330
J . Org. Chem. 2001, 66, 330-333
water is found to accelerate the pinacolic coupling reac-
Red u ction a n d Cou p lin g Rea ction s of
tions of aromatic carbonyl compounds mediated by Sm/
Me3SiCl in THF.5a Reductions of nitrobenzene,5b 1,2-
dibromoalkanes,5c,d benzoic acid derivatives,5e and pyri-
dines5f have been realized by using Sm/I2 or Sm/HClaq in
MeOH. Pinacolic coupling reactions of aromatic ketones
have been achieved by using Sm with alkyl halides in
MeOH.5g The expected Barbier-type addition products are
not found.5g
Ca r bon yl Com p ou n d s Usin g Sa m a r iu m
Meta l in Aqu eou s Med ia
Sanjay Talukdar and J im-Min Fang*
Department of Chemistry, National Taiwan University,
Taipei, Taiwan 106, Republic of China
Our study was initiated by examining the reactivity
of 4-bromobenzaldehyde (1b) with Sm in aqueous media
(Table 1). The Sm ingot was abraded (by a file) to give
shining powders for the present study. Treatment of 1b
with Sm (1.2 molar proportions) in H2O/THF (5:1) for 72
h afforded very low yields of pinacol 2b (3%) and alcohol
3b (2%) accompanied by a 95% recovery of 1b. The
residual Sm had tarnished by the end of the reaction.
The reaction was not significantly improved by sonication
or by using an excessive amount of Sm (entries 2 and 3,
Table 1).
We thus searched for appropriate activators to enhance
the reactivity of Sm in aqueous media.2,5,6 Indeed, treat-
ment of 1b with Sm (3 molar proportions) in the presence
of HgCl2 (1.5 molar proportions) gave much higher yields
of pinacol 2b (48%) and alcohol 3b (38%) in H2O/THF
media (entry 4, Table 1). Iodine was also an effective
activator of Sm (entries 6-8).2f By using Sm (3 molar
proportions) with I2 (0.75 molar proportions), 1b was
completely converted in 16 h to give equal amounts of
2b and 3b. Preferable formation of pinacol 2b over
alcohol 3b was realized by using Sm in saturated NH4-
Cl/THF (5:1) or with FeCl3 activation (entries 9 and 10,
Table 1). The bromine atom of 1b was retained in all of
these reaction conditions.
After a comprehensive survey on the optimization of
reaction conditions, we found that the reaction in aqueous
HCl solution (2 M)5d-f produced an 88% yield of pinacol
2b in a chemoselective manner (entry 12, Table 1). Thus,
Sm (3 molar proportions) was added in several portions
to a suspension of 1b (1 mmol) in 2 M HCl/THF (5:1) over
a period of 1 h at room temperature. Upon addition of
Sm powders, a transient purple color and hydrogen
evolution were observed. The reaction mixture was
continuously stirred without rigorous exclusion of oxygen.
It required 32 h for the consumption of 4-bromobenzal-
dehyde as shown by TLC analyses. The media became
transparent at the end of the reaction, and no residue of
Sm particles remained. The reaction did not proceed to
completion if the amount of Sm was less than 1.2 molar
proportions. A considerable portion of starting material
1b was recovered if the reaction was conducted by
addition of aqueous HCl solution to the suspension of 1b
and Sm in THF (entry 13, Table 1). The reaction in
aqueous HBr was less chemoselective (entry 14, Table
jmfang@mail.ch.ntu.edu.tw
Received September 14, 2000
Direct use of metallic Sm as a reducing agent in
organic transformations has drawn chemists’ attention.1
Such reactions are generally performed in THF. For
example, alkyl iodides are reduced to alkanes by Sm in
THF.2a Barbier reaction of 2-(3-iodopropyl)cycloheptanone
with Sm in THF occurs intramolecularly to give a bicyclic
alcohol.2b Iodomethylations of carbonyl compounds are
achieved by treatment with Sm and CH2I2 in THF.2c
Since water is an environmentally benign medium, we
wish to explore further the reactions of carbonyl com-
pounds with Sm in aqueous media.3 Sm is quite stable
in water even though it has a high reduction potential
(Sm3+/Sm ) -2.41 V).4
There are several methods2,5 for activation of Sm metal
such as amalgamation using I2, HCl, and alkyl halides.
Cyclopropanations of esters, R-halo ketones, and allylic
alcohols are realized by using Sm(Hg)/ICH2Cl or Sm/
HgCl2/ICH2Cl in THF.2d,e Sm with a catalytic amount of
I2 in THF is used in the reductive coupling reactions of
N-alkylideneanilines, giving vicinal diamines.2f Deoxy-
genative coupling reactions of benzamides, giving 1,2-
diaminostilbenes, are carried out by using Sm with a
catalytic amount of SmI2 in THF.2g A minute amount of
* To whom correspondence should be addressed. Fax: (886-2)-
2363-6359.
(1) (a) Kagan, H. B.; Namy, J . L. Tetrahedron 1986, 42, 6573.
(b) Molander, G. A.; Harris, C. R. In Encyclopedia of Reagents for
Organic Synthesis; Paquette, L. A., Ed.; Wiley: Chichester, 1995; Vol.
6, p 4425.
(2) (a) Ogawa, A.; Nanke, T.; Takami, N.; Sumino, Y.; Ryu, I.;
Sonoda, N. Chem. Lett. 1994, 379. (b) Molander, G. A.; Etter, J . B. J .
Org. Chem. 1986, 51, 1778. (c) Imamoto, T.; Takeyam, T.; Koto, H.
Tetrahedron Lett. 1986, 27, 3243. (d) Imamoto, T.; Kamiya, Y.;
Hatajima, T.; Takahashi, H. Tetrahedron Lett. 1989, 38, 5149. (e)
Molander, G. A.; Etter, J . B. J . Org. Chem. 1987, 52, 3942. (f) Yanada,
R.; Negoro, N.; Okaniwa, M.; Miwa, Y.; Taga, T.; Yanada, K.; Fujita,
T. Synlett 1999, 537. (g) Ogawa, A.; Takami, N.; Sekiguchi, M.; Ryu,
I.; Kambe, N.; Sonoda, N. J . Am. Chem. Soc. 1992, 114, 8729.
(3) Zn, In and Sn metals are often operative in aqueous media. For
reviews, see: (a) Li, C. J .; Chan, T. H. Organic Reactions in Aqueous
Media; Wiley: New York, 1997. (b) Chan, T. H.; Li, C. J .; Lee, M. C.;
Wei, Z. Y. Can. J . Chem. 1994, 72, 1181. (c) Li, C. J . Tetrahedron 1996,
52, 5643. (d) Lubineau, A.; Auge, J .; Queneau, Y. Synthesis 1994, 741.
(4) For the reduction potential and stability of Sm in water. See:
(a) Moeller, T. In Comprehensive Inorganic Chemistry; Bailar, J . C.,
Emeleus, H. J ., Nyholm, R., Trotman-Dickenson, A. F., Eds.; Pergamon
Press: Oxford, 1973; Vol. 4, p 5. (b) Latimer, W. M. The Oxidation
States of the Elements and Their Potentials in Aqueous Solution, 2nd
ed.; Prentice Hall Inc.: Englewood Cliffs, NJ , 1952; p 340.
(5) (a) Wang, L.; Zhang, Y. Tetrahedron 1998, 54, 11129. (b) Banik,
B. K.; Mukhopadhyay, C.; Venkatraman, M. S.; Becker, F. F. Tetra-
hedron Lett. 1998, 39, 7243. (c) Yanada, R.; Negora. N.; Yanada, K.;
Fujita, T. Tetrahedron Lett. 1997, 38, 3271. (d) Yanada, R.; Bessho,
K.; Yanada, K. Chem. Lett. 1994, 1279. (e) Komachi, Y.; Kudo, T. Chem.
Pharm. Bull. 1994, 42, 402. (f) Komachi, Y.; Kudo, T. Chem. Pharm.
Bull. 1995, 43, 1422. (g) Ghatak, A.; Becker, F. F.; Banik, B. K.
Tetrahedron Lett. 2000, 41, 3793.
(6) General methods for activation of metals, see: (a) Cintas, P.,
Activated Metals in Organic Synthesis; CRC Press: Boca Raton, 1993.
(b) Furstner, A. Active Metals - Preparation, Characterization and
Application; VCH: Weinheim, 1996. For activation of Sm by ICH2-
CH2I, I2, HgI2, and Et2AlI to generate SmI2, see: (c) Girard, P.; Namy,
J . L.; Kagan, H. B. J . Am. Chem. Soc. 1980, 102, 2693. (Sm/ICH2CH2I).
(d) Imamoto, T.; Ono, M. Chem. Lett. 1987, 501. (Sm/I2). (e) Deacon,
G. B.; Forsyth, C. M. Chem. Lett. 1989, 837. (Sm/HgI2). (f) Nishiyama,
Y.; Shinomiya, E.; Kimura, S.; Itoh, K.; Sonoda, N. Tetrahedron Lett.
1998, 39, 3705.
10.1021/jo001362s CCC: $20.00 © 2001 American Chemical Society
Published on Web 12/13/2000