Iodohydroxylation of alkenes promoted by molecular and hypervalent(III) iodine

Article abstract of DOI:10.1016/S0040-4039(01)01509-X

Several iodohydrins are isolated in good yields starting from the corresponding alkenes and a mixture of molecular iodine and phenyliodine(III)bis(trifluoroacetate) (BTI), in CH₃CN-H₂O as solvent, at -15°C. Hypoiodous acid is added to the terminal carbon-carbon double bond in a Markovnikov fashion. Moreover, the stereochemical features of the products show the anti-stereospecificity of the addition.

Full text of DOI:10.1016/S0040-4039(01)01509-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7245–7247
Iodohydroxylation of alkenes promoted by molecular and
hypervalent(III) iodine
Anna Rita De Corso, Barbara Panunzi and Marco Tingoli*
Dipartimento di Scienza degli Alimenti, Universita` di Napoli ‘Federico II’, I-80055 Portici (NA), Italy
Received 26 July 2001; revised 19 August 2001; accepted 20 August 2001
Abstract—Several iodohydrins are isolated in good yields starting from the corresponding alkenes and a mixture of molecular
iodine and phenyliodine(III)bis(trifluoroacetate) (BTI), in CH3CN–H2O as solvent, at −15°C. Hypoiodous acid is added to the
terminal carbonꢀcarbon double bond in a Markovnikov fashion. Moreover, the stereochemical features of the products show the
anti-stereospecificity of the addition. © 2001 Elsevier Science Ltd. All rights reserved.
The reaction of hypoiodous acid with alkenes is usually
difficult to achieve due to the ready reversibility of IOH
addition to carbonꢀcarbon double bonds. For this rea-
son, in contrast with bromo- and chlorohydrins, iodo-
hydrins are not obtained by the direct treatment of
alkenes with iodine in water.1 Several contributions to
solve this problem appeared in the last few years in the
literature. One of these is based on the in situ genera-
tion of IOH from the direct reduction of periodic acid
(HIO4·2H2O) with sodium bisulphate (NaHSO3).2
Alternatively, a stable neutral solution of hypoiodous
acid, obtained from the dimethyldioxirane oxidation of
iodomethane, is trapped by a series of alkenes that are
readily transformed into the corresponding iodohy-
drins.3 More recently, N-iodosuccinimide, employed in
a mixture of H2O–DME, was reported to act as a
useful electrophilic iodinating agent, being able to
transform in very mild conditions both electron-rich
and electron-poor olefins into iodohydrins.4
formed into the hydroxyphenyl selenenylated com-
pounds in a Markovnikov fashion.6 In the light of these
observations and with the aim to generate an efficient
electrophilic iodinated agent in situ, we have tried to
apply the same experimental conditions described
above to an iodine-containing solution of CH3CN. The
first substrate allowed to react was styrene, treated with
0.6 molar equiv. of I2 followed by 0.7–1.0 molar equiv.
of BTI in 15 ml of anhydrous CH3CN at −15°C. In a
few minutes the complete disappearance of the dark
red–brown colour was observed. The reaction mixture
was allowed to warm up to room temperature and,
after a simple work-up, the corresponding 2-phenyl-2-
hydroxy-1-iodoethane, isolated and fully characterised
as the acetate derivative, was recovered in 89% overall
yield.
This result prompted us to apply our methodology to
different alkenes but unfortunately only unstable iodi-
nated products were isolated from any reaction mix-
tures, which spontaneously liberate I2 after the
evaporation of the extraction solvent.
The ability of iodine(III) species to oxidise a chalco-
genate-type derivative as diphenyl diselenide was exten-
sively studied and applied to the preparation of several
oxy-selenenylated products.5 More recently, we have
observed in our laboratory that the commercially avail-
able phenyliodine(III)bis(trifluoroacetate) (BTI) is able
to promote, at −15°C, the complete decolouration of a
yellow–orange solution containing both the alkene and
diphenyldiselenide in anhydrous CH3CN. Using this
treatment, several phenylethene derivatives were trans-
In the case of styrene, the ligand transfer to the benzylic
position is probably the fastest reaction process. In all
the other cases, the halogen competes with the poor
nucleophilic character of the trifluoroacetate anion.
The participation of water in electrophilic halogenation
reaction of alkenes is one of the most thoroughly
studied classes of cohalogenation.1 So we found that
also in our case the addition of water to CH3CN forces
the halonium ion intermediate to incorporate OH
instead of the iodine anion.7
* Corresponding author. Tel.: +0039-817754903; fax: +0039-
817754942; e-mail: tingoli@unina.it
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01509-X

7246
A. R. De Corso et al. / Tetrahedron Letters 42 (2001) 7245–7247
Indeed, a 4:1 mixture of CH3CN–H2O is an optimum
choice to transform different classes of olefins into the
corresponding iodohydrins in very good yields.8 The
results of these reactions are summarised in Table 1.
It is noteworthy that the amount of iodine used in all
the reactions studied is very low (0.6 equiv.). Neverthe-
less, this quantity is sufficient to transform 1 equiv. of
alkene to the parent iodohydrin derivative in good
Table 1. Conversion of alkenes and enolethers into iodohydrins promoted by I2 and PhI(OCOCF3)2 inCH3CN/H2O at
−15°C

A. R. De Corso et al. / Tetrahedron Letters 42 (2001) 7245–7247
7247
yield. The yields of the reactions are also unaffected
by increasing the amount of BTI initially added.
Acknowledgements
The mechanism aspects of this reaction are not clear
but the ratio of I2/BTI/alkene chosen indicates that
all the molecular halogen initially added is trans-
formed by the hypervalent iodine species into the cor-
responding electrophilic-reactive iodine. For this
reason it is not necessary to add iodine anion-trap-
ping agent to avoid competition of this nucleophilic
halogen anion.9
Financial support from MURST (PRIN 1998 ‘Radi-
cali Liberi e Radicali Ioni nei Processi Chimici e Bio-
logici’) and Universita` di Napoli ‘Federico II’ is
gratefully acknowledged.
References
1. Rodriguez, J.; Dulcere, J.-P. Synthesis 1993, 1177.
2. Masuda, H.; Takase, K.; Nishio, M.; Hasegawa, A.;
Nishiyama, Y.; Ishii, Y. J. Org. Chem. 1994, 59, 5550.
3. Asensio, G.; Andreu, C.; Boix-Bernardini, C.; Mello, R.;
Gonza´lez-Nun˜ez, M. E. Org. Lett. 1999, 1, 2125.
4. Smietana, M.; Gouverneur, V.; Mioskowski, C. Tetra-
hedron Lett. 2000, 41, 193.
5. Tingoli, M.; Tiecco, M.; Testaferri, L.; Temperini, A.
Synth. Commun. 1998, 28, 1769.
6. Unpublished results from this laboratory.
Furthermore, any reaction mixture quenched with
H2O shows an acidic pH (around 3), and all the
attempts to perform the reaction under neutral condi-
tions failed.
As depicted in Table 1 (entries 1, 3, 8 and 9), the
addition of hypoiodous acid to terminal olefins pro-
duced vicinal iodoalcohols in a Markovnikov fashion.
Moreover, in the case of stereodefined double bonds,
an anti addition of IOH was observed (entries 5–7
and 10). In the case of (Z)-2-pentenol (entry 7), in
order to avoid the competition of the free alcohol as
nucleophile, the starting material has to be protected
before use.
7. Typical procedure: BTI (1.0 equiv.) was added at −15°C
to a solution of alkene and I2 (0.6 equiv.) in a 4:1 mixture
of CH3CN and H2O and the vessel was allowed to reach
room temperature. The red–brown colour of the solution
disappears in a few minutes, and all the reactions
described were completed in less than 2 h. After addition
of brine, the reaction mixture was extracted with CH2Cl2
and dried under Na2SO4. Evaporation of the solvent gave
the crude iodohydrin that was, in most cases, character-
ised as the acetate derivative after purification on a silica
gel column, using light petroleum as eluant until iodoben-
zene deriving from the reduction of BTI, eluted out of the
column. A mixture of light petroleum and diethyl ether as
eluant are necessary to recover the iodohydrins. All prod-
Also, an electron-poor olefin like (E)-4-hexen-3-one
reacts smoothly but, in our case, the reaction was not
stereoselective and a 1:3 erythro/threo mixture was
recovered.
The last type of alkene allowed to react was a cyclic
enol ether largely used as a protecting group for pri-
mary alcohols, dihydropyran (entry 11). This com-
pound contains an electron-rich double bond very
sensitive to acidic medium; under our reaction condi-
tions, this did not decompose, but furnished the
desired iodohydrin as a single regio- and trans-isomer
in excellent yield. In the light of this result, we have
tried to apply our mild reaction conditions to glycals
that represent important precursors of 2-deoxysugars.8
1
ucts were fully characterised by H and 13C spectroscopy
and MS spectrometry.
8. Costantino, V.; Imperatore, C.; Fattorusso, E.; Mangoni,
A. Tetrahedron Lett. 2000, 41, 9177.
9. Miljkovic´, D.; Djurendic´, E.; Vukojevic´, N.; Gasˇi, K.;
Csana´di, J. Carbohydr. Res. 1992, 233, 251.
10. Selected experimental data: Compound 1b: solid, mp
112°C (uncorrected); lH (CDCl3, 200 MHz): 7.45–7.35
(m, 1H), 7.35–7.20 (m, 3H), 5.40 (t, J=6.5 Hz, 1H), 4.20
(bq, 1H), 3.58 (dd, J=16.1, 7.1 Hz, 1H), 3.30 (dd,
J=16.1, 8.1 Hz, 1H), 2.40 (d, J=6.5 Hz, OH); lC
(CDCl3, 50 MHz): 127.1, 125.8, 122.6, 122.2, 83.4, 40.6,
28.4; GC–EIMS: m/z 260 (M+) (14), 242 (5), 133 (100),
127 (9), 115 (48), 105 (21). Compound 1k lH (CDCl3, 300
MHz): 4.38 (d, J=8.2 Hz, 1H), 4.3–4.1 (m, 1H), 3.08 (bs,
OH), 3.0–2.7 (m, 1H), 2.7–2.4 (m, 1H), 1.4 (d, J=6.2 Hz,
3H), 1.0 (t, J=7.3 Hz, 3H); lC (CDCl3, 50 MHz): 67.1,
34.3, 31.6, 19.6, 6.7; GC–EIMS: m/z 242 (M+) (0.5), 198
(15), 168 (100), 127 (40), 57 (65). Compound 1m (after
acetylation of the anomeric OH) lH (CDCl3, 200 MHz):
7.6–7.2 (m, 15H), 6.4 (bs, 1H), 4.9–4.4 (m, 8H), 4.1–3.6
(m, 3H), 3.3–3.15 (m, 1H), 2.0 (s, 3H); lC (CDCl3, 50
MHz): 129.9, 129.6, 129.3, 97.0, 77.7, 76.4, 75.0, 72.6,
70.1, 32.6, 22.4.
As reported in Table
1
(entries 12–14), the
hypoiodous acid formed adds to protected glycals
providing the 2-deoxy-2-iodo sugar derivatives in
acceptable yields. Moreover, in the cases of glycals
obtained
from
D
-glucose,
2-deoxy-2-iodo-a-D-
mannopyranose derivatives 1m and 1n were separated
as the sole products.9,10
Finally, our results demonstrate that the use of both
elemental and hypervalent iodine species in CH3CN–
H2O solution represents a good alternative to the
more expensive NIS (N-iodosuccinimide) in the
preparation of iodohydrins.4
An extension of our method to the electrophilic iodi-
nation of aromatic and etheroaromatic molecules is
currently under way.