ORGANIC
LETTERS
2013
Vol. 15, No. 19
5138–5141
Synthesis of (()-Amathaspiramide F and
Discovery of an Unusual Stereocontrolling
Element for the [2,3]-Stevens
Rearrangement
Arash Soheili and Uttam K. Tambar*
Department of Biochemistry, The University of Texas Southwestern Medical Center at
Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States
Received September 8, 2013
ABSTRACT
A formal total synthesis of (()-amathaspiramide F through a tandem palladium-catalyzed allylic amination/[2,3]-Stevens rearrangement is
reported. The unexpected diastereoselectivity of the [2,3]-Stevens rearrangement was controlled by the substitution patterns of an aromatic ring.
This discovery represents a new stereocontrolling element for [2,3]-sigmatropic rearrangements in complex molecular settings.
Since their isolation in 1999, the amathaspiramide alka-
loids have garnered attention from the scientific commu-
nity because of their reported antiviral, cytotoxic, and
antimicrobial activities as well as their unique and intricate
chemical structures.1 Synthetic efforts toward these
polycyclic alkaloids have unveiled important stereocon-
trolling elements for the assembly of contiguous stereo-
centers in complex molecular settings, such as C-1 and C-2
of amathaspiramide F (Scheme 1).2
In this context, we were interested in utilizing a diaster-
eoselective [2,3]-Stevens rearrangement to construct the
two contiguous stereocenters at C-1 and C-2 of amathas-
piramide F. While [3,3]-rearrangements routinely appear
as key transformations in the total synthesis of natural
products, [2,3]-rearrangements have been relatively under-
utilized in complex molecular settings.3 For example, [2,3]-
Stevens rearrangements have been employed in the total
synthesis of natural products for the generation of one
carbon stereocenter.4 The use of [2,3]-Stevens rearrangements
(1) Morris, B. D.; Prinsep, M. l. R. J. Nat. Prod. 1999, 62, 688.
(2) (a) Hughes, C. C.; Trauner, D. Angew. Chem., Int. Ed. 2002, 114,
4738. (b) Sakaguchi, K.; Ayabe, M.; Watanabe, Y.; Okada, Takuya;
Kawamura, K.; Shiada, T.; Ohfune, Y. Org. Lett. 2008, 10, 5449. (c)
Chiyoda, K.; Shimokawa, J.; Fukuyama, T. Angew. Chem., Int. Ed.
2012, 51, 2505.
(3) (a) Stevens, T. S.; Creighton, E. M.; Gordon, A. B.; MacNicol, M.
ꢀ
J. Chem. Soc. 1928, 3193. (b) Marko, I. E. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: New York, 1991;
€
Vol. 3, pp 913À974. (c) Bruckner, R. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 6, pp
873À908. (d) Hoffmann, R. W. Angew. Chem., Int. Ed. Engl. 1979, 18,
563. (e) Honda, K.; Inoue, S.; Sato, K. J. Am. Chem. Soc. 1990, 112, 1999.
(4) (a) Honda, K.; Tabuchi, M.; Inoue, S. Chem. Lett. 1996, 385. (b)
Honda, K.; Yoshii, I.; Inoue, S. Chem. Lett. 1996, 671. (c) Honda, K.;
Igarashi, D.; Asami, M.; Inoue, S. Synlett 1998, 685. (d) Li, W.-D. Z.;
Wang, Y.-Q. Org. Lett. 2003, 5, 2931. (e) Zhou, C.-Y.; Yu, W.-Y.; Chan,
P. W. H.; Che, C.-M. J. Org. Chem. 2004, 69, 7072. (f) Li, W.-D. Z.;
Wang, X.-W. Org. Lett. 2007, 9, 1211. (g) Sakaguchi, K.; Ayabe, M.;
Watanabe, Y.; Okada, T.; Kawamura, K.; Shiada, T.; Ohfune, Y. Org.
Lett. 2008, 10, 5449. (h) Sun, M.-r.; Lu, H.-t.; Wang, Y.-z.; Yang, H.;
Liu, H.-m. J. Org. Chem. 2009, 74, 2213.
ꢀ
(f) Arbore, A. P. A.; Cane-Honeysett, D. J.; Coldham, I.; Middleton, M. L.
Synlett 2000, 236. (g) Moniz, G. A.; Wood, J. L. J. Am. Chem. Soc. 2001,
123, 5095. (h) Workman, J. A.; Garrido, N. P.; Sanc-on, J.; Roberts, E.;
Wessel, H. P.; Sweeney, J. B. J. Am. Chem. Soc. 2004, 127, 1066. (i)
Vanecko, J. A.; Wan, H.; West, F. G. Tetrahedron 2006, 62, 1043. (j)
Sweeney, J. B. Chem. Soc. Rev. 2009, 38, 1027. (k) Mack, D. J.; Batory,
L. A.; Njardarson, J. T. Org. Lett. 2011, 14, 378. (l) Strick, B. F.;
Mundal, D. A.; Thomson, R. J. J. Am. Chem. Soc. 2011, 133, 14252.
r
10.1021/ol4025937
Published on Web 09/25/2013
2013 American Chemical Society