Catalytic cycle for palladium-catalyzed decarbonylative trifluoromethylation using trifluoroacetic esters as the CF3 source

Article abstract of DOI:10.1021/om500398z

This paper demonstrates a catalytic cycle for Pd-catalyzed decarbonylative trifluoromethylation using trifluoroacetic esters as CF₃ sources. The proposed cycle consists of four elementary steps: (1) oxidative addition of a trifluoroacetic ester to Pd⁰, (2) CO deinsertion from the resulting trifluoroacyl Pd^II complex, (3) transmetalation of a zinc aryl to Pd^II, and (4) aryl-CF₃ bond-forming reductive elimination. The use of RuPhos as the supporting ligand enables each of these steps to proceed under mild conditions (<100 °C). These studies set the stage for the development of catalytic arene trifluoromethylation and perfluoroalkylation reactions using inexpensive trifluoroacetic acid derived CF₃ sources.

Full text of DOI:10.1021/om500398z

Article
pubs.acs.org/Organometallics
Catalytic Cycle for Palladium-Catalyzed Decarbonylative
Trifluoromethylation using Trifluoroacetic Esters as the CF3 Source
Ansis Maleckis and Melanie S. Sanford*
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor Michigan 48109, United States
S
* Supporting Information
ABSTRACT: This paper demonstrates a catalytic cycle for Pd-catalyzed
decarbonylative trifluoromethylation using trifluoroacetic esters as CF3 sources.
The proposed cycle consists of four elementary steps: (1) oxidative addition of a
trifluoroacetic ester to Pd0, (2) CO deinsertion from the resulting trifluoroacyl PdII
complex, (3) transmetalation of a zinc aryl to PdII, and (4) aryl−CF3 bond-forming
reductive elimination. The use of RuPhos as the supporting ligand enables each of
these steps to proceed under mild conditions (<100 °C). These studies set the
stage for the development of catalytic arene trifluoromethylation and perfluor-
oalkylation reactions using inexpensive trifluoroacetic acid derived CF3 sources.
INTRODUCTION
■
Trifluoromethyl and other fluoroalkyl groups are prevalent in a
variety of biologically active molecules. They are commonly
used to modulate the bioavailability, binding affinity, and
metabolic stability of pharmaceuticals and agrochemicals.1
However, wider application of fluoroalkylated compounds
(particularly fluoroalkylated aromatics and heteroaromatics) is
field, its practical utility is constrained by the high cost and
limited availability of TESCF3 and perfluoroalkyl derivatives
thereof.
inhibited by limitations in the synthetic methods available for
preparing these molecules. Over the past decade, significant
effort has been directed toward the development of more
ecologically sustainable, inexpensive, and broadly applicable
methods for the late-stage perfluoroalkylation of arenes and
heteroarenes.2 Copper-catalyzed and/or -mediated cross-
coupling reactions have received the most attention.2,3 These
reactions generally proceed with high levels of chemo- and
regioselectivity; furthermore, they can involve diverse perfluor-
oalkylating reagents and aryl precursors. However, the Cu-
mediated/catalyzed reactions are commonly limited by the
requirement for superstoichiometric quantities of metal,
expensive trifluoromethylating reagents, and/or forcing reac-
tion conditions.2,3
We targeted more practical Pd0/II-catalyzed trifluoromethy-
lation reactions using trifluoroacetic ester or anhydride
derivatives (CF3CO2R) as readily available and inexpensive
alternatives to TESCF3. We hypothesized that these reagents
could participate in decarbonylative cross-coupling with
organometallic reagents to form trifluoromethylated products
via the catalytic cycle shown in Scheme 1.15−20 This cycle
would involve (i) oxidative addition of the anhydride/ester at
Pd0 to generate a PdII trifluoroacyl complex, (ii) decarbon-
ylation to release CO and form a PdII−CF3 adduct, (iii)
transmetalation with a M−aryl species to yield a PdII(aryl)-
(CF3) intermediate, and (iv) aryl−CF3 bond-forming reductive
elimination to release the trifluoromethylated product. To our
knowledge, this decarbonylative approach to arene trifluor-
omethylation has not been pursued previously at any metal
center.
In contrast, low-valent Pd and Ni complexes (i.e. Pd0/II and
Ni0/II) have generally proven ineffective as catalysts for arene
trifluoromethylation.4,5 Studies of well-defined Ni and Pd
complexes have shown that, due to the unique electronic
properties of the CF3 ligand,6 aryl−CF3 bond-forming reductive
elimination from nickel(II)7,8 and palladium(II)9,10 centers is
an extremely challenging process.11 As such, only a single
example of Pd0/II-catalyzed trifluoromethylation of aryl halides
has been reported.12 As shown in eq 1, this system utilizes a
biarylmonophosphine ligand (BrettPhos13 or RuPhos14) in
conjunction with TESCF3 as the trifluoromethyl source. While
this transformation represents an exciting breakthrough for the
The proposed step i (oxidative addition of CF3CO2R to
Pd0)21 as well as step iii (transmetalation at PdII)22−24 both
have significant precedent in the literature. However, there are
currently only two reported examples of aryl−CF3 bond-
Received: April 14, 2014
Published: May 12, 2014
© 2014 American Chemical Society
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(Scheme 2).35 This Pd0 intermediate was then reacted in situ
Scheme 1. Proposed Catalytic Cycle for Decarbonylative
Trifluoromethylation
with pentafluorophenyl trifluoroacetate.36,37 Monitoring this
Scheme 2. Oxidative Addition of CF3CO2C6F5 to
(RuPhos)Pd0 To Form 1
forming reductive elimination from PdII centers (step iv).12,25
Furthermore, decarbonylation at trifluoroacylpalladium com-
plexes (step iii) is currently unprecedented.26 Several other
second- and third-row transition-metal trifluoroacyl complexes
are known to undergo decarbonylation; however, these
transformations often require high temperatures and long
reaction times.27−30 For instance, decarbonylation at the PtII
complex CF3COPt(Cl)(PPh3)2 requires heating under vacuum
at 210 °C for 4 h.31 Thus, we anticipated that CO deinsertion
could present a major bottleneck for the envisioned
trifluoromethylation reaction.
In order to identify appropriate supporting ligands, reagents,
and reaction conditions for the proposed decarbonylative
trifluoromethylation sequence, we sought to assess the
feasibility of each elementary step in the proposed catalytic
cycle in Scheme 1. We demonstrate herein that all of the
elementary steps are feasible under relatively mild reaction
conditions (<100 °C) using RuPhos-ligated Pd complexes.
reaction by 1D 19F-NMR and 2D 19F/13C HMBC NMR
spectroscopy showed the formation of oxidative addition
product 2 within 30 min at 20 °C. Upon workup, 2 underwent
ligand exchange with trifluoroacetate in solution (presumably
generated via hydrolysis of the ester) to yield product 1 in 73%
isolated yield over two steps.
Product 1 was characterized via 1D and 2D 13C, 31P, and 19
F
NMR spectroscopy as well as HRMS. The presence of both
trifluoroacyl and trifluoroacetate ligands is apparent from the
13C NMR spectrum of 1. The 13C signal for the CO of the
trifluoroacyl ligand appears as a quartet of doublets (2JCF = 38.2
Hz and 3JCP = 7.5 Hz) at 207.5 ppm. In contrast, the CO of
the trifluoroacetate appears significantly upfield (160.7 ppm)
2
and does not show coupling to phosphorus (quartet, JCF
=
34.7 Hz). The 13C NMR spectrum of 1 implicates bidentate
coordination of RuPhos through phosphorus and one aromatic
carbon. The bound carbon atom appears as a doublet (2JCP
=
4.1 Hz) at 106 ppm. Importantly, similar bidentate binding of
biarylmonophosphines has been documented previously.34,38
To further confirm the structure of 1, we independently
synthesized this complex via an alternative route. As shown in
Scheme 3, the treatment of Pd[P(o-Tol)3]2 with trifluoroacetic
RESULTS AND DISCUSSION
■
Selection of Ligand. The proposed decarbonylative
trifluoromethylation requires a supporting ligand that will
enable both challenging steps of the catalytic cycle: CO
deinsertion and aryl−CF3 bond-forming reductive elimination.
CO insertion/deinsertion reactions generally proceed via three-
center transition states.32 As such, CO deinsertion from a
coordinatively unsaturated three-coordinate PdII species is
expected to be significantly more facile than that from a
square-planar tetracoordinate PdII center.33 On the basis of this
analysis, we hypothesized that a sterically bulky mono-
phosphine ligand such as RuPhos14 would be well suited for
promoting this elementary step. Previous work has shown that
RuPhos (and close analogues thereof) can act as a bidentate
ligand, with the aromatic ring of the biaryl functionality serving
as a second binding site.34 In this binding mode, the aromatic
ring serves as a hemilabile ligand, such that coordinatively
unsaturated tricoordinate PdII species are readily accessible. As
such, bulky biarylmonophosphines such as RuPhos are
predicted to enable CO deinsertion at PdII under mild reaction
conditions. In addition, Buchwald has demonstrated that
RuPhos promotes aryl−CF3 bond-forming reductive elimina-
tion from PdII(aryl)(CF3) complexes.12
Scheme 3. Alternate Synthesis of 1
Step i: Oxidative Addition of Trifluoroacetyl Esters to
Pd0. A RuPhos-ligated Pd0 species was generated by treatment
of (Cp)Pd(allyl) with 2 equiv of RuPhos at 60 °C for 30 min
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anhydride (TFAA) afforded oxidative addition product 3 in
91% isolated yield. The P(o-Tol)3 ligands of 3 were then
displaced by 1.1 equiv of RuPhos to afford 1 in 78% yield. The
approach shown in Scheme 3 was also used to prepare the
corresponding perfluoroethyl complex 5 starting from Pd[P(o-
Tol)3]2 and pentafluoropropionic anhydride.
Scheme 5. Transmetalation and Reductive Elimination
Step ii: CO Deinsertion. We next investigated the key CO
deinsertion reaction at perfluoroacyl complexes 1 and 5.
Gratifyingly, heating benzene solutions of 1 and 5 at reflux for
1.5 h resulted in clean decarbonylation to yield the
corresponding perfluoroalkyl complexes 6 and 7 (Scheme 4).
Scheme 4. Decarbonylation at 1 and 5
Specifically, the reaction of 6 and 7 with salt-free diphenylzinc
and di-o-tolylzinc afforded complexes 9−12 in 42−92% isolated
yields.44 19F and 31P NMR analyses of the crude reaction
mixtures of 9−12 showed no side products; thus, the variation
in isolated yield merely reflects loss of product during the
isolation process. The structures of complexes 9−12 were
1
determined using 1D H, 13C, 31P, and 19F NMR spectroscopy
as well as by 2D 19F/13C and 1H/13C NMR correlation
experiments. The stereochemistry of 9−12 was assigned on the
1
basis of H/1H ROESY NMR spectra (see the Supporting
Information for full details).
Step iv: Reductive Elimination. Complexes 9−12 are
stable in both CDCl3 and benzene solution at room
temperature for at least 10 h. However, heating benzene
solutions of 9−12 at 90 °C for 12 h resulted in aryl−CF3 bond-
forming reductive elimination to yield 13−16 (Scheme 5). The
yields of 13−16 were determined using 19F NMR spectroscopy
with 1,4-bis(trifluoromethyl)benzene as an internal standard. In
all cases, complete consumption of the starting complexes 9−
13 was observed. Compounds 13 and 14 were obtained in only
13% and 20% yields, respectively. In contrast, the 2-
tolylpalladium complexes 10 and 12 afforded reductive
elimination products 15 and 16 in significantly higher yields
(65% and 55%, respectively). These results are consistent with
Buchwald’s prior report of the trifluoromethylation of aryl
chlorides with TESCF3.12 In this system, RuPhos provided
modest yields with simple aryl chlorides; however, a dramatic
enhancement in yield was observed with sterically hindered aryl
chloride electrophiles. Interestingly, in our system the
conversion rates for all of the complexes 9−12 are
approximately the same. This suggests that additional steric
bulk on the σ-aryl ligand does not significantly increase the rate
of reductive elimination but more likely limits unproductive
decomposition pathways.
These decarbonylation reactions proceeded in quantitative
yield as determined by 19F and 31P NMR spectroscopy, and the
pure products were isolated via recrystallization in 78% and
62% yields, respectively.
Interestingly, when benzene solutions of 1 were allowed to
stand at room temperature (rather than reflux), completely
different reactivity was observed. Under these conditions, 1
slowly decomposed to form the dicationic palladium(I) dimer
8, which was isolated in 44% yield after 12 h at room
temperature. The structure of 8 was determined on the basis of
NMR and HRMS analysis (see the Supporting Information for
full spectra and a detailed discussion of assignments).39
Complex 8 has C2h symmetry; therefore, both phosphine
ligands are chemically equivalent, leading to just one set of
1
signals in the 13C and H NMR spectra. However, virtual
coupling is observed in the 13C NMR spectrum, and this is a
diagnostic feature of symmetric trans-diphosphine complexes.40
In addition, in the 13C NMR spectrum, the signals for C1−C4
are shifted to 94.1, 151.4, 86.7, and 80.5 ppm, respectively.
These chemical shifts present strong evidence that aromaticity
in the π-coordinated benzene ring is partially disrupted upon
binding to the dicationic Pd−Pd unit. Moreover, a molecular
ion isotope pattern between 571 and 575 Da with 0.5 Da
spacing in the HRMS of 8 is indicative of a species with the
molecular formula [(RuPhos)2Pd2]2+.41 While the exact
mechanism for the formation of 8 is unclear, it likely involves
conproportionation between (RuPhos)Pd0 and a (RuPhos)-
Pd2+ species.42 A number of related dinuclear PdI−PdI
complexes stabilized by π coordination to arenes have been
reported in the literature.43
CONCLUSIONS
■
This paper describes a detailed study designed to assess the
feasibility of Pd-catalyzed decarbonylative trifluoromethylation
reactions using trifluoroacetate esters as inexpensive and readily
available trifluoromethylating reagents. Each step of the
proposed catalytic cycle has been interrogated using RuPhos
as a supporting ligand. It was found that pentafluorophenyl
trifluoroacetate undergoes oxidative addition to (RuPhos)nPd0
under mild conditions. The resulting product (RuPhos)Pd-
(COCF3)(CO2CF3) eliminates CO in refluxing benzene (80
Step iii: Transmetalation. We next investigated trans-
metalation reactions of the (RuPhos)PdII(perfluoroalkyl)
products 6 and 7. Diarylzincs were found to be particularly
effective transmetalating reagents for this system (Scheme 5).
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Preparation of (RuPhos)Pd(COCF3)(OCOCF3) (1). Method 1:
Oxidative Addition of CF3COOC6F5 to in Situ Generated
(RuPhos)nPd0. CpPd(allyl) (200 mg; 0.94 mmol) and RuPhos (933
mg; 2.00 mmol) were combined in a Schlenk flask. The Schlenk flask
was flushed with nitrogen for 15 min, and then degassed THF (20
mL) was added via cannula. The resulting red solution was heated to
60 °C for 30 min. The solution was cooled to −78 °C, and
CF3COOC6F5 (840 mg; 3.00 mmol) was added dropwise over a
period of 5 min. The reaction mixture was slowly warmed to room
temperature. After it was stirred at room temperature for 1 h, the
reaction mixture was concentrated under reduced pressure at room
temperature. The resulting residue was dissolved in 100 mL of
diisopropyl ether, and this solution was filtered through Celite.
Hexanes (60 mL) were added to the diisopropyl ether solution, and
the resulting mixture was allowed to stand at −20 °C for 8 h. During
this period, the product precipitated in the form of yellowish crystals.
The product was collected by filtration and washed with two 5 mL
portions of cold diisopropyl ether. After drying under vacuum, 541 mg
(73%) of a yellowish crystalline solid was obtained.
°C) to afford (RuPhos)Pd(CF3)(CO2CF3). Next, trans-
metalation with diarylzinc reagents yields (RuPhos)Pd(CF3)-
(aryl). Finally, heating of (RuPhos)Pd(CF3)(aryl) complexes to
90 °C for 12 h affords aryl−CF3 reductive elimination products.
These exciting results demonstrate the potential feasibility of
using perfluoroalkyl esters as CF3 sources in cross-coupling
reactions. The current challenge is to integrate these
elementary steps into a complete catalytic cycle for arene
fluoroalkylation. Key to this goal is identifying perfluoroalkyl
esters and transmetalating reagents that are compatible with
one another. In addition, the relative rates of CO deinsertion,
transmetalation, and reductive elimination must be controlled,
such that the desired aryl-RF bond formation outcompetes
undesired aryl−C(O)RF coupling.21a For instance, currently,
the CO deinsertion reaction and aryl−CF3 reductive
elimination reactions require significantly higher temperatures
than the other two steps of the porposed cycle. Efforts to
address these challenges are currently underway in our
laboratory and will be reported in due course.
Method 2: Ligand Exchange Reaction of P(o-Tol)3)2Pd(COCF3)-
(OCOCF3) (3) with RuPhos. Under a nitrogen atmosphere, a solution
of (P(o-Tol)3)2Pd(COCF3)(OCOCF3)·Et2O (3; 1.00 g, 1.00 mmol)
and RuPhos (513 mg; 1.1 mmol) in THF (20 mL) was stirred at 0 °C
for 10 min. The resulting solution was then concentrated under
reduced pressure at 0 °C. Diethyl ether (10 mL) was added to the
residue, and the resulting suspension was stirred at 0 °C for 15 min.
The product was separated by filtration and then washed with two 5
mL portions of cold diethyl ether. After drying under vacuum, 615 mg
(78%) of a yellowish crystalline solid was obtained. 1H NMR
(acetone-d6 at 25 °C): δ 7.87 (apparent t, J = 7.7 Hz, 1H), 7.56 (t, J =
7.5 Hz, 1H), 7.53−7.48 (multiple peaks, 2H), 6.85 (dd, J = 7.9 and 3.2
Hz, 1H), 6.59 (d, J = 8.6 Hz, 2H), 4.64 (septet, J = 6.1 Hz, 2H), 2.40
(m, 2H), 2.24 (m, 2H), 1.90 (m, 2H), 1.83 (m, 4H), 1.73 (m, 2H),
1.57 (m, 2H), 1.44 (m, 2H), 1.40 (d, J = 6.1 Hz, 6H), 1.36 (m, 2H),
1.16 (m, 2H), 1.04 (m, 2H), 1.02 (d, J = 6.1 Hz, 6H). 13C{1H} NMR
(acetone-d6 at 25 °C; δ): 207.53 (qd, 2JC−F = 38.2 Hz, 3JC−P = 7.5 Hz),
EXPERIMENTAL SECTION
■
General Procedures. All syntheses were conducted under
nitrogen unless otherwise stated. All reagents were purchased from
commercial sources and used as received. Pd[P(o-Tol)3]2 was obtained
according to the literature procedure.45 Tetrahydrofuran, dichloro-
methane, and diethyl ether were purified using an Innovative
Technologies (IT) solvent purification system consisting of a copper
catalyst, activated alumina, and molecular sieves. NMR spectra were
obtained on a Varian VNMRS 700, Varian VNMRS 500, Varian Inova,
1
or Varian MR400 spectrometer. H, 19F, and 13C chemical shifts are
reported in parts per million (ppm) relative to TMS, with the residual
solvent peak used as an internal reference. Mass spectral data was
obtained on a Micromass magnetic sector mass spectrometer with an
electrospray ionization mode. FT-IR spectra were obtained on a
Perkin-Elmer “Spectrum BX” instrument with ATR accessory (ZnSe
ATR crystal). Elemental analyses were performed by Atlantic
Microlab, Inc.
2
161.99, 160.65 (q, JC−F = 34.7 Hz), 145.61 (d, J = 17.7 Hz), 138.25,
133.92 (d, J = 45.0 Hz), 132.76−132.40 (three overlapping signals as
revealed by 1H/13C HMBC), 127.82 (d, J = 6.1 Hz), 117.37 (qd, 1JC−F
4
1
3
= 292.2 Hz, JC−P = 7.5 Hz), 109.99 (qd, JC−F = 300.4 Hz, JC−P
=
17.0 Hz), 106.12 (d, 2JC−P = 4.1 Hz), 106.05, 71.83, 33.31 (d, J = 29.3
Hz), 29.56 (d, J = 2.1 Hz), 29.05 (d, J = 1.3 Hz), 27.27 (d, J = 14.3
Hz), 27.09 (d, J = 11.6 Hz), 26.76, 22.08, 21.92. 19F NMR (acetone-d6
at 25 °C; δ): −74.32 (s, 3F), −75.03 (s, 3F). 31P{1H} NMR (acetone-
d6 at 25 °C; δ): 45.45 (s). 19F/13C HSQC NMR (acetone-d6 at 25 °C;
δF/δC): −74.32/109.99, −75.03/117.37. 19F/13C HMBC NMR
(acetone-d6 at 25 °C; δF/δC): −74.32/207.53, −75.03/117.37 (1J
correlation), −75.03/160.65. IR (ATR; cm−1): 2978 (w), 2937 (m),
2853 (m), 1747 (m), 1702 (s), 1686 (s), 1588 (m), 1450 (m), 1410
(m), 1377 (w), 1256 (s), 1224 (s), 1190 (s), 1178 (s), 1128 (s), 1108
(s). HRMS electrospray (m/z): [M − OOCCF3]+ calcd for
Preparation of (P(o-Tol)3)2Pd(COCF3)(OCOCF3) (3). A Schlenk
flask was charged with a stirbar and Pd[P(o-Tol)3]2 (4.00 g; 6.92
mmol). The flask was sealed, evacuated under reduced pressure, and
then refilled with nitrogen. The flask was evacuated and refilled with
nitrogen three more times. Dry THF (100 mL) was added via cannula.
Trifluoroacetic anhydride (TFAA) (1.13 mL; 8 mmol) was then added
dropwise over a period of 10 min. The resulting solution was stirred at
room temperature for 20 min and then filtered through a pad of Celite.
The volatiles were removed under reduced pressure. The residue was
suspended in diethyl ether (100 mL). Product slowly separated over a
period of 4 h in a form of yellowish crystals. This precipitate was
filtered and washed with several portions of diethyl ether. After drying
C32H43F3O3PPd 669.1931, found 669.1947; [M − OCOCF3
−
CO]+ calcd for C31H43F3O2PPd 641.1982, found 641.2001.
1
under vacuum, 5.08 g (91%) of a yellowish solid was obtained. H
Preparation of (RuPhos)Pd(COC2F5)(OCOC2F5) (5). A Schlenk
flask was charged with a stirbar and Pd[P(o-Tol)3]2 (1.90 g; 2.66
mmol). The flask was sealed, evacuated under reduced pressure, and
then refilled with nitrogen. The flask was evacuated and refilled with
nitrogen three more times. Dry THF (100 mL) was added via cannula.
Perfluoropropionic anhydride (0.66 mL, 3.0 mmol) was then added
dropwise over a period of 5 min. This solution was stirred for 20 min
at room temperature and then filtered through a pad of Celite, and the
volatiles were removed under reduced pressure. The resulting residue
was dissolved in benzene (35 mL), and RuPhos (700 mg; 1.5 mmol)
was added in one portion. The resulting homogeneous solution was
stirred at room temperature for 20 min, and then the volatiles were
removed under reduced pressure. The residue was dissolved in dibutyl
ether (30 mL). The product slowly precipitated in the form of
yellowish crystals. The product was collected by filtration and washed
with several portions of dibutyl ether and then with hexanes. After
drying under vacuum, 989 mg (74% yield based on RuPhos) of
NMR and elemental analysis showed that the crystallized compound
contains exactly 1 equiv of diethyl ether that could not be removed
even after prolonged drying under vacuum. The cocrystallized ether
was taken into account when the reaction yield was calculated. 1H, 19F,
and 31P NMR spectra of 3 contain only very broad resonances. We
explain this on the basis of reversible dissociation of the P(o-Tol)3
ligand and dynamic equilibrium between several species in the
solution. This is supported by the fact that the 31P NMR spectrum of 3
contains a singlet at −29.6 ppm that corresponds to a free P(o-Tol)3
1
ligand. H NMR (CDCl3 at 23 °C; δ): 10.0−6.0 (br, 24H), 4.0−1.0
(br, 18 H), 3.48 (q, J = 7.1 Hz, 4H, diethyl ether), 1.21 (t, J = 7.1 Hz,
6H, diethyl ether). 19F NMR (CDCl3 at 23 °C; δ): −73.2 (br, 3F),
−74.8 (br, 3F). 31P{1H} NMR (CDCl3 at 23 °C; δ): 20.5−6.7 (br). IR
(ATR; cm−1): 3058 (w), 2973 (m), 1700 (s), 1677 (s), 1590 (m),
1566 (m), 1444 (s), 1405 (s), 1381 (m), 1279 (m), 1231 (m), 1191
(s). Anal. Calcd for PdC46H42F6O3P2·C2H5OC2H5: C, 60.10; H,
5.24%; F, 11.41. Found: C, 60.03; H, 5.32; F, 11.69.
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1
product was obtained. H NMR (CDCl3 at 25 °C; δ): 7.59 (apparent
t, J = 7.5 Hz, 1H), 7.49 (t, J = 8.4 Hz, 1H), 7.43 (t, J = 7.5 Hz, 1H),
7.39 (t, J = 7.3 Hz, 1H), 6.76 (dd, J = 7.5 and 2.2 Hz, 1H), 6.48 (d, J =
8.5 Hz, 2H), 4.54 (septet, J = 6.0 Hz, 2H), 2.22−2.15 (multiple peaks,
4H), 1.85−1.76 (multiple peaks, 6H), 1.72−1.66 (br, 2H), 1.62−1.53
(br, 2H), 1.40−1.31 (br, 2H), 1.36 (d, J = 6.0 Hz, 6H), 1.25 (m, 2H),
1.22−1.12 (multiple peaks, 4H), 1.00 (d, J = 6.0 Hz, 6H). 13C{1H}
1.69 (br, 2H), 1.61 (m, 2H), 1.38−1.22 (multiple peaks, 6H), 1.34 (d,
J = 5.8 Hz, 6H), 1.18 (m, 2H), 1.00 (d, J = 6.2 Hz, 6H). 13C{1H}
NMR (CDCl3 at 25 °C; δ): 163.45, 161.63 (t, J = 22.5 Hz), 144.78 (d,
J = 16.4 Hz), 139.14, 133.86 (d, J = 44.3 Hz), 131.90 (d, J = 11.6 Hz),
131.41 (d, J = 1.4 Hz), 131.30, 126.54 (d, J = 6.1 Hz), 121.53−115.68
(three overlapping multiplets CF2, CF3 and CF3), 106.69 (tqd, 1JC−F
=
2
3
263.0 Hz, JC−F = 37.5 Hz, JC−P = 6.8 Hz), 105.61, 103.01, 71.60,
36.14 (d, J = 26.6 Hz), 29.32, 28.92 (d, J = 3.4 Hz), 27.22−26.96 (two
overlapping d), 25.96, 21.73, 21.48. 19F NMR (CDCl3 at 25 °C; δ):
−76.10 (d, J = 34.8 Hz, 2F), −78.98 (s, 2F), −82.58 (s, 3F), −119.10
(s, 3F). 31P{1H} NMR (CDCl3 at 25 °C; δ): 49.11 (t, J = 33.9 Hz).
19F/13C HSQC NMR (CDCl3 at 25 °C; δF/δC): −76.10/118.35,
−78.98/118.46, −82.58/118.75, −119.10/106.64. 19F/13C HMBC
NMR (CDCl3 at 25 °C; δF/δC): −76.10/118.35 (1J correlation),
−76.10/118.46, −78.98/118.35, −78.98/118.46 (1J correlation),
−82.58/106.64, −82.58/118.75 (1J correlation), −119.10/106.64 (1J
correlation), −119.10/118.75, −119.10/161.61. IR (ATR; cm−1):
2987 (w), 2938 (m), 2922 (m), 2859 (m), 1692 (s), 1588 (s), 1570
(m), 1447 (s), 1386 (s), 1333 (s), 1287 (m), 1255 (s), 1206 (s), 1161
(s), 1108 (s), 1061 (s), 1026 (s). HRMS electrospray (m/z): [M −
OCOC2F5]+ calcd for C32H43F5O2PPd 691.1950, found 691.1962.
Preparation of [(RuPhos)2Pd2](CF3COO)2 (8). A solution of
(RuPhos)Pd(COCF3)(OCOCF3) (1; 200 mg; 0.26 mmol) in benzene
(7 mL) was allowed to stand for 24 h at room temperature. During
this time the solution changed from yellow to deep red, and bright red
crystals slowly crystallized from solution. The benzene supernatant was
removed by decanting, and two 2 mL portions of benzene were used
to wash the crystals. After drying under vacuum, 78 mg (44%) of a
2
3
NMR (CDCl3 at 25 °C; δ): 207.98 (td, JC−F = 40.2 Hz, JC−P = 7.0
Hz), 161.37 (t, JC−F = 25.9 Hz), 161.04, 144.68 (d, J = 17.0 Hz),
137.38, 133.07 (d, J = 43.6 Hz), 131.78 (d, J = 11.6 Hz), 131.47 (d, J =
1.7 Hz), 130.94, 126.71 (d, J = 6.1 Hz), 121.44−114.17 (two
overlapping multiplets, 2 × CF2), 106.64 (m, CF3), 105.98, 105.29,
2
1
2
3
101.53 (tqd, JC−F = 269.8 Hz, JC−F = 36.1 Hz, JC−P = 14.3 Hz),
71.19, 34.28 (d, J = 29.3 Hz), 28.26 (two overlapping signals), 26.75
(two overlapping d), 25.85, 21.74, 21.67. 19F NMR (CDCl3 at 25 °C;
δ): −80.18 (s, 3F), −82.40 (s, 3F), −-112.23 (s, 2F), −118.44 (broad
s, 2F). 31P{1H} NMR (CDCl3 at 25 °C; δ): 42.25 (s). 19F/13C HSQC
NMR (CDCl3 at 25 °C; δF/δC): −80.18/117.33, −82.40/118.70,
−112.23/101.53, −118.44/106.64. 19F/13C HMBC NMR (CDCl3 at
25 °C; δF/δC): −80.18/101.53, −80.18/117.33 (1J correlation),
−112.23/101.53 (1J correlation), −112.23/117.33, −112.23/207.98.
IR (ATR): cm−1 2978 (w), 2987 (w), 2937 (m), 2855 (w), 1716 (s),
1684 (s), 1588 (m), 1569 (m), 1451 (s), 1384 (m), 1327 (s), 1256
(s), 1202 (s), 1162 (s), 1110 (s), 1069 (s). HRMS electrospray (m/z):
[M − OCOC2F5]+ calcd for C33H43F5O3PPd 719.1899, found
719.1916; [M − OCOC2F5 − CO]+ calcd for C32H43F5O2PPd
691.1950, found 691.1969.
Preparation of (RuPhos)Pd(CF3)(OCOCF3) (6). (RuPhos)Pd-
(COCF3)(OCOCF3) (1) (300 mg; 0.38 mmol) was refluxed in
benzene (25 mL) for 1.5 h. 19F and 31P NMR analysis of the crude
reaction mixture showed complete conversion to product 6. The
benzene solution was filtered through a pad of Celite, and the volatiles
were removed under reduced pressure. The residue was dissolved in
diisopropyl ether (5 mL). The product slowly crystallized over a
period of 12 h. Yellowish crystals were collected by filtration, washed
with a small amount of diisopropyl ether, and dried under vacuum. A
1
bright orange powder was obtained. H NMR (acetone-d6 at 25 °C;
δ): 8.61 (m, 1H), 8.12 (m, 1H), 7.80 (t, J = 7.3 Hz, 1H), 7.75 (t, J =
7.7 Hz, 1H), 7.41 (d, J = 7.7 Hz, 1H), 5.60 (d, J = 7.0 Hz, 2H), 4.39
(septet, J = 6.1 Hz), 3.26 (m, 2H), 2.19−2.09 (multiple peaks, 4H),
1.83 (m, 4H), 1.74 (m, 2H), 1.59 (m, 2H), 1.51 (m, 2H), 1.46−1.35
(multiple peaks, 4H), 1.23 (m, 2H), 0.95 (d, J = 6.1 Hz, 6H), 0.81 (d, J
= 6.0 Hz, 6H). 13C{1H} NMR (acetone-d6 at 25 °C; δ): 159.03 (q, J =
36.7 Hz), 151.39, 144.54 (virtual t, J = 27.2 Hz), 138.27 (virtual t, J =
42.2 Hz), 133.31, 132.90, 131.41 (virtual t, JC−P = 16.4 Hz), 129.37
(virtual t, JC−P = 6.2 Hz), 116.42 (q, J = 290.9 Hz), 94.08, 86.69, 80.45,
73.30, 36.18 (virtual t, J = 20.6 Hz), 29.83, 29.32, 26.17−26.00 (two
overlapping t), 25.74, 20.58, 19.95. 19F NMR (acetone-d6 at 25 °C; δ):
−76.38 (s). 31P{1H} NMR (acetone-d6 at 25 °C; δ): 61.46 (s).
19F/13C HSQC NMR (acetone-d6 at 25 °C; δF/δC): −76.38/116.45.
19F/13C HMBC NMR (acetone-d6 at 25 °C; δF/δC): −76.38/116.45
(1J correlation), −76.38/159.03. HRMS electrospray (m/z): [M −
OCOCF3]+ calcd for C62H86F3O6P2Pd 1257.3905, found 1257.3921,
[M − 2OCOCF3]2+ calcd for C30H43O2PPd 572.2030, found
572.2049.
1
227 mg amount (78%) of product was obtained. H NMR (CDCl3 at
25 °C; δ): 7.63 (apparent triplet, J = 7.3 Hz, 1H), 7.54 (t, J = 8.5 Hz),
7.43 (t, J = 7.3 Hz), 7.38 (t, J = 7.3 Hz), 6.68 (broad d, J = 6.2 Hz),
6.50 (d, J = 8.5 Hz), 4.60 (septet, J = 6.2 Hz), 2.26 (m, 2H), 2.16 (br,
2H), 1.90 (br, 2H), 1.80 (multiple peaks, 4H), 1.68 (br, 2H), 1.58 (m,
2H), 1.41−1.11 (multiple peaks, 8H), 1.30 (d, J = 5.8 Hz, 6H), 0.99
(d, J = 6.2 Hz, 6H). 13C{1H} NMR (CDCl3 at 25 °C; δ): 163.49,
161.25 (q, J = 34.1 Hz), 144.85 (d, J = 16.3 Hz), 138.82, 134.17 (d, J =
44.3 Hz), 131.75 (d, J = 12.3 Hz), 131.54 (d, J = 1.5 Hz), 131.40,
126.58 (d, J = 6.1 Hz), 118.59 (qd, 1JC−F = 379.4 Hz, 3JC−P = 15.0 Hz),
116.39 (q, 1JC−F = 290.9 Hz), 105.73, 102.92, 71.60, 35.93 (d, J = 27.9
Hz), 29.28, 29.01, 27.00 (two overlapping d), 25.93, 21.96, 21.30. 19F
NMR (CDCl3 at 25 °C; δ): −10.38 (d, J = 29.8 Hz, 3F), −74.90 (s,
3F). 31P{1H} NMR (CDCl3 at 25 °C; δ): 51.35 (q, J = 29.7 Hz).
19F/13C HSQC NMR (CDCl3 at 25 °C; δF/δC): −10.38/118.59,
−74.90/116.39. 19F/13C HMBC NMR (CDCl3 at 25 °C; δF/δC):
−74.90/161.33. IR (ATR; cm−1): 2978 (w), 2931 (m), 2856 (m),
1698 (s), 1589 (m), 1445 (s), 1405 (m), 1378 (m), 1258 (s), 1193
(s), 1173 (s), 1130 (s), 1108 (s), 1068 (s). HRMS electrospray (m/z):
[M − OCOCF3]+ calcd for C31H43F3O2PPd 641.1982, found
641.1994.
Preparation of (RuPhos)Pd(C2F5)(OCOC2F5) (7). (RuPhos)Pd-
(COC2F5)(OCOC2F5) (5; 220 mg; 0.25 mmol) was refluxed in
benzene (50 mL) for 1.5 h. 19F and 31P NMR analysis of the crude
reaction mixture showed complete conversion to product 7. This
benzene solution was filtered through a pad of Celite, and the volatiles
were removed under reduced pressure. The residue was dissolved in
diethyl ether (5 mL). The product slowly crystallized over a period of
several hours. Yellowish crystals were collected by filtration, washed
with a small amount of ether, and dried under vacuum to afford 133
mg (62%) of product 7. 1H NMR (CDCl3 at 25 °C; δ): 7.63 (apparent
t, J = 7.3 Hz, 1H), 7.54 (t, J = 7.5 Hz), 7.42 (t, J = 7.7 Hz), 7.37 (t, J =
7.7 Hz), 6.69 (broad d, J = 7.3 Hz), 6.46 (d, J = 8.5 Hz), 4.55 (septet, J
= 6.2 Hz), 2.29 (m, 2H), 2.22 (br, 2H), 1.91 (br, 2H), 1.81 (br, 4H),
Preparation of (RuPhos)Pd(CF3)(Ph) (9). A Schlenk flask was
charged with a stirbar, diphenylzinc (200 mg; 0.91 mmol), and
(RuPhos)Pd(CF3)(OCOCF3) (6; 450 mg; 0.60 mmol). The flask was
sealed, evacuated under reduced pressure, and then refilled with
nitrogen. The flask was evacuated and refilled with nitrogen three
more times. Dry THF (20 mL) was added via cannula. The resulting
solution was stirred at room temperature for 20 min, and then water
(0.2 mL) was introduced. The reaction mixture was stirred at room
temperature for an additional 20 min. Then the THF solution was
dried over anhydrous Na2SO4 and filtered. The volatiles were removed
under reduced pressure. The resulting residue was dissolved in
diisopropyl ether, and the product was allowed to crystallize from
solution over a period of several hours. Colorless crystals were
collected by filtration, washed with a small amount of diisopropyl
ether, and dried under vacuum. A 180 mg amount (42%) of 9 was
obtained. 1H NMR (CDCl3 at 25 °C; δ): 7.53 (apparent t, J = 6.9 Hz,
1H), 7.42−7.32 (multiple peaks, 3H), 7.23 (d, J = 7.4 Hz, 2H), 7.18
(broad d, J = 4.7 Hz, 1H), 7.02 (d, J = 8.3 Hz, 1H), 6.88 (t, J = 7.4 Hz,
2H), 6.82 (t, J = 7.1 Hz, 1H), 4.52 (septet, J = 6.0 Hz, 2H), 1.88−1.78
(br, 2H), 1.76−1.44 (multiple peaks, 12H), 1.32−1.02 (multiple
peaks, 8H), 1.28 (d, J = 6.0 Hz, 6H), 0.99 (d, J = 6.0 Hz, 6H). 13C{1H}
NMR (CDCl3 at 25 °C; δ): 154.11, 145.09 (br), 141.31 (d, J = 13.6
Hz), 140.84 (m, CF3), 136.54 (d, J = 2.0 Hz), 134.73 (d, J = 6.8 Hz),
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130.73, 129.81, 128.60, 127.20 (d, J = 21.8 Hz), 126.56 (d, J = 4.1 Hz),
126.09, 123.34, 122.57, 110.93, 74.09, 31.82 (d, J = 19.8 Hz), 28.20,
27.28 (d, J = 13.0 Hz), 26.87 (d, J = 9.5 Hz), 26.67, 25.99, 22.30,
21.18. 19F NMR (CDCl3 at 25 °C; δ): −27.80 (d, J = 44.8 Hz).
31P{1H} NMR (CDCl3 at 25 °C; δ): 14.77 (q, J = 45.8 Hz). 19F/13C
HSQC NMR (CDCl3 at 25 °C; δF/δC): −27.80/140.84. 19F/13C
HMBC NMR (CDCl3 at 25 °C; δF/δC): −27.80/140.84 (1J
correlation), −27.80/145.09. IR (ATR; cm−1): 3051 (w), 2968 (w),
2928 (s), 2850 (m), 1598 (m), 1579 (w), 1566 (m), 1450 (s), 1374
(m), 1331 (w), 1270 (s), 1224 (m), 1088 (s), 1046 (s). HRMS
electrospray (m/z): [M − F]+ calcd for C37H48F2O2PPd 699.2389,
found 699.2383.
Preparation of Zn(o-C6H4CH3)2. 2-Iodotoluene (6.00 g; 27.5
mmol) and dry diethyl ether (120 mL) were introduced into a flame-
dried 250 mL Schlenk flask. This ether solution was cooled to −78 °C,
and a 2.5 M solution of nBuLi in hexanes (11.5 mL; 28 mmol) was
added dropwise. The resulting suspension was stirred at −78 °C for 30
min. Then a 1.9 M ZnCl2 solution in 2-methyltetrahydrofuran (7.2
mL; 13.7 mmol) was added slowly over a period of 10 min at −78 °C.
The reaction mixture was warmed to room temperature and stirred at
room temperature for 30 min. The volatiles were removed under
vacuum via the side arm of the Schlenk flask, and the residue was
washed with several portions of dry pentane. Dry toluene (25 mL) was
added to the residue, and the resulting suspension was cannula-
transferred to a septum-sealed centrifuge tube. The LiCl precipitate
was separated by centrifugation, and the remaining clear toluene
solution of Zn(o-C6H4CH3)2 was used directly in the step below. It
was assumed that concentration of the Zn(o-C6H4CH3)2 reagent in
toluene is 0.5 M.
(m), 1578 (m), 1453 (s), 1384 (m), 1373 (m), 1269 (m), 1225 (m),
1105 (m), 1084 (s), 1040 (s), 978 (s). HRMS electrospray (m/z): [M
− F]+ calcd for C38H50F2O2PPd 713.2551, found 713.2538.
Preparation of (RuPhos)Pd(C2F5)(Ph) (11). A Schlenk flask was
charged with a stirbar, diphenylzinc (180 mg; 0.82 mmol), and
(RuPhos)Pd(C2F5)(OCOC2F5) (7; 500 mg; 0.58 mmol). The flask
was sealed, evacuated under reduced pressure, and then refilled with
nitrogen. The flask was evacuated and refilled with nitrogen three
more times. Dry THF (20 mL) was added via cannula. The resulting
solution was stirred at room temperature for 20 min, and then water
(0.2 mL) was introduced. The reaction mixture was stirred at room
temperature for an additional 20 min, and then the THF solution was
dried over anhydrous Na2SO4 and filtered. The volatiles were removed
under reduced pressure. The resulting residue was dissolved in diethyl
ether, and the product slowly crystallized over the period of several
hours. Colorless crystals were collected by filtration, washed with a
small amount of diethyl ether, and dried under vacuum. A 413 mg
1
amount (92%) of 11 was obtained. H NMR (CDCl3 at 25 °C; δ):
7.52 (apparent t, J = 6.7 Hz, 1H), 7.41−7.36 (multiple peaks, 2H),
7.34 (t, J = 7.1 Hz, 1H), 7.18 (ddd, J = 7.5, 3.2, 1.2 Hz, 2H), 7.11 (d, J
= 7.5 Hz, 1H), 7.02 (d, J = 8.3 Hz, 1H), 6.81 (t, J = 6.7 Hz, 2H), 6.78
(t, J = 7.2 Hz, 1H), 4.50 (septet, J = 6.1 Hz, 2H), 1.81−1.73 (br, 2H),
1.73−1.67 (br, 2H), 1.63−1.56 (multiple peaks, 6H, Cy protons),
1.50−1.40 (br, 2H), 1.34−1.27 (br, 2H), 1.25 (d, J = 6.1 Hz, 6H),
1.18−1.09 (multiple peaks, 4H), 1.08−1.00 (multiple peaks, 4H), 0.98
(d, J = 6.0 Hz, 6H). 13C{1H} NMR (CDCl3 at 25 °C; δ): 153.98,
143.41 (broad), 141.34 (d, J = 14.3 Hz), 136.63 (d, J = 2.7 Hz), 134.69
(d, J = 7.5 Hz), 133.08 (m, CF2), 130.80, 129.40, 128.55, 127.37 (d, J
= 21.8 Hz), 126.49 (d, J = 4.8 Hz), 125.94, 123.69, 122.40, 122.26
(qtd, 1JC−F = 286.1 Hz, 2JC−F = 31.3 Hz, 3JC−P = 8.2 Hz), 111.10, 74.05,
32.02 (d, J = 19.1 Hz), 28.15, 27.30 (d, J = 12.3 Hz), 27.10 (d, J = 4.1
Hz), 26.92 (d, J = 9.5 Hz), 26.01, 22.28, 21.19. 19F NMR (CDCl3 at 25
°C; δ): −79.83 (s, 3F), −102.50 (broad doublet, J = 23.2 Hz, 2F).
31P{1H} NMR (CDCl3 at 25 °C; δ): 13.57 (broad triplet, J = 28.6 Hz).
19F/13C HSQC NMR (CDCl3 at 25 °C; δF/δC): −79.83/122.26,
−102.50/133.08. 19F/13C HMBC NMR (CDCl3 at 25 °C; δF/δC):
−79.83/122.26 (1J correlation), −79.83/133.08. IR (ATR; cm−1):
3057 (w), 2974 (w), 2929 (m), 2848 (w), 1596 (m), 1564 (m), 1452
(s), 1384 (m), 1292 (m), 1267 (m), 1231 (w), 1187 (m), 1138 (m),
1101 (m), 1039 (s). HRMS electrospray (m/z): [M − F]+ calcd for
C38H48F4O2PPd 749.2363, found 749.2345; [M − Ph]+ calcd for
C32H43F5O2PPd 691.1956, found 691.1938.
Preparation of (RuPhos)Pd(CF3)(o-C6H4CH3) (10). A Schlenk
flask was charged with a stirbar and (RuPhos)Pd(CF3)(OCOCF3) (6;
400 mg; 0.50 mmol). The flask was sealed, evacuated under reduced
pressure, and then refilled with nitrogen. The flask was evacuated and
refilled with nitrogen three more times. Dry THF (20 mL) was added
via cannula. The resulting solution was cooled to −78 °C, and then the
Zn(o-C6H4CH3)2 solution in toluene (1.2 mL; approximately 0.6
mmol) was added dropwise. The reaction mixture was stirred at room
temperature for 20 min, and then water (0.2 mL) was introduced. The
reaction mixture was stirred at room temperature for an additional 20
min, and then the THF solution was dried over anhydrous Na2SO4
and filtered. The volatiles were removed under reduced pressure. The
resulting residue was dissolved in acetone (1.5 mL), from which the
product slowly crystallized over a period of several hours. The crystals
were collected by filtration, washed with a small amount of acetone,
and dried under vacuum. A 230 mg amount (63%) of colorless crystals
was obtained. Analytical data for 10: rotation about Pd-(o-Tol) bond is
hindered on the NMR time scale at 25 °C. Therefore, several signals in
Preparation of (RuPhos)Pd(C2F5)(o-C6H4CH3) (12). A Schlenk
flask was charged with a stirbar and (RuPhos)Pd(C2F5)(OOCC2F5)
(7; 400 mg; 0.50 mmol). The flask was sealed, evacuated under
reduced pressure, and then refilled with nitrogen. The flask was
evacuated and refilled with nitrogen three more times. Dry THF (20
mL) was added via cannula. The resulting solution was cooled to −78
°C, and then a Zn(o-C6H4CH3)2 solution in toluene (1.2 mL;
approximately 0.6 mmol) was added dropwise. The reaction mixture
was stirred at room temperature for 20 min, and then water (0.2 mL)
was introduced. The reaction mixture was stirred at room temperature
for an additional 20 min, and then the THF solution was dried over
anhydrous Na2SO4 and filtered. The volatiles were removed under
reduced pressure. The resulting residue was dissolved in methanol (1.5
mL), and the product slowly crystallized over a period of several hours.
The crystals were collected by filtration, washed with a small amount
of methanol, and dried under vacuum. A 214 mg amount (55%) of 12
1
1
the H and 13C NMR spectra are broadened at 25 °C. VT H NMR
experiments revealed that at −40 °C rotation about Pd-(o-Tol) is slow
1
on the H NMR time scale (the RuPhos fragment loses the plane of
symmetry in the 1H NMR spectrum). 1H NMR (CDCl3 at 25 °C; δ):
7.50 (apparent t, J = 6.6 Hz, 1H), 7.39−7.33 (multiple peaks, 3H),
7.17 (d, J = 7.5 Hz, 1H), 7.14 (br, 1H), 7.00 (br, 2H), 6.81 (dd, J =
8.3, 1.0 Hz, 1H), 6.77 (t, J = 7.0 Hz, 1H), 6.71 (t, J = 7.7 Hz, 1H),
4.59−4.50 (two overlapping septets, 2H), 2.47 (s, 3H), 1.99−0.63
(overlapping broad resonances, 22H), 1.31 (d, J = 6.0 Hz, 3H), 1.27
(broad d, J = 5.5 Hz, 3H), 1.01 (broad d, J = 4.6 Hz, 3H), 0.97 (d, J =
6.1 Hz, 3H). 13C{1H} NMR (CDCl3 at 25 °C; δ): 154.40, 154.33,
146.47 (br), 141.65 (d, J = 12.9 Hz), 141.35, 140.35 (m, CF3), 135.84,
134.58 (br), 130.91 (br), 129.93 (br), 128.61 (br), 127.88 (br d, J =
19.1 Hz), 127.42, 126.48 (d, J = 4.1 Hz), 123.14 (br), 122.92 (br),
122.58, 110.83, 110.72, 73.98 (br), 73.74 (br), 32.55 (two overlapping
broad resonances, Cy signals), 28.61−25.59 (overlapping broad
resonances, Cy signals), 27.47, 27.40, 26.19, 22.34, 22.27, 21.24
(two overlapping broad resonances). 19F NMR (CDCl3 at 25 °C; δ):
−27.74 (d, J = 46.0 Hz). 31P{1H} NMR (CDCl3 at 25 °C; δ): 13.79
(q, J = 45.8 Hz). 19F/13C HSQC NMR (CDCl3 at 25 °C; δF/δC):
−27.74/140.19. 19F/13C HMBC NMR (CDCl3 at 25 °C; δF/δC):
−27.74/140.19 (1J correlation), −27.74/146.47. IR (ATR; cm−1):
3064 (w), 2918 (s), 2850 (m), 2361 (w), 2338 (w), 2162 (w), 1599
1
was obtained. Analytical data for 12: H, 19F, and 13C NMR spectra
show that rotation about the Pd−(o-Tol) bond is slow on the NMR
time scale at 25 °C. According to 1H and 13C NMR spectra, the
RuPhos fragment does not possess a plane of symmetry. Moreover,
according to the 19F NMR spectrum, the fluorine atoms of the CF2
group are diastereotopic. 1H NMR (CDCl3 at 25 °C; δ): 7.52
(apparent t, J = 6.5 Hz, 1H), 7.40−7.34 (multiple peaks, 2H), 7.32 (t, J
= 7.3 Hz, 1H), 7.19 (m, 2H), 7.12 (m, 1H), 6.85 (d, J = 8.3 Hz, 1H),
6.70 (m, 2H), 6.65 (m, 1H), 4.56−4.48 (two overlapping septets, 2H),
2.23 (m, 1H), 2.12 (s, 3H), 1.93−0.83 (many overlapping multiplets,
19H), 1.21 (two overlapping d, 6H), 1.12 (d, J = 6.0 Hz, 3H), 0.78 (d,
J = 6.0 Hz, 3H), 0.63 (m, 1H), 0.46 (m, 1H). 13C{1H} NMR (CDCl3
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at 25 °C; δ): 155.45, 153.24, 144.63 (br), 141.31 (d, J = 15.0 Hz),
140.98, 136.94, 134.73 (d, J = 8.2 Hz), 133.23 (m, CF2), 131.06,
129.63, 128.58 (d, J = 2.0 Hz), 127.76 (br d, J = 22.9 Hz), 127.54,
126.38 (d, J = 4.1 Hz), 123.56 (broad multiplet), 122.74, 122.50,
122.45 (m, CF3), 112.35, 109.54, 76.73, 71.03, 34.32 (d, J = 19.1 Hz),
32.07 (d, J = 18.4 Hz), 29.83, 29.80, 27.62 (d, J = 12.3 Hz), 27.13 (d, J
= 10.3 Hz), 26.97 (d, J = 2.3 Hz), 26.92 (d, J = 8.8 Hz), 26.71 (d, J =
12.9 Hz), 26.41, 26.35 (d, J = 3.4 Hz), 25.98, 25.87, 22.45, 21.95,
21.64, 20.91. 19F NMR (CD2Cl2 at 25 °C; δ): −79.87 (s, 3F), −101.19
S.; Wang, H.; Vicic, D. A. Organometallics 2013, 32, 7552−7558.
(h) McReynolds, K. A.; Lewis, R. S.; Ackerman, L. K. G.; Dubinina, G.
G.; Brennessel, W. W.; Vicic, D. A. J. Fluorine Chem. 2010, 131, 1108−
1112. (i) Dubinina, G. G.; Brennessel, W. W.; Miller, J. L.; Vicic, D. A.
Organometallics 2008, 27, 3933−39385. (j) Zanardi, A.; Novikov, M.
A.; Martin, E.; Benet-Buchholz, J.; Grushin, V. V. J. Am. Chem. Soc.
2011, 133, 20901−20913. (k) Mormino, M. G.; Fier, P. S.; Hartwig, J.
F. Org. Lett. 2014, 16, 1744−1747. (l) Lishchynskyi, A.; Novikov, M.
A.; Martin, E.; Escudero-Adan
Chem. 2013, 78, 11126−11146. (m) Lishshynskyi, A.; Grushin, V. V. J.
Am. Chem. Soc. 2013, 135, 12584−12587. (n) Novak, P.; Lishshynskyi,
́ ́
, E. C.; Novak, P.; Grushin, V. V. J. Org.
2
3
2
(dd, JF−F = 31.5 Hz, JF−P = 275.3 Hz, 1F), −102.44 (dd, JF−F
=
275.3 Hz, 3J(F−P) = 23.2 Hz, 1F). 31P{1H} NMR (CD2Cl2 at 25 °C; δ):
11.31 (broad multiplet). 19F/13C HSQC NMR (CDCl3 at 25 °C; δF/
δC): −79.87/122.45. 19F/13C HMBC NMR (CDCl3 at 25 °C; δF/δC):
−79.87/122.45 (1J correlation), −79.83/133.23. IR (ATR; cm−1):
3048 (w), 2976 (w), 2927 (m), 2850 (m), 1596 (m), 1577 (m), 1449
(s), 1384 (m), 1373 (m), 1292 (m), 1266 (m), 1228 (m), 1185 (s),
1148 (s), 1101 (s), 1037 (s). HRMS electrospray (m/z): [M − F]+
calcd for C39H50F4O2PPd 763.2519, found 763.2507; [M −
C6H4CH3]+ calcd for C32H43F5O2PPd 691.1956, found 691.1929.
Reductive Elimination Studies: Representative Procedure. A
J. Young NMR tube was charged with (RuPhos)Pd(CF3)(o-
C6H4CH3) (10; 25 mg; 0.034 mmol), C6D6 (0.5 mL) and 1,4-
bis(trifluoromethyl)benzene (approximately 2 mg; 0.01 mmol). The
NMR tube was degassed through three freeze−pump−thaw cycles. A
19F NMR spectrum was acquired to quantify the initial ratio of of 10
and the 1,4-bis(trifluoromethyl)benzene internal standard. The NMR
tube was then heated in the oil bath for 12 h (oil bath kept at 90 °C).
19F NMR spectroscopy was used to determine the yield of α,α,α-
trifluoroxylene, on the basis of the initially determined relative amount
of 1,4-bis(trifluoromethyl)benzene internal standard. The formation of
reductive elimination product was confirmed also by GC-MS.
́
A.; Grushin, V. V. J. Am. Chem. Soc. 2012, 134, 16167−16170.
(4) For Pd0-catalyzed perfluoroalkylation reactions that likely
proceed via radical mechanisms rather than R−CF3 reductive
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Organometallics 2012, 31, 1467−1476.
(7) For an investigation of C−CF3 bond-forming reductive
elimination at NiII, see: Dubinina, G. G.; Brennessel, W. W.; Miller,
J. L.; Vicic, D. A. Organometallics 2008, 27, 3933−3938.
ASSOCIATED CONTENT
* Supporting Information
Figures and tables giving experimental details and spectroscopic
data for new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
■
S
(8) For studies of Ni−CF3 complexes, see (a) Yamaguchi, Y.;
Ichioka, H.; Klein, A.; Brennessel, W. W.; Vicic, D. A. Organometallics
2012, 31, 1477−1483. (b) Kieltsch, I.; Dubinina, G. G.; Hamacher, C.;
Kaiser, A.; Torres-Nieto, J.; Hutchison, J. M.; Klein, A.; Budnikova, Y.;
Vicic, D. A. Organometallics 2010, 29, 1451−1456. (c) Zhang, C.-P.;
Wang, H.; Klein, A.; Biewer, C.; Stirnat, K.; Yamaguchi, Y.; Xu, L.;
Gomez-Benitez, V.; Vicic, D. A. J. Am. Chem. Soc. 2013, 135, 8141−
8144. (d) Klein, A.; Vicic, D. A.; Biewer, C.; Kieltsch, I.; Stirnat, K.;
Hamacher, C. Organometallics 2012, 31, 5334−5341. (e) Madhira, V.
N.; Ren, P.; Vechorkin, O.; Hu, X.; Vicic, D. A. Dalton Trans. 2012, 41,
7915−7919.
AUTHOR INFORMATION
Corresponding Author
*E-mail for M.S.S.: mssanfor@umich.edu.
Notes
■
The authors declare no competing financial interest.
(9) For investigations of C−CF3 bond-forming reductive elimination
at PdII, see: (a) Culkin, D. A.; Hartwig, J. F. Organometallics 2004, 23,
3398. (b) Grushin, V. V.; Marshall, W. J. J. Am. Chem. Soc. 2006, 128,
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(10) For X-ray and NMR studies of Pd−CF3 complexes, see:
(a) Hughes, R. P.; Meyer, M. A.; Tawa, M. D.; Ward, A. J.; Williamson,
A.; Rheingold, A. L.; Zakharov, L. N. Inorg. Chem. 2004, 43, 747−756.
(b) Hughes, R. P.; Overby, J. S.; Williamson, A.; Lam, K.-C.;
Concolino, T. E.; Rheingold, A. L. Organometallics 2000, 19, 5190−
5201.
ACKNOWLEDGMENTS
■
We thank the NSF (CHE-1111563) for support of this
research. A.M. is a Howard Hughes Medical Institute
International Student Research Fellow.
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