Thermomorphic fluorous imine and thioether palladacycles as precursors for highly active Heck and Suzuki catalysts; evidence for palladium nanoparticle pathways

Article abstract of DOI:10.1039/b208545n

p-Iodobenzaldehyde is elaborated to the fluorous alcohol p-R_f8(CH₂)₃C₆H₄CH(OH) (CH₂)₂R_f8 (three steps/80%; R_f8 = n-C₈F₁₇), which is converted to imine p-R_f8(CH₂)₃C₆H₄C(= N(CH₂)₃R_f8)(CH₂)₂R _f8 (6, two steps/93%) and thioether p-R_f8(CH₂)₃C₆H₄CH(S (CH₂)₃R_f8)(CH₂)₂R _f8 (12, 64%). Reactions with Pd(OAc)₂ (AcOH, 95°C) give palladacycles with [RC₆H₃CR′=N(R)Pd(μ-OAc)]₂ (7, 87%) and [RC₆H₃CHR′S(R)Pd(μ-OAc)]₂ (13, 84%) cores. The former reacts with LiCl and LiI to give the corresponding bridging halide complexes (8, 9); LiCl/PPh₃ affords monomeric RC₆H₃CR′=N(R)Pd(Cl)(PPh₃) (10). Palladacycles 7-9 and 13 are poorly soluble or insoluble in many solvents at 20-24°C, but much more soluble at higher temperatures. The CF₃C₆F₁₁/toluene partition coeffcients of 6, 7, 12, and 13 are > 91: < 9 (24°C). Both 7 and 13 are excellent catalyst precursors for Heck reactions of aryl halides. Turnover numbers exceed 10⁶ with phenyl iodide under homogeneous conditions in DMF at 140°C. The palladacycles precipitate as bridging halides upon cooling, and can in theory be recovered by liquid/solid phase separations. However, since the quantities are small, the solvent C₈F₁₇Br is added for recycling. Induction periods in both the first and second cycles, and progressively lower activities, are noted. Transmission electron microscopy indicates the formation of soluble palladium nanoparticles. Together with other data, it is proposed that the nanoparticles are the active catalysts, for which the recyclable palladacycles constitute a steady state source, until exhausted. Complex 7 similarly catalyzes the Suzuki reaction (K₃PO₄, toluene, 130°C).

Full text of DOI:10.1039/b208545n

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Thermomorphic fluorous imine and thioether palladacycles as
precursors for highly active Heck and Suzuki catalysts;
evidence for palladium nanoparticle pathways
Christian Rocaboy and J. A. Gladysz*
Institut f u¨ r Organische Chemie, Friedrich-Alexander-Universit a¨ t Erlangen-N u¨ rnberg,
Henkestrasse 42, 91054, Erlangen, Germany. E-mail: gladysz@organik.uni-erlangen.de
Received (in Montpellier, France) 28th August 2002, Accepted 14th October 2002
First published as an Advance Article on the web 28th November 2002
p-Iodobenzaldehyde is elaborated to the fluorous alcohol p-R (CH ) C H CH(OH)(CH ) R
2 2 f8
f8
2 3
6
4
(
(
three steps/80%; Rf8 ¼ n-C
8
F
17), which is converted to imine p-Rf8(CH
2
)
3
C
R
6
H
4
C(=N(CH
f8 (12, 64%). Reactions with
2 3 2 2 f8
) Rf8)(CH ) R
6, two steps/93%) and thioether p-Rf8(CH
2
)
3
C
6
H
4
CH(S(CH
2
0
)
3
R
f8)(CH
2
)
2
ꢀ
Pd(OAc) (AcOH, 95 C) give palladacycles with [RC H CR =N(R)Pd(m-OAc)] (7, 87%) and
2
6
3
2
0
[RC
bridging halide complexes (8, 9); LiCl/PPh
6
H
3
CHR S(R)Pd(m-OAc)]
2
(13, 84%) cores. The former reacts with LiCl and LiI to give the corresponding
0
affords monomeric RC
Palladacycles 7–9 and 13 are poorly soluble or insoluble in many solvents at 20–24 C, but much more soluble
H
6 3
CR =N(R)Pd(Cl)(PPh
3
) (10).
3
ꢀ
ꢀ
at higher temperatures. The CF 11/toluene partition coefficients of 6, 7, 12, and 13 are > 91: < 9 (24 C).
6
Both 7 and 13 are excellent catalyst precursors for Heck reactions of aryl halides. Turnover numbers exceed 10
with phenyl iodide under homogeneous conditions in DMF at 140 C. The palladacycles precipitate as bridging
halides upon cooling, and can in theory be recovered by liquid/solid phase separations. However, since the
3
C
6
F
ꢀ
8
quantities are small, the solvent C F17Br is added for recycling. Induction periods in both the first and second
cycles, and progressively lower activities, are noted. Transmission electron microscopy indicates the formation
of soluble palladium nanoparticles. Together with other data, it is proposed that the nanoparticles are the active
catalysts, for which the recyclable palladacycles constitute a steady state source, until exhausted. Complex 7
ꢀ
similarly catalyzes the Suzuki reaction (K
3
PO
4
, toluene, 130 C).
2 m 2 nꢁ1
are derivatized with ‘‘pony tails’’ or (CH ) (CF ) -
CF ((CH ) R ) segments that provide high fluorous solvent
Introduction
3
2 m fn
Fluorous biphase catalysis is now a well established technique
for catalyst/product separation and recycling that exploits
the temperature-dependent miscibility of organic and fluorous
affinities. Reactions can be conducted under homogeneous
conditions at the one-phase, high temperature limit. Products
normally have much greater affinities for the non-fluorous
solvent, and are easily separated at the two-liquid-phase, low
temperature limit. A newer-generation protocol is shown in
1
–3
phases. Fig. 1A shows the most common protocol. Catalysts
4
,5
Fig. 1B.
This dispenses with the fluorous solvent, and
instead exploits the temperature-dependent solubility of the
fluorous catalyst in the organic solvent. Such ‘‘thermo-
6
morphic’’ behavior allows homogeneous reaction conditions
at higher temperatures, with catalyst recovery via liquid/solid
phase separation at lower temperatures.
Many fluorous transition-metal catalysts are now known.
They have given impressive results in metal-catalyzed hydro-
formylations, hydrogenations, hydroborations, hydrosilyla-
7
8
9
1
0
11
tions, oxidations, carbon–carbon bond forming reactions
additions of Et Zn to carbonyl com-
2
1
2–14
of aryl halides,
1
5
16
pounds, and other processes. Surprisingly, there have
been no attempts to develop fluorous versions of palladacycle
catalysts, some examples of which are given in Fig. 2.
1
7
18–21
2
2
These are particularly effective for sp –sp carbon coupling
2
2
23
processes such as the Heck and Suzuki reactions. One
contributing factor may be that most palladacycles contain
multiple aromatic rings, which typically require three Rf8
‘‘pony tails’’ for effective immobilization in fluorous sol-
vents.
2
,8b,24
However, since Heck reactions normally require
elevated temperatures, we thought it might be feasible to
employ the newer protocol in Fig. 1B, which reduces the
dependence upon a high fluorous/organic solvent partition
coefficient.
Fig. 1 Traditional (A) and fluorous-solvent-free (B) fluorous biphase
catalysis.
DOI: 10.1039/b208545n
New J. Chem., 2003, 27, 39–49
39
This journal is # The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2003

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from commercial p-iodobenzaldehyde (1). We have previously
shown that aromatic aldehydes undergo high-yield Wittig reac-
tions with the ylide derived from the readily available phos-
+
ꢁ 24,26
phonium salt
procedure with 1 gave the alkene 2 in 96% yield after workup
90:10 Z/E mixture). All new compounds gave satisfactory
R
f8CH
2
CH
2
PPh
3
I .
An analogous
(
1
13
microanalyses, and were characterized by H and C NMR,
and often additional means, as summarized in the experimen-
tal section.
To our initial surprise, we were unable to hydrogenate the
alkene moiety in 2 or closely related compounds such as the
analogous bromide without simultaneous partial hydrogenoly-
3 3
sis of the aryl halide (Pd/C, (Ph P) RhCl catalysts). The
resulting arene was also very difficult to separate from the tar-
get aryl iodide. Accordingly, i-PrMgCl was used to effect
2
7
iodine/magnesium exchange, and subsequent addition of
2
8
the readily available fluorous aldehyde R CH CH CHO
f8
2
2
gave the benzylic alcohol 3 in 93% yield after workup. The
alkene moiety of this two-pony-tail system could be hydro-
genated (7 mol% (Ph P) RhCl) without competing carbon–
3 3
oxygen bond hydrogenolysis, affording 4 in 90% yield.
29
Oxidation of 4 with the Dess–Martin periodinane gave the
Fig. 2 Representative palladacycle catalyst precursors for the Heck
reaction.
aryl ketone 5 in 95% yield. Subsequent condensation with
2
8
the readily available fluorous amine H
the presence of SnCl (H O) (20 mol%) simultaneously intro-
2 2 2 2
NCH CH CH Rf8 in
2
2
2
Our attention was drawn to two types of cyclopalladated
complexes. The first was an imine-based system reported by
duced the third pony tail and generated the imine 6, which
was isolated in 98% yield (35:65 Z/E mixture). Although the
synthesis of 6 required five steps, product purifications—often
the most important consideration in fluorous syntheses—were
1
Milstein (B, Fig. 2), with just one arene per palladium. The
9
second was a similar thioether-derived family described by
2
0
Dupont (C, Fig. 2). Both have been applied to the Heck reac-
tion, and the latter to the Suzuki coupling. We independently
became interested in palladium complexes of simple fluorous
3 6
easy and the overall yield was good. The CF C F11/toluene par-
tition coefficients of 5 and 6 were measured by GC as described
in the experimental section. As summarized in Table 1, the fluor-
ous phase affinity of 6 was very high (98.7:1.3), but that of 5
was—as expected from the number of pony tails—lower.
thioethers (Rf8(CH
2
)
n
)
precursors for Suzuki coupling reactions.
2
S (n ¼ 2, 3), which are also catalyst
1
3d
Hence, we set
out to synthesize fluorous analogs of B and C, evaluate their
efficacies as catalyst precursors, and attempt their recovery
and reuse. A portion of this work has previously been commu-
As shown in Scheme 2, 6 underwent cyclopalladation under
ꢀ
standard conditions (Pd(OAc)
the yellow dimeric N-donor palladacycle 7 in 87% yield. A
2
, AcOH, 95 C). Workup gave
2
5
nicated.
ꢀ
crystallized sample melted at 78–80 C and was thermally
ꢀ
30
stable to 225 C, as assayed by DSC and TGA measure-
Results
3 6 5
ments. When DMF or CF C H solutions of 7 were kept
ꢀ
ꢀ
at 140 C (2 h) or 100 C (16 h), no decomposition was detected
visually or by NMR. Reactions of 7 with LiCl or LiI gave the
corresponding dimeric palladacycle halides 8 and 9 in 85–86%
yields. We thought that monomeric species might be better sui-
ted for X-ray crystallography. Accordingly, reactions of (1) the
1
. Synthesis and characterization of catalyst precursors
We first sought a fluorous imine containing at least three pony
tails. As shown in Scheme 1, a synthesis was developed starting
palladacycle chloride 8 with PPh
acetate 7 with LiCl/PPh , gave the phosphine complex 10 in
9–81% yields. However, all crystals diffracted poorly. The
thermal stabilities of 8–10 were similar to that of 7.
The N-donor palladacycles 7–10 showed IR nC N
lower frequencies than the imine 6 (1583–1587 vs. 1657
3
, and (2) the palladacycle
3
7
=
bands at
ꢁ
1
ꢁ1
=
O
values (1571, 1424 cm ) close
cm ). Complex 7 gave IR nC
to those of other palladacycle bridging acetates.
2
0c,31
1
The H
1
3
and C NMR spectra clearly indicated a trisubstituted arene
ring. Palladacycle bridging acetates exhibit structures that
1
8b,20c
are sharply folded about each O C–CH axis.
This ren-
ders the protons of each methylene group in 7 diastereotopic,
2
3
1
and exchange is slow on the H NMR time scale. Interestingly,
ꢀ
Table 1 Partition coefficients (24 C)
Analyte
CF
3
C
6
F11:toluene
8
C F17Br:DMF
a
Ketone 5
a
84.6:15.4
98.7:1.3
95.5:4.5
99.5:0.5
90.7:9.3
—
—
Imine 6
Imine palladacycle 7
a
95.9:4.1
—
91.4:8.6
Scheme 1 Synthesis of fluorous imine 6. Conditions: (a)
b
+
ꢁ
ꢀ
Thioether 12
Thioether palladacycle 13
R
f8CH
2
CH
2
PPh
3
I , K
CH CHO; (d) (Ph
2
CO
3
, p-dioxane/H
2
O, 95 C; (b) i-PrMgCl,
(75 psi), EtOH/
(f)
b
THF; (c) Rf8CH
2
2
3
P) RhCl, H
3
2
ꢀ
CF
NH
3
C
6
H
5
,
40 C; (e) Dess–Martin periodinane, CF
CH CH CH Rf8 , SnCl (H O) , toluene, reflux, Dean Stark.
2 2 2 2 2 2
3
C
6
H
5
;
a
b
Measured by GC. Measured by HPLC.
2
4
0
New J. Chem., 2003, 27, 39–49

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Scheme 3 Synthesis of a fluorous S-donor palladacycle. Conditions:
ꢀ
(
AcOH, 95 C.
a) Rf8CH
2
CH
2
CH SH (11), ZnI
2
2
, CF
3
C
6
H
5
, 60 C; (b) Pd(OAc)
2
,
ꢀ
NMR spectra were much more complex than those of 7. Ana-
logs of C with n-alkyl sulfur substituents also exist as mixtures
2
0c
of diastereomers. The palladacycle 13 exhibited solubilities
similar to those of 7. However, the partition coefficient was
slightly lower (Table 1), and only a single HPLC peak was
observed.
Scheme 2 Synthesis of fluorous N-donor palladacycles. Conditions:
ꢀ
(
a) Pd(OAc)
c) PPh , CH
2
, AcOH, 95 C; (b) LiX (X ¼ Cl, I), CF
3 6 5
C H /MeOH;
(
3
2
Cl
2
; (d) LiCl, PPh
3
, THF.
2. Catalysis
We first sought to demonstrate that the fluorous N-donor and
S-donor palladacycle acetates 7 and 13 were viable catalyst
precursors for Heck couplings of aryl halides. Note that halide
ions are generated under the reaction conditions—for example
1
the chemical shifts of the =NCH2 H NMR signals of the pal-
ladacycle halides 8 and 9 vary significantly from those of 7 (7,
2
+
ꢁ
.98–3.05 (m, 1H), 3.22–3.29 (m, 1H); 8, 3.84–3.91 (m, 2H); 9,
.15–4.18 (m, 2H).
At room temperature, 7 was soluble in fluorinated solvents
in the form of the ammonium salts Et NH X when Et N is
3 3
4
used as the base. Thus, given the rapid reactions with LiCl
and LiI in Scheme 2, both 7 and 13 should be converted to
bridging halide complexes after the first turnover (even, fore-
shadowing a point below, if catalysis is effected by an entirely
different species). In this context, it is often overlooked that the
properties of the catalyst rest state, not the catalyst precursor,
such as CF
soluble in common organic solvents such as CH
3
C
6
F11 , C
8
F17Br, CF
3
C
6
F
5
, and CF
3
C
6
H
5
, poorly
, CHCl ,
2
Cl
2
3
acetone, and THF, and insoluble in DMF. Complexes 8 and 9
were completely insoluble in organic solvents, and poorly solu-
3
5
ble in the preceding fluorinated solvents. However, solubilities
ꢀ
are of greatest relevance to recycling.
Hence, a solution of an aryl halide in freshly distilled DMF
was sequentially treated with an alkene, Et N, and a standard
solution of 7 or 13 in CF , as summarized in Table 2. In
order to maximize turnover numbers (TON), the catalyst load-
in CF
3
C
6
F
5
were much higher above 50 C, allowing NMR
spectra to be recorded. Complex 10 was much more soluble
than 7 in CH Cl , CHCl , acetone, and THF, and was very
soluble in CF 11 , CF , and CF as well. The
CF 11/toluene partition coefficient of 7 could be deter-
mined by HPLC, but 8 and 9 were too insoluble. As shown
in Table 1, the value was slightly lower than that of imine 6,
and was little changed in C F Br/DMF, a biphase system
employed below.
We next turned our attention to fluorous thioethers that
could serve as precursors to palladacycles similar to C (Fig.
3
2
2
3
3 6 5
C H
3
C
6
F
3
C
6
F
5
3 6 5
C H
ꢁ
4
3
C
6
F
ings were kept low (0.66–1.83 ꢂ 10 mol%). The apparently
ꢀ
homogeneous samples were reacted at 140 C, and then cooled.
GC analyses showed the expected coupling products in 49–
100% yields, corresponding to TON values of 266 000 to
1 510 000. In accord with most other studies involving dimeric
palladacycles, these are based upon the molecular structure
(two palladium atoms). The values place 7 and 13 among the
8
17
2
1
2
the presence of Lewis acids. Accordingly, the known fluorous
). Thiols are known to condense with benzylic alcohols in
best high-turnover Heck catalyst precursors. For the less
reactive aryl bromide (entries 5 and 6), GC monitoring showed
that the lower conversions are due to catalyst deactivation.
Similar reactions were conducted in which 7 was introduced
as a solid, and at much higher loadings (0.5 mol%). The initi-
ally insoluble 7 dissolved as the DMF was warmed. Upon
cooling, palladium complexes precipitated. In reactions of phe-
nyl iodide, NMR analyses showed palladacycle iodide 9 to be
the dominant species ( > 95%). The reaction products and all
other materials remained soluble. These observations raised
the possibility of catalyst recovery by a simple liquid/solid
phase separation of the type in Fig. 1B. However, the catalyst
quantities involved were impracticably small—a problem that
would be ameliorated on industrial process-chemistry scales.
3
2
3
thiol R CH CH CH SH was synthesized by a ‘‘new’’ route
3
f8
2
2
2
3
4
(
previously applied to other fluorous thiols)
involving
1
1a
thiourea and the fluorous iodide R CH CH CH I.
As
shown in Scheme 3, reaction with the fluorous benzylic alcohol
gave the triply pony-tailed fluorous thioether 12 in 64% yield.
f8
2
2
2
4
Cyclopalladation under conditions analogous to those in
Scheme 2 afforded the dimeric S-donor palladacycle 13 in
4% yield.
Unlike the imine 6, thioether 12 is chiral. Accordingly, the
dimeric palladacycle 13 contains two carbon stereocenters—
as well as two sulfur stereocenters not present in the free
ligand. Mixtures of diastereomers are therefore possible, and
8
New J. Chem., 2003, 27, 39–49
41

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Table 2 Heck reactions under high turnover conditions
1
2
c
Conv. (%)
c
Yield (%)
Entry
X
I
R
R
Catalyst, mmol
t/h
TON
d
1
2
3
4
5
6
H
CO CH
2
3
7, 0.00000344
13, 0.0000415
7, 0.00000344
13, 0.0000415
7, 0.00000917
13, 0.0000831
14
18
24
48
48
48
100
100
94
100
100
1 460 000
1 510 000
1 270 000
1 510 000
266 000
d
e
I
H
C
6
H
5
88
e
100
77
100
d
Br
CH
3
CO
CO CH
2
3
49
50
d
66
301 000
a
b
N (ca. 2 equiv), DMF (6.00 mL). Conditions for 13: ArX (ca. 5.000–6.279
Conditions for 7: ArX (ca. 5.000 mmol), alkene (ca. 1.25 equiv), Et
c
3
d
e
3
mmol), alkene (ca. 2 equiv), NEt (ca. 2 equiv), DMF (8.00 mL). Determined by GC. trans only. trans:cis 87:13.
Accordingly, the reactions shown in Table 3 were conducted
with 0.02 mol% of 7, and with periodical monitoring by GC.
Since the catalyst loading was higher than in Table 2, a lower
These observations are consistent with several scenarios.
One would be that the active catalyst is efficiently recycled,
but is of limited stability, resulting in progressively slower
rates. Another would be that catalyst recycling is not as effi-
cient as anticipated—due, for example, to retention in the
DMF phase. Another would be that the active catalysts are
non-recyclable decomposition products of 7 or 13. The remain-
ing palladacycle would then be recycled (as the bridging
halide), with the diminishing activity representing progres-
sively smaller quantities available for catalyst generation.
In the latter context, many metallic palladium catalysts for
ꢀ
temperature (100 C) could be used. After cooling, C F Br
8
17
was added as a ‘‘catalyst carrier’’, giving a liquid/liquid bipha-
sic sample. This fluorous solvent best dissolves the palladacycle
iodide 9. Pictures of a reaction sequence are given in Fig. 3,
using 0.5 mol% of 7 for better visualization. The upper
DMF phase was separated, and the C
with DMF. The combined DMF phases were analyzed to give
the data in Table 3. The C 17Br was removed under vacuum,
8
F17Br phase washed
8
F
2
2,36–41
and the residue charged with fresh educts and DMF for a sec-
ond reaction cycle.
the Heck reaction are known.
solvent-soluble colloidal palladium nanoparticles,
These include organic-
3
6,42
and
The results of four cycles are given in Table 3. The data
show a gradual loss of activity or turnover frequency. With 7
and methyl acrylate, conversion and yield drop in the third
cycle. Only by extending the duration of the fourth cycle from
two varieties of fluorous-solvent-soluble nanoparticles—one
type imbedded in a fluorous dendrimer, and the other stabi-
3
7,38
lized by absorbed fluorous molecules.
tives of the catalyst B (Fig. 2) upon which 7 is based
Also, close rela-
3
9
2
to 10 h are quantitative yields restored. With styrene, activity
decompose to active metallic palladium. Furthermore, col-
loidal palladium nanoparticles often impart a reddish-orange
loss is evident in the second cycle (15 vs. 5 h), and then drops
further. The same protocol was applied to the S-donor palla-
dacycle 13. With methyl acrylate, reaction times must again
be continually lengthened to maintain quantitative yields.
With styrene, no catalyst remains after three cycles. Thus, 13
is consumed at a faster rate than 7. However, additional GC
data showed that 13 gave higher TOF values than 7 in the first
two cycles with methyl acetate.
3
6a
tint to DMF,
and a similar hue is apparent in Fig. 3. We
therefore considered the possibility that 7, 13, and the analo-
gous bridging halides serve mainly as recyclable sources of
soluble non-fluorous colloidal nanoparticle catalysts. To
probe this model, the rate of reaction of phenyl iodide and
methyl acrylate was monitored under the conditions summar-
ized in Fig. 4.
a
Table 3 Heck reactions under recycling conditions
Data for 7
Data for 13
b
Conv. (%)
b
Yield (%)
c
b
Conv. (%)
b
Yield (%)
c
R
Cycle
t/h
TON
t/h
TON
d
d
CO
2
Me
1
2
3
4
1
2
3
4
2
2
100
100
77
100
5100
10 200
13 300
18 100
4 340
1
100
100
100
100
87
100
5100
10 200
15 300
20 400
4 340
d
d
100
1.5
6.5
16
100
d
d
2
55
100
d
d
10
5
100
92
100
85
100
85
e
e
C
6
H
5
5
24
e
e
15
24
24
88
86
80
8 420
12 190
14 840
79
81
72
81
8 010
12 140
12 140
e
e
74
55
132
e
e
74
52
0
0
a
Conditions: 7 or 13 (0.0014 g or 0.0015 g, 0.00044 mmol), phenyl iodide (0.250 mL, 2.24 mmol), alkene (ca. 1.25 equiv), Et
3
N (0.625 mL, 4.48
b
mmol), DMF (4.00 mL). Determined by GC. Cumulative. trans only. trans:cis 87:13.
c
d
e
4
2
New J. Chem., 2003, 27, 39–49

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Fig. 5 Transmission electron microscopy (TEM) image taken from
panel B in Fig. 3.
cases, reddish-orange tints became apparent near the end of
the induction period.
ꢀ
The first cycle with 7 in Table 3 was repeated (100 C), and
Fig. 3 Photographs of a recycling sequence analogous to the first
entry in Table 3 (7, methyl acrylate) but with 0.5 mol% 7. A, before
heating, with undissolved 7; B, after 2 h at 100 C; C, after cooling
to room temperature, with precipitated palladium complexes; D, after
addition of C F17Br. Reprinted from ref. 25 with permission from the
8
American Chemical Society.
the DMF separated from the DMF/C
panel D, Fig. 3). The C 17Br layer was washed with DMF
50% of original DMF volume). The DMF phases were com-
bined, charged with additional educts, and heated to 100 C.
As shown in Fig. 4 (top, black trace), reaction now occurred
without an induction period, indicating a leached catalyst.
Although the activity is somewhat less than for the first or
second cycles (red and blue traces), it should be noted that
all concentrations are ca. 67% lower.
8
F17Br mixture (see
8
F
ꢀ
(
ꢀ
Importantly, both the first and second cycles with 7 in Table
(Fig. 4, top; red and blue traces) appeared to show an induc-
3
tion period, and the second cycle was slightly slower. An
induction period for the first cycle could be rationalized under
any circumstances, but an induction period for the second sug-
gests that the active catalyst is not being recycled. In order to
Next, aliquots from the first cycle in Table 3, at the stage of
panel B in Fig. 3, were examined by transmission electron
microscopy. This is one of the best methods for detecting pal-
3
6,38
ladium nanoparticles.
As shown in Fig. 5, a distribution of
ꢀ
improve the time resolution, reactions were repeated at 80 C
sizes was found, with an average diameter of ca. 10 nm. Given
the above data, and as further elaborated in the discussion sec-
tion, we assign the bulk of the activity of palladacycle catalyst
precursors 7, 9, and 13 to DMF-soluble, non-fluorous palla-
dium nanoparticles.
(Fig. 4, bottom; green and orange traces). The induction peri-
ods and rate differences were markedly enhanced. The pallada-
cycle iodide 9 showed identical activity (purple trace). In all
During the course of the above studies, but before the nature
of the active catalyst was appreciated, we also conducted a
variety of Suzuki reactions, some of which are summarized
in Table 4. We note in passing that the insoluble nature of
the base K PO , which is customarily used in excess, renders
3
4
these reactions less suitable for catalyst recovery by liquid/
solid phase separation (Fig. 1B). Although palladacycle 7 gave
high TON values in the single-cycle experiments in Table 4,
attempted recycling with C F Br always gave dramatically
8
17
lower yields and activities. Indeed, many types of metallic pal-
ladium are known to catalyze the Suzuki reaction, as discussed
3
6a,38a,41
further below.
Discussion
Despite the careful design of the highly fluorophilic, thermo-
morphic palladacycle catalyst precursors 7 and 13, the preced-
ing data clearly indicate that a non-molecular catalyst is
responsible for the Heck and Suzuki reactions in Tables 2–4.
All evidence is consistent with the generation, during the
induction periods illustrated in Fig. 4, of highly active soluble
colloidal palladium nanoparticles—which are physically
detected in Fig. 5. Since the palladacycles are otherwise stable
ꢀ
in DMF and CF
3
C
6
H
5
at 100–140 C, this process must be
triggered by one of the reactants (e.g., phenyl iodide, alkene,
or Et N in Table 3). As 7 and 13 or the corresponding bridging
Fig. 4 Conversion as a function of time for Heck reactions of phenyl
iodide and methyl acrylate.
3
New J. Chem., 2003, 27, 39–49
43

View Article Online
a
Table 4 Selected Suzuki reactions
b
Conv. (%)
b
Yield (%)
X
R
ArX/mmol
7/mmol
t/h
TON
I
H
5.023
5.000
2.374
2.374
2.391
0.00000458
0.00000458
0.0000115
0.0000115
0.0000115
38
24
24
24
24
65
67
98
96
90
40
31
82
76
83
440 000
337 000
170 000
157 000
174 000
Br
Br
Br
Br
CH
H
3
CO
O
CH
CH
3
3
a
b
2 3 4
Conditions: ca. 1.0/1.5/2.0 ArX/PhB(OH) /K PO , toluene (8.00–13.00 mL). Determined by GC.
halide complexes are progressively consumed in each cycle,
catalysis slows and ultimately ceases.
the nature of the catalytically active species appears to be an
extremely sensitive function of structure.
Interestingly, the nanoparticles preferentially partition into
non-fluorous solvents, as shown by the retention of activity
In this regard, it is worth emphasizing that no nanoparticles
are detected during Heck reactions with the Herrmann/Beller
3
6a
in DMF after extraction with C
8
F
17Br. This suggests, in
that they are stabilized by
NH X . However, as noted above, palla-
dium nanoparticles can also be stabilized by certain fluorous
P-donor palladacycle A.
For this reason, we had thought
3
6a,42
accord with much precedent,
that sulfur, another second-row donor atom, might give more
robust fluorous palladacycles. However, the S-donor pallada-
cycle 13 appears to be slightly more labile than 7. There are
no data at present suggesting that Dupont’s similar catalyst
precursor C also functions as a palladium nanoparticle source.
However, several other palladium adducts of sulfur donor
ligands have been evaluated as catalyst precursors for Heck
and Suzuki reactions. In many cases, such as we have
described for the fluorous complexes [(R (CH ) ) S] PdCl
+
ꢁ
the by-product Et
3
3
8
molecules, such as E–G in Fig. 6. Such nanoparticles exhibit
high fluorous phase affinities, and those stabilized by E are
highly active and easily recycled catalysts for the Heck and
3
8a
Suzuki reactions. Unfortunately, the types of fluorous mole-
cules that are able to stabilize palladium nanoparticles can, at
present, only be determined empirically. Certainly the fluorous
ligands of 7 and 13, which must be extruded en route to nano-
particles, could have provided the requisite stabilization. It
therefore remains possible that ligand modifications might
reverse the phase affinity, giving recyclable fluorous catalysts.
What do our and other data suggest regarding the active
Heck catalyst derived from the Milstein palladacycle B (Fig.
f8
2 n 2
2
2
1
3b
(n ¼ 2,3),
there is good evidence that the active catalyst is
a form of metallic palladium.
In view of the above data, it is in our opinion worth critically
examining whether any of the fluorous palladium catalysts so
far applied in carbon–carbon bond forming reactions of aryl
1
2–14
halides
are truly molecular. As pointed out in a recent
3
5
2)? Detailed kinetic studies of the closely related Black-
mond/Pfaltz catalyst precursor D clearly establish homoge-
commentary, activity losses of the type in Table 3 can be
masked in several ways. One is to use a high catalyst loading.
Another is to select a reaction time for the first few cycles that
is much longer than required (e.g., 10 h for the 7/methyl acry-
late runs in Table 3). This can allow high yields to be main-
tained, even when (for example) 90% of the catalyst has been
lost. Rate experiments of the type in Fig. 4 unambiguously
indicate the degree of retained activity and catalyst, but for
some reason are not as frequently conducted. Despite these
question marks, we continue to believe that highly active and
easily recycled molecular fluorous catalysts for the Heck and
Suzuki reactions are realistic objectives. Other types of chelate
ligands appear to offer enhanced stabilities, and are currently
neous pathways, with rates dependent upon concentrations
of dissolved palladium complexes. However, Nowotny has
4
3
found that the similar polystyrene-supported palladacycle H
(
3
9
Fig. 7) exhibits characteristics comparable to 7 and 13.
These include an induction period for the first cycle, little or
no activity in subsequent cycles, and complete retention of
activity in the supernatant after removal of the insoluble poly-
styrene support. Bedford has reported similar behavior for the
0
41a
silica-bound palladacycles I/I in Suzuki reactions.
Hence,
4
4
under active investigation in our laboratory.
This work, together with related studies mentioned
3
9,41a
above,
illustrates the valuable insight that recoverable
Fig. 6 Representative fluorous compounds that stabilize palladium
nanoparticles.
Fig. 7 Other immobilized palladacycles that have been evaluated as
catalyst precursors for Heck and Suzuki reactions.
38
39,41a
4
4
New J. Chem., 2003, 27, 39–49

View Article Online
2
4a
and/or immobilized compounds can offer in the elucidation of
mechanism.
mmol),
and water (0.5 mL), fitted with a condenser, and placed in a
K
2
CO
3
(0.646 g, 4.68 mmol), p-dioxane (15 mL),
4
5,46
In order to rationally design a recoverable cat-
ꢀ
alyst, a model for the active species is necessary. The success or
failure of the recoverable catalyst in turn bears upon the accu-
racy of the model. Whenever (1) induction periods are
observed, and (2) activity remains in a phase different from that
of the recovered ‘‘catalyst’’, and (3) the recovered material
continues to exhibit induction periods, together with reduced
activity, it is highly probable that the immobilized species
bears little relationship to the active catalyst. Naturally, there
are a variety of related scenarios, such as simultaneous cataly-
sis by an immobilized species and a leached species. Regard-
95 C oil bath. The mixture was stirred and monitored by
TLC (1:9 v/v EtOAc/hexanes). After 24 h, reaction was com-
plete. The solvent was removed by rotary evaporation. Water
(25 mL) was added to the yellow oil, and the mixture extracted
with CH
2
Cl
2
(2 ꢂ 50 mL). The extracts were dried (MgSO
4
)
and the solvent removed by rotary evaporation. The oily resi-
due was chromatographed on a silica gel column (eluent hex-
ane) to give 2 as a colorless oil that solidified upon standing
4
8
(1.994 g, 3.011 mmol, 96%, 90:10 Z/E).
Calcd for
17 8
C H F17I: C, 30.83; H, 1.21. Found: C, 31.08; H, 1.08%.
4
5,46
1
3
less, such ‘‘phase tests’’
study of catalyst mechanisms.
deserve more frequent use in the
NMR (CDCl
3
): H 2.97–3.21 (2 overlapping dt, JHF ¼ 18
3
3
Hz, JHH ¼ 7 Hz, CF
2
CH
2
, Z/E), 5.78 (dt, JHH ¼ 11 Hz,
3
3
3
JHH ¼ 7 Hz, CH CH=, Z), 6.16 (dt, J
¼ 16 Hz, J
¼ 7
2
HH
HH
3
7
6.72 (d,
Hz, CH
2
CH=, E), 6.55 (d, JHH ¼ 16 Hz, =CHC
6
H
4
, E),
3
Conclusion
J
HH ¼ 11 Hz, =CHC
H , Z), 6.97 and 7.77 (2d,
6 4
3
J
3
J
HH ¼ 8 Hz, C
6
1
H
4
, Z), 7.13 and 7.68 (2d,
HH ¼ 8 Hz,
1
3
2
This study has established new catalyst systems for the Heck
and Suzuki reactions (Tables 2–4) based upon the novel fluor-
ous palladacycle catalyst precursors 7 and 13. From the stand-
point of TON values, the Heck reactions rank with the best in
the literature. Complexes 7 and 13 represent new examples of
thermomorphic fluorous compounds, with little or no solubi-
lity in organic solvents at room temperature but significant
solubility at elevated temperatures, thus enabling homoge-
C H , E);
6
C{ H} (partial, Z) 30.7 (t, JCF ¼ 22 Hz,
4
3
CF
1
2
CH ), 119.0 (t,
2
=
34.7, 135.5, l38.0 (5s, CHC H ).
J
CF ¼ 5 Hz, CH
2
CH ), 128.4, 130.4,
=
6
4
p-Rf8CH
2
CH CHC
=
6
4
H CH(OH)(CH
2
)
2
Rf8 (3)
A Schlenk flask was charged with 2 (0.795 g, 1.200 mmol) and
THF (10 mL). Then i-PrMgCl (2.4 M in ether, 0.60 mL, 1.44
mmol) was added with stirring over the course of 5 min (room
temperature). The mixture warmed slightly and turned yellow.
4
,5
neous reactions in the absence of fluorous solvents. How-
ever, in apparent contrast to closely related non-fluorous
palladacycles, they act mainly as steady-state sources of extre-
mely reactive, soluble colloidal palladium nanoparticles. Such
2 2
After 30 min, a solution of Rf8CH CH CHO (0.686 g, 1.44
2
8
3
6–42
mmol) in THF (10 mL) was added over 10 min. After an
additional 2 h, aqueous HCl (0.1 M, 25 mL) was added. The
mixture was extracted with ether (2 ꢂ 50 mL). The extracts
species are of great current interest,
but those obtained
from 7 and 13 are not amenable to fluorous recycling proto-
cols. Fluorous analogs of existing Heck catalysts that are
expected to show greater stabilities with respect to nanoparti-
cles, and function as molecular catalysts, will be described in
4
were dried (MgSO ) and the solvent removed by rotary eva-
poration. The yellow oil was chromatographed on a silica gel
column (1:9 v/v ether/hexanes) to give 3 as a colorless oil that
solidified upon standing (1.131 g, 1.117 mmol, 93%, 90:10 Z/
4
4
future reports.
4
8
E). Calcd for C28
H
14
F34O: C, 33.22; H, 1.39. Found: C,
3
3.08; H, 1.28%.
NMR (CDCl
Experimental
1
3
):
H
1.92 (br s, OH), 1.99–2.38 (m,
3
General
CH
Hz,
2
CH CF
2
J
2
, E/Z), 3.14–2.98 (2 overlapping dt, JHF ¼ 18
3
3
HH ¼ 7 Hz, CF
2
CH
2
CH=, Z/E), 4.81 (t,
J
HH ¼ 6
CH=,
CH=, E), 6.63
2
All reactions were conducted under N
2
. Chemicals were trea-
3
3
Hz, CHOH), 5.78 (dt, JHH ¼ 11 Hz, JHH ¼ 7 Hz, CH
2
ted as follows: THF, ether, toluene, hexanes, distilled from
Na/benzophenone; Et N, distilled from Na; CF 11 (Oak-
wood or ABCR), distilled from P ; CF (ABCR), dis-
tilled from CaH ; i-PrMgCl (2.0 M in ether, Aldrich),
(Fluorochem), (Ph P) RhCl,
3
3
Z), 6.16 (dt, JHH ¼ 16 Hz, JHH ¼ 7 Hz, CH
3
3
C
6
F
3
J
3
(
d,
HH ¼ 16 Hz, =CHC
6
H
4
, E), 6.83 (d,
J
HH ¼ 11 Hz,
2
O
5
3
C
6
H
5
3
=
6 4 HH
CHC H , Z), 7.25 and 7.37 (2d, J
¼ 8 Hz, C H , Z),
6
4
2
3
13
1
7
.33 and 7.41 (2d, JHH ¼ 8 Hz, C
6 4
H , E); C{ H} (partial,
4
7
standardized;
Pd(OAc)
mobenzene, p-bromotoluene, p-bromoacetophenone, p-bro-
C
8
F
17Br
3
3
2
Z) 27.5 (t, JCF ¼ 22 Hz, CH CH CF ), 29.5 (br s,
2
2
2
2
(2 ꢂ Strem), PPh
3
, phenyl iodide (2 ꢂ Fluka), bro-
2
CH
2
CH
2
CF
2
), 30.7 (t, JCF ¼ 22 Hz, CF
2
CH
2
CH=), 73.1 (s,
3
CHOH), 118.6 (t, JCF ¼ 5 Hz, =CHCH ), 126.1, 129.0,
2
moanisole, methyl acrylate, PhB(OH) , p-iodobenzaldehyde,
2
1
35.2, 136.0, l43.0 (5s, =CHC
H ).
6 4
aliquat 336 (8 ꢂ Aldrich), styrene (Acros), CDCl
3
(Cambridge
Isotope or Aldrich) and other solvents, used as received. NMR
spectra were recorded on 400 MHz spectrometers at ambient
probe temperatures unless noted and referenced to residual
p-Rf8(CH
2 3 6 4 2 2
) C H CH(OH)(CH ) Rf8 (4)
1
13
internal CHCl
3
( H, d 7.27) or CDCl ( C, d 77.2). IR spectra
3
A Fisher–Porter bottle was charged with 3 (0.770 g, 0.761
were measured on an ASI React-IR spectrometer. GC data
were acquired using a ThermoQuest Trace GC 2000 instru-
ment fitted with a capillary column (OPTIMA-5-0.25 mm; 25
m ꢂ 0.32 mm). HPLC was conducted on a Thermoquest
instrument package (pump/autosampler/detector P4000/
AS3000/UV6000LP). DSC and TGA data were recorded with
a Mettler-Toledo DSC821 instrument and treated by standard
methods. TEM data were obtained with a Philips CM 300
UT instrument. Elemental analyses were conducted with a
Carlo Erba EA1110 instrument (in-house).
3
3
3 6 5
mmol), (Ph P) RhCl (0.053 g, 0.057 mmol), and CF C H /
EtOH (20 mL, 1:1 v/v). The system was purged with H
and
2
ꢀ
pressurized to 75 psig. The bottle was placed in a 40 C oil bath
and the mixture stirred. After 14 h, the bath was removed, the
system vented, and the solvents removed by rotary evapora-
tion. The residue was chromatographed on a silica gel column
(1:9 v/v ether/hexanes) to give 4 as a white solid (0.695 g,
3
0
ꢀ
ꢀ
0.685 mmol, 90%), mp 89 C (capillary), 89.8 C (DSC). Calcd
for C28 34O: C, 33.15; H, 1.59. Found: C, 32.76; H, 1.31%.
NMR (4:1 v/v CDCl
.39 (m, 2CH CH CF
16
H F
1
/CF C F ): H 1.88 (br s, OH), 1.90–
3 6 5
3
3
2
2
2
2
), 2.76 (t, JHH ¼ 7 Hz, CH
2
C
6
H
4
), 4.77
3
3
(
t, J
¼ 6 Hz, CHOH), 7.22 and 7.33 (2d, J
¼ 8 Hz,
HH
13
HH
p-R CH CH=CHC H I (2)
f8
2
6
4
1
); C{ H} (partial) 22.0 (br s, CF
C
6
H
4
2
CH
2
CH
2
CH
2
), 27.6
2
A flask was sequentially charged with p-iodobenzaldehyde (1;
+
(t, J ¼ 22 Hz, CH(OH)CH CH CF ), 29.6 (br s, CH(OH)-
CF
2
2
2
ꢁ
2
0
.724 g, 3.12 mmol), Rf8CH
2
CH
2
PPh
3
I
(3.91 g, 4.68
CH
2 2 2 2 2 2 2
CH
CH
CF
), 30.7 (t, JCF ¼ 22 Hz, CF
CH
CH
), 34.9
New J. Chem., 2003, 27, 39–49
45

View Article Online
(
C H ).
s, CH
2
C
6
4
H ), 73.3 (s, CHOH), 126.3, 129.0, 141.0, l42.0 (4s,
(ca. two times the column volume) and then eluted with
CF C H /EtOH (9:1 v/v). The solvent was removed from
the last fraction by rotary evaporation. The residue was dried
6
4
3
6
5
by oil pump vacuum to give 7 as a dark yellow gum (0.986 g,
p-Rf8(CH
2 3 6 4 2 2
) C H ) Rf8 (5)
C(=O)(CH
0
.301 mmol, 87%). A solution of 7 (0.070 g), in CF
3
ꢀ
C
6
H
5
(2
mL) was layered with toluene (10 mL) and kept at 4 C. This
A Schlenk flask was charged with 4 (0.642 g, 0.632 mmol), the
2
9
ꢀ
ꢀ
Dess–Martin periodinane (0.322 g, 0.759 mmol),
CF (20 mL). The solution was stirred overnight. Ether
50 mL) was added, and the white suspension poured into a
solution of Na SO (1.31 g, 5.31 mmol) in saturated aqueous
and
gave yellow needles of 7, mp 78–80 C (capillary), 78.5 C
(DSC). Calcd for C82 Pd : C, 30.10; H, 1.35.
C N
=
Found: C, 30.15; H, 1.13%. IR (cm , thin film) n 1587,
3
C
H
6 5
H
44
F
102
2
N O
4
2
ꢁ
1
(
2
O
0c,31
2
3
n
C
=
1571, 1424.
5
0
1
KHCO (50 mL). The biphasic mixture was vigorously stirred
3
until the organic phase appeared clear. The organic phase was
washed with saturated aqueous KHCO3 (50 mL) and dried
NMR (4:1 v/v CDCl
3
/CF
CHH ), 1.70–1.81 (m, NCH
CH
), 2.17 (s, CH
3
3
C
6
F
5
):
H 1.35–1.45 (m,
0
0
N=CCH
CHH ), 1.87–1.94 (m, CH
NCH
(m, NCH CHH ), 2.50–2.55 (m, N=CCHH ), 2.61–2.73 (m,
N=CCHH , CH
CHH , N=CCH
), 2.08–2.25 (m,
), 2.40–2.45
2
-
2
2
0
2
2 6 3
C H
(
MgSO
The residue was chromatographed on a silica gel column
3:17 v/v CHCl /hexanes) to give 5 as a white solid (0.608 g,
.600 mmol, 95%), mp 112–113 C (capillary), 110.9 C
DSC). Calcd for C28 34O: C, 33.22; H, 1.39. Found: C,
3.42; H, 1.38%. IR (cm , thin film) nC
4
). The solvent was removed by rotary evaporation.
2
CH
2
CH
2
, CH
2
CH
2
CH
2
C
6
H
3
0
0
2
0
0
(
0
(
3
3
2
C
H
6 3
), 2.98–3.05 (m, NCHH ), 3.22–3.29
ꢀ
ꢀ
0
3
(m, NCHH ), 6.88, 6.92 (2d, JHH ¼ 8 Hz, C H ), 6.98 (s,
6
3
1
3
1
H
14
F
C
6
H
3
);
C{ H} (partial) 18.7 (s, N=CCH
NCH CH ), 22.3 (s, CH CH C H ), 24.0 (s, CH ), 28.8, 31.0
2
), 21.5 (s,
ꢁ
1
=
O
1683.
H
2
2
2
2
6
3
3
1
2
NMR (4:1 v/v CDCl
3
/CF
3
C
6
F
5
):
1.96–2.15 (m,
(2t, JCF ¼ 22 Hz, CH
2
CH
2
CH
2
C
6
H
3
, NCH
2
2 2
CH CH ), 29.4
2
CF CH CH CH ), 2.54–2.68 (m, C(=O)CH CH ), 2.80 (t,
(t, J ¼ 22 Hz, N=CCH CH ), 35.8 (s, CH C H ), 52.2 (s,
2
2
2
2
2
2
CF
2
2
2
6
51
3
3
3
J
HH ¼ 7 Hz, CH
2
C
6
H
4
), 3.30 (t, JHH ¼ 7 Hz, C(=O)CH
2
),
2 6 3
NCH ), 124.3, 126.2, 128.7, 129.1 132.9, 157.1 (6s, C H ),
3
13
1
7
2
.32 and 7.95 (2d, JHH ¼ 8 Hz, C H ); C{ H} (partial)
179.9 (s, C=N), 181.9 (s, C=O).
6
4
2
J
1.7 (br s, CF
2
CH
CH CH
2 2
2
), 25.8 (t,
CF ¼ 22 Hz,
C(=O)CH CH CF ), 29.6 (s, C(=O)CH CH CF ), 30.5 (t,
2
2
2
2
2 2
Imine palladacycle chloride 8
2
J
CF ¼ 22 Hz, CF
2
CH CH
2
28.8, 129.1, 134.9, l47.3 (4s, C
2
CH
2 2 2 2 2
), 35.2 (s, CF CH CH CH ),
1
H
6 4
), 196.3 (s, C=O).
A Schlenk flask was charged with a solution of 7 (0.358 g,
.109 mmol) in CF (8 mL). Then a solution of LiCl
0.070 g, 2.19 mmol) in CH OH (5 mL) was added with stir-
0
3 6 5
C H
(
3
p-Rf8(CH
2
)
3
C
H
6 4
C(=N(CH
2
)
3
Rf8)(CH
2 2
) Rf8 (6)
ring. After 1 h, solvent was removed from the cloudy mixture
by oil pump vacuum. The yellow residue was triturated with
CH OH (10 mL), collected by filtration, washed with CH OH
3 3
A
flask was charged with
5
(0.522 g, 0.516 mmol),
2
8
H NCH CH CH R (0.492 g, 1.031 mmol), SnCl (H O)
2
2
2
2
2
f8
2
2
(
0.017 g, 0.10 mmol), and toluene (50 mL), fitted with a
(3 ꢂ 10 mL) and ether (2 ꢂ 5 mL), and dried by oil pump
ꢀ
Dean–Stark trap, and placed in a 140 C oil bath. After 14 h,
the mixture was cooled and the solvent was removed by oil
pump vacuum. The residue was flash chromatographed (silica
gel dried for a minimum of 5 days at 120 C) using dry hex-
anes/THF (3:1 v/v). The solvent was removed by rotary eva-
poration to give 6 as a colorless oil that solidified upon
vacuum. This gave 8 as a beige powder (0.300 g, 0.0093 mmol,
ꢀ
ꢀ
85%), mp 176 C (capillary), 179.0 C (DSC). Calcd for
Pd : C, 29.05; H, 1.19. Found: C, 29.18; H,
1.69%. IR (cm , thin film) n 1583.
NMR (1:1 v/v CDCl /CF C F , 57 C): H 1.99–2.57 (m,
C
78
H
38
F102Cl
2
N
2
2
ꢀ
ꢁ1
C N
=
ꢀ
1
3
3 6 5
2CH
2
CH
2
CH
2
CF
2
,
N=CCH
CH CF ), 2.78, 2.84 (2t,
2 2 2
4
9
3
standing (0.744 g, 0.506 mmol, 98%, 35:65 Z/E). Calcd for
51N: C, 31.83; H, 1.37. Found: C, 32.06; H, 1.47%.
JHH ¼ 7 Hz, CH C H ), 3.12–3.16 (m, N=CCH ), 3.84–
2
6
3
2
1
3
1
C
39
H
20
F
2 6 3
3.91 (m, NCH ), 7.07–7.23 (m, C H ); C{ H} (partial)
19.6, 22.0, 22.3 (3s, 3CH CH CF ), 29.2, 30.3, 31.3 (3t,
ꢁ
1
IR (cm , thin film) n
=
1657.
N
C
2
2
2
5
): H 1.81–2.30 (m, 2CH
0 1
2
NMR (CDCl
3
CH CH CF
2 2 2
2
, Z/
JCF ¼ 22 Hz, 3CH
2 2 2 6 3
CF ), 36.0 (s, CH C H ), 53.0 (s,
5
CH N), 125.5, 127.3, 134.1, 134.3, 145.1, 156.0 (6s, C H ),
1
E, N=CCH CH CF , Z), 2.49–2.60 (m, N=CCH CH CF ,
E), 2.74 (t,
Hz, CH C H , Z), 2.82 (t, J
2
2
2
2
2
2
2
6
3
3
3
J
HH ¼ 8 Hz, CH
2
C
6
H
4
, E), 2.75 (t,
J
HH ¼ 8
182.7 (s, C=N).
3
¼ 8 Hz, N=CCH , E), 3.01
2
6
4
HH
2
3
3
(
t,
NCH , E), 3.61 (t, J
J
HH ¼ 8 Hz, N=CCH
2
, Z), 3.30 (t,
J
HH ¼ 8 Hz,
3
Imine palladacycle iodide 9
¼ 8 Hz, NCH , Z), 7.07 and 7.25
2
HH
2
3
J
3
J
(
2d,
Hz, C
HH ¼ 8 Hz, C
6
H
4
, E), 7.24 and 7.70 (2d,
HH ¼ 8
3 6 5
Complex 7 (0.240 g, 0.073 mmol), CF C H (8 mL), LiI (0.200
g, 1.49 mmol), and CH OH (5 mL) were combined in a proce-
3
1
3
1
6
H
4
, Z); C{ H} (partial) 19.3 (s, CH
CH , Z), 21.8 (s, NCH CH , E), 22.1 (br s,
CH
, Z/E), 29.0 (t,
2
C=N, Z), 21.7
(s, NCH
CH
2
2
2
2
dure analogous to that given for 8. An identical workup gave 9
ꢀ
2
2
CH
2
C
6
H
4
, Z/E), 27.0 (t, JCF ¼ 22 Hz, N=CCH
2
2
,
as a yellow powder (0.215 g, 0.063 mmol, 86%), mp 182 C
ꢀ
2
E), 28.8 (t, JCF ¼ 22 Hz, CH
2
CH
, Z), 30.3 (t,
2
CH
2
C
6
H
4
(capillary), 188.5 C (DSC). Calcd for C78
H
38
F
102
I
2
N
2
Pd
2
:
2
2
ꢁ1
J
CF ¼ 22 Hz, N=CCH
2
CH
2
2
J
CF ¼ 22 Hz,
CF ¼ 22 Hz, NCH CH CH
C=N, E), 34.8 (s, CH
, Z), 34.9 (s,
, E), 50.0 (s, C=NCH , Z), 51.4 (s, C=NCH
26.7 (s, C , E), 127.2 (s, C , Z), 129.0 (s, C
C, 27.49; H, 1.12. Found: C, 27.54; H, 1.20%. IR (cm , thin
film) n 1583.
NMR (1:1 v/v CDCl
2CH CH CH CF
N=CCH
CH
), 3.15–3.19 (m, N=CCH
7.10–7.16, 7.22–7.24, and 7.71 (m/m/s, C H ); C{ H} (par-
NCH
E), 31.7 (s, CH
CH
2
CH
2
CH
2
, Z), 30.4 (t,
J
2
2
2
,
C N
=
ꢀ
1
2
2
C
H
6 4
3
/CF
3
C
6
F
5
, 57 C): H 2.00–2.75 (m,
CH CF ), 2.80–2.85 (m,
), 4.15–4.18 (m, NCH ),
2
C
6
H
4
2
2
4
, E),
, Z/
2
2
2
2
,
2
2
2
1
6
H
4
6
H
4
6
H
2
C
6
H
3
2
2
1
3
1
E), 136.3 (s, C H , E), 136.8 (s, C H , Z), 141.7 (s, C H ,
6
4
6
4
6
4
6
3
E), 143.3 (s, C
6
H
4
, Z), 166.0 (s, C=N, Z), 168.8 (s, C=N, E).
tial) 20.0, 22.0, 22.6 (3s, 3CH
2
CH
2 2
CF ), 28.7, 30.4, 31.3 (3t,
2
JCF ¼ 22 Hz, 3CH CF ), 36.0 (s, CH C H ), 54.6 (s,
2
2
2
6
3
1
5
CH
1
2 6 3
N), 125.2, 128.0, 128.2, 139.4, 146.5, 159.7 (6s, C H ),
83.1 (s, C=N).
Imine palladacycle acetate 7
A Schlenk flask was charged with 6 (1.019 g, 0.692 mmol),
Pd(OAc)2 (0.155 g, 0.692 mmol), and AcOH (12 mL), and
placed in a 95 C oil bath. The mixture was stirred (1.5 h)
and cooled to room temperature. The solvent was removed
Imine palladacycle phosphine 10
A. A Schlenk flask was charged with 7 (0.450 g, 0.137 mmol),
LiCl (0.058 g, 1.38 mmol), and PPh (0.079 g, 0.302 mmol).
THF (10 mL) was added with stirring, and 7 dissolved over
ca. 0.5 h. After 1 h, the solvent was removed by oil pump
ꢀ
by rotary evaporation, and CF
was poured on top of a short column of silica gel in CF C H
3
C
6
H
5
(10 mL) was added. This
3
3
6
5
5
(
10 cm ꢂ 2.5 cm Ø). The column was washed with CF
New J. Chem., 2003, 27, 39–49
3
C
6
H
4
6

View Article Online
ꢀ
ꢀ
vacuum. The yellow powder was extracted with CH
(
Schlenk flask and taken to dryness by oil pump vacuum. The
residue was triturated with hexanes (5 mL, 15–20 min), col-
lected by filtration, washed with hexanes (2 ꢂ 10 mL) and dried
by oil pump vacuum. This gave 10 as a beige powder (0.408 g,
2
Cl
2
64%), mp 48 C (capillary), 47.8 C (DSC). Calcd for
C H F S: C, 31.42; H, 1.42. Found: C, 31.42; H, 1.34%.
2 ꢂ 10 mL). The extract was filtered under N into a new
2
39 21 51
1
NMR (CDCl
2.19 (m, CF CH
CF
SCHH CH
CF CH CH
3
): H 1.68–1.72 (m, CHCH
2
CH
2
CF
2
), 1.89–
CH
HH ¼ 7 Hz,
2
2
CH CH
2
2
, SCH
2
CH CH
2
HH ¼ 13 Hz,
2
, SCHCH
2
2
-
2
3
2
), 2.32 and 2.42 (2 quint,
J
J
0
0
3
3
2
CH
2
and SCHH CH
2
CH
2
), 2.69 (t, JHH ¼ 7 Hz,
CH CF ),
); C{ H} (partial)
CH CH CH
CH
), 48.6 (s,
).
0
(
(
.217 mmol, 79%). B. A Schlenk flask was charged with 8
0.269 g, 0.083 mmol), PPh (0.048 g, 0.18 mmol), and CH Cl
10 mL). The suspension was vigorously stirred. After 1 h, the
2
2
2
CH
2
), 3.74 (t,
J
HH ¼ 7 Hz, CHCH
2
2
2
3
J
13
1
3
2
2
7.14 and 7.22 (2d,
19.9 (s, CHCH CH
SCH CH CH
30.2 (s, SCH
CHCH CH CF
HH ¼ 8 Hz, C
6 4
H
2
2
CF
2
), 21.6, 27.0 (2s, CF
2
2
2
2
,
2
solvent was removed from the light yellow solution by oil
pump vacuum. Hexanes (5 mL) was added to the solid, which
was isolated by filtration, washed with hexanes (2 ꢂ 10 mL),
and dried by oil pump vacuum to give 10 as a beige powder
2
2
2
), 29.1, 29.4, 30.1 (3t, JCF ¼ 22 Hz, CF
CH CH ), 34.5 (s, CF CH CH CH
), 127.7, 128.8, 139.0, l40.3 (4s, C
2
2
),
2
2
2
2
2
2
2
2
2
2
6 4
H
ꢀ
ꢀ
(
(
3
nC
0.254 g, 0.135 mmol, 81%), mp 135 C (capillary), 138.4 C
ꢀ
Thioether palladacycle acetate 13
DSC). T , 228.4 C (TGA). Calcd for C H ClF NPPd: C,
i
6.52; H, 1.82. Found: C, 36.61; H, 1.89%. IR (cm , thin film)
1586.
57 34
51
1
ꢁ
2
Complex 12 (0.740 g, 0.496 mmol), Pd(OAc) (0.111 g, 0.496
=
N
mmol), and AcOH (15 mL) were reacted in a procedure analo-
gous to that given for 7 (2 h). A similar workup (15 cm ꢂ 2.5
cm Ø column) gave 13 as a dark yellow gum (0.695 g, 0.210
5
0 1
NMR (CDCl
.74 (m, CH CH CH C H ), 2.03 (t, J
3
):
2 2 6 3
H 1.17–1.25 (m, CH CH C H ), 1.63–
3
1
2
2
¼ 8 Hz, CH C H ),
2
2
2
6
3
HH
2
6
3
.10–2.18 (m, NCH
2
CH ), 2.23–2.36 (m, NCH
2
.40–2.49 (m, N=CCH CH ), 3.06–3.10 (m, N=CCH ), 4.20
2
CH
2
CH
2
),
mmol, 84%). Calcd for C82
1.40; S, 1.94. Found: C, 30.54; H, 1.55; S, 1.80%. IR (cm
46 102 2 4 2
H F S O Pd : C, 29.75; H,
ꢁ
1
,
2
3
2
2
20c,31
(
br s, NCH
2
), 6.35 (d, JPH ¼ 5 Hz, 1H of C
H
6 3
), 6.77 and
thin film) n
C
=
O
1567, 1424.
NMR (4:1 v/v CDCl /CF C F ; see text regarding iso-
3
7
P(C
.14 (2d, JHH ¼ 8 Hz, 2H of C H ), 7.36–7.47 (m, 9H of
6
3
3
3 6 5
1
); C{ H} (partial)
3
1
1
mers): H 1.28–2.66 (m, 14H), 2.12 (br s, CH
H
6 5
)
3
), 7.72–7.77 (m, 6H of P(C
6
H
5
)
3
3
) 2.85–4.50 (m,
0
13
CHSCHH ), 6.66–7.20 (m, C H ); C{ H} (partial) 14.1,
1
1
NCH
9.4 (s, N=CCH2), 21.3 (s, CH CH C H ), 22.1 (s,
2
2
6
3
6
3
2
2
CH
2
), 28.3 (t, JCF ¼ 22 Hz, NCH
2
CH
2
CH ), 29.4 (t,
2
20.3, 22.1, 24.2 (4br s, CH
30.1, 30.4 (2s, CH , SCH ), 35.2 (br s, CH C H ), 58.3 (br s,
2 2 2
), 29.6–30.9 (br t, 3CH CF ),
2
2
JCF ¼ 22 Hz, N=CCH CH ), 30.3 (t, JCF ¼ 22 Hz,
2
2
3
2
2
6
3
CH
1
2
CH
2
CH
2
C
6
H
3
), 35.1 (s, CH
2
C
6
H
3
), 51.0 (s, NCH
2
),
SCH
), 181.2 (br s, C=O).
2
2
24.4, 127.0 (2s, 2C of C H ), 128.4 (d, JPC ¼ 11 Hz, m-
6
3
1
PPh), 131.1 (s, p-PPh), 131.2 (d, JPC ¼ 50 Hz, i-PPh), 135.6
3
3
Partition coefficients (Table 1)
(
C
d, JPC ¼ 13 Hz, o-PPh), 139.5 (d,
J
¼ 11 Hz, 1C of
6 3
PC
5
), 143.8, 146.5, 159.9 (3s, 3C of C
1
6
H
3
H
), 181.6 (s,
The following are representative. A. A 10 mL vial was charged
with 6 (0.0236 g, 0.0160 mmol), CF C F (2.000 mL), and
toluene (2.000 mL), fitted with a mininert valve, and vigor-
ously shaken (2 min). After 12 h (24 C), a 0.400 mL aliquot
of each layer was added to a hexane solution of eicosane
3
1
1
C=N); P{ H} 42.9 (s, PPh ).
3
3 6 11
ꢀ
3
3
R
f8CH
2
CH
2
CH
2
SH (11)
(
2.000 mL, 0.0273 M). GC analysis (average of 7–8 injections)
showed 0.00304 mmol of 6 in the CF 11 aliquot and
.000040 mmol in the toluene aliquot (98.7:1.3; a 2.000/
.400 scale factor gives a mass balance of 0.0226 g, 96%). B.
A round bottomed flask was charged with Rf8CH
2
CH
2 2
CH I
1
1a
C F
3 6
(
transfer catalyst aliquat 336 (0.221 g, 0.546 mmol), and water
5.02 g, 8.53 mmol),
thiourea (0.973 g, 12.8 mmol), phase
0
0
ꢀ
(
15 mL), fitted with a condenser, and placed in a 100 C bath.
A 10 mL vial was charged with 7 (0.0104 g, 0.0031 mmol),
CF C F (2.000 mL), and toluene (2.000 mL), fitted with a
The mixture was stirred and a precipitate slowly formed. After
0 h, aqueous KOH (50 mL, 0.1 M) was added. After 0.5 h, the
3
6 11
2
mininert valve, and vigorously shaken (2 min). After 2 h
ꢀ
mixture was allowed to cool to room temperature. Concen-
trated HCl was added until the sample was acidic. The mixture
(
0
24 C), a 0.250 mL aliquot of the fluorous phase and a
.750 mL aliquot of the non-fluorous phase were removed.
was extracted with CH
(
2
Cl
MgSO ), and the solvent was removed by rotary evaporation.
4
2
(2 ꢂ 50 mL). The extract was dried
The solvents were evaporated and the residues dried by oil
pump vacuum (1 h). Each residue was taken up in
CF C H /EtOH (9:1 v/v; 0.500 mL) and analyzed by HPLC
The light brown oil was chromatographed (silica gel column,
hexanes) to give 11 as a clear oil (3.30 g, 6.68 mmol, 78%).
Calcd for C H F S: C, 26.73; H, 1.42. Found: C, 26.83; H,
3
6
5
(
average of 5 injections, 200 ꢂ 4 mm Nucleosil 100-5 column,
1
1
7
17
1
UV/visible detector). The relative peak intensities were (after
normalization to the aliquot volumes) 95.5:4.5.
1
.42%.
3
NMR (CDCl ): H 1.36 (t, J
¼ 8 Hz, SH), 1.87–1.95 (m,
2 2 2 2
3
HH
CF
(
(
2
CH
2
CH
¼ 8 Hz, J
2
CH
2
), 2.14–2.27 (m, CF
CH
¼ 7 Hz, CF CH CH CH ); C{ H}
2 2 2 2 2 2 2
CH CH CH ), 24.6 (s, CF CH CH CH ),
CH CH ), 2.61
3
dt, J
partial) 23.8 (s, CF
3
13
1
Heck and Suzuki reactions
HH
HH
2
2
2
2
2
2
The following are representative. Table 2: A Schlenk tube was
sequentially charged with DMF (6 mL), phenyl iodide (0.560
mL, 5.02 mmol), methyl acrylate (0.565 mL, 6.28 mmol),
2
9.5 (t, J ¼ 22 Hz, CF CH CH CH ).
CF
2
2
2
2
Et
(
3
N (1.400 mL, 10.05 mmol), and a solution of 7 in CF
3
C
6
H
5
p-Rf8(CH
2
)
3
C
6
H
4
CH(S(CH
2
)
3
R
f8)(CH
2
)
2
R
f8 (12)
ꢁ6
0.000229 M; 0.015 mL, 3.44 ꢂ 10 mmol), fitted with a con-
ꢀ
A Schlenk flask was charged with 4 (1.00 g, 0.987 mmol), 11
denser, and placed in a 140 C oil bath. The solution was vig-
orously stirred (14 h), removed from the bath to cool, and
diluted with ether to 25.00 mL. An aliquot (0.500 mL) was
added to a toluene solution of tridecane (0.250 mL, 0.100
M). GC analysis showed only trans-methyl cinnamate (100%,
TON 1 460 000). The aliquot was recombined with the mother
solution. A standard basic aqueous workup and flash chroma-
tography on silica gel (9:1 v/v hexanes/EtOAc) gave trans-
methyl cinnamate in 98% yield (0.797 g, 4.914 mmol). Table
3: A Schlenk tube was sequentially charged with 7 (0.0014 g,
0.00043 mmol), DMF (4 mL), phenyl iodide (0.250 mL, 2.24
(
CF
0.763 g, 1.54 mmol), ZnI2 (0.315 g, 0.986 mmol), and
ꢀ
3
C
6
H
5
(15 mL), and placed in a 60 C bath. The solution
was stirred. After 16 h, water (50 mL) was added. The mixture
was extracted with ether (2 ꢂ 50 mL). The extract was dried
(
MgSO ), and the solvents were removed by rotary evapora-
4
tion. The residue was placed on the top of a silica gel column
packed with hexanes. The column was eluted with hexanes
(removing excess 11) and then hexanes/ether (20:1 v/v). The
solvents were removed from the latter fractions by oil pump
vacuum to give 12 as a white solid (0.929 g, 0.632 mmol,
New J. Chem., 2003, 27, 39–49
47

View Article Online
11 (a) J.-M. Vincent, A. Rabion, V. K. Yachandra and R. H. Fish,
mmol), methyl acrylate (0.250 mL, 2.78 mmol), and Et
ꢀ
3
N
0.625 mL, 4.48 mmol), and placed in a 100 C oil bath. The
Angew. Chem., Int. Ed. Engl., 1997, 36, 2346; J.-M. Vincent, A.
Rabion, V. K. Yachandra and R. H. Fish, Angew. Chem., 1997,
(
solution was vigorously stirred (2 h), and removed from the
bath to cool (0.5 h). Then C 17Br (1 mL) was added to give
a biphasic system. The upper DMF layer was removed by syr-
inge, and the C 17Br phase extracted with DMF (2 mL). The
1
09, 2438; (b) S. Quici, M. Cavazzini, S. Ceragioli, F. Montanari
8
F
and G. Pozzi, Tetrahedron Lett., 1999, 40, 3647; (c) G. Pozzi, M.
Cavazzini, F. Cinato, F. Montanari and S. Quici, Eur. J. Org.
Chem., 1999, 1947; (d ) T. Nishimura, Y. Maeda, N. Kakiuchi
and S. Uemura, J. Chem. Soc., Perkin Trans. 1, 2000, 4301; (e)
S. Colonna, N. Gaggero, F. Montanari, G. Pozzi and S. Quici,
Eur. J. Org. Chem., 2001, 181; ( f ) G. Ragagnin, B. Betzemeier,
S. Quici and P. Knochel, Tetrahedron, 2002, 58, 3985.
8
F
combined DMF extracts were diluted with ether to 20.00 mL.
An aliquot (0.5 mL) was added to a toluene solution of tride-
cane (0.250 mL, 0.100 M). GC analysis showed only trans-
methyl cinnamate (100%; TON 5100 (rounded digits
1
2
3
Heck reactions: (a) J. Moineau, G. Pozzi, S. Quici and D. Sinou,
Tetrahedron Lett., 1999, 40, 7683; (b) L. Xu, W. Chen, J. F.
Bickley, A. Steiner and J. Xiao, J. Organomet. Chem., 2000,
598, 409; (c) Y. Nakamura, S. Takeuchi, S. Zhang, K. Okumura
and Y. Ohgo, Tetrahedron Lett., 2002, 43, 3053.
Suzuki reactions: (a) S. Schneider and W. Bannwarth, Helv. Chim.
Acta, 2001, 84, 735; (b) C. Rocaboy and J. A. Gladysz, Tetra-
hedron, 2002, 58, 4007.
8
included)). The C F17Br phase was taken to dryness by oil
pump vacuum (0.5 h). The tube was recharged with identical
quantities of DMF and all reactants except 7. A second cycle
was analogously conducted. Table 4: A Schlenk tube was
sequentially charged with PhB(OH)2 (1.455 g, 7.534 mmol),
1
K
3 4
PO (2.132 g, 10.05 mmol), toluene (13 mL), phenyl iodide
(
(
0.560 mL, 5.023 mmol), and a solution of 7 in CF C H
3
6
5
14 Stille, Sonogashira, and other reactions: (a) S. Schneider and W.
Bannwarth, Angew. Chem., Int. Ed., 2000, 39, 4142; S. Schneider
and W. Bannwarth, Angew. Chem., 2000, 112, 4293; (b) C.
Markert and W. Bannwarth, Helv. Chim. Acta, 2002, 6, 1877;
ꢁ6
0.000229 M; 0.020 mL, 4.58 ꢂ 10 mmol), fitted with a con-
ꢀ
denser, and placed in a 130 C oil bath. The suspension was
vigorously stirred (38 h), removed from the bath to cool, and
diluted with ether to 25.00 mL. An aliquot (0.5 mL) was added
to a solution of tridecane (0.250 mL, 0.100 M). GC analysis
showed the partial consumption of phenyl iodide (65%) and
formation of biphenyl (40%, TON 440 000).
(c) B. Betzemeier and P. Knochel, Angew. Chem., Int. Ed. Engl.,
1
997, 36, 2623; B. Betzemeier and P. Knochel, Angew. Chem.,
997, 109, 2736; (d ) S. Saito, Y. Chounan, T. Nogami, O. Ohmori
1
and Y. Yamamoto, Chem. Lett., 2001, 444.
15 (a) Y. Tian, Q. C. Yang, T. C. W. Mak and K. S. Chan, Tetrahe-
dron, 2002, 58, 3951; (b) Y. Nakamura, S. Takeuchi, K. Okumura,
Y. Ohgo and D. P. Curran, Tetrahedron, 2002, 58, 3963; (c) see
also H. Kleijn, E. Rijnberg, J. T. B. H. Jastrezebski and G.
van Koten, Org. Lett., 1999, 1, 853.
Acknowledgements
1
6
(a) M. Cavazzini, S. Quici and G. Pozzi, Tetrahedron, 2002, 58,
943; (b) A. Endres and G. Maas, Tetrahedron, 2002, 58, 3999;
(c) K. Mikami, Y. Mikami, H. Matsuzawa, Y. Matsumoto, J.
Nishikido, F. Yamamoto and H. Nakajima, Tetrahedron, 2002,
We thank the Deutsche Forschungsgemeinschaft (DFG; GL
3
3
01/3-1) and Johnson Matthey PMC (palladium loan) for sup-
port, and Dr. Gerhard Frank (Lehrstuhl f u¨ r Mikrocharakter-
isierung, Universit a¨ t Erlangen-N u¨ rnberg) for assistance with
the TEM measurements. This work was conducted as part of
a Ph.D. thesis defended in the Department of Chemistry at
the University of Utah.
5
2
8, 4015; (d ) Q. Zhang, Z. Luo and D. P. Curran, J. Org. Chem.,
000, 65, 8866; (e) R. Kling, D. Sinou, G. Pozzi, A. Choplin, F.
Quignard, S. Busch, S. Kainz, D. Koch and W. Leitner, Tetrahe-
dron Lett., 1998, 39, 9439.
(a) J. Dupont, M. Pfeffer and J. Spencer, Eur. J. Inorg. Chem.,
1
7
2001, 1917; (b) W. A. Herrmann, V. P. W. B o¨ hm and C.-P.
Reisinger, J. Organomet. Chem., 1999, 576, 23.
1
8
9
(a) A. Zapf and M. Beller, Chem. Eur. J., 2001, 7, 2908; (b) V. P.
W. B o¨ hm and W. A. Herrmann, Chem. Eur. J., 2001, 7, 4191.
M. Ohff, A. Ohff and D. Milstein, Chem. Commun., 1999, 357.
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3
9
0
48 The Z/E HC=CH assignments were based upon well established
3
4
trends in the JHH values (Z, ca. 11 Hz; E, ca. 16 Hz).
49 The Z/E C=N assignment is tentative.
50 These NMR assignments were confirmed by COSY and
HETCOR experiments.
51 This signal is assigned to the palladated aryl carbon.
41
New J. Chem., 2003, 27, 39–49
49