Palladium-catalyzed 1,4-addition of terminal alkynes to unsaturated carbonyl compounds promoted by electron-rich ligands

Article abstract of DOI:10.1039/b805946m

The efficient palladium-catalyzed conjugate addition of terminal alkynes to α,β-unsaturated carbonyl compounds has been developed using electron-rich ligands, producing the corresponding γ,δ-alkynyl ketone and γ,δ-alkynyl esters in good yields. The Royal Society of Chemistry.

Full text of DOI:10.1039/b805946m

View Article Online / Journal Homepage / Table of Contents for this issue
PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Palladium-catalyzed 1,4-addition of terminal alkynes to unsaturated carbonyl
compounds promoted by electron-rich ligands
Lei Zhou,†a,b Liang Chen,†c Rachid Skouta,b Huan-feng Jiang*a and Chao-Jun Li*b,c
Received 8th April 2008, Accepted 16th May 2008
First published as an Advance Article on the web 24th June 2008
DOI: 10.1039/b805946m
The efficient palladium-catalyzed conjugate addition of terminal alkynes to a,b-unsaturated carbonyl
compounds has been developed using electron-rich ligands, producing the corresponding c,d-alkynyl
ketone and c,d-alkynyl esters in good yields.
be overcome by tuning the electronic properties of the ligands
1. Introduction
coordinated to palladium.
Within the past few decades, the development of palladium-
Recently, we reported the preliminary results of a simple and
catalyzed C–C bond formation reactions has dramatically ad-
highly efficient Pd-catalyzed addition of terminal alkynes to
vanced the ‘state-of-the-art’ of organic synthesis.1 Well-known
conjugated enones either in water or in acetone under air by using
examples include the Heck reaction,2 the Stille reaction,3 the
Suzuki reaction,4 the Trost–Tsuji reaction,5 and the Sonogashira
coupling,6 to name but a few. Furthermore, reactions involving
overall addition provide an atom-economical way to construct
more complex structures from simpler units.7 Recently, there has
been increased interest in the addition of terminal alkynes to
an electron-rich trimethylphosphine ligand.13 Herein, we describe
the detailed study of this reaction as well as its extension to alkene
esters (Scheme 1).
2
8
=
=
compounds that involve sp carbons such as C O or C N bonds
(Fig. 1, route a).9 However, only a few examples of the addition
=
of terminal alkynes to C C bonds have been reported (Fig. 1,
route b).10
Scheme 1 Conjugate addition of terminal alkynes to enones and alkene
esters.
2. Results and discussion
2.1 General design
To begin with our study, we applied the rationale that the key to
the success of the desired conjugate additions is to increase the
reactivity of the alkynyl C–Pd bond (increasing the polarization
of the r-complex, Fig. 2) and decrease the reactivity of the C–
C triple bond (decreasing p-complex formation, Fig. 2). The use
of an electron-rich ligand14 can potentially serve both purposes:
the donation of electron density from the ligand to palladium
will weaken the C–Pd bond and make alkyne coordination less
favorable.
=
=
Fig. 1 Addition of terminal alkyne to C X and C C bonds.
Furthermore, although palladium is one of the most widely
used metals in catalysis, palladium-catalyzed conjugate addition
of alkynes to enones and alkene esters has not been previously
reported.11 We hypothesized that the failure of palladium in
catalyzing such additions could be attributed to (1) either the
facile homo- or heterodimerization of terminal alkynes (a well-
known and synthetically useful process)12 to form by-products
or (2) the low reactivity of the alkynyl palladium intermediate
towards enones and alkene esters. Conceivably, such obstacles can
Fig. 2 Formation of r- and p-palladium complexes with alkynes.
aCollege of Chemistry, South China University of Technology, Guangzhou,
510640, PR China
2.2 Conjugate addition of terminal alkynes to enones
bDepartment of Chemistry, McGill University, 801 Sherbrooke St. West,
Montreal, Quebec, H3A 2K6, Canada
We started by reacting phenylacetylene with ethyl vinyl ketone
in the presence of 5 mol% of Pd(OAc)2 and 10 mol% of the
common ligand PPh3 in water at 60 ◦C for 40 h. As expected,
the reaction gave only a tiny amount of the desired product
cDepartment of Chemistry, Tulane University, New Orleans, Louisiana,
70118, USA. E-mail: cj.li@mcgill.ca, jianghf@scut.edu.cn; Fax: +1 514
3983797; Tel: +1 514 3988457
† L. Zhou and L. Chen contributed equally on this research.
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 2969–2977 | 2969
©

View Article Online
Table 1 Addition of phenylacetylene to ethyl vinyl ketone catalyzed by various palladium catalysts in watera
Entry
Catalyst
L/C ratio
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Pd(OAc)2/PPh3
2
2
2
2
2
—
2
2
—
2
2
2
2
—
0
0
4
6
<10b
27
31
Pd(OAc)2/tris(4-methoxyphenyl)phosphine
Pd(OAc)2/tris(2,6-dimethoxyphenyl)phosphine
Pd(OAc)2/tris(2,4,6-trimethoxyphenyl)phosphine
Pd(OAc)2/PMe3
PdCl2(PPh3)2
PdCl2(PPh3)2/PMe3
PdCl2(O2CCF3)2/PMe3
Pd(0)(PPh3)4
Pd(0)(PPh3)4/PMe3
Pd(OAc)2/PMe3/Et3N (1 equiv)
Pd(OAc)2/PMe3/NaOAc (1 equiv)
Pd(OAc)2/trimethylphosphine oxide
PMe3
17
77
<10b
<10b
<10b
c
—
32
<10b
43
<10b
c
—
Pd(OAc)2
15
<10b
91
Pd(OAc)2/Et3N (1 equiv)
Pd(OAc)2/PMe3
Pd(OAc)2/PMe3
86
a All reactions were carried out using 1 mmol of phenylacetylene, 2 mmol of vinyl ethyl ketone, 5 mol% of palladium catalyst and the given amount of
ligand in water at 60 ◦C for 40 h. b Measured by 1H NMR. c Not detected by 1H NMR.
(Table 1, entry 1). Then a more electron-rich ligand, tris(4-
methoxyphenyl)phosphine, was tested, and the product yield
increased significantly to 27% (Table 1, entry 2). Encouraged by
this result, we tested other electron-rich ligands (Table 1, entries 3–
5). The use of PMe3, being both electron-rich and smaller, gave the
coupling product in 77% yield (Table 1, entry 5). Other palladium
salts were also tested; the results showed that the counter-ion
of the palladium salt also had an effect on the reaction. With
an electron-deficient trifluoroacetate or chloride as the counter-
ion, the reaction was less effective (Table 1, entries 6–8). To
examine whether the phosphine ligand served as a base or a real
ligand, we also tested the catalyst system in the presence of an
inorganic base as well as an organic base. The Pd(OAc)2/PMe3
combination generated less product in the presence of a base,
especially in the case of NEt3 (Table 1, entries 11 and 12), possibly
because of competing coordination between triethylamine and
the phosphine ligand. In the absence of a phosphine ligand, the
Pd(OAc)2/base system gave only a trace amount of the product.
Pd(OAc)2 alone as the catalyst was only slightly effective, whereas
PMe3 did not show any catalytic activity (although phosphines
are known to catalyze conjugate additions with alcohols, amines,
and activated methylene as nucleophiles).15 Because PMe3 is air-
sensitive and easily oxidized to trimethylphosphine oxide, we also
tested Pd(OAc)2/trimethylphosphine oxide as a catalyst; however,
almost no catalytic activity was observed (Table 1, entry 13);
trimethylphosphine oxide alone did not show any catalytic activity
either. Finally, when the ratio of PMe3/Pd(OAc)2 was increased
from 2 : 1 to 4 : 1, the desired product was obtained in 91% yield
(Table 1, entry 17). However, when the ratio of PMe3/Pd(OAc)2
was increased to 6 : 1, the product yield decreased, which can
be attributed to the lower availability of coordination sites on
palladium and the resulting decreased catalytic activity16 (Table 1,
entry 18).
well as in acetone (Table 2). It was shown that alkynes bearing silyl,
alkenyl, aromatic, aliphatic or halid groups all reacted smoothly
with vinyl ketone to afford good yields of the desired 1,4-addition
products. With diyne as a substrate, a bis-addition adduct was
the major product. In addition to ethyl vinyl ketone, methyl vinyl
ketone also provided the corresponding product in this addition
reaction, albeit in a lower yield. It should be noted that both water
and acetone are effective as solvents, similar results being obtained
with both.
2.3 1,4-Addition of terminal alkynes to acrylate esters
The success of the Pd(OAc)2/PMe3-catalyzed conjugate addition
of terminal alkynes to enones prompted us to explore the
applicability of the catalytic method to less reactive substrates
such as acrylate esters. Although there are a few reports on the 1,4-
addition of terminal alkynes to unsaturated esters, the reactions
are limited to the use of highly reactive diesters17 or a specialized
high-boiling point solvent.18
When phenylacetylene was reacted with methyl acrylate in the
presence of 2.5 mol% of Pd(OAc)2 and 5 mol% of PMe3 as ligand
under the alkyne–enone reaction conditions, only a trace amount
of the desired product was observed. In order to further extend
the scope of this addition, we hypothesized that by using an even
more electron-donating ligand, such as N-heterocyclic carbenes
(NHCs),19 the reactivity of the alkynyl Pd–C bond can be increased
further. Thus, various N-heterocyclic carbene ligands were tested
and compared with the trimethylphosphine ligands under identical
conditions. In order to solubilize the catalyst, the reactions were
performed in THF (Table 3).
Mono-dentate N-heterocyclic carbene ligands, generated in situ
from their commercially available precursors 4a and 4b in THF in
the presence of 1.2 equiv of KO-t-Bu, were tested. The reactions
led to promising yields of 65% and 42% respectively (Table 3,
entries 2 and 3). Encouraged by these initial results, four other
Subsequently, a broad range of substrates were examined for
this new palladium-catalyzed alkyne–enone addition, in water as
2970 | Org. Biomol. Chem., 2008, 6, 2969–2977
This journal is
The Royal Society of Chemistry 2008
©

View Article Online
Table 2 Addition of terminal alkynes 1 to vinyl ketones 2 catalyzed by Pd(OAc)2/PMe3 in water and in acetonea
Entry
1
Terminal alkyne 1
Vinyl ketone 2
Conditions
Product 3
Isolated yield (%)
85
40 h, acetone
2
3
40 h, water
43 h, water
91
74
4
43 h, acetone
61
5
6
43 h, water
42 h, acetone
70
70
7
8
42 h, water
44 h, water
67
65
9
44 h, acetone
63
10
44 h, water
44 h, acetone
72
57
11b
12b
13
44 h, water
42 h, acetone
62
51
14
15
42 h, water
45 h, water
56
58
16
43 h, acetone
49
17
18
43 h, water
45 h, water
52
53
19
20
39 h, acetone
39 h, water
66
61
a The reactions were carried out using 1.0 mmol of a terminal alkyne, 2 mmol of a vinyl ketone, 5 mol% of Pd(OAc)2 and 20 mol% of PMe3 at 60 ◦C in
water or acetone. The product structures were determined by 1H NMR, 13C NMR, MS, and IR. b 1.0 mmol of terminal alkyne was reacted with 4 mmol
of vinyl ketone.
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 2969–2977 | 2971
©

View Article Online
Table 3 Addition of phenylacetylene to methyl acrylate catalyzed by
used as solvent, <10% yield of 5a was obtained (Table 3, entry
14). The best results were obtained by using acetone as solvent
(Table 3, entry 12).
various palladium–NHC complexesa
Subsequently, various terminal alkynes and acrylate esters were
used using the Pd–NHC catalyst under the optimized conditions
in acetone (Table 4). Various aromatic alkynes with an electron-
donating substituent such as the methyl, methoxy group, phenyl
and dimethylamino on the para-positon of the benzene ring gave
the corresponding esters in high yields (Table 4, entries 1–5),
whereas aromatic alkynes with a substituent on the ortho-position
gave the corresponding c,d-alkynyl esters only in modest yields,
most likely due to the steric effect (Table 4, entries 6 and 7). It
is worth mentioning that this catalytic system can tolerate a free
amine in the reaction. The reaction of m-aminophenylacetylene
with methyl acrylate gave the desired product smoothly without
the need for functional group protection (Table 4, entry 8).
The reaction of 2-ethynyl-6-methoxynaphthalene also proceeded
smoothly and gave the corresponding c,d-alkynyl ester in 85% yield
(Table 4, entry 9). When a diyne was used, a mono-addition adduct
was obtained as a major product (Table 4, entry 10). tert-Butyl
acrylate also reacted efficiently (Table 4, entries 11–14). When
aliphatic alkynes such as 1-octyne were used as the substrates,
only trace amounts of the desired products were detected.
Entry
Catalyst
Solventb
Yield (%)c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Pd(OAc)2/PMe3
Pd(OAc)2/4a
Pd(OAc)2/4b
Pd(OAc)2/4c
Pd(OAc)2/4d
Pd(OAc)2/4e
Pd(OAc)2/4f
Pd(dba)2/4a
[PdCl(allyl)]2/4a
Pd(OAc)2
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
Acetone
DMF
Water
<10
65
42
55
31
15
<10
Traced
37
Traced
d
4a
—
Pd(OAc)2/4a
Pd(OAc)2/4a
Pd(OAc)2/4a
79
61
<10
a All reactions were carried out in sealed tubes using 0.5 mmol of
phenylacetylene, 1 mmol of methyl acrylate, 2.5 mol% of palladium
catalysts and 10 mol% of ligand in the desired solvent at 60 ◦C for 24 h. b N-
Heterocyclic carbene ligands were generated in situ from their precursors
in THF with 1.2 equiv of KO-t-Bu; when other solvents were used, THF
was evaporated by pump slowly. c Measured by 1H NMR. d Not detected
by 1H NMR.
2.4 Mechanistic studies
N-heterocyclic carbene ligands were then prepared from their
precursors 4c–f (Fig. 3) and tested. The reaction with NHC
generated from 4c afforded product 5a in 55% yield; whereas the
reaction with NHC from 4d (which coordinates to palladium by
two six memberedrings) gave product 5a inonly31%yield (Table 3,
entries 4 and 5).
To gain insight into the mechanism of the reaction, when
phenylacetylene-d1 was reacted with ethyl vinyl ketone in dry THF,
an a-deuterated alkynyl ketone product was obtained in 76% yield
with 15% d-incorporation. On the other hand, in dry acetone
(which has a relatively active a-H), the deuterated product was
obtained in 79% yield with less than 10% d-incorporation. When
phenylacetylene was reacted with ethyl vinyl ketone in the presence
of 10 equiv D2O in acetone, the addition product was obtained in
68% yield with 55% d-incorporation; while in D2O solvent, the
addition product was obtained in 52% yield with more than 95%
d-incorporation. No deuterium incorporation was observed at any
position when 7-phenyl-6-heptyn-3-one, a c,d-ynone product, was
reacted in D2O.
Based on these results, a tentative mechanism for the palladium-
catalyzed 1,4-addition of terminal alkynes to conjugated enones
2
and esters is illustrated in Scheme 2. The g -coordination of
Fig. 3 Precursors of N-heterocyclic carbene ligands.
The use of the N-heterocyclic carbenes generated from 4e and
4f (both tridentate and sterically hindered ligands) afforded the
desired 5a in 15% and <10% yield respectively (Table 3, entries
6 and 7). The use of Pd(allyl)Cl dimer, instead of Pd(OAc)2, gave
37% yield of the desired product, whereas the use of Pd(dba)2
generated only a trace amount of 5a (Table 3, entries 8 and 9). As a
control, with Pd(OAc)2 alone as the catalyst only a trace amount of
the product was obtained, whereas N-heterocyclic carbene alone
generated from 4a did not show any catalytic activity (although
NHCs have been shown to catalyze addition reactions with enols20
and ketones21) (Table 3, entry 11). Having the preferred catalyst
in hand, different solvents such as THF, DMF, acetone and water
were examined. The use of THF or DMF as solvent gave only
modest yields of 5a (Table 3, entries 3 and 13). When water was
Scheme 2 Tentative mechanism for the palladium-catalyzed 1,4-addition
of terminal alkynes to unsaturated carbonyl compounds.
2972 | Org. Biomol. Chem., 2008, 6, 2969–2977
This journal is
The Royal Society of Chemistry 2008
©

View Article Online
Table 4 Addition of terminal alkynes to acrylic esters catalyzed by Pd(OAc)2/NHCsa
Entry
1
R1
Ph
R2
Time/h
24
Product 5
Yield (%)b
76
OMe
2
p-Ph-C6H4
OMe
24
69
3
4
5
p-Me-C6H4
OMe
OMe
OMe
21
18
18
83
80
55
p-MeO-C6H4
p-Me2N-C6H4
6
o-MeO-C6H4
OMe
23
71
7
8
o-MeOCH2O-C6H4
OMe
OMe
28
24
52
41
m-H2N-C6H4
9
6-Methoxynaphthalen-2-yl
OMe
OMe
20
45
85
10
p-Ethynyl-C6H4
58c
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 2969–2977 | 2973
©

View Article Online
Table 4 (Contd.)
Entry
11
R1
R2
Time/h
24
Product 5
Yield (%)b
74
Ph
t-OBu
12
p-Ph-C6H4
t-OBu
24
62
13
14
p-Me-C6H4
t-OBu
t-OBu
20
25
77
48
o-MeOCH2O-C6H4
a All reactions were carried out in sealed tubes by using 0.5 mmol of terminal alkynes, 1 mmol of acrylate, 2.5 mol% of palladium catalysts and 10 mol%
of 4a in acetone at 60 ◦C. b Isolated yield. c 7% of bis-addition adduct was detected by GC–MS.
the triple bond to the palladium center followed by direct
deprotonation of the coordinated terminal alkyne to palladium
internal solvent signals (central peak is 77.00 ppm). MS data
were obtained by Agilent 6890 N Network GC System/Agilent
5973 Mass Selective Detector. HRMS analyses were carried
out at the Chemistry Department of McGill University. Flash
column chromatography was performed over SORBENT silica
gel 30–60 lm. Thin layer chromatography was performed using
Sorbent Silica Gel 60 F254 TLC plates and visualized with
ultraviolet light. THF was dried under argon over sodium
benzophenone; 1,3-bis(2,4,6-trimethylphenyl)imidazolium chlo-
ride (IMes·HCl, 4a) and 1,3-bis(2,4,6-trimethylphenyl)-4,5-
dihydroimidazolium chloride (SIMes·HCl, 4b) were purchased
from Aldrich and were used as received without further purifi-
cation. 3-Cyanomethyl-1-methyl-3H-imidazolium chloride (4c),23
1,3-bis(cyanomethyl)-3H-imidazolium chloride (4d)23, 4e24 and
4f24 were prepared according to the published procedures.
Terminal alkynes (4-ethynylphenyl)dimethylamine, 1-ethynyl-
2-(methoxy)methoxybenzene, 3-(ethynyl)phenylamine, and 1-
ethynyl-2-(methoxy)methoxybenzene were prepared according to
literature procedures.25 Other reagents were purchased from
Aldrich.
2
catalyst22 generated the alkynyl palladium intermediate. Then, g -
=
coordination of the C C double bond to the palladium center
followed by carbopalladation10b and substitution of Pd with hydro-
gen (either from the solvent or terminal alkyne), produced the c,d-
ynone product with concomitant regeneration of the Pd catalyst.
3. Conclusion
In conclusion, the first palladium-catalyzed conjugate addition
=
of terminal alkynes to the C C double bond of unsaturated
carbonyl compounds under mild conditions has been developed.
The corresponding c,d-alkynyl ketones and alkynyl esters were
obtained in high yields. The asymmetric additions, mechanism
and synthetic applications of this efficient addition reaction are
under investigation.
4. Experimental
General details
Experimental procedure for the 1,4-addition of terminal
alkynes to enones
1H NMR spectra were recorded on Varian 300 and 400 MHz
spectrometers in CDCl3 solution and the chemical shifts were
reported in parts per million (d) relative to internal standard
TMS (0 ppm). The peak patterns are indicated as follows: s,
singlet; d, doublet; t, triplet; q, quartet; m, multiplet; b, broad.
The coupling constants, J, are reported in Hertz (Hz). 13C
NMR spectra were obtained at 75 MHz and referenced to the
A mixture of 0.05 mmol Pd(OAc)2 (11 mg, 5 mol%) and 0. 20 mL
of PMe3 solution (0.20 mmol, 1.0 M PMe3 dissolved in toluene,
◦
20 mol%) was stirred at 60 C in an oil bath for 10 min until all
palladium acetate was dissolved. Then 1 mL of water or acetone
was added, followed by adding a mixture of terminal alkyne
2974 | Org. Biomol. Chem., 2008, 6, 2969–2977
This journal is
The Royal Society of Chemistry 2008
©

View Article Online
(1 mmol) and vinyl ketone (2–3 mmol). The reaction mixture was
then stirred at 60 ◦C in an oil bath. After the consumption of
terminal alkyne starting material, as shown by TLC, the reaction
mixture was extracted with ethyl ether (3 × 10 mL), dried over
anhydrous MgSO4 then concentrated in vacuo. The residue was
purified by flash column chromatography on silica gel (hexane–
ethyl acetate = 4 : 1) to give the pure product 3.
7-Phenyl-6-heptyn-3-one (3a). 1H NMR (CDCl3, 400 MHz)
d 7.29–7.27 (m, 2H), 7.19–7.17 (m, 3H), 2.64–2.57 (m, 4H),
2.38 (q, J = 7.6 Hz, 2H), 0.99 (t, J = 7.2 Hz, 3H); 13C NMR
(CDCl3,100 MHz) d 209.7, 131.7, 128.4, 127.9, 123.8, 88.9, 81.1,
41.4, 36.2, 14.3, 8.0; IR (neat) cm−1: 3055, 2971, 2240, 1712, 1481,
1363; GC–MS (relative intensity): 186 (M+, 17), 171 (6), 157 (100),
128 (33), 115 (28), 102 (9), 89 (8).
100 MHz): d 210.0, 79.9, 79.4, 41.8, 36.2, 28.0, 18.0, 13.7, 7.9;
IR (neat): cm−1 2938, 2331, 1712, 1429, 1363; GC–MS (relative
intensity): 259 (M+ − 1, 8), 243 (7), 231 (25), 189 (81), 175 (41),
159 (43), 131 (100), 117 (39), 105 (30).
5-Tetradecyn-2-one (3h). 1H NMR (CDCl3, 400 MHz) d 2.60
(t, J = 7.2 Hz, 2H), 2.37 (m, 2H), 2.13 (s, 3H), 2.07 (m, 2H), 1.40
(m, 2H), 1.19–1.24 (m, 10H), 0.84 (t, J = 6.8 Hz, 3H); 13C NMR
(CDCl3, 100 MHz) d 207.4, 81.1, 78.6, 43.2, 32.1, 31.8, 29.4, 29.3,
29.2, 29.1, 22.9, 18.9, 14.3, 13.6; IR (neat): cm−1 2919, 2332, 1712;
GC–MS (relative intensity) 209 (M+ + 1, 5), 164 (9), 150 (17), 135
(13), 121 (33), 109 (100), 95 (49), 81 (59).
6-Cyclohexenyl-5-hexyn-2-one (3i). 1H NMR (CDCl3,
400 MHz) d 5.96 (bs, 1H), 2.64 (t, J = 7.2 Hz, 2H), 2.50 (t, J =
7.2 Hz, 2H), 2.13 (s, 3H), 2.04–2.00 (m, 4H), 1.58–1.50 (m, 4H);
13C NMR (CDCl3, 100 MHz): d 207.2, 134.0, 120.9, 85.7, 82.9,
43.0, 30.2, 29.6, 25.7, 22.5, 21.7, 14.1. IR (neat): cm−1 2932, 2219,
1712, 1429, 1356, 1158; GC–MS (relative intensity): 176 (M+, 38),
161 (100), 133 (32), 105 (49), 91 (95).
7-Cyclohexenyl-6-heptyn-3-one(3b). 1H
NMR
(CDCl3,
400 MHz) d 5.94 (bs, 1H), 2.60 (t, J = 7.2 Hz, 2H), 2.50 (t,
J = 7.2 Hz, 2H), 2.40 (q, J = 7.2 Hz, 2H), 2.03–1.99 (m, 4H),
1.56–1.50 (m, 4H), 1.02 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3,
100 MHz): d 209.8, 133.9, 120.9, 85.8, 82.9, 41.6, 36.2, 29.6, 25.7,
22.5, 21.7, 14.2, 7.9; IR (neat) cm−1 2932, 2207, 1705, 1409, 1356;
GC–MS (relative intensity) 190 (M+, 21), 175 (9), 161 (100), 133
(20), 105 (28), 91 (66).
6-Trimethylsilyl-5-hexyn-2-one (3j). 1H NMR (CDCl3,
400 MHz) d 2.67 (t, J = 8.0 Hz, 2H), 2.46 (t, J = 8.0 Hz, 2H),
2.16 (s, 3H), 0.12 (s, 9H); 13C NMR (CDCl3, 100 MHz) d 206.9,
105.9, 85.4, 42.7, 30.2, 14.7, 0.3; IR (neat): cm−1 2952, 2919, 2167,
1719, 835; GC–MS (relative intensity): 168 (M+, not seen), 153
(100), 125 (27), 109 (23), 83 (31).
6-Pentadecyn-3-one (3c). 1H NMR (CDCl3, 400 MHz) d 2.56
(t, J = 7.6 Hz, 2H), 2.42 (t, J = 7.6 Hz, 2H), 2.37 (m, 2H), 2.06
(m, 2H), 1.35–1.19 (m, 12H), 1.02 (t, J = 7.6 Hz, 3H), 0.84 (t,
J = 6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz) d 210.0, 81.0, 78.7,
41.9, 36.2, 32.1, 29.4, 29.3, 29.2, 29.1, 22.9, 18.9, 14.3, 13.7, 7.9; IR
(neat) cm−1: 2920, 2850, 1719, 1461, 1369, 1106; GC–MS (relative
intensity): 223 (M+ + 1, 11), 207 (2), 193 (14), 165 (7), 150 (29),
135 (16), 123 (100), 121 (42), 109 (46), 95 (61), 81 (59).
5-Dodecyn-2-one (3k). 1H NMR (CDCl3, 400 MHz) d 2.59 (t,
J = 7.6 Hz, 2H), 2.37 (m, 2H), 2.13 (s, 3H), 2.07 (m, 2H), 1.40
(m, 2H), 1.20–1.31 (m, 6H), 0.85 (t, J = 7.2 Hz, 3H); 13C NMR
(CDCl3, 100 MHz): d 207.4, 81.1, 78.6, 43.2, 31.6, 30.1, 29.1, 28.7,
22.8, 18.9, 14.3, 13.6; IR (neat): cm−1 2925, 2853, 2200, 1712, 1461,
1356; GC–MS (relative intensity): 181 (M+ + 1, 3), 165 (3), 151
(7), 137 (13), 122 (30), 109 (100), 95 (46).
7-Trimethylsilyl-6-heptyn-3-one (3d). 1H NMR (CDCl3,
400 MHz): d 2.64 (t, J = 8.0 Hz, 2H), 2.47 (t, J = 8.0 Hz, 2H),
2.34 (q, J = 7.2 Hz, 2H), 1.06 (t, J = 7.2 Hz, 3H), 0.12 (s, 9H);
13C NMR (CDCl3, 100 MHz) d 209.7, 106.0, 85.3, 41.4, 36.3, 14.8,
8.0, 0.3; IR (neat) cm−12958, 2207, 1705, 1455; GC–MS (relative
intensity): 183 (M+ + 1, 25), 167 (100), 153 (42), 109 (60).
6-Phenyl-5-hexyn-2-one (3l). 1H NMR (CDCl3, 400 MHz) d
7.34–7.31 (m, 2H), 7.22–7.15 (m, 3H), 2.69 (dt, tJ = 8.0 Hz, dJ =
1.6 Hz, 2H), 2.60 (dt, tJ = 8.0 Hz, dJ = 1.6 Hz, 2H), 2.13 (s, 3H);
13C NMR (CDCl3, 100 MHz) d 207.0, 131.7, 128.4, 128.0, 123.8,
88.8, 81.1, 42.6, 30.1, 14.2; IR (neat): cm−1 3057, 2899, 2226, 1719,
1481, 1363; GC–MS (relative intensity): 172 (M+, 28), 171 (30),
157 (75), 129 (68), 128 (83), 115 (64), 102 (26), 77 (25), 63 (22), 51
(22), 43 (100).
11-Chloro-6-undecyn-3-one
(3e). 1H
NMR
(CDCl3,
400 MHz): d 3.49 (t, J = 6.4 Hz, 2H), 2.55 (t, J = 8.0 Hz,
2H), 2.39 (q, J = 7.2 Hz, 2H), 2.35 (t, J = 8.0 Hz, 2H), 2.11
(m, 2H), 1.82–1.55 (m, 4H), 1.02 (t, J = 7.2 Hz, 3H); 13C NMR
(CDCl3, 100 MHz) d 209.9, 79.9, 79.6, 44.8, 41.7, 36.2, 31.7, 26.2,
18.2, 13.6, 7.9; IR (neat): cm−1 2932, 2859, 2213, 1725, 1448;
GC–MS (relative intensity): 203 (M+ + 3, 2), 201 (M+ + 1, 8), 187
(4), 185 (14), 171 (18), 165 (29), 131 (6), 129 (14), 123 (100), 109
(28), 81 (80).
Experimental procedure for the 1,4-addition of terminal alkynes to
acrylate esters
1,3-Bis(2,4,6-trimethylphenyl)imidazolium chloride (34 mg,
1 mmol), Pd(OAc)2 (5.6 mg, 0.025 mmol) and t-BuOK(13.5 mg,
1.2 mmol) were added to a 10 mL Schlenk tube under N2. Dry
THF (1.5 mL) was injected and the mixture was stirred at rt for
2 h; then THF was slowly removed in vacuo, followed by the
addition of acetone (2 mL), phenylacetylene (102 mg, 1 mmol)
and methyl acrylate (172 mg, 2 mmol). The mixture was stirred at
60 ◦C until the reaction had reached completion (as determined by
TLC analysis). The solvent was evaporated and the crude reaction
mixture was then purified by flash chromatography on silica gel
with EtOAc–hexane (1 : 10) as the eluant.
6-Tridecyn-3-one (3f). 1H NMR (CDCl3, 400 MHz) d 2.56 (t,
J = 7.6 Hz, 2H), 2.42–2.36 (m, 4H), 2.07 (m, 2H), 1.40 (m, 2H),
1.20–1.31 (m, 6H), 1.03 (t, J = 7.6 Hz, 3H), 0.85 (t, J = 7.2 Hz,
3H); 13C NMR (CDCl3, 100 MHz) d 210.0, 81.0, 78.7, 41.9, 36.2,
31.6, 29.2, 28.7, 22.8, 18.9, 14.2, 13.7, 7.8; IR (neat): cm−1 2952,
2886, 2174, 1718; GC–MS (relative intensity): 195 (M+ + 1, 33),
165 (22), 123 (100), 109 (44), 95 (56), 81 (61).
6,11-Heptadecadiyne-3,15-dione (3g). 1H NMR (CDCl3,
400 MHz) d 2.57 (t, J = 7.2 Hz, 4H), 2.45–2.37 (m, 8H), 2.25–2.17
(m, 4H), 1.65 (m, 2H), 1.04 (t, J = 7.2 Hz, 6H); 13C NMR (CDCl3,
5-Phenylpent-4-ynoic acid methyl ester (5a). 1H NMR (CDCl3,
300 MHz) d 7.37–7.40 (m, 2H), 7.26–7.29 (m, 3H), 3.72(s, 3H), 2.73
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 2969–2977 | 2975
©

View Article Online
(t, J = 6.3 Hz, 2H), 2.64 (t, J = 6.39 Hz, 2H); 13C NMR (CDCl3,
75 MHz) d 172.6, 166.3, 131.8, 128.4, 128.0, 123.7, 88.2, 81.4,
52.1, 33.7, 15.6; MS (70 eV) m/z: 188 (M+), 173, 160, 145, 128
(100), 115; HRMS(EI) calc. for C12H12O2 [M+]: 188.08373, found:
188.08342.
(M+,100), 188, 174, 144, 130, 115; HRMS(EI) calc. for C12H13O2N
[M+]: 203.09463, found: 203.09422.
5-(6-Methoxynaphthalen-2-yl)pent-4-ynoic acid methyl ester
(5i). 1H NMR (CDCl3, 300 MHz) d 7.83 (s, 1H), 7.65 (t, J =
8.1 Hz, 2H), 7.40 (d, J = 5.1 Hz, 1H), 7.08–7.15 (m, 2H), 3.92 (s,
3H), 3.74 (s, 3H), 2.78 (t, J = 7.8 Hz, 2H), 2.67 (t, J = 7.8 Hz,
2H); 13C NMR (CDCl3, 75 MHz) d 172.6, 166.3, 158.3, 134.0,
131.3, 129.43,129.40, 128.7, 126.9, 119.5, 105.9, 87.7, 81.8, 55.5,
52.0, 33.8, 15.7; MS (70 eV) m/z: 268 (M+,100), 253, 239, 209, 195,
165, 152; HRMS(EI) calc. for C17H16O3 [M+]: 268.10994, found:
268.11020.
5-(p-(Phenyl)phenyl)pent-4-ynoic acid methyl ester (5b). 1H
NMR (CDCl3, 300 MHz) d 7.51–7.59 (m, 5H), 7.41–7.46 (m, 4H),
3.73 (s, 3), 2.76 (t, J = 7.8 Hz, 2H), 2.65 (t, J = 7.8 Hz, 2H); 13
C
NMR (CDCl3, 75 MHz) d 171.8, 140.2, 132.6, 128.8, 127.7, 127.1,
127.0, 126.9, 123.2, 89.3, 80.6, 51.9, 33.3, 15.8; MS (70 eV) m/z:
264 (M+,100), 249, 236, 205, 191, 178, 165, 148; HRMS(EI) calc.
for C18H16O2 [M+]: 264.11503, found: 264.11524.
5-(4-Ethynylphenyl)pent-4-ynoic acid methyl ester (5j). 1H
NMR (CDCl3, 300 MHz) d 7.39 (d, J = 7.5 Hz, 2H), 7.32 (d,
J = 8.1 Hz, 2H), 3.72 (s, 3H), 3.13 (s, 1H), 2.74 (t, J = 6.8 Hz,
2H), 2.65 (t, J = 6.8 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 172.5,
132.2, 131.7, 124.3, 121.7, 90.4, 83.5, 80.9, 78.8, 52.1, 33.5, 15.6;
MS (70 eV) m/z: 212 (M+),197, 184, 152, 139 (100); HRMS(EI)
calc. for C14H12O2 [M+]: 212.08373, found: 212.08347.
5-(p-Tolyl)pent-4-ynoic acid methyl ester (5c). 1H NMR
(CDCl3, 300 MHz) d 7.28 (d, J = 6.0 Hz, 2H), 7.08 (d, J = 6.0 Hz,
2H), 3.72 (s, 3H), 2.71 (t, J = 6.0 Hz, 2H), 2.65 (t, J = 6.3 Hz, 2H),
2.32 (s, 3H); 13C NMR (CDCl3, 75 MHz) d 172.6, 138.0, 131.7,
129.2, 120.6, 87.4, 81.4, 51.9, 33.7, 21.7, 15.6; MS (70 eV) m/z:
202 (M+), 187, 174, 159 (100),141, 129,115; HRMS(EI) calc. for
C13H14O2 [M+]: 202.09938, found: 202.09916.
5-Phenylpent-4-ynoic acid tert-butyl ester (5k). 1H NMR
(CDCl3, 300 MHz) d 7.36–7.38 (m, 2H), 7.26–7.29 (m, 3H), 2.68
(t, J = 6.9 Hz, 2H), 2.53 (t, J = 6.9 Hz, 2H), 1.45 (s, 9H); 13C NMR
(CDCl3, 75 MHz) d 171.5, 131.8, 129.1, 128.4, 123.9, 88.5, 81.7,
35.1, 29.9, 28.3, 15.8; MS (70 eV) m/z: 230 (M+),215, 174, 157,
146(100),128, 115; HRMS(EI) calc. for C15H18O2 [M+]: 230.13068,
found: 230.13040.
5-(p-Methoxyphenyl)pent-4-ynoic acid methyl ester (5d). 1H
NMR (CDCl3, 300 MHz) d 7.31 (d, J = 6.6 Hz, 2H), 6.80 (d,
J = 6.6 Hz, 2H), 3.79 (s, 3H), 3.71 (s, 3H), 2.73 (t, J = 5.4 Hz,
2H), 2.62 (t, J = 5.7 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 172.4,
159.1, 132.9, 115.6, 113.8, 86.3, 80.9, 55.2, 51.8, 33.5, 15.3; MS
(70 eV) m/z: 218 (M+), 203, 190, 175, 159, 144, 115 (100).
5-(4-(Dimethylamino)phenyl)pent-4-ynoic acid methyl ester (5e).
1H NMR (CDCl3, 300 MHz) d 7.25 (d, J = 8.4 Hz, 2H), 6.59 (d,
J = 8.4 Hz, 2H), 3.70 (s, 3H), 2.94 (s, 6H), 2.71 (t, J = 7.5 Hz,
2H), 2.61 (t, J = 7.5 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 172.8,
150.0, 132.8, 112.1, 110.8, 85.5, 82.0, 51.9, 40.5, 34.0, 15.7; MS
(70 eV) m/z: 231 (M+), 216, 202, 188, 158 (100); HRMS(EI) calc.
for C14H17O2N [M+]: 231.1293, found: 231.12564.
5-(p-(Phenyl)phenyl)pent-4-ynoic acid tert-butyl ester (5l). 1H
NMR (CDCl3, 300 MHz) d 7.54–7.60 (m, 5H), 7.41–7.47 (m,
4H), 2.72 (t, J = 7.8 Hz, 2H), 2.56 (t, J = 7.8 Hz, 2H), 1.50 (s,
9H); 13C NMR (CDCl3, 75 MHz) d 171.5, 140.7, 132.2, 129.0,
127.73, 127.67, 127.21, 127.12, 122.9, 89.3, 81.1, 35.1, 28.3, 15.1;
MS (70 eV) m/z: 306 (M+), 250 (100), 222, 191, 154; HRMS(EI)
calc. for C21H22O2 [M+]: 306.16198, found: 306.16164.
5-(2-Methoxyphenyl)pent-4-ynoic acid methyl ester (5f). 1H
NMR (CDCl3, 300 MHz) d 7.35 (d, J = 7.8 Hz, 1H), 7.25 (t,
J = 7.8 Hz, 1H), 6.83–6.90 (m, 2H), 3.86 (s, 3H), 3.71 (s, 3H),
2.78 (t, J = 7.8 Hz, 2H), 2.67 (t, J = 7.8 Hz, 2H); 13C NMR
(CDCl3, 75 MHz) d 172.6, 160.3, 134.0, 129.4, 120.6, 112.8, 110.8,
92.3, 76.8 56.0, 52.0, 33.7, 15.9; MS (70 eV) m/z: 218 (M+), 203,
190, 175, 159, 144, 115 (100); HRMS(EI) calc. for C13H14O3 [M+]:
218.09429, found: 218.09397.
5-(p-Tolyl)pent-4-ynoic acid tert-butyl ester (5m). 1H NMR
(CDCl3, 300 MHz) d 7.28 (d, J = 6.0 Hz, 2H), 7.07 (d, J =
6.0 Hz, 2H), 3.72 (s, 3H), 2.67 (t, J = 6.3 Hz, 2H), 2.54 (t, J =
6.3 Hz, 2H), 2.32 (s, 3H), 1.46 (s, 9H); 13C NMR (CDCl3, 75 MHz)
d 171.5, 137.9, 131.6, 129.7, 120.8, 87.7, 80.9, 35.1, 28.3, 21.6, 15.8;
MS (70 eV) m/z: 244 (M+), 229, 188, 171, 160, 145(100), 129, 115;
HRMS(EI) calc. for C16H20O2 [M+]: 244.14633, found: 244.14599.
5-(2-(Methoxymethoxy)phenyl)pent-4-ynoic acid tert-butyl ester
(5n). 1H NMR (CDCl3, 300 MHz) d 7.35 (d, J = 7.5 Hz, 1H),
7.22 (t, J = 6.6 Hz, 1H), 7.07 (d, J = 8.4 Hz, 1H), 6.94 (t, J =
7.8 Hz, 1H), 5.23 (s, 2H), 3.51 (s, 3H), 2.71 (t, J = 7.5 Hz, 2H),
2.57 (t, J = 7.5 Hz, 2H), 1.46 (s, 9H); 13C NMR (CDCl3, 75 MHz)
d 171.7, 166.3, 158.0, 133.9, 129.2, 122.1, 115.7, 95.3, 92.2, 81.4,
35.1, 28.3, 16.1; MS (70 eV) m/z: 290 (M+), 234, 202 (100), 189,
174, 157; HRMS(EI) calc. for C17H22O4 [M+]: 290.15181, found:
290.15152.
5-(o-(Methoxymethoxy)phenyl)pent-4-ynoic acid methyl ester
(5g). 1H NMR (CDCl3, 300 MHz) d 7.35 (d, J = 7.5 Hz, 1H),
7.22 (t, J = 6.6 Hz, 1H), 7.07 (d, J = 8.4 Hz, 1H), 6.94 (t, J =
7.8 Hz, 1H), 5.22 (s, 2H), 3.71 (s, 3H), 3.51 (s, 3H), 2.78 (t, J =
7.5 Hz, 2H), 2.65 (t, J = 7.5 Hz, 2H; 13C NMR (CDCl3, 75 MHz)
d 172.6, 166.3, 157,9, 133.9, 129.3, 122.1, 115.6, 96.8, 95.3, 92.2,
56.4, 52.0, 33.8, 15.9; MS (70 eV) m/z: 248 (M+), 233, 216, 201,
175, 157 (100); HRMS(EI) calc. for C14H16O4 [M+]: 248.10486,
found: 248.10457.
5-(3-Aminophenyl)pent-4-ynoic acid methyl ester (5h). 1H
NMR (CDCl3, 300 MHz) d 7.05 (t, J = 7.8 Hz, 1H), 6.79 (d,
J = 6.0 Hz, 1H), 6.70 (s, 1H), 6.59 (d, J = 8.1 Hz, 1H), 3.69 (s,
3H), 3.65 (br, 2H), 2.71 (t, J = 7.8 Hz, 2H), 2.61 (t, J = 7.8 Hz, 2H);
13C NMR (CDCl3, 75 MHz) d 172.6, 146.4, 129.4, 124.4, 122.2,
118.2, 115.1, 87.5, 81.6, 52.0, 33.7, 15.7; MS (70 eV) m/z: 203
Acknowledgements
We are grateful to the Canada Research Chair (Tier I) foundation
(to CJL), the CFI, NSERC and the US NSF-EPA Joint Program
for a Sustainable Environment for support of our research. LZ
thanks the China Scholarship Council for a Visiting Scholarship.
2976 | Org. Biomol. Chem., 2008, 6, 2969–2977
This journal is
The Royal Society of Chemistry 2008
©

View Article Online
Lett., 2003, 5, 4473; (f) C. Fischer and E. M. Carreira, Org. Lett., 2001,
3, 4319.
References
1 For monographs on palladium catalysis, see: (a) Handbook of
Organopalladium Chemistry for Organic Synthesis, ed. E. Negishi,
Wiley, Hoboken, NJ, 2002; (b) Handbook of Palladium-Catalyzed
Organic Reactions, ed. J.-L. Malleron, J.-C. Fiaud and J.-Y. Legros,
Academic Press, London, 1997; (c) Palladium Reagents and Catalysts,
ed. J. Tsuji, Wiley, Chichester, 1995.
2 (a) I. P. Beletskaya and A. Cheprokov, Chem. Rev., 2000, 100, 3009;
(b) A. de Meijere and S. Brase, J. Organomet. Chem., 1999, 576, 88;
(c) M. Shibasaki and E. M. Vogl, J. Organomet. Chem., 1999, 576, 1;
(d) R. F. Heck, Org. React., 1982, 27, 345; (e) R. F. Heck, Acc. Chem.
Res., 1979, 12, 146; (f) N. A. Cortese, C. B. Ziegler, B. J. Hrnjez and
R. F. Heck, J. Org. Chem., 1978, 43, 2852; (g) H. A. Dieck and R. F.
Heck, J. Organomet. Chem., 1975, 93, 259.
3 (a) M. Kosugi and K. Fugami, J. Organomet. Chem., 2002, 653, 50;
(b) V. Farina and G. P. Roth, Adv. Met.–Org. Chem., 1996, 5, 1; (c) A. M.
Echavarren and J. K. Stille, J. Am. Chem. Soc., 1988, 110, 1557; (d) J. W.
Labadie, D. Tueting and J. K. Stille, J. Org. Chem., 1983, 48, 4634.
4 (a) H. N. Nguyen, X. Huang and S. L. Buchward, J. Am. Chem. Soc.,
2003, 125, 11818; (b) M. Sato, N. Miyaura and A. Suzuki, Chem.
Lett., 1989, 1405; (c) A. Suzuki, Pure Appl. Chem., 1985, 57, 1749;
(d) N. Miyaura, T. Yanagi and A. Suzuki, Synth. Commun., 1981, 11,
513.
5 (a) B. G. Jellerichs, J.-R. Kong and M. J. Krische, J. Am. Chem. Soc.,
2003, 125, 7758; (b) D. Ferroud, J. P. Genet and J. Muzart, Tetrahedron
Lett., 1984, 25, 4379; (c) C. deBellefon, E. Pollet and P. Grenouillet,
J. Mol. Catal. A, 1999, 145, 121.
6 (a) K. Sonogashira, J. Organomet. Chem., 2002, 653, 46; (b) K.
Sonogashira, Y. Tohda and N. Hagihara, Tetrahedron Lett., 1975, 50,
4467; (c) K. Sonogashira, Y. Tohda and N. Hagihara, Tetrahedron Lett.,
1975, 4467.
7 (a) B. M. Trost, F. D. Toste and K. Greenman, J. Am. Chem. Soc., 2003,
125, 4518; (b) B. M. Trost, Acc. Chem. Res., 2002, 35, 695; (c) B. M.
Trost, Angew. Chem., Int. Ed. Engl., 1995, 34, 259; (d) B. M. Trost,
Science, 1991, 254, 1471.
8 (a) D. Boyall, D. E. Frantz and E. M. Carreira, Org. Lett., 2002, 4,
2605–2606; (b) H. Sasaki, D. Boyall and E. M. Carreira, Helv. Chim.
Acta, 2001, 84, 964; (c) N. K. Anand and E. M. Carreira, J. Am. Chem.
Soc., 2001, 123, 9687; (d) D. E. Frantz, R. Fassler and E. M. Carreira,
J. Am. Chem. Soc., 2000, 122, 1806; (e) X. Yao, X. and C. J. Li, Org.
Lett., 2005, 7, 4395; (f) X. Yao, X. and C. J. Li, Org. Lett., 2006, 8,
1953.
9 (a) R. Shintani and G. C. Fu, J. Am. Chem. Soc., 2003, 125, 10778;
(b) C. Wei and C.-J. Li, J. Am. Chem. Soc., 2003, 125, 9584; (c) C.-J.
Li and C. Wei, Chem. Commun., 2002, 268; (d) C. Wei and C.-J. Li,
J. Am. Chem. Soc., 2002, 124, 5638; (e) J. Zhang, C. Wei and C.-J. Li,
Tetrahedron Lett., 2002, 43, 5731; C. M. Wei, Z. G. Li and C. J. Li, Org.
10 (a) S. Chang, Y. Na, E. Choi and S. Kim, Org. Lett., 2001, 3, 2089;
(b) M. Picquet, C. Bruneau and P. H. Dixneuf, Tetrahedron, 1999, 55,
3937; (c) G. I. Nikishin and I. P. Kovalev, Tetrahedron Lett., 1990, 31,
7063; (d) T. F. Knopfel and E. M. Carreira, J. Am. Chem. Soc., 2003,
125, 6054; (e) M. Kanai and M. Shibasaki, in Catalytic Asymmetric
Synthesis, ed. I. Ojima, Wiley-VCH, New York, 2nd edn, 2000, p. 569.
11 V. Ritleng, C. Sirlin and M. Pfeffer, Chem. Rev., 2002, 102, 1731.
12 (a) B. M. Trost and A. E. Harms, Tetrahedron Lett., 1996, 37, 3971;
(b) B. M. Trost, C. Chan and G. Ruhter, J. Am. Chem. Soc., 1987, 109,
3486; (c) B. M. Trost and C. J. Li, Synthesis, 1994, 1267.
13 L. Chen and C.-J. Li, Chem. Commun., 2004, 2362.
14 For examples involving Pd catalysts with electron rich ligands, see: V.
Ritleng, C. Sirlin and M. Pfeffer, Chem. Rev., 2002, 102, 1731; B. M.
Trost, M. T. Sorum, C. Chan, A. E. Harms and G. Ruhter, J. Am.
Chem. Soc., 1997, 119, 698.
15 Alcohols: B. M. Trost and C. J. Li, J. Am. Chem. Soc., 1994, 116,
10819. Amines: B. M. Trost and G. R. Dake, J. Am. Chem. Soc., 1997,
62, 5670. Activated methylenes: B. M. Trost and C. J. Li, J. Am. Chem.
Soc., 1994, 116, 3167.
16 T. Sakakura, H. Yamashita, T. Kobayashi, T. Hayashi and M. Tanaka,
J. Org. Chem., 1987, 52, 5733.
17 (a) S. Fujimori and E. M. Carreira, Angew. Chem., Int. Ed., 2007, 46,
4964; (b) T. F. Knoepfel and E. M. Carreira, J. Am. Chem. Soc., 2003,
125, 6054; (c) T. F. Knoepfel, P. Zarotti, T. Ichikawa and E. M. Carreira,
J. Am. Chem. Soc., 2005, 127, 9682.
18 T. Nishimura, Y. Washitake, Y. Nishiguchi, Y. Maeda and S. Uemura,
Chem. Commun., 2004, 1312.
19 (a) N-Heterocyclic Carbenes in Synthesis, ed. S. P. Nolan, Wiley,
Weinheim, 2006; (b) N-Heterocyclic Carbenes in Transition Metal
Catalysis, ed. F. Glorius, Springer, Berlin, 2006; (c) E. A. B. Kantchev,
C. J. O’Brien and M. G. Organ, Angew. Chem., Int. Ed., 2007, 46, 2768;
(d) R. Dorta, E. D. Stevens, C. D. Hoff and S. P. Nolan, J. Am. Chem.
Soc., 2003, 125, 10490.
20 E. M. Phillips, M Wadamoto, A. Chan and K. A. Scheidt, Angew.
Chem., Int. Ed., 2007, 46, 3107.
21 P.-C. Chiang, J. Kaeobamrung and J. W. Bode, J. Am. Chem. Soc., 2007,
129, 3520.
22 For previous examples involving direct deprotonation of terminal
alkynes by palladium catalysts, please see: C. Scheffknecht and P.
Peringer, J. Organomet. Chem., 1997, 535, 77.
23 W. A. Herrmann, L. J. Goossen and M. Spiegler, Organometallics, 1998,
17, 2162.
24 D. J. Nielsen, K. J. Cavell, B. W. Skelton and A. H. White, Inorg. Chim.
Acta, 2006, 359, 1855.
25 N. Paul, Y. Zheng, A. Lisa, L. Gerald and B. M. Todd, Inorg. Chim.
Acta, 1994, 220, 289.
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 2969–2977 | 2977
©