An intriguing hydroiodination of alkenes and alkynes with titanium tetraiodide

Article abstract of DOI:10.1055/s-2005-872679

Olefins and acetylenes were hydroiodinated with titanium tetraiodide to give alkyl iodides, vinyl iodides, and alkyl diiodides in good yields. In the presence of acetals, the reaction gave intriguing C-C bond-forming products. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-872679

2516
LETTER
An Intriguing Hydroiodination of Alkenes and Alkynes with Titanium
Tetraiodide
An
Intriguing
Hydroioa
kAlkenes and
o
Alkynes wit
t
h Titan
o
ium
T
etraiodide Shimizu,* Tadahiro Toyoda, Toru Baba
Department of Chemistry for Materials, Mie University, Tsu, Mie 514-8507, Japan
Fax +81(59)2319413; E-mail: mshimizu@chem.mie-u.ac.jp
Received 29 June 2005
lent of TiI4 was found to give the best yield. Hydroiodina-
tion of a variety of olefins was carried out under optimum
conditions and the results are summarized in Table 1.3
Abstract: Olefins and acetylenes were hydroiodinated with titani-
um tetraiodide to give alkyl iodides, vinyl iodides, and alkyl diio-
dides in good yields. In the presence of acetals, the reaction gave
intriguing C–C bond-forming products.
Cyclooctene (Table 1, entry 3) and (E)-6-dodecene
Key words: titanium tetraiodide, hydroiodination, alkene, alkyne, (Table 1, entry 5) gave iodocyclooctane and 6-iododode-
Prins reaction, alkyl iodide, alkyl diiodide
cane in 51% and 54% yields, respectively, whereas only a
trace amount of iodide was obtained from cyclohexene
(Table 1, entry 4). Regarding the terminal olefins, 4-phe-
nylbutene and styrene gave secondary iodinated products
regioselectively in good yields (Table 1, entries 6 and 9).
The presence of 4 Å molecular sieves did not noticeably
alter the product yield, whereas the addition of water
decreased the yield (Table 1, entries 7 and 8). Electron-
poor olefins are not good substrates for the present
hydroiodination, although diisopropyl succinate gave the
desired product in 34% yield and the starting material was
recovered in the case of chalcon (Table 1, entries 10 and
11). Tetrasubstitued olefin did not give the addition prod-
uct (Table 1, entry 12). Furthermore, chloroiodination
product 4 was observed when the reaction was carried out
in the presence of NCS (Scheme 2).
Hydrohalogenation reaction is one of the most fundamen-
tal yet important reactions in organic synthesis. Among
them hydroiodination1 of olefins and acetylenes provides
alkyl and alkenyl iodides, which are important building
blocks due to their high reactivity compared with their
bromo and chloro counterparts. However, conventional
methods using hydrogen iodide often suffer from low
yields of products and side reactions.1a
We have recently described useful reactions using titani-
um tetraiodide,2 where the ability of titanium tetraiodide
to iodinate and reduce organic molecules is responsible
for the success of facile transformations. In an effort to
utilize more effectively the iodination ability of titanium
tetraiodide, we examined the hydroiodination reaction of
olefins 1 and acetylenes 2 with titanium tetraiodides
(Scheme 1). This paper describes a convenient method for
the synthesis of alkyl and alkenyl iodides as well as alkyl
diiodides, and intriguing Prins-type reactions promoted
by titanium tetraiodide are also reported.
I
Cl
TiI4 (1.0 equiv)
NCS (1.0 equiv)
CH2Cl2, r.t., 22 h
70%
4
Scheme 2
I
+ TiI4
R
R
R
R
When hydroiodination was carried out with alkynes, ei-
ther hydroiodination or bis-hydroiodination was obtained
depending on the substrates (Scheme 3). Phenylacetylene
gave a-iodostyrene 5 in 59% yield, whereas bis-hydroio-
dinated products 6 were obtained from aliphatic counter-
parts. This selectivity may be explained by considering
the instability of 1,1-diiodo-1-phenylethane, which on
standing at room temperature under the present reaction
conditions gave a-iodostyrene 5.5 Furthermore, the inter-
nal acetylene 7 gave a mixture of vinyl iodide 8 and gem-
diiodinated compound 9 in 30% and 18% yields, respec-
tively (Scheme 4).
1
2
I
R = Aryl
+ TiI4
I
I
R = Alkyl
R
Scheme 1
Treatment of cyclododecene with TiI4 (0.5 equiv) in
CH2Cl2 at room temperature gave iodocyclododecane in
83% yield. Optimum reaction conditions were examined
utilizing hydroiodination of cyclododecene, one equiva-
Intriguing C–C bond-forming reactions were observed,
when the hydroiodination reaction was carried out in the
presence of acetals 10a–c (Schemes 5 and 6). Styrene 1a
underwent a Prins-type addition6 followed by iodination
of the resulting methoxy species to give 1,3-diiodo deriv-
SYNLETT 2005, No. 16, pp 2516–2518
Advanced online publication: 06.09.2005
DOI: 10.1055/s-2005-872679; Art ID: U19905ST
© Georg Thieme Verlag Stuttgart · New York
0
4
.1
0
.2
0
0
5

LETTER
An Intriguing Hydroiodination of Alkenes and Alkynes with Titanium Tetraiodide
2517
Table 1 Hydroiodination of Olefinsa
R3
1) TiI4 (1.0 equiv)
CH2Cl2, r.t.
R3
R1
R4
R2
I
R4
R1
R2
2) H2O
1
3
Entry
1c
2
R1
R2
R3
H
H
H
H
H
H
H
H
H
H
H
Me
R4
Hd
Hd
H
Time (h)
19.0
12.0
11.0
13.0
12.0
8.0
Yield (%)b
-(CH2)10-
83
91
51
trace
54
78
74
67
53
34
0
-(CH2)10-
-(CH2)6-
-(CH2)4-
3
4
H
5
C5H11
H
H
H
H
H
C5H11
H
6
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
Ph
7e
8f
H
12.0
12.0
12.0
8.0
H
9
H
10
11
12
i-PrO2C
PhCO
i-PrO2C
H
H
Ph
Me
17.0
12.0
Me
Me
0
a Reaction was carried out according to the typical procedure.3,
b Isolated yield.
c TiI4 (0.5 equiv) was used.
d A mixture of E,Z isomers.
e In the presence of rigorously dried 4 Å molecular sieves.
f In the presence of 4 Å molecular sieves containing H2O (1 equiv).4
stereoselectivity (Scheme 6).7 These reactions are pro-
posed to occur by the mechanisms shown in Schemes 5
and 6. So far, these types of reactions have been success-
fully carried out only with styrene and phenylacetylene
derivatives, and we are currently investigating the scope
of the reactions in more detail.
1) TiI4 (1.0 equiv)
I
CH2Cl2, r.t., 8 h
Ph
R
Ph
5, 59%
2) H2O
2a
1) TiI4 (1.0 equiv)
CH2Cl2, r.t., 16 h
I
I
R
2) H2O
Regarding the hydroiodination mechanism, we have not
yet confirmed the possible intermediates 13 and 14
(Scheme 7) and we are currently trying to elucidate the in-
2b: R = n-C4H9
2c: R = n-C6H13
6b, 21%
6c, 70%
Scheme 3
I
I
OMe
TiI4 (1.0 equiv)
I
+
Ph
Ar
Ph
nC4H9
CH2Cl2, 0 oC, 12 h
Ar
(1.0 equiv)
10a: Ar = Ph
OMe
nC4H9
1) TiI4 (1.0 equiv)
CH2Cl2, r.t., 12 h
1a
30% (E:Z = 1:1)
8
11a, 55%
11b, 62%
nC4H9
nC4H9
10b: Ar = p-ClC6H4
+
2) H2O
I
I
7
nC4H9
18%
nC4H9
I
TiI3
OMe
TiI4
TiI4
9
OMe
+
Ph
Ar
OMe
Ph
I
Scheme 4
MeO
Ar
1a
10
I3Ti
I
I–
OMe
atives 11a,b as almost a 1:1 mixture of diastereomers in
good yield (Scheme 5). In the case of phenylacetylene
(2a), two equivalents of the acetal participated in the
addition reaction to give 1,4-diene 12 in good yield, where
the presence of a good leaving group resulted in high
I
I
Ph
Ar
Ph
Ar
11
Scheme 5
Synlett 2005, No. 16, 2516–2518 © Thieme Stuttgart · New York

2518
M. Shimizu et al.
LETTER
V. P.; Craig, S. L.; Baillargeon, M. M.; Breton, G. W. J. Am.
Chem. Soc. 1993, 115, 3071. (f) Campos, P. J.; Garcia, B.;
Rodriguez, M. A. Tetrahedron Lett. 2002, 43, 1447; and
earlier references therein.
I
Ph
I
OR
TiI4 (1.0 equiv)
+
Ph
Ph
Ph
Ph
OR
CH2Cl2, 0 °C to r.t.
18 h
12
2a (2.0 equiv)
(2) (a) Hayakawa, R.; Shimizu, M. Org. Lett. 2000, 2, 4079.
(b) Hayakawa, R.; Shimizu, M. Chem. Lett. 2000, 724.
(c) Shimizu, M.; Shibuya, K.; Hayakawa, R. Synlett 2000,
1437. (d) Hayakawa, R.; Sahara, T.; Shimizu, M.
Tetrahedron Lett. 2000, 41, 7939. (e) Shimizu, M.;
Kobayashi, F.; Hayakawa, R. Tetrahedron 2001, 57, 9591.
(f) Shimizu, M.; Sahara, T.; Hayakawa, R. Chem. Lett. 2001,
792. (g) Hayakawa, R.; Makino, H.; Shimizu, M. Chem.
Lett. 2001, 756. (h) Shimizu, M.; Takeuchi, Y.; Sahara, T.
Chem. Lett. 2001, 1196. (i) Shimizu, M.; Sahara, T. Chem.
Lett. 2002, 888. (j) Shimizu, M.; Goto, H. Lett. Org. Chem.
2004, 1, 346. (k) Shimizu, M.; Goto, H.; Hayakawa, R. Org.
Lett. 2002, 4, 4097. (l) Shimizu, M.; Toyoda, T. Org.
Biomol. Chem. 2004, 2, 2891. (m) Shimizu, M.; Inayoshi,
K.; Sahara, T. Org. Biomol. Chem. 2005, 3, 2237.
(3) A typical procedure is as follows: To a suspension of TiI4
(Soekawa Chemical Co., used after sublimation,2a 111 mg,
0.20 mmol) in CH2Cl2 (1.0 mL) was added a solution of
cyclododecene (33.3 mg, 0.20 mmol) in CH2Cl2 (1.0 mL) at
r.t. After stirring at r.t. for 12 h, the reaction was quenched
by the addition of sat. aq NaHCO3 and aq NaHSO3 (5%).
The mixture was filtered through a Celite pad. The layers
were separated and the aqueous layer was extracted with
EtOAc (3 × 10 mL). The combined organic extracts were
washed with sat. aq NaHCO3 and brine, and then dried over
anhyd Na2SO4. Purification by silica gel TLC (hexane) gave
iodocyclododecane (53.8 mg, 91%) as a colorless oil.
(4) Shimizu, M.; Ogawa, T.; Nishi, T. Tetrahedron Lett. 2001,
42, 5463.
10a: R = Me
10c: R = Ac
(Z,Z):(E,Z) = 76:24, 67%
(Z,Z):(E,Z) = 100:0, 41%
I
TiI3
RO
OR
TiI4
TiI4
OR
Ph
+
Ph
Ph
Ph
OR
2a
10
I3Ti I
I
Ph
I
I
RO
Ph
Ph
Ph
Ph
Ph
12
Scheme 6
termediates by spectral methods.8 For reactions with ace-
tals, Prins-type intermediates may account for the facile
C–C bond formations.7
I
I
TiI4
TiI4
H2O
H2O
TiI3
R
R
R
13
1
2
I
I
I
I
TiI3
R
R
R
TiI3
14
Scheme 7
(5) The reaction of phenylacetylene with TiI4 at low
temperatures sometimes gave diiodinated product of type 6
(R = Ph) in the crude reaction mixture. Upon standing at
room temperature, this product underwent
In conclusion, we have found that TiI4 is a good reagent
for hydroiodination of olefins and acetylenes. When the
reactions were carried out in the presence of acetals, facile
Prins-type C–C bond-forming reactions proceeded to give
1,3-diiodides from olefins and 1,5-diiodo-1,4-dienes from
acetylenes.
dehydroiodination to give the vinyl iodide 5.
(6) (a) Arundale, R.; Mikeska, L. A. Chem. Rev. 1952, 51, 505.
(b) Adams, D. R.; Bhatnagar, S. P. Synthesis 1977, 661.
(c) El Gharbi, R.; Delmas, M.; Gaset, A. Synthesis 1981,
361.
(7) Kabalka, G. W.; Wu, Z.; Ju, Y. Org. Lett. 2002, 4, 3415.
(8) We have carried out several experiments quenching the
reaction mixtures derived from alkenes or alkynes and TiI4
with D2O. However, little or no deuterium incorporation was
observed.
Acknowledgment
This work was supported by a Grant-in-Aid for Scientific Research
from the Ministry of Education, Science, Sports, Culture, and Tech-
nology, Japan.
1) TiI4 (1.0 equiv)
I
CD2Cl2, r.t.
Ph
Ph
References
2) H2O
67%
no D-incorporation
(1) (a) Stone, H.; Shechter, H. Org. Synth., Coll. Vol. 4; Wiley:
New York, 1963, 543. (b) Irifune, S.; Kibayashi, T.; Ishii,
Y.; Ogawa, M. Synthesis 1988, 366. (c) Kamiya, N.;
Scheme 8
Chikami, Y.; Ishii, Y. Synlett 1990, 675. (d) Reddy, C. K.;
Periasamy, M. Tetrahedron Lett. 1990, 31, 1919. (e)Kropp,
P. J.; Daus, K. A.; Tubergen, M. W.; Kepler, K. D.; Wilson,
The reaction in CD2Cl2 also did not give the deuteriated
product (vide supra). Elucidation of the intermediary species
will be reported in due course.
Synlett 2005, No. 16, 2516–2518 © Thieme Stuttgart · New York