reactions at nickel with a unique regioselectivity and a prefer-
ence for C–F over C–H activation have been studied before.8–10
We have now demonstrated that the scope of these reactions
can be expanded to the activation of a carbon–fluorine bond
in 5-chloro-2,4,6-trifluoropyrimidine using a sterically more
hindered phosphine. The described reaction provides an
unusual entry to new fluoropyrimidines bearing three different
substituents by selective replacement of one fluorine atom at
the already functionalised heterocycle.
Acknowledgements
We would like to acknowledge the Deutsche Forschungs-
gemeinschaft (grants BR-2065/1-1 and BR-2065/1-2) for finan-
cial support. We are also grateful to Ms. J. Grota for recording
the mass spectra. T. B. thanks Professor P. Jutzi for his generous
support.
Notes and references
‡ Selected data for 1, 2 and 3. 1: (Found: C, 40.84; H, 6.53; N, 5.99%.
C16H30ClF3N2NiP2 requires: C, 41.46; H, 6.52; N, 6.04%). 31P NMR
(202.5 MHz, C6D6, 300 K): δ 15.83 (s). 19F NMR (470.4 MHz, C6D6,
300 K): δ Ϫ37.77 (s, br, 2 F), Ϫ55.72 (s, br, 1 F). 2: (Found: C, 60.50; H,
8.35; N, 3.59%. C40H66ClF3N2NiP2 requires: C, 60.97; H, 8.44; N,
Scheme 2 Reactivity of 2.
3.55%). 31P NMR (202.5 MHz, C6D6, 300 K): δ 19.65 (d, JPF 39 Hz). 19
F
NMR (470.4 MHz, C6D6, 300 K): δ Ϫ49.86 (s, 1 F), Ϫ73.67 (s, 1 F),
Ϫ377.56 (t, JPF 40 Hz, 1 F). 3: (Found: C, 59.92; H, 8.70; N, 3.10%.
C40H66Cl2F2N2NiP2 requires: C, 59.72; H, 8.27; N, 3.48%). 31P NMR
(202.4 MHz, C6D6, 300 K): δ 15.67 (s). 19F NMR (470.4 MHz, C6D6,
300 K): δ Ϫ48.91 (s, 1 F), Ϫ73.77 (s, 1 F).
§ Crystal data for 2: C40H66ClF3N2NiP2, M = 788.05, monoclinic, space
group P21/n, a = 13.8320(10), b = 20.2110(15), c = 14.5510(10) Å,
β = 90.459(6)Њ, U = 4067.7(5) Å3, T = 100 K, µ(Mo-Kα) = 0.665 mmϪ1
,
Z = 4, Dc = 1.287 g cmϪ3, 28171 reflections measured, 9114 unique
(Rint = 0.0409). The disorder of the pyrimidyl ligand on two positions
was refined to an occupancy of 62 : 38. Final R1, wR2 values on all
data 0.06457, 0.0942. R1, wR2 values on [Io > 2σ(Io), 7325 reflections]
data 0.0449, 0.0890. CCDC reference number 173741. See http://
www.rsc.org/suppdata/dt/b1/b110128e/ for crystallographic data in CIF
or other electronic format.
1
¶ Selected spectroscopic data for 4 and 5. 4: NMR (C6D6, 300 K): H
(500.1 MHz): δ 7.37 (d, br, JFH 11 Hz, CH), 19F (470.4 MHz): δ Ϫ45.69
(s, br, 1 F), Ϫ59.15 (s, br, 1 F). Mass spectrum (EI) m/z 152 (Mϩ, 33%),
150 (Mϩ, 100). Accurate mass spectrum (EI) m/z calcd. for C4HN2F2Cl,
149.9796; found, 149.9814. 5: NMR (C6D6, 300 K): 19F (470.4 MHz):
δ Ϫ45.64 (s, 1 F), Ϫ55.36 (s, 1 F). Mass spectrum (EI) m/z 278 (Mϩ,
30%), 276 (Mϩ, 100).
Fig. 1 An ORTEP18 diagram of 2. Ellipsoids are drawn at the 50%
probability level. Note that the rotational disorder (62 : 38) about Cl(1),
N(1), N(2), F(2), F(3) and C(37)–C(40) leads to average locations
across the pyrimidyl ring. The two rotamers have identical bond
distances within 3σ. Data for the second rotamer are marked by a #.
Selected bond lengths (Å) and angles (Њ): Ni(1)–F(1) 1.845 (2), Ni(1)–
C(37) 1.828(8), Ni(1)–C(37#) 1.863(12), N(2)–C(37) 1.362(7), N(2)–
C(40) 1.307(6), N(1)–C(40) 1.297(7), N(1)–C(39) 1.30(2), C(37)–C(38)
1.398(7), C(38)–C(39) 1.40(2), Cl(1)–C(38) 1.713(4), F(2)–C(39)
1.31(2), F(3)–C(40) 1.344(5); C(37)–Ni(1)–F(1) 172.98(18), C(37#)–
Ni(1)–F(1) 170.4(3), P(1)–Ni(1)–P(2) 168.74(2).
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we also cannot exclude that instead of a concerted oxidative
addition mechanism an electron transfer process precedes the
activation of the C–X bond.16 Further mechanistic investiga-
tions are under way.
Treatment of 2 or 3 with an excess HCl in C6D6–diethyl ether
affords, after distillation under vacuum, a solution of 5-chloro-
2,4-difluoropyrimidine 4 (Scheme 2).¶ The reaction of 2 with
iodine in C6D6 yields a solution of 5-chloro-2,6-difluoro-4-
iodopyrimidine 5.¶ The reactions are quantitative according to
the NMR spectra. We have found no previous description of
compound 4 or 5. Fluorinated pyrimidines are of general inter-
est as building blocks in agrochemicals, dyes and because of
their antitumor activity.6,17
In conclusion, we have shown the first activation of an
aromatic carbon–fluorine bond at a metal centre in the presence
of a C–Cl bond in the same ring. Comparable C–F activation
11 M. Crespo, M. Martinez and J. Sales, J. Chem. Soc., Chem.
Commun., 1992, 822; see also: M. Crespo, M. Martinez and
E. de Pablo, J. Chem. Soc., Dalton Trans., 1997, 1231.
298
J. Chem. Soc., Dalton Trans., 2002, 297–299