Indium tribromide-catalyzed deacetoxylation of propargylic acetate with triethylsilane

Article abstract of DOI:10.1016/j.tetlet.2005.07.118

Indium(III) bromide catalyzed the deacetoxylation of propargylic acetates with Et₃SiH to produce the corresponding internal alkynes containing a variety of functional groups in good yields.

Full text of DOI:10.1016/j.tetlet.2005.07.118

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 6407–6409
Indium tribromide-catalyzed deacetoxylation of propargylic
acetate with triethylsilane
Norio Sakai,* Maki Hirasawa and Takeo Konakahara*
Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science,
Noda, Chiba 278-8510, Japan
Received 22 June 2005; revised 23 July 2005; accepted 25 July 2005
Abstract—Indium(III) bromide catalyzed the deacetoxylation of propargylic acetates with Et3SiH to produce the corresponding
internal alkynes containing a variety of functional groups in good yields.
Ó 2005 Elsevier Ltd. All rights reserved.
Indium(III) halide has attracted considerable attention
in synthetic organic chemistry due to its low toxicity in
the laboratory, high stability under aqueous conditions,
and strong tolerance to oxygen- and nitrogen containing
functional groups.1 As a result, many groups have uti-
lized indium halide and indium metal to develop syn-
thetic methodologies including high regio- and chemo
selectivity and to synthesize key compounds and mate-
rial sources in material and medicinal chemistry.2 On
the other hand, during our continuing research on the
indium halide-promoted substitution of functional
groups on propargylic alcohols and acetates,3 one of
us found that the use of triethylsilane as a nucleophile
in a reaction involving propargylic acetate in the pres-
ence of quite a small amount of InBr3 leads to the
smooth production of an internal alkyne. Thus, we be-
came interested in developing a method for a highly effi-
cient reduction of propargylic acetate, prepared from
propargylic alcohol and acetic anhydride in the presence
of a catalytic amount of InBr3, by an indium halide–
hydrosilane catalytic system leading to an internal
alkyne. In this context, Baba and co-workers reported
that a combination of InCl3 and diphenylchlorosilane
effectively reduced secondary and tertiary alcohol deriva-
tives to form alkane derivatives,4 and Gevorgyan and
Yamamoto et al. found that B(C6F5)3–Et3SiH catalyzed
the reduction of alcohols including a primary alcohol.5
In addition, Hatakeyama and co-workers reported that
TFA–Et3SiH promoted the removal of benzylic acetoxy
groups under cryophilic conditions.6 We report herein
on a highly simple method for the deacetoxylation of
secondary propargylic acetates by Et3SiH in the pres-
ence of a catalytic amount of InBr3 under mild condi-
tions, to give internal alkynes containing a variety of
functional groups.
Initially, we investigated the reduction of propargylic
acetate 1a, which was prepared from 1,3-diphenyl-1-
hydroxy-2-propyne and acetic anhydride in the presence
of InBr3 (0.1 equiv),7 with InBr3 and triethylsilane as a
model reaction.8 Table 1 shows the results of a search
for optimized conditions. Consequently, we found that
dichloromethane was the best solvent for this reaction.
When the reaction was conducted in ether and tetra-
hydrofuran, the reaction did not proceed (entries 3
and 4), and the use of toluene and acetonitrile also
resulted in decreased yields (entries 5 and 6). On the
other hand, increasing the amount of triethylsilane
shortened the reaction time to 10 min, and dramatically
improved the yield of 2a up to 67% (entries 7 and 8).
Moreover, when 0.05 equiv of indium salt per mole of
propargylic acetate was used, the yield of the internal al-
kyne further increased up to 80% (entry 9). Needless to
say, in the absence of indium salt, no reduction occurred
(entry 10), and running this reaction with InCl3 gave the
product in slightly lower yield than a reaction with InBr3
(entry 11). A combination of InBr3 and reducing
reagents, such as DIBAL, LiAlH4, and NaBH4 were
not effective for this reaction. Consequently, it was
found that the combination of 0.05 equiv of indium
Keywords: Indium bromide; Propargylic acetate; Silane; Internal
alkyne; Deacetoxylation.
*
Corresponding authors. Tel.: +81 4 7124 1501; fax: +81 4 7123
9890; e-mail: sakachem@rs.noda.tus.ac.jp
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.07.118

6408
N. Sakai et al. / Tetrahedron Letters 46 (2005) 6407–6409
Table 1. Examination of the reduction of propargylic acetate
InX3
OAc
Ph
Et3SiH
Ph
solv, rt
Ph
Ph
2a
Solvent
1a
Run
InX3 (equiv)
Et3SiH (equiv)
Time (h)
Yield (%)a
1
2
3
4
5
6
7
8
InBr3 (0.1)
InBr3 (0.1)
InBr3 (0.1)
InBr3 (0.1)
InBr3 (0.1)
InBr3 (0.1)
InBr3 (0.1)
InBr3 (0.1)
InBr3 (0.05)
None
1.1
1.1
1.1
1.1
1.1
1.1
1.5
2
CH2Cl2
CH3Cl
Et2O
THF
PhMe
MeCN
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
<0.2
1
10
10
10
47
46
NR
NR
28
22
48
67
80
10
<0.2
<0.2
<0.3
10
9
10
11
2
1.1
2
NR
58
InCl3 (0.05)
3
a Isolated yields.
bromide and 2 equiv of triethylsilane showed the best
result for the reaction.
to excellent yields (runs 6–10). In addition, when the
reaction of a compound containing a silyl group was
carried out, the corresponding products were produced
in moderate to good yields along with the starting mate-
rials (runs 11–13). Moreover, we found that this system
selectively reduces only the acetoxy moiety without
dehalogenation and reduction of the nitro group.9,10
On the other hand, in case of 3-acetoxy-1-(4-methoxy-
phenyl)-1-butyne (R1 = 4-MeO–C6H4, R2 = Me), the
yield of the desired reductive product was rather low
(<2%).
To extend generality of this reaction, the reduction of
various propargylic acetates was then carried out under
optimized conditions, in which the reactions were typi-
cally run at room temperature in a CH2Cl2 solution,
the results of which are displayed in Table 2. Reduction
of an acetate having two benzene rings was complete in
a short time, producing the corresponding internal alky-
nes in good yields (runs 1–5). A longer reaction time was
required for the reaction of an acetate having an elec-
tron-withdrawing group on the R2 group to reach com-
pletion (runs 4, 5, and 8). A propargylic acetate having
an alkyl group, such as a hexyl group and a tert-butyl
group next to the triple bond also underwent the desired
reaction to produce the corresponding products in good
Although, there is no clear explanation for the reaction
path at present, we assume that an indium radical spe-
cies, such as Br2InÅ mediates this reaction process. Actu-
ally, when 2,2,6,6-tetramethyl-1-piperidinyloxy radical
(TEMPO), a radical trapping agent, was added to the
Table 2. Reduction of various propargylic acetates by InBr3–Et3SiH leading to internal alkynesa
InBr3 (0.05 equiv)
Et3SiH (2 equiv)
OAc
R2
R2
R1
CH2Cl2, rt
R1
2
1
Run
Propargylic acetate 1
Time (h)
Yield (%)b
R1
R2
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
1a
1b
1c
1d
1e
1f
0.2
0.2
0.2
3
0.5
0.2
0.2
3
0.2
0.1
0.2
0.5
0.2
2a
2b
2c
2d
2e
2f
80
84
58
50
74
99
97
87
77
70
61
45
44
4-MeO–C6H4
4-Me–C6H4
4-NO2–C6H4
4-Cl–C6H4
Ph
4-MeO–C6H4
4-Cl–C6H4
Ph
4-MeO–C6H4
Ph
4-Cl–C6H4
4-MeO–C6H4
Ph
C6H13
C6H13
C6H13
t-Bu
t-Bu
Me3Si
Me3Si
Me3Si
1g
1h
1i
2g
2h
2i
9
10
11
12
13
1j
2j
1k
1l
2k
2l
1m
2m
a Propargylic acetate 1 (0.5 mmol), InBr3 (0.05 equiv), and Et3SiH (2 equiv) were used in CH2Cl2 solution (2 mL).
b Isolated yields.

N. Sakai et al. / Tetrahedron Letters 46 (2005) 6407–6409
6409
5. (a) Gevorgyan, V.; Liu, J.-X.; Rubin, M.; Benson, S.;
Yamamoto, Y. Tetrahedron Lett. 1999, 40, 8919; (b)
Gevorgyan reported B(C6F5)3-catalyzed allylation of
propargylic acetate with allylsilane, see: Schwier, T.;
Rubin, M.; Gevorgyan, V. Org. Lett. 2004, 6, 1999.
6. Luo, M.; Matsui, A.; Esumi, T.; Iwabuchi, Y.; Hatake-
yama, S. Tetrahedron Lett. 2000, 41, 4401.
reaction mixture including acetate 1a, InBr3, and trieth-
ylsilane, the desired reduction did not proceed, and the
starting acetate was recovered in 94% yield. In this con-
text of these radical species, quite recently, Baba and
co-workers reported that the InCl3–Et3SiH or –Bu3SnH
system acts as a radical reagent.11
7. Chauhan, K. K.; Frost, C. G.; Love, I.; Waite, D. Synlett
1999, 1743.
In conclusion, we demonstrated that the InBr3 and
Et3SiH reagent system promotes the deacetoxylation
of propargylic acetates to produce internal alkynes. This
simple catalytic system is remarkably tolerant of a vari-
ety of functional groups on the acetate, and a radical
intermediate is generated in situ. Further investigations
of the mechanism of this reaction are currently in
progress.
8. General procedure for the reduction of propargylic
acetate: propargyl acetate 1a (0.50 mmol) and triethyl-
silane (1.0 mmol) were successively added to anhydrous
CH2Cl2 (2 mL) at room temperature under a N2 atmo-
sphere. After 5 min, InBr3 (5 mol %, 0.025 mmol) was
added to the solution. The mixture was stirred at the
same temperature until the reaction reached completion,
as shown by TLC (hexane/AcOEt = 95:5). After an
appropriate reaction time shown in Table 2, a saturated
solution of NaHCO3 was added to the reaction mixture
to quench the reaction. The combined organic layer was
washed with brine, dried over Na2CO3, and evaporated
under reduced pressure. The crude product was purified
by silica gel chromatography (hexane/AcOEt = 95:5) to
give the corresponding internal alkynes 2a (80%).
Spectral data for new compounds: 1-(4-methoxyphenyl)-
Acknowledgements
Authors thank Mr. Masaki Ohshima for his experimen-
tal assistance. This work was partially supported by a
grant from the Japan Private School Promotion Foun-
dation and a fund for ÔHigh-Tech Research CenterÕ Pro-
ject for Private Universities: a matching fund subsidy
from MEXT, 2000–2004.
1
2-nonyne (2g): yellow oil; H NMR (CDCl3, 500 MHz) d
0.8 (t, 3H, J = 7.0 Hz), 1.2–1.4 (m, 8H), 2.1 (t, 2H, J =
1.0 Hz), 3.42 (s, 2H), 3.69 (s, 3H), 6.75 (d, 2H,
J = 8.5 Hz), 7.16 (d, 2H, J = 8.5 Hz); 13C NMR (CDCl3,
125 MHz) d 14.0, 18.8, 22.5, 24.2, 28.6, 29.0, 31.4, 55.2,
77.9, 82.3, 113.7, 128.7, 129.7, 158.2; MS (EI) m/z 230;
HRMS (FAB): calcd for C16H22O: 230.1671, found
230.1670; 1-(4-chlorophenyl)-2-nonyne (2h): yellow oil;
1H NMR (CDCl3, 500 MHz) d 0.8 (t, 3H, J = 7.0 Hz),
1.2–1.5 (m, 8H), 2.1 (m, 2H), 3.45 (s, 2H), 7.18 (m, 4H);
13C NMR (CDCl3, 125 MHz) d 14.0, 18.8, 22.6, 24.6,
28.6, 28.9, 31.3, 76.9, 83.1, 128.4, 129.1, 132.1, 136.1; MS
(EI) m/z 234; HRMS (FAB): calcd for C15H20Cl (M+H):
235.1253, found 235.1262; 4,4-dimethyl-1-(4-methoxy-
References and notes
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1
phenyl)-2-pentyne (2j): pale yellow oil, H NMR (CDCl3,
500 MHz) r 1.25 (s, 9H), 3.50 (s, 2H), 3.81 (s, 3H), 6.81
(d, 2H, J = 7.5 Hz), 7.21 (d, 2H, J = 7.5 Hz); 13C NMR
(CDCl3, 125 MHz) r 24.1, 27.4, 31.3, 55.2, 76.3, 91.1,
113.7, 128.6, 129.7, 158.1; MS (EI) m/z 222; HRMS
(FAB): calcd for C14H18O: 222.1358, found 222.1361; 3-
(4-chlorophenyl)-1-(trimethylsilyl)-1-propyne (2l): yellow
oil; 1H NMR (CDCl3, 500 MHz) d 0.02 (s, 9H), 3.4 (s,
2H), 7.1 (s, 4H); 13C NMR (CDCl3, 125 MHz) d 0.02,
25.6, 87.4, 103.6, 128.6, 129.2, 132.4, 134.8; MS (EI) m/z
222; HRMS (FAB): calcd for C12H15ClSi: 222.0632,
found 222.0616.
9. When a reduction involving the secondary propargylic
alcohol, 4-(1-hydroxy-3-phenyl-2-propynyl)-benzonitrile
was conducted under optimized conditions, the desired
internal alkyne was obtained in low yield (20%).
10. A referee pointed out that whether B(C6F5)3–Et3SiH
catalytic system undertook the present reaction or not.
Thus, when the reduction of alkyne 1a with Et3SiH was
carried out in the presence of 0.10 equiv of B(C6F5)3, the
desired reaction proceeded smoothly (<0.2 h) to give the
corresponding alkyne 2a in 58% yield.
3. Sakai, N.; Hirasawa, M.; Konakahara, T. Tetrahedron
Lett. 2003, 44, 4171.
4. Yasuda, M.; Onishi, Y.; Ueba, M.; Miyai, T.; Baba, A.
J. Org. Chem. 2001, 66, 7741.
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4981; (b) Inoue, K.; Sawada, A.; Shibata, I.; Baba, A.
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