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In conclusion, we have developed a novel protocol for the
synthesis of functionalized 1,3-enyne motifs using Rh(III)-
catalyzed C–H olefinic alkynylation of enamides. By taking
advantage of the ortho-directing effect of the amide group, this
reaction underwent stereospecific activation of olefinic C–H
bonds, thus providing a straightforward and efficient method
for the construction of cis-enynamide frameworks. Because of
the very mild reaction conditions, a large variety of synthetically
useful functional groups were nicely tolerated. Furthermore,
the enynamide products thus obtained through C–H alkynyla-
tion could be easily transformed into structurally relevant
motifs by virtue of Sonogashira coupling or cycloaddition
reactions.
We gratefully acknowledge USTC Research Fund, the
Nanyang Technological University, Singapore Ministry of Edu-
cation Academic Research Fund (ETRP 1002 111, MOE2010-T2-
2-067, MOE 2011-T2-1-013) for the funding of this research. We
also thank Dr Y. X. Li for X-ray support.
Notes and references
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Scheme 2 Alkynylation using other alkynyl reagents and the isotope
experiment.
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Scheme 3 Synthetic transformations of enynamide 3a.
which produced a KIE value of 1.5 (refer to the ESI†). Furthermore,
when 13C labelled alkynyliodonium reagent 1-C13 was subjected to
the standard reaction conditions with 2a, the desired product was
obtained in 80% yield, indicating that no silyl-migration occurred
during the catalytic cycle (Scheme 2).
In order to showcase the applicability of alkynylation
products, further transformations by taking advantage of
the alkynyl group were explored (Scheme 3). Desilylation of
3a worked smoothly with the TBAF/HOAc system, which
generated the terminal alkyne 6a in 91% yield. In addition,
desilylation–Sonogashira coupling between 3a and 4-iodo-
benzonitrile also proceeded nicely to afford 5a in 78% yield.
In addition, triazole 7a could be generated in 88% yield by the
copper-catalyzed cycloaddition between terminal alkyne 6a
and benzyl azide.
9 For a review on the synthetic applications of enamides, see:
D. R. Carbery, Org. Biomol. Chem., 2008, 6, 3455.
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