Iodoxolone-based hypervalent iodine reagents

Article abstract of DOI:10.1021/ol9014688

Image Persented The fast access to simple (Z)-3-iodo acrylic acid derivatives which can be easily oxidized to the corresponding hypervalent iodine(III) reagents is described. They can be used for various reactions with superior or similar reactivity as conventional hypervalent iodine(III) reagents.

Full text of DOI:10.1021/ol9014688

ORGANIC
LETTERS
2009
Vol. 11, No. 16
3578-3581
Iodoxolone-Based Hypervalent Iodine
Reagents
Azhar-ul-Haq A. Shah,† Zulfiqar A. Khan, Naila Choudhary, Christine Loho¨lter,
Sascha Scha¨fer, Guillaume P. L. Marie, Umar Farooq,‡ Bernhard Witulski,§ and
Thomas Wirth*
School of Chemistry, Cardiff UniVersity, Park Place,
Cardiff CF10 3AT, United Kingdom
wirth@cf.ac.uk
Received June 10, 2009
ABSTRACT
The fast access to simple (Z)-3-iodo acrylic acid derivatives which can be easily oxidized to the corresponding hypervalent iodine(III) reagents
is described. They can be used for various reactions with superior or similar reactivity as conventional hypervalent iodine(III) reagents.
The past decades have revealed the use of hypervalent iodine
compounds as very versatile and mild oxidation and oxy-
genation reagents1 replacing toxic and heavy metal-contain-
ing reagents, thus providing more environmental friendly
reaction conditions. Especially cyclic iodanes and periodanes,
such as IBA 1, IBX 2, and DMP 32 (Figure 1) are frequently
used reagents which have found wide applications in
synthesis.3 IBX 2 can mediate many useful transformations3b
Figure 1. Cyclic iodanes IBA 1, IBX 2 and DMP 3.
such as the R,ꢀ-unsaturation of carbonyl compounds,4
oxidation of benzylic methylene, and methyl groups or
cyclizations by single electron transfer-based processes.5 The
Dess-Martin periodane 3 has shown great use in selective
oxidation of alcohols to carbonyl compounds and in cascade
reactions.6
Herein we report the synthesis of new and simple
hypervalent iodine(III) reagents, which can be regarded as
simplified IBA analogues. The aryl moiety of IBA has been
replaced by a substituted double bond. The synthesis of (Z)-
3-iodo acrylic acid derivatives is straightforward and iodi-
nations of the corresponding alkyne compounds have been
performed according to literature procedures.
† Present address: Kohat University of Science and Technology, Kohat,
Pakistan.
‡ Present address: COMSATS Institute of Information Technology,
Abbottabad, Pakistan.
§ Present address: Institute of Organic Chemistry, University of Mainz,
Germany.
(1) (a) Zhdankin, V. V.; Stang, P. J. Chem. ReV. 2008, 108, 5299–5358.
(b) Zhdankin, V. V. In Science of Synthesis; Thieme: Stuttgart, Germany,
2007; Vol. 31a, pp 161-234. (c) Wirth, T. Angew. Chem., Int. Ed. 2005,
44, 3656–3665. (d) Tohma, H.; Kita, Y. AdV. Synth. Catal. 2004, 346, 111–
124. (e) HyperValent Iodine Chemistry; Wirth, T., Ed.; Springer: Berlin,
Germany, 2003. (f) Zhdankin, V. V.; Stang, P. J. Chem. ReV. 2002, 102,
2523–2584. (g) Ochiai, M. In Chemistry of HyperValent Compounds; Akiba,
K., Ed.; VCH: New York, 1999; pp 359-387. (h) Varvoglis, A. The Organic
Chemistry of Polycoordinated Iodine; VCH: New York, 1992.
(2) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155–4156.
(3) (a) Wirth, T. Angew. Chem., Int. Ed. 2001, 40, 2812–2814. (b) Wirth,
T. In Organic Synthesis Highlights; Schmalz, H.-G., Wirth, T., Eds.; Wiley-
VCH: Weinheim, Germany, 2003; Vol. V, pp 144-150. (c) Ladziata, U.;
Zhdankin, V. V. Synlett 2007, 527–537.
(5) (a) Nicolaou, K. C.; Baran, P. S.; Zhong, Y.-L.; Barluenga, S.; Hunt,
K. W.; Kranich, R.; Vega, J. A. J. Am. Chem. Soc. 2002, 124, 2233–2244.
(b) Nicolaou, K. C.; Montagnon, T.; Baran, P. S.; Zhong, Y.-L. J. Am.
Chem. Soc. 2002, 124, 2245–2258.
(6) (a) Nicolaou, K. C.; Baran, P. S.; Zhong, Y.-L.; Sugita, K. J. Am.
Chem. Soc. 2002, 124, 2212–2220. (b) Nicolaou, K. C.; Sugita, K.; Baran,
P. S.; Zhong, Y.-L. J. Am. Chem. Soc. 2002, 124, 2221–2232.
(4) Nicolaou, K. C.; Montagnon, T.; Baran, P. S. Angew. Chem., Int.
Ed. 2002, 41, 1035–1038.
10.1021/ol9014688 CCC: $40.75
Published on Web 07/17/2009
 2009 American Chemical Society

The iodination of 4 proceeded quantitatively to 5, which
was subsequently hydrolyzed to 6.7 The synthesis of 8 also
followed literature procedures.8 While 8a was obtained as a
single (Z)-stereoisomer, the addition of HI to phenylpropiolic
acid resulted in a mixture of (E)- and (Z)-isomers 8b in a
ratio of 1:4 in 75% yield (Scheme 1), which is in contrast to
conditions as shown in Scheme 2 decarboxylation occurred,
resulting in λ3-iodane 9 in good yields. After having
performed the synthesis we found that this compound has
already been described in the literature.12 A similar decar-
boxylation has been observed upon heating although a
different oxidant (chlorine) has been used. Other compounds
such as diiodomethane and diiodoethene containing two
iodine atoms could also only be oxidized at one iodine
atom.13 When diiodide 10, prepared from 7a by reaction with
iodine,14 is oxidized, no decarboxylation occurred and
hypervalent compound 11 was obtained. Further ligand
substitution resulted in the tosylate derivative 12.
Scheme 1
.
Synthesis of (Z)-3-Iodo Acrylic Acid Derivatives 6
and 8 by Iodination of Alkynes
Similar routes have been used previously by Moss et al.
for the synthesis of closely related organoiodanes, which have
been investigated as nucleophilic reagents for phosphate
cleavage reactions,15 These authors have performed mecha-
nistic investigations16 and also calculations on the iodoxolone
moiety and their results regarding angles and distances
closely match our X-ray structural data.10,17
Different oxidants can also be employed for the synthesis
of the λ3-iodane derivative 13 from precursor (Z)-8a.
Interestingly, oxidation of (Z)-8b always led to decomposi-
tion of the starting material under various reaction conditions
successful for the other substrates (NaBrO3, NaIO4, AcO2H).
Interestingly, we were also unable to oxidize the diiodo
derivative obtained by iodination of 7b under various
conditions.
the literature where it has been described that only the (Z)-
isomer was obtained in 70% yield.8 By varying the reaction
conditions 1:1 (E:Z) ratios could be obtained. The NMR data
reported were also not conclusive with other references.9
After recrystallization of the product mixture we were able
to separate the differently colored crystals of the two isomers
manually. X-ray structural analysis of (E)-8b and (Z)-8b
We have obtained X-ray analyses for some of the
hypervalent iodine compounds (9, 13).17 The angles and
distances found in the five-membered-ring system containing
the iodine(III) moiety are very similar in structures 9 and
13 and directly comparable to the X-ray structure of IBA18
or FIBA (FIBA: 3,4,5,6-F4-IBA).19 As an example, the X-ray
structure of 9 is shown in Figure 2.
10
1
allowed us to assign unambiguously the H NMR data.
The desired isomer (Z)-8b can be prepared exclusively by
the reaction of 7b with sodium iodide in acetic acid.11
The (Z)-3-iodo acrylic acid derivatives 6 and 8 were then
oxidized to λ3-iodanes by using different reagents as shown
in Scheme 2. Depending on the reagents and the reaction
(7) Hollins, R. A.; Campos, M. P. A. J. Org. Chem. 1979, 44, 3931–
3934.
(8) Abarbri, M.; Thibonnet, J.; Parrain, J.-L.; Duchene, A. Synthesis
2002, 543–551.
Scheme 2.
Synthesis of λ3-Iodanes
(9) Xu, W.; Chen, Q.-Y. J. Org. Chem. 2002, 67, 9421–9427.
(10) CCDC 718610 ((E)-8b) and CCDC 718612 ((Z)-8b) contain 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 CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax +44 1223
336033 or e-mail deposit@ccdc.cam.ac.uk).
(11) Piers, E.; Wong, T.; Coish, P. D.; Rogers, C. Can. J. Chem. 1994,
72, 1816–1819.
(12) (a) Peter, W. Justus Liebigs Ann. Chem. 1910, 369, 128–130. (b)
Willgerodt, C. In Die organischen Verbindungen mit mehrwertigem Iod;
Enke: Stuttgart, Germany, 1914; pp 257-258.
(13) (a) Thiele, J.; Haakh, H. Justus Liebigs Ann. Chem. 1910, 369,
131–147. (b) Thiele, J.; Peter, W. Justus Liebigs Ann. Chem. 1910, 369,
149–156.
(14) Langle, S.; Ngi, S. I.; Anselmi, E.; Abarbri, M.; Thibonnet, J.;
Ducheˆne, A. Synthesis 2007, 1724–1728.
(15) (a) Moss, R. A.; Wilk, B.; Krogh-Jespersen, K.; Blair, J. T.;
Westbrook, J. D. J. Am. Chem. Soc. 1989, 111, 250–258. (b) Moss, R. A.;
Bose, S.; Krogh-Jespersen, K. J. Phys. Org. Chem. 1997, 10, 27–32.
(16) Moss, R. A.; Zhang, H. J. Am. Chem. Soc. 1994, 116, 4471–4472.
(17) CCDC 718611 (9) and CCDC 718613 (13) contain the supple-
mentary 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
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax +44 1223 336033
or e-mail deposit@ccdc.cam.ac.uk).
conditions usually moderate to good yields are obtained and
different oxidants can be used for these transformations.
In case of substrate 6 we were expecting that both iodide
moieties would become oxidized, but under various reaction
(18) Shefter, E.; Wolf, W. Nature 1964, 203, 512–513.
(19) Richardson, R. D.; Zayed, J. M.; Altermann, S.; Smith, D.; Wirth,
T. Angew. Chem., Int. Ed. 2007, 46, 6529–6532.
Org. Lett., Vol. 11, No. 16, 2009
3579

with IBA 1. This might be due to the complete solubility of
the new reagents in acetone and acetonitrile as opposed to
IBA, as this reagent has only limited solubility under the
reaction conditions.
The novel reagents can also be used as stoichiometric
oxidants for the selenium-catalyzed cyclization of the
unsaturated acid 20 to butenolide 21 as shown in Scheme
4.21 It was found that the addition of trifluoroacetic anhydride
Figure 2. X-ray structure of compound 9.
Scheme 4
.
Synthesis of Lactones from Carboxylic Acid
Similarities were also found in the corresponding NMR
data.20 Upon oxidation from iodine(I) to iodine(III) the ipso-
carbon atom attached to the iodine undergoes a downfield
shift of approximately 25 ppm. The same is observed for 13
(∆δ ) 23.7 ppm), whereas the other two hypervalent
derivatives 9 and 11, which contain an additional iodine
substituent, show downfield shifts of ∆δ ) 40.5 ppm for 9
and ∆δ ) 47.7 ppm for 11 compared to their iodine(I)
counterparts. Although downfield shifts of 40-50 ppm
relative to the iodine(I) have previously been assigned to
the corresponding iodine(V) compounds, we have not formed
such derivatives as clearly shown by X-ray analysis. The
larger downfield shifts might be due to the additional
iodine substituent adjacent to the carboxylic acid moiety. The
hypervalent iodine compounds 9, 11, 12, and 13 are stable
at room temperature without exclusion of oxygen as are IBA
1, IBX 2, and DMP 3.
Derivatives 20 and 22
a The hypervalent iodine compound was prepared in situ from 6,
mCPBA, and (F3CCO)2O before addition of (PhSe)2 and 20.
Different oxidative transformations have been performed
with these new hypervalent iodine reagents. Simple oxidation
reactions such as benzyl alcohol 14 to benzaldehyde 15,
R-oxytosylations of acetophenone derivatives 16 to com-
pounds 17a and 17b, as well as the synthesis of heterocyclic
compounds such as thiadiazole 19 from thioamide 18 have
been investigated and are summarized in Scheme 3. In almost
increases their reactivity in this reaction probably via a ligand
exchange reaction to the corresponding trifluoroacetoxy
derivatives. Even an in situ generation of the hypervalent
iodine species from 6 and mCPBA was sufficient for a
successful reaction to 21 (Scheme 4, footnote a).
Oxyfunctionalizations of ketones in the R-position with
use of hypervalent iodine compounds as stoichiometric
reagents are known22svery recently a catalytic procedure
has been published.23 The iodine derivatives 6, (Z)-8a, (Z)-
8b, and 10 have been successfully used as catalysts in the
synthesis of ketolactone 23 from acid 22, and yields up to
80% have been obtained.
Scheme 3
.
Reactions with Hypervalent Iodine Compounds IBA
1, 9, 11, and 13
In conclusion, these hypervalent iodine(III) reagents are
novel oxidants for the facile oxidation of various substrates.
They are rapidly prepared from easily accessible starting
materials and offer similar reactivities to known derivatives.
Acknowledgment. We thank the Higher Education Com-
mission (HEC), Pakistan (A.A.S., Z.A.K., U.F.), and the
(20) Katritzky, A. R.; Gallos, J. K.; Durst, H. D. Magn. Reson. Chem.
1989, 27, 815–822.
(21) (a) Browne, D. M.; Niyomura, O.; Wirth, T. Org. Lett. 2007, 9,
3169–3171. (b) Browne, D. M.; Niyomura, O.; Wirth, T. Phosphorus Sulfur
2008, 183, 1026–1035.
(22) (a) Moriarty, R. M.; Vaid, R. K.; Hopkins, T. E.; Vaid, B. K.;
Prakash, O. Tetrahedron Lett. 1990, 31, 201–204. (b) Moriarty, R. M.;
Prakash, O. Org. React. 1999, 54, 273–418.
all cases the yields obtained with the new hypervalent
compounds 9, 11, and 13 are similar or better than the yields
(23) Uyanik, M.; Yasui, T.; Ishihara, K. Bioorg. Med. Chem. Lett. 2009,
19, 3848–3851.
3580
Org. Lett., Vol. 11, No. 16, 2009

Deutsche Forschungsgemeinschaft, Germany (S.S.) for fel-
lowships, Cardiff University, The Royal Society (S.S., B.W.,
T.W.), the University of Bonn, Germany (C.L.), the Ecole
Supe´rieure de Chimie Organique et Mine´rale (ESCOM),
France (N.C.), and the University of Nantes, France (G.M.)
for support and the National Mass Spectrometry Service
Centre, Swansea, for mass spectrometric data.
Supporting Information Available: Experimental pro-
cedures for the synthesis of compounds 5,6, (Z)-8a, (E)-
8b, (Z)-8b, 9, 11, 12, 13, 15, 17a, 17b, 19, 21, and 23
and spectral data for new compounds. This material is
available free of charge via the Internet at http://pubs.acs.
org.
OL9014688
Org. Lett., Vol. 11, No. 16, 2009
3581