Sequential C-F activation and borylation of fluoropyridines via intermediate Rh(i) fluoropyridyl complexes: A multinuclear NMR investigation

Article abstract of DOI:10.1039/b707840d

The C-F bond activation of fluoropyridines by [Rh(SiPh₃) (PMe₃)₃] afforded Rh(i) fluoropyridyl complexes of the type [Rh(Ar^F)(PMe₃)₃] with concomitant formation of fluorotriphenylsilane; subsequent treatment with bis-catecholatodiboron yielded fac-[Rh(Bcat)₃(PMe₃) ₃] and the free fluoropyridyl boronate esters (Ar^FBcat). The Royal Society of Chemistry.

Full text of DOI:10.1039/b707840d

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Sequential C–F activation and borylation of fluoropyridines via
intermediate Rh(I) fluoropyridyl complexes: a multinuclear NMR
investigation{
Richard J. Lindup,a Todd B. Marder,b Robin N. Perutz*a and Adrian C. Whitwooda
Received (in Cambridge, UK) 23rd May 2007, Accepted 5th June 2007
First published as an Advance Article on the web 26th June 2007
DOI: 10.1039/b707840d
bond activation is the Rh(I) silyl complex [Rh(SiR3)(PMe3)3].25,26
The C–F bond activation of fluoropyridines by
On the basis of these reports, we investigated the reactivity of
[Rh(SiPh3)(PMe3)3] towards fluoropyridines and sought to estab-
lish whether C–F bond borylation could be achieved by reaction
with a diborane. Here we show that rhodium complexes can be
used for the borylation of fluoroaromatics.
[Rh(SiPh3)(PMe3)3] afforded Rh(I) fluoropyridyl complexes of
the type [Rh(ArF)(PMe3)3] with concomitant formation of
fluorotriphenylsilane; subsequent treatment with bis-catechola-
todiboron yielded fac-[Rh(Bcat)3(PMe3)3] and the free fluoro-
pyridyl boronate esters (ArFBcat).
Reaction of [Rh(SiPh3)(PMe3)3] 1 with a number of fluoropyr-
idines yielded new square-planar Rh(I) fluoropyridyl complexes of
the type [Rh(ArF)(PMe3)3] (Scheme 1). The new rhodium
fluoropyridyl complexes formed at room temperature and were
identified by multinuclear NMR spectroscopy. According to these
spectra, the consumption of starting material was complete after
1–4 days. The extreme sensitivity of the complexes towards air and
moisture prevented isolation of pure samples. In all cases, the C–F
activation reactions generated fluorotriphenylsilane as the fluorine
containing by-product. Treatment of 1 with 1 equiv. of C5NF5
produced [Rh(2-C5NF4)(PMe3)3] 2a and [Rh(4-C5NF4)(PMe3)3]
2b in a 3 : 1 ratio (determined by integration of the 19F NMR
spectrum).§ The 19F NMR spectrum displays seven new
resonances due to the three products. 2a exhibits 19F resonances
at d 287.0 (td, JFF 5 31, 15 Hz), 2128.4 (tm, JFF 5 33 Hz),
2154.0 (m) and 2175.8 (dd, JFF 5 31, 15 Hz) corresponding to
the F atoms at the 6, 3, 4 and 5 positions of the ring, respectively."
Aryl boronate esters, ArB(OR)2, have
a wide variety of
applications in boron neutron capture therapy, in sugar receptors
and as versatile reagents in organic chemistry. In particular, they
are used as precursors to alcohols and as synthetic intermediates in
Suzuki–Miyaura couplings.1,2 The importance and variety of
compounds with metal–boron bonds is growing rapidly.3–5 C–H
bond borylation as a route to ArB(OR)2 was first demonstrated by
Marder et al. in 1993, when the borylation of toluene was observed
during the room temperature reaction of [Ir(g5-C9H7)(cod)] with
HBcat (cat 5 1,2-O2C6H4).6 Since 1999, transition metal boryl
complexes of groups 6–9 have been found to be active for the
direct catalytic borylation of unreactive, saturated and unsaturated
hydrocarbons by C–H activation. In particular, iridium systems
such as [Ir(Bpin)3(dtbpy)] catalyse selective C–H bond borylation
at room temperature.7–13 In contrast, no definitive examples of
C–F bond borylation reactions have been reported, despite the
developments in metal-mediated C–F bond activation.{14,15 One
well-established system for C–F oxidative addition is [Ni(COD)2]
which reacts with a variety of fluoropyridines (ArF–F) in the
presence of excess PR3 (R 5 Et, Cy, PPh3) to yield complexes of
the type trans-[NiF(ArF)(PR3)2].16 In a different type of C–F
activation process, [RhH(PEt3)3] reacts with pentafluoropyridine
to afford [Rh(4-C5NF4)(PEt3)3] with loss of HF. The same product
is obtained via C–H activation of 2,3,5,6-tetrafluoropyridine, with
loss of H2.17 Only a few examples of C–F bond functionalisation
have been reported, where a fluorine in an organic molecule is
replaced by a new group through metal-mediated reaction.18–22
Furthermore, many of these reactions are limited to hydrode-
fluorination, i.e. conversion to C–H bonds.14,23,24 Milstein
demonstrated that the catalytic hydrodefluorination of C6F6 to
C6F5H is achieved in the presence of [Rh(C6F5)(PMe3)3] and
HSiR3 (R 5 Ph or OEt). In this case, the active species for C–F
aDepartment of Chemistry, University of York, York, UK YO10 5DD.
E-mail: rnp1@york.ac.uk; Fax: +44 (0) 1904 43 2516;
Tel: +44 (0) 1904 43 2549
bDepartment of Chemistry, Durham University, Durham, UK DH1 3LE.
E-mail: todd.marder@durham.ac.uk; Fax: +44 (0) 191 384 4737;
Tel: +44 (0) 191 334 2037
Scheme 1 Reactions of 1 with fluoropyridines.
{ For CIF file of 2b (CCDC 648397) see DOI: 10.1039/b707840d
3664 | Chem. Commun., 2007, 3664–3666
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These assignments are consistent with those for [NiF(2-
C5NF4)(PEt3)2] and are characteristic of tetrafluoropyridyl coor-
dinated to a metal ortho to nitrogen.27 The 19F NMR resonances
for 2b are at d 2100.7 (m) and d 2117.3 (m) for the atoms ortho
and meta to nitrogen, respectively. These resonances are consistent
with other transition metal complexes with a tetrafluoropyridyl
ligand coordinated para to nitrogen. The 19F NMR spectrum also
displays a singlet at d 2169.0 with silicon satellites (JSiF 5 280 Hz)
for Ph3SiF, which is formed in a 1 : 1 ratio with respect to the total
amount of 2a and 2b. The 31P{1H} NMR spectrum of the product
mixture reveals a complex second order pattern in the region d
213 to 216. This chemical shift region is characteristic of PMe3
ligands in Rh(I) aryl complexes including [RhPh(PMe3)3] and
[Rh(C6F5)(PMe3)3].25,28
competitive C–H and C–F activation to yield 2b and [Rh(2-
C5NF3H)(PMe3)3] 2d as the initial products in a 1 : 1.3 ratio, along
with Ph3SiF and Ph3SiH. A secondary reaction then occurs
between 2d and Ph3SiH to yield 2,3,5-trifluoropyrdine and an
unidentified Rh complex. Overall, this product corresponds to
hydrodefluorination of 2,3,5,6-tetrafluoropyridine at the 2-posi-
tion. As a test of this reaction sequence, we added Ph3SiH to a
mixture of 2a and 2b, which afforded 2,3,4,5-tetrafluoropyridine
from the reaction of silane with 2a (Scheme 2). Complex 2b did not
react with Ph3SiH.
Prior to attempting the borylation reactions of 2a–d, the known
complexes [Rh(C6F5)(PMe3)3] 2e and [RhPh(PMe3)3] 2f were
treated with the diborane B2cat2 (Bcat 5 B{1,2-O2C6H4}) in order
to produce the free boronate esters (Ar–Bcat).25,28 We found that
2 equiv. of B2cat2 was required to produce stable products.
Addition of 2 equiv. of B2cat2 to solutions of 2e and 2f in d8-
toluene afforded fac-[Rh(Bcat)3(PMe3)3] 4 and the corresponding
free aryl boronate ester C6F5Bcat and PhBcat, respectively. The
formation of the boronate esters was confirmed by GC-MS. The
tris-boryl complex 4 has been described in the literature following
the reaction of [RhMe(PMe3)4] with B2cat2.30 At room tempera-
ture, the 31P{1H} NMR spectrum of 4 displays a broad signal at
d 226.2 as a result of the quadrupolar boron nuclei coordinated
trans to the PMe3 ligands. We have now discovered that this signal
resolves to a doublet (JRhP 5 72.4 Hz) at d 224.9 on cooling to
210 K, indicative of the fac geometry. This coupling constant is
remarkably low for a Rh(III) species and is a measure of the
exceptionally strong trans influence of Bcat which is a very strong
s-donor ligand.31
Complex 2b was synthesised and characterised independently by
treatment of [Rh(PMe3)4]Cl with 2,3,5,6-tetrafluoropyridyl mag-
nesium bromide.29 Extractions with toluene and heptane allowed
isolation of pure yellow crystals of 2b. The structure of 2b was
confirmed by X-ray crystallography (Fig. 1).I The pyridyl ligand
lies approximately perpendicular to the coordination plane, with
an 88.75(5)u angle between the planes. The sum of the angles at Rh
is 359.89u, as expected for a square-planar complex. For the plane
defined by C(1), P(1), P(2) and P(3), the deviations from the plane
˚
are: P(1) 0.041(1) A, P(2) 0.040(1) A, P(3) 20.035(1) A, C(1)
˚
˚
˚
20.046(1) A and Rh(1) 0.064(1) A. The Rh–C bond length C(1)–
˚
˚
Rh(1) is 2.0700(13) A, which compares with 2.078(8) A for
˚
˚
A
[Rh(C6F5)(PMe3)3] and 2.0623(14)
for [Rh(4-C5NF4)-
(PEt3)3].17,25 The 31P{1H} NMR spectrum of isolated 2b exhibits
an approximate doublet of doublets at d 216.0 (JPP 5 44,
JRhP 5 136 Hz) for the two mutually trans PMe3 ligands, and a
broad doublet of triplets of multiplets at d 213.9 (JPP 5 44,
JRhP 5 127 Hz) for the unique phosphorus (second order
distortion is observed as before). This spectrum is comparable to
the PEt3 analogue of 2b, which has been described by Braun et al.17
Treatment of 1 with 1 equiv. of 2,3,5,6-tetrafluoro-4-methylpyr-
idine produced [Rh(2-C5NF3Me)(PMe3)3] 2c exclusively because
neither C–F or C–H activation at the 4-position are possible.
Treatment of the C–F activation product mixture of 2a and 2b
(generated in-situ) with 2 equiv. of B2cat2 resulted in complete
conversion to C5N-2-(Bcat)-3,4,5,6-F4 3a, C5N-4-(Bcat)-2,3,5,6-F4
3b together with 4 (Scheme 3).** The 19F NMR spectrum of the
product mixture shows complete consumption of the 2a and 2b,
and six new resonances for the boronate ester reductive elimination
products. 3a exhibits four signals at d 281.7 (td, JFF 5 27, 19 Hz)
2135.3 (m), 2141.5 (m) and 2152.4 (m), while 3b displays two
multiplet resonances at d 292.1 (m) and 2131.0 (m).{{ The 11B
NMR spectrum shows overlapping resonances at d 29 for 3a and
3b, which is consistent with other aryl boronate esters.32
Reaction of 2,3,5,6-tetrafluoropyridine with
1 resulted in
Scheme 2 Reactions of 2a and 2d with Ph3SiH.
Fig. 1 A view of the molecular structure of 2b. Ellipsoids are drawn at
the 50% probability level and hydrogens are omitted for clarity. Selected
˚
bond lengths [A] and angles [u]: Rh(1)–C(1) 2.0700(13), Rh(1)–P(1)
2.3094(4), Rh(1)–P(2) 2.2838(4), Rh(1)–P(3) 2.2821(4); Rh(1)–C(1)–C(2)
124.22(10), Rh(1)–C(1)–C(5) 124.59(10), C(2)–C(1)–C(5) 111.07(12), C(1)–
Rh(1)–P(1) 84.64(4), P(2)–Rh(1)–P(3) 95.043(14), P(2)–Rh(1)–C(1)
86.21(4), P(1)–Rh(1)–P(3) 174.29(4).
Scheme 3 Reactions of 2a–d with B2cat2.
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High-resolution mass spectrum (EI) 3a/3b m/z 269.027496 (269.027122
Formation of the pyridyl boronate esters was confirmed by high-
resolution mass spectrometry. Corresponding reactivity was found
for the other fluoropyridyl complexes described above. Compound
2c reacted with the diborane to yield C5NMe-2-(Bcat)-3,5,6-F3 3c
and 4, exclusively. When the mixture of 2b and 2d was treated with
2 equiv. of B2cat2 the products were 3b, C5NH-2-(Bcat)-3,5,6-F3 3d
and 4.
calcd. for C11H4BNO2F4, D 5 0. 374 mDa). 3c 19F (470.59 MHz) d 287.9
(t, JFF 5 28 Hz, 1 F), 2118.0 (dd, JFF 5 9, 30 Hz, 1 F), 2134.3 (dd,
JFF 5 9, 29 Hz, 1 F). 11B (160.46 MHz) d 28. High-resolution mass
spectrum (EI) 3c m/z 265.052453 (265.052194 calcd. for C12H7BNO2F3,
D 5 0.259 mDa). 3d 19F (470.59 MHz) d 287.4 (m, 1 F), 2113.1 (m, 1 F),
2128.5 (m, 1 F). 11B (160.46 MHz) d 28.
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To conclude, we have demonstrated the first definitive examples
of C–F bond borylation, via intermediate Rh(I) fluoroaryl or
fluoropyridyl species. Furthermore, both the C–F activation and
C–B bond formation steps are achieved at room temperature. The
borylation step generates fac-[Rh(Bcat)3(PMe3)3] which acts as a
thermodynamic sink. It should be possible to develop catalytic
versions of this process in the future.
We would like to acknowledge the EPSRC (grants GR/R61604/
01 and GR/R61598/01) for financial support.
9 T. Ishiyama, J. Takagi, J. F. Hartwig and N. Miyaura, Angew. Chem.,
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Notes and references
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{ Smith et al. observed formation of small quantities of C6HF4(Bpin) and
C6H3F2(Bpin) during the borylation reactions of C6HF5 and 1,3,5-C6H3F3,
respectively, catalysed by [Rh(g5-C5Me5)(g4-C6Me6)] or [Ir(g5-
C5Me5)(H)(Bpin)(PMe3)]. However, the authors state that the fluoroaro-
matic starting materials contained impurities (C6H4F2 isomers in
1,3,5-C6H3F3) and that the borylation products were not rigorously
quantified. Therefore, they conclude that it is unclear whether these
products arose from C–F borylation of the principal fluoroaromatic or
from C–H borylation of the impurities.32
§ In a typical experiment, 1 (10 mg, 0.017 mmol) was dissolved in d8-
toluene (500 mL) in a dried Young’s tap NMR tube. A stock solution of
fluoropyridine (1 mmol dm23) in d8-toluene was prepared and 17 mL
(0.017 mmol) was added to the NMR tube by microsyringe, followed by
mixing. The solution changed colour from red to yellow after 1–4 days at
25 uC, with quantitative formation of the C–F/C–H activation products
and silane by-product. The products were analysed by NMR spectroscopy.
" Selected NMR spectroscopic data for 2a–d (d8-toluene, 300 K): 2a 1H
(500.1 MHz) d 1.0 to 0.8 (br m). 31P{1H} (202.46 MHz) d 213.0 to 216.0
(complex 2nd order pattern). 19F (470.59 MHz) d 287.0 (td, JFF 5 15,
31 Hz, 1 F), 2128.4 (tm, JFF 5 33 Hz, 1 F), 2154.0 (m, 1 F), 2175.8 (dd,
JFF 5 15, 31 Hz, 1 F). 2b 1H (500.1 MHz) d 0.95 (br d, JPH 5 6 Hz, 9 H),
0.81 (d vt, JRhH 5 1 Hz, JPH 5 3 Hz, 18 H). 31P{1H} (202.46 MHz) d
216.0 (dd, JPP 5 44 Hz, JRhP 5 136 Hz, 2 P), 213.9 (br dtm, JPP 5 44 Hz,
JRhP 5 127 Hz, 1 P). 19F (470.59 MHz) d 2100.5 (m, 2 F), 2117.2 (m, 2 F).
2c 1H (500.1 MHz) d 2.04 (s, 3 H), 1.06 (br s, 9 H), 0.90 (br s, 18 H).
31P{1H} (202.46 MHz) d 212.9 to 215.3 (complex 2nd order pattern). 19
F
(470.59 MHz) d 292.3 (t, JFF 5 34 Hz, 1 F), 2111.3 (d, JFF 5 34 Hz, 1 F),
2158.4 (d, JFF 5 34 Hz, 1 F). 2d 1H (500.1 MHz) d 6.52 (m), 1.0 to 0.8 (br
m). 31P{1H} (202.46 MHz) d 213.0 to 215.0 (complex 2nd order pattern).
19F (470.59 MHz) d 292.5 (td, JFF 5 32 Hz, JHF 5 8 Hz, 1 F), 2106.5 (dt,
JFF 5 32 Hz, JHF 5 6 Hz, JPF 5 6 Hz, 1 F), 2152.9 (dd, JFF 5 32 Hz,
JHF 5 10 Hz, 1 F).
I Crystal data for 2b: C14H27F4NP3Rh, M 5 481.19, monoclinic, space
group P21/c (no. 14), a 5 12.1172(6) A, b 5 9.2891(5) A, c 5 20.422(3) A,
˚
˚
˚
b 5 102.8010(10)u, U 5 2012.48(18) A , Z 5 4, Dc 5 1.588 Mg m23
,
3
˚
l 5 0.71073 A, m 5 1.118 mm21, F(000) 5 976, T 5 120(2) K. Data were
˚
collected on a Bruker SMART Apex X-ray diffractometer for 1.72 , h ,
29.99u. The structure was solved by direct methods using SHELXS-97 and
refined by full-matrix least squares using SHELXL-97.33,34
30 C. Dai, G. Stringer, T. B. Marder, A. J. Scott, W. Clegg and
N. C. Norman, Inorg. Chem., 1997, 36, 272–273.
31 J. Zhu, Z. Lin and T. B. Marder, Inorg. Chem., 2005, 44, 9384–9390.
32 J.-Y. Cho, C. N. Iverson and M. R. Smith, III, J. Am. Chem. Soc., 2000,
122, 12868–12869.
33 G. M. Sheldrick, SHELXS-97, Program for solution of crystal structures,
University of Go¨ttingen, Germany, 1997.
34 G. M. Sheldrick, SHELXL-97, Program for refinement of crystal
structures, University of Go¨ttingen, Germany, 1997.
** Compounds 2a–d were generated by C–F/C–H activation, as described
above. B2cat2 (8 mg, 0.034 mmol) was added to the solution and the sample
was mixed. After several minutes, the solution changed from yellow to
colourless due to quantitative formation of 4 and 3a–d. The products were
analysed by NMR spectroscopy and mass spectrometry.
{{ Selected spectroscopic data for 3a–d (d8-toluene, 300 K): 3a 19F
(470.59 MHz) d 281.7 (td, 1 F, JFF 5 27, 19 Hz), 2135.3 (m, 1 F),
2141.5 (m, 1 F), 2152.4 (m, 1 F). 11B (160.46 MHz) d 29. 3b 19F
(470.59 MHz) d 292.1 (m, 2 F), 2131.0 (m, 2 F). 11B (160.46 MHz) d 29.
3666 | Chem. Commun., 2007, 3664–3666
This journal is ß The Royal Society of Chemistry 2007