Indium-mediated reductive elimination of halohydrins

Article abstract of DOI:10.1021/jo0262964

Olefin formation has been successfully carried out by reductive elimination reactions of halohydrins with Pd(PPh₃)₄/In/InCl₃ in aqueous media.

Full text of DOI:10.1021/jo0262964

SCHEME 1. In d iu m -Med ia ted Red u ctive
Elim in a tion of Ha loh yd r in Com p ou n d s
In d iu m -Med ia ted Red u ctive Elim in a tion of
Ha loh yd r in s
Sangwon Cho,†,‡ Soyeon Kang,†,‡ Gyochang Keum,†
Soon Bang Kang,† So-Yeop Han,‡ and Youseung Kim*,†
Biochemicals Research Center,
Korea Institute of Science and Technology, P.O. Box 131,
Cheongryang, Seoul 130-650, Korea, and
Department of Chemistry and Division of Molecular Life
Sciences, Ewha Womans University, Seoul 120-750, Korea
TABLE 1. Rea ction of 1-Br om o-2-in d a n ol u n d er Va r iou s
Con d ition sa
yosekim@kist.re.kr
Received August 7, 2002
Abstr a ct: Olefin formation has been successfully carried
out by reductive elimination reactions of halohydrins with
Pd(PPh3)4/In/InCl3 in aqueous media.
yield of
yield of
product debrominated
entry
solvent
reagent
4b (%) compd 5b (%)
1
2
3
4
THF/H2O
THF/H2O
THF/H2O
THF/H2O
Pd(PPh3)4/In/InCl3
Pd(PPh3)4/In
Pd(PPh3)4/InCl3
Pd(PPh3)4/InI
65
0
28
The carbon-carbon double bond is a basic structural
unit in organic chemistry, particularly in complex natural
products with interesting biological activities, and nu-
merous reports have been published on the syntheses and
chemical reactivities of alkenes.1 Among many reported
methods, the 1,2-elimination reaction is one of the most
effective for forming alkenes.2 Halohydrins are good
alkene precursors for the reductive 1,2-elimination be-
NRd
43
25
23
18
5
MeOH/H2O Pd(PPh3)4/In/InCl3
6
DMF/H2O
THF/H2O
THF/H2O
Pd(PPh3)4/In/InCl3
Pd(PPh3)4/Zn/InCl3
Pd(PPh3)4/Sn/InCl3
7c
8c
NRd
a
Reactions were carried out on a 0.5 mmol scale at rt; halohy-
drin:Pd(PPh3)4:metal:InCl3 ) 1:0.02:2:0.5. b GC yield. c 50 °C. No
reaction.
d
cause they can be prepared by diverse methods.3
A
number of reductive elimination reactions of halohydrin
compounds proceed under various metal-mediated condi-
tions.4 However, these reactions are limited by their poor
stereoselectivities, acidic conditions, or application of
heat. Therefore, an investigation of the mild and stereo-
selective methodology for carbon-carbon double bond
formation should be valuable.
Indium-mediated organic reactions in aqueous media
have become one of the most challenging areas in organic
synthesis due to the environmental benefits and favor-
able effects of indium metal on chemical transforma-
tions.5 Among many indium-mediated organic reactions,
the allylation reaction of carbonyl compounds with allylic
halides to afford the homoallylic alcohols is probably the
most widely used one in organic synthesis.6
In the course of our extensive studies on utilizing
indium metal, we reported carbon-carbon bond forma-
tion reactions7 and reductive dehalogenation reactions.8
To further explore the potentials of indium metal, we
studied the roles of indium metal on the reductive 1,2-
elimination. The use of indium metal in reductive elimi-
nation reactions has not been studied as widely as other
transformations. Herein we report that halohydrin com-
pounds undergo reductive elimination to produce the
corresponding olefins when treated with indium metal
in the presence of Pd(PPh3)4 catalyst and InCl3 in
aqueous media (Scheme 1).
* To whom correspondence should be addressed. Fax: (82)2-958-
5189.
† Korea Institute of Science and Technology.
‡ Ewha Womans University.
(1) (a) The Chemistry of Alkenes; Patai, S., Ed.; Interscience: New
York, 1968; Vol. 2. (b) Shen, Y. Acc. Chem. Res. 1998, 31, 584.
(2) (a) Krebs, A.; Swienty-Busch, J . In Comprehensive Organic
Synthesis; Trost, B. M., Flemming, I., Winterfeldt, E., Eds.; Perga-
mon: Oxford, 1991; Vol. 6, pp 949-973. (b) Kocienski, P. In Compre-
hensive Organic Synthesis; Trost, B. M., Flemming, I., Winterfeldt, E.,
Eds.; Pergamon: Oxford, 1991; Vol. 6, pp 975-1010.
Thus, halohydrins were reacted with indium powder
(200 mol %) and InCl3 (50 mol %) in the presence of
tetrakis(triphenylphospine)palladium(0) (2 mol %) in a
mixture of THF and H2O (1:1, v/v) at ambient tempera-
(3) (a) House, H. O. J . Am. Chem. Soc. 1955, 77, 3070. (b) Guindon,
Y.; Therien, M.; Girard, Y.; Yoakim, C. J . Org. Chem. 1987, 52, 1680.
(c) Chini, M.; Crotti, P.; Gardelli, C.; Macchia, F. Tetrahedron 1992,
48, 3805. (d) Cabon, O.; Buisson, D.; Larcheveque, M.; Azerad, R.
Tetrahedron: Asymmetry 1995, 6, 2199. (e) Choi, O. K.; Cho, B. T.
Tetrahedron: Asymmetry 2001, 12, 903. (f) Araki, S.; Hirashita, T.;
Shimizu, H.; Yamamura, H.; Kawai, M.; Butsugan, Y. Tetrahedron
Lett. 1996, 37, 8417. (g) Andrus, M. B.; Poehlein, B. W. Tetrahedron
Lett. 2000, 41, 1013. (h) Knapp, S.; Kukkola. P. J .; Sharma, S.;
Pietranico, S. Tetrahedron Lett. 1987, 28, 5399. (i) Meth-Cohn, S.;
Moore, C.; Taljaard, H. C. J . Chem. Soc., Perkin Trans. 1 1988, 2663.
(4) (a) Williams, D. R.; Nishitani, K.; Bennett, W.; Sit, S. Y.
Tetrahedron Lett. 1981, 22, 3745. (b) Fukuyama, T.; Chen, X. J . Am.
Chem. Soc. 1994, 116, 3125. (c) Concellon, J . M.; Bernad, P. L.; Perez-
Andres, J . A. Angew. Chem., Int. Ed. 1999, 38, 2384.
(5) (a) Li, C.-J .; Chan, T.-H. Organic Reactions in Aqueous Media;
J ohn Wiley & Sons: New York, 1997. (b) Cintas, P. Synlett 1995, 1087.
(c) Hashmi, A. S. K. J . Prakt. Chem. 1998, 340, 84.
(6) Li, C.-J .; Chan, T.-H. Tetrahedron 1999, 55, 11149.
(7) (a) Lim, H. J .; Keum, G.; Kang, S. B.; Chung, B. Y.; Kim, Y.
Tetrahedron Lett. 1998, 39, 4367. (b) Lim, H. J .; Keum, G.; Kang, S.
B.; Chung, B. Y.; Kim, Y. Tetrahedron Lett. 1999, 40, 1547. (c) Lim,
H. J .; Keum, G.; Kang, S. B.; Chung, B. Y.; Kim, Y. Bull. Korean Chem.
Soc. 2000, 21, 809. (d) Kang, S.; J ang, T.-S.; Keum, G.; Kang, S. B.;
Han, S.-Y.; Kim, Y. Org. Lett. 2000, 2, 3615.
(8) (a) Chae, H.; Cho, S.; Keum, G.; Kang, S. B.; Pae, A. N.; Kim, Y.
Tetrahedron Lett. 2000, 41, 3899. (b) Park, L.; Keum, G.; Kang, S. B.;
Kim, K. S.; Kim, Y. J . Chem. Soc., Perkin Trans. 1 2000, 4462.
10.1021/jo0262964 CCC: $25.00 © 2003 American Chemical Society
Published on Web 12/10/2002
180
J . Org. Chem. 2003, 68, 180-182

TABLE 2. Red u ctive Elim in a tion of Va r iou s Ha loh yd r in sa
a
b
All reactions were carried out on a 0.5 mmol scale at rt; halohydrin:Pd(PPh3)4:In:InCl3 ) 1:0.02:2:0.5. GC yield.
ture for 8-12 h. After the addition of 1 N HCl to the
reaction mixture, the desired olefins were obtained in
good to moderate yields. To elucidate the optimized
reaction conditions, we first used a model substrate,
1-bromo-2-indanol (3),9 under various systems. As shown
in Table 1, only the reaction conditions of entry 1 afforded
desired indene product 4. With the absence of either In
or InCl3 from the system of Pd(PPh3)4/In/InCl3, the
reaction did not occur (entry 3) or gave a debrominated
compound, 5 (entries 2 and 4). Employing other solvent
systems besides THF/H2O also led to poor results (entries
5 and 6). When other metals, such as Zn and Sn instead
of In, were used, the reaction did not proceed (entry 8)
or gave a debrominated compound, 5 (entry 7), even at
50 °C for 10 h.
The results of indium-mediated reductive elimination
of various halohydrins are summarized in Table 2. The
requisite halohydrin derivative starting materials were
easily prepared from the commercially available alkenes
following known procedures.3 Some halohydrins were
then acylated to give good yields of the corresponding
O-acetylated starting materials. As shown in Table 2, the
Pd(PPh3)4/In/InCl3 system was effective for the reductive
elimination of various halohydrin compounds in aqueous
media. The reactions proceeded smoothly under mild
conditions, and simple workup of the reaction mixture
(9) Kotsuki, H.; Shimanouchi, T. Tetrahedron Lett. 1996, 37, 11,
1845.
J . Org. Chem, Vol. 68, No. 1, 2003 181

Chemical shifts are given in δ units relative to the tetrameth-
ylsilane (TMS) signal as an internal reference in CDCl3.
Coupling constants (J ) are reported in hertz. Electron-impact
(EI) mass spectra were recorded in the form of m/z (intensity
relative to base 100) on a GC-MSD system. High-resolution
mass spectral analyses were carried out at the Korea Basic
Science Institute, Taejon, or Korea Basic Science Institute, Seoul,
Korea. For thin-layer chromatography (TLC), precoated plates
(silica gel, 0.25 mm) were used. Silica gel (230-400 mesh) was
used for column chromatography.
Gen er a l P r oced u r e for th e Syn th esis of Ha loh yd r in s.
The halohydrin in entry 1 of Table 2 was prepared by indium-
mediated allylation of benzaldehyde with 1,3-dichloropropene.3f
That in entry 2 was prepared by indium-mediated allylation of
phthalic dicarboxaldehyde with chloro-3-iodopropene. Those in
entries 5 and 6 were prepared from the epoxidation of the
corresponding alkenes with m-CPBA followed by halogenation
with a 1.0 M HCl solution in Et2O.3g Those in entries 3, 4, 7,
and 12 were prepared from the reaction of the corresponding
alkenes with N-bromosuccinimide in H2O.3h That in entry 11
was prepared from the epoxidation of ethyl trans-crotonate with
tert-butyl hydroperoxide followed by halogenation with a 1.0 M
HCl solution in Et2O.3i That in entry 13 was prepared from the
epoxidation of indene with m-CPBA followed by treatment with
300 mol % lithium bromides.9 Those in entries 8, 9, 14, and 15
were prepared from the acetylation of the corresponding halo-
hydrins using Ac2O, pyridine, and DMAP in CH2Cl2.
Gen er a l P r oced u r e for th e In d iu m -Med ia ted Elim in a -
tion of Ha loh yd r in s. The following procedure is representative.
A mixture of chlorohydrin 1 (Table 2, entry 2) (580.0 mg, 2.87
mmol), indium (329.5 mg, 2.87 mmol), indium(III) chloride (159.7
mg, 0.72 mmol), and Pd(PPh3)4 (83.7 mg, 2 mol %) in THF/H2O
(1:1; 1 mL) was stirred at rt for 8 h. The reaction was quenched
with 1 N HCl (1 mL) and EtOAc (1 mL), and the whole mixture
was filtered through Celite. After general workup, purification
by flash chromatography on silica gel using an n-hexane/EtOAc
(6:1) mixture as an eluent afforded the product olefin 2 (18.6
mg, 0.14 mmol) in 80% yield: 1H NMR (300 MHz, CDCl3) δ
7.48-7.42 (m, 2H), 7.23-7.16 (m, 2H), 6.86 (d, 2H, J ) 15.1 Hz),
6.69-6.47 (m, 4H), 5.35-5.30 (d, 2H, J ) 15.3), 5.20-5.16 (d,
2H, J ) 8.9); 13C NMR (75 MHz, CDCl3) δ 137.8, 135.9, 132.4,
132.2, 131.5, 128.1, 126.9, 126.7, 126.0, 125.9, 118.3; MS (EI)
m/z (rel intensity) 182 (M+, 3), 167 (32), 140 (41), 111 (41), 71
(100), 57 (84); HRMS (EI) m/z 182.1069 (calcd for C14H14
182.1096).
allowed generation of the corresponding product olefins
in good yields. Generally, with a few exceptions, the
yields of the desired products 2 were not much affected
by the nature of the halohydrins such as chlorohydrin,
bromohydrin, and O-acetyl halohydrin. Under the same
conditions of the Pd(PPh3)4/In/InCl3 system, the reductive
elimination reaction of cyclic halohydrins of entries 12-
15 gave the (Z)-olefins and the reaction of the acyclic syn-
and anti-halohydrins afforded the corresponding (E)-
olefins exclusively. The stereochemistry of the product
olefins was determined by comparison of the 1H NMR
spectrum and GC-MS spectrum of the authentic olefins,
and only a single stereoisomer was shown. The reductive
elimination also proceeded for unactivated halides (en-
tries 5, 10, 12, and 15).
During the course of this study to further explore the
scope of this reaction, we have found that peracetylated
glycosyl bromides undergo indium-mediated reductive
elimination to form the corresponding glycals in neutral
aqueous media (entries 16 and 17). Because of the
importance of glycals as the key building blocks in
carbohydrate chemistry and the synthesis of optically
active natural products,10 the development of new and
improved methods for their preparation would be of great
value. Along with some reported procedures,11 the reac-
tion system described here represents one of the most
efficient and convenient procedures for the synthesis of
peracetylated glycal derivatives.
In conclusion, we have developed a versatile, effective,
and convenient reductive elimination procedure for con-
verting various halohydrin compounds to the correspond-
ing olefins using palladium catalyst, indium metal, and
indium trichloride salts in neutral aqueous media in good
yields. The present method also offers a simple and
efficient alternative to other known procedures for the
preparation of glycals.
Exp er im en ta l Section
Gen er a l Meth od s. All reagents were obtained from com-
mercial sources and used without further purification. 1H and
13C NMR spectra were recorded at 300 and 75 MHz, respectively.
Ack n ow led gm en t. This work was fully supported
by the Korea Institute of Science & Technology and the
Ministry of Science & Technology.
(10) Bols, M. Carbohydrate Building Blocks; J ohn Wiley and Sons:
New York, 1996.
(11) (a) Shull, B. K.; Wu, Z.; Koreeda, M. J . Carbohydr. Chem. 1996,
15, 955. (b) Kovacs, G.; Toth, K.; Dinya, Z.; Somsak, L.; Micskei, K.
Tetrahedron 1999, 55, 5253. (c) Cavallaro, C. L.; Schwartz, J . J . Org.
Chem. 1995, 60, 7055.
Su p p or tin g In for m a tion Ava ila ble: Text describing
experimental details. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O0262964
182 J . Org. Chem., Vol. 68, No. 1, 2003