5486
L. Zhou et al. / Tetrahedron Letters 52 (2011) 5484–5487
the furan 3j was obtained in 58% yield after stirring in MeCN at
80 °C for 20 h (Eq. 2). These results suggest that without the
promotion of CuI the triple bond cannot be attacked by carbonyl
oxygen directly.
In conclusion, we have developed a copper-catalyzed cascade
coupling/cyclization of terminal alkynes with -alkyl substituted
a
diazoesters. This new method furnished a straightforward route
to 2,3,5-trisubstituted furans derivatives with good efficiency and
selectivity. The scope, mechanism and synthetic application of this
efficient coupling/cyclization reaction are now under investigation
in our lab.
MeCN, 80 o
C
OEt
Ph
OEt
O
ð1Þ
ð2Þ
20 h
Ph
Ph
O
3j
5
<10%
Acknowledgments
CuI/phenanthroline
MeCN, 80 oC, 20 h
OEt
Ph
3j
OEt
The project is supported by Natural Science Foundation of China
(Grant Nos. 20902005, 20832002, 20772003, 20821062), National
Basic Research Program of China (973 Program, No.
2009CB825300). LZ thanks the financial support from GSK R&D
China and China Postdoctoral Science Foundation.
O
O
, 58% by 1H NMR
5
Based on our understanding on the Cu(I)-catalyzed cross cou-
pling reaction of N-tosylhydrazones with terminal alkynes,7,11c
we proposed a plausible mechanism to account for the current
Cu(I)-catalyzed coupling of diazo compounds, as shown in path a
of Scheme 1. Copper acetylide A is formed from phenylacetylene
and Cu(I) salt, followed by the reaction of copper acetylide A with
diazo substrate leading to the formation of copper carbene species
B. Migratory insertion of alkynyl group to the carbenic carbon gives
the intermediate C, which affords 3-alkynoate 4a by the direct pro-
tonation. The intramolecular nucleophilic attack of the carbonyl
group to triple bond produces the intermediate D. The latter under-
goes a subsequent proton transfer to afford furan 3a with simulta-
neous regeneration of the Cu(I) catalyst.
Supplementary data
Supplementary data associated with this article can be found, in
References and notes
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Me
Cu(I)L
path a
Ph
Ph
OMe
LCu
O
3a
H
CuI
Me
OMe
Ph
Cu(I)L
Ph
O
A
N2
Me
CO2Me
D
Me
Ph
CO2Me
4a
Ph
L
Ph
H
LCu
Me
Cu
O
Me
CO2Me
OMe
B
C
6. Suarez, A.; Fu, G. C. Angew. Chem., Int. Ed. 2004, 43, 3580.
7. Xiao, Q.; Xia, Y.; Li, H.; Zhang, Y.; Wang, J. Angew. Chem., Int. Ed. 2011, 50, 1114.
8. Hassink, M.; Liu, X.; Fox, J. M. Org. Lett. 2011, 13, 2388.
path b
N2
CuI
Me CO2Me
Ph
Ph
CuI
9. For selected examples of cycloisomerization approaches to substituted furans
from alkynes, see: (a) Zhang, M.; Jiang, H.; Neumann, H.; Beller, M.; Dixneuf, P.
H. Angew. Chem., Int. Ed. 2009, 48, 1681; (b) Xiao, Y.; Zhang, J. Angew. Chem., Int.
Ed. 2008, 47, 1903; (c) Zhang, J.; Schmalz, H.-G. Angew. Chem., Int. Ed. 2006, 45,
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Hashmi, A. S. K.; Sinha, P. Adv. Synth. Catal. 2004, 346, 432.
10. For selected examples of cycloisomerization approaches to substituted
furans from allenyl ketones, see: (a) Dudnik, A. S.; Sromek, A. W.; Rubina,
M.; Kim, J. T.; Kel’in, A. V.; Gevorgyan, V. J. Am. Chem. Soc. 2008, 130, 1440;
Me
CO2Me
Me
CO2Me
N2
F
E
Me
OMe
ring-opening
cycloisomerization
reaction
Ph
O
Scheme 1. Mechanistic rationale.