Journal of the American Chemical Society
Page 4 of 5
mechanism albeit with an especially short-lived zwitterion inter-
1
2
3
nak, A.; Yang, L.; Zhou, C.; Moyes, C. R. US Patent 7,598,243, October
mediate. The successful development of these transformations
allows envisioning the use of new classes of olefins in the TMM
cycloaddition beyond the typical Michael-type acceptors.
6, 2009. (d) Bichler, P; R.; Chowdhury, S.; Decker, S. M.; Dehnhardt, C.
M.; Focken, T.; Grimwood, M. E.; Hemeon, I. W.; Safina, B.; Sheng, T.;
Sun, S.; Wilson, M. S.; Zenova, A. Y. Int. Patent WO 2014/153037,
September 25, 2014.
4
Scheme 4. Functionalization of the cycloadducts
(5) The construction of such trifluoromethylated cyclopentanes has es-
sentially relied on the trifluoromethylation of dicarboxylic acid with the
hazardous SF4(g):(a) Dmowski, W.; Wolniewicz, A. J. Fluorine Chem.
2000, 102, 141. See also: (b) O’Connor, M. J.; Boblak, K. N.; Toponka,
M. J.; Kindelin, P. J.; Briski, J. M.; Zeng, C.; Klumpp, D. A. J. Am. Chem.
Soc. 2010, 132, 3266.
(6) (a) McBee, E.; Pierce, O. R.; Roberts, C. W. J. Am. Chem. Soc.
1955, 77, 915. (b) Gaede, B.; Balthazor, T. M. J. Org. Chem. 1983, 48,
276. (c) Ojima, I.; Yanatabe, M.; Fucikami, T. J. Org. Chem. 1982, 47,
2051. (d) Tanaka, K. ; Mori, T.; Mitsuhashi, K. Bull. Chem. Soc. Jpn.
1993, 66, 263.
(7) For [3+2] cycloadditions, see: Bonnet-Delpon, D.; Bégué, J. P.;
Lequeux, T. Tetrahedron Lett. 1993, 34, 3279.
(8) For thermal [4+2] cycloadditions, and nitrone 1,3-dipolar cycload-
ditions, see: Bonnet-Delpon, D.; Bégué, J. P.; Lequeux, T.; Ourevitch, M.
Tetrahedron 1996, 52, 59.
5
6
7
8
a) Osminum catalyzed selective alkene oxidation
O
OsO4 (5 mol%), NaIO4
R
R
THF/H2O, 2:1
CF3
CF3
3 or 11
9
15
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
O
MeO
O
O
O
O
Br
O
CF3
CF3
15a: 82%
CF3
15b: 91%
15c: 54%
b) Alternative oxidation procedure
O
O
HIO4, THF:Et2O
93%
mCPBA, DCM
F3C
F3C
11c
(9) For reviews, see: (a) Trost, B. M. Angew. Chem, Int. Ed. 1986, 25,
1. (b) Chan, D. M. T. Recent Advances in Palladium-Catalyzed Cycload-
ditions Involving Trimethylenemethane and its Analogs. In Cycloaddition
Reactions in Organic Synthesis; Kobayashi, S., Jorgensen, K. A., Eds.;
Wiley-VCH: Weinheim, Germany, 2002; pp 57−83.
OPiv
OPiv
rt, 92%, dr = 1:1
16
15d
c) Alkyne hydrosilylation
(10) Singleton 13C kinetic isotope effect experiments are suggestive of a
stepwise mechanism: (a) Singleton, D. A.; Schulmeier, B. E. J. Am. Chem.
Soc. 1999, 121, 9313 and references cited therein. Our result with ste-
reodefined oxindoles and an enol ether are also supportive of a concerted
mechanism: (b) Trost, B. M.; Cramer, N.; Silverman, S. M. J. Am. Chem.
Soc. 2007, 127, 12396. On the other hand, our earlier results with ste-
reodefined α,β-unsaturated esters could be indicative of a stepwise reac-
tion mechanism, see: (c) Trost, B. M.; Miller, M. J. Am. Chem. Soc. 1988,
110, 3687. (d) Trost, B. M.; Yang, B.; Miller, M. J. Am. Chem. Soc. 1989,
111, 6482.
O
Si
1. nBuLi, THF, -40 °C, 81%
F3C
2. HN(HSiMe2)2, 60 °C
then CpRu(MeCN)3PF6, DCM
73%
F3C
PivO
11c
17
ASSOCIATED CONTENT
Supporting Information
Experimental procedures and characterization spectral data. This
material is available free of charge via the Internet at
(11) α-trifluoromethylstyrenes have been reported to react with nucleo-
philes to give the corresponding difluoromethylstyrenes. For organolithi-
um reagents additions, see: (a) Bégué, J.-P.; Bonnet-Delpon, D.; Rock, M.
H. Tetrahedron Lett. 1995, 36, 5003. (b) Bégué, J.-P.; Bonnet-Delpon, D.;
Rock, M. H. J. Chem. Soc., Perk. Trans 1 1996, 1409. (c) Junji, I.; Hi-
royuki, M.; Kotaro, S.; Yukinori, W. J. Fluorine Chem. 2004, 125, 585.
For nitrogen nucleophiles, see: (d) Hamlin, T. A.; Kelly, C. B.; Cywar, R.
M.; Leadbeater, N. E. J. Org. Chem. 2014, 79, 1145. (e) Kohei, F.; Masa-
ki, T.; Junji, I. Angew. Chem., Int. Ed. 2012, 51, 12059. For reactions with
catalytically generated organometallic species, see: (f) Miura, T.; Ito, Y.;
Murakami, M. Chem. Lett. 2008, 37, 10006. (g) Corberan, R.; Mszar, M.
W.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2011, 50, 7079.
(12) For selected examples of phosphoramidites in TMM cycloaddi-
tions, see: (a) Trost, B. M.; Silverman, S. M.; Stambuli, J. P. J. Am. Chem.
Soc. 2011, 133, 19483. (b) Trost, B. M.; Bringley, D. A.; Seng, P. S. Org.
Lett. 2012, 14, 234. (c) Trost, B. M.; Maruniak, A. Angew. Chem. Int. Ed.
2013, 52, 6262. (d) Trost, B. M.; Cramer, N.; Silverman, S. M. J. Am.
Chem. Soc. 2007, 129, 12396.
(13) Trost, B. M.; Lam, T. M. J. Am. Chem. Soc. 2012, 134, 11319.
(14) A similar competition between the desired cycloaddition and addi-
tion-fluoride elimination was observed with α-difluoromethylstyrene. In
this case the reaction resulted in the formation of the cycloadduct in 23%
isolated yield along with the product of fluoride elimination in 44% isolat-
ed yield and as a 1:1 mixture of geometric isomers.
(15) Trost, B. M.; Ehmke, V. Org. Lett. 2014, 16, 2708.
(16) Engman, M.; Cheruku, P.; Tolstoy, P.; Bergquist, J.; Volker, S. F.;
Anderson, P. G. Adv. Synth. Catal. 2009, 351, 375.
(17) For the Pd-catalyzed [4+2]-benzanulation of 1,3-enynes with al-
kynes, the presence of the CF3 group was tolerated but not required for
reactivity, see: Zatolochnaya, O. V.; Gevorgyan, V. Org. Lett. 2013, 15,
2562 and references therein.
(18) Illustrative of this concept are cycloaddition reactions, see: Schore,
N. E. Chem. Rev. 1988, 88, 1081.
(19) Ligand L2 was identified as a competent ligand for the transfor-
mation in the course of the reaction optimization. Reaction with ligand L4
delivered 13c/14c in a 33:67 ratio and 82% yield.
(20) For the reactivity of such vinylsiloxanes, see: Trost, B. M.; Ball, Z.
T. J. Am. Chem. Soc. 2003, 125, 30.
AUTHOR INFORMATION
Corresponding Author
ACKNOWLEDGMENT
We thank the National Science Foundation (CHE-1360634) and
the National Institutes of Health (GM-033049) for their generous
support of our programs. We also thank Ecole polytechnique for
partial funding for L.D. We are grateful to Johnson-Matthey for
generous gifts of palladium salts.
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