A convenient high activity catalyst for the Sonogashira coupling of aryl bromides

Article abstract of DOI:10.1002/adsc.200505095

A mixture of Na₂PdCl₄, CuI and (t-Bu) ₃PH⁺BF₄^- (molar ratio 4:3:8) dispersed in H₂N(i-Pr)₂ Br can be used as a "single source" precatalyst for the Sonogashira coupling of aryl bromides with various aryl- and alkylacetylenes in HN(i-Pr)₂ solvent. Arylacetylenes require just 0.005 mol % of Pd catalyst at 80°C, with TOFs ranging between 3,200 and 10,000 h^-1.

Full text of DOI:10.1002/adsc.200505095

UPDATES
A Convenient High Activity Catalyst for the Sonogashira
Coupling of Aryl Bromides
Axel Kçllhofer, Herbert Plenio*
Anorganische Chemie im Eduard-Zintl-Institut, TUDarmstadt, Petersenstr. 18, 64287 Darmstadt, Germany
E-mail: plenio@tu-darmstadt.de
Received: February 21, 2005; Accepted: April 18, 2005
Abstract:
A
mixture of Na PdCl , CuI and
(molar ratio 4:3:8) dispersed in
bromides at elevated temperatures (1308C) in the pres-
ence of 5 mol % CuI and small amounts of Pd using a
palladium-tetraphosphine complex [cis,cis,cis-1,2,3,4-
tetrakis(diphenylphosphinomethyl)cyclopentane],
which gave excellent results for activated aryl bro-
2
4
þ
À
4
(
t-Bu) PH BF
3
þ
À
H N(i-Pr) Br can be used as a “single source” pre-
2
2
catalyst for the Sonogashira coupling of aryl bro-
mides with various aryl- and alkylacetylenes in
HN(i-Pr)2 solvent. Arylacetylenes require just
[
11]
mides. Comparable results were obtained when using
the palladium complex of a novel tridentate ferrocenyl-
0.005 mol % of Pd catalyst at 808C, with TOFs rang-
À1
[12]
ing between 3,200 and 10,000 h
.
phosphine.
We believe that the development of ever new and ever
more complex ligands for palladium is only one part of
the story. The other, presently somewhat underdevel-
oped, side is the selection of ideal reaction conditions
through the proper choice of reaction solvent, base, pal-
ladium source and certain additives. In order to optimize
the catalyst performance of Pd-phosphine complexes
for Sonogashira coupling of aryl bromides, we have re-
Keywords: cross-coupling; homogeneous catalysis;
palladium; phosphane ligands; Sonogashira reaction
Introduction
In the last few years various palladium catalyzed cross- evaluated the performance of two established phos-
coupling reactions for CÀC, CÀN and CÀO bond forma- phines, P(t-Bu) and (Ad) PBn (Ad¼1-adamantyl),
3
2
tion have evolved to powerful synthetic tools due to dra- which have been used for the Sonogashira coupling of
matic progress in the development of catalysts for such aryl bromides at room temperature at catalyst loadings
[1]
À1 [13]
reactions. Now that the problems of activating even of 0.5–2 mol % and TOFs of below 50 h
.
We want
the formerly difficult substrates such as (sterically de- to demonstrate here that apparently simple modifica-
manding and electron-rich) aryl chlorides have essen- tions of the reaction conditions – primarily the use of
[
2,3]
tially been solved,
new challenges have to be met. the right solvent – can lead to a drastic increase in the ac-
In a recent review on palladium-catalyzed alkynylation tivity of such catalysts. This is basically one lesson we
reactions Negishi and Anastasia have defined the need learned from our studies of cross-coupling reactions un-
[
14]
for significantly more active catalysts in terms of turn- der biphasic reaction conditions.
over numbers (>10 ) and turnover frequencies as the
3
prohibitive costs of active palladium complexes have
[
4]
prevented many of their applications.
The recent advances in catalyst development for
Results and Discussion
cross-coupling reactions have been driven mainly by In a first round of screening a number of solvents were
the development of ever more elaborate phosphines employed in the Sonogashira coupling of bromoben-
[
5]
and N-heterocyclic carbenes. Nonetheless, the overall zene with phenylacetylene at a catalyst loading of
catalyst activity for Sonogashira type reactions is still 0.1 mol % Na PdCl , 0.075 mol % CuI and 2 mol %
2
4
modest and nowhere near the level realized in the Suzu- (1-Ad) PBn with HN(i-Pr) as the base. Significantly im-
2
2
[
6]
ki coupling reactions. Typically more than 0.5 mol % proved results were obtained with DME (yield 99%),
of catalyst is required to effect quantitative transforma- while dioxane (yield 68%), toluene (yield 35%) and
tion of substrates other than the commercially less at- DMSO (yield 28%) are less efficient. Other solvents,
[
7]
tractive aryl iodides. For the latter substrates, excellent like DMF, DMA, acetonitrile, propylene carbonate,
[
8]
TONs have been realized, while the less reactive aryl methanol, ethanol and halogenated solvents are of lim-
bromides have proven to be more resilient. Notable in ited or no use at all (yield < <10%). A single explana-
[
9]
this respect is work from Arques, Molina et al. and Na- tion for this behaviour is less obvious since solvents
[10]
jera et al. In particular, Doucet, Santelli et al. ob- can influence the catalytic activity in many ways, i.e.,
served excellent turnover numbers for activated aryl through coordination of the active metal center, solvent
Adv. Synth. Catal. 2005, 347, 1295–1300
DOI: 10.1002/adsc.200505095
ꢀ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1295

UPDATES
Axel Kçllhofer, Herbert Plenio
effects on dipolar (Hughes–Ingold rules) and isopolar without loss in activity. It is important to note in this re-
þ
2
À
transitions states, the solubility of the ionic components spect that H N(i-Pr) Br is not very hygroscopic.
or special anionic or cationic solvation.
2
[
15]
With these two highly active catalysts at hand Sonoga-
Under the conditions determined in the first screen, shira-type coupling reactions of various aryl bromides
the concentration of catalyst was reduced successively and phenylacetylene were performed at catalyst load-
for the reaction of bromobenzene with phenylacetylene: ings of 0.005 mol % Pd in excellent yields, with
0
.1 mol % Pd (8 h, yield 97%), 0.05 mol % Pd (20 h, (t-Bu) P being superior for most substrate combinations
3
yield 98%) and 0.01 mol % (20 h, yield 74%). It should (Table 1).
be noted that the outcome of the reaction is strongly de-
Activated aryl bromides react within a few hours,
pendent on the quality of the DME; the best results are while deactivated, electron-rich or sterically hindered
obtained with scrupulously dried (over potassium) sol- aryl bromides couple within less than 20 h at 808C. An
vent. This motivated us to look for other suitable sol- illustration of the high efficiency of such catalysts is
vents. Fortunately, a very simple approach was success- the fact that for the synthesis of 1 mol coupling product
ful. Using HN(i-Pr) not only asa base but also assolvent (ca. 200 g of a 200 Dalton compound), 5 mg Pd are suf-
2
[
19]
results in another significant increase of the catalytic ac- ficient.
tivity: 0.05 mol % (5 h, yield 95%), 0.01 mol % (18 h, Other acetylenes like trialkylsilylacetylenes, propar-
yield 93%), 0.005 mol % (36 h, 89%, TON 17,800), gylic alcohol and alkylacetylenes are also of great syn-
[
4]
0
.002 mol % (72 h, yield 56%, TON 28,000). The use thetic value. In order to broaden the scope of the cata-
of HN(i-Pr)2 gives excellent yields even with lysts presented here, we investigated the coupling of var-
.005 mol % of catalyst. We also tested other amines ious aryl bromides with such acetylenes at low catalyst
like NEt and HNEt as cheap solvent/bases for the So- loading. As shown in Table 2 all coupling reactions pro-
0
3
2
nogashira coupling. However, the activity of the catalyst ceeded smoothly at catalyst concentrations of 0.01 to
in these solvents is only modest, while with Cy NH the 0.1 mol %.
2
results are comparable to (i-Pr) NH. It is important to
Even propargylic alcohol, which is normally difficult
2
note that homocoupling of acetylenes, which is a typical to activate in Sonogashira reactions can be coupled in
problem in Sonogashira reactions with copper co-cata- excellent yields using only 0.01 mol % Pd. The key to
[16]
lysts and which has led to the development of numer- success, i.e., high TON, lies in carefully drying the prop-
[
17]
ous copper-free protocols, does not occur to a signifi- argyl alcohol prior to use with anhydrous K CO . As ex-
2
3
cant extent with the catalytic system described here.
pected 1-hexyne is the least reactive substrate and there-
When dealing with extremely small amounts of highly fore requires by far the highest catalyst loading
efficient catalyst, we obviously ran into problems on (0.1 mol %). We attribute this to the contamination of
weighing sub-mg amounts of Na PdCl , CuI and the re- commercially available 1-hexyne with 1-bromobutane.
2
4
spective phosphine. It is obvious that this effort is re- The reactions involving 2-methyl-3-butyn-2-ol are use-
quired for each coupling reaction. Consequently, we ful since the respective coupling products can be con-
were interested in increasing the efficiency of the prep-
arative work and decided to premix all of the three
þ
À
4
components [Na PdCl , CuI and (t-Bu) PH BF ]
2
4
3
Table 1. Reactions of phenylacetylene and aryl bromides.
needed to form the catalyst. The phosphonium salt
þ
À
(
t-Bu) PH BF is not sensitive to oxidation, but imme-
3 4
[
18]
diately generates P(t-Bu) in the basic amine solvent.
3
Furthermore, in order to obtain weighable amounts of
catalyst, we diluted the mixture of the pre-catalyst
with an inert solid. Since all coupling reactions are per-
[a]
[b]
R
T [h]
Yield [%]/TON
Yield[%]/TON
4
4
4
-NO2
-CH CO
-COOEt
5
6
7
9
7
96/19,200
94/18,800
98/19,600
93/18,600
93/18,600
94/18,800
92/18,400
94/18,800
90/18,000
84/16,800
92/18,400
87/17,400
93/18,600
91/18,200
94/18,800
94/18,800
92/18,400
89/17,800
88/17,600
90/18,000
91/18,200
88/17,600
82/16,400
91/18,200
86/17,200
92/18,400
formed in (i-Pr) NH which acts as the solvent/base and
2
3
since the respective ammonium salt is a product of all re-
þ
À
actions, we decided to use (i-Pr) NH Br as an inert
2
2
4-Cl
-CF3
a ready-made Sonogashira catalyst we mixed the appro- 2-CF3
priate amounts of Na PdCl , CuI and (t-Bu) P and add-
matrix for the catalyst components. In order to prepare
3
9
H
11
11
14
20
20
20
20
2
4
3
þ
À
ed the nine-fold mass of (i-Pr) NH Br . After intimate 4-Me
2
2
2
-Me
mixing a pale brownish powder was obtained, consisting
þ
2,6-Me2
of (i-Pr) NH Br- and 10 mass % of catalyst compo-
2
2
4-MeO
2-MeO
4-NMe2
nents, which essentially is a “single source” (pre)-cata-
lyst. For small-scale reactions it may be convenient to di-
lute the active component further to 1% content. This
Sonogashira catalyst mixture can be weighed in air and
stored under a nitrogen atmosphere for many weeks
[
[
a]
Using P(t-Bu)3.
b]
Using (Ad) PBn.
2
1296
ꢀ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2005, 347, 1295–1300

Sonogashira Coupling of Aryl Bromides
UPDATES
[a]
Table 2. Reactions of aryl bromides and various acetylenes.
R
R’
t [h]
[Pd] [mol%]
Yield [%]/TON
4
4
H
-NO2
-CH CO
TMS
TMS
TMS
TMS
TMS
12
12
20
20
20
5
0.01
0.01
0.01
0.01
0.02
0.01
0.01
0.01
0.01
0.01
0.02
0.02
0.02
0.02
0.02
0.1
94/9,400
96/9,600
93/9,300
95/9,500
92/4,600
92/9,200
93/9,300
90/9,000
93/9,300
87/8,700
97/4,850
94/4,700
93/4,650
97/4,850
94/4,700
93/930
3
4
4
4
4
-Me
-MeO
-NO2
CH OH
2
-CH CO
CH OH
6
3
2
H
CH OH
12
14
20
20
20
20
20
20
12
16
24
2
4
4
4
4
4
3
4
4
-Me
-MeO
-Ac
CH OH
2
CH OH
2
CMe OH
CMe OH
CMe OH
2
-Cl
2
-OMe
-NO2
-Me
2
CM OH
e2
CMe OH
2
-CH CO
n-Bu
n-Bu
n-Bu
3
H
0.1
0.1
88/880
85/850
4-MeO
[
a]
þ
2
À
Catalyst: Na PdCl , CuI and (t-Bu) P (4: 3: 8 molar ratio) dispersed in (i-Pr) NH Br .
2
4
3
2
verted into the respective terminal acetylenes by base-
induced cleavage of acetone.
Finally, the lack of understanding of when and why a
certain Pd catalyst is highly active, highlights the urgent
[
20]
Finally, we took a closer look at basic kinetic aspects of need for a more detailed mechanistic understanding of
the coupling reactions and determined the turnover fre- the Sonogashira reaction. In this respect, a recent study
quencies (TOF) of the respective catalysts, all of which on the Heck coupling by Hills and Fu may shed more
were resolved on incomplete reaction (20–40% conver- light on why amine bases render Pd-based catalysts so
sion) of the reactants (Table 3).
much more effective. In contrast to commonly used bas-
Again, the coupling of phenylacetylene is the fastest es like Cs CO or other metal carbonates, amines like
2
3
À1
[21]
reaction with a TON of close to 10,000 h for 4-nitro- Cy NMe, appear to be much more efficient in restor-
bromobenzene. Even deactivated 4-bromoanisole re- ing the active PdL species from L PdHCl.
acts at arateof 3,240 h with the (t-Bu) P-based Pd-cat- though the mechanistic setup of the Sonogashira reac-
2
[
22]
Even
2
2
À1
3
alyst, while coupling reactions with (Ad) PBn as ligand tion is different, especially when it comes to the formal
2
proceed more slowly. Excellent TOFs are also observed abstraction of HX, the role of the amine is notable and
for propargylic alcohol and aryl bromides with TOFs might have implications for the Sonogashira coupling
À1
À1
ranging from 1,240 h to 2,900 h
.
reactions described here.
À1
[a]
Table 3. Determination of the TOF [h ] for several Sonogashira coupling reactions.
À1
R
R’
PR3
[Pd] [mol%]
TOF [h ]
4
4
H
H
-NO2
-NO2
Ph
Ph
Ph
Ph
Ph
CH OH
CH OH
CH OH
(Ad) PBn
0.005
0.005
0.005
0.005
0.005
0.01
2,990
9,900
1,640
4,860
3,240
2,900
2,460
1,240
2
(t-Bu) P
3
(Ad) PBn
2
(t-Bu) P
3
4
4
4
-MeO
-NO2
-CH CO
(t-Bu) P
3
(t-Bu) P
2
3
(t-Bu) P
0.01
0.01
3
2
3
H
(t-Bu) P
2
3
[
a]
þ
2
À
Catalyst: Na PdCl , CuI and (t-Bu) P (4: 3: 8 molar ratio) dispersed in (i-Pr) NH Br .
2
4
3
2
Adv. Synth. Catal. 2005, 347, 1295–1300
asc.wiley-vch.de
ꢀ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1297

UPDATES
Axel Kçllhofer, Herbert Plenio
À
Br was added and the mixture was intimately mixed. At a
.005 mol % level, this catalyst mixture is sufficient for the syn-
Conclusions
0
thesis of 1.3 mol of coupling product.
We have shown here that minor variations in the reac-
tion conditions lead to catalytic systems with drastically
increased activity. The advantages of the present ap-
proach in the context of Sonogashira coupling reactions
are obvious:
General Procedure for the Sonogashira Coupling of
Aryl Bromides and Acetylenes
.
The ready-made Sonogashira catalyst provides a sim- A solution of the aryl bromide (10 mmol) and the respective
acetylene (10.3 mmol) in HN(i-Pr) (10 mL) was carefully de-
ple and general recipe for the user of the Sonogashira
coupling.
The choice of the best conditions in the well known
Sonogashira coupling protocol results in a drastic in-
crease in the activity of the catalyst, such that only
2
gassed (freeze and thaw). After addition of the ready-made So-
nogashira catalyst (0.005–0.1 mol %) the mixture was heated
.
þ
to 808C with vigorous stirring. Precipitation of H N(i-Pr)
2
2
À
Br indicated the start of the reaction and stirring was contin-
ued for the given time. After cooling to room temperature, the
reaction mixture was filtered and the precipitate washed with
HN(i-Pr) (25 mL) or Ef O. The volatiles were removed under
0
.005 mol % of Pd are required for the reactions of
aryl bromides and phenylacetylene.
2
2
.
.
The key to such high activity catalysts with TOFs of vacuum and the residue was purified by flash column chroma-
À1
up to 10,000 h is the use of HN(i-Pr) as solvent tography on silica (heptane or cyclohexane/ethyl acetate).
2
and base.
It is also important to note that another pertinent
problem of Sonogashira coupling reactions, i.e., the
1
H NMR Spectra (200 MHz, CDCl ) of the Coupling
formation of homocoupling product does not occur
to a significant extent (<1%) and consequently an
excess of acetylene is not required.
3
Products
[23]
4
2
-(Phenylethynyl)nitrobenzene: d¼8.19 (m, 2H), 7.64 (m,
H), 7.54 (d, J¼7.6 Hz, 2H), 7.41–7.32 (m, 3H).
[24]
Phenyl-(2-trifluoromethylphenyl)acetylene:
d¼7.61 (d,
J¼7.6 Hz, 2H), 7.56 (d, J¼7.8 Hz, 1H), 7.50 (d, J¼7.6 Hz,
Experimental Section
1
H), 7.41 (dd, J¼7.6 and 7.4 Hz, 1H), 7.35–7.28 (m, 4H).
[24]
Phenyl-(3-trifluoromethylphenyl)acetylene:
H), 7.62 (m, 1 H), 7.56–7.42 (m, 4H), 7.36 (m, 2 H), 7.29 (m,
H).
d¼7.78 (s,
1
1
General Experimental Procedures
[
24]
4
-(Phenylethynyl)acetophenone:
d¼7.90 (d, J¼8.0 Hz,
All reactions were carried out under an inert atmosphere of ar-
gon using standard Schlenk techniques. Aryl bromides and
acetylenes were used as received and deoxygenated prior to
the coupling reactions, except for propargylic alcohol which
was dried over K CO , deoxygenated and stored over mo-
2
(
H), 7.58 (d, J¼8.0 Hz, 2H), 7.54 (m, 2H), 7.33 (m, 3H), 2.56
s, 3H).
-(Phenylethynyl)chlorobenzene: d¼7.54–7.43 (m, 4H,),
.36–7.31 (m, 5H).
Diphenylacetylene: d¼7.51–7.46 (m, 4H,), 7.34–7.30 (m,
H).
[25]
4
7
6
2
2
3
[11c]
lecular sieve (4 Š). HN(i-Pr) was dried over KOH, distilled,
2
1
deoxygenated and stored over molecular sieve (4 Š).
NMR spectroscopy was performed on a Bruker 200 AC at
93 K. Column chromatography was carried out on silica
H
[23]
Ethyl 4-(phenylethynyl)benzoate: d¼8.03 (d, J¼8.1 Hz,
H), 7.61 (d, J ¼8.1 Hz, 2H), 7.56–7.51 (m, 2H), 7.41–7.32
2
(
m, 3H), 4.39 (q, J¼7.2 Hz, 2H), 1.41 (t, J¼7.2 Hz, 3H).
MN60 (63–200 mm), TLC on Merck plates coated with silica
[10]
4
-(Phenylethynyl)toluene: d¼7.54–7.31 (m, 7H), 7.15 (d,
gel 60, F254. The identity and purity of all compounds describ-
1
J¼7.8 Hz, 2H), 2.34 (s, 3H).
ed here was established by H NMR (all compounds have been
[10]
2
-(Phenylethynyl)toluene: d¼7.53–7.49 (m, 2H), 7.46 (d,
described in the literature previously, references given) and by
gas chromatography. GC(/MS): GC-MS Fisons “GC 8000”
with integrated MS “MD 800”. Carrier gas: He at 50 kPa
with a 1:25 split. Injection temperature: 2308C. Column: Var-
ian “CP-Sil 8 CB”, length 15 m, inner diameter 0.25 mm, layer
thickness 1 mm. Temperature program: 608C for 9 min, heating
to 2108C with 58C/min, 2108C for 9 min, heating to 2658C at
J¼8.7 Hz, 2H), 7.32 (m, 3H), 6.86 (d, J¼8.7 Hz, 2H), 3.81 (s,
3
H).
,6-Dimethylpheny-phenylacetylene:
.44–7.28 (m, 3H), 7.19 (m, 3H), 2.56, (s, 6H).
[13a]
2
d¼7.59 (m, 2H),
-(Phenylethynyl)anisole: d¼7.53–7.49 (m, 2H), 7.46 (d,
7
[25]
4
J¼8.7 Hz, 2H), 7.32 (m, 3H), 6.86 (d, J¼8.7 Hz, 2H), 3.81 (s,
3
H).
-(Phenylethynyl)anisole: d¼7.94–6.73 (m, 9H), 3.81 (s,
H).
-(Phenylethynyl)-N,N-dimethylaminobenzene:
m, 2H), 7.42 (m, 2H), 7.33 (m, 2H), 6.42 (m, 3H), 3.01 (s, 6H).
6
8C/min.
[26]
2
3
[13a]
4
d¼7.55
Ready-Made Sonogashira Catalyst
(
[27]
A mixture of CuI (9.5 mg, 0.05 mmol) Na PdCl (19.7 mg,
2-(4-Nitrophenyl)-1-ethynyl(trimethyl)silane: d¼8.21 (d,
2
4
0
.067 mmol) and the respective phosphonium salt [(t-Bu) P·
J¼10.3 Hz, 2H), 7.52 (d, J ¼10.3 Hz, 2H) 0.12 (s, 9H).
2-(4-Acetylphenyl)-1-ethynyl(trimethyl)silane:
3
[27]
HBF : 38.7 mg, 0.133 mmol or (Ad) PBn·HBr: 63.0 mg,
d¼7.87
4
2
0
4
.133 mmol] was finely ground. The molar ratio of Pd:Cu:P is
(d, J¼8.2 Hz, 2H), 7.57 (d, J¼8.2 Hz, 2H), 2.57 (s, 3H) 0.09
þ
:3:8. Subsequently, the nine-fold amount of H N(i-Pr)
(s, 9H).
2
2
1298
ꢀ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2005, 347, 1295–1300

Sonogashira Coupling of Aryl Bromides
UPDATES
[
27]
2
-Phenyl-1-ethynyl(trimethyl)silane:
H,), 7.37–7.31 (m, 3H), À0.01 (s, 9H).
-(4-Methylphenyl)-1-ethynyl(trimethyl)silane:
d¼7.53–7.42 (m, References and Notes
2
[27]
2
d¼7.41
[1] Metal-Catalyzed Cross-Coupling Reactions, (Eds.: A. de -
(
(
d, J¼8.1 Hz, 2H), 7.16 (d, J¼8.1 Hz, 2H), 2.35 (s, 3H,), 0.07
Meijere, F. Diederich), 2nd edn., Wiley-VCH, Weinheim,
s, 9H).
2
2
004.
2] A. F. Littke, G. C. Fu, Angew. Chem. Int. Ed. 2002, 41,
176.
3] a) A. Kçllhofer, T. Pullmann, H. Plenio, Angew. Chem.
Int. Ed. 2003, 42, 1056; b) D. Gelman, S. L. Buchwald,
Angew. Chem. Int. Ed. 2003, 42, 6175.
[25]
-(4-Methoxyphenyl)-1-ethynyl(trimethyl)silane: d¼7.40
[
[
(
(
d, J¼8.4 Hz, 2H), 6.84 (d, J¼8.4 Hz, 2H), 3.79 (s, 3H,), 0.08
4
s, 9H).
3
[28]
-(4-Nitrophenyl)prop-2-yn-1-ol: d¼8.14 (d, J¼10.5 Hz,
2
H), 7.55 (d, J¼10.5 Hz, 2H), 4.47 (d, J¼6.2 Hz, 2H), 1.67 (t,
J¼6.2 Hz, 1H).
[
[
4] E. Negishi, L. Anastasia, Chem. Rev. 2003, 103, 1979.
5] a) G. Altenhoff, R. Goddard, C. W. Lehmann, F. Glorius,
Angew. Chem. Int. Ed. 2003, 42, 3690; b) C. W. K. Gstçtt-
mayr, V. P. W. Bçhm, E. Herdtweck, M. Grosche, W. A.
Herrmann, Angew. Chem. Int. Ed. 2002, 41, 1363; c) N.
Kataoka, Q. Shelby, J. P. Stambuli, J. F. Hartwig, J. Org.
Chem. 2002, 67, 5553; d) A. Zapf, R. Jackstell, F. Rata-
boul, T. Riermeier, A. Monsees, C. Fuhrmann, N. Shaikh,
U. Dingerdissen, M. Beller, Chem. Commun. 2004, 38;
e) S. D. Walker, T. E. Barder, J. R. Martinelli, S. L. Buch-
wald, Angew. Chem. Int. Ed. 2004, 43, 1871.
[
30]
3
-(4-Acetylphenyl)prop-2-yn-1-ol: d¼7.87 (d, J¼8.4 Hz,
2
1
H), 7.46 (d, J¼8.4 Hz, 2H), 4.63 (s, 2H), 2.58 (s, 3H), 2.21 (s,
H).
3
[29]
-(Phenyl)prop-2-yn-1-ol: d¼7.51–7.46 (m, 2H), 7.34–
7
.30 (m, 3H), 4.37 (d, J¼6.0 Hz, 2H), 1.73 (t, J¼6.0 Hz, 1H).
[
30]
3
-(4-Methylphenyl)prop-2-yn-1-ol: d¼7.37 (d, J¼8.4 Hz,
2
3
H), 7.18 (d, J¼8.4 Hz, 2H), 4.73 (d, J¼6.0 Hz, 2H), 2.36 (s,
H), 1.94 (t, J¼6.0 Hz, 1H).
[
30]
3
-(4-Methoxyphenyl)prop-2-yn-1-ol:
d¼7.41 (d, J¼
8
.5 Hz, 2H), 6.82 (d, J¼8.5 Hz, 2H), 4.67 (d, J¼6.1 Hz, 2H),
3
.82 (s, 3H), 1.81 (t, J¼6.1 Hz, 1H).
[31]
[
6] a) G. Altenhoff, R. Goddard, C. W. Lehmann, F. Glorius,
J. Am. Chem. Soc. 2004, 126, 15195; b) S. D. Walker, T. E.
Barder, J. R. Martinelli, S. L. Buchwald, Angew. Chem.
2004, 116, 1907.
4
-(1-Hexyn-1-yl)acetophenone:
d¼7.83 (d, J¼8.1 Hz,
2
2
H), 7.44 (d, J¼8.1 Hz, 2H), 2.58 (s, 3H), 2.43 (t, J¼7.0 Hz,
H,), 1.53–1.17 (m, 4H), 0.87 (t, J¼7.0 Hz, 3H).
[31]
1
-Hexyn-1-yl)benzene: d¼7.62–7.49 (m, 2H), 7.38–7.29
(
m, 3H), 2.45 (t, J¼6.9 Hz, 2H,), 1.56–1.21 (m, 4H), 0.88 (t,
J¼7.2 Hz, 3H).
-(1-Hexyn-1-yl)anisole: d¼7.45 (d, J¼8.3 Hz, 2H), 6.81
d, J¼8.3 Hz, 2H), 3.79 (s, 3H), 2.39 (t, J¼7.1 Hz, 2H,), 1.54–
.20 (m, 4H), 0.91 (t, J¼7.2 Hz, 3H).
-(4-Methoxyphenyl)-2-methyl-but-3-in-2-ol:
J¼7.1 Hz, 2H), 6.82 (d, J¼8.9 Hz, 2H,), 3.78 (s, 3H), 2.02 (s,
H), 1.58 (s, 6H).
-(4-Acetylphenyl)-2-methyl-but-3-in-2-ol:
J¼8.2 Hz, 2H), 7.48 (d, J¼8.2 Hz, 2H), 2.57 (s, 3H) 2.20 (s,
H), 1.60 (s, 6H).
-(4-Methylphenyl)-2-methyl-but-3-in-2-ol:
[7] A. Soheili, J. Albaneze-Walker, J. A. Murray, P. G.
Dormer, D. L. Hughes, Org. Lett. 2003, 5, 4191.
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4
[8] a) C. Najera, J. Gil-Molto, S. Karlstrçm, L. R. Falvello,
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Chem. Commun. 2003, 1934; c) W. A. Herrmann, C.-P.
Reisinger, K. Öfele, C. Broßmer, M. Beller, H. Fischer,
J. Mol. Cat. A 1996, 108, 51; d) J. Cheng, Y. Sun, F.
Wang, M. Guo, J.-H. Xu, Y. Pan, Z. Zhang, J. Org.
Chem. 2004, 69, 5428; e) A. Soheili, J. Albaneze-Walker,
J. A. Murray, P. G. Dormer, D. L. Hughes, Org. Lett.
(
1
[13a]
4
d¼7.35 (d,
1
[13a]
4
d¼7.88 (d,
1
2
003, 5, 4191.
9] A. Arques, D. Aunon, P. Molina, Tetrahedron Lett. 2004,
5, 4337.
[32]
4
d¼7.31 (d,
[
J¼8.05 Hz, 2H, ArH-2), 7.10 (d, J¼7.95 Hz, 2H, ArH-3),
4
2
.31 (s, 3H), 2.20 (s, 1H), 1.59 (s, 6H).
4
[
10] D. A. Alonso, C. Najera, M. C. Pacheco, Adv. Synth. Cat-
al. 2003, 345, 1146.
[33]
-(3-Nitrophenyl)-2-methyl-but-3-in-2-ol: d¼8.23 (s, 1H),
8
7
.15 (d, J¼8.2 Hz, 1H), 7.70 (d, J¼7.5 Hz, 1H), 7.50 (dd, J¼
[
11] a) M. Feuerstein, F. Berthiol, H. Doucet, M. Santelli,
Synthesis 2004, 1281; b) M. Feuerstein, F. Berthiol, H.
Doucet, M. Santelli, Org. Biomol. Chem. 2003, 1, 2235.
.9 Hz, 7.8 Hz, 1H), 2.27 (s, b, 1H), 1.61 (s, 6H).
[32]
4
-Methoxyphenyl acetylene: d¼7.43 (d, J¼8.7 Hz, 2H),
6
.84 (d, J¼8.7 Hz, 2H), 3.79 (s, 3H), 2.98 (s, 1H).
[32]
[12] J. C. Hierso, A. Fihri, R. Amardeil, P. Meunier, H. Dou-
cet, M. Santelli, V. V. Ivanov, Org. Lett. 2004, 6, 3473.
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Fu, Org. Lett. 2000, 2, 1729; b) V. P. W. Bçhm, W. A.
Herrmann, Eur. J. Org. Chem. 2000, 3679.
4
-Chlorophenylacetylene: d¼7.30 (d, J¼8.6 Hz, 2H), 7.18
(
d, J¼8.6 Hz, 2H), 2.96 (s, 1H).
[32]
4
-Methylphenyl acetylene:
d¼7.26 (d, J¼7.6 Hz, 2H),
7
.00 (d, J¼7.6 Hz, 2H), 2.88 (s, 1H), 2.21 (s, 3H).
[
14] a) A. Kçllhofer, H. Plenio, Chem. Eur. J. 2003, 9, 1416;
b) M. an der Heiden, H. Plenio, Chem. Eur. J. 2004, 10,
1
789.
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Y. Pan, Z. Zhang, J. Org. Chem. 2004, 69, 5428; d) A. Ar-
Acknowledgements
This work was supported by the DFG and the TU Darmstadt. A
gift of Na PdCl from the Degussa AG is acknowledged.
2
4
Adv. Synth. Catal. 2005, 347, 1295–1300
asc.wiley-vch.de
ꢀ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1299

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2
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asc.wiley-vch.de
Adv. Synth. Catal. 2005, 347, 1295–1300