T.-P. Loh et al. / Tetrahedron Letters 44 (2003) 507–509
509
This method11 has several advantages for the following
reasons: (1) its experimental is simple and applicable to
various aldehydes; (2) the chiral promoters, both (−)-
cinchonidine and the corresponding pseudo-enantiomer
(+)-cinchonine can be purchased as inexpensive com-
modities. In conclusion, we have discovered a simple
and convenient method for the regioselective and enan-
tioselective synthesis of homopropargylic alcohols. We
believe this will make a useful and important addition
to the existing methods and will find practical applica-
tions in organic synthesis. The identity of the propargyl
indium-chiral promoter complexes and reaction mecha-
nism still remains obscure, and further work in this area
is underway in our laboratory.
Ishiguro, M.; Ikeda, N.; Yamamoto, H. J. Am. Chem.
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Chem. Commun. 1997, 763; (e) Iseki, K.; Kuroki, Y.;
Kobayashi, Y. Tetrahedron: Asymmetry 1998, 9, 2889.
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Kimura, M. Angew. Chem., Int. Ed. Engl. 1996, 35, 878;
(b) Keck, G. E.; Krishnamurthy, D.; Chen, X. Tetra-
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919.
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H. Chem. Commun. 1995, 2485; (b) Doherty, S.; Corri-
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Acknowledgements
We thank the National University of Singapore for
generous financial support.
9. (a) Isaac, M. B.; Chan, T. H. Chem. Commun. 1995,
1003; (b) Yi, X. H.; Meng, Y.; Hua, X. G.; Li, C. J. J.
Org. Chem. 1998, 63, 7472; (c) Yoo, B. W.; Lee, S. J.;
Choi, K. H.; Keum, S. R.; Ko, J. J.; Choi, K. I.; Kim, J.
H. Tetrahedron Lett. 2001, 42, 7287.
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1855; (b) Loh, T. P.; Zhou, J. R.; Li, X. R. Tetrahedron
Lett. 1999, 40, 9333.
11. Typical experimental procedure: To a 50 mL round-bot-
tom flask containing an egg-shaped stirring bar were
added (−)-cinchonidine 3 (294 mg, 1.0 mmol) and indium
powder (114 mg, 1.0 mmol). The solids were azeotropi-
cally dried twice with 3 mL of dry THF and then treated
with 3 mL of dry THF and propargyl bromide (226 mL,
3.0 mmol). The mixture was stirred vigorously until it
turned into a clear solution, to which was added dropwise
1 mL of dry hexane following by introduction of ben-
zaldehyde (0.5 mL, 0.5 mmol) dropwise at rt. The reac-
tion mixture was stirred at rt for 15 h, and finally
quenched with 10 mL of dilute HCl solution. The
aqueous layer was extracted with hexane (10 mL×3). The
combined organic extracts were washed with brine, dried
over anhydrous magnesium sulfate, concentrated under
vacuum, and purified by flash silica gel column chro-
matography to afford 71% of the homopropargylic alco-
hol as a colorless oil (52 mg, 0.356 mmol).
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