ORGANIC
LETTERS
2007
Vol. 9, No. 9
1643-1646
Palladium-Catalyzed Diastereoselective
Coupling of Propargylic Oxiranes with
Terminal Alkynes
Masahiro Yoshida,* Maiko Hayashi, and Kozo Shishido
Graduate School of Pharmaceutical Sciences, The UniVersity of Tokushima, 1-78-1
Sho-machi, Tokushima 770-8505, Japan
Received January 29, 2007
ABSTRACT
A diastereoselective coupling of propargylic oxiranes with terminal alkynes has been developed with use of a palladium catalyst. The
stereochemistries of the resulting 4-alkynyl-substituted 2,3-allenols have been altered depending on the palladium catalyst. An optically active
anti-substituted allene was synthesized from the reaction of an enantiomerically enriched propargylic oxirane without loss of chirality.
Substituted allenes are versatile building blocks for organic
synthesis because of the inherent reactivity of their axially
chiral backbones.1 In addition, many natural products
containing the allenic moiety have been isolated, and most
of these have axial chirality.2 As a result, the synthesis of
substituted allenes has been extensively studied,1 especially
the palladium-catalyzed coupling of propargylic oxiranes,
which is one of the most common methods. Organozinc,3
stannane,4 and -boron reagents5 and carbon monoxide6 were
reacted with propargylic oxiranes in the presence of pal-
ladium to furnish the corresponding 4-substituted 2,3-allenols.
The diastereoselectivity of the couplings was further exam-
ined,4,5 and anti-substituted allenols were diastereoselectively
produced via an anti-SN2′ attack of palladium on the
propargylic oxiranes. During the course of our studies on
the reaction of propargylic oxiranes in the presence of
palladium catalysts,5,7 we focused on the diastereoselective
coupling with terminal alkynes.8 Herein we describe a
palladium-catalyzed coupling of propargylic oxiranes with
terminal alkynes. The stereochemistries of the resulting
4-alkynyl-substituted 2,3-allenols have been altered depend-
ing on the palladium catalyst.
(1) For selected reviews, see: (a) Marshall, J. A. Chem. ReV. 2000, 100,
3163. (b) Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan, F. A. Chem.
ReV. 2000, 100, 3067. (c) Ma, S. Acc. Chem. Res. 2003, 36, 701. (d) Hashmi,
A. S. K. Angew. Chem., Int. Ed. 2000, 39, 3590. (e) Hoffmann-Ro¨der, A.;
Krause, N. Angew. Chem., Int. Ed. 2002, 41, 2933. (f) Krause, N.;
Hoffmann-Ro¨der, A.; Canisius, J. Synthesis 2002, 1759. (g) Hoffmann-
Ro¨der, A.; Krause, N. Angew. Chem., Int. Ed. 2004, 43, 1196.
(2) (a) Krause, N.; Hoffmann-Ro¨der, A. Allenic Natural Products and
Pharmaceuticals. In Modern Allene Chemistry; Krause, N., Hashmi, A. S.
K., Eds.; Wiley-VCH: Weinheim, Germany, 2004; p 997. (b) Landor S.
R. Naturally Occurring Allenes. In The Chemistry of the Allenes; Landor
S. R., Ed.; Academic Press: London, UK, 1982; p 679. (c) Claesson, A.
Biologically Active Allenes. In The Chemistry of the Allenes; Landor S.
R., Ed.; Academic Press: London, UK, 1982; p 709. (d) Robinson, C. H.;
Covey, D. F. Biological Formation and Reactions; In The Chemistry of
Ketenes, Allenes and Related Compounds; Patai S., Ed.; Wiley: Chichester,
UK, 1980; p 451.
The initial reactions were carried out with the phenyl-
substituted propargylic oxirane 1a and trimethylsilylacetylene
(2a). When 1a and 2a were subjected to the reaction with
(4) Kjellgren, J.; Sunde´n, H.; Szabo´, K. J. J. Am. Chem. Soc. 2005, 127,
1787.
(5) Yoshida, M.; Ueda, H.; Ihara, M. Tetrahedron Lett. 2005, 46, 6705.
(6) Knight, J. G.; Ainge, S. W.; Baxter, C. A.; Eastman T. P.; Harwood,
S. J. J. Chem. Soc., Perkin Trans. 1 2000, 3188.
(7) Yoshida, M.; Morishita, Y.; Ihara, M. Tetrahedron Lett. 2005, 46,
3669.
(8) It has been reported that palladium-catalyzed coupling reactions of
optically active propargylic carbonates with alkynylzinc reagents afford
optically active allenes in an enantiospecific manner; however, the absolute
configuration of the resulting allenes has not been determined: Dixneuf,
P. H.; Guyot, T.; Ness, M. D.; Roberts, S. M. Chem. Commun. 1997, 2083.
(3) Kleijn, H.; Meijer, J.; Overbeek, G. C.; Vermeer, P. Recl. TraV. Chim.
Pay-Bas. 1982, 101, 97.
10.1021/ol070224n CCC: $37.00
© 2007 American Chemical Society
Published on Web 03/28/2007