An improved synthesis of β-iodo ethers and iodohydrins from alkenes

Article abstract of DOI:10.1055/s-1998-2187

The preparation of diverse β-iodo ethers and iodohydrins is efficiently achieved in mild conditions by reaction of alkenes with two equivalents of I₂ and alcohols (EtOH, i-PrOH, t-BuOH) or water, respectively.

Full text of DOI:10.1055/s-1998-2187

SHORT PAPERS
1584
An Improved Synthesis of â-Iodo Ethers and Iodohydrins from Alkenes
Antonio M. Sanseverino, Marcio C. S. de Mattos*
Instituto de Química, Departamento de Química Orgânica, Universidade Federal do Rio de Janeiro, 21949-900, Rio de Janeiro, Brazil
Fax +55(21)2904746; E-mail: mmattos@iq.ufrj.br
Received 26 November 1997; revised 6 April 1998
Dedicated to Prof. W. Bruce Kover on the occasion of his 60th birthday
1Abstract: The preparation of diverse β-iodo ethers and iodohy-
drins is efficiently achieved in mild conditions by reaction of
alkenes with two equivalents of I2 and alcohols (EtOH, i-PrOH, t-
BuOH) or water, respectively.
Table 1. Products Obtained from the Reaction of Alkenes with I2
(2 equiv.)/Alcohol or Water.
Key words: β-iodo ethers, iodohydrin, cohalogenation, alkene,
electrophilic addition
β-Iodo ethers are useful intermediates for stereoselective
radical reactions1 and for the synthesis of E or Z alkenes
with good to moderate diastereoselectivity.2 Traditional
methods for preparing these compounds are the reaction
of alkenes with N-iodosuccinimide/alcohols3 or I2/alco-
hols and a metal salt, such as Cu(II),4 Ag(I)1 and Ce(IV).5
Although Rutledge and co-workers6 reported a method of
synthesis of iodohydrins (β-iodo alcohols) by reaction of
alkenes with 2.4 equivalents of iodine in a biphasic sys-
tem (water, chloroform, and sulfolane) as well as a similar
route to β-iodo ethers with alkenes, iodine, sulfolane and
an alcohol, this system is somewhat complicated due to
the possibility of the sulfone participating in the reaction,6
prolonged reaction times (24–25 h), and more complex
experimental procedures (such as anhydrous solvents).
Product R1
R2
R3
R4
Time (h) Yield
(%)b
1a
a
Ph
H
H
H
H
H
H
H
H
Me
H
H
Me
H
Me
H
H
Et
i-Pr
t-Bu
Et
Et
Et
Et
H
H
H
H
H
2.5
3.0
3.0
1.0
6.0
6.0
1.5
7.5
7.5
8.0
7.0
7.0
75
75
80
81
65
82
67
75
92
80
86
72
b
Ph
c
Ph
d
Ph
Bu
–(CH2)4–
–(CH2)4–
Ph
ec
fd
gd
h
H
H
H
i
Ph
Bu
–(CH2)4–
–(CH2)4–
je
kd
ld
Me
a
The following compounds are described in the literature: 1a,6 1b,8
1c,8 1f,6 1h–l,7b
b
c
In previous work we studied an easy route for the prepa-
ration of iodohydrins from alkenes by reaction with iodine
and water in the presence of diverse metal salts, and
showed that the readily available and inexpensive
Fe2(SO4)3 gave the best yields.7a This methodology does
not require special techniques and we decided to extend it
to the reaction of alkenes with iodine/Fe2(SO4)3 in the
presence of alcohols as a possible route to β-iodo ethers.
Isolated yield of pure product based on alkene.
Obtained predominantly (85:15 by HRGC) with 1-ethoxy-2-iodo-
hexane.
trans.
d
e
Obtained predominantly (ca. 80:20 by HRGC) with 2-iodohexan-1-
ol.
the formation of 1a–g in Table 1. In all the reactions the
purity of the isolated products (>95%) was confirmed by
1H NMR, 13C NMR, FT-IR and HRGC and the yields of
the β-iodo ethers were good to moderate even with sec-
ondary and tertiary alcohols. Only in the case of hex-1-ene
did the reaction give predominantly the secondary ether
mixed with some of its regioisomer (85:15 by HRGC).
Applying our methodology we obtained 1-ethoxy-2-iodo-
1-phenylethane (1a) in 63% isolated yield by the reaction
of styrene with I2, Fe2(SO4)3 and ethanol (solvent) at room
temperature. Surprisingly, when a second equivalent of
iodine was used in place of the ferric salt, we obtained the
same product 1a in a shorter reaction time (2.5 h) and
slight higher isolated yield (75%). This was unexpected,
since according to the literature information the metal salt
was supposed to be necessary in order to obtain good
yields and avoid the formation of 1,2-diiodoalkanes as un-
desirable side products.4a In our hands, no diiodo com-
pound was detected by the analytical procedures em-
The proposed methodology also proved suitable for io-
dohydrin formation, as verified in the reaction of alkenes
with 2 equivalents of iodine in aqueous dioxane (Table 1,
1h–l). The yields were rather similar and the reaction time
considerably shorter when compared with the reaction
promoted by Fe(III).7a As before, no byproducts were de-
tected by HRGC and spectroscopic methods and the puri-
ty of the isolated products were greater than 95%. Once
more, with hex-1-ene both regioisomeric iodohydrins
were obtained (the secondary alcohol predominantly,
80:20 by HRGC).
1
ployed [HRGC (high resolution GC), H NMR and 13C
NMR] and although we have used ethanol without further
purification, no iodohydrin arising from small amounts of
water in the solvent was detected either.
Based on the above results, we decided to investigate the
preparation of diverse β-iodo ethers using alkenes, alco-
hols and 2 equivalents of I2 and the results are shown for
A reasonable proposal for the explanation of our results is
that the second equivalent of iodine solvates in the decom-

SYNTHESIS
November 1998
1585
Alkenes were purified by standard methods13 and all other chemicals
were used without further purification. HRGC analyses were per-
formed on a HP-5890-II gas chromatograph with FID by using a 30 m
(length), 0.25 mm (ID) and 25 µm (phase thickness) RTX-5 silica cap-
illary column and on a Varian 3400 CX gas chromatograph with FID
using a 30 m (length), 0.25 mm (ID), 0.25 µm (phase thickness) CAR-
BOWAX 20 M capillary column. MS were obtained on a Hewlett–
Packard HP5896-A HRGC-MS using electron impact (70 eV). HRMS
were performed on a VG Autospec at 70 eV. 1H NMR and 13C NMR
were acquired on a Bruker DRX-300 (300 MHz and 75 MHz, respec-
tively) or on a Bruker AC-200 (200 MHz and 50 MHz, respectively)
spectrometers for CDCl3 solutions with TMS as internal standard. FT-
IR spectra were recorded on a Perkin–Elmer 1600 FT-IR or on a Nico-
let 740 FT-IR spectrometer (NaCl film). Analytical data for compounds
1 are summarized in Table 2. The isolated products 1 are stable at r.t.
for several hours and can be stored in a freezer for at least two months
without significant detectable decomposition.
position of the π complex formed between the alkene and
iodine, forming an iodonium ion that is opened by a nu-
cleophilic attack (H2O or ROH) to give the product
(Scheme). According to the literature a metal salt would
be necessary to perform this decomposition.4a, 9 It should
be also mentioned that in terms of kinetics, iodine addi-
tion to an alkene is not a simple process,10 with the order
of reaction varying tremendously with the nature of the
solvent. On the other hand, the absence of diiodoalkane in
this reaction could be explained by the low nucleophilici-
ty of the triiodide ion.11
â-Iodo Ethers 1a–g; Typical Procedure:
To a stirred solution of the alkene (5 mmol) in the appropriate alcohol
(15 mL), I2 (10 mmol) was added at r.t. in small portions. After the
time shown in Table 1, CH2Cl2 or Et2O (25 mL) was added and the
resulting solution was treated with 5% Na2SO3 until discharge of the
iodine color. The organic layer was washed with water (4 × 15 mL),
dried (anhyd Na2SO4) and filtered through a small silica gel column.
The solvent was removed under reduced pressure and heating (bath:
50 ˚C) followed by final concentration at r.t. and 2.67 mbar to give the
corresponding 1a–g as a colorless or light yellow liquid.
Scheme
In summary, the reaction of alkenes with 2 equivalents of
iodine and alcohols or water is a simple and general meth-
od to prepare β-iodo ethers or iodohydrins in good yields
and high purity. The reaction conditions are mild, there is
no need for special techniques and reagents, and in our
opinion the method is simpler than the traditional routes
to these compounds from alkenes.6–8, 12
Iodohydrins 1h–l; Typical Procedure:
Same as above, a solution of dioxane/water (12 mL/3 mL) was used
instead of the alcohol.
AMS thanks CNPq for a fellowship. We also thank W. Bruce Kover
and Joel Jones Jr. (IQ/UFRJ) for helpful discussions and Dr. Antonio
Jorge R. da Silva and NPPN/UFRJ for the HRMS spectra.
Table 2. Data for Products 1 Prepared
1
a
1H NMR δ (ppm), J (Hz)
13C NMR δ (ppm)
IR ν (cm–1)
MS m/z (%)
1.15–1.22 (t, J = 7.0, 3 H), 3.27–3.30 (m, 11.1, 15.3, 65.2, 82.0, 3055, 2968, 1558, 1490, 276 (M+), 149, 135 (100),
2 H), 3.37–3.44 (m, 2 H), 4.38–4.44 (dd, 126.4, 128.7, 128.8, 140.7
1 H), 7.26–7.35 (m, 5 H)
1376, 1170, 1070, 762, 698 107, 79, 51
b
0.90 (d, 3 H), 1.21 (d, 3 H), 3.27 (d, 2 H), 11.5, 21.4, 23.2, 70.4, 79.6, 3060, 2966, 2879, 1171, 290 (M+), 231, 149 (100),
3.53 (d, 1 H), 4.47 (t, 1 H), 7.23–7.41 (m, 126.2, 127.8, 128.5, 141.4
5 H)
1118, 1091, 1064, 763, 699 107, 104, 79
c
1.08 (s, 9 H), 3.12–3.20 (d, 2 H), 4.52– 13.5, 28.8, 31.4, 74.9, 75.2, 2973, 1556, 1337, 1188, 231 (M+ – Ot– Bu), 163,
4.57 (dd, 1 H), 7.20–7.28 (m, 5 H) 125.9, 127.2, 128.5, 143.8 1127, 1068, 699, 667 107 (100), 104, 77, 57
da
1.20 (t, J = 7.0, 3 H), 1.79 (s, 3 H), 3.14– 15.9, 19.9, 24.7, 58.6, 2974, 1599, 1445, 1170, 247 (M+ – OEt), 149 (100),
3.24 (m, 1 H), 3.28–3.38 (m, 1 H), 3.43– 125.5, 127.4, 128.2, 142.3
3.53 (q, 2 H), 7.33–7.48 (m, 5 H)
1073, 761, 700
121, 77, 43
eb
0.89–0.94 (m, 3 H), 1.22 (t, J = 7.0, 3 H), 7.7, 14.0, 15.5, 22.6, 27.5, 2955, 2865, 1559, 1456, 256 (M+), 199, 171, 115
1.31–1.35 (m, 4 H), 1.36–1.59 (m, 2 H), 32.3, 64.9, 78.3
3.15–3.26 (m, 3 H), 3.45–3.70 (m, 2H)
1376, 1109, 668
(100), 69, 55
f
1.27 (t, J = 7.0, 3 H), 1.30–2.30 (com- 15.7, 23.8, 27.4, 31.6, 36.3,
plex m, 8 H), 3.29 (m, 1 H), 3.50–3.66 38.1, 65.0, 82.6
(m, 2 H), 4.03 (m, JCHI-CHOEt = 8.9, 1 H)
254 (M+), 127, 81 (100), 57
g
1.18 (t, J = 7.0, 3 H), 1.34 (s, 3 H), 1.38– 16.1, 22.4, 23.8, 26.2, 33.4, 2930, 2859, 1559, 1443, 268 (M+), 223, 141 (100),
1.46 (m, 2 H), 1.57–1.74 (m, 3 H), 1.92– 35.8, 42.9, 56.1, 73.3
2.02 (m, 2 H), 2.27–2.34 (m, 1 H), 3.39
1374, 1168, 1127, 1065, 95, 98, 43
962
(q, 2 H), 4.39–4.44 (dd, 1 H)

SYNTHESIS
Short Papers
Table 2 (continued)
1586
1
1H NMR δ (ppm), J (Hz)
13C NMR δ (ppm)
IR ν (cm–1)
MS m/z (%)
h
2.80 (d, 1 H), 3.36–3.51 (m, 2 H), 4.81– 15.3, 73.8, 125.6, 128.2, 3410 (br), 3029, 2956,
4.84 (m, 1 H), 7.36 (m, 5 H)
128.5, 141.1
2892, 1175, 1055, 845,
764, 700
i
1.74 (s, 3 H), 2.45 (br s, 1 H), 3.65 (d, 2 24.0, 28.8, 66.9, 124.5, 3530 (br), 3057, 3024, 262 (M+), 244, 204, 169,
H), 7.36 (m, 5 H)
127.3, 128.3, 141.1
2957, 2929, 2891, 1275, 135, 121 (100)
1168, 1030, 849, 780, 700
j
0.91 (t, 3 H), 1.20–2.09 (m, 7 H), 3.18– 14.0, 16.8, 22.5, 27.8, 36.3,
3.77 (m, 3 H) 71.0
228 (M+), 171, 142, 127,
101, 83, 69, 55 (100)
k
1.25–1.55 (m, 4 H), 1.79–1.81 (m, 2 H), 24.2, 27.7, 33.5, 38.3, 42.9, 3380, 2920, 2840, 1440, 226 (M+), 180, 170, 155,
1.99–2.07 (m, 2 H), 2.65 (br s, 1 H), 3.64 75.6
(m, 1 H), 3.99–4.03 (m, JCHI-CHOH = 9.7,
1 H)
1350, 1150, 1060, 940
141, 127, 99, 81 (100)
l
1.34 (s, 3 H), 1.37–1.42 (m, 4 H), 1.53– 22.9, 25.5, 27.6, 37.1, 37.3,
1.71 (m, 1 H), 1.97–2.03 (m, 2 H), 2.27– 49.3, 71.8
2.32 (m, 2 H), 4.24–4.29 (dd, 1 H)
225 (M+ – Me), 197, 154,
141, 127, 113, 95 (100)
a HRMS: C11H15OI requires MR 290.016767, found M+ 290.015800.
b HRMS: C8H17OI requires MR 256.032417, found M+ 256.030166.
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