Journal of the American Chemical Society
COMMUNICATION
5a. It is noteworthy that the energy barrier from IN5 to TS2 is
only +5.6 kcal/mol, indicating a very fast elimination. This may
explain why only a trace amount of 5a is produced. In the
catalytic cycle, the rate-limiting step corresponds to the Heck-like
four-membered-ring transition state TS1a. The overall barrier is
+27.2 kcal/mol, which is a reasonable value as judged by the
reaction temperature (40 °C). Thus the Heck-like mechanism is
consistent with most of the observations in our experiments.26
Importantly, this Heck-like mechanism distinguishes the present
reaction from the previous Cu-catalyzed allylic CÀH activation/
functionalization reactions.14
In summary, we have reported an unprecedented type of Cu-
catalyzed trifluoromethylation reaction involving allylic CÀH
bond activation. This reaction provides a rare instance of catalytic
trifluoromethylation through C(sp3)ÀH activation. It also pre-
sents a mechanistically uncommon example of Cu-catalyzed
allylic CÀH activation/functionalization. Both experimental
tests and theoretical analysis indicate that the reaction may
proceed through a Heck-like four-membered-ring transition state.
The reaction can be conducted under mild conditions without
the need for anhydrous solvents and shows good functional group
tolerance. The presence of an olefin moiety in the product also
promises the subsequent conversion to more functionalized
trifluoromethylated compounds.
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’ ASSOCIATED CONTENT
S
Supporting Information. Experimental details and com-
(14) Previous Cu-catalyzed allylic CÀH functionalization mostly
proceeds through a radical-type mechanism involving allylic H abstrac-
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b
pound characterizations. This material is available free of charge
’ AUTHOR INFORMATION
Corresponding Authors
fuyao@ustc.edu.cn; lliu@mail.tsinghua.edu.cn
(17) (a) Su, D.-B.; Duan, J.-X.; Chen, Q.-Y. Tetrahedron Lett. 1991,
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61, 279. (d) Kim, J.; Shreeve, J. M. Org. Biomol. Chem. 2004, 2, 2728.
(18) We tested only Umemoto’s reagents 2a and 2b because other
CF3+ reagents were either not commercially available or too expensive
and less stable (such as Tongi’s reagent).
’ ACKNOWLEDGMENT
This study was supported by NSFC (20832004 and 20972148),
CAS, FRFCU (WK2060190003), and NCET (08-0519).
(19) Mitchell, J. M.; Finney, N. S. J. Am. Chem. Soc. 2001, 123, 862.
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2009, 323, 1593. (b) Duong, H. A.; Gilligan, R. E.; Cooke, M. L.; Phipps,
R. J.; Gaunt, M. J. Angew. Chem., Int. Ed. 2011, 50, 463.
(24) Chen, B.; Hou, X.-L.; Li, Y.-X.; Wu, Y.-D. J. Am. Chem. Soc.
2011, 133, 7668.
(25) Similar computational methods have been used to study related
Cu-catalyzed reactions. For recent examples, see: (a) Zhang, S.-L.; Liu, L.;
Fu, Y.; Guo, Q.-X. Organometallics 2007, 26, 4546. (b) Dang, L.; Lin, Z.;
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(26) Coordination of solvent molecules to the Cu center in the
intermediates and transition states remains challenging to describe by
computational methods. Therefore, more detailed theoretical analysis
is needed to accurately explain the experimental regioselectivity (in
particular, the strange regioselectivity observed in CD3OD).
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dx.doi.org/10.1021/ja206330m |J. Am. Chem. Soc. 2011, 133, 15300–15303