Platinum(II) mediated Csp3-H activation of tetramethylthiourea

Article abstract of DOI:10.1039/b911164f

The C-H activation of the methyl group of tetramethylthiourea by cis-[PtL₂(NO₃)₂] (L = phosphine or N-heterocyclic carbene) has been investigated as a function of the ligand L. The presence of an electron-withdrawing group on the tertiary phosphine was found to promote the process. Moreover, when an excess of nitrate anion is present in the reaction mixture, the rate of C-H bond activation is retarded, suggesting the key role of an unsaturated tri-coordinate Pt^II species as intermediate.

Full text of DOI:10.1039/b911164f

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www.rsc.org/dalton | Dalton Transactions
Platinum(II) mediated Csp3-H activation of tetramethylthiourea†
Serena Fantasia,a,b Alessandro Pasini*a and Steven P. Nolan*b,c
Received 8th June 2009, Accepted 21st July 2009
First published as an Advance Article on the web 10th August 2009
DOI: 10.1039/b911164f
The C–H activation of the methyl group of tetramethylthiourea by cis-[PtL2(NO3)2] (L = phosphine or
N-heterocyclic carbene) has been investigated as a function of the ligand L. The presence of an
electron-withdrawing group on the tertiary phosphine was found to promote the process. Moreover,
when an excess of nitrate anion is present in the reaction mixture, the rate of C–H bond activation is
retarded, suggesting the key role of an unsaturated tri-coordinate PtII species as intermediate.
Introduction
Results and discussion
Since the groundbreaking report of Shilov and co-workers in
1969,1 platinum(II)-mediated C–H activation is a topic of con-
tinued great interest.2 Despite all efforts made, general, selective
and efficient catalytic functionalization of Csp3–H bond remains
a challenge.3 Hence, an understanding of the factors affecting
the reactivity of metal complexes towards C–H bond activation
is of paramount importance. Notably, the electronic and steric
properties of the ancillary ligands appear to be a key factor in
achieving some control in this reaction.2a
A range of ancillary ligands were chosen for both their intrinsic
steric and electronic characteristics. These ligands are shown in
Fig. 1. A sample of possible phosphine ligands including a tertiary
phosphine bearing an electron withdrawing group (P(4-F–Ph)3 4),
the unsubstituted PPh3 2, a phosphine bearing a slightly electron-
donating group (P(4-tol)3 3) and the more electron donating dppp
5, in which a phenyl group is substituted by an alkyl chain,
were selected for use in this study. In addition, we included the
N-heterocyclic carbene 6 (ICy),6 which is recognized to be even
more s-donating than alkyl phosphines.7 Of note, despite the great
performance NHCs display as supporting ligands in several metal-
catalyzed reactions,8 they are far less studied in platinum-mediated
C–H activation.9
In our previous work, we reported that cis-[Pt(PPh3)2(NO3)2] is
able to activate the sp3 C–H bond of tetramethylthiourea, tmtu,
to afford complex 1 (Scheme 1).4
Scheme 1 cyclometalation of tetramethylthiourea by cis-[Pt(PPh3)2-
(NO3)2].
Proton abstraction is very likely to be driven by the nitrate
anion, since nitric acid was detected at the end of the reaction.
The cyclometalated product [Pt(PPh3)2(tmtu*)]NO3 1 is stable to
air and moisture. More importantly, the Pt–C bond is not cleaved
under the acidic reaction conditions.5 Encouraged by the stability
of 1, which implied the possibility of detection of the amount of
product formed at different reaction stages, we decided to study the
rate of the cyclometalation reaction as a function of the electronic
properties of the ancillary ligand.
Fig. 1 Ligands (L) utilized in this study.
The tertiary phosphine-containing PtII complexes cis-[PtL2
(NO3)2] were synthesized according to Scheme 2. Compounds 7a-
d were obtained in good yields from the reaction of cis-[PtL2Cl2]
and an excess of AgNO3 in refluxing DCM.10 The chloride
precursors were synthesized according to the literature procedure
(Scheme 2).11
aDipartimento di Chimica Inorganica, Metallorganica e Analitica (CIMA),
Universita´ degli Studi di Milano, Via Venezian 21, 20133, Milan, Italy.
E-mail: alessandro.pasini@unimi.it
bInstitute of Chemical Research of Catalonia (ICIQ), Av. Pa¨ısos Catalans
16, 43007, Tarragona, Spain
cSchool of Chemistry, University of St Andrews, St Andrews, KY16 9ST,
UK. E-mail: snolan@st-andrews.ac.uk
† Electronic supplementary information (ESI) available: Experimental
synthetic details. Crystallographic information files (CIF) for complex 8.
CCDC reference number 630114. For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/b911164f
Scheme 2 Synthesis of cis-[Pt L2(NO3)2].
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Table 1 31P NMR data for platinum complexesa
For the synthesis of the NHC-containing complex cis-
[Pt(ICy)2(NO3)2] an alternative synthetic route was employed and
is depicted in Scheme 3.
P(4–F–Ph)3
P(4–tol)3
PPh3
d
31P
JPt–P
13.1
3666
1.8
4021
-1.0
3838
19.7
17.7
3284
15.6
2010
22.9
20.7
3483
JP–P
d
31P
13.2
3698
2.2
4028
0.2
3823
19.0
17.2
3293
15.1
2037
22.9
20.2
3406
JPt–P
JP–P
d
31P
14.9
3572
3.6
4010
1.7
3830
19.4
19
3257
17.1
2022
22.8
22.2
3462
Scheme 3 Synthesis of cis-[Pt(ICy)2(NO3)2] 9.
JPt–P
JP–P
Addition of two equivalents of free ICy to cis-[Pt(dmso)2Cl2]
in THF afforded cis-[Pt(ICy)2Cl2] in quantitative yield.12 The
new complex 8 was fully characterized by NMR spectroscopy
and bulk purity was confirmed by elemental analysis. In order
to unambiguously determine its structure, X-ray analysis was
performed on a single crystal grown from CH2Cl2/pentane. Ball-
and-stick representation of 8 with a selection of bond distances
and angles are given in Fig. 2. Reaction of 8 with excess AgNO3
in refluxing CH2Cl2 afforded the target complex 9.10
dppp
d
31P
JPt–P
-5.0
-13.4
-13.3
3513
26.7
-1.6
-5.4
1877
34.3
0.7
3189
3410
3664
2972
JP–P
a CDCl3 solution, d values in ppm, J values in Hz.
formation of the cyclometalated product.11 A summary of relevant
NMR data is reported in Table 1.
Very interestingly when the reaction was performed with cis-
[Pt(ICy)2(NO3)2] no C–H bond activation was observed. In order
to gain insight into the factors favoring this C–H activation, the
formation of 1 was monitored by 31P NMR. The complex cis-
[PtL2(NO3)2] was dissolved in an NMR tube in CH2Cl2/CDCl3
(1:1) and tmtu was then added. Spectra were recorded immediately
after the addition of tmtu. Fig. 3 illustrates the formation of the
cyclometalated product as a function of time. It is worth noting
that, as previously reported for cis-[Pt(PPh3)2(NO3)2],4 substitu-
tion of one nitrate by tmtu proves rapid for all complexes, affording
[PtL2(NO3)(tmtu)](NO3) in a quantitative fashion in seconds.
Fig. 2 Ball-and-stick representation of 8 cis-[Pt(ICy)2Cl2]. Selected bond
◦
˚
distances (A) and angles ( ): Pt–C(1) 1.979(2), Pt–C(16) 1.991(2), Pt–Cl(1)
2.3657(6), Pt–Cl(8) 2.3701(6), C(1)–Pt–C(2) 94.66(9), Cl(1)–Pt–Cl(8)
89.70(2), N(1)–C(1)–N(2) 104.8(2).
Fig. 3 Formation of cyclometalated product with different ancillary
ligands.
The complexes were then reacted with an equimolar amount
of tetramethylthiourea. From the complexes bearing tertiary
phosphine 7a-d, quantitative formation of the cyclometalated
products 7*a-d was obtained.11 The activation of the methyl
C–H bond and the formation of the Pt–C bond were confirmed by
comparison of their NMR spectroscopic data with the previously
fully characterized complex 1.7 Of note is the appearance in the 1H
NMR spectra of a typical resonance around 3.50 ppm (triplet with
satellites) for the CH2–Pt protons and low J coupling constant for
the phosphorus trans to CH2 (J = 1800–2100 Hz) diagnostic of the
The data in Fig. 3 clearly shows that the reaction is faster
for P(4–F–Ph)3, the less electron rich tertiary phosphine. With
dppp (diphenylphosphinopropane), the more electron donating
phosphine, the reaction is considerably slower. A chelating ligand
such as dppp might also play a role in stabilizing keys interme-
diates, thereby slowing the overall reaction. Despite this, it seems
that the more s-donor the ligand, the slower the cyclometalation
of tmtu. The complete inhibition of C–H bond activation when
ICy is used as a ligand follows this trend. NHCs are stronger
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s donor ligand than tertiary alkyl phosphines.7 Surprisingly,
complex 7b bearing P(4–tol)3 reacted faster then 7a bearing PPh3,
although this difference is small when compared to the reactivity
of complexes 7c, 7d and 9. The reason for this inverted trend with
respect to the Tolman electronic properties of the ligands13 is still
unclear and is currently under investigation.
(d = 8.7 ppm, J = 3720 Hz). The identity of this compound was
confirmed by independent synthesis from cis-[Pt(PPh3)2(NO3)2]
and an excess of NEt3. Only after refluxing the mixture for 5 h did
we observe the formation of some cyclometalated product. How-
ever, another compound was present as the major product (5:1). Its
31P NMR spectrum displayed a doublet of doublets at d = 6.7 ppm
(J = 3243 Hz) and d = 17.1 ppm (J = 3243 Hz). The chemical
shift and the coupling constant of the upfield resonance are very
similar to that of [Pt(PPh3)2(NEt3)2]2+ (d = 8.7 ppm, J = 3720 Hz),
while the downfield resonance had similar values to the resonance
for P trans S in [Pt(PPh3)2(S–tmtu)(NO3)]+ (d = 18.95 ppm, J =
3225 Hz). Thus, we attribute these resonances to [Pt(PPh3)2(S–
tmtu)(NEt3)]2+. Hence, NEt3, being a less labile ligand than the
nitrate anion, disfavors the formation of the vacant coordination
site in the Pt sphere. A higher temperature is therefore required to
promote its dissociation and drive the C–H bond activation.
As further support, an excess of triphenyl phosphine in the
reaction mixture had the same rate decelerating effect. After 5 h
refluxing in DCM, the cyclometalated product was present only
in a small amount. With these data in hand, we propose the
mechanism depicted in Scheme 5.
The role of the nitrate counter anion was then examined.
Notably, when cis-[Pt(PPh3)2Cl2] was used as a starting reagent, no
cyclometalation occurred. On the other hand, addition of AgNO3
salts to the reaction mixture effectively promoted C–H activation.
This experiment suggests that formation of a coordinatively
unsaturated PtII species, formed by abstraction of chlorides by
Ag+, is key in leading to a Pt species capable of C–H activation.
In order to verify this hypothesis, we explored the influence of
excess nitrate ligand on the reaction rate. Fig. 4 shows the reaction
profiles obtained for the formation of [Pt(P(4–tol)3)2(tmtu*)]+ at
-
different [NO3 ] concentrations. In these experiments, (Et4N)NO3
was employed as the nitrate anion source.
Fig. 4 Formation of cyclometalated product in the presence of different
[Pt]/[NO3-] ratio.
-
Scheme 5 Proposed mechanism for the formation of cyclometalated
product.
Clearly, the reaction rate decreases with an increasing NO3
-
concentration. These data suggest that dissociation of NO3 from
[PtL2(S-tmtu)(NO3)]+ and creation of a vacant coordination site
likely facilitates C–H bond activation. To gain further evidence
supporting our hypothesis, we performed the cyclometalation
reaction in the presence of a coordinating ligand. We first tested tri-
ethylamine (Scheme 4). After 24 h stirring at room temperature, the
reaction showed no evidence of cyclometalated product. Instead,
we observed by 31P NMR the formation of [Pt(PPh3)2(NEt3)2]2+
Reaction of 9 with tmtu, a fast process,4 would lead to the
cationic complex 10. Dissociation of one nitrate anion would
lead to a tricoordinated dicationic species 11, both species very
likely being in equilibrium. It has already been postulated that
the formation of a vacant coordination site by dissociation of a
labile ligand is a key step enabling C–H bond activation.14 Indeed,
formation of unsaturated species such as 11, would allow an agos-
tic interaction between the C–H bond and the platinum, leading
to a s complex such as 12,15 a critical intermediate for the C–H
activation processes.2f This dissociative mechanism is very likely
to be also in play in the present case, as suggested by the decrease
of reaction rate when excess coordinative ligand is present.
One of the mechanistic hypothesis for C–H bond activation
addresses the uptake of the C–H bond by a tricoordinated
T-shaped platinum species (like 11) as the rate-determining step.16
Once the C–H bond is coordinated, its rupture is a fast process.
Coordination of C–H bond would then be favored in Pt species
with a high cationic character. Hence, less electron-donating
ligands would stabilize the [PtL2(tmtu)]2+ species to a lesser extent,
promoting the formation of the agostic interaction.17 The trend
observed in the present system for the cyclometalation rate as a
function of L supports this hypothesis.
Scheme 4 Cyclometalation reaction in the presence of NEt3.
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Escudero Ada´n for the resolution of the X-ray structure. SPN
thanks the ERC for an Advanced Researcher Award (FUNCAT).
Conclusion
In summary, we showed that the activation of a Csp3–H bond
of tetramethylthiourea by cis-[PtL2(NO3)2] is faster with a less
electron-donating ligand L, while a strong s-donor ligand such
as a NHC can completely inhibit the reaction. This behavior
supports the role of the cationic unsaturated species 11 as a key
intermediate for the cyclometalation reaction. Moreover, increase
References
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Experimental
General considerations
The reaction was carried out in a MBraun glove box containing
dry argon and less than 1 ppm of oxygen. Anhydrous solvent was
either distilled from appropriate drying agents or purchased from
Aldrich and degassed prior to use by purging with dry argon and
kept over molecular sieves. Solvents for NMR spectroscopy were
degassedwith argonand dried over molecular sieves. NMRspectra
were collected on 300 MHz and 400 MHz Bruker spectrometers.
Elemental analyses were performed by Robertson Microlit Labs.
Synthesis of cis-[Pt(ICy)2(Cl)2] (8). In a 50 mL Schlenk flask,
215 mg (0.509 mmol) of cis-[Pt(dmso)2(Cl)2] was suspended in
20 mL of THF; a solution of 235 mg (1.02 mmol) of ICy in 10 mL
of THF was added to the slurry which was then stirred overnight
at room temperature. During this time, the cis-[Pt(dmso)2(Cl)2]
gradually dissolved and a white precipitate formed. This solid
was collected by filtration and washed with pentane. (322 mg,
87% yield). dH (CDCl3, 300 MHz) 6.93 (s, 4H, CH imidazole),
5.05 (m, 4H, CH cyclohexyl), 2.64 (d br, 4H, CH2 cyclohexyl),
1.79 (m, 16H, CH2 cyclohexyl), 1.55 (m, 12H, CH2 cyclohexyl),
1.22 (m, 8H, CH2 cyclohexyl). dC (CDCl3, 300 MHz) 145.79 (s,
JPt–C = 1499 Hz, C carbene), 117.96 (s, JPt–C = 45.0 Hz, CH
imidazole), 59.25 (s, JPt–C = 36.7 Hz, CH cyclohexyl), 35.91 (s, CH2
cyclohexyl), 33.34 (s, CH2 cyclohexyl), 25.59 (s, CH2 cyclohexyl),
25.51 (s, CH2 cyclohexyl), 25.39 (s, CH2 cyclohexyl). dPt(CD2Cl2,
400 MHz) 976.97 ppm. Anal. calcd for C30H50Cl2N4Pt (732.73):
C, 49.18; H, 6.88; N, 7.65. Found: C, 49.07; H 6.64; N, 7.54.
10 (a) A. Pasini, S. Rizzato and D. de Cillis, Inorg. Chim. Acta, 2001, 315,
196; (b) For characterization of new compounds, see the Supporting
Information.
X-ray data for 8. Crystals suitable for X-ray diffraction
studies were grown from slow evaporation of a DCM/heptane
solution. Formula: C33H51Cl11N4Pt, Fw: 1088.82, T/K: 100 (2);
11 See the Supporting Information.
12 This synthetic route is a variation of a previously reported procedure. Of
note with more sterically hindered NHC, substitution of only one dmso
ligand occurs, affording cis-[(NHC)Pt(dmso)Cl2], see: S. Fantasia, J. L.
Petersen, H. Jacobsen, L. Cavallo and S. P. Nolan, Organometallics,
2007, 26, 5880.
˚
˚
l/A: 0.71073; Cryst. Syst.: monoclinic; Space gr◦oup: P2(1); a/A:
9.6623(8); b/A: 24.792(2); c/A: 9.7344(8); a/ : 90.00; b/◦
:
˚
˚
109.9250(10); g /◦ : 90.00; V/A : 2192.3(3); Z :2; Dc/g cm :
1.649; m/mm-1:3.900; F(000):1084; cryst. size/mm: 0.40 ¥ 0.30 ¥
0.10; q range/◦: 5.38–36.83; No. of reflns collected: 16621; No. of
ind. reflns /Rint: 16371/0.0228 No. of parameters: 442; GoF on
F2:1.223; R1, wR2 (I > 2s(I)): 0.0211, 0.0528; R1, wR2 (all data):
0.0228, 0.0708; Flack parameter: 0.027(3).
3
-3
˚
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Acknowledgements
The Petroleum Research Fund administered by the ACS and
the ICIQ Foundation are gratefully acknowledged for financial
support. We thank Dr. Jordi Benet-Buchholz and Eduardo
17 For a related Ru-based system and activation of C(sp3)-H bonds, see:
C. Zhang, Y. Zhao, B. Li, H. Song, S. Xua and B. Wang, Dalton Trans.,
2009, (26), 5182–5189.
8110 | Dalton Trans., 2009, 8107–8110
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The Royal Society of Chemistry 2009
©