T. K. Chakraborty, P. Laxman / Tetrahedron Letters 43 (2002) 2645–2648
2647
Scheme 2. Final steps in the synthesis of (+)-crocacin D (4).
References
(NMM) led to a mixed anhydride which reacted suc-
cessfully with glycine methyl ester to furnish 16 in 77%
yield. Finally, deprotection of the TBS group of 16
using tetra-n-butylammonium fluoride (TBAF) in THF
led to the formation of an oxy anion intermediate that
underwent a smooth in situ Peterson elimination pro-
cess, in 78% yield, to install the final and most impor-
tant cis enamide moiety in the framework with
complete stereoselectivity resulting in the successful
completion of the first total synthesis of crocacin D (4).
Our synthetic crocacin D (4) showed rotation [h]D20
+100.3 (c 0.13, MeOH); lit. value: [h]2D2 +109.6 (c 0.56,
MeOH)2 and was identical in all respects with the
naturally occurring crocacin D having all spectroscopic
data9 matching with those reported for the natural
product.2
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In conclusion, a mild method for the synthesis of a cis
enamide starting from an epoxysilane following two
simple steps, silyl-directed epoxide opening with an
azide ion and a Peterson elimination, has been devel-
oped leading to the first total synthesis of (+)-crocacin
D. Although a similar approach using epoxysilanes as
substrates for the synthesis of simple enamides has very
recently been reported,6a its efficacy in the synthesis of
a complex natural product containing this very chal-
lenging structural moiety is realized here for the first
time. This will help us to achieve the total synthesis of
the other members of the family. Further work is
currently in progress.
Acknowledgements
The authors wish to thank Drs. A. C. Kunwar and M.
Vairamani for NMR and mass spectroscopic assistance,
respectively, and CSIR, New Delhi for a research fel-
lowship (P.L.).
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