9-Fluorenylphosphines for the Pd-catalyzed Sonogashira, Suzuki, and Buchwald-Hartwig coupling reactions in organic solvents and water

Article abstract of DOI:10.1002/chem.200601142

The lithiation/alkylation of fluorene leads to various 9-alkyl-fluorenes (alkyl = Me. Et, /Pr, -Pr. -C₁₈H₂₅) in > 95% yields, for which lithiation and reaction with R₂PCl (R = Cy, iPr, tBu) generates 9-alkyl, 9-PR₂fluorenes which constitute electron-rich and bulky phosphine ligands. The in-situ-formed palladium-phosphinc complexes ([Na₂PdCl₄], phosphonium salt, base, substrates) were tested in the Sonogashira. Suzuki, and Buchwald-Hartwig reactions of aryl chlorides and aryl bromides in organic solvents. The Sonogashira coupling of aryl chlorides at 100-120°C leads to >90% yields with 1 mol % of Pd catalyst. The Suzuki coupling of aryl chlorides typically requires 0.05 mol % of Pd catalyst at 100°C in dioxane for quantitative product formation. To carry out "green" cross-coupling reactions in water, 9-ethylfluorenyldicyclohexylphosphine was reacted in sulphuric acid to generate the respective 2-sulfonated phosphonium salt. The Suzuki coupling of activated aryl chlorides by using this water-soluble catalyst requires only 0.01 mol% of Pd catalyst, while a wide range of aryl chlorides can be quantitatively converted into the respective coupling products by using 0.1-0.5 mol % of catalyst in pure water at 100°C. Difficult substrate combinations, such as naphthylboronic acid or 3-pyridylboronic acid and aryl chlorides are coupled at 100°C by using 0.1-0.5 mol % of catalyst in pure water to obtain the respective N-heterocycles in quantitative yields. The copper-free aqueous Sonogashira coupling of aryl bromides generates the respective tolane derivatives in > 95 % yield.

Full text of DOI:10.1002/chem.200601142

FULL PAPER
DOI: 10.1002/chem.200601142
9-Fluorenylphosphines for the Pd-Catalyzed Sonogashira, Suzuki, and
Buchwald–Hartwig Coupling Reactions in Organic Solvents and Water
Christoph A. Fleckenstein and Herbert Plenio*[a]
Abstract: The lithiation/alkylation of
fluorene leads to various 9-alkyl-fluo-
renes (alkyl=Me, Et, iPr, -Pr, -C18H25)
in >95% yields, for which lithiation
and reaction with R2PCl (R=Cy, iPr,
tBu) generates 9-alkyl, 9-PR2-fluorenes
which constitute electron-rich and
bulky phosphine ligands. The in-situ-
formed palladium–phosphine com-
plexes ([Na2PdCl4], phosphonium salt,
base, substrates) were tested in the So-
nogashira, Suzuki, and Buchwald–Hart-
wig reactions of aryl chlorides and aryl
bromides in organic solvents. The So-
nogashira coupling of aryl chlorides at
100–1208C leads to >90% yields with
1 mol% of Pd catalyst. The Suzuki
coupling of aryl chlorides typically re-
quires 0.05 mol% of Pd catalyst at
1008C in dioxane for quantitative prod-
uct formation. To carry out “green”
cross-coupling reactions in water, 9-
ethylfluorenyldicyclohexylphosphine
was reacted in sulphuric acid to gener-
ate the respective 2-sulfonated phos-
phonium salt. The Suzuki coupling of
activated aryl chlorides by using this
water-soluble catalyst requires only
0.01 mol% of Pd catalyst, while a wide
range of aryl chlorides can be quantita-
tively converted into the respective
coupling products by using 0.1–
0.5 mol% of catalyst in pure water at
1008C. Difficult substrate combina-
tions, such as naphthylboronic acid or
3-pyridylboronic acid and aryl chlor-
ides are coupled at 1008C by using 0.1–
0.5 mol% of catalyst in pure water to
obtain the respective N-heterocycles in
quantitative yields. The copper-free
aqueous Sonogashira coupling of aryl
bromides generates the respective
tolane derivatives in >95% yield.
Keywords: Buchwald–Hartwig
amination · palladium · phosphines ·
Sonogashira coupling
·
Suzuki
coupling · water
Introduction
examples of trialkyl phosphines are PCy3, PtBu3, and ligands
of the Ad2PR (Ad=1-adamantyl, R=CH2Ph, nBu)[50] type.
PtBu3, especially, is highly useful; its utility for a wide range
of different coupling reactions has been established.[51]
A significant disadvantage of Pd catalysts based on bulky
trialkylphosphines, primarily PtBu3, is the lack of flexibility
in the design of ligands and catalysts. Detailed structural
and electronic modifications (catalyst fine-tuning) are diffi-
cult to realize and this could be the reason why in cross-cou-
pling chemistry this class of ligands was “leader of the pack”
only about five years ago. Today numerous other specialized
and more powerful catalysts, often based on phosphines and
N-heterocyclic carbenes as ligands for Pd[49,52–61] are avail-
able. The advantages of a highly variable ligand backbone
are demonstrated convincingly by the enormous success of
Buchwald-type biphenyl-based phosphines,[62–64] as evi-
denced by the excellent performance of the respective Pd
complexes in numerous coupling reactions.[65,66] The high
level of sophistication concerning the fine-tuning of steric
and electronic properties of such ligands was recently dem-
onstrated by Buchwald et al. for Suzuki and amination reac-
tions.[67–69]
Trialkylphosphines with bulky substituents are highly useful
ligands for palladium-complex catalysts in various types of
cross-coupling reactions of the Suzuki,[1–11] Sonogashira,[12–21]
Heck,[22–27] Buchwald–Hartwig amination[28–34] and ether for-
mation,[35] Negishi,[36] Stille,[37–39] Hiyama,[40] Kumada,[41] a-ar-
ylation,[42,43] and carbonylation type.[44] The main reasons for
the favorable catalytic properties of trialkylphosphine–palla-
dium complexes are the electron-richness and the steric
bulk of trialkylphosphine ligands, which favor the formation
of low-coordinate and highly active Pd complexes, possibly
of the L1Pd type,[45–48] also observed with N-heterocyclic car-
benes as Pd ligands in cross-coupling reactions.[49] Prominent
[a]Dipl.-Ing. C. A. Fleckenstein, Prof. Dr. H. Plenio
Anorganische Chemie im Zintl-Institut
Petersenstrasse 18, 64287 Darmstadt (Germany)
E-mail: plenio@tu-darmstadt.de
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
Chem. Eur. J. 2007, 13, 2701 – 2716
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2701

However, as crucial proper-
ties for good ligands, such as
electron-richness and efficient
s-donation, are perfectly met in
trialkyphosphines, we became
interested in developing novel
phosphines, lacking the disad-
vantages of PtBu3. In this vain,
we want to demonstrate here
the synthesis of a new class of
Scheme 1. Reagents and conditions: a) nBuLi, RX, THF, À608C; b) nBuLi, R’2PCl, Et2O, À608C;
c) HBF4·Et2O.
trialkylphosphines based on the 9-fluorenyl group and the
application of their Pd-complexes in Sonogashira, Suzuki,
and Buchwald–Hartwig coupling reactions.
into the 9-position in virtually quantitative yield. This first
alkylation step is essential as our very first catalysis screens
had revealed that phosphines with 9-R=H produce Pd-com-
plex catalysts with modest activities in cross-coupling reac-
tions. For the introduction of the R2P group, the 9-alkylated
fluorene is again deprotonated with nBuLi and reacted with
various chlorophosphines (iPr2PCl, Cy2PCl) to result in the
respective phosphines, which are conveniently converted
into the respective phosphonium salts for easier storage and
handling.[72]
Results and Discussion
Synthesis of 9-fluorenyldialkylphosphines: The combination
of 9-fluorenyl substituents with R2P groups (Figure 1) in the
corresponding phosphines appears to have numerous advan-
tages: 1) a 9-fluorenyl group acts as an electron-rich alkyl
substituent, 2) due to the formation of a resonance-stabi-
lized anion, the 9-position is easily and selectively deproton-
ated and reacts smoothly as a soft nucleophile, 3) fluorenone
is an umpoled synthon for the
To further increase the steric bulk close to the phosphine
donor, the related 1-methyl- and 1,8-dimethyl-substituted
fluorenes were synthesized, as described below (Schemes 2
and 3; Table 10).
9-fluorenyl group, 4) the close
proximity of 6p-systems facili-
tates the stabilization of low-co-
ordinate Pd species, 5) substitu-
ents at the 1,8-position allow
the modulation of the steric
bulk close the phosphorous
donors, 6) the 2,7-positions
allow the easy introduction of
various functional groups.
Scheme 2. Reagents and conditions: a) nBuLi, EtI; b) nBuLi, Cy2PCl; c) HBF4·Et2O.
Only a few fluorenyl-based
trialkyphosphines have been
described in the literature and
none of them have been utiliz-
ed in catalysis.[70,71] Simple (no
additional substituents) 9-sub-
stituted
fluorenylphosphines
are prepared (Scheme 1) by re-
actions of the deprotonated flu-
orene (nBuLi) with various
alkyl halides (MeI, EtI, iPrI,
PhCH2Cl, C18H37Br) to selec-
tively introduce alkyl groups
Scheme 3. Reagents and conditions: a) 1,3-propanediol, ZrCl4; nBuLi, MeI, H2SO4; b) Pd(OAc)2, SIMES,
A
Cs2CO3, 3,5-Me2-C6H3B(OH)2, dioxane; c) NaClO2, H2O2; d) H2SO4; e) HI, red P, propionic acid; f) nBuLi,
EtI, THF, À608C; g) nBuLi, Cy2PCl, Et2O, À608C; h) HBF4·Et2O.
1-Methylfluorenone was prepared according to Mortier
et al.,[73] deprotonated and reacted with ethyliodide to result
in 1-methyl-9-ethylfluorene. Another sequence of deproto-
nation and quenching with Cy2PCl gave the 9,9-disubstituted
1-methylfluorene, which was isolated as the respective phos-
phonium salt after protonation with HBF4 (Scheme 2).
1,3,8-Trimethylfluorenone was prepared by a multistep re-
action (Scheme 3). Ortho lithiation of 1,3-dibromobenzene
Figure 1. Variability of 9-fluorenylphosphines.
by using the protocol of Servatovski et al. and subsequent
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Chem. Eur. J. 2007, 13, 2701 – 2716

Palladium Catalysis
FULL PAPER
Table 1. Primary Sonogashira screen for the reaction of phenylacetylene
and 4-bromotoluene by utilizing various phosphines.
quenching with DMF resulted in 1,6-dibromobenzalde-
hyde,[74] which was protected as an acetal[75] and treated with
nBuLi, followed by quenching the lithiated intermediate
with methyliodide to yield the desired deprotected 1-bromo-
6-methylbenzaldehyde in nearly quantitative yield. The
Suzuki coupling of the bromo-aldehyde with 3,5-dimethyl-
phenylboronic acid[76] afforded 3,3’,5’-trimethylbiphenylcar-
baldehyde, which was converted into the respective carbox-
ylic acid with H2O2/NaClO2 by using the method of Dalca-
nale.[77] The resulting carboxylic acid gave 1,3,8-trimethyl-
fluorenone in quantitative yield after condensation in con-
centrated sulfuric acid. By using the method of
Carruthers,[78] the desired fluorene derivative was obtained
by reduction of the fluorenone with HI and red phospho-
rous in propionic acid. Deprotonation of 1,3,8-trimethyl-
fluorenone with nBuLi by using the standard protocol and
quenching with ethyliodide gave the 9-ethylated fluorene
derivative. Following the next deprotonation with nBuLi
and reaction with Cy2PCl, the respective 9-fluorenylphos-
phine was isolated as the phosphonium salt.
Phosphine
ton[a,b]
C18FluPCy2 (17i)
EtFluPCy2 (17c)
MeFluPCy2 (17a)
C18FluPiPr2 (17j)
Ad2PBn
MeFluPiPr2 (17b)
EtFluPiPr2 (17d)
1-Me-9-EtFluPCy2 (17o)
iPrFluPCy2 (17e)
1,3,8-Me3EtFluPCy2 (17p)
iPrFluPiPr2 (17 f)
HFluPtBu2 (17h)
PhFluPiPr2 (17 q)
5900
5600
5600
5500
3600
3500
3200
2600
906
850
500
330
250
[a]4-Bromotoluene (10 mmol), phenylacetylene (11 mmol), iPr2NH
(10 mL), 508C, 24 h. Catalyst: [Na2PdCl4]/ligand/CuI 4:8:3, catalyst mix-
ture in iPr2NH2Br, max. ton=15000. [b]Average of two runs. Deter-
mined by the mass of the isolated ammonium salt.
To demonstrate the variability of the 9-fluorenylphos-
phine chemistry, we have also synthesized a 2,7-dibromo de-
rivative, which enables the easy introduction of additional
functional groups at the 2,7-positions (Scheme 4).
surprise, the performance of the 1,8-Me2-substituted 9-fluo-
renylphosphines 17p is poor (ton=850), while the related
compound with a single methyl group at the 1-position
shows a good performance (ton=2600), even though it is
not among the top performers. However, given the signifi-
cantly increased effort required for the synthesis of the 1-
and the 1,8-substituted fluorenes, we did not consider it
worthwhile to study the performance of these phosphines in
more detail.
Among the best phosphines in Table 1, EtFluPCy2 17c
was tested for the conversion of a number of aryl bromides
(Table 2). Quantitative yields are possible with various acti-
Scheme 4. Reagents and conditions: a) bromine, FeCl3, CHCl3, 08C–RT;
b) LDA, Et2O, À608C, iPr2PCl, HBF4·Et2O.
Pd complexes of 9-fluorenyldialkylphosphines in the Sono-
gashira reaction: As a first test of the performance of the
various Pd 9-fluorenylphosphine complexes, we determined
the ton (turnover number) for the Sonogashira cross-cou-
pling of phenylacetylene and 4-bromotoluene, applying the
conditions described previously by us (Table 1).[17] In this
first screen, the nature of the groups 9-R and 9-PR’2 were
varied. There are a number of phosphines (9-R=H, Ph, iPr,
tBu) that display ton of smaller than 1000. This is signifi-
cantly smaller than that of our reference phosphine Ad2PBn
(ton=3200). Consequently, these phosphines were excluded
from future catalytic test reactions. There are several phos-
phines for which the performance is comparable or superior
to that of our reference system. The best 9-fluorenylphos-
phines are characterized by an unbranched alkyl group (R=
Me, Et, etc.) at the 9-position, -PiPr2 or -PCy2 units at the
Table 2. Sonogashira coupling of various aryl bromides with phenylacety-
lene[a] by using EtFluPCy2·HBF4.
Entry Aryl bromide
Product
t
Yield
[h] [%][b]
4-bromoacetophe-
none
1
2
3
4
3
ꢀ99
4-bromoanisol
24 ꢀ99
24 ꢀ99
24 ꢀ99
4-bromodimethylani-
line
4-bromotoluene
5
2-bromotoluene
24
95
phosphorous atom.
2
À
It is known that sp CH bonds close to the binding site of
palladium can easily undergo CH-activation reactions,[79,80]
[a]Aryl bromide (10 mmol), phenylacetylene (11 mmol), HN iPr2
(10 mL), 508C, 24 h. Catalyst: [Na2PdCl4](0.02 mol%), phosphine
(0.04 mol%), CuI (0.015 mol%), catalyst mixture in iPr2NH2Br.
[b]Average of two runs, determined by GC analysis (hexadecane as an
internal standard) and by the mass of the isolated ammonium salt. Both
analytical methods gave similar results.
3
[68]
À
which is less likely with sp CH bonds. With this in mind
and with a view to further increasing the steric bulk of the
phosphines, we synthesized two fluorenyl dialkylphosphines
with methyl groups in the 1- or in the 1,8-position. To our
Chem. Eur. J. 2007, 13, 2701 – 2716
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www.chemeurj.org
2703

H. Plenio and C. A. Fleckenstein
vated and deactivated aryl bromides when applying
0.02 mol% of Pd complex. To test the limits of catalytic per-
formance, the catalyst concentration was decreased to
0.0033% (Table 3). Even at such low catalyst concentrations,
Pd complexes of 9-fluorenyldialkylphosphines in the Suzuki
reaction: We first tested Pd complexes of several phos-
phines, EtFluPCy2 17c, BnFluPCy2 17k, iPrFluPCy2 17e,
and MeFluPiPr2 17b, in the Suzuki coupling. In the reaction
of 4-chloroacetophenone with
4-tolylboronic acid by using
Table 3. Sonogashira coupling of aryl bromides. Determination of ton.[a]
0.5 mol%
[Na2PdCl4]and
[c]
Entry Aryl bromide
Acetylene
R3PH+[b] Pd [mol%] t [h]Yield [%]
ton
1 mol% phosphonium salt with
Cs2CO3 in dioxane at 808C, the
following yields were observed:
17c (77%), 17k (13%), 17e
(5%), and 17b (21%). Again,
the phosphine with a 9-Et and
the 9-PCy2 group is the top per-
former in this series. It is inter-
esting to observe that too much
bulk at the 9-position (iPr, Bn)
appears to be detrimental for
1
2
3
4
5
6
7
8
9
bromobenzene
bromobenzene
2-bromotoluene
2-bromo-m-xylene
phenylacetylene
phenylacetylene
phenylacetylene
phenylacetylene
a
b
a
a
b
c
a
b
d
0.0033
0.0033
0.0033
0.0067
0.0033
0.0033
0.0033
0.0033
0.0033
16
16
16
16
16
20
20
20
20
81
88
83
57
51
41
78
84
43
24300
26400
24900
8550
15300
12200
23300
25200
12600
2-bromo-benzotrifluoride phenylacetylene
4-bromoanisol
4-bromoanisol
4-bromoanisol
4-bromoanisol
phenylacetylene
phenylacetylene
phenylacetylene
phenylacetylene
[a]Aryl bromide (10 mmol), acetylene (11 mmol), HN iPr2 (10 mL), 808C, 24 h. Catalyst: [Na2PdCl4]/phospho-
nium salt/CuI 4:8:3, catalyst mixture in iPr2NH·HBr. [b]Ligand: a: MeFluP iPr2 (17b); b: EtFluPiPr2 (17d); c:
MeFluPCy2 (17a); d: iPrFluPiPr2 (17 f). [c]Average of two runs.
the
coupling
reactions
(Table 5), while too little bulk
deactivated substrates can be converted in more than 80%
yield with ton around 8.500 for sterically hindered substrates
and up to 25.000 with deactivated substrates (4-bromoani-
sol). The turnover frequencies (tof) for two Sonogashira re-
actions applying MeFluPiPr2 were determined at 808C: 2-
bromotoluene and phenylacetylene at 0.0033 mol% Pd cata-
lyst concentration yield tof of 3600 hÀ1; the analogous reac-
tion with 4-bromoanisol gives tof of 2650 hÀ1.
of substituents directly attached to the phosphorous atom
(9-PiPr2) is not favorable. An amount of 0.05 mol% of cata-
lyst is sufficient to reach full conversion during 24 h; only 4-
chloroanisol requires 0.1 mol% of catalyst to reach full con-
version.
Pd complexes of 9-fluorenyldialkylphosphines in the Buch-
wald–Hartwig reaction: To demonstrate the broad applica-
bility of the fluorenyl-based phosphines for coupling reac-
tions, we carried out a few test reactions for the amination
of aryl bromides and chlorides.[28,34,66,86] When applying the
conditions recently reported by Beller et al. without further
optimization,[63] the screening of several fluorenyldialkyl-
phosphines in the reaction of 4-chlorotoluene with 3,5-dime-
thylaniline revealed EtFluPCy2 as the most active ligand for
palladium (Table 6, entry 1). Typical catalyst loadings of be-
tween 0.1–0.5 mol% Pd were applied at 1208C by using
NaOtBu as the base in toluene (Table 6). Overnight reac-
tions of various aryl bromides gave quantitative conversion
of different amines (aniline, morpholine, a-methylbenzyla-
mine). Activated and nonactivated aryl chlorides were con-
verted into the respective anilines under the same conditions
in quantitative yields.
Finally, the Sonogashira coupling of phenylacetylene with
several aryl chlorides was tested (Table 4). Excellent conver-
Table 4. Sonogashira reactions with aryl chlorides.[a]
[b]
Entry
Aryl chloride
T [8C]
t [h]Yield [%]
1
2
3
4
5
6
7
4-chloroanisol
110
100
100
100
120
120
120
16
12
12
12
16
16
20
43, 44,[c] 47,[d] 23[e]
4-nitrochlorobenzene
4-chloroacetophenone
4-CF3-chlorobenzene
chlorobenzene
4-chlorotoluene
4-chloroanisol
88
94
92
87
91
73
[a]Aryl chloride (1.5 mmol), phenylacetylene (2.1 mmol), Na 2CO3
(3 mmol), DMSO (5 mL), catalyst: 1 mol% [Na2PdCl4]/ligand/CuI 4:8:3;
phosphonium salt: MeFluiPr2·HBF4 (17 b·HBF4). Reaction conditions
have not been optimized. [b]Average of two runs. Purified by chroma-
tography through a short silica pad. Eluent: cyclohexane/ethyl acetate
100:2. [c]Ligand: EtFluPCy 2 (17c). [d]Ligand: BnFluPCy 2 (17 k).
[e]Ligand: Ad 2PBn.
Sulfonation of 9-ethylfluorenyldicyclohexylphosphine and
the catalytic activity of the respective Pd complexes in the
Sonogashira and the Suzuki coupling in water: Water is a
cheap, inflammable, and nontoxic solvent from which organ-
ic products are easily separated. It is therefore an attractive
target to render palladium–phosphine complexes water-solu-
ble in order to allow cross-coupling reactions in this “green”
solvent.[87,88] Only a few examples of aqueous Suzuki cou-
pling of aryl chlorides have been described, notable in this
respect are recent publications by Buchwald et al.[89,90] and
Fu et al.[11] who report on the facile Suzuki coupling in
sions of the reactants were observed for all substrates at
100–1208C with 1 mol% of catalyst. Again, the 9-fluorenyl-
phosphine-based palladium catalysts compare favorably
with other catalytic systems described by us and by others
for the conversion of aryl chlorides.[14,19,81–85]
water and water/dioxane for
a broad range of sub-
strates.[4,91–93] Consequently, to render the 9-fluorenylphos-
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Chem. Eur. J. 2007, 13, 2701 – 2716

Palladium Catalysis
FULL PAPER
Table 5. Suzuki reaction with aryl chlorides.[a]
pling reactions of 1-naphthyl-
boronic acid (Table 7, en-
tries 19, 20, 23) occur at elevat-
ed temperatures with 0.5 mol%
of catalyst to produce the re-
spective coupling products in
nearly quantitative yields.
Entry
Aryl chloride
Boronic acid
Product
Catalyst
[mol%][b]
t [h]Conversion
G
[%][c]
0.5
0.05
2
ꢀ99
ꢀ99
24
1
N-Heterocycles, such as pyri-
dines, are an important class of
substances for pharmaceutical
applications.[95] Due to the coor-
dinating nature of pyridines
such compounds are a challeng-
ing class of substrates in the
Suzuki coupling of aryl chlor-
ides.[68,96–98] Recently, Fu et al.
and Buchwald et al. reported
catalysts that are able to couple
various substituted pyridylbor-
onic acids and aryl chlorides in
90–95% yield by using 2–
3 mol% of Pd catalyst at 90–
1008C during 24 h in n-butanol
or in dioxane/water as sol-
vents.[11,68] Encouraged by the
high activity of the Pd com-
plexes of the sulfonated fluore-
0.5
0.05
2
24
ꢀ99
ꢀ99
2
3
0.5
0.05
2
24
ꢀ99
ꢀ99
0.5
0.1
0.05
0.5
0.05
5
20
24
5
ꢀ99
ꢀ99
65
4
5
ꢀ99
24
ꢀ99
[a]Aryl chloride (1 mmol), boronic acid (1.5 mmol), Cs 2CO3 (2.0 mmol), dioxane (5 mL), 1008C, reaction con-
ditions and the amount of catalyst have not been optimized. [b]Catalyst: [Na 2PdCl4]/ligand 1:2, ligand: Et-
FluPCy2 (17c). [c]Average of two runs, determined by GC analysis using hexadecane as an internal standard.
phines water soluble, the aromatic ring was sulfonated by
treatment of the phosphonium salt 17c with concentrated
sulphuric acid, resulting in the formation of the respective 2-
sulfonated fluorene in 77% yield (Scheme 5).
nene 18, we also tried coupling reactions of pyridylboronic
acid in the aqueous Suzuki coupling (Table 7, entries 24–28).
Activated aryl chlorides (2-CF3-chlorobenzene, Table 7,
entry 26) require only 0.1 mol% of catalyst at 1008C for
quantitative conversion, while nonactivated (chlorobenzene)
aryl chlorides work with 0.5 mol% (entry 25). It is remarka-
ble that even pyridyl chlorides can be coupled with pyridyl
boronic acids to result in the formation of the respective bi-
pyridines by applying 0.5 mol% of Pd catalyst (entries 27,
28), even at 0.1 mol%, a respectable 43% yield is observed.
It is obvious from our experiments carried out in pure water
as the solvent that the catalysts reported appear to be the
most active ones reported so far for this class of challenging
substrates. In conclusion, we were able to demonstrate the
excellent activity of the sulfonated 18 in the aqueous Suzuki
coupling for a wide range of different substrates.
We studied a range of different aryl bromides and aryl
chlorides in Suzuki coupling reactions by using 4-toluene-
boronic acid, 1-naphthylboronic acid, and 3-pyridylboronic
acids (Table 7). Aryl bromides react smoothly at room tem-
perature when using 0.1 mol% of catalyst to form the cou-
pling product in quantitative yield, while a sterically de-
manding substrate (1-bromo-2,6-dimethylbenzene) requires
1 mol% and overnight reaction at the same temperature. A
variety of bases (NaOH, K2CO3, Cs2CO3, K3PO4) were used,
significant differences in the outcome of the coupling reac-
tion were not observed and only KF gave poor results in
aqueous Suzuki reactions. The addition of a surfactant (Lab-
rasol)[94] leads to slightly improved yields in some cases. The
aryl chlorides listed in Table 7 are quantitatively converted
by using between 0.1–1 mol% of catalyst during 1–2 h at
1008C. Activated aryl chlorides, such as 4-chlorobenzonitrile
(entry 11), require only 0.1 mol% of catalyst to produce the
coupling product in quantitative yield within 30 min. Cou-
We also studied the copper-free Sonogashira coupling
(also referred to as the Cassar–Heck coupling) by using vari-
ous aryl bromides in water/isopropanol; yields in excess of
95% are observed for a variety of substrate combinations
(Table 8),[18,99–102] while aryl chlorides could not be reacted
under these conditions.
Conclusions
The 9-fluorenylphosphines described here, constitute a ver-
satile new class of phosphorous ligands, for which the palla-
dium complexes were shown to be high activity catalysts for
the Buchwald–Hartwig, Sonogashira, and Suzuki coupling of
Scheme 5. Reagents and conditions: a) H2SO4, 408C.
Chem. Eur. J. 2007, 13, 2701 – 2716
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2705

H. Plenio and C. A. Fleckenstein
Table 6. Buchwald–Hartwig amination[a] of aryl bromides and chlorides.
Suzuki coupling in pure water
with a wide range of substrates,
including sterically demanding
or heterocyclic boronic acids,
which exceed those recently re-
ported by others for the notori-
ously difficult synthesis of nitro-
gen-containing heterocycles.
Entry
Aryl halide
Amine
Product
Catalyst
[mol%]
t [h]Conversion
G
[%][b]
0.5
12
12
12
12
16
<5
<5
<5
0.5[c]
0.5[d]
0.5[e]
1
2
3
0.1
0.5
3
2
ꢀ99
ꢀ99
Experimental Section
General experimental: All chemicals
were purchased as reagent grade from
commercial suppliers and used without
further purification, unless otherwise
noted. THF was distilled over potassi-
um and benzophenone under an argon
atmosphere, diethyl ether was distilled
over sodium/potassium alloy and ben-
zophenone under an argon atmos-
phere. Diisopropylamine was dried
over potassium hydroxide, dioxane
was dried over calcium hydride.
Proton (1H NMR), carbon (13C NMR)
and phosphorus (31P NMR) NMR
spectra were recorded on Bruker
DRX 500 at 500, 125.75, and
202.46 MHz, respectively or on Bruker
DRX 300 at 300 and 75.07 MHz, re-
spectively. The chemical shifts are
given in parts per million (ppm) on
the delta scale (d) and are referenced
to TMS (d=0 ppm), 1H NMR and
65% aq H3PO4 (d=0 ppm), 31P NMR.
Abbreviations for NMR data: s=sin-
glet, d=doublet, t=triplet, q=quar-
tet, dd=doublet of doublets, dt=dou-
blet of triplets, dq=doublet of quar-
tets, tt=triplet of triplets, m=multip-
let. IR spectra were recorded on
Perkin–Elmer 1600 series FTIR. Mass
spectra were recorded on a Finigan
MAT 95 magnetic sector spectrometer.
TLC was performed by using Fluka
silica gel 60 F254 (0.2 mm) on alumi-
num plates. Silica-gel columns for
chromatography were prepared with
E. Merck silica gel 60 (0.063–0.20
mesh ASTM).
4
5
0.5
0.5
2
6
ꢀ99
91
6
7
0.25
0.5
2
2
ꢀ99
ꢀ99
8
0.5
12
ꢀ99
9
0.5
0.5
12
12
ꢀ99
10
48
[a]Toluene (5 mL), aryl halide (5 mmol), amine (6 mmol),NaO tBu (6 mmol), Pd/ligand 1:2, phosphonium salt:
EtFluPCy2·HBF4 (17c·HBF4), 1208C, reaction conditions have not been optimized. [b]Average of two runs,
determined by GC analysis using hexadecane as internal standard. [c]Ligand: PhFluP iPr2 (17q). [d]Ligand:
iPrFluPiPr2 (17 f). [e]Ligand: BnFluPCy 2 (17k).
aryl chlorides. Fluorenyl-based phosphines are trialkylphos-
General procedure for the preparation of 9-substituted fluorenes
(Table 9): nBuLi (40 mmol, 2.5m in hexane) was added at À608C to a so-
lution of 9H-fluorene (30 mmol) in dry THF (60 mL). The solution im-
mediately turned brownish and was stirred for 1.5 h at RT. After cooling
to À608C again, the reaction mixture was quenched with alkylhalide
(45 mmol, 1.5 equiv), stirred for 10 min at À608C, then for an additional
2 h at RT. Water (100 mL) was added to the reaction mixture which was
then extracted with diethyl ether (3”100 mL). The combined organic
phases were subsequently washed with an aqueous solution of Na2S2O3,
brine, and dried over MgSO4. After filtration and removal of the volatiles
under vacuum, the crude product was purified by filtration on a short
silica-gel pad (5 cm, eluent: cyclohexane) and concentrated under
vacuum, resulting in the pure 9-substituted fluorenes typically in near
quantitative yield.
phines with excellent electron-donating properties and large
steric bulk similar to PtBu3. However, in contrast to the
latter ligand, the fluorenylphosphines can be modified easily
at various positions of the fluorene to allow the design of
numerous modified catalysts. The catalytic performance of
the Pd complexes of the first generation of 9-alkyl, 9-di-
alkylphosphinofluorenes reported here is already impressive.
Aryl chlorides can be coupled in quantitative yields in the
Sonogashira, Suzuki, and Buchwald–Hartwig reaction in or-
ganic solvents or in water by using between 0.01 and
1 mol% of catalyst for the various reactions and substrates
listed here. Noteworthy, are the excellent activities of Pd
complexes of sulfonated 9-dialkylphosphinofluorenes for the
9-Methylfluorene (2a): Fluorene (1a) (15.0 g, 90.4 mmol), nBuLi
(48.1 mL, 120 mmol, 2.5m in hexane), iodomethane (19.3 g, 136 mmol).
2706
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 2701 – 2716

Palladium Catalysis
FULL PAPER
Table 7. Suzuki coupling of aryl bromides and aryl chlorides in water.
[f]
Entry
Halide
Boronic acid
Product
Pd [mol%]Conditions
Yield [%]
0.1
0.01
0.005
RT, 20 h
1008C, 2 h
1008C, 3.5 h
ꢀ99
ꢀ99
ꢀ99
1
0.5
0.5
908C, 45 min
908C,30 min[a]
ꢀ99
ꢀ99
2
3
0.5
508C, 1.5 h
ꢀ99
4
5
6
7
0.5
0.5
1
508C, 4 h
508C, 1.5 h
RT, 20 h
RT, 3 h
ꢀ99
ꢀ99
ꢀ99
ꢀ99
0.25
0.1
0.1
RT, 2.5 h
50
66
RT, 2.5 h[a]
8
1
1008C, 20 h
ꢀ99
9
0.5
1
658C, 20 h
908C, 20 h
ꢀ99
ꢀ99
10
0.05
0.1
1
1008C, 2 h
ꢀ99
ꢀ99
ꢀ99
ꢀ99
ꢀ99
ꢀ99
ꢀ99
ꢀ99
92
1008C, 30 min
408C, 10 h
1
RT, 20 h[a]
11
12
0.1
0.1
0.1
0.1
0.5
0.5
1008C, 45 min[b]
1008C, 1 h[c]
1008C, 1 h[d]
1008C, 25 min[e]
908C, 4 h
908C, 4 h[a]
98
0.5
1
1008C, 2 h
ꢀ99
ꢀ99
RT, 20 h[a]
13
14
15
0.5
1
1008C, 2.5 h[a]
ꢀ99
ꢀ99
RT, 20 h[a]
0.5
1008C, 90 min
ꢀ99
Chem. Eur. J. 2007, 13, 2701 – 2716
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2707

H. Plenio and C. A. Fleckenstein
Table 7. (Continued)
[f]
Entry
Halide
Boronic acid
Product
Pd [mol%]Conditions
Yield [%]
ꢀ99
16
1
1008C, 24 h
1
0.5
908C, 30 min
RT, 4 h
ꢀ99
ꢀ99
17
18
19
0.5
0.5
908C, 20 h
658C, 20 h
74
80
20
0.5
908C, 20 h
ꢀ99
21
22
0.5
0.5
1008C, 12 h[a]
1008C, 12 h[a]
ꢀ99
ꢀ99
23
0.5
1008C, 12 h[a]
ꢀ99
24
25
0.1
0.5
1008C, 12 h[a]
1008C, 12 h[a]
ꢀ99
ꢀ99
26
27
28
0.1
0.5
1008C, 12 h[a]
1008C, 12 h[a]
ꢀ99
ꢀ99
0.5
0.1
1008C, 20 h[a]
1008C, 20 h[a]
ꢀ99
43
29
30
1.0
1008C, 20 h[a]
97
1.0
0.5
1008C, 20 h[a]
1008C, 20 h[a]
96
90
Reaction conditions: aryl halide (1.0 equiv), boronic acid (1.2 equiv), K2CO3 (3.2 equiv), degassed water (4 mL, mmolÀ1), cat. [Na2PdCl4], ligand 18,
ligand/Pd 2:1. Reaction times and temperatures were not optimized. [a]Additive: Labrasol (0.05 mL). [b]Aryl halide (1 equiv), boronic acid (1.2 equ iv),
CsCO3 (3.2 equiv). [c]Aryl halide (1 equiv), boronic acid (1.2 equiv), KF (3.2 equiv). [d]Aryl halide (1 equiv), boronic acid (1.2 equiv), NaOH
(3.2 equiv). [e]Aryl halide (1 equiv), boronic acid (1.2 equiv), K 3PO4 (3.2 equiv). [f]Average of two runs, determined by GC analysis using hexadecane
as an internal standard.
(d, 3J=5.5, 7.5 Hz, 3H; CH3); 13C{1H) NMR (125.77 MHz, CDCl3): d=
Product 2a was isolated as a yellowish waxy solid (16.2 g, quant.). The
analytical data were identical to those in the literature.[103]1 H NMR
149.4, 141.0, 127.4 (2”), 124.5, 120.3, 42.9, 18.6 ppm.
(500 MHz, CDCl3): d=7.74 (d, 3J=7.5 Hz, 2H; Ar), 7.49–7.48 (m, 2H;
Ar), 7.34–7.28 (m, 4H; Ar), 3.92 (q, 3J=7.5 Hz, 1H; 9HFlu), 1.50 ppm
9-Ethylfluorene (2b): Fluorene (1a) (5.0 g, 30.1 mmol), nBuLi (16 mL,
40 mmol, 2.5m in hexane), iodoethane (7.04 g, 45.1 mmol). Product 2b
2708
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Chem. Eur. J. 2007, 13, 2701 – 2716

Palladium Catalysis
FULL PAPER
Table 8. Sonogashira reaction of aryl bromides in an aqueous system.[a]
[b]
Entry
Aryl bromide
Acetylene
Product
t [h]Conversion [%]
Yield [%][c]
97
1
1
ꢀ99
ꢀ99
ꢀ99
2
3
1.5
2
98
95
4
4
ꢀ99
95
5
6
4
4
ꢀ99
ꢀ99
94
95
[a]Aryl bromide (1 mmol), acetylene (1.2 mmol), Cs 2CO3 (1.5 mmol), [Na2PdCl4](1 mol%), ligand ((9-ethyl-2-sulfonic acid-fluorenyl)dicyclohexyl phos-
phonium HSO4À, 2 mol%); 9-SO3H-EtFluPCy2·H2SO4 (18), H2O/isopropanol (4 mL, 1:1), 1008C. Reaction times and temperatures were not optimized.
[b]Average of two runs, determined by GC analysis using hexadecane as an internal standard. [c]Average of two runs. Purified by column chromatogra-
phy (silica gel, eluent: cyclohexane/ethyl acetate 10:1).
3J=7.5 Hz, 3H; CH3); 13C{1H} NMR (125.77 MHz, CDCl3): d=147.7,
141.1, 126.8, 126.7, 124.4, 119.8, 47.4, 35.4, 19.0, 14.4 ppm.
Table 9. 9-Substituted fluorenes.
9-n-Octadecylfluorene (2e): Fluorene (1a) (7.0 g, 42.1 mmol), nBuLi
(17.35 mL, 43.4 mmol, 2.5m in hexane), 1-bromooctadecane (14.53 g,
43.6 mmol). Following the usual workup, 2e was isolated as a white solid
(15.5 g, 88%). Rf =0.73 (cyclohexane); 1H NMR (300 MHz, CDCl3): d=
7.76–7.73 (m, 2H; Ar), 7.52–7,49 (m, 2H; Ar), 7.38–7,27 (m, 4H; Ar),
3.96 (t, 3J=6.0 Hz, 1H; 9HFlu), 3.02–1.95 (m, 2H; CH2), 1.31–1.14 (m,
32H; CH2), 0.88 ppm (t, 3J=6.6 Hz, 3H; CH3); 13C{1H} NMR
(75.42 MHz, CDCl3): d=147.7, 141.1, 126.8, 126.7, 124.3, 119.8, 47.5, 33.1,
31.9, 30.0, 29.7 (CH2, 7”), 29.6 (CH2, 3”), 29.4, 29.3, 25.7, 22.7,
14.1 ppm.
Compound
R1
R2
R3
R4
2a
2b
2c
2d
2e
2 f
2g
2h
H
H
H
H
H
H
Me
Me
Me
Et
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
Me
iPr
nPr
C18
Bn
Et
9-Benzylfluorene (2 f): Fluorene (1a) (19.0 g, 114 mmol), nBuLi
(54.9 mL, 137 mmol, 2.5m in hexane), benzylchloride (17.03 mL,
148 mmol). After the usual workup, 2a was isolated and recrystallized
from heptane to give a white solid (25.8 g, 88.4%). The analytical data
were identical to those in the literature.[106]1 H NMR (500 MHz, CDCl3):
d=7.72 (d, 3J=8 Hz, 2H; Ar), 7.37–7.13 (m, 11H; Ar), 4.22 (t, 3J=
7.5 Hz, 9H; Flu), 3.10 ppm (d, 3J=7.5 Hz, 2H; CH2); 13C{1H} NMR
(125.77 MHz, CDCl3): d=146.8, 140.8, 139.8, 129.5, 128.3, 127.1, 126.6,
126.4, 124.8, 119.8, 48.7, 40.1 ppm.
Et
was isolated as yellow oil (5.7 g, 97%). Analytical data were identical to
those in the literature.[104]1 H NMR (500 MHz, CDCl3): d=7.73 (d, 3J=
10.0 Hz, 2H; Ar), 7.50–7.48 (m, 2H; Ar), 7.36–7.27 (m, 4H; Ar), 3.94 (t,
3J=6.0 Hz, 1H; 9HFlu), 2.07 (dq, J=5.5, 7.0 Hz, 2H; CH2), 0.71 ppm (t,
1-Methyl-9-ethylfluorene (2g): Fluorene (1b) (3.01 g, 16.7 mmol), nBuLi
(8.06 mL, 20 mmol, 2.5m in hexane), 1-iodoethane (3.39 g, 21.7 mmol).
Product 2h was isolated to give a colorless oil (3.33 g, 95%). 1H NMR
(500 MHz, [D6]acetone): d=7.79–7.77 (m, 1H; Ar), 7.64 (d, 3J=7.5 Hz,
1H; Ar), 7.55–7.53 (m, 1H; Ar), 7.34–7.24 (m, 3H; Ar), 7.10–7.08 (m,
1H; Ar), 4.11 (t, 3J=4.5 Hz, 1H; 9HFlu), 2.46 (s, 3H; CH3), 2.26–2.20
(m, 2H; CH2), 0.35 ppm (t, 3J=7.5 Hz, 3H; CH3); 13C{1H} NMR
(125.75 MHz, [D6]acetone): d=148.0, 145.4, 142.6, 142.4, 135.2, 129.4,
128.0, 127.7, 127.6, 124.9, 120.4, 118.1, 48.5, 24.3, 19.2, 8.3 ppm.
3
3J=7.5 Hz, 3H, CH3); 13C{1H} NMR (125.77 MHz, CDCl3): d=147.2,
141.3, 126.8, 126.7, 124.3, 119.7, 48.5, 25.7, 9.7 ppm.
9-Isopropylfluorene (2c): Fluorene (1a) (15.0 g, 90.4 mmol), nBuLi
(48.1 mL, 120 mmol, 2.5m in hexane), 2-iodopropane (14.0 mL,
139.6 mmol). Product 2c was isolated as a yellowish solid (18.7 g, quant.).
The analytical data were identical with these to be found in the litera-
ture.[103]1 H NMR (500 MHz, CDCl3): d=7.73 (d, 3J=7.5 Hz, 2H; Ar),
7.52–7.51 (m, 2H; Ar), 7.37–7.25 (m, 4H; Ar), 3.91 (d, 3J=3.0 Hz, 1H;
9HFlu), 2.59–2.52 (m, 1H; CH), 0.84 ppm (d, 3J=7.0 Hz, 6H; CH3);
13C{1H} NMR (125.77 MHz, CDCl3): d=146,7, 142.1, 127.3, 127.1, 125.2,
120.0, 54.2, 32.6, 19.5 ppm (CH3, 2”).
1,3,8-Trimethyl-9-ethylfluorene (2h): Fluorene (1c) (1.2 g, 5.77 mmol),
nBuLi (3.0 mL, 2.5m in hexane, 7.5 mmol), 1-iodoethane (1.35 g,
8.65 mmol). Product 2h was isolated to give a white solid (1.36 g, quant.).
1H NMR (300 MHz, CDCl3): d=7.55 (d, 3J=7.2 Hz, 1H; Ar), 7.40 (s,
1H; Ar), 7.27 (t, 3J=7.2 Hz, 1H; Ar), 7.08 (d, 3J=7.5 Hz, 1H; Ar), 6.93
(s, 1H; Ar), 4.23 (t, 3J=4.2 Hz, 1H; 9HFlu), 2.49 (s, 3H; CH3), 2.46 (s,
9-n-Propylfluorene (2d): Fluorene (1a) (15.0 g, 90.4 mmol), nBuLi
(48.1 mL, 120 mmol, 2.5m in hexane), 1-iodopropane (20.8 g,
122.3 mmol). Product 2d was isolated as
quant.). The analytical data were identical to those found in the litera-
ture.[105]1 H NMR (500 MHz, CDCl3): d=7.73 (d, 3J=7.0 Hz, 2H; Ar),
7.51–7.49 (m, 2H; Ar), 7.36–7.27 (m, 4H; Ar), 3.97 (t, 3J=6.0 Hz, 1H;
9HFlu), 1.99–1.94 (m, 2H; CH2), 1.27–1.19 (m, 2H; CH2), 0.86 ppm (t,
a yellowish solid (18.6 g,
3
3H, CH3), 2.43 (s, 3H, CH3), 2.30 (dq, J=4.2 Hz, 2H; CH2), 0.19 ppm (t,
3J=7.8 Hz, 3H; CH3); 13C{1H} NMR (75.4 MHz, CDCl3): d=145.3, 142.1,
136.7, 134.1, 133.7, 129.6, 128.5, 127.0, 118.0, 117.2, 46.7, 21.5, 21.1, 19.2,
19.1, 7.2 ppm.
Chem. Eur. J. 2007, 13, 2701 – 2716
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2709

H. Plenio and C. A. Fleckenstein
1-Methylfluorene (1b): 1-Methylfluoren-9-one (8) (6.8 g, 35 mmol) was
dissolved in propionic acid (450 mL). Red phosphorus (7.4 g) and con-
centrated HI (100 mL) were added and the reaction mixture was refluxed
for 24 h. Quantitative conversion was shown by TLC. The reaction mix-
ture was diluted with water (500 mL), neutralized with NaOH, and ex-
tracted with Et2O (4”125 mL). The combined organic layers were
washed with brine (2”125 mL), dried over MgSO4, filtered, and the vola-
tiles removed in vacuo to afford 6.1 g (97%) of 1b as a white solid. The
analytical data were consistent with the literature.[107,108]1 H NMR
(500 MHz, [D6]acetone): d=7.82 (d, 3J=8.0 Hz, 1H; Ar), 7.67 (d, 3J=
7.5 Hz, 1H; Ar), 7.58–7.56 (m, 1H; Ar), 7.36–7.34 (m, 1H; Ar), 7.30–7.26
(m, 2H; Ar), 7.12–7.10 (m, 1H; Ar), 3.78 (s, 2H; 9HFlu), 2.39 ppm (s,
3H; CH3); 13C{1H} NMR (125.77 MHz, [D6]acetone): d=144.4, 143.3,
143.3, 142.5, 135.5, 128.9, 128.4, 127.9, 127.9, 126.3, 121.2, 118.6, 36.6,
19.2 ppm.
21.7, 21.4 ppm; IR (KBr): n˜ =3436 (br), 2920, 2858, 2765, 1689, 1677,
1600, 1584, 1463, 1191 cmÀ1
.
3,3’,5’-Trimethylbiphenylcarboxylic acid (15): Aldehyde 14 (2.75 g,
11.5 mmol) was dissolved in acetonitrile (18 mL, technical grade).
NaH2PO4 (0.453 g, dissolved in 5.5 mL water) and H2O2 (1.93 mL of a
30% solution) were added. The reaction mixture was cooled to 08C (ice/
water) and NaClO2 (2.2 g, dissolved in 19 mL water) was added within
60 min by a syringe. The solution was left to warm to ambient tempera-
ture and was stirred for an additional 3.5 h. Then Na2SO3 (100 mg) was
added and the resulting reaction mixture was stirred for 5 min. After
treatment with HCl (50 mL of a 10% solution), the reaction mixture was
extracted with ether (3”75 mL). The combined organic phase was ex-
tracted with NaOH (4”75 mL, 1n). The combined NaOH layers were
acidified with HCl to pH 1 and extracted again with Et2O. The combined
organic layers were dried over MgSO4 and the volatiles were removed in
vacuo to afford 15 (2.95 g, quant.) as a colorless oil. The product was
used without any further purification. 1H NMR (300 MHz, CDCl3): d=
7.36–7.18 (m, 3H; Ar), 7.04 (s, 2H; Ar), 6.98 (s, 1H; Ar), 2.45 (s, 3H;
CH3), 2.32 ppm (s, 6H, CH3); 13C{1H} NMR (75.4 MHz, CDCl3): d=
180.7, 140.6, 140.4, 138.0, 135.4, 132.1, 129.8, 129.4, 129.1, 127.6, 126.3,
21.4, 20.0 ppm.
2-(2,6-Dibromophenyl)-1,3-dioxane (11): 2,6-Dibromobenzaldehyde (10)
(10.0 g, 37.9 mmol) was dissolved in dry CH2Cl2 (160 mL). Propanediol
(6.4 mL, 88.5 mL), triethyl orthoformate (6.83 mL, 41 mmol), and anhy-
drous ZrCl4 (1.0 g) were added at ambient temperature and stirred over-
night. Then, NaOH (50 mL of a 10% solution) was added and stirred for
an additional 1h. The organic phase was separated and the aqueous
phase was extracted with Et2O (2”40 mL). The combined organic phases
were washed with water (3”60 mL), dried over MgSO4, and the volatiles
were removed in vacuo to afford 12.0 g (98%) of 11 as a slightly yellow
solid. 1H NMR (500 MHz, CDCl3): d=7.55 (d, 3J=8.0 Hz, 2H; Ar), 7.00
1,3,8-Trimethylfluoren-9-one (16): In a 250 mL one-necked round-bot-
tomed flask, the biphenylcarboxylic acid 15 (3.0 g, 12.9 mmol) was treat-
ed with concentrated sulphuric acid (40 mL) at 08C (ice bath). The re-
sulting dark-brown solution was stirred for 15 min at 08C, then for addi-
tional 1 h at ambient temperature. After this time, the reaction mixture
was poured onto ice (100 g) whereupon the color changed to a bright
yellow. The suspension was neutralized with K2CO3 and extracted with
Et2O (3”100 mL). The combined organic phases were washed with brine
(75 mL), dried over MgSO4, filtered, and the volatiles removed in vacuo
to afford 16 (2.8 g, 98%) as yellow crystals. Rf =0.52 (cyclohexane/ethyl
acetate 10:1). The product was used without any further purification.
1H NMR (500 MHz, CDCl3): d=7.30–7.28 (m, 2H; Ar), 7.14 (s, 1H; Ar),
7.02–7.00 (m, 1H; Ar), 6.82 (s, 1H; Ar), 2.61 (s, 3H; CH3), 2.57 (s, 3H;
CH3), 2.38 ppm (s, 3H; CH3); 13C{1H} NMR (125.77 MHz, CDCl3): d=
196.3, 144.7, 144.5, 144.2, 138.9, 138.8, 133.4, 132.2, 131.7, 131.5, 128.8,
118.6, 117.4, 21.9, 17.7, 17.6 ppm; IR (KBr): n=3049, 3020, 2919, 1698,
3
(t, J=8.0 Hz, 1H; Ar), 6.19 (s, 1H; CH), 4.33–4.29 (m, 2H; CH2), 4.02–
3.97 (m, 2H; CH2), 2.44–2.34 (m, 1H; CH2), 1.44–1.40 ppm (m, 1H,
CH2); 13C{1H} NMR (125.77 MHz, CDCl3): d=133.9, 132.5, 129.8, 122.9,
101.6, 66.7, 24.1 ppm.
2-Bromo-6-methylbenzaldehyde (12): Acetal 11 (10.1 g, 31.25 mmol) was
dissolved in dry THF (200 mL). At À788C nBuLi (15.1 mL, 2.5m in
hexane, 37.8 mmol) was added within 25 min, followed by 90 min addi-
tional stirring at that temperature. Then the reaction mixture was treated
with methyliodide (5.99 g, 42.2 mmol) and stirred for 25 min at À788C.
Next, the reaction mixture was allowed to warm to ambient temperature
within 1.5 h. The resulting solution was quenched with HCl (290 mL, 5n)
and stirred for 1.5 h at ambient temperature. The complete deprotection
of the aldehyde was checked by GC analysis. Then the reaction mixture
was subsequently extracted with diethyl ether (4”100 mL), the combined
organic layers were washed with a 10% solution of sodium thiosulfate
(100 mL), water (100 mL), dried over MgSO4, filtered, and the volatiles
were removed in vacuo. The resulting slightly yellow solid was purified
by Kugelrohr distillation to afford 12 (5.97 g, 96%) as white crystals. Rf =
0.56 (cyclohexane/ethyl acetate 10:1). 1H NMR (500 MHz, CDCl3): d=
1615, 1595, 1454, 1373, 1296, 1170 cmÀ1
.
1,3,8-Trimethylfluorene (1c): 1,3,8-Trimethylfluoren-9-one (16) was re-
duced according to the general procedure of Carruthers et al.[8] 1,3,8-Tri-
methylfluoren-9-one (16) (2.74 g, 12.3 mmol) was dissolved in propionic
acid (235 mL). Red phosphorus (3.0 g) and concentrated HI (40 mL)
were added and the reaction mixture was refluxed for 24 h. Quantitative
conversion was shown by TLC. The reaction mixture was diluted with
water (250 mL), neutralized with NaOH, and extracted with Et2O (4”
125 mL). The combined organic layers were washed with brine (2”
125 mL), dried over MgSO4, filtered, and the volatiles were removed in
3
10.52 (s, 1H; CHO), 7.52–7.50 (m, 1H; Ar), 7.26 (t, J=7.0 Hz, 1H; Ar),
7.22–7.20 (m, 2H; Ar), 2.58 ppm (s, 3H; CH3); 13C{1H} NMR
(125.77 MHz, CDCl3): d=194.6, 142.7, 133.6, 131.8, 131.7, 131.4, 128.3,
21.2 ppm.
vacuo to afford 2.56 g (quant.) of 1c as
a
white solid. 1H NMR
(500 MHz, CDCl3): d=7.60 (d, 3J=7.5 Hz, 1H; Ar), 7.44 (s, 1H; Ar),
7.28 (t, 3J=7.5 Hz, 1H; Ar), 7.10 (d, 3J=7.0 Hz, 1H; Ar), 6.95 (s, 1H;
Ar), 3.63 (s, 2H; CH2), 2.44 (s, 3H; CH3), 2.42 (s, 3H; CH3), 2.40 ppm (s,
3H; CH3); 13C{1H} NMR (125.77 MHz; CDCl3): d=141.3, 140.9, 140.8,
138.0, 135.6, 133.1, 132.8, 127.6, 126.4, 125.9, 117.1, 116.4, 33.4, 20.4, 17.9,
17.8 ppm; IR (KBr): n˜ =3038, 3012, 2964, 2917, 2874, 1612, 1592, 1455,
3,3’,5’-Trimethylbiphenylcarbaldehyde (14): In a 250 mL Schlenk flask,
dry dioxane (60 mL), Pd(OAc)2 (175 mg), SIMES (N,N’-bis(2,4,6-trime-
A
thylphenyl)imidazolinium chloride, 777 mg), and Cs2CO3 (12.4 g) were
stirred for 45 min at 808C until a grey solution had formed. Benzalde-
hyde 12 (3.1 g, 15.6 mmol) and 3,5-dimethylphenylboronic acid (13) were
added and the mixture was stirred for 2 h at 808C (quantitative conver-
sion, GC analysis). The reaction mixture was left to cool to ambient tem-
perature and was then treated with NaOH (100 mL, 1n) and diethyl
ether (200 mL) and transferred into a separating funnel. The aqueous
phase was extracted with Et2O (2”100 mL) and the combined organic
layers were subsequently washed with NaOH (100 mL, 1n), brine
(100 mL), dried over MgSO4, and the volatiles were removed in vacuo.
The resulting brown oil was purified by filtration over a short pad of
silica gel (10”5 cm, eluent: cyclohexane/ethyl acetate 20:1) to afford 14
(3.1 g, 89%) as a yellow oil. Rf =0.66 (cyclohexane/ethyl acetate 10:1).
The product was used without any further purification. 1H NMR
(300 MHz, CDCl3) d=9.96 (s, 1H; CHO), 7.44 (t, 3J=7.8 Hz, 1H; Ar),
7.25 (d, 3J=3.6 Hz, 2H; Ar), 7.04 (s, 1H; Ar), 6.95, (s, 2H; Ar), 2.65 (s,
3H; CH3), 2.36 ppm (s, 6H; CH3); 13C{1H} NMR (75.4 MHz, CDCl3) d=
195.0, 140.0, 139.0, 138.0, 132.7, 132.2, 131.9, 131.0, 129.7, 128.6, 128.2,
1261 cmÀ1
.
9-Ethyl-2,7-dibromofluorene (19): In a 250 mL four-necked round-bot-
tomed flask (wrapped with aluminum foil), 9-ethylfluorene (2b) (5 g,
25.7 mmol) was dissolved in dry CHCl3 (50 mL). Anhydrous FeCl3 (0.1 g,
0.63 mmol) was added. Under an argon atmosphere, bromine (8.64 g,
54.1 mmol, dissolved in 25 mL CHCl3) was added dropwise at 08C over
20 min while stirring. After completion of the addition, the reaction mix-
ture was stirred for 3 h at ambient temperature. Then a solution of
Na2S2O3 (20% w/w in water) was added and the mixture was transferred
to a separation funnel. The aqueous phase was discarded and the organic
layer was subsequently washed with a solution of NaHCO3 (saturated,
3”40 mL) and water (1”40 mL). The organic layer was dried over
MgSO4, filtered, and the volatiles were removed in vacuo to afford a
yellow solid. Recrystallization from ethanol afforded 19 (6.3 g, 70%) as
2710
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 2701 – 2716

Palladium Catalysis
FULL PAPER
Table 10. Fluorenyl phosphonium salts.
(m, 2H; CH), 2.15 (d, 3J
3J(P,H)=18.3 Hz, 6H; CH3), 1.06 ppm (dd, 3J=7.5, 3J
6H; CH3); 13C{1H} NMR (75.4 MHz, CDCl3): d=142.2 (d,
2.2 Hz), 140.2 (d, J(P,C)=4.3 Hz), 130.3, 129.2 (d, J(P,C)=1.7 Hz), 125.2
(d, J(P,C)=3.7 Hz), 121.2, 47.9 (d, J(P,C)=34 Hz), 22.7, 21.2 (d, J(P,C)=
36.3 Hz), 19.3 (d, (P,C)=2.9 Hz), 17.8 ppm (d, (P,C)=3.0 Hz);
31P{1H} NMR (121.4 MHz, CDCl3): d=39.4 ppm; 31P NMR (121.4 MHz,
CDCl3): d=39.4 ppm (d, J(P,H)=482 Hz).
ACHTREUNG
G
ACHTREUNG
J
ACHTREUNG
U
ACHTREUNG
T
N
ACHTREUNG
J
A
J
ACHTREUNG
AHCTREUNG
HBF4 salt
R1
R2
R3
R4
R5
R6
EtFluPCy2·HBF4 (17c·HBF4): 9-Ethylfluorene (2b) (1.65 g, 8.55 mmol),
nBuLi (3.3 mL, 2.5m in hexane, 8.25 mmol), Cy2PCl (1.26 g, 5.43 mmol),
HBF4·Et2O (2.2 mL, 8.7 mmol). Product 17c·HBF4 was isolated as a
white solid (1.97 g, 76%). 1H NMR (300 MHz, CDCl3): d=7.90–7.87 (m,
2H; Ar), 7.79 (d, 3J=7.9 Hz, 2H; Ar), 7.61–7.49 (m, 4H; Ar), 6.54 (d,
1J=480 Hz, 1H; PH), 2.80–2.71 (m, 2H; CH2 (ethyl)), 2.30–2.18 (m, 2H;
CH), 1.91–1.08 (m, 19H; CH2), 0.32 ppm (t, 3J=6.9 Hz, 3H; CH3);
17a
17b
17c
17d
17e
17 f
17g
17h
17i
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Me
H
Me
Me
Et
Cy
iPr
Cy
iPr
Cy
iPr
Cy
tBu
Cy
iPr
Cy
iPr
tBu
tBu
Cy
Cy
iPr
Cy
iPr
Cy
iPr
Cy
iPr
Cy
tBu
Cy
iPr
Cy
iPr
nBu
nBu
Cy
Cy
iPr
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
Et
iPr
iPr
nPr
H
C18H25
C18H25
Bn
Bn
Bn
Et
13C{1H} NMR (75.4 MHz, CDCl3) d=141.6 (d, J
ACHTREUNG
J
J
J
C
ACHTREUNG
R
ACHTREUNG
17j
E
ACHTREUNG
17k
17 L
17m
17n
17o
17p
17q
24.9, 6.7 ppm (d, J
(P,C)=11 Hz); 31P{1H} NMR (121.4 MHz, CDCl3): d=
34.4 ppm; 31P NMR (121.4 MHz, CDCl3): d=34.4 ppm (d,
J(P,H)=
E
480 Hz).
EtFluPiPr2·HBF4 (17d·HBF4): 9-Ethylfluorene (2b) (0.54 g, 2.78 mmol),
nBuLi (1.35 mL, 2.0m in hexane, 2.7 mmol), iPr2PCl (0.269 g, 1.76 mmol),
HBF4·Et2O (0.55 mL, 2.7 mmol). Product 17d·HBF4 was isolated as a
white solid (0.69 g, 99%). 1H NMR (300 MHz, CDCl3): d=7.90–7.82 (m,
Et
Et
Ph
1
4H; Ar), 7.61–7.50 (m, 4H; Ar), 6.70 (d, J=480 Hz, 1H; PH), 2.79–2.72
3
3
ACHTREUNG
(m, 2H; CH2 (ethyl)), 2.64–2.54 (m, 2H; CH), 1.30 (dd, J=7.2, J
18.3 Hz, 6H; CH3), 1.05 (dd, 3J=7.2, 3J
ACHTREUNG
white crystals. 1H NMR (500 MHz, CDCl3): d=7.61 (s, 2H; Ar), 7.56 (d,
3J=8.5 Hz, 2H; Ar), 7.48 (dd, 3J=8.5, 4J=1.5 Hz, 2H; Ar), 3.94 (t, 3J=
0.33 ppm (t, J=6.9 Hz, 3H; CH3); 13C{1H} NMR (75.4 MHz, CDCl3): d=
3
3
3
141.6 (d, J
2.1 Hz), 129.2 (d, J
(d, J(P,C)=34 Hz), 27.6, 21.3 (d, J
2.4 Hz), 17.8 (d, (P,C)=3.5 Hz), 6.6 ppm (d,
31P{1H} NMR (121.4 MHz, CDCl3): d=40.8 ppm; 31P NMR (121.4 MHz,
CDCl3): d=40.8 ppm (d, J(P,H)=478 Hz).
A
G
A
5.0 Hz, 1H; 9HFlu), 2.06 (dq, J=5.5, 7.5 Hz, 2H; CH2), 0.68 ppm (t, J=
7.5 Hz, 3H; CH3); 13C{1H} NMR (125.77 MHz, CDCl3): d=148.9, 139.4,
130.3, 127.7, 121.2, 48.4, 25.3, 9.4 ppm; HRMS: m/z: calcd. for C15H12Br2:
349.9305; found: 349.9286.
A
ACHTREUNG
A
N
ACHTREUNG
J
A
J
ACHTREUNG
General procedure for the synthesis of fluorenyl phosphonium salts
(Table 10): nBuLi (29 mmol, 2.5m solution in hexane) was added to a so-
lution of 9-substituted fluorene (31 mmol) in dry Et2O (100 mL) at
À608C. The solution immediately turned red and was stirred for 10 min
at À608C, then for additional 2 h at ambient temperature. After cooling
to À608C again, the dialkyl phosphonium chloride (22 mmol) was added.
The reaction mixture was stirred for 10 min at À608C, then overnight at
RT. After removing the LiCl by filtration over a short pad of Celite, the
resulting clear filtrate was quenched with HBF4 (31.5 mmol of a diethyl
ether complex). After separation by means of suction filtration, the crude
product was dissolved in CHCl3 (20 mL) and added dropwise into Et2O
(1 L, vigorously stirred). Filtration and removal of the volatiles in vacuo
afforded the pure product as a white solid.
AHCTREUNG
iPrFluPCy2·HBF4 (17e·HBF4): 9-Isopropylfluorene (2c) (1.15 g,
5.54 mmol), nBuLi (2.7 mL, 2.0m in hexane, 5.4 mmol), Cy2PCl (0.9 mL,
4.08 mmol), HBF4·Et2O (1.2 mL, 4.76 mmol). Product 17e·HBF4 was iso-
1
lated as a white solid (1.30 g, 64%). H NMR (300 MHz, CDCl3): d=7.89
(d, 3J=6.9 Hz, 2H; Ar), 7.79 (d, 3J=7.5 Hz, 2H; Ar), 7.62–7.50 (m, 4H;
Ar), 6.79 (d, 1J=479 Hz, 1H; PH), 3.01 (dq, 3J=6.6, 4.8 Hz, 1H;
CHCH3), 2.21–2.09 (m, 2H; CH), 1.97–1.86 (m, 2H; CH2), 1.81–1.59 (m,
6H; CH2), 1.51–1.37 (m, 4H; CH2), 1.23–1.07 (m, 8H; CH2), 0.93 ppm
(d, 3J=6.6 Hz, 6H; CH3); 13C{1H} NMR (75.4 MHz, CDCl3) d=141.5 (d,
J
J
C
J
ACHTREUNG
J
A
J
ACHTREUNG
35.6 Hz), 29.3 (d,
J
A
J
ACHTREUNG
MeFluPCy2·HBF4 (17a·HBF4): 9-Methylfluorene (2a) (1.0 g, 5.55 mmol),
J
N
G
ACHTREUNG
nBuLi (2.7 mL of
a 2.0m in hexane, 5.4 mmol), Cy2PCl (0.95 g,
4.08 mmol), HBF4·Et2O (1.4 mL, 5.55 mmol). 17a·HBF4 was isolated to
give a white solid (1.35 g, 71%). 1H NMR (300 MHz, CD3CN) d=8.02–
7.99 (m, 2H; Ar), 7.81–7.78 (m, 2H; Ar), 7.66–7.61 (m, 2H; Ar), 7.56–
AHCTREUNG
iPrFluPiPr2·HBF4 (17 f·HBF4): 9-Isopropylfluorene (2c) (1.16 g,
5.57 mmol), nBuLi (2.7 mL, 2.0m in hexane, 5.4 mmol), iPr2PCl (0.66 g,
4.1 mmol), HBF4·Et2O (1.2 mL, 4.76 mmol). Product 17 f·HBF4 was iso-
lated as a white solid (1.20 g, 71%). 1H NMR (300 MHz, CDCl3): d=
7.90–7.82 (m, 4H; Ar), 7.62–7.50 (m, 4H; Ar), 6.99 (d, 1J=477 Hz, 1H;
PH), 3.09–2.99 (m, 1H; CH), 2.59–2.44 (m, 2H; CH), 1.32 (dd, 3J=7.5,
1
7.50 (m, 2H; Ar), 6.00 (d, J=464 Hz, 1H; PH), 2.44–2.30 (m, 4H; CH2),
2.03 (d, 3J=16.8 Hz, 3H; CH3), 1.96–1.92 (m, 2H; CH), 1.75–1.49 (m,
8H; CH2), 1.31–1.04 ppm (m, 8H; CH2); 13C{1H} NMR (75.4 MHz,
CD3CN): d=140.9 (d, J
(d, J(P,C)=2.0 Hz), 128.6 (d, J
121.3, 47.6 (d, J(P,C)=33.9 Hz), 30.4 (d, J
3.9 Hz), 27.5 (d, (P,C)=3.8 Hz), 25.8 (d,
C
ACHTREUNG
3J
CH3), 0.94 ppm (d, 3J=6.9 Hz, 6H; CH3); 13C{1H} NMR (75.4 MHz,
CDCl3): d=141.5 (d, J(P,C)=5.1 Hz), 139.4 (d, J(P,C)=2.4 Hz), 130.3 (d,
(P,C)=1.6 Hz), 129.1 (d, (P,C)=1.3 Hz), 125.7 (d, (P,C)=3.6 Hz),
121.2, 56.1 (d, J(P,C)=33.2 Hz), 34.4, 21.1 (d, J(P,C)=38.5 Hz), 19.5 (d,
(P,C)=2.2 Hz), 17.8 (d, J(P,C)=2.6 Hz), 6.6 ppm (d, J(P,C)=6.5 Hz);
31P{1H} NMR (121.4 MHz, CDCl3): d=31.3 ppm; 31P NMR (121.4 MHz,
CDCl3): d=31.3 ppm (d, J(P,H)=473 Hz).
nPrFluPCy2·HBF4 (17g·HBF4): 9-n-Propylfluorene
(P,H)=18.9 Hz, 6H; CH3), 1.03 (dd, 3J=7.5, 3J
(P,H)=17.7 Hz, 6H;
N
G
U
ACHTREUNG
G
U
ACHTREUNG
J
G
J
ACHTREUNG
U
ACHTREUNG
G
J
N
J
N
J
ACHTREUNG
38.8 ppm; 31P NMR (121.4 MHz, CD3CN): d=38.8 ppm (d,
J(P,H)=
N
N
ACHTREUNG
463 Hz).
J
G
ACHTREUNG
MeFluPiPr2·HBF4 (17b·HBF4): 9-Methylfluorene (2a) (1.5 g, 8.31 mmol),
nBuLi (4.05 mL, 2.0m in hexane, 8.1 mmol), iPr2PCl (0.9 mL, 5.67 mmol),
HBF4·Et2O (2.4 mL, 9.51 mmol). Product 17b·HBF4 was isolated as a
white solid (1.37 g, 63%). 1H NMR (300 MHz, CDCl3): d=7.94–7.86 (m,
AHCTREUNG
(2d)
(3.0 g,
14.4 mmol), nBuLi (5.6 mL, 2.5m in hexane, 14.0 mmol), Cy2PCl (2.37 g,
10.2 mmol), HBF4·Et2O (2.0 mL, 14 mmol). Product 17g·HBF4 was isolat-
1
4H; Ar), 7.60–7.49 (m, 4H; Ar), 7.27 (d, J=483 Hz, 1H; PH), 2.65–2.50
Chem. Eur. J. 2007, 13, 2701 – 2716
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2711

H. Plenio and C. A. Fleckenstein
ed as a white solid (4.13 g, 73%). 1H NMR (500 MHz, CDCl3): d=7.87
(d, 3J=7.5 Hz, 2H; Ar), 7.79 (d, 3J=7.5 Hz, 2H; Ar), 7.59–7.50 (m, 4H;
Ar), 6.54 (d, 1J=480.5 Hz, 1H; PH), 2.67–2.63 (m, 2H; CH2 (propyl)),
2.24–2.21 (m, 2H; CH), 1.91–1.10 (m, 19H; CH2), 0.73 (t, 3J=7.5 Hz,
3H; CH3), 0.66–0.58 ppm (m, 2H; CH2 (propyl)); 13C{1H} NMR
1.8 Hz), 17.8 (d, J
CDCl3): d=40.8 ppm; 31P NMR (121.4 MHz, CDCl3): d=40.8 ppm (d,
(P,H)=480 Hz).
(P,C)=2.5 Hz), 14.1 ppm; 31P{1H} NMR (121.4 MHz,
J
ACHTREUNG
BnFluPCy2·HBF4 (17k·HBF4): 9-Benzylfluorene (2 f) (6.0 g, 23.2 mmol),
nBuLi (8.6 mL, 2.5m in hexane, 21.5 mmol), Cy2PCl (3.85 g, 16.5 mmol),
HBF4·Et2O (3.22 mL, 23.6 mmol). Product 17k·HBF4 was isolated as a
white solid (5.43 g, 61%). 1H NMR (500 MHz, [D6]acetone): d=8.32–
8.30 (m, 2H; Ar), 7.88–7.86 (m, 2H; Ar), 7.60–7.57 (m, 4H; Ar), 6.90–
(125.75 MHz, CDCl3): d=141.4 (d, J
3.8 Hz), 130.2, 129.1, 125.1 (d, J(P,C)=2.8 Hz), 121.1, 52.4 (d, J
33 Hz), 40.0, 31.3 (d, J(P,C)=34.6 Hz), 29.4 (d, J(P,C)=3.6 Hz), 28.1 (d,
(P,C)=3.3 Hz), 26.8 (d, (P,C)=13.8 Hz), 26.5 (d, (P,C)=12.4 Hz),
24.9, 16.0 (d, J
(P,C)=10.4 Hz), 13.6 ppm; 31P{1H} NMR (202.45 MHz,
CDCl3): d=34.9 ppm; 31P NMR (202.45 MHz, CDCl3): d=34.9 ppm (d,
(P,H)=483 Hz).
A
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
1
J
A
J
A
J
ACHTREUNG
6.87 (m, 1H; Ar), 6.82–6.79 (m, 2H; Ar), 6.70 (d, J=472.5 Hz, 1H; PH),
6.69–6.67 (m, 2H; Ar), 4.25 (d, 3J=7 Hz, 2H; CH2), 2.88–2.79 (m, 2H;
CH), 1.96–1.94 (m, 2H; CH2), 1.77–1.08 ppm (m, 18H; CH2);
ACHTREUNG
13C{1H} NMR (125.77 MHz, [D6]acetone): d=142.7 ppm (d,
J
ACHTREUNG
J
ACHTREUNG
4.5 Hz), 140.5 (d, J
127.3 (d, J
ACHTREUNG
HFluPtBu2·HBF4 (17h·HBF4): Fluorene (1a) (0.505 g, 3.04 mmol) dis-
solved in dry THF (10 mL) was treated with nBuLi (1.5 mL, 2.0m in
hexane) at À808C. The mixture turned orange and was stirred for an ad-
ditional 4 h at ambient temperature. Then tBu2PCl (0.476 g, 2.6 mmol)
and dry heptane (10 mL) were added at À808C. The reaction mixture
was refluxed overnight, filtered under Schlenk conditions over a short
pad of Celite, and the clear filtrate was quenched with HBF4·Et2O
(0.7 mL, 2.8 mmol) to afford a white residue, which could be crystallized
from ethyl acetate. After separation of the solids by means of suction fil-
tration, the crude product was dissolved in CHCl3 (3 mL) and added
dropwise into Et2O (200 mL, vigorously stirred). Filtration and removal
of the volatiles in vacuo afforded pure 17h·HBF4 (0.54 g, 52%) as a
white solid. 1H NMR (300 MHz, CD3CN): d=8.05–7.98 (m, 2H; Ar),
7.86–7.77 (m, 2H; Ar), 7.63–7.54 (m, 4H; Ar), 6.27 (d, 1J=463 Hz, 1H;
G
ACHTREUNG
J
J
U
N
ACHTREUNG
J
ACHTREUNG
(202.46 MHz, [D6]acetone) d=35.7 ppm; 31P NMR (202.46 MHz,
[D6]acetone) d=35.7 ppm (d, J(P,H)=472.6 Hz).
A
BnFluPiPr2·HBF4 (17 L·HBF4): 9-Benzylfluorene (2 f) (8.1 g, 31.3 mmol),
nBuLi (11.6 mL, 2.5m in hexane, 29 mmol), (iPr)2PCl (3.32 g, 22.3 mmol),
HBF4·Et2O (4.35 mL, 31.9 mmol). After separation by means of suction
filtration, the crude product was dissolved in acetonitrile (20 mL) and
added dropwise into Et2O (1 L, vigorous stirring). Filtration and removal
of the volatiles in vacuo afforded the pure product 17l·HBF4 as a white
solid (9.8 g, 95%). 1H NMR (500 MHz, CD3CN): d=8.04–8.02 (m, 2H;
Ar), 7.79–7.77 (m, 2H; Ar), 7.56–7.54 (m, 4H; Ar), 6.92–6.90 (m, 1H;
Ar), 6.84–6.81 (m, 2H; Ar), 6.61–6.60 (m, 2H; Ar), 6.35 (d, 1J=470 Hz,
1H; PH), 4.00 (d, 3J=6.00 Hz, 2H; CH2), 2.83–2.75 (m, 2H; CH), 1.18
PH), 5.37 (d, 2J
CH3), 0.91 ppm (d, 3J
(75.4 MHz, CD3CN): d=139.0, 135.1, 129.4 (d, J
(P,C)=32 Hz), 125.7 (d, J(P,C)=87 Hz), 121.2 (d, J
(d, J(P,C)=34 Hz), 36.5 (d, J(P,C)=23.7 Hz), 34.5 (d, J
27.5, 26.6 ppm; 31P{1H} NMR (121.4 MHz, CD3CN): d=52.1 ppm;
31P NMR (121.4 MHz, CD3CN): d=52.1 ppm (d, J
(P,H)=462 Hz).
A
N
AHCTREUNG
(dd, 3J=7.5, 3J
3J(P,H)=17.5 Hz, 6H; CH3); 13C{1H} NMR (125.8 MHz, CD3CN): d=
141.2 (d, J(P,C)=4.8 Hz), 138.7, 132.2 (d, J(P,C)=14.3 Hz), 130.0, 129.9,
128.2, 127.1, 126.7, 125.8 (d, J(P,C)=31.8 Hz), 38.5, 21.0 (d, J(P,C)=
36.2 Hz), 18.3 (d, (P,C)=2.3 Hz), 17.0 ppm (d, (P,C)=1.4 Hz);
31P{1H} NMR (202.5 MHz, CD3CN): d=43.8 ppm; 31P NMR (202.5 MHz,
CD3CN): d=43.8 ppm (d, J(P,H)=465.2 Hz).
Synthesis of the fluorenyl phosphonium salts 17m and 17n
BnFluP(nButBu)·HBF4 (17m·HBF4): nBuLi (13.8 mL, 2.5m in hexane,
A
AHCTREUNG
J
N
G
ACHTREUNG
AHCTREUNG
A
N
ACHTREUNG
A
ACHTREUNG
R
ACHTREUNG
N
J
G
J
ACHTREUNG
C18FluPCy2·HBF4 (17i·HBF4): 9-Octadecylfluorene (2e) (2.48 g,
5.9 mmol), nBuLi (2.1 mL, 2.5m in hexane, 5.25 mmol), Cy2PCl (0.92 g,
3.94 mmol), HBF4·Et2O (1.8 mL). In the absence of precipitation, water
(80 mL, treated with aqueous HBF4 (8n)) was added, whereupon a white
solid precipitated. The solid was removed by means of suction filtration
to afford 17i·HBF4 as a white solid (2.6 g, 94%). 1H NMR (300 MHz,
CDCl3): d=7.87 (d, 3J=7.2 Hz, 2H; Ar), 7.79–7.77 (m, 2H; Ar), 7.60–
AHCTREUNG
AHCTREUNG
34.7 mmol) was added to a solution of 9-benzylfluorene (2 f) (9.24 g,
35.7 mmol) in dry THF (75 mL at À608C. The solution immediately
turned red. After stirring for 1 h at ambient temperature, the reaction
1
[109]
7.50 (m, 4H; Ar), 6.59 (d, J=483 Hz, 1H; PH), 2.71–2.59 (m, 2H; CH2),
mixture was added to a solution of tBuPCl2
(5.2 g, 32.7 mmol, dis-
2.27–2.13 (m, 2H; CH), 1.92–1.02 (m, 50H; CH2), 0.87 (t, 3J=6.6 Hz,
3H; CH3), 0.60–0.49 ppm (m, 2H; CH2); 13C{1H} NMR (75.4 MHz,
solved in 50 mL dry Et2O) at À808C. At the end of the addition, the red
color remained. After stirring overnight at ambient temperature, nBuLi
(16.8 mL, 2.5m in hexane, 41.9 mmol) was added at À608C. The reaction
mixture was stirred for 10 min at À608C, then for 2 h at ambient temper-
ature. The suspension was filtered over a small pad of Celite and the
clear reddish filtrate was quenched with HBF4·Et2O (4.0 mL, 29.3 mmol)
to precipitate the phosphonium salt. After separation by means of suc-
tion filtration, the crude product was dissolved in acetonitrile (20 mL)
and the solution was added dropwise to vigorously stirred Et2O (1 L) to
obtain a colorless precipitate. Filtration and removal of the volatiles in
vacuo afforded 17m·HBF4 as a white solid (2.65 g, 17%). 1H NMR
(500 MHz, CD3CN): d=8.19–8.18 (m, 1H; Ar), 8.10–8.08 (m, 1H; Ar),
7.78–7.77 (m, 1H; Ar), 7.73–7.71 (m, 1H; Ar), 7.56–7.50 (m, 4H; Ar),
6.93–6.89 (m, 1H; Ar), 6.82–6.79 (m, 2H; Ar), 6.62–6.60 (m, 2H; Ar),
4.09–4.00 (m, 2H; CH2, Bn), 2.81–2.77 (m, 1H; CH2, nBu), 2.42–2.38 (m,
1H; CH2, nBu), 1.95–1.94 (m, 2H; CH2, nBu), 1.66–1.59 (m, 2H; CH2,
nBu), 1.01 (t, 3J=7.6 Hz, 3H; CH3, nBu), 0.74 ppm (d, 3J=17.5 Hz, 9H;
CDCl3): d=141.4 (d, J
52.4 (d, J(P,C)=32.2 Hz), 34.0, 31.9, 31.3 (d, J
(CH2, 14”), 28.1 (d, J(P,C)=3.2 Hz), 26.8(d, J
(P,C)=12.6 Hz), 24.9, 22.7, 22.4 (d, (P,C)=9.9 Hz), 14.1 ppm;
31P{1H} NMR (121.4 MHz, CDCl3): d=34.1 ppm; 31P NMR (121.4 MHz,
CDCl3): d=34.1 ppm (d, J(P,H)=482 Hz).
ACHTREUNG
A
ACHTREUNG
A
N
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J
A
J
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AHCTREUNG
C18FluPiPr2·HBF4 (17j·HBF4): 9-Octadecylfluorene (2e) (2.38 g,
5.7 mmol), nBuLi (2.0 mL, 2.5m in hexane, 5.0 mmol), iPr2PCl (0.575 g,
3.77 mmol), HBF4·Et2O (2.0 mL, 9.8 mmol). In the absence of precipita-
tion, the volatiles were evaporated in vacuo to give a colorless solid,
which was dissolved in diethyl ether (50 mL) and treated with
HBF4·Et2O (1 mL). Aqueous HBF4 (50 mL, 4n) was added, the mixture
was stirred vigorously, and then the aqueous phase was separated and
kept in an open beaker overnight. After this time, the crystals which had
formed were separated by means of suction filtration and dried in vacuo
to afford 17j·HBF4 (1.90 g, 81%) as white crystals. 1H NMR (300 MHz,
CDCl3): d=7.88 (d, 3J=6.9 Hz, 2H; Ar), 7.81 (d, 3J=6.9 Hz, 2H; Ar),
7.59–7.53 (m, 4H; Ar), 6.65 (d, 1J=481 Hz, 1H; PH), 2.71–2.61 (m, 2H;
CH3, tBu); 13C{1H} NMR (125.77 MHz, CD3CN): d=141.2 (d, J
4.5 Hz), 141.0 (d, J(P,C)=4.4 Hz), 139.5 (d, J(P,C)=2.5 Hz), 138.4 (d,
(P,C)=1.9 Hz), 132.0 (d, J(P,C)=13.8), 132.1, 131.9, 130.0, 130.0, 129.8,
128.0 (d, J(P,C)=6.5 Hz), 127.0, 126.7, 126.4 (d, J(P,C)=3.4 Hz), 125.7 (d,
(P,C)=2.8 Hz), 121.1, 120.9, 52.1 (d, J(P,C)=32.8 Hz), 38.9, 33.5 (d,
(P,C)=34.0 Hz), 29.1 (d, (P,C)=7.5 Hz), 25.2, 23.2 (d, (P,C)=
(P,C)=37.7 Hz), 12.3 ppm; 31P{1H} NMR (202.5 MHz,
A
G
ACHTREUNG
J
A
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CH2), 2.61–2.49 (m, 2H; CH), 1.31 (dd, 3J=7.2, 3J
CH3), 1.27–1.11 (m, 30H; CH2), 1.05 (dd, 3J=7.5, 3J
CH3), 0.88 (t, 3J=6.9 Hz, 3H; CH3), 0.61–0.50 ppm (m, 2H; CH2);
13C{1H} NMR (75.4 MHz, CDCl3): d=141.4 (d, J
(P,C)=5.1 Hz), 139.9 (d,
(P,C)=2.9 Hz), 121.3, 52.3 (d,
(P,C)=33.5 Hz), 34.1, 31.9, 29.6 (CH2, 11”), 29.5, 29.4, 29.3, 29.1, 22.7,
(P,H)=12.3 Hz, 6H;
(P,H)=17.4 Hz, 6H;
R
ACHTREUNG
J
J
U
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AHCTREUNG
J
A
J
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14.5 Hz), 14.5 (d, J
CD3CN): d=39.8 ppm.
EtFluP(nButBu)·HBF4 (17n·HBF4): 9-Ethylfluorene (2b) (5.85 g,
30.0 mmol) was dissolved in dry THF (50 mL), treated with nBuLi
ACHTREUNG
AHCTREUNG
J
J
N
ACHTREUNG
ACHTREUNG
22.2 (d,
J
(P,C)=10.5 Hz), 21.3 (d,
J
U
J(P,C)=
N
2712
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 2701 – 2716

Palladium Catalysis
FULL PAPER
(11.5 mL, 2.5m in hexane, 29.0 mmol) at À308C and stirred for 1 h at am-
PhFluPiPr2·HBF4 (17q·HBF4): 9-Phenylfluorene (5) (0.72 g, 2.97 mmol),
nBuLi (1.08 mL, 2.5m solution in hexane), iPr2PCl (0.33 mL, 2.03 mmol),
HBF4·Et2O (0.6 mL, 2.37 mmol). Product 17q·HBF4 was isolated to give
[12]
bient temperature. Then tBuPCl2 (4.36 g, 27.4 mmol) dissolved in dry
THF (50 mL) was added at À808C to the red solution. The reaction mix-
ture was stirred at ambient temperature for 14 h and the color turned
slightly greenish. Completeness of the conversion was checked by
31P NMR spectroscopy which showed one single signal at d=162.91 ppm
(in benzene) for EtFluPtBuCl. At À308C, nBuLi (14.0 mL, 2.5m in
hexane, 35.0 mmol) was added and the reaction mixture stirred at ambi-
ent temperature overnight. The suspension was filtered over a small pad
of Celite by using Schlenk technique. The clear reddish filtrate was treat-
ed with HBF4·Et2O (5.2 mL, 38 mmol). The volatiles were removed in
vacuo to give a yellow residue, which was extracted with chloroform
(6 mL), filtered, and the clear filtrate was added dropwise into Et2O
(200 mL, vigorously stirred) to precipitate the product. Filtration and re-
moval of the volatiles in vacuo afforded 17n·HBF4 (5.3 g, 45%) as a
white solid. 1H NMR (500 MHz, CDCl3): d=7.95 (d, 3J=6.5 Hz, 1H;
Ar), 7.89–7.84 (m, 2H; Ar), 7.72 (d, 3J=8 Hz, 1H; Ar), 7.60–7.49 (m,
4H; Ar), 6.77 (d, 1J=481 Hz, 1H; PH), 2.81–2.73 (m, 1H; CH2 (ethyl)),
2.69–2.61 (m, 1H; CH2 (ethyl)), 2.42–2.32 (m, 1H; CH2 (butyl)), 2.18–
2.08 (m, 1H; CH2 (butyl)), 1.88–1.77 (m, 2H; CH2 (butyl)), 1.57–1.43 (m,
1
1
a white solid (0.84 g, 93%). H NMR (300 MHz, CDCl3): d=9.49 (d, J=
490 Hz, 1H; PH), 7.98–7.91 (m, 4H; Ar), 7.85 (d, 3J=8.1 Hz, 2H; Ar),
7.64–7.52 (m, 4H; Ar), 7.45 (t, 3J=7.2 Hz, 2H; Ar), 7.37–7.32 (m, 1H;
Ar), 2.30–2.21 (m, 2H; CH), 1.14 (dd, 3J=7.2, 3J
ACHTREUNG
CH3), 1.02 ppm (dd, 3J=7.5, 3J
ACHTREUNG
J
A
J
ACHTREUNG
AHCTREUNG
A
N
ACHTREUNG
J
A
J
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AHCTREUNG
AHCTREUNG
a solution of EtFluPCy2·HBF4 (17c·HBF4) (2.35 g, 4.92 mmol) in dry
CH2Cl2 (1 mL) at 08C. After stirring the solution at 408C overnight, ice
was added (5 g). The reaction mixture was extracted with chloroform (3”
10 mL). The combined organic layers were dried over MgSO4. After fil-
tration, the clear filtrate was reduced to a final volume of 5 mL in vacuo.
The concentrate was added dropwise to diethyl ether (500 mL, vigorously
stirred) to precipitate the product. Filtration and removal of the volatiles
in vacuo afforded the pure product 18·H2SO4 (1.8 g, 77%) as a white
solid. 1H NMR (500 MHz, [D4]methanol): d=8.22 (s, 1H; Ar), 8.10 (s,
2H; Ar), 8.09 (s, 1H; Ar), 7.86 (d, 3J=10 Hz, 1H; Ar), 7.68 (t, 3J=
7.5 Hz, 1H; Ar), 7.60 (t, 3J=7.5 Hz, 1H; Ar), 2.87–2.81 (m, 1H; CH2),
2.79–2.74 (m, 1H; CH2), 2.69–2.61 (m, 1H; CH), 2.51–2.46 (m, 1H; CH),
2.05–1.05 (m, 20H; CH2), 0.34 ppm (t, 3J=6.5 Hz, 3H; CH3).
2H; CH2 (butyl)), 0.97 (t, 3J=7.5 Hz, 3H; (butyl)), 0.85 (d, 3J
17 Hz, 9H; CH3), 0.32 ppm (t, 3J=7.5 Hz, 3H; (ethyl)); 13C{1H} NMR
(125.75 MHz, CDCl3): d=141.7 (d, J(P,C)=4.4 Hz), 141.3 (d, J(P,C)=
4.5 Hz), 139.9, 139.0 (d, J(P,C)=2.8 Hz), 130.4, 130.2, 129.3, 128.9, 125.9
(d, (P,C)=3.3 Hz), 124.7 (d, (P,C)=2.3 Hz), 121.4, 121.0, 52.2 (d,
(P,C)=34 Hz), 33.7 (d, J(P,C)=36.3 Hz), 28.8 (d, J(P,C)=5.5 Hz), 28.1,
26.5, 24.1 (d, J(P,C)=13.1 Hz), 15.0 (d, J(P,C)=37.7 Hz), 13.2, 6.3 ppm
(d, J
(P,C)=9.3 Hz); 31P{1H} NMR (202.45 MHz, CDCl3): d=39.4 ppm;
31P NMR (202.45 MHz, CDCl3): d=39.4 ppm (d, J
(P,H)=480 Hz).
(P,H)=
A
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J
A
J
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J
N
G
ACHTREUNG
A
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ACHTREUNG
AHCTREUNG
9-Et-1-MeFluPCy2·HBF4 (17o·HBF4): 9-Ethyl-1-methylfluorene (2g)
(2.0 g, 9.56 mmol), nBuLi (3.67 mL, 2.5m in hexane, 9.18 mmol), Cy2PCl
(1.78 g, 7.65 mmol), HBF4·Et2O (1.25 mL, 9.18 mmol). Product 17o·HBF4
was isolated as a white solid (3.5 g, 93%). 1H NMR (500 MHz, CDCl3):
d=7.86 (d, 3J=7.5 Hz, 1H; Ar), 7.74 (d, 3J=7.5 Hz, 1H; Ar), 7.68 (d,
13C{1H} NMR (125.75 MHz, [D4]methanol): d=147.5, 144.8 (d, J
4.8 Hz), 142.5 (d, J(P,C)=4.5 Hz), 141.8 (d, J(P,C)=2.9 Hz), 141.0 (d,
(P,C)=2.0 Hz), 131.8, 130.6, 129.4, 126.4 (d, J(P,C)=4.0 Hz), 124.0 (d,
(P,C)=3.9 Hz), 123.2, 122.4, 53.9 (d, J(P,C)=33.7 Hz), 32.4 (d, J(P,C)=
(P,C)=8.7 Hz), 30.8 (d, (P,C)=3.8 Hz), 30.4 (d,
(P,C)=3.4 Hz), 29.6 (d, J(P,C)=4.0 Hz), 29.5 (d, J(P,C)=5.4 Hz), 28.9
(d, (P,C)=3.8 Hz), 28.5, 27.7 (d, (P,C)=4.9 Hz), 27.6 (d, (P,C)=
4.3 Hz), 27.4 (d, J(P,C)=11.3 Hz), 27.2 (d, J(P,C)=11.9 Hz), 26.0 (d,
(P,C)=2.8 Hz), 6.9 ppm (d, (P,C)=11.7 Hz);
31P{1H} NMR
(202.46 MHz, [D4]methanol): d=34.9 ppm; ESI-MS: positive ions 18+
C
G
ACHTREUNG
J
J
G
ACHTREUNG
N
9.2 Hz), 32.1 (d,
J
J
A
J
ACHTREUNG
3
3J=7.5 Hz, 1H; Ar), 7.59 (t, J=7.5 Hz, 1H; Ar), 7.54–7.47 (m, 2H; Ar),
G
ACHTREUNG
7.24 (d, 3J=7.5 Hz, 1H; Ar), 6.50 (dd, 1J=465.5, 3J=4.0 Hz, 1H; PH),
3.06–2.97 (m, 1H; CH2 (ethyl)), 2.79–2.68 (m, 2H; CH2 (ethyl)+CH
(Cy)), 2.66 (s, 3H; CH3), 2.35–2.32 (m, 1H; CH(Cy)), 2.02–1.65 (m, 7H;
CH2), 1.56–1.34 (m, 7H; CH2), 1.13–1.08 (m, 1H; CH2), 0.91–0.87 (m,
4H; CH2), 0.68–0.59 (m, 1H; CH2), 0.39 ppm (t, 3J=7.0 Hz, 3H; CH3);
J
G
J
U
J
G
ACHTREUNG
J
J
ACHTREUNG
À
À
(471.3), negative ions HSO3 (97.3), BF4 not observed. elemental analy-
sis calcd for C27H37O7PS2 (568.7): C 57.02, H 6.56; found: C 56.93, H 7.26.
13C{1H} NMR (125.75 MHz, CDCl3): d=142.6 (d, J
(d, J(P,C)=4.5 Hz), 139.8 (d, J(P,C)=4.5 Hz), 137.4 (d, J
136.8 (d, J(P,C)=2.8 Hz), 132.2, 131.0, 130.8, 129.2 (d, J
124.6 (d, J(P,C)=4.1 Hz), 121.4, 119.1, 54.7 (d, J(P,C)=31.3 Hz), 32.1 (d,
(P,C)=37.3 Hz), 31.8 (d, J(P,C)=33.3 Hz), 30.6 (d, J(P,C)=3.8 Hz), 28.7
(d, J(P,C)=3.6 Hz), 28.5 (d, J(P,C)=3.4 Hz), 27.2, 27.2, 27.2, 27.1, 27.1,
27.0, 26.9, 26.8, (d, J(P,C)=13.2 Hz), 27.1 (d, J(P,C)=13.2 Hz),25.2, 20.1,
ACHTREUNG
A
N
ACHTREUNG
9-Et-2,7-dibromo-FluPiPr2·HBF4 (20·HBF4): In a 100 mL Schlenk flask,
G
A
ACHTREUNG
diisopropylamine (1.03 mL, 7.4 mmol) was dissolved in dry THF (20 mL).
At À608C, nBuLi (2.7 mL of a 2.0m solution in hexane, 6.8 mmol) was
added. The solution was stirred at À608C for 10 min, then for an addi-
tional 30 min at 08C. The formed LDA (LDA=lithium diisopropyl-
amide) solution was added to a solution of 9-ethyl-2,7-dibromofluorene
(19·HBF4) (2.5 g, 7.08 mmol) in Et2O (40 mL) at À608C. The red reaction
mixture was stirred for 30 min at À608C, then for 1.5 h at ambient tem-
perature (at lower temperatures a thick reddish precipitate was formed).
Then iPr2PCl (0.9 mL, 5.66 mmol) was added at À608C. The reaction
mixture was stirred at ambient temperature for 2 h (color changed from
red to yellow) and filtered over a small pad of Celite. The clear, slightly
yellow filtrate was quenched with HBF4·Et2O (1.80 mL, 13.2 mmol)
which led to precipitation of the phosphonium salt as a white solid. The
solid was separated by means of suction filtration, slurried in water
(15 mL, to remove residual ammonium salt) and filtered again. The col-
lected white solid was dissolved in CHCl3 (10 mL) and acetonitrile
(1 mL), and the solution was added dropwise to vigorously stirred Et2O
(400 mL) to give a colorless precipitate. Filtration and removal of the vol-
A
ACHTREUNG
J
N
G
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
7.4 ppm (d,
J
(P,C)=11 Hz); 31P{1H} NMR (202.5 MHz, CDCl3) d=
U
J(P,H)=
G
471 Hz).
9-Et-1,3,8-Me3-FluPCy2·HBF4 (17p·HBF4): 9-Ethyl-1,3,8-trimethylfluor-
ene (2h) (0.8 g, 3.4 mmol), nBuLi (1.29 mL, 2.5m in hexane), Cy2PCl
(0.633 g, 2.72 mmol), HBF4·Et2O (0.8 mL, 3.2 mmol). Product 17p·HBF4
was isolated as a white solid (1.29 g, 92%). 1H NMR (300 MHz, CDCl3):
3
d=7.89 (d, J=7.5 Hz, 1H; Ar), 7.52 (s, 1H; Ar), 7.49–7.43 (m, 1H; Ar),
7.22 (d, 3J=7.5 Hz, 1H; Ar), 7.05 (s, 1H; Ar), 6.30 (dt, 1J=469, 3J=
4.5 Hz, 1H; PH), 2.96 (dq, 3J
(P,H)=5.7, 7.2 Hz, 2H; CH2 (ethyl)), 2.66
G
(s, 3H; CH3), 2.62 (s, 3H; CH3), 2.44 (s, 3H; CH3), 2.24–2.19 (m, 2H;
CH), 2.12–1.04 (m, 20H; CH2), 0.44 ppm (t, 3J=7.2 Hz, 3H; CH3);
13C{1H} NMR (75.4 MHz, CDCl3): d=142.6 (d, J
ACHTREUNG
1
J
A
J
G
J
N
atiles in vacuo afforded 20·HBF4 as a white solid (2.82 g, 90%). H NMR
A
N
(500 MHz, CD3CN): d=7.98 (t, 4J=1.5 Hz, 2H; Ar), 7.91 (d, 3J=8.0 Hz,
2H; Ar), 7.81 (dt, 3J=8.0, 4J=1.5 Hz, 2H; Ar), 6.24 (d, 1J=470 Hz, 1H;
PH), 2.80–2.71 (m, 2H; CH), 2.70–2.64 (m, 2H; CH2), 1.17 (dd, 3J=7.5,
J
A
J
A
J
ACHTREUNG
A
ACHTREUNG
J
A
G
N
3J
A
ACHTREUNG
3
A
N
ACHTREUNG
A
N
ACHTREUNG
J
A
J
A
J
ACHTREUNG
A
N
ACHTREUNG
Chem. Eur. J. 2007, 13, 2701 – 2716
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2713

H. Plenio and C. A. Fleckenstein
J
A
G
A
Suzuki reaction of aryl halides (in water)
Preparation of the catalyst stocksolution : The catalyst stock solution was
prepared as described for the aqueous Sonogshira reaction; K2CO3 in-
stead of Cs2CO3.
AHCTREUNG
General procedures for the cross-coupling reactions: All cross-coupling
reactions were carried out under an argon atmosphere in deaerated sol-
vents (freeze and thaw).
Cross-coupling reaction: Water (4 mL), the catalyst stock solution, and
two drops of Labrasol were added to a mixture of aryl halide (1 mmol),
boronic acid (1.2 mmol), and K2CO3 (3.2 mmol). The reaction mixture
was stirred at the respective temperatures (see tables) for 0.5–20 h (see
tables). After cooling to RT, the reaction mixture was diluted with dieth-
yl ether (15 mL) and washed with water (10 mL). Then the organic phase
was dried over MgSO4, filtered, and concentrated in vacuo. The product
was isolated by column chromatography (silica gel, cyclohexane/ethyl
acetate 100:2). Alternatively, the yield was determined by GC analysis
with hexadecane or diethylene glycol di-n-butyl ether as an internal stan-
dard.
Sonogashira reaction of aryl bromides (in diisopropylamine): Dry diiso-
propylamine (10 mL), aryl bromide (10 mmol), and acetylene (11 mmol)
were placed in a Schlenk tube. Then the catalyst was added in the given
concentration as a ready-made mixture[17] of [Na2PdCl4]/ligand (phospho-
nium salt)/CuI 4:8:3 under argon. Unless otherwise noted, the reaction
mixture was stirred at 508C in an aluminum block. After cooling to RT,
the reaction mixture was diluted with diethyl ether (15 mL) and washed
with water (10 mL), then the organic phase was dried over MgSO4, fil-
tered, and concentrated in vacuo. The product was isolated by column
chromatography (silica gel, cyclohexane/ethyl acetate 100:2). Alternative-
ly, the yield was either determined by GC analysis with hexadecane or di-
ethylene glycol di-n-butyl ether as an internal standard or by determina-
tion of the mass of the isolated iPr2NH2+BrÀ.
Buchwald–Hartwig amination of aryl halides: Dry toluene (5 mL), aryl
halide (5 mmol), amine (6 mmol), and NaOtBu (6 mmol) were placed in
a Schlenk tube. Next, the catalyst was added in the given concentration
([Na2PdCl4]/ligand phosphonium salt 1:2). The reaction mixture was stir-
red at 1208C in an aluminum block. After cooling to RT, the reaction
mixture was diluted with diethyl ether (15 mL) and washed with water
(10 mL). Then the organic phase was dried over MgSO4, filtered, and
concentrated in vacuo. The product was isolated by column chromatogra-
phy (silica gel, cyclohexane/ethyl acetate 9:1). Alternatively, the yield
was determined by GC analysis with hexadecane or diethylene glycol di-
n-butyl ether as an internal standard.
Sonogashira reaction of aryl chlorides (in DMSO): Dry DMSO (5 mL,
crown cap), aryl chloride (1.5 mmol), acetylene (2.1 mmol), and Na2CO3
(3 mmol) were placed in a Schlenk tube. Then the catalyst was added in
the given concentration, [Na2PdCl4]/ligand (phosphonium salt)/CuI 4:8:3
under argon. The reaction mixture was stirred at 100–1208C in an alumi-
num block for 12 to 20 h. After cooling to RT, the reaction mixture was
diluted with diethyl ether (15 mL) and washed with water (10 mL), then
the organic phase was dried over MgSO4, filtered, and concentrated in
vacuo. The product was isolated by column chromatography (silica, cyclo-
hexane/ethyl acetate 100:2. Alternatively, the yield was determined by
GC analysis with hexadecane or diethylene glycol di-n-butyl ether as an
internal standard.
Acknowledgements
We wish to thank the Fonds der Chemischen Industrie and the Studien-
stiftung des Deutschen Volkes for a fellowship to C.F.; for financial sup-
port from the Degussa AG and Provadis, Partner für Bildung und Bera-
tung and for experimental assistance by cand.-chem. S. Wolf and Dr. A.
Kçllhofer.
Sonogashira reaction of aryl bromides (in water)
Preparation of the catalyst stocksolution : [Na2PdCl4](0.05 mmol), 9-Et-2-
SO3HFlu-PCy2·HSO4 (18·H2SO4) (0.1 mmol) and Cs2CO3 (0.4 mmol)
were placed in a Schlenk tube under argon. Degassed water (5.0 mL) was
À
added and the mixture was stirred at 458C for 2 h until the solution
turned off white. The stock solution had
1 mol%mLÀ1 mmolÀ1 aryl halide).
a
concentration of
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ture was stirred at 1008C in an aluminum block for 1.5 to 4 h. After cool-
ing to RT, the reaction mixture was diluted with diethyl ether (15 mL)
and washed with water (10 mL), then the organic phase was dried over
MgSO4, filtered, and concentrated in vacuo. The product was isolated by
column chromatography (silica gel, cyclohexane/ethyl acetate 100:2. Al-
ternatively the yield was determined by means of GC analysis with hexa-
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ethyl ether (15 mL) and washed with water (10 mL), then the organic
phase was dried over MgSO4, filtered, and concentrated in vacuo. The
product was isolated by column chromatography (silica gel, cyclohexane/
ethyl acetate 100:2). Alternatively, the yield was determined by GC anal-
ysis with hexadecane or diethylene glycol di-n-butyl ether as an internal
standard.
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Chem. Eur. J. 2007, 13, 2701 – 2716

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Published online: January 2, 2007
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Chem. Eur. J. 2007, 13, 2701 – 2716