preparative yields (Scheme 4); furthermore,
small amounts of MeSOEt were also isolated. It is notable
that oxidation of the thioalcohol 28 using DMP gives only
20% yield of the aldehyde 29.[12]
In conclusion, the design, preparation, structure, and
oxidative properties of novel N-(2-iodylphenyl)acylamides
14–17 have been described herein, and a mechanistic proposal
that accounts for the reactivity pattern of 14–17 has also been
sufficiently espoused. X-ray studies of 15e revealed a unique
pseudo-benziodoxazine structure, the first reported example
of a six-membered pseudocyclic scaffold for iodine(v), with
intramolecular secondary I···O bonding interactions. Prelimi-
nary experiments indicate that the reagents 14–17 can oxidize
alcohols and sulfides and that the reactivity largely depends
on the substitution pattern of the amide group adjacent to the
iodyl moiety. This discovery suggests that the pseudo-
benziodoxazine scaffold is a promising lead structure for the
design of new regio- and stereoselective hypervalent iodine
oxidants. Investigations into mechanistic and reactivity
aspects of 14–17, as well as the design of a polymer-supported
derivative of the described reagents is ongoing and will be
reported in due course.
Angew. Chem. Int. Ed. 2001, 40, 4393; b) G. Sorg, A. Mengel, G.
Jung, J. Rademann, Angew. Chem. 2001, 113, 4532; Angew.
Chem. Int. Ed. 2001, 40, 4395; c) N. N. Reed, M. Delgado, K.
Hereford, B. Clapham, K. D. Janda, Bioorg. Med. Chem. Lett.
2002, 12, 2047; d) Z. Lei, C. Denecker, S. Jegasothy, D. C.
Sherrington, N. K. H. Slater, A. J. Sutherland, Tetrahedron Lett.
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[7] a) D. Macikenas, E. Skrzypczak-Jankun, J. D. Protasiewicz,
Angew. Chem. 2000, 112, 2063; Angew. Chem. Int. Ed. 2000,
39, 2007; b) B. V. Meprathu, M. W. Justik, J. D. Protasiewicz,
Tetrahedron Lett. 2005, 46, 5187; c) U. H. Hirt, M. F. H. Schuster,
A. N. French, O. G. Wiest, T. Wirth, Eur. J. Org. Chem. 2001,
1569; d) U. H. Hirt, B. Spingler, T. Wirth, J. Org. Chem. 1998, 63,
7674; e) T. Wirth, U. H. Hirt, Tetrahedron: Asymmetry 1997, 8,
23; f) V.V Zhdankin, A. Y. Koposov, B. C. Netzel, N. V. Yashin,
B. P. Rempel, M. J. Ferguson, R. R. Tykwinski, Angew. Chem.
2003, 115, 2244; Angew. Chem. Int. Ed. 2003, 42, 2194; g) V.V
Zhdankin, D. N. Litvinov, A. Y. Koposov, M. J. Ferguson, R.
McDonald, R. R. Tykwinski, Chem. Commun. 2004, 106;
h) A. Y. Koposov, D. N. Litvinov, V. V. Zhdankin, Tetrahedron
Lett. 2004, 45, 2719.
[8] a) V. V. Zhdankin, A. Y. Koposov, D. N. Litvinov, M. J. Fergu-
son, R. McDonald, T. Luu, R. R. Tikwinski, J. Org. Chem. 2005,
70, 6484; b) A. Y. Koposov, V. V. Zhdankin, Synthesis 2005, 22;
c) W. J. Chung, D. K. Kim, Y. S. Lee, Tetrahedron Lett. 2003, 44,
9251.
[9] Representative procedure for the preparation of 15e: A freshly
prepared solution of 3,3-dimethyldioxirane in acetone (0.1m,
30 mL, 3.0 mmol) was added to a stirred solution of amide 11e
(0.317 g, 1.0 mmol) in CH2Cl2 (5 mL) at 08C (ice bath). The
reaction mixture was stirred for 1 h at 08C, the ice bath was
removed, and the solution was additionally stirred for 2 h at
room temperature. The solvent was removed under reduced
pressure, the remaining white solid was stirred with Et2O (5 mL)
for 15 min, filtered, washed with cold Et2O (2 ” 2.5 mL), and
dried in vacuum to afford analytically pure 15e (0.293 g, 84%) as
a snow-white solid. M.p. 1728C (decomp.); 1H NMR (300 MHz,
CD3OD): d = 8.00 (dd, 3J = 8.0 Hz, 4J = 1.5 Hz, 1H, Ar), 7.69 (td,
3J = 7.7 Hz, 4J = 1.5 Hz, 1H, Ar), 7.51–7.59 (m, 2H, Ar), 3.68 (s,
3H, CH3), 1.43 ppm (s, 9H, 3CH3); 13C NMR (75.5 MHz,
Received: August 1, 2005
Keywords: alcohols · hypervalent iodine · oxidation ·
.
regioselectivity · thiols
ꢀ
CD3OD): d = 182.0, 147.0, 144.7 (C IO2), 134.9, 128.4, 128.3,
ꢀ1
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=
127.0, 41.5, 41.0, 28.2 ppm; IR (NaCl): n˜ = 1602 (C O), 760 cm
+
=
(I O); ESI-HRMS: m/z (%) 372.0075 (23) [M+Na] , 721.0684
(100) [2M+Na]+. Refer to the Supporting Information for
additional synthetic protocols and spectral data.
[10] E. Pretsch, P. Bühlmann, C. Affolter, Structure Determination of
Organic Compounds: Tables of Spectral Data, 3rd ed., Springer,
Berlin, 2001.
[11] X-ray diffraction data were collected on Rigaku AFC-7R
diffractometer using graphite-monochromated molybdenum
Ka radiation (l = 0.71073 Š) at 293 K. Psi-scan absorption
corrections were applied to the data using TeXsan 10.3b program
(Rigaku Inc. 1997). The structure was solved by direct methods
(SIR-92) and refined by full-matrix least-squares refinement on
F2 using Crystals for Windows program. Crystal data for 15e
C12H16INO3: Mr = 349.17, tetragonal, space group I41, a = b =
14.268(2), c = 12.832(3) Š, a = b = g = 908, V= 2612.3(7) Š3,
Z = 8, m = 2.448 mmꢀ1, 1685 reflections measured, 1568 unique
(Rint = 0.10); final R1 = 0.040, Rw = 0.101. CCDC-279792 (15e)
contains the supplementary crystallographic data for this paper.
These data can be obtained free of charge from the Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
[12] G. Xu, M. Micklatcher, M. A. Silvestri, T. L. Hartman, J. Burrier,
M. C. Osterling, H. Wargo, J. A. Turpin, R. W. Buckheit, Jr., M.
Cushman, J. Med. Chem. 2001, 44, 4092.
Angew. Chem. Int. Ed. 2005, 44, 7127 –7131
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
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