The synthesis and oxidative properties of polymer-supported IBX

Article abstract of DOI:10.1002/1521-3773(20011203)40:23<4393::AID-ANIE4393>3.0.CO;2-2

Primary and secondary alcohols are oxidized smoothly under mild conditions and in high yields to the corresponding aldehydes and ketones by 1 (see scheme), the first polymer-supported IBX.

Full text of DOI:10.1002/1521-3773(20011203)40:23<4393::AID-ANIE4393>3.0.CO;2-2

COMMUNICATIONS
The Synthesis and Oxidative
Properties of Polymer-Supported
IBX
Marcel M¸lbaier and
Athanassios Giannis*
Inthe last 20 years hypervaletn iodien
reagents have enjoyed an increasing popular-
[1 6]
ity inorganic synthesis.
They canbe used
for a wide range of chemical transformations,
11]
especially as reagents for oxidations.[7
For
these purposes iodinanes such as (diacetoxy-
iodo)benzene, [bis(trifluoroacetoxy)iodo]ben-
zene, the Dess Martin periodinane (DMP),
and
1-hydroxy-1,2-benziodoxol-3(1H)-one
1-oxide (IBX, 1) are partic-
ularly suitable. The advan-
tages of these reagents are:
high efficiency, easy availa-
bility, mild reactioncodni-
Scheme 1. Synthesis of 7: a) NaNO2, H2SO4, KI, 90%; b) N,N-dimethylformamide di-tert-
butyl acetal 50%; c) NaH, BrCH2COOEt, thenNaOH; 84%; d) aminopropylsilica gel, DIC,
HOBt, 92%; e) trifluoroacetic acid (10%), thenoxoen; DIC ˆ diisopropylcarbodiimide,
HOBt ˆ 1-hydroxy-1H-benzotriazole.
tions, and (with the exception
of DMP) stability against
moisture and oxygen. Fur-
thermore, they are environmentally safe and
canbe regenerated. The combinationof these properties with
oxidation of primary alcohols to the corresponding aldehydes
no overoxidation to the carboxylic acid was detected. It is
particularly interesting that the oxidation of 4a leads to 4b
with only the primary hydroxy group oxidized, even if 7 is
added inthreefold excess. [20] We tried to oxidize menthol and
3-methyl-2-butanol with 7 to get some clues of that remark-
able selectivity. The yields of the corresponding ketones were
poor (<5%) and cannot be increased even after longer
reactiontimes (48 h). However, 2-methylcyclohexanol ( 11a)
is oxidized easily and in high yield to 2-methylcyclohexanone
(11b). The exact reasonfor this diverse reactivity is not yet
fully understood and is the subject of current investigations.
15]
the advantages of polymer-supported reagents[12
is an
attractive and worthwhile aim. Recently, we reported on the
synthesis and oxidative properties of two aminomethylpoly-
styrene-bound (diacetoxyiodo)benzene derivatives.[16] Inthe
context of these investigations we envisaged the development
of a polymer-supported IBX reagent. Here we present the
synthesis of such an IBX derivative and show that it is a
powerful oxidant with broad applicability.
The synthesis of reagent 7 was accomplished starting from
commercially available 2-amino-5-hydroxybenzoic acid (2;
Scheme 1). Treatment of compound 2 with NaNO2/H2SO4 and
excess KI afforded derivative 3, which was transformed to the
tert-butyl ester 4 using N,N-dimethylformamide di-tert-butyl
acetal.[17] Compound 5 was obtained after alkylation of the
phenolic hydroxy group with ethyl a-bromoacetate and
subsequent hydrolysis with NaOH. This linker was subse-
quently coupled to aminopropylsilica gel with DIC/HOBt to
give compound 6. Cleavage of the tert-butyl ester with
trifluoroacetic acid and oxidation with oxone[18] (potassium
peroxymonosulfate) afforded the final reagent 7.[19]
Insummary, we have discovered a powerful and versatile
[21]
oxidationsystem
which is particularly suitable for the
oxidation of alcohols to the corresponding aldehydes and
ketones under mild conditions. This method combines the
advantages of polymer-supported reagents with the advan-
tages of IBX, which is superior to the Dess Martinreagent in
terms of stability, efficiency, and versatility.[7] The reduced
form of 7 is easily separated by simple filtrationand canbe
regenerated by oxidation with oxone.[19] The products are
obtained in high purity and side reactions were not detected.
Finally our system could be suitable for the polymer-
supported synthesis of amino sugars[22] and the cyclization of
anilides.[23, 24]
Various primary and secondary alcohols can be oxidized
with 7 (Table 1). Whereas DMSO is indispensable as a solvent
inthe case of IBX, 7 also works inTHF; infact reactions
proceed faster inTHF thanDMSO. Eventhe presence of
water (1 10%) has no negative influence on the yields and
reaction times. The products are obtained with high purity and
the yields are generally high to excellent. During the
Experimental Section
7: Compound 5 (1.28 g, 3.39 mmol) was dissolved inDMF (5 mL) and
HOBt (0.57 g, 3.73 mmol) was added. This mixture was added to a
suspension of aminopropylsilica gel (3.00 g, 2.7 mmol, ꢀ0.8 mmolgÀ1
amino groups) in DMF (30 mL). Thereafter, DIC (0.52 mL, 3.39 mmol)
was added and the mixture was stirred for 16 h. Pyridine (0.11 mL,
1.35 mmol) and acetic anhydride (0.13 mL, 1.35 mmol) were then added
and the mixture was stirred again for 2 h to block any possible free amino
groups. Polymer 6 was thenfiltered, thoroughly washed with DMF and
[*] Prof. Dr. A. Giannis, M. M¸lbaier
Institut f¸r Organische Chemie
Universit‰t Karlsruhe
Richard-Willst‰tter-Allee 2, 76128 Karlsruhe (Germany)
Fax : (‡49)721-608-7652
E-mail: giannis@ochhades.chemie.uni-karlsruhe.de
Angew. Chem. Int. Ed. 2001, 40, No. 23
¹ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4023-4393 $ 17.50+.50/0
4393

COMMUNICATIONS
Table 1. Oxidationof alcohols with reagent 7.
methanol, and then dried in vacuo to constant weight. Yield 3.68 g (92%).
Derivative was suspended in mixture of dichloromethane and
6
a
Entry
Substrate
Product
Purity [%][a]
quant.[b]
trifluoroacetic acid (9:1, 30 mL) and was agitated overnight at RT. The
obtained compound was then washed thoroughly with methanol and dried
in vacuo to constant weight. A solution of oxone (5.0 g, 8.1 mmol) in water
(50 mL) was added to the dry polymer. This suspension was stirred at 708C
for 3 h. The final product 7 was filtered off, washed with water, and dried
in vacuo. To determine the activity, compound 7 (100 mg) was suspended in
THF (0.5 mL) and benzylic alcohol (6.0 mg, 0.055 mmol) added and this
suspension was agitated overnight. The activity was determined by the ratio
of starting material to product and is normally in the range of 0.3
1
2
3
97
96
0.4 mmolgÀ1
.
IR (drift): nÄ ˆ 3304, 2941, 1661(br), 1573, 1462, 1424, 1100, 950, 799 cmÀ1
;
elemental analysis (%) calcd for 7: N 1.1, C 10.8, H 0.9; found: N 0.8, C 10.1,
H 1.8.
Oxidationof alcohols: The alcohol was dissolved inTHF (5 mL/1 g
polymer) and 1.2 equivalents of polymer 7 were added. After agitating the
mixture overnight at RT, the reaction mixture was filtered and washed. The
combined organic layers were dried over Na2SO4 and the solvent was
removed invacuo. If necessary, the products were purified by flash
chromatography.
4
86[b]
Received: June 13, 2001 [Z17284]
Publicationdelayed at author×s request.
5
84[b]
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[2] A. Varvoglis, Tetrahedron 1997, 53, 1179 1255.
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1995, 60, 7272 7276.
6
7
90[b]
[8] M. Frigerio, M. Santagostino, S. Sputore, J. Org. Chem. 1996, 61,
9272 9279.
[9] M. Frigerio, M. Santagostino, Tetrahedron Lett. 1995, 35, 8019 8022.
[10] D. B. Dess, J. C. Martin, J. Org. Chem. 1983, 48, 4156 4158.
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94[b]
[13] J. Clark, D. Macquarrie, Chem. Commun. 1998, 853 860.
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669 671.
[15] A. Kirschning, H. Monenschein, R. Wittenberg, Angew. Chem. 2001,
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[17] U. Widmer, Synthesis 1983, 135 136.
8
92[b]
[18] M. Frigerio, M. Santagostino, S. Sputore, J. Org. Chem. 1999, 64,
4537 4538.
[19] No remarkable loss of activity has been noticed after compound 7 was
used four times.
9
83[b]
[20] Substrates 4a and 5a were kindly provided by Dipl.-Chem. P.
Baumhof and Dipl.-Chem. R. Mazitschek. Analytical data for 4b:
1H NMR (400 MHz, CDCl3): d ˆ 9.80 (d, J ˆ 3.1 Hz, 1H, CHO), 4.21
(d, J ˆ 3.0 Hz , 1H, CH), 3.98 3.79 (m, 5H, 2  CH2 ‡ CH), 3.41 (s,
3H, CH3), 3.04 (dd, J ˆ 11, 3 Hz, 1H, CH), 2.29 (d, J ˆ 1.6 Hz, OH),
1.97 1.85 (m, 2H, CH2), 1.62 1.50 (m, 2H, CH2); HR-MS (458C)
calcd: 216.0997, found: 216.0983.
10
80
[21] Recently, a new and efficient method for the oxidation of alcohols
with oxoammonium resins was published: S. Weik, G. Nicholson, G.
Jung, J. Rademann, Angew. Chem. 2001, 113, 1489 1492; Angew.
Chem. Int. Ed. 2001, 40, 1436 1439.
11
82
[22] K. C. Nicolaou, P. S. Baran, Y. Zhong, J. A. Vega, Angew. Chem. 2000,
112, 2625 2629; Angew. Chem. Int. Ed. 2000, 39, 2525 2529.
[23] K. C. Nicolaou, Y. Zhong, P. S. Baran, Angew. Chem. 2000, 112, 636
639; Angew. Chem. Int. Ed. 2000, 39, 622 625.
[a] Purity estimated by GC-MS. [b] Yield after flash chromatography on
silica gel.
[24] K. C. Nicolaou, Y. Zhong, P. S. Baran, Angew. Chem. 2000, 112, 639
642; Angew. Chem. Int. Ed. 2000, 39, 625 628.
4394
¹ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4023-4394 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2001, 40, No. 23