Highly selective hydroiodation of alkynes using an iodine-hydrophosphine binary system

Article abstract of DOI:10.1021/ol1005246

Figure presented A novel hydroiodation of alkynes (1) using an iodine/hydrophosphine binary system takes place regioselectively to provide the corresponding Markovnikov-type adducts (2) in good yield. This hydroiodation is advantageous in terms of mild conditions, convenient operation, and tolerance to various functional groups.

Full text of DOI:10.1021/ol1005246

ORGANIC
LETTERS
2010
Vol. 12, No. 9
1893-1895
Highly Selective Hydroiodation of
Alkynes Using an Iodine-
Hydrophosphine Binary System
Shin-ichi Kawaguchi and Akiya Ogawa*
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture
UniVersity, Gakuen-cho 1-1, Nakaku, Sakai, Osaka 599-8531, Japan
ogawa@chem.osakafu-u.ac.jp
Received March 3, 2010
ABSTRACT
A novel hydroiodation of alkynes (1) using an iodine/hydrophosphine binary system takes place regioselectively to provide the corresponding
Markovnikov-type adducts (2) in good yield. This hydroiodation is advantageous in terms of mild conditions, convenient operation, and tolerance
to various functional groups.
Vinyl iodides are important intermediates in organic synthesis
and are often employed for transition-metal-catalyzed cross-
coupling reactions, halogen-metal exchange reactions, radi-
cal reactions, and displacement reactions by nucleophiles.
Therefore, the development of highly regio- and stereose-
First, we conducted the hydroiodation of 1-octyne under
lective methods for synthesis of vinyl iodides has been
several conditions (Table 1). The hydroiodation of 1-octyne
desired strongly. Although one of the most straightforward
did not take place without hydrophosphine (entry 1). In this
synthetic methods of vinyl iodides is the addition of HI to
case, only diiodation of 1-octyne proceeded slightly. In contrast,
alkynes; this reaction commonly does not take place at
the hydroiodation of 1-octyne took place with several hydro-
preparatively useful rates.1 Therefore, several methods to
phosphines: diphenylphosphine, diphenylphosphine oxide, or
diethylphosphite (entries 2-6). When Ph2P(O)H/I2 with the ratio
of 1/1 was used, a certain amount of 1,2-diiodido-1-octene
synthesize vinyl iodides from the corresponding alkynes have
been reported.2-5 However, highly selective synthetic meth-
ods to give 2-iodo-1-alkenes are still rare. We report here a
was obtained as byproduct (entry 3). The ratio of Ph2P(O)H/
novel synthetic method of 2-iodo-1-alkenes from the corre-
sponding alkynes by using a novel I2/hydrophosphine binary
system (eq 1).
(3) For the synthesis methods of R-vinyl iodides except the methods
from alkynes, see: (a) Byrd, L. R.; Caserio, M. C. J. Org. Chem. 1972, 37,
3881. (b) Lee, K.; Wiemer, D. F. Tetrahedron Lett. 1993, 34, 2433. (c)
Furrow, M. E.; Myers, A. G. J. Am. Chem. Soc. 2004, 126, 5436. (d) Krafft,
M. E.; Cran, J. W. Synlett 2005, 1263.
(1) Kropp, P. J.; Crawford, S. D. J. Org. Chem. 1994, 59, 3102.
(2) (a) Pross, A.; Sternhell, S. Aust. J. Chem. 1970, 23, 989. (b) Hara,
S.; Dojo, H.; Takinami, S.; Suzuki, A. Tetrahedron Lett. 1983, 24, 731. (c)
Brown, H. C.; Somayaji, V.; Narasimhan, S. J. Org. Chem. 1984, 49, 4822.
(d) Reddy, Ch. K.; Periasamy, M. Tetrahedron Lett. 1990, 31, 1919. (e)
Kamiya, N.; Chikami, Y.; Ishii, Y. Synlett 1990, 675. (f) Gao, Y.; Harada,
K.; Hata, T. J. Org. Chem. 1995, 60, 290. (g) Campos, P. J.; Garc´ıa, B.;
Rodr´ıguez, M. A. Tetrahedron Lett. 2002, 43, 6111. (h) Shimizu, M.;
Toyoda, T.; Baba, T. Synlett 2005, 2516. (i) Moleele, S. S.; Michael, J. P.;
(4) For the synthesis methods of (E) or (Z)-ꢀ-vinyl iodides, see: (a)
Kluge, A. F.; Untch, K. G.; Fried, J. H. J. Am. Chem. Soc. 1972, 94, 9256.
(b) Piers, E.; Grierson, J. R.; Lau, C. K.; Nagakura, I. Can. J. Chem. 1982,
60, 210. (c) Brown, H. C.; Subrahmanyam, C.; Hamaoka, T.; Ravindran,
N.; Bowman, D. H.; Misumi, S.; Unni, M. K.; Somayaji, V.; Bhat, N. G.
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Shinokubo, H.; Oshima, K. J. Org. Chem. 2003, 68, 6627.
(5) For the synthesis methods of vinyl iodides using iodoarylation, see:
Rahman, M. A.; Kitamura, T. Tetrahedron Lett. 2009, 50, 4759.
de Koning, C. B. Tetrahedron 2006, 62, 2831
.
10.1021/ol1005246  2010 American Chemical Society
Published on Web 04/01/2010

Table 1. Optimization of Hydroiodation Using an I2/
Hydrophosphine Binary System
Table 3. Selective Hydroiodation of Alkynes Using an
Iodine-Hydrophosphine Binary System
a
Determined by H NMR. b Based on phosphine. c Based on alkyne.
1
I2 (2/1) at room temperature is the most suitable conditions
for the desired hydroiodation (entry 4). In this condition, the
result indicates that both iodine atoms from one iodine
molecule can be used for the hydroiodation.
Next, the hydroiodation of 1-dodecyne using the Ph2P(O)H/
I2 binary system was conducted in several solvents (Table
2). In halogenated solvents, the hydroiodation took place
Table 2. Hydroiodation in Several Solvents Using the Ph2(O)H/
I2 Binary System
a Reaction conditions A: alkyne (alkene) (1, 0.20 mmol), Ph2P(O)H
(0.30 mmol), I2 (0.15 mmol), CDCl3 (0.5 mL), room temperature. Reaction
conditions B: alkyne (1, 0.60 mmol), Ph2P(O)H (0.20 mmol), I2 (0.10 mmol),
CDCl3 (0.5 mL), 0 °C to room temperature. b Isolated yield. c Determined
entry
solvent
yielda
by H NMR. d For 5 h. e Ph2P(O)H (0.50 mmol) and I2 (0.25 mmol) were
1
used. f After the reaction, EtOH was added. g At 0 °C to room temperature
for 4 h.
1
2
3
4
5
6
7
CHCl3
CH2Cl2
EtOH
67%
62%
4%
THF
0%
MeCN
toluene
benzene
33%
61%
49%
hydroiodation was conducted under two conditions: (A)
alkyne (alkene) (1, 0.20 mmol), Ph2P(O)H (0.30 mmol), I2
(0.15 mmol), CDCl3 (0.5 mL), room temperature; (B) alkyne
(alkene) (1, 0.60 mmol), Ph2P(O)H (0.20 mmol), I2 (0.10
mmol), CDCl3 (0.5 mL), 0 °C to room temperature. Aliphatic
alkynes (1a, 1b, 1d-1g, 1m) underwent the hydroiodation
under condition A, providing the corresponding 2-substituted
vinyl iodides (2a, 2b, 2d-2g, 2m), regioselectively. In the
case of condition A, the yields were determined based on
the employed alkynes. The hydroiodation of alkene such as
1-octene also took place to give the corresponding Mark-
ovnikov-type adducts in good yield (entry 3). When the
aliphatic alkynes bearing chloro and cyano groups were
employed, the hydroiodation proceeded in moderate yields
(entries 4 and 5). In the case of the aliphatic alkyne bearing
hydroxyl groups, the iodation proceeded simultaneously at
a
1
Determined by H NMR.
efficiently (entries 1 and 2). When EtOH or THF6 was used,
iodation of the solvent occurred in preference to the
hydroiodation of 1-dodecyne (entries 3 and 4). On the other
hand, the hydroiodation in toluene proceed successfully
(entry 6). These results seem to be influenced partly by the
solubility of I2 for each solvent.
Table 3 represents the results of the hydroiodation of
several alkynes using a Ph2P(O)H/I2 binary system. The
(6) Gomelya, N. D.; Feshchenko, N. G. Zh. Obshch. Khim. 1988, 58,
2652.
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Org. Lett., Vol. 12, No. 9, 2010

both the alkyne and hydroxyl moieties (entry 6).7 In the case
of the aliphatic alkyne bearing carboxylic acid, the iodation
also proceeded simultaneously at both the alkyne and
carboxylic acid moieties, providing ethyl 5-iodo-5-hexenoate
(2g) after quenching iodations with EtOH (entry 7). Entries
6 and 7 clearly indicate that the present system is available
to iodations of OH and COOH groups. Aromatic alkynes
(1h-1k) underwent the hydroiodation at 0 °C to room
temperature, providing the corresponding R-iodostyrene
derivatives (2h-2k) in good yields (entries 8-11). In the
case of condition B, the yields were determined based on
the iodine atom employed. When an internal alkyne such as
4-octyne was used in the present system, (Z)-4-iodo-4-octene
was obtained quantitatively and stereoselectively (entry 13).
To get some information about the mechanism for this
hydroiodation, several reactions were examined. The hydroio-
dation of alkynylphosphine oxide (1n)8 afforded 1-phosphinyl-
2-iodo-1-octene (3a), regioselectively (eq 2).9 When the reaction
of (E)-1-phosphinyl-2-iodo-1-octene with diphenylphosphine
oxide was conducted, any product with loss of a phosphinyl
group was not obtained at all (eq 3). This result indicates that
the present hydroiodation does not proceed via 1-phosphinyl-
2-iodoalkene species (3) as an intermediate.
A plausible pathway for the present hydroiodation is
shown in Scheme 1. First, Ph2P(O)H reacts with I2, generat-
Scheme 1. Plausible Pathway of Hydroiodation
ing Ph2P(O)I and HI. HI is immediately complexed with
Ph2P(O)H11 to generate complex 3, which acts as an active
species for the Markovnikov-type hydroiodation of alkynes
to give the vinyl iodide 2. On the other hand, Ph2P(O)H has
the tautomeric form of three-valent phosphinious acid
(Ph2POH) (eq 5).12 Alkynes react with Ph2P(O)I and
Ph2POH, generating vinyl iodides 2. The resulting phosphine
oxide finally changes diphenylphosphinic acid upon treatment
with oxygen and proton source.
In summary, we have developed a novel hydroiodation
of alkynes using an iodine/hydrophosphine binary system.
This hydroiodation proceeds to provide Markovnikov-type
adducts in good yield. The advantages of this system are
mild conditions, easy handling, and tolerance to functional
groups. Furthermore, this system is available to iodations of
OH and COOH groups. We hope that this hydroiodation is
used in various stages of organic synthesis.
When 2 equiv of diphenylphosphine oxide was allowed to
react with 1 equiv of iodine, 31P NMR measurement indicated
that diphenylphosphine oxide (δ 21.6 ppm, in CDCl3) com-
pletely converted to two different phosphorus compounds (δ
36.6 and 40.8 ppm, in CDCl3). We assume these two peaks
are assigned to Ph2P(O)I6,10 and Ph2P(O)H·HI,11 respectively
(eq 4).
Acknowledgment. This work is supported by a Grant-
in-Aid for JSPS Fellows (No. 21-10516) from Japan Society
for the Promotion of Science and supported by the Iodine
Utilization Support Program in the 2009 fiscal year from the
Society of Iodine Science. We thank Kyoto-Nrara Advanced
Nanotechnology Network, Japan, for FAB-MS measurement.
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R. K.; Holden, M. Aust. J. Chem. 1982, 35, 517. (c) Iranpoor, N.;
Firouzabadi, H.; Aghapour, Gh.; Vaezzadeh, A. R. Tetrahedron 2002, 58,
8689. (d) Hajipour, A. R.; Falahati, A. R.; Ruoho, A. E. Tetrahedron Lett.
2006, 47, 4191.
Supporting Information Available: Detailed experimen-
tal procedures and compound characterization data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(8) Beletskaya, I. P.; Afanasiev, V. V.; Kazankova, M. A.; Efimova,
I. V. Org. Lett. 2003, 5, 4309.
(9) The product 3a was obtained as an E/Z mixture, most probably because
acid-induced isomerization might occur during the reaction due to the conjugated
system (CdC-PdO). Pure E isomer isolated is stable at ambient temperature
and does not isomerize to the corresponding Z isomer.
OL1005246
(10) Gomelya, N. D.; Matyusha, A. G.; Feshchenko, N. G. Zh. Obshch.
Khim. 1984, 54, 1242
(11) Gomelya, N. D.; Feshchenko, N. G. Zh. Obshch. Khim. 1987, 57,
1702.
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