Iodomethane oxidation by dimethyldioxirane: A new route to hypoiodous acid and iodohydrines

Article abstract of DOI:10.1021/ol9903281

matrix presented The oxidation of iodomethane with dimethyldioxirane allows the generation of stable neutral solutions of hypoiodous acid in the absence of any trapping agent for iodide anion. Hypoiodous acid is trapped in situ by addition to representative olefins to give iodohydrines in good yields. The stereochemical study of the products shows the anti-stereospecific nature of the iodohydroxylation reaction.

Full text of DOI:10.1021/ol9903281

ORGANIC
LETTERS
1999
Vol. 1, No. 13
2125-2128
Iodomethane Oxidation by
Dimethyldioxirane: A New Route to
Hypoiodous Acid and Iodohydrines
Gregorio Asensio,* Cecilia Andreu, Carmen Boix-Bernardini, Rossella Mello, and
Mar´ıa Elena Gonza´lez-Nun˜ez
Departamento de Qu´ımica Orga´nica, Facultad de Farmacia, UniVersidad de Valencia,
AVda. Vicente Andre´s Estelle´s s/n, 46100-Burjassot (Valencia), Spain
gregorio.asensio@uV.es
Received October 22, 1999
ABSTRACT
The oxidation of iodomethane with dimethyldioxirane allows the generation of stable neutral solutions of hypoiodous acid in the absence of
any trapping agent for iodide anion. Hypoiodous acid is trapped in situ by addition to representative olefins to give iodohydrines in good
yields. The stereochemical study of the products shows the anti-stereospecific nature of the iodohydroxylation reaction.
The oxidation of alkyl iodides1,2 occurs with the formation
of iodoso compounds. Polyvalent iodine derivatives with
alkyl substituents at iodine are generally highly unstable and
can exist only as short-lived reactive intermediates in the
oxidation of alkyl iodides with peracids. These compounds,
despite their lack of stability, have found several synthetic
applications.2 In the course of our continuing work on the
reactivity of functional groups toward dioxiranes,3 we
determined to study the oxidation of alkyl iodides with
dimethyldioxirane (DMDO) (2) with the aim, at first, of
obtaining iodoso compounds under mild conditions that could
be stable compounds in the reaction medium. Recently,
Minisci et al.,4 in a search for evidence of radical intermedi-
ates in oxidations with DMDO, reported the formation of
2-iodocyclohexanol in the DMDO oxidation of cyclohexyl
iodide. This reaction illustrates the expected chemistry of
secondary alkyl iodoso compounds,1,2 i.e., the intramolecular
elimination of hypoiodous acid, which then adds to the olefin
generated in the elimination step. Iodohydrines are interesting
synthetic intermediates whose preparation has been the
subject of several recent reports.5 In contrast with their
homologous chloro- and bromohydrines, they cannot be
prepared by the direct reaction of olefins with water solutions
of the halogen, since the iodide anion generated in this
(1) (a) Macdonald, T. L.; Narasimhan, N.; Burka, L. T. J. Am. Chem.
Soc. 1980, 102, 7760. (b) Cambie, R. C.; Chambers, D.; Lindsay, B. G.;
Rutledge, P. S.; Woodgate, P. D. J. Chem. Soc., Perkin Trans. 1 1980,
822. (c) Cambie, R. C.; Lindsay, B. G.; Rutledge, P. S.; Woodgate, P. D.
J. Chem. Soc., Chem. Commun. 1978, 919. (d) Reich, H. J.; Peake, S. L. J.
Am. Chem. Soc. 1978, 100, 4888. (e) Ogata, Y.; Aoki, K. J. Org. Chem.
1969, 34, 3974, 3978.
(2) (a) Kim, S.; Fuchs, P. L. Tetrahedron Lett. 1994, 35, 7163. (b) Lee,
J.; Oh, J.; Jin, S.; Choi, J.; Atwood, J. L.; Cha, J. K. J. Org. Chem. 1994,
59, 6955. (c) Knapp, S.; Naughton, A. B. J.; Dhar, T. G. M. Tetrahedron
Lett. 1992, 33, 1025. (d) Guivisdalsky, P. N.; Bittman, R. J. Org. Chem.
1989, 54, 4637. (e) Sicinski, R. R.; Szczepek, W. J. Tetrahedron Lett. 1987,
28, 5729. (f) Eaton, P. E.; Cunkle, G. T. Tetrahedron Lett. 1986, 27, 6055.
(g) Zefirov, N. S.; Zhdankin, V. V.; Makhon’kova, G. V.; Dan’kov, Y. V.;
Koz’min, A. S. J. Org. Chem. 1985, 50, 1872. (h) Yamamoto, S.; Itani, H.;
Tsuji, T.; Nagata, W. J. Am. Chem. Soc. 1983, 105, 2908. (i) Davidson, R.
L.; Kropp, P. J. J. Org. Chem. 1982, 47, 1904. (j) Greenhouse, R.;
Muchowski, J. M. Can. J. Chem. 1981, 59, 1025. (k) Beeley, N. R. A.;
Sutherlan, J. K. J. Chem. Soc., Chem. Commun. 1977, 321.
(3) (a) Asensio, G.; Castellano, G.; Mello, R.; Gonza´lez-Nun˜ez, M. E.
J. Org. Chem. 1996, 61, 5564. (b) Asensio, G.; Mello, R.; Gonza´lez-Nun˜ez,
M. E.; Castellano, G.; Corral, J. Angew. Chem., Int. Ed. Engl. 1996, 35,
217. (c) Asensio, G.; Mello, R.; Gonza´lez-Nun˜ez, M. E. Tetrahedron Lett.
1996, 37, 2299. (d) Asensio, G.; Mello, R.; Boix-Bernardini, C.; Gonza´lez-
Nun˜ez, M. E.; Castellano, G. J. Org. Chem. 1995, 60, 3692. (e) Asensio,
G.; Gonza´lez-Nun˜ez, M. E.; Boix-Bernardini, C.; Mello, R.; Adam, W. J.
Am. Chem Soc. 1993, 115, 7250.
(4) (a) Bravo, A.; Fontana, F.; Fronza, G.; Minisci, F.; Zhao, L. J. Org.
Chem. 1998, 63, 254. (b) Bravo, A.; Fontana, F.; Fronza, G.; Minisci, F.;
Serri, A. Tetrahedron Lett. 1995, 36, 6945.
10.1021/ol9903281 CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/03/1999

process itself reacts with iodine or the intermediate iodonium
ion to give the I3 anion or iodine, respectively. For this
in the deep-orange solution (eq 2) and responsible for the
R-iodination of acetone (eq 3). In fact, some synthetic
applications of hypervalent iodine derivatives6 are based on
the leaving group ability of the hypervalent iodine moiety.
On the other hand, hypoiodous acid has been reported to be
an unstable species which undergoes dismutation to iodine
and oxygen under acidic conditions.7 In addition, iodoso
derivatives show a clear tendency to form polymeric materi-
als in which each iodine atom is coordinated to two oxygen
atoms. An example of these structures is amorphous io-
dosobenzene.8 All of these processes would account for the
yellow iodine solution and the solid with oxidizing properties
obtained in the last step of the oxidation of iodomethane
described above (eq 3). Dismutation of hypoiodous acid to
iodide and iodate ions can be disregarded under our condi-
tions, provided that it only takes place in basic medium.
To determine unequivocally that hypoiodous acid can be
readily generated in a synthetically useful form by DMDO
oxidation of sacrificial iodomethane, we performed the in
situ trapping of 4 with a series of representative alkenes 5,
which afforded the expected iodohydrines 69 (see Scheme
2). This process represents the first practical example of the
preparation of hypoiodous acid from an iodine source other
than molecular iodine and its application to the synthesis of
iodohydrines by direct electrophilic addition to CdC double
bonds. The electrophilic character of the iodination process
was ascertained by measuring the corresponding rate con-
stants in competition experiments between styrene and para-
substituted styrenes. The F value found for the reaction
(-5.65) shows that the reagent is highly sensitive to the
effects of substituents. The regioselectivity of the iodo-
hydroxylation shows that the hydroxy group is bonded to
the carbon atom which better supports the positive charge
density in the iodonium intermediate (I), with the only
exception being the reaction with allylbenzene (5d) in which
the iodonium ring opens in part due to nucleophilic attack
of the less hindered terminus (see Scheme 2). Epoxidation
of the alkene by iodosomethane was not observed in any of
the cases.
-
reason, all known methods for the generation of electrophilic
iodine species require the presence of a trapping agent for
iodide anion, whether by precipitation with mercury(II) salts5l
or oxidation with Fe(III),5d Cu(II),5f or Ce(IV)5e salts, CrO3/
pyridine,5b and others.5
In this Letter, we report the DMDO (2) oxidation of
iodomethane (1) to iodosomethane (3) and its further
decomposition in solution to hypoiodous acid (4) which is
trapped by addition to representative olefins (5) to give
iodohydrines (6) in good yields.
The oxidation was performed by mixing acetone solutions
of DMDO and iodomethane at -70 °C. Under these
conditions, a pale yellow precipitate thought to be iodoso-
methane was formed. Unfortunately, this precipitate, although
stable in suspension at -70 °C, is very difficult to handle,
and decomposed in all attempts at isolation for spectroscopic
characterization. Upon raising the temperature of the suspen-
sion to -40 °C, the yellow solid gave rise first to a deep-
orange solution and finally, when allowed to warm to room
temperature, to a yellow solution, a new precipitate and
1-iodopropanone, as determined by GC-MS analysis. The
final pH of the solution was neutral or slightly acidic. The
UV spectrum of the latter yellow solution was identical to
that of a solution of iodine in acetone. The latter solid was
isolated and exhibited oxidant behavior toward an acid
solution of potassium iodide but was unstable, decomposed
to give iodine, and could not be further characterized.
These observations can be explained by considering an
initial oxygen transfer process from DMDO to iodomethane
to generate iodosomethane, which is stable and insoluble in
acetone at -70 °C (Scheme 1, eq 1), becomes soluble at
Scheme 1
Regarding the stereochemistry of this process (see Figure
1), the iodohydroxylation of trans-3-nonene (5c) followed
(6) (a) Ochiai, M. In Chemistry of HyperValent Compounds; Kin-ya
Akiba, Ed.; Wiley-VCH: Weinheim, 1999; pp 359-387. (b) Stang, P. J.;
Zhdankin, V. V. Chem. ReV. 1996, 96, 1123. (c) Stang, P. J. Angew. Chem.,
Int. Ed. Engl. 1992, 31, 274.
(7) Cotton, F. A.; Wilkinson, G.; Murillo, C. A.; Bochmann, M. AdVanced
Inorganic Chemistry, 6th ed.; John Wiley & Sons: New York, 1999.
(8) Carmalt, C. J.; Crossley, J. G.; Knight, J. G.; Lightfoot, P.; Martin,
A.; Muldowney, M. P.; Norman, N. C.; Orpen, A. G. J. Chem. Soc., Chem.
Commun. 1994, 2367.
-40 °C, and undergoes nucleophilic substitution by water
in the medium to give hypoiodous acid, which was present
(5) (a) Cornforth, J. W.; Green, D. T. J. Chem. Soc. C 1970, 846. (b)
Antonioletti, R.; D’Auria, M.; De Mico, A.; Piancatelli, G.; Scettri, A.
Tetrahedron 1983, 39, 1765. (c) Cambie, R. C.; Noall, W. I.; Potter, G. J.;
Rutledge, P. S.; Woodgate, P. D. J. Chem. Soc., Perkin Trans. 1 1977,
226. (d) deMattos, M. C. S.; Sanseverino, A. M. J. Chem. Res., Synop.
1994, 440. (e) Horiuchi, C. A.; Ikeda, A.; Kanamori, M.; Hosokawa, H.;
Sugiyama, T.; Takahashi, T. J. Chem. Res., Synop. 1996, 60. (f) Barluenga,
J.; Rodr´ıguez, M. A.; Campos, P. J.; Asensio, G. J. Chem. Soc., Chem.
Commun. 1987, 1491. (g) Georgoulis, C.; Valery, J. M. Synthesis 1978,
402. (h) Rozen, S.; Brand, M. J. Org. Chem. 1985, 50, 3342. (i) Jalai-
Naini, M.; Lallemand, J. Y. Tetrahedron Lett. 1986, 27, 497. (j) Acton, E.
M.; Ryan, K. J.; Tracy, M.; Arora, S. K. Tetrahedron Lett. 1986, 27, 4245.
(k) Naz, N.; Al-Tel, T. H.; Al Abed, Y.; Voelter, W. J. Org. Chem. 1996,
61, 3250. (l) Barluenga, J.; Gonza´lez, J. M.; Campos, P. J.; Asensio, G.
Angew. Chem., Int. Ed. Engl. 1984, 24, 319.
(9) Preparation of Iodohydrines. Typical Experimental Procedure.
To a solution of iodomethane (1) (1.19 mmol, 0.75 mL) in acetone cooled
to -70 °C was added an aliquot of a DMDO (2) acetone solution (1.13
mmol) with stirring. After a few seconds the formation of a white solid
was observed. The mixture was allowed to stand for 1 h, and then the olefin
5 (0.56 mmol) in 2 mL of acetone was added at once. The resulting mixture
was then allowed to warm slowly (20 h) to reach room temperature. The
solvent was removed under vacuum and the residue redissolved in CH2Cl2
(20 mL). The solution was washed with aqueous Na2S2O3 (1 N, 2 × 15
mL) and distilled water (1 × 15 mL). The organic layer was dried over
anhydrous MgSO4 and the solvent removed under vacuum. GC-MS analysis
of the reaction mixture showed in most cases the nearly total conversion of
5 into the expected iodohydrine 6 and the presence of variable amounts of
2-iodopropanone. Products were purified by column chromatography (silica,
hexane:ethyl acetate 95:5).
2126
Org. Lett., Vol. 1, No. 13, 1999

Scheme 2. Synthesis of Iodohydrines (6) from Olefins (5) by Electrophilic Addition of IOH (4) Generated by Oxidation of
Iodomethane (1) with DMDO (2)a
a Molar ratio iodomethane:DMDO:5 2:2:1. b Products were isolated by column chromatography. c 1:1 mixture of two regioisomers. d 65:
35 mixture of two regioisomers. e Iodohydrine could not be isolated in this case.
by treatment with base (potassium carbonate, dichlo-
romethane) yielded quantitatively a single (()-trans-epoxide
(7c) that was identified by comparison with the product
obtained by direct syn-stereospecific epoxidation of 5c with
DMDO (2). This observation shows the anti-stereospecific
nature of the iodohydroxylation reaction. This is also revealed
in the stereospecific transformation of cyclohexene (5a) into
(()-trans-2-iodocyclohexanol (6a) under our conditions (see
Scheme 2) and indicates the participation of cyclic iodonium
ion intermediate 8a. The addition of IOH (4) to norbornene
(5l) took place with rearrangement of the intermediate cyclic
iodonium ion intermediate 8l to give 6l. In this case, the
presence of small amounts of 3-cyclohexencarbaldehyde (9l)
was also observed. In general, steric congestion and an
enhanced tendency for ionization of the C-I bond appear
to decrease the stability of iodohydrines, and for this reason
the reaction of IOH (4) with tetramethylethylene (5m) and
cis-stilbene (5n) led exclusively to the formation of the
corresponding epoxide (7m) and diphenylacetaldehyde (9n),
respectively. This latter compound is most probably derived
from a simple pinacol type rearrangement of the correspond-
ing iodohydrine or, alternatively, by rearrangement of the
epoxide 7n formed by nucleophilic displacement of iodide
ion by the anti-hydroxy group in the precursor iodohydrine
6n.
The synthesis of iodohydrines described here represents
a new strategy for these compounds with the added merit
and novelty of generating stable IOH neutral solutions based
on the quantitative and stoichiometric DMDO oxidation of
sacrificial iodomethane to iodosomethane at low temperature,
and hence without the involvement of any trapping reagent
for iodide ion. The scope of this new and general synthesis
of iodohydrines is somewhat limited by the inherent lack of
stability of some of these compounds that undergo anchi-
merically assisted displacement of iodide ion by the neigh-
boring hydroxy group to afford the epoxide. Work is in
progress to identify new applications for the stable IOH
solutions that are now available by this synthesis.
Figure 1.
Org. Lett., Vol. 1, No. 13, 1999
2127

Acknowledgment. This work was supported by the
Spanish Direccio´n General de Investigacio´n Cient´ıfica y
Te´cnica (PB96-0757). C.B.B. thanks the Spanish Ministerio
de Educacio´n y Ciencia, and C. A. thanks the Conseller´ıa
de Cultura de la Generalitat Valenciana for fellowships. We
gratefully acknowledge the Servicio Central de Soporte a la
Investigacio´n Experimental (Universidad de Valencia) for
access to their instrumental facilities.
Supporting Information Available: Experimental details
for the preparation of IOH (4) and iodohydrines 6, structural
information, NMR and HRMS spectral data for compounds
6. This material is available free of charge via the Internet
at http:/pubs.acs.org
OL9903281
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