Insight into the mechanism of platinum-catalyzed cross-coupling of polyfluoroaryl imines

Article abstract of DOI:10.1021/om800247p

We recently reported the first examples of Pt-catalyzed methylation of polyfluorinated arenes as a means to generate partially fluorinated aromatic building blocks. The reaction is selective for cleavage of C-F bonds ortho to an imine substituent and allows for preferential cleavage of C-F bonds in the presence of considerably weaker bonds (e.g., C-Br). We report herein the proposed mechanism for this reaction. Initial C-F activation generates a Pt(IV)-F intermediate, which then reacts with (CH₃)₂Zn via transmetalation. Subsequent reductive elimination from the Pt(IV) species generates a new sp²-sp³ C-C bond. In addition, we have identified a species present during the catalytic reaction and propose this to be the catalyst resting state.

Full text of DOI:10.1021/om800247p

3290
Organometallics 2008, 27, 3290–3296
Insight into the Mechanism of Platinum-Catalyzed Cross-Coupling
of Polyfluoroaryl Imines
Tongen Wang and Jennifer A. Love*
Department of Chemistry, 2036 Main Mall, UniVersity of British Columbia,
VancouVer, British Columbia, V6T 1Z1, Canada
ReceiVed March 16, 2008
We recently reported the first examples of Pt-catalyzed methylation of polyfluorinated arenes as a
means to generate partially fluorinated aromatic building blocks. The reaction is selective for cleavage
of C-F bonds ortho to an imine substituent and allows for preferential cleavage of C-F bonds in the
presence of considerably weaker bonds (e.g., C-Br). We report herein the proposed mechanism for this
reaction. Initial C-F activation generates a Pt(IV)-F intermediate, which then reacts with (CH3)2Zn via
transmetalation. Subsequent reductive elimination from the Pt(IV) species generates a new sp2-sp3 C-C
bond. In addition, we have identified a species present during the catalytic reaction and propose this to
be the catalyst resting state.
Introduction
The catalytic cross-coupling of aryl fluorides has received
considerably less attention than that of other aryl halides.
Although several protocols have emerged,1–3 beginning with
the report from Kumada in 1973, only a few examples of these
involve cross-coupling of polyfluoroarenes.2 We recently re-
ported the first examples of Pt-catalyzed cross-coupling of
polyfluorinated aryl imines.3 Our inspiration came from the
report by Crespo and Martinez that [(CH3)2Pt(µ-SMe2)]24 effects
the stoichiometric C-F activation of a number of polyfluorinated
aryl imines (eq 1).5 We sought to explore the reaction mech-
anism as a means to develop catalysts with broader substrate
scope.
addition of C(aryl)-X bonds (X ) F, Cl, Br) to [(CH3)2Pt(µ-
SMe2)]2.6 Coordination of imine leads to Pt(II) intermediate I.
Loss of SMe2 generates Pt(II) intermediate II. Oxidative addition
of the C-X bond leads, initially, to intermediate III, in which
the C(aryl) and X are in a cis relationship. This species
undergoes facile Berry pseudorotation. Consequently, upon
coordination of SMe2, the isomer with a trans relationship
between C(aryl) and X (complex IV) is generated. Martinez
has shown that Pt(IV) complexes of this type can undergo both
dissociative6,7 and associative7,8 substitution reactions.
We anticipated that a Pt(IV)-F intermediate (e.g., A in eq
1, III and IV in Scheme 1) could undergo cross-coupling with
a suitable organometallic reagent to permit formation of a new
C-C bond. Consistent with this hypothesis, we found that the
addition of 0.6 equiv of (CH3)2Zn to a mixture of 1a and 5 mol
% [(CH3)2Pt(µ-SMe2)]2 afforded methylated product 2a in high
isolated yield (eq 2).3 A variety of other fluoroaryl imines were
successfully methylated using this protocol, including those
bearing potentially reactive functional groups, such as aryl
bromides and nitriles.
Based on detailed kinetic and mechanistic analyses, Martinez
proposed the mechanism outlined in Scheme 1 for the oxidative
* Corresponding author. E-mail: jenlove@chem.ubc.ca.
(1) (a) Kiso, Y.; Tamao, K.; Kumada, M. J. Organomet. Chem. 1973,
50, C12–C14. (b) Bo¨hm, V. P. W.; Gsto¨ttmayr, C. W. K.; Weskamp, T.;
Herrmann, W. A. Angew. Chem., Int. Ed. 2001, 40, 3387–3389. (c) Mongin,
F.; Mojovic, L.; Guillamet, B.; Tre´court, F.; Que´guiner, G. J. Org. Chem.
2002, 67, 8991–8994. (d) Terao, J.; Ikumi, A.; Kuniyasu, H.; Kambe, N.
J. Am. Chem. Soc. 2003, 125, 5646–5647. (e) Ackermann, L.; Born, R.;
Spatz, J. H.; Meyer, D. Angew. Chem., Int. Ed. 2005, 44, 7216–7219. (f)
Dankwardt, J. W. J. Organomet. Chem. 2005, 690, 932–938. (g) Liu, J.;
Robins, M. J. Org. Lett. 2005, 7, 1149–1151. (h) Wilhelm, R.; Widdowson,
D. A. J. Chem. Soc., Perkin Trans. 1 2000, 3808–3813. (i) Kim, Y. M.;
Yu, S. J. Am. Chem. Soc. 2003, 125, 1696–1697. (j) Mikami, K.; Miyamoto,
T.; Hatano, M. Chem. Commun. 2004, 2082–2083. (k) Guo, H.; Kong, F.;
Kanno, K-i.; He, J.; Nakajima, K. Organometallics 2006, 25, 2045–2048.
(2) Zr: (a) Edelbach, B. L.; Kraft, B. M.; Jones, W. D. J. Am. Chem.
Soc. 1999, 121, 10327–10331. (b) Braun, T.; Perutz, R. N.; Sladek, M. I.
Chem. Commun. 2001, 2254–2255. (c) Steffen, A.; Sladek, M. I.; Braun,
T.; Neumann, B.; Stammler, H.-G. Organometallics 2005, 24, 4057–4064.
(d) Yoshikai, N.; Mashima, H.; Nakamura, E. J. Am. Chem. Soc. 2005,
127, 17978–17979. (e) Schaub, T.; Backes, M.; Radius, U. J. Am. Chem.
Soc. 2006, 128, 15964–15965. (f) Saeki, T.; Takashima, Y.; Tamao, K.
Synlett 2005, 11, 1771–1774. (g) Braun, T.; Izundu, J.; Steffen, A.;
Neumann, B.; Stammler, H.-G. Dalton Trans. 2006, 5118–5123. (h) Korn,
T. J.; Schade, M. A.; Wirth, S.; Knochel, P. Org. Lett. 2006, 8, 725–728.
(i) Korn, T. J.; Schade, M. A.; Cheemala, M. N.; Wirth, S.; Guevara, S. A.;
Cahiez, G.; Knochel, P. Synthesis 2006, 21, 3547–3574.
During the course of our investigation, we noticed consider-
able similarities between our catalytic results3 and the stoichio-
(3) Wang, T.; Alfonso, B. J.; Love, J. A. Org. Lett. 2007, 9, 5629–
5631.
(6) Bernhardt, P. V.; Gallego, C.; Martinez, M. Organometallics 2000,
19, 4862–4869.
(4) Hill, G. S.; Irwin, M. J.; Levy, C. J.; Rendina, L. M.; Puddephatt,
R. J.; Andersen, R. A.; McLean, L. Inorg. Synth. 1998, 32, 149–151.
(5) Crespo, M.; Martinez, M.; Sales, J. Organometallics 1993, 12, 4297–
4304.
(7) Bernhardt, P. V.; Gallego, C.; Martinez, M.; Parella, T. Inorg. Chem.
2002, 41, 1747–1754.
(8) Gallego, C.; Gonzalez, G.; Martinez, M.; Merbach, A. E. Organo-
metallics 2004, 23, 2434–2438.
10.1021/om800247p CCC: $40.75
2008 American Chemical Society
Publication on Web 06/11/2008

Pt-Catalyzed Cross-Coupling of Polyfluoroaryl Imines
Organometallics, Vol. 27, No. 13, 2008 3291
metric C-F activation results previously reported. In particular,
after a detailed study, Crespo and Martinez established that at
least three electron-withdrawing groups were needed in order
for C-F activation to occur efficiently and that the activation
barrier for C-F activation decreased as the number of fluorine
substituents increased. Likewise, we found that difluoroaryl
imine (1b), which did not undergo appreciable stoichiometric
C-F activation (eq 3), also did not fare well in the catalytic
reaction (eq 4). In addition, the selectivity of the cross-coupling
of unsymmetrically substituted trifluoroimine 1c is the same in
both the stoichiometric and catalytic studies (eq 5). Crespo and
Martinez attributed the selectivity for activation of the more
hindered C-F bond to the electron-withdrawing ability of the
adjacent fluorine substituent.5
to increased substrate scope in the catalytic reaction. We report
herein the results of our study.
Results and Discussion
1
We began by monitoring the conversion of 1a to 2a by H
and 19F NMR spectroscopy. Trifluoroimine (1a, 8.5 mg, 0.034
mmol), (CH3)2Zn (11.0 µL of a 2.0 M solution in toluene), and
[(CH3)2Pt(µ-SMe2)]2 (100 µL of a 0.017 M solution in CD3CN)
were dissolved in 1.1 mL of CD3CN in an NMR tube. The
reaction was monitored over several hours at 60 °C. A plot
showing the consumption of 1a and formation of 2a as measured
1
by integration of the imine CHdN resonances using H NMR
spectroscopy (300 MHz, CD3CN) is shown in Figure 1. During
the course of the reaction, in addition to the resonances attributed
to 1a and 2a, a number of smaller resonances were observed;
importantly, A was not observed during the catalytic reaction.
To gain better information about these additional resonances,
the reaction was repeated at higher concentration. Trifluoroimine
(1a, 85 mg, 0.34 mmol), (CH3)2Zn (110 µL of a 2.0 M solution
in toluene), and [(CH3)2Pt(µ-SMe2)]2 (10 mg, 0.017 mmol) were
dissolved in 1.1 mL of CD3CN in an NMR tube. Again, in
addition to 1a and 2a, a number of additional resonances
We also discovered that the reaction products could undergo
a second methylation, provided that the arene ring was suf-
ficiently electron deficient. For example, the reaction of pen-
tafluoroimine 1d can be selectively monomethylated in good
yield; only 3% of the dimethylated product was formed (eq 6).
The product of this reaction, 2d, can subsequently be methylated
with excess (CH3)2Zn (eq 7).
These observations led us to hypothesize that the catalytic
reaction does involve C-F activation (eq 1) as a catalytically
relevant step. Importantly, if this hypothesis is correct, efforts
to design and synthesize complexes with greater ability to
promote stoichiometric C-F activation should eventually lead
1
appeared in the H NMR spectrum. The chemical shifts and
their relative intensities are given in Table 1. The resonance at
δ 8.87 (entry 1) is attributed to the CHdN of a bound imine,
with a Pt satellite coupling constant of 39 Hz. The multiplet at
δ 4.98 is consistent with the methylene of a bound imine. The
signal at δ 1.77 is assigned as coordinated SMe2 (JPt-H ) 12
Hz). The three resonances at δ 0.78, 0.41, and 0.20, which are
of equivalent intensity, are attributed to Pt-CH3 groups. The
coupling constants of the signals at δ 0.78 and 0.41 (69 and 73
Hz, respectively) are consistent with methyl groups trans to
Scheme 1. Mechanism of C-X Activation (see refs 5 and 6)

3292 Organometallics, Vol. 27, No. 13, 2008
Wang and LoVe
Figure 2. Proposed structure of observed Pt complex.
Figure 1. Plot of [1a] (mM) vs time (min) (9) and [2a] (mM) vs
time (min) (2) at 60 °C.
Table 1. 1H NMR Spectroscopic Data for Observed Species
entry
δ
multiplicity
rel intensity
1
2
3
4
5
6
8.87
4.98
1.77
0.78
0.41
0.20
s (JPtH ) 39 Hz)
m
s (JPtH ) 12 Hz)
s (JPtH ) 69 Hz)
s (JPtH ) 73 Hz)
s (JPtH ) 46 Hz)
1
2
6
3
3
3
Figure 3. Plot of [1a] (mM) vs time (min) (9) and [A] (mM) vs
time (min) (2) at 60 °C.
L-type ligands (presumably imine and SMe2).9 The coupling
constant for the signal at δ 0.20 (46 Hz) is typical of a methyl
group trans to a carbon. The six signals are present in a 1:2:
6:3:3:3 ratio, which suggests that all these components are in
1
the same species. On the basis of integration of the H NMR
spectrum, this species is present as ∼5% of the reaction mixture
(i.e., ∼50% of the amount of Pt).10 In addition, the 19F NMR
spectrum shows 1a and 2a, as well as two resonances at δ 104.1
and 111.4, which were present in considerably lower intensity
than either 1a or 2a. On the basis of this data, we have assigned
the structure as complex D (Figure 2). Given that this complex
is observed for the duration of the reaction, this species is
proposed as the resting state of the catalytic cycle.
To provide support for the C-F activation mechanism
outlined in Scheme 1, we attempted the stoichiometric C-F
activation of 1a (44.0 mg, 0.177 mmol) with [(CH3)2Pt(µ-
SMe2)]2 (50.5 mg, 0.088 mmol) in the presence of SEt2 (15.5
mg, 0.172 mmol). Two complexes were formed in a 2.3:1 ratio;
based on H NMR spectroscopic data, we have assigned these
as complex A (eq 1) and A · SEt2, respectively. This result
indicates that exchange of thioether ligands is feasible.
Our next objective was to determine whether A could generate
2a. Experiments were performed in both the absence and
presence of (CH3)2Zn. The reaction of 1 equiv of [(CH3)2Pt(µ-
SMe2)]2 (9.8 mg, 0.017 mmol) with 2.0 equiv of trifluoroimine
1a (8.5 mg, 0.034 mmol) in 1.1 mL of CD3CN (0.016 mM in
[(CH3)2Pt(µ-SMe2)]2) generated Pt-F complex A at 60 °C, as
established by comparing the 19F NMR spectrum to the reported
data.5,11,12 After 6 h at 60 °C, the majority of the starting material
Figure 4. Plot of [A] (mM) vs time (min) (9) and [2a] (mM) vs
time (min) (2) at 60 °C.
was consumed and complex A was formed in 70% yield. A
plot showing the consumption of 1a and formation of A as
measured by integration of the imine CH2 resonances using 1H
NMR spectroscopy (300 MHz, CD3CN) is shown in Figure 3.
It is noteworthy that the catalytic methylation of 1a requires
8 h at this temperature (Figure 1).
In the absence of (CH3)2Zn, A does not generate product 2a
(eq 8).13 In contrast, when 1.2 equiv of (CH3)2Zn is added to
preformed A, the Pt-F signal of A in the 19F NMR spectrum
immediately disappears and new signals emerge in the 1H NMR
spectrum indicative of formation of 2a, as well as D. The
reaction is complete within 30 min, which is considerably faster
than both the stoichiometric C-F activation and the catalytic
methylation reaction (eq 9). Imine 2a is formed in 69% overall
yield from 1a (>98% based on the amount of A formed from
1a), consistent with the catalytic results (eq 2). A plot showing
the consumption of A and formation of 2a as measured by
integration of the imine CH2 resonances using 1H NMR
spectroscopy (300 MHz, CD3CN) is shown in Figure 4. These
1
(9) (a) van Asselt, R.; Rjinberg, E.; Elsevier, C. J. Organometallics 1994,
13, 706–720. (b) Clegg, D. E.; Hall, J. R.; Swile, G. A. J. Organomet.
Chem. 1972, 38, 403–420. (c) Ruddick, J. R.; Shaw, B. L. J. Chem. Soc. A
1969, 2969–2970.
(10) Although accurate determination of the amount is rendered difficult
based on the inherent error in integration, we are able to observe the 13C
satellites for PhCH3, indicative of a good signal-to-noise ratio.
(11) Although the stoichiometric studies (ref 5) were conducted in
acetone-d6, we used CD3CN because this is the solvent used in the catalytic
study. As such, the chemical shifts in the 19F NMR spectrum were slightly
different than those reported in ref 5.
(12) Formation of A from 1a is not quantitative; see Figure 3.
(13) Likewise, no evidence for ethane formation is observed.

Pt-Catalyzed Cross-Coupling of Polyfluoroaryl Imines
Organometallics, Vol. 27, No. 13, 2008 3293
results indicate that addition of (CH3)2Zn is needed to promote
formation of 2a from A. During the course of the reaction of A
with (CH3)2Zn, the 1H NMR spectroscopic resonances for
[(CH3)2Pt(µ-SMe2)]2, which had been depleted in the formation
of A, re-emerge, indicating that the original Pt species can be
regenerated. In addition, it is noteworthy that the conversion of
A to 2a is considerably faster than the conversion of 1a to A.
These findings are consistent with A being either part of the
derived from 1d. Addition of 10 equiv of 1d to a solution of A
in CD3CN does not result in the formation of a new Pt-F
species, based on the 1H or 19F NMR spectra, even after 8 h at
60 °C (eq 12).15 This result indicates that formation of A is not
reversible on the time scale of the catalytic process.
catalytic cycle or able to enter the catalytic cycle. The reaction
of A with (CH3)2Zn is slowed considerably by the addition of
SMe2, suggesting that conversion of A to 2a involves dissocia-
tion of SMe2. Martinez and co-workers had previously shown
that the formation of complexes similar to A proceeds through
a five-coordinate Pt(IV) complex (e.g., III in Scheme 1).6
Martinez and Crespo also showed that A can undergo dissocia-
tive exchange of SMe2 for PPh3, indicating that there is an
equilibrium between A and a five-coordinate species.5–7 This
information led us to conclude that a five-coordinate species,
B, is part of the catalytic pathway and that B is in equilibrium
with A (eq 10). This indicates that A should be able to enter
the catalytic cycle.
To test whether the conversion of A to 2a is accompanied
by the regeneration of a species capable of subsequent C-F
activation, we examined the reaction of A16 with (CH3)2Zn (8.5
µL of a 2.0 M solution in toluene, 0.5 equiv relative to 1a) in
the presence of 1d (19.4 mg, 0.068 mmol, 2.0 equiv relative to
1a). Within 30 min at 60 °C, A was completely consumed.
Product 2a was formed in 79% yield, along with a 75% yield
of complex A′ (eq 13).17 This result is consistent with initial
reaction of A with (CH3)2Zn to generate 2a, similar to that
outlined in eqs 9 and 11. The resultant Pt(II) species then reacts
with 1d (which is more reactive toward C-F activation than
2a) to generate A′ upon coordination of SMe2.
To further explore this possibility, we used A as a catalyst
for methylation of imine 1c (eq 11).14 Presumably, A would
first react with (CH3)2Zn to generate up to 10 mol % of 2a
(equivalent to the amount of A added, though the formation of
A from 1a is not quantitative, as previously mentioned). The
formation of 2a would presumably be accompanied by the
regeneration of [(CH3)2Pt(SMe2)(imine)], which is the species
postulated to be involved in C-F activation (see Scheme 1).5,6
This Pt(II) species could then catalyze the methylation of 1c.
Consistent with this hypothesis, we found that A does indeed
permit the catalytic formation of 2c, in a yield comparable to
that obtained using 5 mol % [(CH3)2Pt(µ-SMe2)]2 (eq 5). This
reaction also produces 8% of 2a, as expected. This result is
also consistent with the propensity of A to enter the catalytic
cycle.
We next explored the reversibility of formation of A.
Pentafluoroimine 1d was selected for study, as this imine
undergoes stoichiometric C-F activation at a significantly faster
rate than 1a; the experimentally determined enthalpies of
activation for C-F activation of 1a and 1d were reported by
Crespo and Martinez and are 54 ( 1 and 30 ( 4 kJ/mol,
respectively.5 Thus, if formation of A were reversible, we would
expect to see the preferential formation of the Pt-F species
Based on these observations, a plausible mechanism is
outlined in Scheme 2. The platinum dimer [(CH3)2Pt(µ-SMe2)]2
reacts with imine 1a to generate [(CH3)2Pt(SMe2)(imine)].5–7
After dissociation of SMe2, [(CH3)2Pt(imine)] undergoes rate-
limiting C-F activation of 1a to produce B (or an isomer).18
This species is in equilibrium with A, consistent with the results
(15) The Pt-F signal of A diminishes over time, presumably due to
decomposition.
(16) Complex A was formed from the stoichiometric reaction of 1a and
[(CH3)2Pt(µ-SMe2)]2, as in eqs 8 and 9.
(17) Yields for formation of 2a and A′ are based on the percent yield
of A formed from the stoichiometric reaction of 1a with (CH3)2Zn.
(14) The use of metal fluorides to catalyze cross-coupling of aryl
fluorides has been previously reported. See refs 2b,c,g.

3294 Organometallics, Vol. 27, No. 13, 2008
Wang and LoVe
coordinate Pt(IV)22,23 has been observed. Given that D builds
up and accounts for approximately half of the Pt in the reaction
(vide infra), as well as the observation that excess SMe2 slows
the conversion of A to 2a, we propose that complex D is not
part of the catalytic cycle.24 As such, reductive elimination
would occur from the five-coordinate species, C. We are
currently attempting to isolate complex D to verify its structure,
as well as its ability to undergo reductive elimination. In
addition, a detailed kinetic investigation of the transmetalation
and reductive elimination steps is underway.
Scheme 2. Proposed Mechanism of Cross-Coupling
Conclusions
In conclusion, we have established the general mechanism
for the Pt-catalyzed methylation of polyfluorinated aryl imines
and that the process does involve C-F activation as a
fundamental step. Given that C-F activation is substantially
slower than the subsequent transmetalation and reductive
elimination steps and that aryl fluorides that cannot undergo
stoichiometric C-F activation also do not undergo catalytic
cross-coupling, we are currently developing new Pt(II) com-
plexes capable of C-F activation with an expanded substrate
scope.
Experimental Section
General Procedures. Manipulation of organometallic com-
pounds was performed using standard Schlenk techniques under
an atmosphere of dry nitrogen or in a nitrogen-filled Vacuum
Atmospheres drybox (O2 < 2 ppm). NMR spectra were recorded
1
on Bruker Avance 300 or Bruker Avance 400 spectrometers. H
and 13C chemical shifts are reported in parts per million and
referenced to residual solvent. 19F NMR spectra are reported in
parts per million and referenced to C6F6 in acetone-d6 (-162.9
ppm). Coupling constant values were extracted assuming first-order
coupling. The multiplicities are abbreviated as follows: s ) singlet,
d ) doublet, t ) triplet, m ) multiplet. All spectra were obtained
at 25 °C. Mass spectra were recorded on a Kratos MS-50 mass
spectrometer.
Materials and Methods. Acetonitrile was dried by heating to
reflux over calcium hydride. Acetonitrile-d3 and all organic reagents
were obtained from commercial sources and used as received.
K2PtCl4 was purchased from Strem Chemicals and was used without
further purification. PtCl2(SMe2)2 was prepared by a previously
reported procedure.4 Pt2Me4(SMe2)2 was prepared by a previously
reported procedure.3,4 All imines were prepared by previously
reported procedures.3,5 Dimethyl zinc (2.0 M solution in toluene)
was purchased from Aldrich.
Preparation of N-(4,6-Difluoro-2-methylbenzylidene)benzy-
lamine (2a). In a 20 mL vial, N-(2,4,6-trifluorobenzylidene)ben-
zylamine (1a) (0.4 mmol, 100.0 mg) and Pt2Me4(SMe2)2 (0.02
mmol, 11.5 mg) were dissolved in CH3CN (3 mL). The resulting
solution was transferred into a test tube fitted with a screw cap
containing a septum. Me2Zn (0.240 mmol, 120 µL of a 2.0 M
solution in toluene) was then added by syringe. The resulting
solution was heated at 60 °C for 8 h. The solution was then cooled
to room temperature, and the solvent was removed by rotary
evaporation. n-Pentane (3 × 20 mL) was then added, and the
resulting mixture was shaken. The n-pentane solution was collected
and filtered through Celite. The filtrate was concentrated by rotary
of Crespo and Martinez.5 Complex B then undergoes trans-
metalation with (CH3)2Zn to provide C (or an isomer).18,19
Intermediate C can react in two ways: (1) coordination of SMe2
to generate D, the species observed during the catalytic reaction,
or (2) reductive elimination to provide 2a and, after association
of another equivalent of imine 1a, [(CH3)2Pt(imine)].
Reductive elimination of both sp3-sp3 C-C bonds20 and
sp2-sp2 C-C bonds21 from five-coordinate Pt(IV) species is
well-documented. Alternatively, reductive elimination could
occur directly from D; sp2-sp2 C-C bond formation from six-
(18) Berry pseudorotation in five-coordinate Pt(IV) species is assumed
to be fast, on the basis of precedent from Martinez and others.
(19) We do not observe buildup of CH3ZnF during the catalytic reaction.
Presumably, the CH3ZnF generated upon transmetalation reacts with another
equivalent of B, as only 0.6 equiv of (CH3)2Zn was used in the catalytic
reaction. Consistent with this hypothesis, we have found that CH3ZnCl reacts
rapidly with B. In contrast, in the stoichiometric reaction of A with
(CH3)2Zn, a new species with a 1H NMR chemical shift of-0.86 ppm in
CD3CN is observed, which is presumably CH3ZnF. For comparison,
(CH3)2Zn has a 1H NMR chemical shift of-0.76 ppm in CD3CN.
(20) (a) Brown, M. P.; Puddephatt, R. J.; Upton, C. E. E. J. Chem. Soc.,
Dalton Trans. 1974, 2457–2465. (b) Roy, S.; Puddephatt, R. J.; Scott, J. D.
J. Chem. Soc., Dalton Trans. 1989, 2121–2125. (c) Goldberg, K. I.; Yan,
J.; Winter, E. L. J. Am. Chem. Soc. 1994, 116, 1573–1574. (d) Goldberg,
K. I.; Yan, J. Y.; Breitung, E. M. J. Am. Chem. Soc. 1995, 117, 6889–
6896. (e) Hill, G. S.; Puddephatt, R. J. Organometallics 1997, 16, 4522–
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Soc. 1999, 121, 252–253. (g) Hill, G. S.; Yap, G. P. A.; Puddephatt, R. J.
Organometallics 1999, 18, 1408–1418. (h) Crumpton, D. M.; Goldberg,
K. I. J. Am. Chem. Soc. 2000, 122, 962–963. (i) Williams, B. S.; Goldberg,
K. I. J. Am. Chem. Soc. 2001, 123, 2576–2587. (j) Crumpton-Bregel, D. M.;
Goldberg, K. I. J. Am. Chem. Soc. 2003, 125, 9442–9456. (k) Procelewska,
J.; Zahl, A.; Liehr, G.; van Eldik, R.; Smythe, N. A.; Williams, B. S.;
Goldberg, K. I. Inorg. Chem. 2005, 44, 7732–7742. (l) Luedtke, A. T.;
Goldberg, K. I. Inorg. Chem. 2007, 46, 8496–8498.
(22) Edelbach, B. L.; Lachiotte, R. J.; Jones, W. D. J. Am. Chem. Soc.
1998, 120, 2843–2853.
(23) Gallego, C.; Martinez, M.; Safont, V. S. Organometallics 2007,
26, 527–537.
(24) Excess SMe2 could slow transmetalation, reductive elimination, or
both. Excess SMe2 is also known to slow stoichiometric C-F activation
(see ref 5).
(21) Yahav-Levi, A.; Goldberg, I.; Vigalok, A.; Vedernikov, A. N. J. Am.
Chem. Soc. 2008, 130, 721–731.

Pt-Catalyzed Cross-Coupling of Polyfluoroaryl Imines
Organometallics, Vol. 27, No. 13, 2008 3295
evaporation to provide the crude imine product. Column chroma-
tography (SiO2, 70-230 mesh, n-pentane-Et3N ) 100:6 as eluant)
provided imine product 2a as a yellow oil in 95% yield. NMR
spectroscopic data of 2a correspond with those previously reported.3
a 0.34 M solution in CD3CN) were then added by syringe. The
resulting solution was transferred into an NMR tube fitted with a
screw cap containing a septum. Me2Zn (0.022 mmol, 11 µL of a
2.0 M solution in toluene) was then added by syringe. The resulting
solution was heated in the NMR machine at 60 °C. The reaction
Preparation of N-(6-Fluoro-2-methylbenzylidene)benzylamine
(2b). In a 20 mL vial, N-(2,6-difluorobenzylidene)benzylamine (1b)
(0.034 mmol, 8.5 mg) was dissolved in CD3CN (1.1 mL).
Pt2Me4(SMe2)2 (0.0017 mmol, 100 µL of a 0.017 M solution in
CD3CN) and 1,3,5-trimethoxybenzene (0.034 mmol, 100 µL of a
0.34 M solution in CD3CN) were then added by syringe. The
resulting solution was transferred into an NMR tube, which was
then fitted with a screw cap containing a septum. Me2Zn (0.022
mmol, 11 µL of a 2.0 M solution in toluene) was then added by
syringe. The resulting solution was heated at 60 °C for 8 h. The
reaction progress was monitored by 1H NMR and 19F NMR
spectroscopy. The yield of 2b was <10%, based on 1H NMR
spectroscopy by comparison of the methyl resonance of 2b with
the aryl resonances of the internal standard 1,3,5-trimethoxybenzene.
1
was monitored by H NMR spectroscopy every 10 min for 9 h.
The concentration of 2a did not change after 8 h. During the course
of the reaction, in addition to the resonances attributed to 1a and
2a, a number of smaller resonances were observed, which are
attributed to complex D.
Formation of Complex D (Figure 2). In a 20 mL vial, N-(2,4,6-
trifluorobenzylidene)benzylamine (1a) (0.34 mmol, 85 mg) and
Pt2Me4(SMe2)2 (10.0 mg, 0.017 mmol) were dissolved in 1.1 mL
of CD3CN. The resulting solution was transferred into an NMR
tube, which was then fitted with a screw cap containing a septum.
Me2Zn (0.22 mmol, 110 µL of a 2.0 M solution in toluene) was
subsequently added by syringe. The resulting solution in a NMR
tube was heated at 60 °C and monitored by 1H NMR and 19F NMR
spectroscopy. 1H NMR (acetonitrile-d3, 300 MHz): δ 8.87 (s, JPt-H
) 39.0 Hz, 1H), 4.98 (m, 2H), 1.77 (s, JPt-H ) 12.0 Hz, 6H), 0.78
(s, JPt-H ) 69.2 Hz, 3H), 0.41 (s, JPt-H ) 72.6 Hz, 3H), 0.20 (s,
JPt-H ) 45.9 Hz, 3H). (Resonances of aryl protons overlapped with
aryl resonances for 1a and toluene). 19F NMR (acetonitrile-d3, 282
MHz): δ -104.1 (m, this resonance overlapped with resonance for
1a), -111.4 (m).
Preparation of Pt-F Complex A (Figure 3). In a 20 mL vial,
N-(2,4,6-trifluorobenzylidene)benzylamine (1a) (0.034 mmol, 8.5
mg) and Pt2Me4(SMe2)2 (0.017 mmol, 9.8 mg) were dissolved in
CD3CN (1.1 mL). 1,3,5-Trimethoxybenzene (0.034 mmol, 100 µL
of a 0.34 M solution in CD3CN) was then added by syringe. The
resulting solution was transferred into an NMR tube, which was
then fitted with a screw cap containing a septum. The NMR tube
was placed in the NMR machine at 60 °C. The reaction was
monitored by 1H NMR spectroscopy every 10 min for 8 h. No
evidence of formation of 2a was observed (eq 8). 1H NMR
(acetonitrile-d3, 400 MHz): δ 8.78 (s, JPt-H ) 47.5 Hz, 1H), 5.05
(m, 2H), 1.90 (s, JPt-H ) 12.1 Hz, 6H), 1.11 (d, JPt-H ) 65.6 Hz,
JF-H ) 7.1 Hz, 3H), 0.72 (d, JPt-H ) 68.3 Hz, JF-H ) 7.1 Hz, 3H).
(Resonances of aryl protons overlapped with aryl resonances for
1a). 19F NMR (acetonitrile-d3, 282 MHz): δ -103.2 (m, 1F),
-111.9 (m, 1F), -262.3 (br s, 1F).
Preparation of 2a by the reaction between Pt-F complex A
and Me2Zn (eq 9, Figure 4). Step 1: Preparation of Pt-F Complex
A: In a 20 mL vial, N-(2,4,6-trifluorobenzylidene)benzylamine (1a)
(0.034 mmol, 8.5 mg) and Pt2Me4(SMe2)2 (0.017 mmol, 9.8 mg)
were dissolved in CD3CN (1.1 mL). 1,3,5-Trimethoxybenzene
(0.034 mmol, 100 µL of a 0.34 M solution in CD3CN) was
subsequently added by syringe. The resulting solution was trans-
ferred into an NMR tube, which was then fitted with a screw cap
containing a septum. The NMR tube was heated at 60 °C for 8 h
to obtain Pt-F complex A in situ, as evidenced by 1H and 19F
NMR spectroscopy. Step 2: Reaction between Pt-F Complex A
and Me2Zn: Me2Zn (0.044 mmol, 22.0 µL of a 2.0 M solution in
toluene) was added by syringe to the NMR tube containing A in
CD3CN. The reaction was heated at 60 °C in the NMR machine,
and the reaction was monitored by 1H NMR spectroscopy every 2
min for 1 h. The formation of 2a was completed in 30 min. The
yield of 2a was 69%, based on 1H NMR spectroscopy by
comparison of the methyl resonance of 2a with the aryl resonance
of the internal standard 1,3,5-trimethoxybenzene.
Preparation of N-(3,6-Difluoro-2-methylbenzylidene)benzy-
lamine (2c). In a 20 mL vial, N-(2,3,6-trifluorobenzylidene)ben-
zylamine (1c) (0.034 mmol, 8.5 mg) was dissolved in CD3CN (1.1
mL). Pt2Me4(SMe2)2 (0.0017 mmol, 100 µL of a 0.017 M solution
in CD3CN) and 1,3,5-trimethoxybenzene (0.034 mmol, 100 µL of
a 0.34 M solution in CD3CN) were then added by syringe. The
resulting solution was transferred into an NMR tube fitted with a
screw cap containing a septum. Me2Zn (0.022 mmol, 11 µL of a
2.0 M solution in toluene) was then added by syringe. The resulting
solution was heated at 60 °C for 11 h. The sample was monitored
by 1H NMR and 19F NMR spectroscopy. The yield of 2c was 97%,
based on 1H NMR spectroscopy by comparison of the methyl
resonance of 2c with the aryl resonance of the internal standard
1,3,5-trimethoxybenzene. NMR data of 2c correspond with those
previously reported.3
Preparation of N-(3,4,5,6-Tetrafluoro-2-methylbenzylidene)ben-
zylamine (2d). In a 20 mL vial, N-(2,3,4,5,6-pentafluoroben-
zylidene)benzylamine (1d) (0.034 mmol, 9.7 mg) was dissolved
in CD3CN (1.1 mL). Pt2Me4(SMe2)2 (0.0017 mmol, 100 µL of a
0.017 M solution in CD3CN) and 1,3,5-trimethoxybenzene (0.034
mmol, 100 µL of a 0.34 M solution in CD3CN) were added by
syringe. The resulting solution was transferred into an NMR tube
fitted with a screw cap containing a septum. Me2Zn (0.022 mmol,
11 µL of a 2.0 M solution in toluene) was then added by syringe.
The resulting solution was heated at 80 °C for 12 h. The sample
was monitored by 1H NMR and 19F NMR spectroscopy. The yield
of 2d was 74%, based on 1H NMR spectroscopy by comparison of
the methyl resonance of 2d with the aryl resonance of the internal
standard 1,3,5-trimethoxybenzene. NMR data correspond with those
previously reported.3
Preparation of N-(3,4,5-Trifluoro-2,6-dimethylbenzylidene)ben-
zylamine (3d). N-(3,4,5,6-Tetrafluoro-2-methylbenzylidene)ben-
zylamine (2d) was prepared as above. Additional Me2Zn (0.022
mmol, 11 µL of a 2.0 M solution in toluene) was then added by
syringe into the NMR tube containing 2d. The resulting solution
was heated at 80 °C for an additional 15 h. The yield of 3d was
72%, based on 1H NMR spectroscopy by comparison of the methyl
resonance of 3d with the aryl resonance of the internal standard
1
1,3,5-trimethoxybenzene. H NMR (acetonitrile-d3, 300 MHz): δ
8.65 (s, 1H), 4.84 (s, 2H), 2.29 (t, J ) 2.0 Hz, 6H). (Resonances
of aryl protons overlapped with aryl resonances for toluene). 19F
NMR (acetonitrile-d3, 282 MHz): δ -141.2 (d, J ) 19.8 Hz, 2F),
-160.3 (t, J ) 19.8 Hz, 1F). HRMS (EI) m/z calcd for C16H14F3N:
277.1078; found: 277.1080.
Formation of 2a monitored by 1H NMR spectroscopy
(Figure 1). In a 20 mL vial, N-(2,4,6-trifluorobenzylidene)benzy-
lamine (1a) (0.034 mmol, 8.5 mg) was dissolved in CD3CN (1.1
mL). Pt2Me4(SMe2)2 (0.0017 mmol, 100 µL of a 0.017 M solution
in CD3CN) and 1,3,5-trimethoxybenzene (0.034 mmol, 100 µL of
Cross-Coupling Reaction between 1c and Me2Zn Catalyzed
by Pt-F Complex A (eq 11). Step 1: Preparation of Pt-F
Complex A: In a 20 mL vial, N-(2,4,6-trifluorobenzylidene)ben-
zylamine (1a) (0.0034 mmol, 100 µL of a 0.034 M solution in
CD3CN) and Pt2Me4(SMe2)2 (0.0017 mmol, 100 µL of a 0.017 M
solution in CD3CN) were dissolved in CD3CN (1.1 mL). The
resulting solution was transferred into an NMR tube, which was

3296 Organometallics, Vol. 27, No. 13, 2008
Wang and LoVe
then fitted with a screw cap containing a septum. The NMR tube
was heated at 60 °C for 8 h to obtain Pt-F complex A in situ, as
evidenced by 1H and 19F NMR spectroscopy. Step 2: Cross-
coupling of 1c and Me2Zn Catalyzed by Pt-F Complex A: N-(2,3,6-
Trifluorobenzylidene)benzylamine (1c) (0.034 mmol, 8.5 mg) was
weighed into a 20 mL vial. The solution of Pt-F complex A
prepared above was transferred into the vial from the NMR tube.
1,3,5-Trimethoxybenzene (0.034 mmol, 100 µL of a 0.34 M solution
in CD3CN) was then added by syringe. The resulting solution was
transferred back into the NMR tube, which was then fitted with a
screw cap containing a septum. Me2Zn (0.022 mmol, 11.0 µL of a
2.0 M solution in toluene) was subsequently added by syringe. The
resulting solution was heated at 60 °C, and the reaction was
monitored by 1H NMR and 19F NMR spectroscopy over 11 h. The
then fitted with a screw cap containing a septum. The NMR tube
was heated at 60 °C for 8 h to obtain Pt-F complex A in situ, as
evidenced by 1H and 19F NMR spectroscopy. Step 2: Reaction
between Pt-F Complex A, Me2Zn, and 1d: N-(2,3,4,5,6-Pentafluo-
robenzylidene)benzylamine (1d) (0.068 mmol, 19.4 mg) was
weighed into a 20 mL vial. The solution of Pt-F complex A
prepared above was transferred into the vial from the NMR tube.
The resulting solution was transferred back into the NMR tube,
which was then fitted with a screw cap containing a septum. Me2Zn
(0.017 mmol, 8.5 µL of a 2 M solution in toluene) was subsequently
added by syringe. The tube was heated at 60 °C for 30 min. The
1
reaction was monitored by H NMR and 19F NMR spectroscopy.
1
Complex A′ was evidenced by H NMR and 19F NMR spectro-
scopic data, with a yield of 75%, and the yield of 2a was 79%.
1
yield of 2c was 92%, based on H NMR spectroscopy integration
Reaction between 1a, Pt2Me4(SMe2)2, and SEt2. In a 20 mL
vial, N-(2,4,6-trifluorobenzylidene)benzylamine (1a) (0.18 mmol,
44 mg) and Pt2Me4(SMe2)2 (0.088 mmol, 50 mg) were dissolved
in CD3CN (1.1 mL). The resulting solution was transferred into an
NMR tube, which was then fitted with a screw cap containing a
septum. Diethyl sulfide (18.5 µL, 0.172 mmol) was subsequently
added by syringe. The NMR tube was heated at 60 °C for 9 h and
then cooled to room temperature. The complex A · SEt2 was as
of methyl resonance of 2c, compared to integration of the aryl
resonance of the internal standard 1,3,5-trimethoxybenzene. The
yield of 2a was 8%, based on 1H NMR spectroscopy by comparison
of the methyl resonance of 2a with the internal standard 1,3,5-
trimethoxybenzene.
Reaction between Pt-F Complex A and 1d (eq 12). Step 1:
Preparation of Pt-F Complex A: In a 20 mL vial, N-(2,4,6-
trifluorobenzylidene)benzylamine (1a) (0.034 mmol, 8.5 mg) and
Pt2Me4(SMe2)2 (0.017 mmol, 9.8 mg) were dissolved in CD3CN
(1.1 mL). 1,3,5-Trimethoxybenzene (0.034 mmol, 100 µL of a 0.34
M solution in CD3CN) was subsequently added by syringe. The
resulting solution was transferred into an NMR tube, which was
then fitted with a screw cap containing a septum. The tube was
heated at 60 °C for 8 h to obtain Pt-F complex A in situ, as
evidenced by 1H and 19F NMR spectroscopy. Step 2: Reaction
between Pt-F Complex A and 1d: N-(2,3,4,5,6-Pentafluoroben-
zylidene)benzylamine (1d) (0.34 mmol, 97.3 mg) was weighed into
a 20 mL vial. The solution of Pt-F complex A prepared above
was transferred into the vial from the NMR tube. The resulting
solution was transferred back into the NMR tube fitted with a screw
cap containing a septum. The tube was heated in oil bath at 60 °C
for 8 h. Reactions were monitored by 1H NMR and 19F NMR
spectroscopy. No evidence was observed for complex A′, and the
resonance of Pt-F of complex A decreased with time.
observed in the H and 19F NMR spectra. H NMR (acetonitrile-
d3, 400 MHz): δ 8.76 (s, JPt-H ) 46.9 Hz, overlapped with CHdN
for complex A), 5.05 (m, overlapped with CH2Ph for complex A),
2.44 (m, overlapped with CH2 for free SEt2), 1.15 (d, JPt-H ) 66.0
Hz, JF-H ) 7.0 Hz, 3H), 0.98 (t, JH-H ) 7.4 Hz, 3H), 0.72 (d,
JPt-H ) 68.3 Hz, JF-H ) 7.1 Hz, 3H). (Resonances of aryl protons
overlapped with aryl resonances for 1a and A.) 19F NMR
(acetonitrile-d3, 282 MHz): δ -103.3 (m, overlapped with reso-
nances for complex A), -112.0 (m, overlapped with resonances
for complex A), -262.0 (br s).
1
1
Acknowledgment. We thank the following for support
of this research: University of British Columbia, NSERC
(Discovery Grant, Research Tools and Instrumentation
Grants), Merck Frosst, the Canada Foundation for Innovation
(new Opportunities Grant), and the British Columbia Knowl-
edge Fund.
Reaction between Pt-F Complex A, Me2Zn, and 1d (eq 13).
Step 1: Preparation of Pt-F Complex A: In a 20 mL vial, N-(2,4,6-
trifluorobenzylidene)benzylamine (1a) (0.034 mmol, 8.5 mg) and
Pt2Me4(SMe2)2 (0.017 mmol, 9.8 mg) were dissolved in CD3CN
(1.1 mL). 1,3,5-Trimethoxybenzene (0.034 mmol, 100 µL of a 0.34
M solution in CD3CN) was subsequently added by syringe. The
resulting solution was transferred into an NMR tube, which was
Supporting Information Available: Complete experimental
details. This material is available free of charge via the Internet at
http://pubs.acs.org.
OM800247P