Preparation and reactivity of 1,3,5,7-tetrakis[4-(diacetoxyiodo)phenyl] adamantane, a recyclable hypervalent iodine(III) reagent

Article abstract of DOI:10.1002/anie.200454234

A wide range of oxidative reactions are mediated by novel, nonpolymeric, and recyclable hypervalent I^III reagents (e.g. 2). In all cases, tetraiodide 1 was recovered nearly quantitatively in pure form after a simple workup. Reoxidation of 1 to

Full text of DOI:10.1002/anie.200454234

Angewandte
Chemie
Oxidations
made the marketing of polymer-supported iodine reagents
difficult; 2) the degradative loss of resin is accompanied by
benzylic oxidation of the polystyrene chain after repeated
diacetoxyiodo)phenyl]adamantane, a Recyclable use; and 3) they are much less reactive than the correspond-
Preparation and Reactivity of 1,3,5,7-Tetrakis[4-
(
Hypervalent Iodine(iii) Reagent**
ing monomeric forms owing to steric hindrance of the reactive
sites as well as their low solubility in various solvents.
Therefore, slightly vigorous conditions and/or an excess
amount of reagents are generally needed. Herein we report
the preparation and characterization of a novel, recyclable,
and nonpolymeric hypervalent iodine(iii) reagent, 1,3,5,7-
tetrakis[4-(diacetoxyiodo)phenyl] adamantane (1), and its
derivatives.
Hirofumi Tohma,* Akinobu Maruyama,
Akihisa Maeda, Tomohiro Maegawa, Toshifumi Dohi,
Motoo Shiro, Tetsuichiro Morita, and Yasuyuki Kita*
[
1]
Over the past decade, the use of hypervalent iodine reagents
has gained importance as a safe alternative to heavy-metal
reagents for performing a variety of organic transformations.
In view of recent demands for ecologically friendly chemical
processes in the agrochemical and pharmaceutical industries,
polymer-supported hypervalent iodine reagents should be a
new and useful tool as a result of their versatility, low toxicity,
high yields, simple work-up procedures, and recyclability.
As a part of our continuing research into the development
of new hypervalent iodine compounds, we planned to
synthesize an unprecedented tetrahedral I compound 1,
III
which should be a precursor to build a unique hypervalent
iodine-based supramolecular structure as well as a new
oxidizing agent. We prepared 1,3,5,7-tetrakis(4-iodophenyl)-
adamantane (2) in good yield in two steps from commercially
available 1-bromoadamantane according to a literature
[
1h,2]
[3]
Accordingly, Togo and co-workers,
Ley and co-workers,
[
4]
[6]
[7]
and we demonstrated that both poly(diacetoxyiodo)styrene
procedure. Oxidation of 2 by conventional methods with
[
5]
(
PDAIS)
and
polybis(trifluoroacetoxyiodo)styrene
peracetic acid (30% H O and acetic anhydride), sodium
2
2
(
PBTIS) exhibit reactivities similar to those of phenyliodine
perborate (NaBO ) in acetic acid, or sodium periodate
3
diacetate (PIDA) and phenyliodine bis(trifluoroacetate)
PIFA), respectively, and utilized them as environmentally
benign replacements for I reagents such as PIDA, PIFA, and
iodosyl benzene (PhIO) (Scheme 1).
(NaIO ) unexpectedly gave 1 in low yield, accompanied by
4
(
poorly soluble and unidentifiable polymeric products. After
further investigations, we finally succeeded in synthesizing 1
in 97% yield by using m-chloroperbenzoic acid (MCPBA) in
CH Cl /AcOH (1:1) under dilute conditions (Scheme 2).
III
Despite the utility and versatility of these polymer-
supported reagents, they still have several drawbacks: 1) the
2
2
III
loading efficiency of I sites is difficult to control, which has
Scheme 1. Hypervalent iodine(iii) reagents.
[
*] Dr. H. Tohma, A. Maruyama, A. Maeda, T. Maegawa, T. Dohi,
Prof. Y. Kita
Graduate School of Pharmaceutical Sciences
Osaka University
Scheme 2. Preparation of 1,3,5,7-tetrakis[4-(diacetoxyiodo)phenyl]ada-
mantane (1). Ts=tosyl=p-toluenesulfonyl.
1-6 Yamada-oka, Suita, Osaka 565-0871 (Japan)
Fax: (+81)6-6879-8229
E-mail: kita@phs.osaka-u.ac.jp
Adamantane 1 was fully characterized by single-crystal X-
[
8]
ray analysis as well as elemental and spectroscopic analysis.
Asingle crystal of 1 suitable for X-ray crystallographic
analysis was obtained through slow growth by the vapor
diffusion from CH Cl /AcOH/hexanes. Figure 1 reveals the
M. Shiro
Rigaku Corporation
3-9-12 Matsubara
Akishima, Tokyo 196-8666 (Japan)
2
2
T. Morita
geometry around the iodine in 1 to be a pentagonal-planar
arrangement of three strong (e.g. I1-C14, I1-O1, and I1-O3)
and two weak secondary (e.g. I1-O2 and I1-O4) bonds similar
to the well-known geometry of PIDA, and the unit cell
consists of a tetrahedral structure.
Group 2 Analytical Instruments Division, JEOL Ltd.
3-2-1 Musashino, Akishima, Tokyo 196-8558 (Japan)
[
**] This work was financially supported by the Industrial Technology
ResearchGrant Program from t he New Energy and Industrial
Technology Development Organization (NEDO) of Japan and by a
Grant-in-Aid for Scientific Research(S) and for Encouragement of
Young Scientists from the Ministry of Education, Science, Sports
and Culture, Japan. H.T. also thanks the Takeda Science Foundation.
III
[9]
Several I derivatives such as 1,3,5,7-tetrakis[4-bis(tri-
fluoroacetoxyiodo)phenyl]adamantane (3), 1,3,5,7-tetrakis[4-
{hydroxy(tosyloxy)iodo}phenyl]adamantane (4), and 1,3,5,7-
Angew. Chem. Int. Ed. 2004, 43, 3595 –3598
DOI: 10.1002/anie.200454234
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3595

Communications
Scheme 4. Reactivity of 1, 3, and 4. Conditions: a) l-menthol, 1
0.28 equiv), KBr, H O, room temperature, 4 h, quant. (95% recovery
(
2
of 2); b) geraniol, 1 (0.25 equiv), TEMPO (0.2 equiv), CH Cl , room
2
2
temperature, 1 h, 91% (95% recovery of 2); c) phenylacetamide, 4
0.25 equiv), CH CN, reflux, 1 h, 82% (quant. recovery of 2); d) propio-
(
3
phenone, 4 (0.25 equiv), CH CN, reflux, 3 h, 76% (98% recovery of 2);
3
e) 4-bromoveratrole, 3 (0.14 equiv), BF ·Et O, CH Cl , À408C, 3 h, 98%
3
2
2
2
(quantitative recovery of 2); f) 3,4,5-trimethoxyphenol, 1 (0.25 equiv),
MeOH, room temperature, 10 min, quant. (quant. recovery of 2);
g) methyl p-tolylsulfide, 1 (0.25 equiv), CH Cl (1% H O), reflux, 2 h,
2
2
2
Figure 1. ORTEP drawing of 1. Selected bond lengths [Š] and angles
8]: I1-C14 2.097(6), I1-O1 2.170(5), I1-O2 2.863(6), I1-O3 2.174(6), I1-
97% (quant. recovery of 2).
[
O4 2.875(5), O1-I1-C1 80.6(2), C14-I1-O3 81.9(2), O1-I1-O3 162.4(2).
conditions (except for reaction a) to afford oxidation products
in excellent yields (Scheme 4).
tetrakis[4-(4-tolyliodonium)phenyl]adamantane (5) were also
prepared from 1 by conventional procedures (Scheme 3).
[
10]
In all cases, tetraiodide 2 was recovered nearly quantita-
tively in pure form after a simple work-up (i.e. quenching the
reaction with MeOH followed by filtration or centrifugation),
and reoxidation of 2 to 1 with MCPBAalso proceeded
quantitatively without loss of activity. Next, we compared the
III
reactivity of 1 or 3 with other I reagents. As a result,
reagents 1 and 3 showed high reactivities equal to those of
PIDA, PIFA, and PhIO, as well as excellent recyclability (95–
Scheme 3. Transformation of 1 into other iodanes. Tf=trifluoro-
methanesulfonyl.
1
00%) similar to that of PDAIS (Scheme 4 and Table 1).
The high reactivity of 1 is probably caused by the
tetrahedral structure, whose reactive sites do not interfere
with each other. Furthermore, no degradation loss was
observed in the reoxidation step to 1, even after repeated
use, because 2 has no benzylic proton. The key features of
During the above study, we found that 2 is poorly soluble
in polar protic solvents, especially in MeOH. This prompted
us to develop 1 and its derivatives as new and recyclable
reagents, because 2 is generated as the reduced form after
oxidation reactions with 1. Thus, we tested several oxidative
transformations with 1, 3, and 4 to confirm the reactivity and
recyclability. Consequently, all the reactions, such as phenolic
III
these unique I reagents are highlighted as follows: 1) high
reactivity in a variety of solvents owing to their tetrahedral
structure and to their improved solubility over those of
III
conventional polymer-supported I reagents; 2) high recy-
[
4b,11]
[4a,d,12]
oxidation,
oxidation of alcohols,
oxidation of sul-
and Hofmann-type
clability without degradation loss; and 3) well-defined struc-
ture and convenient preparation, suitable for commercializa-
tion.
[
2b]
[13]
fides,
a-tosyloxylation of ketones,
[
14]
rearrangement, proceeded smoothly under homogeneous
[
a]
Table 1: Comparison of reactivities of 1 and 3 withPIDA, PIFA, P hI O, and PDAIS.
[
b]
[b]
[b]
Reaction a
Reaction e
Reaction g
quant. (1 (0.28 equiv), 4 h, RT)
quant. (PhIO (1.1 equiv), 7 h, RT)
98% (3 (0.14 equiv), 3 h, À408C)
97% (1 (0.25 equiv), 2 h, reflux)
97% (PIDA (1.0 equiv), 2 h, reflux)
83% (PDAIS (1.0 equiv), 24 h, reflux)
97% (PIFA (0.55 equiv), 1.5 h, À408C)
[
c]
8
6% (PDAIS (1.1 equiv), 20 h, RT)
58% (PDAIS (0.55 equiv), 24 h, RT)
[
[
a] See Scheme 4: reaction a: oxidation of l-menthol, reaction e: biaryl coupling of 4-bromoveratrole, reaction g: oxidation of methyl p-tolyl sulfide.
b] Yield (reagent (equiv), time, temperature). [c] No reaction at À408C.
3
596
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Angew. Chem. Int. Ed. 2004, 43, 3595 –3598

Angewandte
Chemie
In conclusion, we have developed novel, nonpolymeric,
and recyclable hypervalent iodine(iii) reagents. These
reagents show promise as useful and safe tools for a wide
range of pharmaceutical and agrochemical research, as they
are highly reactivity and recyclable. Application of 1 and
related compounds to the construction of supramolecular
structures as well as in oxidation reactions is now underway.
[4] a) H. Tohma, S. Takizawa, T. Maegawa, Y. Kita, Angew.Chem.
2000, 112, 1364 – 1368; Angew.Chem.Int.Ed. 2000, 39, 1306 –
1308; b) H. Tohma, H. Morioka, S. Takizawa, M. Arisawa, Y.
Kita, Tetrahedron 2001, 57, 345 – 352; c) H. Tohma, H. Morioka,
Y. Harayama, M. Hashizume, Y. Kita, Tetrahedron Lett. 2001, 42,
6899 – 6902; d) H. Tohma, T. Maegawa, S. Takizawa, Y. Kita,
Adv.Synth.Catal. 2002, 344, 328 – 337; e) H. Tohma, T.
Maegawa, Y. Kita, ARKIVOC 2003, VI, 62 – 70; f) H. Tohma,
T. Maegawa, Y. Kita, Synlett 2003, 723 – 725.
[
5] a) M. Okawara, K. Mizuta, Kogyo Kagaku Zasshi 1961, 64, 232 –
235; b) Y. Yamada, M. Okawara, Makromol.Chem. 1972, 152,
Experimental Section
1
53 – 162; c) H. K. Livingston, J. W. Sullivan, J. I. Musher, J.
Polym.Sci.Part C 1968, 195 – 202; d) M. L. Hallensleben,
Angew.Makromol.Chem. 1972, 27, 223 – 227.
MCPBA(3.12 g, 18 mmol) was added to a stirred solution of
2
(
1.416 g, 1.5 mmol) in CH Cl (150 mL) and AcOH (150 mL) at room
2 2
temperature. The mixture was stirred for 12 h under the same
reaction conditions. The resultant mixture was filtered, and CH Cl
was removed from the filtrate by using a rotary evaporator. Hexanes
were added to the residue to precipitate 1. After filtration, crude 1
was washed with hexanes several times, and was dried in vacuo to give
[6] a) H. Newman, Synthesis 1972, 692 – 693; b) E. B. Merkushev,
N. D. Simakhina, G. M. Koveshnikova, Synthesis 1980, 486 – 487;
c) V. R. Reichert, L. J. Mathias, Macromolecules 1994, 27, 7015 –
7023; d) L. J. Mathias, V. R. Reichert, A. V. G. Muir, Chem.
Mater. 1993, 5, 4 – 5.
[7] a) J. G. Sharefkin, H. Saltzman, Org.Synth.Coll. 1973, 5, 660 –
662; b) A. McKillop, D. Kemp, Tetrahedron 1989, 45, 3299 –
3306; c) P. Kazmierski, L. Skulski, Synthesis 1998, 1721 – 1723.
[8] Crystal data for 1 (C H I O ): M = 1452.60, monoclinic, C2/c
2
2
1
(2.07 g, 97%), colorless crystal; m.p. (decomp.) 195–1968C (from
1
AcOH-CH Cl -hexanes by vapor diffusion method); H NMR
2
2
3
(
300 MHz, CDCl , 258C, TMS): d = 8.09 (d, J(H,H) = 8.7 Hz, 8H;
3
3
ArH), 7.56 (d, J(H,H) = 8.7 Hz, 8H; ArH), 2.20 (s, 12H; AdH),
1
3
2
.01 ppm (s, 24H; OCOCH ); C NMR (75 Hz, CDCl , 258C, TMS):
3
3
50 56
4
18
w
d = 176.5, 151.9, 135.2, 127.7, 119.5, 46.4, 39.6, 20.4 ppm; elemental
(no. 15), a = 24.11(1), b = 17.011(9), c = 33.45(2) Š, b = 91.57(4),
analysis: calcd for C H I O ·2H O: C 41.34, H 3.89, I 34.95; found:
3
À3
5
0
52
4
16
2
V= 13711(11) Š , Z = 8, T= 90 K, 1
radiation, m = 18.74 cm
0
0
corrected reflections [(I > 3.00s(I)), 2q = 60.1], 700 parameters.
CCDC 232058 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cam-
bridge Crystallographic Data Centre, 12, Union Road, Cam-
bridge CB21EZ, UK; fax: (+ 44)1223-336-033; or deposit@
ccdc.cam.ac.uk).
= 1.407 gcm , MoKa
calcd
C 41.30, H 3.70, I 35.03.
Typical Oxidation Procedure: Adamantane
.25 mmol) was added to a stirred solution of 3,4,5-trimethoxyphenol
184.2 mg, 1.0 mmol) in MeOH (5 mL) at room temperature. The
À1
,
colorless block 0.30 ” 0.15 ”
1
(354.2 mg,
3
2
.05 mm ; 78690 measured reflections, F refinement, R =
1
0
(
.067, wR = 0.183, 19969 independent observed absorption-
2
mixture was stirred for 10 min. MeOH (10 mL) was then added to the
reaction mixture, and the mixture was filtered. The residue was
washed with MeOH several times, and the residue was recovered as
pure 2 quantitatively. The filtrate was then centrifuged. The super-
natant liquid was evaporated in vacuo to give 3,4,4,5-tetramethoxy-
[
15]
cyclohexa-2,5-dienone quantitatively.
1
[
9] 3: m.p. (decomp.) 196–2038C (from CH Cl /hexanes); H NMR
2
2
Received: March 11, 2004 [Z54234]
(
300 MHz, CDCl /CF CO H (10:1), 258C, TMS): d = 8.24 (d,
3 3 2
3
3
J(H,H) = 8.7 Hz, 8H; ArH), 7.73 (d, J(H,H) = 8.7 Hz, 8H;
1
9
Keywords: green chemistry · hypervalent compounds · iodine ·
ArH), 2.30 ppm (s, 12H; AdH); F NMR (200 MHz, CDCl3/
.
oxidation · synthetic methods
CF CO H (10:1), 258C, hexafluorobenzene (À162.9 ppm)): d =
3
2
À74.51 ppm (s, 24F; OCOCF ); elemental analysis: calcd for
3
C H F I O : C 32.49, H 1.53; found: C 32.82, H 1.86. 4: m.p.
5
0
28 24
4
16
1
(decomp.) 183–1908C; H NMR (300 MHz, CDCl /CF CO H
3 3 2
3
(10:1), 258C, TMS): d = 8.25 (d, J(H,H) = 8.9 Hz, 8H; ArH),
[
1] For recent reviews, see: a) P. J. Stang, V. V. Zhdankin, Chem.
Rev. 1996, 96, 1123 – 1178; b) Y. Kita, T. Takada, H. Tohma, Pure
Appl.Chem. 1996, 68, 627 – 630; c) A. Varvoglis, Hypervalent
Iodine in Organic Synthesis, Academic Press, San Diego, 997;
3
3
7
8
.70 (d, J(H,H) = 8.9 Hz, 8H; ArH), 7.65 (d, J(H,H) = 8.4 Hz,
3
H; ArH), 7.26 (d, J(H,H) = 8.1 Hz, 8H; ArH), 2.38 (s, 12H;
1
3
ArCH ), 2.26 ppm (s, 12H; AdH); C NMR (75 Hz, CDCl3/
CF CO H (10:1), 258C, TMS): d = 154.2, 144.5, 135.9, 135.1,
1
analysis: calcd for C H I O S ·4H O: C 42.09, H 3.87, I
2
3
3
2
d) T. Kitamura, Y. Fujiwara, Org.Prep.Proced.Int.
09 – 458; e) M. Ochiai in Chemistry in Hypervalent Compounds
Ed.: K. Akiba), Wiley-VCH, New York, 1999, chap. 12; f) T.
1997, 29,
29.8, 129.0, 126.3, 121.1, 45.8, 39.9, 21.4 ppm; elemental
4
(
6
2
60
4
16
4
2
8.69, S 7.25; found: C 42.03, H 3.64, I 28.32, S 7.25. 5: m.p.
Wirth, U. H. Hirt, Synthesis 1999, 1271 – 1287; g) V. V. Zhdankin,
P. J. Stang, Chem.Rev. 2002, 102, 2523 – 2584; h) H. Togo, K.
Sakuratani, Synlett 2002, 1966 – 1975; i) Hypervalent Iodine
Chemistry (Ed.: T. Wirth), Springer, Berlin, 2003.
1
(decomp.) 186–1908C; H NMR (270 MHz, CD CN, 258C,
3
3
TMS): d = 8.00 (d, J(H,H) = 8.6 Hz, 8H; ArH), 7.94 (d,
3
3
J(H,H) = 8.4 Hz, 8H; ArH), 7.62 (d, J(H,H) = 8.6 Hz, 8H;
3
ArH), 7.32 (d, J(H,H) = 8.1 Hz, 8H; ArH), 2.37 (s, 12H;
ArCH ), 2.04 ppm (s, 12H; AdH); C NMR (67.8 Hz, CD CN,
2
1
[
2] a) H. Togo, G. Nogami, M. Yokoyama, Synlett 1998, 534 – 536;
b) H. Togo, S. Abe, G. Nogami, M. Yokoyama, Bull.Chem.Soc.
Jpn. 1999, 72, 2351 – 2356; c) S. Abe, K. Sakuratani, H. Togo, J.
Org.Chem. 2001, 66, 6174 – 6177; d) H. Togo, K. Sakuratani,
Synthesis 2003, 21 – 23.
1
3
3
3
58C, TMS): d = 154.6, 145.1, 136.2, 136.1, 133.8, 130.3, 124.0,
12.0, 110.9, 45.8, 40.6, 21.4 ppm; High-resolution cold-spray
ionization
(CSI-MS;
CH CN):
m/z = 1755.88990
3
+
+
(
C H F I O S ) [(MÀOTf) ].
[
3] a) S. V. Ley, A. W. Thomas, H. Finch, J.Chem.Soc.Perkin Trans.
65 56
9
4
9 3
1
1999, 669 – 671; b) S. V. Ley, O. Schucht, A. W. Thomas, P. J.
[10] For the preparation of 3, see: a) J. Gallos, A. Varvoglis, N. W.
Alcock, J.Chem.Soc.Perkin Trans.1 1985, 757 – 763; for the
Murray, J.Chem.Soc.Perkin Trans.1 1999, 1251 – 1252; c) I. R.
Baxendale, S. V. Ley, C. Piutti, Angew.Chem. 2002, 114, 2298 –
preparation of 4, see: b) G. F. Koser, A. G. Relenyi, A. N. Kalos,
L. Rebrovic, R. H. Wettach, J.Org.Chem. 1982, 47, 2487 – 2489;
for the preparation of 5, see: c) T. Kitamura, J. Matsuyuki, H.
Taniguchi, Synthesis 1994, 147 – 148.
2
301; Angew.Chem.Int.Ed.
Baxendale, A.-L. Lee, S. V. Ley, J.Chem.Soc.Perkin Trans.1
002, 1850 – 1857.
2002, 41, 2194 – 2197; d) I. R.
2
Angew. Chem. Int. Ed. 2004, 43, 3595 –3598
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3597

Communications
[
11] Y. Tamura, T. Yakura, J. Haruta, Y. Kita, J.Org.Chem. 1987, 52,
927 – 3930.
3
[
12] A. De Mico, R. Margarita, L. Parlanti, A. Vescovi, G. Piancatelli,
J.Org.Chem. 1997, 62, 6974 – 6977.
[
[
[
13] S. Abe, K. Sakuratani, H. Togo, Synlett 2001, 22 – 24.
14] I. M. Lazbin, G. F. Koser, J.Org.Chem. 1986, 51, 2669 – 2671.
1
15] M.p. 122–1238C (from AcOH/hexanes); H NMR (300 MHz,
CDCl , 258C, TMS): d = 5.59 (s, 2H; 2-H, 6-H), 3.78 (s, 6H; 3-, 5-
3
C-OMe), 3.25 ppm (s, 6H; 4-C-(OMe) ); elemental analysis:
2
calcd for C H O : C 56.07, H 6.59; Found: C 55.74, H 6.58.
1
0
14
5
3
598
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Angew. Chem. Int. Ed. 2004, 43, 3595 –3598