A remarkably efficient coupling of acid chlorides with alkynes in water

Article abstract of DOI:10.1021/ol048789w

(Chemical Equation Presented) A highly effective direct coupling of acid chloride with terminal alkynes catalyzed by PdCl₂(PPh ₃)₂/Cul together with a catalytic amount of sodium lauryl sulfate as the surfactant and K₂

Full text of DOI:10.1021/ol048789w

ORGANIC
LETTERS
2004
Vol. 6, No. 18
3151-3153
A Remarkably Efficient Coupling of Acid
Chlorides with Alkynes in Water
,†,‡
Liang Chen† and Chao-Jun Li*
Department of Chemistry, Tulane UniVersity, New Orleans, Louisiana 70118, and
Department of Chemistry, McGill UniVersity, 801 Sherbrooke St. West, Montreal,
Quebec H3A 2K6, Canada
cj.li@mcgill.ca
Received June 24, 2004
ABSTRACT
A highly effective direct coupling of acid chloride with terminal alkynes catalyzed by PdCl2(PPh3)2/CuI together with a catalytic amount of
sodium lauryl sulfate as the surfactant and K CO3 as the base provided ynones in high yields in water.
2
The utilization of ynones is a common strategy in the
synthesis of many biologically important compounds.1
Traditionally, ynones are generally synthesized via the
coupling of carboxylic acid chlorides and lithium acetylides.2
However, such a reaction is quite drastic and lacks chemical
selectivity in the presence of other electrophiles. Functional
groups such as hydroxyls, acids, amines, aldehydes, ketones,
etc. also have to be protected prior to the reaction. More
recently, an alternative coupling of carboxylic acid halides
with terminal alkynes has been developed by using pal-
ladium3 and copper catalysts,4 which can proceed at mild
conditions and enhanced chemoselectivities. However, an-
hydrous conditions, protected acidic functional groups (such
as hydroxyl), and an organic base are essential for such
reactions.
There has been considerable recent attention toward the
development of carbon-carbon bond formation reactions in
water.5 An underlining implication of such reactions is their
tolerance to various functional groups, and thus the protec-
tion-deprotection processes for certain acidic-hydrogen-
containing functional groups can be avoided, which contrib-
utes to the overall synthetic efficiency.6 Additionally, water-
soluble compounds, such as carbohydrates, can be directly
(3) Alonso, D. A.; Najera, C.; Pacheco, M. C. J. Org. Chem 2004, 69,
1615. Yin, J.; Wang, X.-j; Liang, Y.; Wu, X.; Chen, B.; Ma, Y. Synthesis
2004, 3, 331. Wang, J.-X.; Wei, B.; Huang, D.; Hu, Y.; Bai, L. Synth.
Commun. 2001, 31, 3337.
† Tulane University.
‡ McGill University.
(4) Gallagher, W. P.; Maleczka, R. E., Jr. J. Org. Chem 2003, 68, 6775.
Wang, J.-X..; Wei, B.; Hu, Y.; Liu, Z. X.; Fu, Y. Synth. Commun. 2001,
31, 3527. Chowdhury, C.; Kundu, N. G. Tetrahedron 1999, 55, 7011.
Chowdhury, C.; Kundu, N. G. Tetrahedron Lett. 1996, 37, 7323. Shergina,
S. I.; Sokolov, I. E.; Anaina, A. S. MendeleeV Commun. 1994, 6, 207.
(5) Li, C. J. Angew. Chem., Int. Ed. 2003, 42, 4856. Okuhara, T. Chem.
ReV. 2002, 102, 3641. Lindstro¨m, U. M. Chem. ReV. 2002, 102, 2751. Li,
C. J. Acc. Chem. Res. 2002, 35, 533. Kobayashi, S.; Manabe, K. Acc. Chem.
Res. 2002, 35, 209. Uozumi, Y.; Shibatomi, K. J. Am. Chem. Soc. 2001,
123, 2919. Li, C. J.; Chan, T. H. Organic Reactions in Aqueous Media;
John Wiley & Sons: New York, 1997. Cornils, B., Herrmann, W. A., Eds.;
Aqueous-Phase Organometallic Catalysis, Concepts and Applications;
Wiley-VCH: Weinheim, 1996. Breslow, R. Acc. Chem. Res. 1991, 24, 159.
Grieco, P. A. Aldrichimica Acta 1991, 24, 59. Organic Synthesis in Water;
Greico, P. A., Ed.; Thomson Science: Glasgow, 1998. Li, C. J. Chem. ReV.
1993, 93, 2023. Lubineau, A.; Auge, J.; Queneau, Y. Synthesis 1994, 741.
Reissig, H. U. Org. Synth. Highlights 1991, 71. Engberts, J. B. F. N. Pure
Appl. Chem. 1982, 54, 1797.
(1) Karpov, A. S.; Muller, T. J. J. Org. Lett. 2003, 5, 3451. Grotjahn, D.
B.; Van, S.; Combs, D.; Lev, D. A.; Schneider, C.; Rideout, M.; Meyer,
C.; Hernandez, G.; Mejorado, L. J. Org. Chem. 2002, 67, 9200. Dieter, R.
K.; Lu, K. J. Org. Chem. 2002, 67, 847. Kel’in, A. V.; Gevorgyan, V. J.
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Lett. 2002, 4, 2071. Kel’in, A. V.; Sromek, A. W.; Gevorgyan, V. J. Am.
Chem. Soc. 2001, 123, 2074. Jeevanandam, A.; Narkunan, K.; Ling, Y. C.
J. Org. Chem. 2001, 66, 6014. Williams, D. R.; Fromhold, M. G.; Earley,
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Asymmetry 1999, 10, 1163. Kerdesky, F. A. J.; Schmidt, S. P.; Brooks, D.
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10.1021/ol048789w CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/31/2004

Table 1. Direct Coupling of Phenylacetylene and Benzoyl Chloride in Watera
entry
catalyst
additive/base
yield (%)
1
2
3
4
5
6
7
8
5% CuI
5% Pd(OAc)2
5% Pd(OAc)2/10%TDMPPc
2% PdCl2(PPh3)2
sodium laurylsulfate/K2CO3
sodium laurylsulfate/K2CO3
sodium laurylsulfate/K2CO3
sodium laurylsulfate/K2CO3
sodium laurylsulfate/K2CO3
sodium laurylsulfate/K2CO3
sodium laurylsulfate/K2CO3
sodium laurylsulfate/K2CO3
sod iu m la u r ylsu lfa te/K2CO3
sodium laurylsulfate/K2CO3
sodium laurylsulfate/K2CO3
sodium laurylsulfate/K2CO3
sodium laurylsulfate/K2CO3
cetyltrimethylammonium bromide/K2CO3
triethylbenzylammonium bromide/K2CO3
none/K2CO3
<5b
nr
nr
nr
nr
5% Pd(OAc)2/5% CuI
5% Pd(OAc)2/10% tricyclohexylphosphine/5% CuI
5% Pd(OAc)2/10% TDMPPc/5% CuI
5% Pd(OAc)2/10% P(OMe)3
2% P d Cl2(P P h 3)2/5% Cu I
2% PdCl2(PPh3)2/5% CuBr
2% PdCl2(PPh3)2/5% CuCl
2% PdCl2(PPh3)2/5% CuCN
2% PdCl2(PPh3)2/5% AgI
2% PdCl2(PPh3)2/5% CuI
2% PdCl2(PPh3)2/5% CuI
2% PdCl2(PPh3)2/5% CuI
2% PdCl2(PPh3)2/5% CuI
2% PdCl2(PPh3)2/5% CuI
nr
29
83
98
92
11
50
<5b
33
27
9
9
10
11
12
13
14
15
16
17
18
sodium laurylsulfate/NaOH
sodium laurylsulfate/NaHCO3
46
16
a Conditions: 1 mmol of phenylacetylene, 2 mmol of benzoyl chloride, 20 mg of additives, and 3 mmol of base were used in 1 mL of water at 65 °C for
1
4 h. b Determined by H NMR. c Tris(2,6-dimethoxylphenyl)phosphine.
reacted without the need for derivatization and water-soluble
catalysts provide a way for product isolation and catalyst
recycling.7 Among the many carbon-carbon bond formation
reactions, recently various Barbier-Grignard reactions have
been successful in water.8
coupling reaction with terminal alkynes in the presence of a
catalyst. Furthermore, the solvent water molecule has a
stronger nucleophilicity (compared to that of the terminal
alkynes) toward the carboxylic acid chlorides. To overcome
the thermodynamically unfavorable reactivity of carboxylic
acid chlorides with alkynes in the presence of water, we
hypothesized that the use of a surfactant would decrease the
kinetics of hydrolysis by preventing and/or diminishing the
acid chlorides from encountering the water molecules.10 In
addition, water can dissolve the HCl generated from the
coupling reaction, which will further drive the reaction
toward the formation of the desired product. The coupling
of phenylacetylene with benzoyl chloride was used to
optimize the reaction conditions, and the results are sum-
marized in Table 1.
In light of the current interest in developing new funda-
mental reactions that could lead to high synthetic efficiency,
it is highly desirable to develop a direct coupling of
carboxylic acid chlorides with terminal alkynes in water.
However, as it is common knowledge that carboxylic acid
halides are quite water-sensitive (leading to rapid hydrolysis),
such an aspiration seems virtually impossible. On the other
hand, the well-known Schotten-Baumann method utilizes
strong nucleophiles, such as alcohols or amines, to attack
acid chloride in aqueous media.9 Nevertheless, herein we
wish to report for the first time a remarkably efficient
coupling of carboxylic acid chlorides with terminal alkynes
that has a relatively weak nucleophilicity in water (Scheme
1).
At first, we tested the stability of carboxylic acid chlorides
in water. It showed benzoyl chloride was converted into
benzoic acid completely (recovery of benzoic acid >99%)
at 65 °C for 4 h. The use of PdCl2(PPh3)2/CuI as cocatalysts
together with a catalytic amount of sodium lauryl sulfate as
the surfactant and K2CO3 as the base provided the desired
Scheme 1
(7) For examples, see: Abraham, B.; McMasters, S.; Mullan, M. A.;
Kelly, L. A. J. Am. Chem. Soc. 2004, 126, 4293. Christian, D.; Fitremann,
J.; Bouchu, A.; Queneau, Y. Tetrahedron Lett. 2004, 45, 583. Bazito, R.
C.; El Seoud, O. A. Carbohydr. Res. 2001, 332, 95. Diaz Perez, V. M.;
Ortiz Mellet, C. O.; Fuentes, J.; Garcia Fernandez, J. M. Carbohydr. Res.
2000, 326, 161.
(8) Keh, C. C. K.; Wei, C.; Li, C. J. J. Am. Chem. Soc. 2003, 125, 4062.
Matsukawa, S.; Hinakubo, Y. Org. Lett. 2003, 5, 1221. Lombardo, M.;
Morganti, S.; Trombini, C. J. Org. Chem. 2003, 68, 997. Li, C. J. Green
Chem. 2002, 4, 1.
(9) Georg, G. I. Bioorg. Med. Chem. Lett. 1994, 4, 335. Tsuchiga, M.
Bull. Chem. Soc. Jpn. 1969, 42, 1756. Sonntag, N. O. V. Chem. ReV. 1953,
52, 272. Baumann, E. Ber. 1886, 19, 3218. Schotten, C. Ber. 1884, 17,
2544.
(10) For examples of using surfactant in water for stabilizing silyl enol
ethers, see: Kobayashi, S.; Wakabayashi, T. Tetrahedron Lett. 1998, 39,
5389. Tian, H. Y.; Chen, Y. J.; Wang, D.; Zeng, C. C.; Li, C. J. Tetrahedron
Lett. 2000, 41, 2529.
There are two competitive reactions related to carboxylic
acid chlorides in water: (1) hydrolysis by water and (2)
(6) For examples, see: Schmid, W.; Whitesides, G. M. J. Am. Chem.
Soc. 1991, 113, 6674. Chan, T. H.; Li, C. J. J. Chem. Soc., Chem. Commun.
1992, 747. Chappell, M. D.; Halcomb, R. L. Org. Lett. 2000, 2, 2003.
Warwel, M.; Fessner, W. D. Synlett 2000, 865. Canac, Y.; Levoirier, E.;
Lubineau, A. J. Org. Chem. 2001, 66, 3206.
3152
Org. Lett., Vol. 6, No. 18, 2004

Table 2. Ynones via the Coupling of Terminal Alkynes with Acid Chlorides in Watera
a Reactions were carried out using 1 mmol of terminal alkynes, 2 mmol of acid chlorides, 20 mg of sodium lauryl sulfate (7 mol%), 14 mg of PdCl2(PPh3)2(2
mol%), 10 mg of CuI (5 mol%), and 414 mg of K2CO3 (3 mmol) in 1 mL of water at 65 °C for 4 h. b 4-Nitrobenzoyl chloride was dissolved in 200 mg of
toluene before adding as a starting material.
product in 98% isolated yield (entry 9). No reaction was
observed when either Cu(I) alone or Pd(II) alone was used
as the catalyst (entries 1-4). The use of surfactant is also
critical for the success of the reaction; without a surfactant/
phase-transfer reagent the yield dropped from 98% to 9%
(compare entries 9 and 16). Sodium lauryl sulfate is the most
effective surfactant/ phase-transfer agent (compare entries
9, 14, 15) for the current coupling under the same reaction
conditions. The strength of the base also played a role in
the reaction: the use of either stronger base NaOH or weaker
base NaHCO3 decreased the yield of the reaction (entries
17 and 18).
Subsequently, various acid chlorides were coupled with
terminal alkynes under the optimized conditions (Table 2).
Both aliphatic and aromatic alkynes are effective for the
current reaction. Nearly quantitative yields were obtained
in almost all cases when both aromatic acid chlorides and
aromatic alkynes were used, with an exception of p-
nitrobenzoyl chloride, which can be attributed to the solid
nature of the compound. The use of aliphatic alkynes
decreased the yields slightly. It is interesting to note that
the aryl bromide functionality remained unaffected during
the reaction (entry 12).
In summary, a highly effective direct coupling of acid
chlorides with terminal alkynes catalyzed by PdCl2(PPh3)2/
CuI together with a catalytic amount of sodium lauryl sulfate
as the surfactant and K2CO3 as the base provided ynones in
high yields in water. The scope, mechanism, and synthetic
applications of this reaction are currently under investigation.
Acknowledgment. We are grateful to NSF (No.0207363)
and NSF-EPA Joint Program for a Sustainable Environment
for support of our research. L.C. thanks a Cancer Research
Fellowship by the Tulane University Cancer Center. C.J.L.
is a Canada Research Chair (Tier I) at McGill University.
Supporting Information Available: Representative ex-
perimental procedure and the full characterization of all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL048789W
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