Angewandte
Chemie
[5] Prepared analogously to (R)-3, see: T. J. Heckrodt,
J. Mulzer, Synthesis 2002, 1857 – 1866.
[6] E. Dimitriadis, R. A. Massy-Westropp, Aust. J.
Chem. 1984, 37, 619 – 627.
[7] G. F. Solberghe, I. E. Marko, Tetrahedron Lett.
2002, 43, 5061 – 5066.
[8] A comparison of the analytical data of the natural
material and synthetic compounds 1a and 1b can be
found in the Supporting Information.
Scheme 4. Fragment coupling through Cu-catalyzed sp3–sp3 cross coupling. Synthesis
of (+)-1a and (+)-1b.
To prove the identity of the natural and synthetic material
13C NMR spectra of 1a and 1b were recorded in the presence
of an internal glass-capillary tube containing a solution of the
natural product in CDCl3.[8] Comparison of these spectra
showed a perfect match for diastereomer 1b. Finally, compar-
ison of the optical-rotation studies of the natural material
([a]2D0 + 10.7 (c = 0.44, CHCl3)) and the synthetic product 1b
([a]2D0 + 8.5 (c = 1.21, CHCl3)) determined the absolute
configuration of the natural product as that depicted in
Scheme 4.
In conclusion, the enantioselective total synthesis of the
(4S,6R,8R,10S,16R,18S)-hexamethyldocosane from Antitro-
gus parvulus has been accomplished, thus enabling the
relative and the absolute configuration of the natural product
to be determined. The successful enantioselective synthesis of
1b (and its diastereomer 1a) highlights the synthetic power of
our recent methodology for deoxypropionate construction,
which relies on an o-DPPB-directed and copper-mediated
allylic substitution by Grignard reagents. Furthermore, the
synthetic utility of copper-catalyzed sp3–sp3 cross-coupling for
fragment coupling in a total synthesis has been demonstrated.
Received: May 11, 2005
Published online: July 20, 2005
À
Keywords: asymmetric synthesis · C C coupling · Grignard
reaction · organocopper reagents · total synthesis
.
[1] P. G. Allsopp, K. J. Chandler, Proc. Int. Soc. Sugar-Cane Technol.
1989, 20, 810 – 816.
[2] a) M. T. Fletcher, S. Chow, L. K. Lambert, O. P. Gallagher, B. W.
Cribb, P. G. Allsopp, C. J. Moore, W. Kitching, Org. Lett. 2003, 5,
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Gallagher, C. J. Moore, B. W. Cribb, P. G. Allsopp, W. Kitching, J.
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[3] B. Breit, C. Herber, Angew. Chem. 2004, 116, 3878 – 3880; Angew.
Chem. Int. Ed. 2004, 43, 3790 – 3792.
[4] For previous reports on copper-catalyzed sp3–sp3 cross-coupling
reactions, see: a) M. Tamura, J. Kochi, Synthesis 1971, 303 – 305;
b) G. Fouquet, M. Schlosser, Angew. Chem. 1974, 86, 82 – 83;
Angew. Chem. Int. Ed. Engl. 1974, 13, 701 – 702; c) H. Kotsuki, I.
Kadota, M. Ochi, J. Org. Chem. 1990, 55, 4417 – 4422; d) T.
Netscher, Chimia 1996, 50, 563 – 567; e) G. Cahiez, C. Chaboche,
M. Jezequel, Tetrahedron 2000, 56, 2733 – 2737.
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ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim