Phosphine oxides as stabilizing ligands for the palladium-catalyzed cross-coupling of potassium aryldimethylsilanolates

Article abstract of DOI:10.1016/j.tet.2007.02.017

The palladium-catalyzed cross-coupling reaction of potassium (4-methoxyphenyl)dimethylsilanolate (K⁺1^-) with aryl bromides has been demonstrated using triphenylphosphine oxide as a stabilizing ligand. Unsymmetrical biaryls can be prepared from a variety of aryl bromides in good yield with short reaction times. Qualitative kinetic studies compared effects of different phosphine oxides on the rate of cross-coupling and established the beneficial effect of these ligands in the reaction of electron-rich arylsilanolates. The improved yield and reproducibility of the cross-coupling of several bromides was demonstrated by direct comparison of reactions performed with and without triphenylphosphine oxide under non-rigorous exclusion of oxygen.

Full text of DOI:10.1016/j.tet.2007.02.017

Tetrahedron 63 (2007) 5730–5738
Phosphine oxides as stabilizing ligands for the palladium-catalyzed
cross-coupling of potassium aryldimethylsilanolates
*
Scott E. Denmark, Russell C. Smith and Steven A. Tymonko
Roger Adams Laboratory, Department of Chemistry, University of Illinois, 600 South Mathews Avenue,
Urbana, IL 61801, United States
Received 12 January 2007; revised 31 January 2007; accepted 5 February 2007
Available online 9 February 2007
Abstract—The palladium-catalyzed cross-coupling reaction of potassium (4-methoxyphenyl)dimethylsilanolate (K+1ꢀ) with aryl bromides
has been demonstrated using triphenylphosphine oxide as a stabilizing ligand. Unsymmetrical biaryls can be prepared from a variety of aryl
bromides in good yield with short reaction times. Qualitative kinetic studies compared effects of different phosphine oxides on the rate of
cross-coupling and established the beneficial effect of these ligands in the reaction of electron-rich arylsilanolates. The improved yield
and reproducibility of the cross-coupling of several bromides was demonstrated by direct comparison of reactions performed with and without
triphenylphosphine oxide under non-rigorous exclusion of oxygen.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
Ag2O8 and KOSiMe3 as activators for the cross-coupling of
alkenyl-7b and alkynylsilanols.9
The palladium-catalyzed cross-coupling reaction of organo-
metallic nucleophiles is one of the premier methods for car-
bon–carbon bond formation.1 The use of organostannanes,2
organoboranes,3 and organozinc4 reagents as nucleophilic
partners has been comprehensively studied and has been
elevated to name reaction status.5 Although these reactions
have been used extensively for myriad synthetic transforma-
tions, there are nevertheless inherent limitations that warrant
the development of new methods. Organosilanes, initially
investigated by Hiyama and co-workers, have become an at-
tractive alternative to some of the more commonly used do-
nors. Early implementation of organosilanes as donors with
different transferable groups required the use of fluoride to
promote the cross-coupling process (Hiyama–Hatanaka par-
adigm).6 Despite the broad applicability of this procedure
for the cross-coupling of organosilanes, the requirement
for fluoride activation is a significant disadvantage because
of, inter alia, the incompatibility with silicon protecting
groups and the aggressive nature of fluoride. Therefore, the
development of fluoride-free cross-coupling reactions of or-
ganosilanols that display the same substrate scope and rate
as the fluoride-promoted processes would be valuable.7 This
objective has been realized, in part, with the introduction of
However, the formation of biaryls from cross-coupling of
the corresponding arylsilanes (such as aryl(halo)silanes,10
aryl(halo)silylcyclobutanes,7c aryl(triallyl)silanes,11 and
aryl(trialkoxy)silanes12) has been dominated by the use of
fluoride activation.13 Although these reactions are effective,
the coupling of the arylsilanes requires more forcing condi-
tions. To address this concern and remove the requirement
for fluoride activation, we have recently demonstrated that
electron-rich aryldimethylsilanols undergo cross-coupling
reactions with aryl iodides and bromides under the action
of Cs2CO3.14 Although the scope of electrophile for the
cross-coupling of (4-methoxyphenyl)dimethylsilanol (1) is
good, the reactions are slow (3–24 h), additives are needed
to suppress homocoupling, and other arylsilanols are poor
substrates.14b Because of our continued interest in the devel-
opment of milder and more general cross-coupling reactions
of organosilanes, we made recourse to our recent discovery
that alkali metal silanolates are key reactive intermediates in
these transformations.15,16 The ease of preparation, stability,
and competence of metal silanolates have been illustrated in
the cross-coupling of both alkenyl-17 and heteroaryl18 sila-
nolates. The preformed silanolate can be directly charged
into the reaction mixture and affords a significant rate in-
crease compared to the use of TMSOK as the activator.19
Thus, we sought to develop cross-coupling conditions for
the formation of biaryls with preformed silanolates to im-
prove both the reaction time as well as the scope of the
substrates.
Keywords: Cross-coupling; Biaryls; Phosphine oxides; Silanols.
* Corresponding author. 245 Roger Adams Laboratory, Box 18, Depart-
ment of Chemistry, University of Illinois, 600 South Mathews Avenue,
Urbana, IL 61801, United States. Tel.: +1 217 333 0066; fax: +1 217
333 3984; e-mail: denmark@scs.uiuc.edu
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.02.017

S. E. Denmark et al. / Tetrahedron 63 (2007) 5730–5738
5731
2. Results
2.1. Orienting experiments
Although control experiments have unambiguously estab-
lished that phosphine oxides are not formed from the
reduction of APC,20 our misconception has led to the seren-
dipitous discovery that phosphine oxides are useful ligands
that allow for considerably faster cross-coupling reactions
compared to the use of phosphine ligands. On the basis of
these insights, we undertook a systematic study of the effect
of triphenylphosphine oxide on the cross-coupling of K+1ꢀ
with a variety of electronically and sterically demanding
aryl bromides to expand the scope of biaryl synthesis with
arylsilanolates.
Initial studies focused on the cross-coupling of preformed,
alkali metal silanolates in the presence of various additives.
Because the previous conditions for the coupling of silanols
employed phosphine ligands in conjunction with the
Cs2CO3/H2O activator,14 we were concerned about the in
situ formation of phosphine oxides through reduction of the
palladium(II) precatalyst, allylpalladium(II)chloride dimer
(APC) by the phosphine.20 The cross-coupling of potassium
(4-methoxyphenyl)dimethylsilanolate K+1ꢀ with 4-bromo-
benzotrifluoride using APC (2.5 mol %) and dppb (5 mol %)
in toluene at 90 ꢁC reached 80% conversion in 100 min,
(compared to ca. 180 min with Cs2CO3/H2O) (Fig. 1). To
test the effect of phosphine oxides on the reaction rate and
efficiency, the monoxide dppb(O) was employed and a simi-
lar conversion was reached, but in a shorter time (70 min).
Much to our surprise the use of dppb(O)2 dramatically
increased the rate and the reaction went to completion in
less than 15 min! Other phosphine oxides were then tested
to establish if this phenomenon was unique to dppb(O)2. A
more basic, chelating bisphosphine oxide, dppf(O)2 gave
identical results. Remarkably either 1 or 2 equiv of triphe-
nylphosphine oxide per palladium gave rates and conver-
sions nearly indistinguishable from those with dppb(O)2.
The beneficial effect of phosphine oxide ligands was clearly
demonstrated in the ‘ligandless’ experiment shown in
Figure 1. Under identical conditions but without a phosphine
oxide additive, the initial rate of the coupling was good,
nearly matching the rate in the presence of dppb(O), how-
ever, the reaction stalled after 30 min with the obvious for-
mation of palladium black.
2.2. Expansion of scope of aryl bromide
To establish the utility of phosphine oxides in a preparative
cross-coupling reaction, K+1ꢀ and 4-bromobenzotrifluoride
2c were combined in toluene at 90 ꢁC with APC (2.5 mol %)
and triphenylphosphine oxide (Ph3P(O), 5 mol %). The
cross-coupling product was obtained in good yield (79%)
after only 30 min. From this initial encouraging result, the
cross-coupling with a variety of aryl bromides in the pres-
ence of Ph3P(O) was undertaken to fully establish reaction
scope. The results are compiled in Table 1. Gratifyingly,
aryl bromides of diverse structural and electronic nature
underwent smooth cross-coupling to form unsymmetrical
biaryl products rapidly and in good yield. Both electron-
deficient (entries 1–3) and electron-rich (entries 5–7) 4-
substituted aryl bromides reacted within 60 min to afford
moderate to good yields. Unexpectedly, these reaction con-
ditions were not compatible with certain sensitive functional
groups. For example, aryl bromides containing a keto or cy-
ano substituent led to poor conversions (<10%) in contrast
to their behavior in Cs2CO3-promoted cross-coupling reac-
tions.14 Further complications arose in the reaction of ethyl
CH3
[(C3H5PdCl)]2 (2.5 mol %)
+
Br
CF3
H3CO
Si OK
CH3
H3CO
CF3
ligand (1-5 mol %)
toluene, 90 °C
K+1-
3c
2c
120
100
80
60
40
20
0
dppb
ligandless
dppb(O)
dppb(O)2
dppf(O)2
2 equiv Ph3PO
1 equiv Ph3PO
0
20
40
60
80
100
time (min)
Figure 1. Rate of cross-coupling as a function of ligand.

5732
S. E. Denmark et al. / Tetrahedron 63 (2007) 5730–5738
Table 1. Cross-coupling of K+1ꢀ with substituted aryl bromides using phosphine oxidesa
R
3
H3CO
CH3
[(C3H5PdCl)]2 (2.5 mol %)
+
Br
Si OK
CH3
H3CO
Ph3P(O) (5 mol %)
toluene, 90 °C
+
R
R
R
K+1-
2
4
Entry
Aryl bromide
Product
3a
Time, min
Yield,b
82
%
Product ratioc (cross-/homocoupling, 3:4)
CO2t-Bu
1
2
60
45
98:2
Br
Cl
3b
80
90:10
Br
CF3
3
4
5
3c
3d
3e
30
30
35
79
72
63
—
Br
88:12
83:17
Br
Me
Br
On-Bu
OMe
6
7
3f
60
60
61
81
82:18
—
Br
3g
Br
8
9
3h
3i
60
60
86
93:7
—
Br
Cl
67d
OTES
Br
Cl
10
11
3j
30
30
86
85
—
—
Br
Me
3k
Br
Br
12
3l
35
85
—
Me
Br
Me
13e
3m
3n
60
90
77
—
Me
NO2
14e
80f
99:1g
Br
Reaction employed 1.3 equiv of K+1ꢀ.
Yields are based on chromatographically homogeneous products.
a
b
c
d
e
f
Ratios of cross-/homocoupling are based on isolated yields unless otherwise mentioned.
Product was found to be 97% pure by GC analysis.
Reaction employed 1.5 equiv of K+1ꢀ and dppb(O) (5 mol %).
Yield based on conversion as determined by 1H NMR analysis.
Ratio of cross-/homocoupling determined by 1H NMR analysis.
g
4-bromobenzoate where unproductive consumption of the
starting aryl bromide was observed. The loss of starting
material was attributed to ester cleavage by the arylsilano-
late at elevated temperatures. This problem could be easily
remedied by making recourse to a tert-butyl ester.
Compound 2a reacted smoothly to afford an 82% yield
of the desired biaryl product (Table 1, entry 1). In all
cases, the symmetrical biaryl (formed through homocou-
pling of the bromide) was the primary side product (7–14%
yield).

S. E. Denmark et al. / Tetrahedron 63 (2007) 5730–5738
Table 2. Ligandless cross-coupling of K+1ꢀ with substituted aryl bromidesa
5733
R
3
H3CO
CH3
[(C3H5PdCl)]2 (2.5 mol %)
toluene, 90 °C
+
Br
H3CO
Si OK
+
R
CH3
R
R
K+1-
2
4
Entry
1
Aryl bromide
Product
Time, min
Conversionb
100
%
Cl
3b
60
30
60
Br
CF3
2
3
3c
3f
100 (76%)c,d
Br
OBu
>99
Br
Br
Br
4
3j
30
30
100
Cl
5
3k
>95
Me
Reaction employed 1.3 equiv of K+1ꢀ.
a
Conversion determined by 1H NMR integration of the corresponding aryl bromide.
Yield in parentheses based on pure, isolated material.
Homocoupling product (7%) isolated.
b
c
d
The rate of the reaction was not sensitive to sterically
demanding groups on the aryl bromide. Indeed, the 2-
substituted aryl bromides reacted at rates comparable to the
corresponding 4-substituted isomers. Substrates bearing
both electron-withdrawing (Table 1, entry 10) and electron-
donating (Table 1, entry 11) substituents at the 2-position re-
acted to give the desired biaryl products in good yields. The
successful coupling of the sterically hindered 2-bromomesi-
tylene dramatically illustrated this point (Table 1, entry 13).
The standard reaction conditions afforded only a 60% con-
version with visible formation of Pd black after 10 min. Us-
ing 1.5 equiv of the arylsilanolate and the hemilabile ligand
dppb(O), the reaction was complete in 90 min and the biaryl
product was isolated in good yield (77%). Cross-coupling re-
actions of aryl bromides bearing a heteroatom substituent at
the 2-position were problematic and provided only 20% con-
version in the best case. These groups containing Lewis basic
atoms (e.g., O, N) most likely coordinate to the metal center
and thus inhibit productive cross-coupling from occurring.21
On the other hand, reaction of K+1ꢀ with meta-substituted
aryl bromides proceeded smoothly as both the 3-chloro as
well the labile 3-triethylsilyloxymethyl substituents were
compatible (Table 1, entries 8 and 9). The stability of the sen-
sitive silicon protecting group illustrates the mildness of the
reaction conditions even at elevated temperatures.
4-bromobenzotrifluoride using APC (2.5 mol %) in toluene
at 90 ꢁC went to completion in 30 min without Ph3P(O).
This result was contrary to the results obtained during the ki-
netic studies of this system. Interestingly, the cross-coupling
in the absence of the ligand was rapid and general for the
cases tested (Table 2). Both ortho- and para-substituted
aryl bromides reacted quickly all reaching >99% conver-
sion. The reaction with the 4-bromobenzotrifluoride was re-
peated on a preparative scale and a 76% isolated yield was
achieved with 7% undesired homocoupling product. These
results contradicted those obtained during the kinetic analy-
sis of this system. Thus, to reconcile the disparate behavior,
it was necessary to revisit the previous examples to more
precisely understand the effect of added phosphine oxide.
2.3. The role of phosphine oxide
The principle difference between the kinetic runs illustrated
in Figure 1, and the results in Table 2 was the frequent sam-
pling of the former reactions that could have compromised
the inert atmosphere. To identify the impact of phosphine
oxide additives on the rate and reproducibility of the cross-
coupling under non-optimal reaction conditions, several rep-
resentative bromides (2b, 2c, 2f, 2k) were re-examined. For
operational simplicity and to assay the robustness of the pro-
cedure, all reagents (except the hygroscopic silanolate) were
weighed open to the atmosphere and added to the reaction
flask without taking the usual precautions to remove oxygen.
Each reaction (0.5 mmol) was performed in triplicate in
side-by-side experiments both with and without Ph3P(O)
and the progress was monitored by GC analysis. The graphs
in Figure 2 show the results for each of the four substrates.
The blue lines represent the reactions run with Ph3P(O)
Although the effectiveness of Ph3P(O) as a ligand had
been established for the cross-coupling of K+1ꢀ, we none-
theless needed to perform the preparative reactions in the
absence of a ligand for direct comparisons. Therefore, a
representative set of substrates was subjected to the cross-
coupling reaction conditions in the absence of Ph3P(O).
Surprisingly, the preparative cross-coupling of K+1ꢀ with

5734
S. E. Denmark et al. / Tetrahedron 63 (2007) 5730–5738
4-Bromobenzotrifluoride (2c)
4-Bromochlorobenzene (2b)
100
100
90
80
70
60
50
40
30
20
10
0
90
80
70
60
50
40
30
20
10
0
Ph3P(O)
ligandless
Ph3P(O)
ligandless
Ph3P(O)
(2 mmol)
ligandless
(2 mmol)
Ph3P(O)
ligandless
Ph3P(O)
ligandless
Ph3P(O)
ligandless
0
10
20
30 40
time (min)
50
60
70
0
10
20
time (min)
30
40
4-Bromobutoxybenzene (2f)
2-Bromotoluene (2k)
100
90
80
70
60
50
40
30
20
10
0
100
90
80
70
60
50
40
30
20
10
0
Ph3P(O)
ligandless
Ph3P(O)
ligandless
Ph3P(O)
ligandless
Ph3P(O)
ligandless
Ph3P(O)
ligandless
Ph3P(O)
(2 mmol)
ligandless
(2 mmol)
0
10
20
30 40
time (min)
50
60
70
0
10
20
time (min)
30
40
Figure 2. Comparison of reaction profiles.
and the red lines represent those without. As indicated in the
legend, pairs of experiments executed side-by-side are repre-
sented by the same icons (squares, circles, diamonds, etc.).
In addition, the effect of scale was examined and is illus-
trated by the dashed lines (2.0 mmol scale) on the charts
for 2c and 2f. The beneficial effect of Ph3P(O) is immedi-
ately apparent in the coupling with 2b (Fig. 2). In the pres-
ence of this ligand, the reaction proceeded smoothly and
with excellent reproducibility (conversions 59–67%). In
contrast, in the absence of Ph3P(O) the reaction was irrepro-
ducible and afforded consistently lower yields (18–57%). A
similar irreproducibility was seen with 2c. In the presence of
Ph3P(O) the reactions tracked nearly identically affording
76–78% conversion in 35 min, whereas the ligandless runs
afforded 34–62% conversion in the same time. When the
scale was increased 4-fold, the yields for both reaction im-
proved, nonetheless, the yield in the presence of Ph3P(O) re-
mained higher (89 vs 74%). Similar results were seen with
bromides 2f and 2k. In both cases the presence of Ph3P(O)
resulted in improved conversion and reproducibility of the
reaction. The striking behavior of 2-bromotoluene (2k) de-
serves comment. Despite the steric encumbrance, this sub-
strate reacted faster than any other in the group reaching
completion in less than 10 min in the presence of the ligand.
As clearly seen in the graph, the ligandless reactions were
slower and less reproducible.
coupling reaction. However, the origin of this effect is not
well understood, but may arise from a weak stabilizing inter-
action with the palladium catalyst. Because these reactions
are performed in a non-coordinating solvent (toluene), stabi-
lization from the solvent is not likely. Therefore, the phos-
phine oxide could be serving as a labile ligand that can
prevent catalyst decomposition by a number of mechanisms
including oxidation or agglomeration.
Although phosphine oxides are not generally recognized
as good ligands for late transition metals22 a dppf(O)2palla-
dium(II)Cl2 complex has been reported.23 The existence of
this complex demonstrates the ability of phosphine oxides
to bind directly to Pd(II), but no discrete coordination
chemistry to Pd(0) has been reported and no synthetic
transformation of these species has been described. On
the other hand, there is a wealth of knowledge (both struc-
tural and synthetic) on the use of bisphosphine monoxides
as ‘hemilabile’ ligands for palladium. Hemilabile ligands,
which contain both soft and hard coordinating atoms are
a promising new class of ligands for a variety of synthetic
transformations.24 The ability of these ligands to stabilize
late transition metals while forming weak metal complexes
affording more active metal centers is of interest. The bis-
phosphine monoxides are effective in reactions such as
carbonylation,25 cycloaddition,26 and oligomerization of
olefins.27
3. Discussion
How then does Ph3P(O) influence the coupling reactions
by itself? An intriguing hypothesis is that the phosphine
oxide stabilizes the Pd(0) atoms/particles formed from di-
rect reduction of APC by the silanolate.20 The reduction
The results in Table 1 and Figure 2 clearly show that the
phosphine oxide additive has a salutary effect in the cross-

S. E. Denmark et al. / Tetrahedron 63 (2007) 5730–5738
5735
of APC leads to the formation of highly active Pd nanopar-
5.2. General Procedure I: analysis and kinetic mea-
surements for cross-coupling of KD1L with 4-bromo-
benzotrifluoride using different phosphines (oxides)
ticles that can readily catalyze reactions, but that can also
form inactive clusters.28 Several methods have been devel-
oped to stabilize Pd nanoparticles, such as the use of
aminomethylated TentaGel in a resin form.29 In addition,
Li has described the use of secondary phosphine oxides
(P-bound) in the palladium-catalyzed coupling of aryl chlo-
rides with phenylboronic acid.30 One of the more creative
uses of phosphine oxides as labile ligands was reported
by Bawendi and co-workers who prepared a poly(ethylene
glycol) phosphine oxide polymer to stabilize water-soluble
palladium nanoparticles.31 Interestingly, an example of a
Suzuki cross-coupling was provided, clearly demonstrating
the ability of phosphine oxides to intervene productively in
catalytic processes. In addition, phosphine oxides have
been used extensively to stabilize nanoparticles of other
metals.32
5.2.1. Kinetic measurement using 1,3-bis(diphenylphos-
phino)butane dioxide (dppb(O)2). In a dry box, naphthal-
ene (48 mg), APC (4.6 mg, 0.0125 mmol, 0.025 equiv),
dppb(O)2 (11.0 mg, 0.025 mmol, 0.05 equiv), and 4-bromo-
benzotrifluoride (70 mL, 0.50 mmol, 1.0 equiv) were dis-
solved in dry toluene (1.0 mL) at rt in a one-neck, 5-mL
round-bottom flask with a magnetic stir bar and fitted with
a reflux condenser and three-way stop-cock (fitted with an
argon inlet and a rubber septum). To this solution was added
K+1ꢀ (165 mg, 0.75 mmol, 1.5 equiv). The flask was re-
moved from the dry box, the stop-cock purged with argon,
and was placed in a 90 ꢁC oil bath. Reaction progress was
monitored by GC analysis. Sampling of the reaction was per-
formed by removing 30-mL aliquots of the mixture by sy-
ringe and quenching the aliquots at regular intervals. The
quench was performed as follows: the withdrawn aliquot
of the reaction mixture was injected into 100 mL of a 10%
aqueous solution of 2-dimethylaminoethanethiol hydrochlo-
ride. This yellow solution was diluted with 1.5 mL of ether
and the organic layer was filtered through a 0.5ꢂ1.0 cm
plug of silica gel. The filtrate was analyzed by GC. Naphtha-
lene, tR 1.53 min; 3c, tR 5.72 min (HP-1, 170 ꢁC (5 min),
50 ꢁC/min, 225 ꢁC (2 min), 16 psi).
The weak coordination of the phosphine oxide to the palla-
dium catalyst prevents the precipitation of palladium black.
Therefore, a constant catalyst loading is maintained through-
out the reaction resulting in good reaction rates and repro-
ducible yields. In the absence of this additive, the reactions
proceed, but with varying rates and conversions. The irrepro-
ducibility might arise from variable degrees of oxygen con-
tamination of the reaction apparatus resulting in inconsistent
rates of catalyst decomposition. Thus, under rigorously
controlled anaerobic conditions, the effect of the phosphine
oxide is negligible and reactions proceed rapidly and with
excellent conversion as was seen in the control experiments
in Table 2. However, the reactions become more robust and
do not require special precautions if Ph3P(O) is added. In this
sense, the phosphine oxide can be seen as a ‘buffer’ or scav-
enger that allows reactions to proceed, even under less than
ideal conditions.
5.3. General Procedure II: cross-coupling of potassium
dimethyl(4-methoxyphenyl)silanolate with aryl
bromides (Table 1)
5.3.1. Butyl 40-methoxy-4-biphenylcarboxylate (3a)
(Table 1, entry 1). In a dry box, an oven-dried, 5-mL,
one-neck, round-bottom flask containing a magnetic stir
bar equipped with a reflux condenser and a three-way argon
inlet capped with a septum, APC (9 mg, 0.025 mmol,
2.5 mol %) and triphenylphosphine oxide (Ph3P(O), 14 mg,
0.05 mmol, 5 mol %) were combined. Dry, deoxygenated
toluene (2.0 mL) and 4-bromo(tert-butyl)benzoate (257 mg,
1.0 mmol, 1.0 equiv) were added followed by potassium
dimethyl(4-methoxyphenyl)silanolate K+1ꢀ (286 mg,
1.3 mmol, 1.3 equiv). The flask was closed-off to the atmo-
sphere and transferred to a hood. The reaction mixture was
heated to 90 ꢁC under argon. After TLC analysis showed
complete consumption of the aryl bromide, the mixture
was cooled to rt and subjected to an aqueous work-up. The
reaction mixture was poured onto H2O (10 mL) and was ex-
tracted with ethyl acetate (3ꢂ10 mL). The organics were
washed with brine (10 mL) and dried (MgSO4). The
combined organics were concentrated in vacuo and the
residue was purified by column chromatography (SiO2,
30 mmꢂ200 mm, CH2Cl2/hexanes, 1/1) followed by recrys-
tallization from ethanol to afford 234 mg of 3a as analyti-
cally pure colorless plates. Mp 107–108 ꢁC (EtOH); 1H
NMR (500 MHz, CDCl3) d 8.04 (d, 2H, J¼8.8 Hz,
HC(3)), 7.60 (d, 2H, J¼8.8 Hz, HC(2)), 7.57 (d, 2H,
J¼8.8 Hz, HC(20)), 7.00 (d, 2H, J¼8.8 Hz, HC(30)), 3.86
(s, 3H, H3CO(300)), 1.62 (s, 9H, H3C(200)); 13C NMR
(126 MHz, CDCl3) d 165.7 C(5), 159.7 C(40), 144.7 C(20),
132.5 C(1), 130.1 C(10), 129.9 C(3), 128.3 C(20), 126.3
C(2), 114.3 C(30), 80.8 C(100), 55.3 C(300), 28.2 C(200); IR
(KBr) 2979 (m), 2925 (m), 2827 (w), 1938 (w), 1892 (w),
4. Conclusions
In summary, the cross-coupling of an electron-rich arylsila-
nolate with a variety of aryl bromides proceeds smoothly
with Ph3P(O) as a ligand. The use of a preformed arylsilano-
late in combination with an extremely labile ligand to pro-
vide unsymmetrical biaryls compares very favorably with
the use of Cs2CO3 and arylsilanols. This method has the ad-
ditional advantage that the silanolate is easily prepared and
stored, and can be charged directly into the reaction vessel.
Although the cross-coupling reactions also function in the
absence of ligands, control studies showed that this process
is sensitive to oxygen or moisture and Ph3P(O) can serve as
a ‘buffering’ ligand that helps to stabilize highly active
palladium nanoparticles throughout the catalytic cycle. Fur-
ther studies to extend this process to other arylsilanolates
along with investigations into the mechanism of the homo-
coupling pathway are ongoing and will be reported in due
course.
5. Experimental section
5.1. General experimental methods
See the Supplementary data.

5736
S. E. Denmark et al. / Tetrahedron 63 (2007) 5730–5738
1871 (w), 1709 (s), 1601 (s), 1531 (m), 1497 (m), 1452 (m),
1372 (m), 1301 (s), 1170 (s), 1112 (s), 1037 (s), 1015 (m),
833 (s), 774 (s), 698 (w) cmꢀ1; MS (EI, 70 eV) m/z 284
(M+, 4), 228 (100), 213 (21), 185 (21), 139 (12), 117 (9),
91 (6); Rf 0.30 (hexanes/CH2Cl2, 2/1) [silica gel, UV (256,
366)]. Anal. Calcd for C18H20O3: C, 76.03; H, 7.09. Found:
C, 75.86; H, 7.22.
139 (15), 113 (9), 98 (5), 87 (13), 75 (19), 63 (27); Rf 0.28
(hexanes/CH2Cl2, 6/1) [silica gel, UV]. Anal. Calcd for
C13H11ClO: C, 71.40; H, 5.07. Found: C, 71.25; H, 4.99.
5.3.4. 40-Methoxy-3-(triethylsilyloxymethyl)biphenyl (3i)
(Table 1, entry 9). Following General Procedure II, APC
(9 mg, 0.025 mmol, 2.5 mol %), Ph3P(O) (14 mg,
0.05 mmol, 5 mol %), toluene (2.0 mL), 1-bromo-3-(tri-
ethylsilyloxymethyl)benzene (301 mg, 1.0 mmol, 1.0 equiv),
and K+1cꢀ (286 mg, 1.3 mmol, 1.3 equiv) were combined
and heated to 90 ꢁC. After 60 min, the mixture was cooled
to rt and subjected to an aqueous work-up. Purification by
column chromatography (SiO2, 30 mmꢂ220 mm, hexanes/
CH2Cl2, 6/1) followed by reverse phase chromatography (re-
verse phase silica, 20 mmꢂ150 mm, MeOH/H2O, 12/1) af-
5.3.2. 4-Butoxy-40-methoxybiphenyl (3f) (Table 1, entry
6). Following General Procedure II, APC (15 mg,
0.025 mmol, 2.5 mol %), Ph3P(O) (23 mg, 0.05 mmol,
5 mol %), toluene (3.3 mL), 1-bromo-4-butoxybenzene
(174 mL, 1.0 mmol, 1.0 equiv), and K+1cꢀ (286 mg,
1.3 mmol, 1.3 equiv) were combined and heated to 90 ꢁC.
After 60 min, the mixture was cooled to rt and subjected to
an aqueous work-up. Purification by column chromato-
graphy (SiO2, 40 mmꢂ200 mm, hexanes/CH2Cl2, gradient
4/1 to 2/1) followed by recrystallization afforded 155 mg
(61%) of 3f as colorless plates. Mp 132–133 ꢁC (EtOH);
1H NMR (500 MHz, CDCl3) d 7.49 (d, 2H, J¼8.6 Hz,
HC(2)), 7.48 (d, 2H, J¼8.8 Hz, HC(20)), 6.97 (d, 2H,
J¼8.6 Hz, HC(3)), 6.96 (d, 2H, J¼8.8 Hz, HC(30)), 4.01 (t,
2H, J¼6.5 Hz, HC(100)), 3.85 (s, 3H, HC(1000)), 1.80 (tt,
2H, J1¼6.5 Hz, J2¼7.5 Hz, HC(200)), 1.52 (tq, 2H,
J1¼J2¼7.5 Hz, HC(300)), 1.00 (t, 3H, J¼7.5 Hz, HC(400));
13C NMR (126 MHz, CDCl3) d 158.6 C(4), 158.3 C(40),
133.5 C(1), 133.2 C(10), 127.7 C(2), 127.7 C(20), 114.7
C(3), 114.1 C(30), 67.7 C(100), 55.3 C(1000), 31.3 C(200), 19.2
C(300), 13.8 C(400); IR (KBr) 2950 (s), 2925 (s), 2873 (m),
2372 (w), 2056 (w), 1891 (w), 1602 (s), 1501 (s), 1470
(m), 1398 (m), 1323 (m), 1274 (s), 1263 (s), 1178 (s),
1137 (m), 1121 (m), 1075 (w), 1044 (s), 1005 (m), 969
(w), 819 (s), 806 (s) cmꢀ1; MS (EI, 70 eV) m/z 256 (M+,
91), 200 (100), 185 (49), 157 (15), 128 (12), 102 (3); Rf
0.27 (hexanes/CH2Cl2, 2/1) [silica gel, UV]. Anal. Calcd
for C17H20O2: C, 79.65; H, 7.86. Found: C, 79.85; H, 7.90.
1
forded 220 mg (67%) of 3i as a colorless oil. H NMR
(500 MHz, CDCl3) d 7.57 (m, 1H, HC(2)), 7.56 (d, 2H,
J¼8.8 Hz, HC(20)), 7.46 (d, 1H, J¼7.6 Hz, HC(6)), 7.40 (t,
1H, J¼7.6 Hz, HC(5)), 7.31 (d, 1H, J¼7.6 Hz, HC(4)),
7.00 (d, 2H, J¼8.8 Hz, HC(30)), 4.82 (s, 2H, HC(200)), 3.87
(s, 3H, HC(100)), 1.03 (t, 9H, J¼7.8 Hz, HC(400)), 0.70 (q,
6H, J¼7.8 Hz, HC(300)); 13C NMR (126 MHz, CDCl3)
d 159.1 C(4), 141.7 C(3), 140.7 C(10), 133.8 C(1), 128.6
C(5), 128.1 C(2 and 20), 125.4 C(6), 124.6 C(4), 114.1
C(30), 64.8 C(7), 55.3 C(100), 6.8 C(300), 4.5 C(200); IR
(neat) 3023 (w), 2950 (s), 2909 (s), 2863 (s), 2361 (w),
2046 (w), 1886 (w), 1697 (w), 1607 (s), 1519 (s), 1483 (s),
1460 (s), 1439 (s), 1411 (m), 1372 (m), 1284 (s), 1248 (s),
1181 (s), 1108 (s), 1074 (s), 1008 (s), 971 (m), 858 (m),
829 (s), 783 (s), 744 (s) cmꢀ1; MS (EI, 70 eV) m/z 328
(M+, 56), 299 (70), 269 (26), 197 (100), 165 (9), 154 (7),
99 (9), 59 (4); HRMS (EI, 70 eV) m/z calcd for
C20H28O2Si (M+): 328.1859; found: 328.1862; Rf 0.38 (hex-
anes/CH2Cl2, 1/1) [silica gel, UV, CAN]; GC tR¼9.00 min
(HP-1, 150 ꢁC, 2 min, 50 ꢁC/min, 250 ꢁC, 6.5 min, 16 psi).
5.3.5. 2-Chloro-40-methoxybiphenyl (3j) (Table 1, entry
10). Following General Procedure II, APC (9 mg,
0.025 mmol, 2.5 mol %), Ph3P(O) (14 mg, 0.05 mmol,
5 mol %), toluene (2.0 mL), 2-chlorobromobenzene
(116 mL, 1.0 mmol, 1.0 equiv), and K+1cꢀ (286 mg,
1.3 mmol, 1.3 equiv) were combined and heated to 90 ꢁC.
After 30 min, the mixture was cooled to rt and subjected to
an aqueous work-up. Purification by column chromato-
graphy (SiO2, 30 mmꢂ220 mm, hexanes/CH2Cl2, 6/1) fol-
lowed by Kugelrohr distillation afforded 188 mg (86%) of
3j as an analytically pure, colorless oil. Bp 130 ꢁC (ABT,
5.3.3. 3-Chloro-40methoxybiphenyl (3h) (Table 1, entry
8). Following General Procedure II, APC (9 mg,
0.025 mmol, 2.5 mol %), Ph3P(O) (14 mg, 0.05 mmol,
5 mol %), toluene (2.0 mL), 3-chlorobromobenzene
(117 mL, 1.0 mmol, 1.0 equiv), and K+1cꢀ (286 mg,
1.3 mmol, 1.3 equiv) were combined and heated to 90 ꢁC.
After 60 min, the mixture was cooled to rt and subjected to
an aqueous work-up. Purification by column chromato-
graphy (SiO2, 30 mmꢂ200 mm, hexanes/CH2Cl2, gradient
7/1 to 6/1) followed by recrystallization afforded 189 mg
(86%) of 3h as analytically pure colorless plates. Mp 56–
1
0.2 mmHg); H NMR (500 MHz, CDCl3) d 7.49 (dd, 1H,
1
57 ꢁC (EtOH); H NMR (500 MHz, CDCl3) d 7.55 (t, 1H,
J1¼1.3 Hz, J2¼7.9 Hz, HC(3)), 7.42 (d, 2H, J¼8.8 Hz,
HC(20)), 7.36 (dd, 1H, J1¼1.9 Hz, J2¼7.3 Hz, HC(6)),
7.32 (ddd, 1H, J1¼1.5 Hz, J2¼J3¼7.9 Hz, HC(5)), 7.28
(ddd, 1H, J1¼1.9 Hz, J2¼J3¼7.9 Hz, HC(4)), 7.01 (d, 2H,
J¼8.8 Hz, HC(6)), 3.88 (s, 3H, H3CO(100)); 13C NMR
(126 MHz, CDCl3) d 159.1 C(40), 140.1 C(1), 132.6 C(2),
131.7 C(10), 131.4 C(6), 130.6 C(20), 129.9 C(3), 128.2
C(4), 126.8 C(5), 113.4 C(30), 55.2 C(100); IR (neat) 3062
(m), 3002 (m), 2957 (m), 2935 (m), 2836 (m), 2546 (w),
2359 (w), 2047 (w), 1888 (w), 1613 (w), 1579 (m), 1516
(s), 1469 (s), 1441 (s), 1408 (m), 1296 (s), 1250 (s), 1179
(s), 1126 (m), 1109 (m), 1074 (m), 1037 (s), 1018 (m),
1002 (m), 946 (w), 831 (s), 805 (m), 757 (s), 733 (s), 665
(m) cmꢀ1; MS (EI, 70 eV) m/z 220 (36), 218 (M+, 100),
205 (5), 203 (15), 177 (5), 175 (13), 149 (4), 139 (10), 115
J1¼J2¼1.9 Hz, HC(2)), 7.51 (d, 2H, J¼8.8 Hz, HC(20)),
7.43 (dt, 1H, J1¼J2¼1.3 Hz, J3¼7.7 Hz, HC(4)), 7.34 (t,
1H, J¼7.7 Hz, HC(5)), 7.28 (dq, 1H, J1¼1.3 Hz,
J2¼2.1 Hz, J3¼7.7 Hz, HC(6)), 6.99 (d, 2H, J¼8.8 Hz,
HC(30)), 3.86 (s, 3H, H3CO(100)); 13C NMR (126 MHz,
CDCl3) d 159.5 C(40), 142.6 C(1), 134.6 C(3), 132.2 C(10),
129.9 C(5), 128.1 C(20), 126.8 C(2), 126.6 C(6), 124.8
C(4), 114.3 C(30), 55.3 C(100); IR (KBr) 3059 (w), 2956
(m), 2935 (w), 2904 (w), 2832 (w), 2362 (m), 2341 (w),
1894 (w), 1605 (m), 1576 (m), 1561 (m), 1512 (m), 1470
(m), 1390 (w), 1290 (m), 1279 (m), 1248 (s), 1184 (m),
1101 (m), 1021 (s), 884 (w), 832 (s), 786 (s), 687 (s), 667
(m) cmꢀ1; MS (EI, 70 eV) m/z 220 (33), 218 (M+, 100),
205 (12), 203 (38), 177 (13), 175 (41), 168 (3), 149 (15),

S. E. Denmark et al. / Tetrahedron 63 (2007) 5730–5738
5737
(3), 75 (2), 63 (2); TLC Rf 0.43 (hexanes/CH2Cl2, 6/1) [silica
gel, UV]. Anal. Calcd for C13H11ClO: C, 71.40; H, 5.07.
Found: C, 71.21; H, 4.99.
The reaction was sampled by removing 30-mL aliquots of the
mixture using syringe and quenching the aliquots at regular
intervals (5 min). The quench was performed as follows: the
withdrawn aliquot of the reaction mixture was injected into
100 mL of a 10% aqueous solution of 2-dimethylaminoetha-
nethiol hydrochloride. This yellow solution was diluted with
1.5 mL of ether and the organic layer was filtered through a
0.5ꢂ1.0 cm plug of silica gel. The filtrate was subjected to
GC analysis. Naphthalene, tR 1.53 min; 3c, tR 5.72 min
(HP-1, 170 ꢁC (5 min), 50 ꢁC/min, 225 ꢁC (2 min), 16 psi).
5.4. General Procedure III: cross-coupling of potassium
dimethyl(4-methoxyphenyl)silanolate with aryl
bromides without a ligand (Table 2)
5.4.1. 40-Methoxy-4-(trifluoromethyl)biphenyl (3c)
(Table 2, entry 2). In an oven-dried, 5-mL, one-neck, round-
bottom flask containing a magnetic stir bar equipped with
a reflux condenser and an argon inlet capped with a septum,
was charged APC (9 mg, 0.025 mmol, 2.5 mol %). The flask
was sequentially evacuated and purged with argon twice.
Toluene (1.0 mL) and 4-bromobenzotrifluoride (138 mL,
1.0 mmol, 1.0 equiv) were added followed by dimethyl-
(4-methoxyphenyl)silanolate K+1cꢀ (286 mg, 1.3 mmol,
1.3 equiv). The reaction mixture was heated to 90 ꢁC under
argon. After TLC analysis showed complete consumption of
the aryl bromide, the mixture was cooled to rt and subjected
to an aqueous work-up. The reaction mixture was poured
onto H2O (10 mL) and was extracted with ethyl acetate
(3ꢂ10 mL). The organics were washed with brine (10 mL)
and dried (MgSO4). The combined organics were concen-
trated in vacuo and the residue was purified by column chro-
matography (SiO2, 30 mmꢂ200 mm, hexanes/CH2Cl2, 5/1)
followed by recrystallization from ethanol to afford 191 mg
of 3c as colorless flake crystals. The spectroscopic data
matched those from the literature.14 Mp 121–122 ꢁC
Acknowledgements
We are grateful to the National Institutes of Health for gen-
erous financial support (GM 63167). R.C.S. acknowledges
the University of Illinois for a graduate fellowship. S.A.T.
thanks Johnson and Johnson PRI for a graduate fellowship.
Supplementary data
Complete experimental details for all preparative procedures
along with full characterization of all starting materials and
products as well as raw data for kinetic analyses (48 pages)
are provided. Supplementary data associated with this article
can be found in the online version, at doi:10.1016/j.tet.2007.
02.017.
1
References and notes
(EtOH); H NMR (500 MHz, CDCl3) d 7.68–7.64 (m, 4H,
HC(2), HC(3)), 7.55 (d, 2H, J¼8.8 Hz, HC(20)), 7.01 (d,
2H, J¼8.8 Hz, HC(30)), 3.87 (s, 3H, H3CO(100)); 13C NMR
(126 MHz, CDCl3) d 159.9 C(40), 144.3 C(1), 132.2 C(10),
128.7 (q, JCF¼32.2 Hz, C(4)), 128.3 C(20), 126.9 C(2),
125.7 (q, JCF¼3.7 Hz, C(3)), 124.4 (q, JCF¼271.6 Hz,
C(5)), 114.4 C(30), 55.3 C(100); 19F NMR (376 MHz,
CDCl3) d ꢀ62.6 CF3(5); TLC Rf 0.63 (hexanes/CH2Cl2,
4/1) [silica gel, UV]; GC tR¼6.55 min (HP-1, 150 ꢁC
(5 min), 50 ꢁC/min, 250 ꢁC (2 min), 16 psi).
1. Metal-Catalyzed Cross-Coupling Reactions; de Meijere, A.,
Diederich, F., Eds.; Wiley-VCH: Weinheim, 2004.
2. (a) Farina, V.; Krishnamurthy, V.; Scott, W. J. The Stille
Reaction; Wiley-Interscience: New York, NY, 1998; (b)
Stille, J. Angew. Chem., Int. Ed. Engl. 1986, 25, 508–524; (c)
Mitchell, T. N. Metal-Catalyzed Cross-Coupling Reactions;
de Meijere, A., Diederich, F., Eds.; Wiley-VCH: Weinheim,
Germany, 2004; Vol. 1, Chapter 3.
3. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483;
(b) Suzuki, A. J. Organomet. Chem. 1999, 576, 147–168; (c)
Miyaura, N. Metal-Catalyzed Cross-Coupling Reactions; de
Meijere, A., Diederich, F., Eds.; Wiley-VCH: Weinheim,
Germany, 2004; Vol. 2, Chapter 2.
5.5. General Procedure IV: comparison of cross-
coupling of potassium dimethyl(4-methoxyphenyl)-
silanolate with aryl bromides with and without
triphenylphosphine oxide
4. Knochel, P.; Calaz, M. I.; Hupe, E. Metal-Catalyzed Cross-
Coupling Reactions; de Meijere, A., Diederich, F., Eds.;
Wiley-VCH: Weinheim, Germany, 2004; Vol. 1, Chapter 11.
5.5.1. 4-Bromobenzotrifluoride using Ph3P(O). In a dry
box, K+1ꢀ (143 mg, 0.50 mmol, 1.3 equiv) was charged into
an oven-dried vial and sealed. The vial was transferred from
the dry box into the hood. Naphthalene (31.7 mg), APC
(4.6 mg, 0.0125 mmol, 0.025 equiv), Ph3P(O) (7.0 mg,
0.025 mmol, 0.05 equiv) were charged into a one-neck,
5-mL round-bottom flask with a magnetic stir bar and fitted
with a reflux condenser (during weighing, the round-bottom
flask was kept open to an ambient atmosphere). The con-
denser capped with an argon adapter and the solids were
dissolved in dry toluene (1.0 mL added via syringe) resulting
in a yellow solution. 4-Bromobenzotriflouride (69 mL,
0.5 mmol, 1.0 equiv) was then added by removing the argon
adapter and adding the material via syringe. To this solution
was added the solid K+1ꢀ by again removing the argon
adapter and adding the material as a solid. The flask was
opened to an argon atmosphere and was placed in a 90 ꢁC
oil bath. Reaction progress was monitored by GC analysis.
€
ꢀ
5. Kurti, L.; Czako, B. Strategic Application of Named Reaction in
Organic Syntheses; Elsevier: Burlington, 2005; pp 310, 438,
448.
6. (a) Hiyama, T. J. Organomet. Chem. 2002, 653, 58–61; (b)
Hiyama, T.; Hatanka, Y. Pure Appl. Chem. 1994, 66, 1471–
1478; (c) Hiyama, T. Metal-Catalyzed Cross-Coupling
Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH:
Weinheim, Germany, 1998, Chapter 10.
7. (a) Denmark, S. E.; Sweis, R. F. Acc. Chem. Res. 2002, 35, 835–
846; (b) Denmark, S. E.; Sweis, R. F. J. Am. Chem. Soc. 2001,
123, 6439–6440; (c) Denmark, S. E.; Sweis, R. F. Metal-
Catalyzed Cross-Coupling Reactions; de Meijere, A.,
Diederich, F., Eds.; Wiley-VCH: Weinheim, Germany, 2004;
Vol. 1, Chapter 4.
8. Hirabayashi, K.; Mori, A.; Kawashima, J.; Sugoro, M.;
Nishihara, Y.; Hiyama, T. J. Org. Chem. 2000, 65, 5342–5349.

5738
S. E. Denmark et al. / Tetrahedron 63 (2007) 5730–5738
9. Denmark, S. E.; Tymonko, S. A. J. Org. Chem. 2003, 68, 9151–
9154.
21. Basu, B.; Freijd, T. Acta Chem. Scand. 1996, 50, 316–322.
22. (a) Slone, C. S.; Weinberger, D. A.; Mirkin, C. A. Prog. Inorg.
Chem. 1999, 48, 233–350; (b) Parr, J. Comprehensive
Coordination Chemistry II; McCleverty, J. A., Meyer, T. J.,
Eds.; Elsevier: Amsterdam, 2004; Vol. 1, p 280; (c) Burford,
N. Coord. Chem. Rev. 1992, 112, 1–18.
10. (a) Hatanaka, Y.; Hiyama, T. Tetrahedron Lett. 1990, 31, 2719–
2722; (b) Hatanaka, Y.; Fukushima, S.; Hiyama, T. Chem. Lett.
1989, 1711–1714; (c) Homsi, F.; Hosoi, K.; Nozaki, K.;
Hiyama, T. J. Organomet. Chem. 2001, 624, 208–216; (d)
Hagiwara, E.; Gouda, K.; Hatanaka, Y.; Hiyama, T.
Tetrahedron Lett. 1997, 38, 439–442; (e) Hatanaka, Y.; Goda,
K.; Okahara, Y.; Hiyama, T. Tetrahedron 1994, 50, 8301–8316.
11. (a) Nakao, Y.; Oda, T.; Sahoo, A. K.; Hiyama, T. J. Organomet.
Chem. 2003, 687, 570–573; (b) Sahoo, A. K.; Nakao, Y.;
Hiyama, T. Chem. Lett. 2004, 33, 632–633.
12. (a) Mowery, M. E.; DeShong, P. Org. Lett. 1999, 1, 2137–2140;
(b) Lee, H. M.; Nolan, S. P. Org. Lett. 2000, 2, 2053–2055; (c)
Mowery, M. E.; DeShong, P. J. Org. Chem. 1999, 64, 1684–
1688.
13. A clever, internally activated, non-fluoride coupling of aryl[(2-
hydroxymethyl)phenyl]dimethylsilanes has also been reported:
Nakao, Y.; Imanaka, H.; Sahoo, A. K.; Yada, A.; Hiyama, T.
J. Am. Chem. Soc. 2005, 127, 6952–6953.
14. (a) Denmark, S. E.; Ober, M. H. Org. Lett. 2003, 5, 1357–1360;
(b) Denmark, S. E.; Ober, M. H. Adv. Synth. Catal. 2004, 346,
1703–1714.
15. Denmark, S. E.; Sweis, R. F. J. Am. Chem. Soc. 2004, 126,
4876–4882.
16. For a discussion of cross-coupling reactions using silanolates
see: Denmark, S. E.; Baird, J. D. Chem.—Eur. J. 2006, 12,
4954–4963.
17. Denmark, S. E.; Kallemeyn, J. M. J. Am. Chem. Soc. 2006, 128,
15958–15959.
23. Yeo, J. S. L.; Vittal, J. J.; Hor, T. S. A. Chem. Commun. 1999,
1477–1478.
24. Grushin, V. V. Chem. Rev. 2004, 104, 1629–1662.
25. (a) Wegman, R. W.; Abatjoglou, A. G.; Harrison, A. M.
J. Chem. Soc., Chem. Commun. 1987, 1891–1892; (b)
Wegman, R. W.; Schrek, D. J. Eur. Pat. Appl. EP 173170,
1986; (c) Wegman, R. W.; Abatjoglou, A. G. PCT Int. Appl.
8600888, 1986; U.S. Patent 4,670,570, 1987.
26. (a) Faller, J. W.; Liu, X.; Parr, J. Chirality 2000, 12, 325–337;
(b) Faller, J. W.; Parr, J. Organometallics 2000, 19, 1829–1832;
(c) Faller, J. W.; Grimmond, B. J.; Curtis, M. Organometallics
2000, 19, 5174–5181; (d) Faller, J. W.; Lavoie, A. R.;
Grimmond, B. J. Organometallics 2002, 21, 1662–1666; (e)
Faller, J. W.; Parr, J. Organometallics 2000, 19, 3556–3561;
(f) Faller, J. W.; Parr, J. Organometallics 2001, 20, 697–699.
27. Brassat, I.; Keim, W.; Killat, S.; Mothrath, M.; Mastrorilli,
P.; Nobile, C. F.; Suranna, G. P. J. Mol. Catal. A 2000,
157, 41–58.
28. (a) Moreno-Man˜as, M.; Pleixats, R. Acc. Chem. Res. 2003,
36, 638–643; (b) Hu, J.; Liu, Y. Langmuir 2005, 21, 2121–
2123.
29. Cho, J. K.; Najman, R.; Dean, T. W.; Ichihara, O.; Muller, C.;
Bradley, M. J. Am. Chem. Soc. 2006, 128, 6276–6277.
30. (a) Li, G. Y. Angew. Chem., Int. Ed. 2001, 40, 1513–1516; (b)
Li, G. Y. (E.I. du Pont de Nemours and Co.). U.S. Patent
6,124,462, 2000.
18. Denmark, S. E.; Baird, J. D. Org. Lett. 2006, 8, 793–795.
19. For comparison see: Denmark, S. E.; Baird, J. D. Org. Lett.
2004, 6, 3649–3652.
20. We have subsequently found that the reduction of APC does
not involve phosphines, but rather silanolates, see: Denmark,
S. E.; Smith, R. C. Synlett 2006, 2921–2928.
31. Kim, S.-W.; Kim, S.; Tracy, J. B.; Jasanoff, A.; Bawendi, M. G.
J. Am. Chem. Soc. 2005, 127, 4556–4557.
32. Masala, O.; Seshadri, R. Annu. Rev. Mater. Res. 2004, 34,
41–81.