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Table 3 Pd-catalyzed aminofluorination of alkenesa
yield (entry 6). But CsOPiv was ineffective for this transformation.
These results suggested that ArIF2 may act as a true oxidant to
achieve C–F bond formation.
In summary, we have developed a Pd-catalyzed regioselective
intramolecular aminofluorination of unactivated alkenes, in which a
primary Csp3–Pd bond was selectively fluorinated by AgF/PhI(OPiv)2 in
the presence of HFIP. Preliminary mechanistic studies demonstrated
that PhI(OPiv)2 and/or PhIF2 might act as a real active oxidant. This
methodology is an efficient route to synthesize a variety of mono-
fluoromethylated nitrogen-containing heterocycles.
We are grateful for financial support from the 973 program
(No. 2011CB808700), NSFC (No. 2125210, 21202185, 20923005, and
21121062), STCSM (11JC1415000), and the CAS/SAFEA International
Partnership Program for Creative Research Teams.
Notes and references
1 For some recent reviews on the transition metal-catalyzed fluorination,
see: (a) V. V. Grushin, Acc. Chem. Res., 2010, 43, 160; (b) T. Furuya,
A. S. Kamlet and T. Ritter, Nature, 2011, 473, 470; (c) A. Vigalok, Organo-
metallics, 2011, 30, 4802; (d) C. Hollingworth and V. Gouverneur, Chem.
Commun., 2012, 48, 2929; (e) G. Liu, Org. Biomol. Chem., 2012, 10, 6243.
2 For the stoichiometric reactions of high-valent Pd complexes, see:
(a) T. Furuya, H. M. Kaiser and T. Ritter, Angew. Chem., Int. Ed., 2008,
47, 5993; (b) N. D. Ball and M. S. Sanford, J. Am. Chem. Soc., 2009,
131, 3796; (c) T. Furuya, D. Benitez, E. Tkatchouk, A. E. Strom, P. Tang,
W. A. Goddard III and T. Ritter, J. Am. Chem. Soc., 2010, 132, 3793.
3 (a) K. L. Hull, W. Q. Anani and M. S. Sanford, J. Am. Chem. Soc., 2006,
128, 7134; (b) X. Wang, T.-S. Mei and J.-Q. Yu, J. Am. Chem. Soc.,
2009, 131, 7520; (c) K. S. L. Chan, M. Wasa, X. Wang and J.-Q. Yu,
Angew. Chem., Int. Ed., 2011, 50, 9081; (d) K. B. McMurtrey,
J. M. Racowski and M. S. Sanford, Org. Lett., 2012, 14, 4094.
a
Reaction conditions: 4 (0.2 mmol), Pd(O2CCF3)2 (5 mol%), Phl(OPiv)2
(3 equiv.), AgF (3 equiv.), 2-MeO-BQ (1 equiv.), (CF3)2CHOH (3 equiv.) in
toluene (1.0 mL) at r.t. for 24 hours. Isolated yield. Diastereoselec-
tivity. Only trans-isomer detected.
b
c
d
4 In the case of a highly valent R–PdIV(F)N(SO2Ph)2 complex, its reductive
elimination afforded the amination product, rather than the fluorination
´
´
´
product. For details, see: (a) A. Iglesias, R. Alvarez, A. R. de Lera and
a
Table 4 Pd-catalyzed aminofluorination with ArIF2
˜
K. Muniz, Angew. Chem., Int. Ed., 2012, 51, 2225; (b) E. L. Ingalls,
P. A. Sibbald, W. Kaminsky and F. E. Michael, J. Am. Chem. Soc., 2013,
135, 8854; (c) P. A. Sibbald and F. E. Michael, Org. Lett., 2009, 11, 1147.
5 T. Wu, G. Yin and G. Liu, J. Am. Chem. Soc., 2009, 131, 16354.
´
6 (a) N. A. Cochrane, H. Nguyen and M. R. Gagne, J. Am. Chem. Soc., 2013,
´
135, 628; (b) S.-B. Zhao, J. J. Becker and M. R. Gagne, Organometallics, 2011,
`
30, 3926; (c) A. Simonneau, P. Garcia, J.-P. Goddard, V. Mouries-Mansuy,
M. Malacria and L. Fensterbank, Beilstein J. Org. Chem., 2011, 7, 1379.
7 (a) N. P. Mankad and F. D. Toste, Chem. Sci., 2012, 3, 72; (b) J. M. Racowski,
J. B. Gary and M. S. Sanford, Angew. Chem., Int. Ed., 2012, 51, 3414.
8 A similar pathway in Pd-catalyzed aminochlorination of alkenes was
reported. For details, see: (a) G. Yin, T. Wu and G. Liu, Chem.–Eur. J.,
2012, 18, 451. The reversible aminopalladation also reported by
Stahl, see: (b) P. B. White and S. S. Stahl, J. Am. Chem. Soc., 2011,
133, 18594.
9 For the synthesis of monofluoromethylated compounds from alkenes
via an alternative fluoropalladation pathway, see: S. Qiu, T. Xu, J. Zhou,
Y.-L. Guo and G. Liu, J. Am. Chem. Soc., 2010, 132, 2856.
10 Very recently, synthesis of monofluoromethylated heterocycles was
reported through a silver-catalyzed radical process, see: Z. Li,
L. Song and C. Li, J. Am. Chem. Soc., 2013, 135, 4640.
Entry
[Pd]
[O]/F
Additive
2a
3a
1
2
3
4
5
6
Pd(OAc)2
—
Pd(OAc)2
Pd(OAc)2
—
ArlF2
ArlF2
ArlF2/AgOPiv
ArlF2/AgOPiv
ArlF2/AgOPiv
ArlF2/AgF
—
—
—
HFIP
HFIP
HFIP
0
0
13%
45%
0
0
0
0
0
0
0
Pd(OAc)2
27%
a
Reaction conditions: 1a (0.2 mmol), Pd(OAc)2 (5 mol%), ArlF2 (2 equiv.),
b
AgOPiv (2 equiv.), additive (2 equiv.) in toluene (1 mL) at r.t. NMR yield.
11 Metal-free aminofluorination of alkenes, see: (a) Q. Wang,
W. Zhong, X. Wei, M. Ning, X. Meng and Z. Li, Org. Biomol. Chem.,
2012, 10, 8566; (b) W. Kong, P. Feige, T. de Haro and C. Nevado,
Angew. Chem., Int. Ed., 2013, 52, 2469; (c) H. T. Huang, T. C. Lacy,
B. Błachut, G. X. Ortiz and Q. Wang, Org. Lett., 2013, 15, 1818;
(d) Y. Kishi, H. Nagura, S. Inagi and T. Fuchigami, Chem. Commun.,
2008, 3876; (e) G. Verniest, K. Piron, E. V. Hende, J. W. Thuring,
G. Macdonald, F. Deroose and N. de Kimpe, Org. Biomol. Chem.,
2010, 8, 2509. However, these reaction conditions in ref. 11a and b
are not compatible for the substrates 1 and 4.
I(III) reagent could deliver fluorination products. Thus, it is possible
that high-valent iodine reagent PhIF2, generated in situ, might act
as a true oxidant. In order to address the possibility, ArIF2 (Ar =
2,4-xylenyl) was independently synthesized and subjected to stan-
dard conditions (see Table 4).13 Unfortunately, the reaction of ArIF2
failed to give fluorination product 2a in the presence or absence of a
palladium catalyst (entries 1 and 2). Interestingly, the reaction
occurred in the presence of AgOPiv to give fluorination products 12 The role of 2-MeOBQ is possible to promote reductive elimination of
Pd(IV) complexes. For details, see: (a) K. L. Hull and M. S. Sanford,
J. Am. Chem. Soc., 2009, 131, 9651; (b) X. Chen, J.-J. Li, X.-S. Hao,
C. E. Goodhue and J.-Q. Yu, J. Am. Chem. Soc., 2006, 128, 78.
as single products in albeit low yield (entry 3). And addition of HFIP
could significantly enhance the yield to 45% (entry 4). Besides
AgOPiv, the additive AgF also provided the desired product in 27% 13 C. Ye, B. Twamley and J. M. Shreeve, Org. Lett., 2005, 7, 3961.
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 8707--8709 8709