The selective deiodination of iodoheterocycles using the PhSiH3 - In(OAc)3 system

Article abstract of DOI:10.3987/COM-09-S(S)19

Nitrogen-containing π-deficient heterocyclic iodides such as iodoquinolines or iodopyridines were deiodinated by treatment with phenylsilane catalyzed by indium acetate to give the corresponding deiodinated heterocycles at ambient temperature.

Full text of DOI:10.3987/COM-09-S(S)19

HETEROCYCLES, Vol. 80, No. 1, 2010
601
HETEROCYCLES, Vol. 80, No. 1, 2010, pp. 601 - 606. © The Japan Institute of Heterocyclic Chemistry
Received, 6th March, 2009, Accepted, 1st July, 2009, Published online, 1st July, 2009
DOI: 10.3987/COM-09-S(S)19
THE SELECTIVE DEIODINATION OF IODOHETEROCYCLES USING
THE PhSiH3 – In(OAc)3 SYSTEM
Osamu Sugimoto,* Minami Sugiyama, and Ken-ichi Tanji*
Laboratory of Organic Chemistry, School of Food and Nutritional Sciences
University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
osamu@smail.u-shizuoka-ken.ac.jp; tanji@smail.u-shizuoka-ken.ac.jp
Abstract – Nitrogen-containing π-deficient heterocyclic iodides such as
iodoquinolines or iodopyridines were deiodinated by treatment with phenylsilane
catalyzed by indium acetate to give the corresponding deiodinated heterocycles at
ambient temperature.
Halogen groups on heterocyclic rings are among the most useful and versatile functional groups in
organic synthesis. Heterocyclic halides react with organometallics, such as alkyllithiums,1
alkylmagnesium halides,2 lithium naphthalenide,3 and active magnesium4 to give the corresponding
metalated heterocycles. Subsequent addition of electrophiles introduces an electrophilic substituent into
the heterocyclic ring. π-Deficient nitrogen-containing heterocyclic iodides, in which the iodo group is at
the α- or γ- position relative to the ring nitrogen, react with nucleophiles to give addition-elimination
substitution (SNAE) products.5 On the other hand, removal of the halogen group is often required.
Commonly, the dehalogenation of aromatic halides is carried out by palladium-catalyzed hydrogenations6
or halogen-metal exchange reactions.7 However, the reagents used in these reactions, e.g., H2 gas, Pd-C,
or alkyllithiums, require careful handling. Recently we have developed a facile deiodination of
nitrogen-containing π-deficient heterocyclic iododes using indium metal in aqueous media.8 In this paper
we report the facile deiodination of nitrogen-containing π-deficient heterocyclic iodides in organic

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HETEROCYCLES, Vol. 80, No. 1, 2010
solvents using phenylsilane (PhSiH3) in the presence of indium acetate [In(OAc)3] according to the
method reported by Hosomi, et al.9
First, the dehalogenation of haloquinolines using PhSiH3 in the presence of In(OAc)3 and 2,6-lutidine was
carried out according to the method reported by Hosomi, et al. (Table 1). 3-Iodoquinoline was used as the
substrate in order to determine the optimized reaction conditions (Entries 1-3). When the reaction time
was extended to 120 h, the desired deiodinated product 1 and 1,2,3,4-tetrahydroquinoline (2) were
obtained in 88% and 8% yields, respectively. The yield of 2 was improved when the amount of PhSiH3
was increased to 3.0 eq (Entry 4). The results of entries 5-7 shows that In(OAc)3 and 2,6-lutidine are
indispensable for this deiodinating system. The debromination of 3-bromoquinoline failed even when the
reaction was carried out under reflux for 22 h (Entry 8). Both 4-iodoquinoline and 2-iodoquinoline were
deiodinated to give 1 in high yield with some of 2 (Entries 9 and 10).
Table 1 Indium-catalyzed dehalogenation of haloquinolines
PhSiH3, In(OAc)3, 2,6-lutidine
X
+
EtOH, condition
N
N
N
H
1
2
Reagents (eq)
Yields (%)
Entry
X
Condition
PhSiH3 / In(OAc)3 / 2,6-lutidine
1.3 / 0.2 / 0.5
1.2 / 0.2 / 0.6
1.2 / 0.2 / 0.5
3.0 / 0.2 / 0.6
1.3 / 0.2 / 0
1
2
0
Recovery
1
2
3-I
3-I
3-I
3-I
3-I
3-I
3-I
3-Br
4-I
2-I
rt, 8 h
rt, 25 h
53
79
88
29
23
0
31
13
0
0
3
rt, 120 h
rt, 48 h
8
4
48
44
0
0
5
rt, 62 h
11
98
88
96
0
6
3.0 / 0 / 0.5
rt, 162 h
rt, 47 h
7
3.0 / 0 / 0
0
0
8
1.2 / 0.2 / 0.5
1.3 / 0.2 / 0.5
1.2 / 0.2 / 0.6
reflux, 22 h
rt, 23 h
0
0
9
85
84
9
10
rt, 19 h
16
0
Scheme 1 shows the speculated mechanism for the deiodination of iodoquinolines using PhSiH3 /
In(OAc)3 system. In this mechanism, In(OAc)3 plays as a deiodinating catalyst whereas indium metal
which is used by deiodination of haloheterocycles, requires an stoichiometric amount.8,10

HETEROCYCLES, Vol. 80, No. 1, 2010
603
I
N
N
InH(OAc)2
PhSiH2I
1
PhSiH2(OAc)
InI(OAc)2
In(OAc)3
PhSiH3
Scheme 1 Speculated mechanism for conversion of iodoquinolines into 1
Next, the deiodination of several iodoheterocycles was carried out in order to clarify the generality of the
deiodination as shown in Table 2. Iodopyridines (Entries 1,2), iodoquinolines (Entries 3,4),
iodoisoquinolines (Entries 5,6), and 4-iodo-1H-pyrazolo[3,4-d]pyrimidines (Entry 7) were deiodinated
using PhSiH3 (1.0 – 1.3 eq), In(OAc)3 (0.2 eq), and 2,6-lutidine (0.5 – 0.7 eq) in EtOH to give the
corresponding deiodinated heterocycles in good to moderate yields. On the other hand, deiodination of
2-iodoquinoxaline (Entry 8) and 5-iodoindole (Entry 9) did not proceed.
In conclusion, we have accomplished the selective deiodination of heterocycles. Since the reagents used
in this method are safe to handle, this provides a useful synthetic method for many chemists.
Table 2 Deiodination of iodoheterocycles using PhSiH3 in the presence of In(OAc)3 and 2,6-lutidine
PhSiH3, In(OAc)3
Het-I
Het-H
2,6-lutidine, EtOH
Substrate
(Het-I)
PhSiH3 / In(OAc)3 / 2,6-lutidine (eq)
Condition
Product
(Het-H)
Yield
(%)
Entry
EtO2C
EtO2C
1.2 / 0.2 / 0.5
rt, 18 h
1
2
75
51
N
I
N
N
I
1.3 / 0.2 / 0.5
rt, 22 h
OH
tBuCH
OH
tBuCH
N
1.0 / 0.2 / 0.5
rt, 16 h
I
3
4
64 (23)1)
69 (19)2)
1.2 / 0.2 / 0.5
rt, 48 h
Cl
N
Cl
N

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HETEROCYCLES, Vol. 80, No. 1, 2010
I
I
1.2 / 0.2 / 0.5
rt, 16 h
N
5
6
40
41
N
1.2 / 0.2 / 0.5
rt, 89 h
N
N
N
N
I
1.2 / 0.2 / 0.7
rt, 23 h
N
7
48
N
N
N
N
N
Ph
Ph
N
N
N
N
1.2 / 0.2 / 0.5
rt, 64.5 h
8
9
0 (87)1)
0 (97)1)
I
I
1.2 / 0.2 / 0.5
rt, 66 h
N
N
H
H
1) Substrate was recovered.; 2) 7-Chloro-1,2,3,4-tetrahydroquinoline was obtained.
EXPERIMENTAL
1
Melting points were not corrected. H-NMR spectra were measured with a Hitachi R-90H spectrometer
(90 MHz) using tetramethylsilane as an internal standard.
General procedure for dehalogenation of haloheterocycles using PhSiH3 in the presence of In(OAc)3
and 2,6-lutidine: A mixture of haloheterocycles (1.00 mmol), 2,6-lutidine (0.50 mmol), EtOH (3 mL),
PhSiH3 (1.20 mmol), and In(OAc)3 (0.20 mmol) was stirred under the appropriate conditions. EtOH was
removed under reduced pressure and the residue was purified by silica gel column chromatography to
give the corresponding dehalogenated heterocycles.
Quinoline: Pale yellow liquids. Purified with silica gel column chromatography [eluted with hexane -
1
EtOAc (2:1)]. H-NMR (CDCl3):  7.38 (1H, dd, J = 8.4 Hz, 4.1 Hz, C3-H), 7.48-7.95 (3H, m,

HETEROCYCLES, Vol. 80, No. 1, 2010
605
C5,C6,C7-H), 7.95-8.37 (2H, m, C4,C8-H), 8.91 (1H, dd, J = 4.1 Hz, 1.5 Hz, C2-H).
1,2,3,4-Tetrahydroquinoline: Slightly yellow liquids. Purified with silica gel column chromatography
1
[eluted with hexane - EtOAc (15:1)]. H-NMR (CDCl3 1.72-2.11 (2H, m, C3-H), 2.75 (2H, t, J = 6.4
Hz, C4-H), 3.03 (1H, br s, N1-H), 3.28 (2H, t, J = 5.5 Hz, C2-H), 6.28-6.70 (2H, m, C6,C8-H), 6.76-7.07
(2H, m, C5,C7-H).
Ethyl nicotinate: Slightly yellow liquids. Purified with silica gel column chromatography [eluted with
hexane - EtOAc (2:1)]. 1H-NMR (CDCl3 1.41 (3H, t, J = 7.1 Hz, CH3), 4.42 (2H, q, J = 7.1 Hz, CH2),
7.37 (1H, dd, J = 8.0 Hz, 4.9 Hz, C5-H), 8.29 (1H, dt, J = 8.0 Hz, 1.7 Hz, C4-H), 8.76 (1H, dd, J = 4.9 Hz,
1.7 Hz, C6-H), 9.22 (1H, d, J = 1.7 Hz, C2-H).
1
2,2-Dimethyl-1-(2-pyridinyl)-1-propanol: White solids. Mp 53.7-58.2 °C (lit.,8 53-57 °C). H-NMR
t
(CDCl3 0.92 (9H, s, Bu), 4.32 (2H, br s, CHOH), 6.98-7.37 (2H, m, C3,C5-H), 7.62 (1H, td, J = 7.6
Hz, 1.7 Hz, C4-H), 8.53 (1H, d, J = 4.0 Hz, C6-H).
7-Chloroquinoline: Slightly yellow liquids. Purified with silica gel column chromatography [eluted with
hexane - EtOAc (7:1)]. 1H-NMR (CDCl3 7.24-7.62 (2H, m, C3,C6-H), 7.76 (1H, d, J = 8.7 Hz, C5-H),
7.97-8.28 (2H, m, C4,C8-H), 8.91 (1H, dd, J = 4.1 Hz, 1.5 Hz, C2-H).
7-Chloro-1,2,3,4-tetrahydroquinoline: Yellow solids. Purified with silica gel column chromatography
1
[eluted with hexane - EtOAc (7:1)]. Mp 58-60.5 °C (lit.,11 63-63.5 °C). H-NMR (CDCl3 1.62-2.09
(2H, m, C3-H), 2.70 (2H, t, J = 6.4 Hz, C4-H), 3.28 (2H, t, J = 5.5 Hz, C2 -H), 6.42 (1H, d, J = 1.9 Hz,
C8-H), 6.52 (1H, dd, J = 7.9 Hz, 1.9 Hz, C6-H), 6.82 (1H, d, J = 7.9 Hz, C5-H).
Isoquinoline: Slightly yellow liquids. Purified with silica gel column chromatography [eluted with
1
hexane - EtOAc (4:1)]. H-NMR (CDCl3 7.40-8.08 (5H, m, C4,C5,C6,C7,C8-H), 8.51 (1H, d, J = 5.7
Hz, C3-H), 9.24 (1H, s, C1-H).
1-Phenyl-1H-pyrazolo[3,4-d]pyrimidine: White solids. Purified with silica gel column chromatography
[eluted with hexane - EtOAc (2:1)]. Mp 82.2 °C (lit.,12 79-81 °C). 1H-NMR (CDCl3 7.23-7.71 (3H, m,
phenyl-H), 8.23 (2H, d, J = 8.2 Hz, phenyl-H), 8.31 (1H, s, C3-H), 9.12 (1H, s, C6-H), 9.26 (1H, s, C4-H).
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