C O M M U N I C A T I O N S
Table 2. C-H Insertion into Cyclohexane and Tetrahydrofuran
with EDA and Percentage of cis Isomer in the Styrene
Cyclopropanation Reaction Catalyzed by TpXCua,b
a For experimental details, see ref 13. b Percentage of the insertion product
at the end of the reaction (diethyl fumarate and maleate accounted for 100%
of EDA), determined by GC after total consumption of EDA. c Reference
11. d Not determined.
Figure 1. Plot of the yield of the C-H insertion products vs percentage
of the cis isomer in the styrene cyclopropanation reaction.
In conclusion, we have presented a series of catalysts of general
formula TpXCu that, by using ethyl diazoacetate as the carbene
source, catalyze the insertion of :CHCO2Et into the carbon-
hydrogen bonds of cycloalkanes and cyclic ethers in moderate-to-
high yield, and efficient use of Cu for this transformations should
rekindle interest in this inexpensive metal for these synthetically
useful reactions.
al.8a with the aforementioned rhodium catalyst (78 and 50% for
cyclohexane and cyclopentane, respectively). The almost quantita-
tive conversion13 of THF into the acetate derivative compares well
with Davies’ results4,5 with this cyclic ether (70-90%), in our case
with EDA as the carbene source. For tetrahydrofuran and tetrahy-
dropyran, the R-carbon-hydrogen bond was the preferred reaction
site, whereas for dioxolane the only product observed was that
derived from insertion into the C-H bond of the singular methylene
group between the oxygen atoms. These results are in accord with
those from Adams and co-workers14 who showed the preferential
insertion of carbenoids into C-H bonds adjacent to ether oxygens.
The relative reactivities of the substrates employed have also
been determined by means of competition experiments. The results
displayed in Table 1 show that the cycloalkane substrates were less
reactive than the cyclic ethers, with the exception of dioxolane.
Regarding the cyclic ethers, two trends are clearly observed (i) five-
membered rings are more reactive than six-membered rings, and
(ii) those with one oxygen atom are more reactive than the two-
oxygen-containing cycles.
Acknowledgment. We thank the Direccio´n General de Ensen˜an-
za Superior (Proyecto PB98-0958) and the Universidad de Huelva
(Servicio de Resonancia Magne´tica Nuclear).
References
(1) (a) Shilov, A. E.; Shul’pin, G. B. Chem. ReV. 1997, 97, 2879. (b) Arndtsen,
B. A.; Bergman, R. G.; Mobley, T. A.; Peterson, T. H. Acc. Chem. Res.
1995, 28, 154.
(2) (a) Dyker, G. Angew. Chem., Int. Ed. Engl. 1989, 28, 1698. (b) Guari,
Y.; Sabo-Etienne, S.; Chaudret, B. Eur. J. Inorg. Chem. 1999, 1047.
(3) (a) Doyle, M. P. In ComprehensiVe Organometallic Chemistry II; Abel,
E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon Press: Oxford,
U.K., 1995; Vol 12, p 387. (b) Doyle, M. P.; McKervey, M. A.; Ye, T.
Modern Catalytic Methods for Organic Synthesis with Diazo Compounds;
John Wiley & Sons: New York, 1998.
We have also tested the influence of the groups attached to the
TpX-pyrazolyl rings on the activity of the corresponding TpXCu
catalysts. Several catalysts have been employed under the same
experimental conditions, using cyclohexane or tetrahydrofuran as
the substrates. The results are shown in Table 2. For THF, the
aforementioned mesityl derivative provided the highest degree of
conversion, whereas the unsubstituted Tp ligand only gave 27%
yield. The TpPh ligand also afforded a good yield (82%), very close
to that of the cyclohexyl derivative, TpCy (72%). Regarding the
cycloalkane, the same order in reactivity was observed although
yields were considerably lower, as expected from Table 1. Thus, it
seems that the activation of these carbon-hydrogen bonds is
achievable in a general way for this family of TpXCu catalysts,
with the mesityl-derived catalyst being the most active of them.
Since a metal-carbene has been proposed to be the key intermediate
in both processes, that is, the C-H activation and the cyclopro-
panation reaction,3 some information could be gained comparing
experimental data of both reactions with the same catalysts. Figure
1 displays the plot of the yields in C-H insertion products for THF
and cyclohexane versus the percentage of the cis isomer obtained
in the styrene cyclopropanation reaction with those catalysts (Table
2).11 There is clearly a correlation between the cis diastereoselection
and the yields of C-H activation products. Somewhat similar results
were reported by Callot et al. for rhodium porphyrins as the
catalyst.9b This observed correlation may be related to the existence
of a limited catalytic pocket that would be responsible of the cis
diastereoselection and suggests that other cis-selective cyclopro-
panation catalysts3 should be revisited to test their capabilities
toward the activation of carbon-hydrogen bonds via carbene
insertion.
(4) Davies, H. M. L.; Antoulinakis, E. G. J. Organomet. Chem. 2001, 617-
618, 39.
(5) Davies, H. M. L.; Hansen, T.; Churchill, M. R. J. J. Am. Chem. Soc.
2000, 122, 3063.
(6) Scott, L. T.; DeCicco, G. J. J. Am. Chem. Soc. 1974, 96, 322.
(7) Wulfman, D. S.; McDaniel, R. S.; Peace, B. W. Tetrahedron, 1976, 32,
1241.
(8) (a) Demonceau, A.; Noels, A. F.; Hubert, A.; Teyssie´, P. J Chem. Soc.
Chem. Commun. 1981, 688. (b) Demonceau, A.; Noels, A. F.; Hubert,
A.; Teyssie´, P, Bull. Soc. Chim. Belg. 1984, 93, 945.
(9) (a) Callot, H. J.; Metz, F. Tetrahedron Lett. 1982, 23, 4321. (b) Callot,
H. J.; Metz, F. NouV. J. Chim. 1985, 9, 167.
(10) (a) Davies, H. M. L.; Grazini, M. V. A.; Aouad, E. Org. Lett. 2001, 3,
1475. (b) Davies, H. M. L.; Antoulinakis, E. G. Org. Lett. 2000, 2, 4153.
(c) Davies, H. M. L.; Stafford, D. G.; Hansen, T.; Churchill, M. R.; Keil,
K. M. Tetrahedron Lett. 2000, 41, 2035.
(11) D´ıaz-Requejo, M. M.; Belderrain, T. R.; Trofimenko, S.; Pe´rez, P. J. J.
Am. Chem. Soc. 2001, 123, 3167.
(12) Trofimenko, S. Scorpionates, The Coordination Chemistry of Polypyra-
zolylborate Ligands; Imperial College Press: London, 1999.
(13) Experimental Section: (a) 0.05 mmol of CuI and an equimolar amount
of the TlTpMs salt were dissolved in CH2Cl2, and the mixture was stirred
for 2-3 h. Volatiles were removed under vacuum, and the residue was
extracted with 15 mL of cyclohexane. To the resulting filtrate, a solution
of 1.25 mmol of EDA (50 equiv relative to Cu) dissolved in 5 mL of
cyclohexane was slowly added at a 1 mL/h rate (total time 5 h). No EDA
was detected at the end of the reaction by GC. (b) Relative reactivities:
after catalyst generation, it was dissolved in an equimolar mixture of
substrates (e.g., cyclohexane and THF). EDA (1 mmol) was dissolved in
10 mL of dichloroethane and added at a 1 mL/h (total time 10 h). (c)
TpXCu (0.05 mmol, generated as above) was dissolved in 10 mL of THF,
and a solution of EDA (1.25 mmol, 25 equiv relative to Cu) in THF (10
mL) was added at a 2.5 mL/h (total time 4 h). The cyclohexane
experiments were nearly identical (total time 20 h) but required a 1:1
mixture of the cycloalkane and CH2Cl2 due to the insolubility of some
catalysts in neat C6H12. No reaction was observed in a control experiment
carried out with CH2Cl2 as the solvent, with only diethyl fumarate and
maleate being obtained in this case.
(14) Adams, J.; Poupart, M.-A.; Schller, C.; Ouimet, N.; Frenette, R.
Tetrahedron Lett. 1989, 14, 1749.
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