Csp3-F bond activation by nucleophilic attack of the {Pt 2S2} core assisted by non-covalent interactions

Article abstract of DOI:10.1039/b801889h

The high nucleophilicity of the sulfur atoms in [Pt₂(dppp) ₂(μ-S)₂] triggers a C-F activation process in 1,3-difluoro-2-propanol that leads to the [Pt₂(dppp) ₂(μ-S)(μ-SCH₂CH(OH)CH₂F]F product through a S_N2 mechanism, where the O-H...F hydrogen bond established from the alcohol group of the organic substrate is essential for assisting the departure of the fluoride anion. The Royal Society of Chemistry.

Full text of DOI:10.1039/b801889h

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Csp –F bond activation by nucleophilic attack of the {Pt2S2} core
assisted by non-covalent interactionsw
3
a
ab
a
a
´ ´ ´
Ainara Nova, Ruben Mas-Balleste, Gregori Ujaque, Pilar Gonzalez-Duarte*
a
and Agustı Lledos*
´
´
Received (in Cambridge, UK) 1st February 2008, Accepted 27th March 2008
First published as an Advance Article on the web 29th April 2008
DOI: 10.1039/b801889h
The high nucleophilicity of the sulfur atoms in [Pt2(dppp)2(l-S)2]
triggers a C–F activation process in 1,3-difluoro-2-propanol that
leads to the [Pt2(dppp)2(l-S)(l-SCH2CH(OH)CH2F]F product
through a SN2 mechanism, where the O–Hꢀ ꢀ ꢀF hydrogen bond
established from the alcohol group of the organic substrate is
essential for assisting the departure of the fluoride anion.
philes.11,12 Regarding the last species, a complete description
of the reaction pathways by which complexes [Pt2(m-S)2-
13
(P-P)2] (P-P = dppe; dppp) react with CH2Cl2 was
reported in 2002. Hor and co-workers also reported the
reactivity of the sulfide bridges in [Pt2(m-S)2(PPh3)4] towards
a series of organic dihalides.14 These results provided evidence
for the exceptional ability of the {Pt2S2} core to cleave C–Cl
bonds and prompted us to investigate the activation of the less
reactive C–F bonds.
The carbon–fluorine bond is among the strongest single bonds
formed by carbon. Its activation attracts interest for the many
technological applications of fluorocarbon compounds as well
as for their involvement in environmental issues.1 While a
variety of methods have been developed to activate the C–F
bond in fluoroarenes and fluoroalkenes,2 activation of the
saturated counterparts has been less successful.3 Current
strategies focus mainly on the use of transition metal com-
plexes as reducing agents.4 In addition, cleavage of aliphatic
C–F bonds has been achieved by means of the nucleophilic
attack of sulfur-,5 oxygen- or nitrogen-containing com-
pounds.6 Also, an unusual mechanism involving phosphine
ligands has been recently proposed by Macgregor.7 Here we
present the activation of a Csp3–F bond as a result of a SN2
process assisted by non-covalent interactions under rather
moderate reaction conditions.
In order to attempt the cleavage of a Csp3–F bond we
selected 1,3-difluoro-2-propanol (1), which is the major com-
ponent of the pesticide Gliftor.15 Moreover, the presence of an
OH group in the selected compound should allow us to test the
effect of hydrogen bonding in the C–F activation. Reagent 1
and [Pt2(m-S)2(dppp)2] (2) were made to react in refluxing
toluene for one day16 affording a new product, which accord-
ing to the spectroscopic data (vide infra) can be described
as
a
complex
of
formula
[Pt2(dppp)2(m-S)-
(m-SCH2CH(OH)CH2F]F (3) (see Scheme 1).
The reaction product was characterized in solution by
means of multinuclear NMR (Fig. 1) and ESI and FAB mass
spectrometry (see Fig. S1–S5 in supporting informationw).
NMR data of 3 confirm that 2 reacts selectively with only
one of the two C–F bonds in 1. Thus, while the 31P{1H} NMR
spectrum of 2 shows four chemically equivalent phosphorus
nuclei (d ꢁ0.08 ppm, 1JPt,P = 2615 Hz), that of 3 is indicative
of an asymmetric structure (Fig. 1(A)). At high temperature
(50 1C), two signals centred at 2.98 ppm (1JPt,P1 = 2405 Hz)
and 2.45 ppm (1JPt,P2 = 3010 Hz) are observed, suggesting
that the structure of 3 contains two inequivalent pairs of
phosphorus atoms. In contrast, at low temperature (ꢁ40 1C)
The role of non-covalent interactions as a factor that can
determine the kinetics and output of diverse reactions in
biological systems is well known. For instance hydrogen bonds
are involved in regulating chemical processes observed in
respiratory proteins8 and metal-containing hydrolases.9
Despite these phenomena having been observed in biological
systems for decades, only during the last few years have these
concepts been applied successfully to synthetic bioinspired
model systems.10 Along this line, this work presents evidence
that hydrogen bonding assists the Csp3–F activation by a SN2
process using as nucleophile a metal complex containing the
{Pt2S2} core.
four inequivalent phosphorus nuclei are observed (dP1 3.69
1
ppm, 1JPt,P1 = 2417 Hz; dP1 3.00 ppm, JPt,P1 = 2370 Hz; dP2
0
0
1
1
0
0
3.21 ppm, JPt,P2 = 2960 Hz; dP2 2.54 ppm; JPt,P2
=
2985 Hz). These results are indicative of a dynamic process,
which we attribute to the rotation of the alkyl group around
the C–S bond. At low temperature, this rotation is stopped
Complexes of general formula [Pt2(m-S)2L4] have been
found to possess an outstanding ability to behave as nucleo-
philes towards metal centres, protic acids and organic electro-
a
´
´
Departament de Quımica, Universitat Autonoma de Barcelona,
08193 Bellaterra, Barcelona, Catalonia, Spain.
E-mail: agusti@klingon.uab.es; Pilar.Gonzalez.Duarte@uab.es;
Tel: +34-935811363
b
´ ´ ´
Departamento de Quımica Inorganica, Universidad Autonoma de
Madrid, Madrid, 28049, Spain
w Electronic supplementary information (ESI) available: Experimental
and computational details and tables of the optimized geometries
(cartesian coordinates). See DOI: 10.1039/b801889h
Scheme
[Pt2(dppp)2(m-S)2] (2).
1 Reaction between 1,3-difluoro-2-propanol (1) and
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thiols often used in C–F bond activations oxidize easily in
the presence of oxygen.4,5
The effect of the OH group in the organic substrate in order
to facilitate the C–F activation was evaluated by comparing
the reactivity of 2 towards an analogue of 1 devoid of the
alcohol group, 1,3-difluoropropane (4). As we observed that 4
does not react with 2, we conclude that the OH group assists
somehow the C–F bond cleavage. Insights into the mechanism
of this reaction and about the role of the OH group were
obtained from DFT calculations.
Theoretical calculations confirm that the reaction mechan-
ism leading to 3 is of the SN2 type,18 where the entering
nucleophile is the bridging sulfide ligand in 2 that replaces
the leaving fluoride in 1. Given the generally observed inability
of the Fꢁ ion to act as leaving group in SN2 reactions, the
proposed pathway is very unusual for activating C–F bonds
and exemplifies the outstanding nucleophilicity of the {Pt2S2}
core. According to the SN2 mechanism, the transition state
TS1 presents an S–C–F angle of 171.91 and Sꢀ ꢀ ꢀC bond
forming and Cꢀ ꢀ ꢀF bond breaking distances of 2.341 and
2.036 A, respectively (Fig. 2). In TS1 as well as in the final
complex the thiolate group lies in an exo position. On the basis
of the calculated geometry for both species, the leaving
fluoride ion is involved in a strong hydrogen bond interaction
with the alcohol function [(O)Hꢀ ꢀ ꢀF 1.696 A]. The role of the
OH group in the fluoride elimination can also be evaluated by
taking into account theoretical results we have recently re-
ported on the reaction between 4 and 2.19 For the calculated
transition state TS2 we reported that Sꢀ ꢀ ꢀC bond forming and
Cꢀ ꢀ ꢀF bond breaking distances values are 2.372 and 2.035 A,
respectively. In this case, in the absence of an alcohol group,
the leaving fluoride can be suitably located to be slightly
stabilized by weak C–Hꢀ ꢀ ꢀF interactions with the alkyl chain
of the chelating diphosphane ligand. These interactions
Fig. 1 Spectroscopic characterization of product 3 by multinuclear
NMR recorded in CDCl3: (A) VT-31P{1H} NMR, (B) 19F NMR, (C)
DEPT135-13C NMR
and the alkyl group is oriented towards one of the phosphine
ligands making the four phosphorus atoms inequivalent. In
addition, the 19F NMR spectrum of 3 showed two signals, one
3
at d ꢁ229.1 ppm (2JF,H = 47.3 Hz, JF,H = 19.3 Hz, see
Fig. 1(B)) that corresponds to the fluorine atom still bound to
the aliphatic chain (19F NMR signal corresponding to un-
reacted 1 appears at d ꢁ232.2 ppm), and a second signal at d
ꢁ161.8 ppm, which is within the expected chemical shift range
for fluoride ions forming hydrogen bonds in species such as
[F2H]ꢁ or [(FH)nF]ꢁ.17
Consistently with the proposed structure, the DEPT135-13C
NMR spectrum of 3 exhibits three different chemical shifts for
the carbon atoms of the thiolate chain (CH2: d 37.1 ppm,
84.9 ppm (1JC,F = 171 Hz); CH: d 70.1 ppm (2JC,F = 19 Hz)).
As shown in Fig. 1(C), the fact that these signals are only
coupled to one fluorine atom indicates that one C–F bond has
1
been broken. The H NMR spectrum recorded at room tem-
perature allows to locate every proton in the
[SCH2CH(OH)CH2F]ꢁ chain including a broad signal at d
4.13 ppm attributable to the OH group (see supporting
informationw). The ESI and FAB mass spectra of 3 show
one major peak whose position and isotope distribution are
consistent with the molecular mass of the [Pt2(dppp)2(m-S)
(m-SCH2CH(OH)CH2F)]+ cation (m/z =1355) (see Fig. S4
and S5 in supporting informationw). Overall, spectroscopic
data offer no doubt about the activation of one C–F bond in 1.
In addition to achieving the Csp3–F bond activation, the
reported synthetic procedure offers the advantage of a one step
reaction, which is based on a nucleophile-containing species
that is highly stable under open atmosphere and soluble in
many organic solvents. In contrast, aromatic or aliphatic
Fig. 2 Geometries of the transition states for the reaction of 2 with 1
(TS1) or 4 (TS2). Distances in A. TS2 geometry obtained from ref. 19.
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account for the greater deviation of the S–C–F angle in TS2
(156.51) from the ideal value of 1801 than in TS1 (171.91).
The calculated values for the reaction barriers assess the role
of the OH group adjacent to the C–F bond in assisting the
release of the fluoride leaving group. The gas-phase energy
barrier calculated for the reaction between 1 and 2 is 44.7 kcal
molꢁ1, and that for 2 and 4 is 51.9 kcal molꢁ1. When the
solvent toluene is included in the calculation by the PCM
method, the difference in the energy barriers for these two
reactions is even larger, with values of 36.6 and 46.4 kcal
molꢁ1, respectively. These theoretical results agree well with
the experimental observation that 2 does react with 1 but it
does not with 4. In addition, the large value of the activation
energy barrier agrees well with the experimental conditions
required for the reaction of 1 with 2 (refluxing toluene).
Overall, we have shown that the presence of the OH group
stabilizes the transition state by means of the Fꢀ ꢀ ꢀH–O supra-
molecular interaction that provides an electrophilic assistance
to the C–F cleavage.
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Hydrogen bond interactions have been proved in this work
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The authors thank the financial support from the Ministerio
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18. The geometries of the minima and transition states were fully
optimized at the B3LYP level and the energies here presented were
those obtained from single point calculations at the MP2 level. See
supporting informationw for more detail.
de Ciencia y Tecnologı
and CTQ2005-09000-C02-01). G. U. and R. M. B. thank the
Spanish MEC for funding through the ‘‘Ramon y Cajal’’
´
a of Spain (projects CTQ2004-01463
´
program.
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