New Palladium-Catalyzed Cascades: 4-exo-dig Cyclocarbopalladation Reaction
Table 5. 4-exo-dig/Sonogashira cascade with enynes.
Entry
R1
R2
X
Yield [%]
1
2
3
4
CH3
H
CH3
p-MeOCOC6H4
(Z)-CH2OTBS
CH
CH
N
23: 79
(E)-C
N
24: 83[a]
25: 64[b]
26: 70[c]
(E)-OH
(E)-t-Bu
N
[a]
14% of 1a was recovered.
40 min at 1308C. 10% of 1a were recovered.
The desired product cannot be separated from the starting material. The yield is calculated from the H NMR spectra,
[b]
[c]
1
28% of 1a were recovered.
is not satisfactory, a terminal Sonogashira cross-cou-
pling instead of Suzuki–Miyaura cross-coupling has
been developped. Optimized conditions appear to be
applicable to many other alkynes: propargylic alco-
hols, ethers, and amines, as well as aliphatic and aro-
matic alkynes. The same starting material readily un-
dergoes the cascade reaction as well with enynes, al-
kynylimines and oximes. Studies concerning the trans-
formations of these azatrienynes to azafenestradienes
are still in progress. Finally, when the hydroxy group
in the starting material is replaced with a nitrogen,
the cascade proceeds also in good yields affording the
desired products.
microwave. The reaction mixture was then filtered through
celite to eliminate the metal traces and then concentrated
under reduced pressure. The crude product was purified by
flash column chromatography.
Acknowledgements
We thank the CNRS, the ANR (A.S.) and Prestwick chemical
(A.B.) for financial support and the MNERT (M.C.) for fel-
lowships.
The tricyclic product including a cyclobutane is ob-
tained in high yields and in a one-pot operation. This
References
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Experimental Section
General Procedure for the Cyclocarbopalladtion 4-
exo-dig/Sonogashira Cascade
In a 2–5 mL microwave vial were added the compound 1a
or 1d–1i (1 equiv.), PdACHTUNTRGNEUNG(OAc)2 (0.05 equiv.), copper iodide
(0.1 equiv.), and PPh3 (0.1 equiv.). The vial was sealed with a
teflon cap and the reaction mixture was then dissolved in
distilled diisopropylamine (3 mL). The reaction mixture was
placed under argon, frozen in liquid nitrogen and put under
vacuum. The O2 liberation proceeds when the temperature
rises back to ambient temperature. The operation was re-
peated two times. Then, the terminal alkyne (1.5 equiv.) was
added to the reaction mixture. The vial was irradiated in the
Adv. Synth. Catal. 2011, 353, 3151 – 3156
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