Pt(II)Cl2(DMSO)2-catalyzed cross-coupling of polyfluoroaryl imines

Article abstract of DOI:10.1016/j.jfluchem.2010.06.018

PtCl₂(DMSO)₂ has been identified as a readily accessible and effective C-F activation precatalyst. We report herein the study of reaction optimization and substrate scope. A comparison is made with previously reported [Pt₂Me₄(SMe₂)₂] and PtCl₂(SMe₂)₂ precatalysts.

Full text of DOI:10.1016/j.jfluchem.2010.06.018

Journal of Fluorine Chemistry 131 (2010) 1237–1240
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Pt(II)Cl2(DMSO)2-catalyzed cross-coupling of polyfluoroaryl imines
*
Alex D. Sun, Jennifer A. Love
Department of Chemistry, 2036 Main Mall, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z1
A R T I C L E I N F O
A B S T R A C T
Article history:
PtCl2(DMSO)2 has been identified as a readily accessible and effective C–F activation precatalyst. We
report herein the study of reaction optimization and substrate scope. A comparison is made with
previously reported [Pt2Me4(SMe2)2] and PtCl2(SMe2)2 precatalysts.
Received 26 April 2010
Received in revised form 28 June 2010
Accepted 29 June 2010
Available online 6 July 2010
ß 2010 Elsevier B.V. All rights reserved.
Keywords:
Platinum(II)
Polyfluoroarene
Cross-coupling
Dedicated to Professor Russell P. Hughes,
Recipient of the 2010 ACS Award for
Creative Work in Fluorine Chemistry.
1. Introduction
(2) transmetalation with dimethylzinc to generate C and (3)
reductive elimination to furnish a Csp2–Csp3 bond, regenerating
The activation of carbon–fluorine bonds has been an active
research area for more than 20 years. The challenge of activating C–
F bonds has been overcome by numerous metal complexes and the
results have been summarized in several reviews [1]. Up until
recently, the research focus has been dominated by metal-
mediated and metal-catalyzed hydrodefluorination reactions [2],
resulting in reduction of the strong C–F bond. Such strategies have
potential for use in fluorocarbon remediation. Over the last decade,
considerable attention has been devoted to the selective activation
and cross-coupling of polyfluorinated compounds [3–5]. Given the
emergence of fluorine in bioactive molecules [6], such strategies
have the potential for generating fluoroaromatic building blocks
for use in pharmaceutical and industrial applications.
In 2007, our group reported the first example of Pt-catalyzed
cross-coupling of aryl fluorides. A range of polyfluoroaryl imines
with different substitution patterns can be methylated in high
yield and selectivity using [Pt2Me4(SMe2)2] (1) and dimethylzinc,
even in the presence of other potentially reactive functionalities
[4a]. In a subsequent paper, we reported that the mechanism is
consistent with the following steps (Scheme 1): (1) C–F oxidation
addition of a low-valent, electron-rich Pt(II) complex to generate B;
the active catalyst A [4b]. Each Pt(IV) intermediate in the catalytic
cycle was postulated to be a 5-coordinate species, based on the
observation that additional SMe2 decelerated each stoichiometric
step, as well catalysis. Moreover, a 6-coordinate trimethyl Pt(IV)
species formed (C-SMe2) was thought to be a resting state for the
catalytic cycle; this species can re-enter the cycle by dissociation of
SMe2 [4b]. We have also shown that the same precatalyst can be
used in catalytic C–O bond formation, by a different (and as yet,
undefined) mechanism [4c].
Although (1) is a highly efficient precatalyst, its low stability
even under inert atmosphere at À30 8C makes it less than ideal for
synthetic applications. In an effort to discover a more user-friendly
precatalyst, we recently reported that PtCl2(SMe2)2 (2), a precursor
of (1), is a viable as a air-, water- and thermal stable alternative to
(1) [4d]. It is believed that (2) generates the active catalyst or some
related species in situ by reacting with dimethylzinc. This
precatalyst shares the same high selectivity and functional group
tolerance as (1). However, although the practical advantage of
using (2) is undoubtedly desirable, the major drawback it suffers is
the lower reactivity compared to (1). With few exceptions, a
significant decrease has been observed. Pre-treatment of (2) with
dimethylzinc affords comparable activity to (1); however, this
protocol is still less efficient than simply using (1).
In order to further extend the utility of Pt(II)-catalyzed C–F
cross-coupling, we sought to test related platinum(II) complexes.
* Corresponding author. Tel.: +1 6048223187; fax: +1 604822b3187.
E-mail address: jenlove@chem.ubc.ca (J.A. Love).
0022-1139/$ – see front matter ß 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2010.06.018

[
A.D. Sun, J.A. Love / Journal of Fluorine Chemistry 131 (2010) 1237–1240
Scheme 1. Proposed mechanism of cross-coupling of aryl fluorides using precatalyst 1.
We hypothesized that the use of a complex bearing a less-
coordinating ligand than SMe2 would facilitate the reaction.
Presumably, such a species would generate the active catalyst
faster than (2). Moreover, because 5-coordinate complexes are
for 6 h, higher yields can be obtained. Thus, complex (3)
achieved comparable reactivity to (1), without requiring pre-
activation.
The reaction of a series of imines was then explored. Table 1
shows a direct comparison of complexes 1–3. The reaction
conditions indicated in Scheme 2 were found to be the optimal
conditions and were used for further studies. All spectroscopic data
for known compounds matched the characterization data obtained
in our earlier work [4a,d]. Overall, the complex (3) shows the same
level of ortho-selectivity and functional group tolerance when
compared to (1) and (2). Under the standard condition, the
majority of the substrates reacted in comparable yield and reaction
time to (1), which is a significant improvement over (2). These
results indicate that cis-PtCl2(DMSO)2 (3) has the practical
advantages afforded by PtCl2(SMe2)2 (2) without compromising
the efficiency and reactivity of [Pt2Me4(SMe2)2] (1).
After successfully demonstrated the utility of complex (3) in C–
F cross-coupling, we sought to investigate the nature of the
catalytic species, anticipating that the outcome would be similar
to that postulated for (2). In our previous work [4b], (1) was shown
to be highly efficient in C–F activation, which is believed to be the
rate determining step in the overall catalytic cycle. In comparison,
heating the mixture of 0.8 equiv. of (2) [4d] or (3) with 1.0 equiv.
of imine 4a in CD3CN failed to achieve any observable C–F
activation after 24 h at 60 8C. This result is consistent with a
requirement for electron-rich late transition metal complexes to
promote oxidative addition of the aryl C–F bond [8]. Likewise, this
result is consistent with (2) and (3) generating the active catalyst
in situ.
postulated to be involved in the catalytic cycle,
a less-
coordinating ligand should minimize the formation of off-cycle
6-coordinate species, such as B-SMe2 and C-SMe2 that could
slow catalysis. We thus selected cis-PtCl2(DMSO)2 (3) for
investigation.
2. Results and discussion
Cis-PtCl2(DMSO)2 (3) is an off-yellow microcrystalline that is
indefinitely stable under air at ambient temperature [7]. This
complex was readily synthesized from commercially available
K2PtCl4 and DMSO in quantitative yield. Imine 4a (0.034 mmol),
cis-PtCl2(DMSO)2, (0.0034 mmol, 10 mol.%), dimethylzinc
(0.041 mmol, 1.2 equiv.) were dissolved in CD3CN (1 mL) in a
nitrogen-filled glovebox. The solution was transferred to an
NMR tube, which was then removed from the glovebox. The
solution was heated in an oil bath at 60 8C. Reaction progress
was monitored periodically by 1H and 19F NMR spectroscopy. By
comparison with 1,3,5-trimethoxybenzene as an internal
standard, the reaction had proceeded cleanly to 95% yield in
12 h; no more imine starting material was observed (Scheme 2).
In comparison, while complex (1) achieved the same result in
approximately 8 h, complex (2) produced only 60% of the
desired product even after 12 h. If (2) is pre-treated with Me2Zn
[(Schme_2)TD$FIG]
In the stoichiometric reaction between dimethylzinc and
PtCl2(DMSO)2 (3), resonances in the 1H NMR spectrum were
observed, consistent with the formation of a Pt-CH3 species. This
species disappears over time and thus appears to be catalytically
relevant. This result is also consistent with our earlier studies using
(2) [4d]. Presumably, in both cases, it is such a Pt-CH3 species that
is the active catalyst, as addition of imine does result in cross-
coupling. It is also noteworthy that despite the insolubility of (2)
Scheme 2. PtCl2(DMSO)2-catalyzed cross-coupling.

A.D. Sun, J.A. Love / Journal of Fluorine Chemistry 131 (2010) 1237–1240
1239
Table 1
Comparison of precatalysts 1–3 in aryl fluoride cross-coupling. [TD$LINE]
.
Pt2Me4(SMe2)2 (1)a,b
PtCl2(SMe2)2 (2)a,c
PtCl2(DMSO)2 (3)a,d
[
4a
4b
4c
4d
95%
60% (95%)e
95%
85%
95%
90%
]
85%
85%
92%
63%
95%
50%
[TD$LINE]
[TD$LINE]
[
4e
95%
30%
95%
[
4f
95%
60% (95%)e
95%
[
4g
86%
30% (95%)e
85%
[
4h
85%
30% (85%)e
85%

1240
A.D. Sun, J.A. Love / Journal of Fluorine Chemistry 131 (2010) 1237–1240
Table 1 (Continued )
Pt2Me4(SMe2)2 (1)a,b
PtCl2(SMe2)2 (2)a,c
20%
PtCl2(DMSO)2 (3)a,d
[
4i
74%
70%
a
b
c
Yields based on 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as an internal standard.
Taken from Ref. [4a]; condition: 0.6 equiv. Me2Zn, 8 h.
Condition: 0.6 equiv. Me2Zn, 8 h.
d
e
Taken from Ref. [4d]; condition: 1.2 equiv. Me2Zn, 12 h.
Pre-treated with Me2Zn for 6 h.
and (3) in CD3CN, both are readily solubilized by the addition of
imine. This is consistent with imine coordination prior to C–F
activation. Overall, this data is indicative of the same general
mechanism being operative for complexes 1–3.
Acknowledgements
We thank the following for support of this research: University
of British Columbia, NSERC (Discovery Grant, Research Tools and
Instrumentation Grants), AstraZeneca Canada (Award in Chemistry
2008), the Canada Foundation for Innovation (new Opportunities
Grant) and the British Columbia Knowledge Development Fund.
3. Conclusion
In summary, we have established the general protocol for the
PtCl2(DMSO)2-catalyzed methylation of polyfluorinated aryl imi-
nes. This precatalyst is an improvement over previous complexes,
in that it is both highly active and is user-friendly. We believe this
complex will prove to be very useful in Pt-catalyzed cross-coupling
of aryl fluorides.
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