Organometallic reactions in aqueous media. Indium-mediated 1,3-butadien-2-ylation of carbonyl compounds

Article abstract of DOI:10.1021/ol000239k

(Equation Presented) Indium-mediated coupling of 1,4-dibromo-2-butyne with carbonyl compounds in aqueous media gave good yields of the 1,3-butadien-2-ylmethanols.

Full text of DOI:10.1021/ol000239k

ORGANIC
LETTERS
2000
Vol. 2, No. 22
3469-3471
Organometallic Reactions in Aqueous
Media. Indium-Mediated
1,3-Butadien-2-ylation of Carbonyl
Compounds
Wenshuo Lu, Jihai Ma, Yang Yang, and Tak Hang Chan*
Department of Chemistry, McGill UniVersity, Montreal, Quebec,Canada, H3A 2K6
thchan@chemistry.mcgill.ca
Received August 23, 2000
ABSTRACT
Indium-mediated coupling of 1,4-dibromo-2-butyne with carbonyl compounds in aqueous media gave good yields of the 1,3-butadien-2-
ylmethanols.
In view of the usefulness of functionalized dienes in organic
synthesis, a number of reagents have been developed for the
1,3-butadien-2-ylation of carbonyl compounds (Scheme 1).
compounds to give regioselective 1,3-butadien-2-ylmetha-
nols, are not convenient to prepare. From the viewpoint of
atom economy,6 reagents 3-6, requiring the use of a silyl,
stannyl, or boron appendage, cannot be considered as atom
economical.7 Finally, all these reactions must be carried out
in anhydrous organic solvents.
The discovery8 in the past decade that the allylation of
carbonyl compounds could be achieved in aqueous media
through a Barbier-type reaction9 has drawn much interest.
Metals such as Zn,10 In,11 Bi,12 Sn,13 Pb,14 Mn,15 Mg,16 or
Scheme 1
(2) Wada, E.; Kanemasa, S.; Fujiwara, I.; Tsuge, O. Bull. Chem. Soc.
Jpn. 1985, 58, 1942.
(3) (a) Nishiyama, T.; Esumi, T.; Iwabuchi, Y.; Irie, H.; Hatakeyama,
S. Tetrahedron Lett. 1998, 39, 43. (b) Hatakeyama, S.; Yoshida, M.; Esumi,
T.; Iwabuchi, Y.; Irie, H.; Kawamoto, T.; Yamada, H.; Nishizawa, M.
Tetrahedron Lett. 1997, 38, 7887.
(4) (a) Luo, M.; Iwabuchi, Y.; Hatakeyama, S. J. Chem. Soc., Chem.
Commun. 1999, 267. (b) Yu, C.-M.; Lee, S.-J.; Jeon, M. J. Chem. Soc.,
Perkin Trans. 1 1999, 3557.
(5) (a) Zheng, B.; Srebnik, M. J. Org. Chem. 1995, 60, 486. (b)
Soundararajan, R.; Li, G.; Brown, H. C. J. Org. Chem. 1996, 61, 100.
(6) Trost, B. M. Science 1991, 254, 1471.
(7) In the case of 4 or 5, a stoichiometric amount of Lewis acid is further
required to promote the reaction.
(8) For reviews, see: (a) Li, C. J.; Chan, T. H. Organic Reactions in
Aqueous Media; John Wiley & Sons Inc.; New York, 1993. (b) Li, C. J.
Chem. ReV. 1993, 93, 2023. (c) Chan, T. H.; Li, C. J.; Lee, M. C.; Wei, Z.
Y. Can. J. Chem. 1994, 72, 1181. (d) Lubineau, A.; Auge, J.; Queneau, Y.
Synthesis 1994, 741. (e) Li, C. J. Tetrahedron 1996, 52, 5643.
Of these, 2-(1,3-butadienyl)magnesium chloride (1) suffers
from poor regioselectivity.1 The corresponding lithium
compound 2 has to be prepared indirectly from the 2-stannyl
compound 3.2 Homoallenylic silane 4,3 stannane 5,4 and
boronate 6,5 though quite effective in reacting with carbonyl
(1) Nunomoto, S.; Yamashita, Y. J. Org. Chem. 1979, 44, 4788.
10.1021/ol000239k CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/05/2000

cursors for an intramolecular Diels-Alder (IMDA) reac-
tion.21 Indeed, when compound 20 was heated in xylene at
160° for 8 h, adduct 24 was obtained in 84% yield (Scheme
3). The possibility of such an IMDA approach to the
Scheme 2
Scheme 3
Sb17 have been reported to be effective in mediating the
coupling between allyl halides and carbonyl compounds to
give the corresponding homoallylic alcohols in aqueous
media. Among these reported metals, indium appears to be
the metal of choice because it requires no activation, causes
few side reactions, and is quite regio- and stereoselective.18
The indium-mediated coupling reaction has been extended
to propargyl bromides.19 We report here that indium can
effectively mediate the coupling between 1,4-dibromobut-
2-yne (7) and carbonyl compounds in aqueous media to give
regioselective 1,3-butadien-2-ylmethanols 8 in good yields
(Scheme 2).20
construction of the taxoid skeleton has been noted previ-
ously.20,22,23
The results are summarized in Table 1. The reaction works
The reaction is likely to proceed via an organoindium
intermediate24 which reacts with the aldehyde to give adduct
26 (Scheme 4). Further reaction of the bromide with indium
can lead to another organoindium intermediate, 27, which
is quenched by water to give 1,3-butadienyl-2-methanol 8.
Reaction of 27 with another molecule of aldehyde to give
di-adduct 28 was not observed, presumably because of steric
hindrance. However, we were able to show that with glutaric
dialdehyde 29 intramolecular trapping of intermediate 27 was
possible and the cyclic di-adduct 30 was obtained in 40%
isolated yield.
Table 1. Indium-Mediated 1,3-Butadien-2-ylation of Carbonyl
Compounds in Water
(10) (a) Nokami, J.; Otera, J.; Sudo, T.; Okawara, R. Organometallics
1983, 2, 191. (b) Petrier, C.; Luche, J. L. J. Org. Chem. 1983, 50, 910.
(11) (a) Li, C. J.; Chan, T. H. Tetrahedron Lett. 1991, 32, 7017. (b)
Paquette, L. A.; Bennett, G. D.; Isaac, M. B.; Chhatriwalla, A. J. Org. Chem.
1998, 63, 1836. (c) Li, C. J.; Chan, T. H. Tetrahedron 1999, 55, 11149 and
references therein.
(12) Wada, M.; Ohki, H.; Akiba, K. Y. Bull. Chem. Soc. Jpn. 1990, 63,
2751; J. Chem. Soc., Chem. Commun. 1987, 708.
(13) (a) Nokami, J.; Otera, J.; Sudo, T.; Okawara, R. Organometallics
1983, 2, 191. (b) Nokami, J.; Wakabayashi, S.; Okawara, R. Chem. Lett.
1984, 869. (c) Uneyama, K.; Kamaki, N.; Moriya, A.; Torii, S. J. Org.
Chem. 1985, 50, 5396. (d) Wu, S. H.; Huang, B. Z.; Zhu, T. M.; Yiao, D.
Z.; Chu, Y. L. Acta Chim. Sin. 1990, 48, 372. (e) Einhorn, C.; Luche, J. L.
J. Organomet. Chem. 1987, 322, 177.
(14) Zhou, J. Y.; Jia, Y.; Sun, G. F.; Wu, S. H. Synth. Commun. 1997,
27, 1899.
(15) Li, C. J.; Meng, Y.; Yi, X. H.; Ma, J. H.; Chan, T. H. J. Org. Chem.
1998, 63, 7498; J. Org. Chem. 1997, 62, 8632.
a Isolated yield.
(16) Zhang, W. C.; Li, C. J. J. Org. Chem. 1999, 64, 3230.
(17) (a) Wang, W.; Shi, L.; Huang, Y. Tetrahedron 1990, 46, 3315. (b)
Ren, P. D.; Jin, Q. H.; Yao, Z. P. Synth. Commun. 1997, 27, 2761.
(18) Isaac, M. B.; Chan, T. H. Tetrahedron Lett. 1995, 36, 8957.
(19) Isaac, M.; Chan, T. H. J. Chem. Soc., Chem. Commun. 1995, 1003.
(20) For recent reports of indium-mediated synthesis of 1,4-butadien-3-
ylation of carbonyl compounds, see: (a) Melekhov, A.; Fallis, A. G.
Tetrahedron Lett. 1999, 40, 7867. (b) Woo, S.; Squires, N.; Fallis, A. G.
Org. Lett. 1999, 1, 573.
equally well for aryl and aliphatic aldehydes. With cinna-
maldehyde (entry 3), the coupling occurred selectively in
the 1,2-addition fashion. The ester function is not affected
(entries 6 and 7). The incorporation of an R,â-unsaturated
ester function into the structure as in compounds 20 or 22
is interesting since these compounds may serve as pre-
(21) For recent review, see: (a) Fallis, A. G. Acc. Chem. Res. 1999, 32,
464. (b) Fallis, A. G. Can. J. Chem. 1999, 77, 159.
(22) For recent reports, see: (a) Phillips, A. J.; Morris, J. C.; Abell, A.
D. Tetrahedron Lett. 2000, 41, 2723 (b) Forgione, P.; Wilson, P. D.; Yap,
G. P. A.; Fallis, A. G. Synthesis 2000, 921.
(23) IMDA reaction of 22 under the same reaction condition did not
give the bicyclic adduct. See, however, ref 22.
(9) Barbier, P. Comp. Rend. 1899, 128, 110. For a recent monograph,
see Blomberg, C. The Barbier Reaction and Related One-Step Processes.
In ReactiVity and Structure: Concepts in Organic Chemistry; Hafner, K.,
Lehn, J. M., Rees, C. W., von Rague Schleyer, P., Trost, B. M., Zahradnik,
R., Eds.; Springer-Verlag: 1993.
(24) Chan, T. H.; Yang, Y. J. Am. Chem. Soc. 1999, 121, 3228.
3470
Org. Lett., Vol. 2, No. 22, 2000

Scheme 4
In view of the simplicity of the present process for the
synthesis of 2-substituted 1,3-butadienes, the reaction is likely
to find considerable applications.25
Acknowledgment. We thank NSERC for financial
support.
Supporting Information Available: Experimental details
and spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
(25) Standard procedures for the reaction of aldehydes with 7 are as
follows: To a mixture of aldehyde (1 mmol) in water (5 mL) and the
bromide 7 (1.5 mmol),26 was added indium powder (3 mmol) in one portion,
and the mixture was vigorously stirred for 6 h. Ethyl ether was added to
the reaction mixture, and the organic layer was separated. The aqueous
phase was extracted with ethyl ether. The organic extracts were combined,
dried over Na2SO4, filtered, and evaporated. The residue, for most of the
aldehydes, afforded the corresponding 1,3-butadien-2-ylmethanols 8 as the
major product according to 1H NMR. If necessary, purification was
performed by flash chromatography over silica gel using hexane and ethyl
acetate as eluent.
OL000239K
(26) Compound 7 was synthesized according to the literature: Johnson,
A. W. J. Chem. Soc. 1946, 1009.
Org. Lett., Vol. 2, No. 22, 2000
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