R. C. Larock, Y. Wang / Tetrahedron Letters 43 (2002) 21–23
23
59% isolated yield as a pure isomer, along with 11% of
the expected isomer 13. Hydrogenation of the desired
tosylamide under 1 atm of H2 using 5% Pd/C as a catalyst
and 95% ethanol as the solvent for 3 h afforded the
saturated tosylamide 14 in 92% yield. Subsequent deto-
sylation with Na and naphthalene provided theonelladin
D (2) in 90% yield as a single pure product.
is only commercially available as the hydrochloride salt,
a base is needed in the reaction system to release the
hydroxylamine. After optimization work on model sys-
tems, the coupling of 3-iodopyridine, 1,13-tetradecadiene
and the hydrochloride salt of N,O-dimethylhydroxyl-
amine provided the desired coupling product 18a,
alongside a small amount of an isomer 18b, in 45%
overall yield. The efficient catalytic room temperature
hydrogenation of this mixture afforded xestamine D (7)
and its branched isomer 19 in a 91:9 ratio in 94% overall
yield.
The similarity of niphatescine C and theonelladin C
suggested that we ought to be able to prepare the former
natural product using 2-methyl-1,11-dodecene with N-
benzyl tosylamide as the nucleophile (Scheme 3). The
required diene was prepared by the CuI-catalyzed cou-
pling of 10-iodo-1-decene and isopropenylmagnesium
bromide (97% yield). The palladium reaction was very
slow and only after 5 days was a 61% yield of the desired
tosylamide 15 obtained, along with 13% of the expected
isomer 16. The tosyl group was removed in 91% yield
using Na and naphthalene, and the resulting product 17
was hydrogenated and the benzyl group removed using
20% Pd(OH)2 in MeOH under 1 atm of H2, followed by
the addition of ammonium formate and heating for 20
min at 70 °C to afford the natural product niphatesine
C (3) in 70% overall yield.
Acknowledgements
We thank the donors of the Petroleum Research Fund,
administered by the America Chemical Society, for
partial support of this research and Johnson Matthey,
Inc., and Kawaken Fine Chemicals Co., Ltd., for dona-
tions of palladium salts.
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Scheme 4.