organic fluoro compounds.4ꢀ7 In this context, palladium
and gold are among the most promising metals for CꢀF
bond formation. While palladium has had much success in
the formation of an aromatic CꢀFbond5aꢀf and less success
in the fluorination of alkenes,5g,h gold has had major
success in the fluorination of alkynes.6 For example, in
2007, Sadighi and co-workers reported a gold(I)-catalyzed
efficient ways to form the CꢀF bond based on ubiquitous
alkyne moieties as backbones involving a redox Au(I)/
Au(III) catalytic cycle,8,9 yet the examples remain very
sparse.6 Herein, we report the first gold-catalyzed amino-
fluorination10 of alkynes to give fluorinated pyrazoles at
room temperature as part of our studies on the construction
of heterocycles via gold-catalyzed tandem reactions.11ꢀ13
hydrofluorination of alkynes using Et3N 3HF as a nucleo-
3
philic source of fluorine.6b Following the same principle,
Miller et al. achieved a regio- and stereoselective hydro-
fluorination of alkynes by using carbonyl groups as the
directing group.6c In 2008, Gouverneur pioneered an alter-
native approach for the fluorination of alkynes by combi-
nation of a gold(I) catalyst with an electrophilic fluorine
source, such as Selectfluor.6d Then, Gouverneur, Nevado,
and Hammond et al. successfully applied this strategy
for 1,3-acyloxy rearrangement/fluorination of propargyl
acetates,6e,f alkoxylation/hydration/fluorination of alkynes,6g
and arylation/hydration/fluorination of alkynes.6h These
studies have enabled chemists to develop direct and
Table 1. Optimization of Reaction Conditionsa
yield
entry
reaction condition
AuCl, MeCN
2a/20ab
(%, 2a)c
1
2
1:1.2
5.3:1
6.2:1
3.8:1
1:1.3
5.9:1
4.1:1
1.9:1
3.6:1
4.7:1
3.1:1
1:1.6
6.1:1
12
76
81
55
39
61
36
44
29
46
33
8
Ph3PAuCl, MeCN
3
Ph3PAuNTf2, MeCN
Ph3PAuCl/AgOTf, MeCN
Ph3PAuCl/AgSbF6, MeCN
Ph3PAuCl/AgF, MeCN
Ph3PAuCl/AgCN, MeCN
Ph3PAuCl/AgNO2, MeCN
IMesAuNTf2, MeCN
AuCl3/3AgNTf2, MeCN
AuCl/AgNTf2, MeCN
AuCl3, MeCN
(5) Examples of palladium-mediated CꢀF bond formation: (a) Hull,
K. L.; Anani, W. Q.; Sanford, M. S. J. Am. Chem. Soc. 2006, 128, 7134.
(b) Furuya, T.; Kaiser, H. M.; Ritter, T. Angew. Chem., Int. Ed. 2008, 47,
5993. (c) Furuya, T.; Ritter, T. J. Am. Chem. Soc. 2008, 130, 10060.
(d) Ball, N. D.; Sanford, M. S. J. Am. Chem. Soc. 2009, 131, 3796.
(e) Wang, X.; Mei, T.-S.; Yu, J.-Q. J. Am. Chem. Soc. 2009, 131, 7520. (f)
Watson, D. A.; Su, M.; Teverovskiy, G.; Zhang, Y.; Garcia-Fortanet, J.;
Kinzel, T.; Buchwald, S. L. Science 2009, 325, 1661. (g) Wu, T.; Yin, G.;
Liu, G. J. Am. Chem. Soc. 2009, 131, 16354. (h) Qiu, S.; Xu, T.; Zhou, J.;
Guo, Y.; Liu, G. J. Am. Chem. Soc. 2010, 132, 2856. (i) Peng, H.; Liu, G.
Org. Lett. 2010, 13, 772. (j) Grushin, V. V. Chem.;Eur. J. 2002, 8, 1006.
(6) A review article on gold catalysis and fluorine: (a) Hopkinson,
M. N.; Gee, A. D.; Gouverneur, V. Isr. J. Chem. 2010, 50, 675. Recent
examples of gold-catalyzed fluorination of alkynes: (b) Akana, J. A.;
4
5
6
7
8
9
10
11
12
13
14
15
Ph3PAuNTf2, MeCN, 40 °C
Ph3PAuNTf2, MeCN, no base
Ph3PAuNTf2, MeCN/H2O =
20:1, no base
79
48
trace
1.2:1
d
€
Bhattacharyya, K. X.; Muller, P.; Sadighi, J. P. J. Am. Chem. Soc. 2007,
129, 7736. (c) Gorske, B. C.; Mbfana, C. T.; Miller, S. J. Org. Lett. 2009,
11, 4318. (d) Schuler, M.; Silva, F.; Bobbio, C.; Tessier, A.; Gouverneur, V.
Angew. Chem., Int. Ed. 2008, 47, 7927. (e) Hopkinson, M. N.; Giuffredi,
G. T.; Gee, A. D.; Gouverneur, V. Synlett 2010, 2737. (f) de Haro, T.;
Nevado, C. Chem. Commun. 2011, 47, 248. (g) de Haro, T.; Nevado, C. Adv.
Synth. Catal. 2010, 352, 2767. (h) Wang, W.; Jasinski, J.; Hammond, G. B.;
Xu, B. Angew. Chem., Int. Ed. 2010, 49, 7247.
16
17
18
19
20
AgNTf2, MeCN
1.5:1
1.1:1
2.5:1
22
8
PdCl2, MeCN
FeCl3, MeCN
9
CuI, MeCN
1.6:1
15
e
e
no catalyst, MeCN
(7) Selected examples for other transition-metal-mediated CꢀF bond
formation: (a) Furuya, T.; Strom, A. E.; Ritter, T. J. Am. Chem. Soc.
2009, 131, 1662. (b) Furuya, T.; Ritter, T. Org. Lett. 2009, 11, 2860. (c)
a Reaction conditions: 1a (0.2 mmol), Selectfluor (2 equiv), NaHCO3
(2 equiv), catalyst (2.5 mol %), solvent (2 mL), rt, 2.0 h. b Determined by
GC. c Isolated yields. d Only 20a was isolated in 72% yield. e Both 2a and
20a were not detected.
€
Barthazy, P.; Stoop, R. M.; Worle, M.; Togni, A.; Mezzetti, A.
Organometallics 2000, 19, 2844. (d) Kaspi, A. W.; Goldberg, I.; Vigalok,
A. J. Am. Chem. Soc. 2010, 132, 10626. (e) Kang, S. H.; Kim, D. Y. Adv.
Synth. Catal. 2010, 352, 2783.
(8) For review articles concerning redox Au(I)/Au(III) catalytic
cycles, see: (a) Garcia, P.; Malacria, M.; Aubert, C.; Gandon, V.;
Fensterbank, L. ChemCatChem 2010, 2, 493. (b) Wegner, H. A. Chimia
2009, 63, 44. (c) Engle, K. M.; Mei, T.-S.; Wang, X.; Yu, J.-Q. Angew.
Chem., Int. Ed. 2011, 50, 2.
For the initial attempt, 1-phenyl-2-(4-phenylbut-3-yn-2-
ylidene)hydrazine 1a was chosen as a model substrate to
optimize the suitable conditions for this fluorinating reac-
tion (Table 1). When the reaction was carried out in the
presence of AuCl (2.5 mol % base on 1a), Selectfluor
(2 equiv), and NaHCO3 (2 equiv) in MeCN at room
(9) Recent examples other than CꢀF bond formation concerning
redox Au(I)/Au(III) catalytic cycles: (a) Zhang, G.; Luo, Y.; Wang, Y.;
Zhang, L. Angew. Chem., Int. Ed. 2011, 50, 4450. (b) de Haro, T.;
Nevado, C. Angew. Chem., Int. Ed. 2011, 50, 906. (c) Zhang, G.; Cui, L.;
Wang, Y.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 1474. (d) Melhado,
A. D.; Brenzovich, W. E., Jr.; Lackner, A. D.; Toste, F. D. J. Am. Chem.
Soc. 2010, 132, 8885. (e) Brenzovich, W. E., Jr.; Benitez, D.; Lackner,
A. D.; Shunatona, H. P.; Tkatchouk, E.; Goddard, W. A., III; Toste,
F. D. Angew. Chem., Int. Ed. 2010, 49, 5519. (f) Brenzovich, W. E., Jr.;
Brazeau, J.-F.; Toste, F. D. Org. Lett. 2010, 12, 4728. (g) Ball, L. T.;
Green, M.; Lloyd-Jones, G. C.; Russell, C. A. Org. Lett. 2010, 12, 4724.
(h) Hopkinson, M. N.; Tessier, A.; Salisbury, A.; Giuffredi, G. T.;
Combettes, L. E.; Gee, A. D.; Gouverneur, V. Chem.;Eur. J. 2010, 16,
4739. (i) Hopkinson, M. N.; Ross, J. E.; Giuffredi, G. T.; Gee, A. D.;
Gouverneur, V. Org. Lett. 2010, 12, 4904. (j) de Haro, T.; Nevado, C.
J. Am. Chem. Soc. 2010, 132, 1512. (k) Zhang, G.; Peng, Y.; Cui, L.;
Zhang, L. Angew. Chem., Int. Ed. 2009, 48, 3112. (l) Peng, Y.; Cui, L.;
Zhang, G.; Zhang, L. J. Am. Chem. Soc. 2009, 131, 5062.
(10) Palladium-catalyzed aminofluorination of alkenes have been
reported; see refs 5g and 5h.
(11) For selected reviews on gold catalysts, see: (a) Hashmi, A. S. K.;
Hutchings, G. J. Angew. Chem., Int. Ed. 2006, 45, 7896. (b) Hashmi,
ꢀ
ꢀ~
A. S. K. Chem. Rev. 2007, 107, 3180. (c) Jimenez-Nunez, E.; Echavarren,
A. M. Chem. Commun. 2007, 333. (d) Li, Z.; Brouwer, C.; He, C. Chem.
Rev. 2008, 108, 3239. (e) Arcadi, A. Chem. Rev. 2008, 108, 3266.
(f) Hashmi, A. S. K.; Rodolph, M. Chem. Soc. Rev. 2008, 37, 1766.
ꢀ
ꢀ~
(g) Jimenez-Nunez, E.; Echavarren, A. M. Chem. Rev. 2008, 108, 3326.
(h) Skouta, R.; Li, C.-J. Tetrahedron 2008, 64, 4917. (i) Muzart, J.
Tetrahedron 2008, 64, 5815. (j) Marion, N.; Nolan, S. P. Chem. Soc. Rev.
2008, 37, 1776.
Org. Lett., Vol. 13, No. 16, 2011
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