Palladium-catalyzed coupling of alkynes with alcohols and carboxylic acids

Article abstract of DOI:10.1016/S0040-4039(02)01436-3

The palladium-catalyzed coupling of alkynes with alcohols and carboxylic acids to give allylic ethers and esters has been achieved. With phenols, these conditions furnish the C-alkylation products.

Full text of DOI:10.1016/S0040-4039(02)01436-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6575–6578
Palladium-catalyzed coupling of alkynes with alcohols and
carboxylic acids
Weijiang Zhang,* Anthony R. Haight and Margaret C. Hsu
GPRD Process Chemistry & Engineering, Abbott Laboratories, 1401 Sheridan Road, North Chicago, IL 60064, USA
Received 2 July 2002; revised 11 July 2002; accepted 12 July 2002
Abstract—The palladium-catalyzed coupling of alkynes with alcohols and carboxylic acids to give allylic ethers and esters has been
achieved. With phenols, these conditions furnish the C-alkylation products. © 2002 Elsevier Science Ltd. All rights reserved.
Palladium-catalyzed couplings of allenes, allyl esters,
and allyl carbonates with nucleophiles such as mal-
onates, amines, and alcohols are widely employed in
organic synthesis. These condensations proceed
through a common reaction mechanism, via the forma-
case of t-butanol (entry 4), the yield of the correspond-
6
ing product 6d was lower. For acids, the yields of allyl
6
esters 6e–h varied from 75 to 90% (entries 5–8). In
1
these cases, a catalytic amount of triethylamine was
found to improve the yield, presumably by deprotona-
tion of the carboxylic acids to enhance the nucleophilic-
ity of the resultant carboxylates. It is worthwhile to
note that the cis-allyl ether or ester products were not
detected under these conditions. In the case of 3-prop-
1-ynyl-pyridine, a disappointing 30% yield of 6i was
isolated under the standard conditions (entry 9, Table
tion of the p-allyl palladium complex and subsequent
2
nucleophilic attack to complete the allylation process.
The isomerization of alkynes to allenes by palladium
hydride complexes is also well known in the chemical
3
literature. The coupling of these two transformations
offers the opportunity to generate alkene derivatives in
tandem from an alkyne and a nucleophile (Scheme 1).
6
1).
4
It has been previously reported that malononitrile and
5
amines can be allylated using alkynes with palladium
To determine the scope of the alkyne substrates, 3-
phenylpropyne was subjected to the coupling condi-
tions. Although this system was expected to react
similarly to 1-phenylpropyne, only a trace amount of
catalysis. We wish to report here on the allylation
reaction of 1-arylpropynes with oxygen nucleophiles
such as alcohols and carboxylic acids.
6
product 6b was observed (Scheme 2). Aliphatic alkynes
Excellent yields of the allyl ethers using primary or
such as 3-hexyne and 1-hexyne gave indeterminate mix-
tures of products.
6
secondary alcohols were observed (entries 1–3). In the
Scheme 1.
*
0
Corresponding author. Fax: (847)938-2258; e-mail: weijiang.zhang@abbott.com
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01436-3

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W. Zhang et al. / Tetrahedron Letters 43 (2002) 6575–6578
Table 1. Alkylation reactions of 1-arylpropynes to alcohols and acids
C-alkylated and the O-alkylated products formed ini-
tially under the reaction conditions, but with prolonged
6
reaction time, the amount of ethers (13–14) decreased
Scheme 2.
with a concomitant increase in the C-alkylation products
10–11). Presumably, two competitive reaction pathways
(
(
a and b in Scheme 4) furnish the mixture of products.
The phenolic ethers, obtained by pathway b, can then
undergo palladium-catalyzed rearrangement to the more
When the allylation reaction with phenolic nucleophiles
–9 was carried out, the C-alkylation products, 10–12,
were isolated in 76, 65, and 35% yields, respectively
7
7
6
stable C-allylated product.
(
Scheme 3). Further investigation revealed that both the
Heating independently prepared 13 to 100°C in 1,4-diox-
8
ane for 15 h produced no discernable reaction. However,
under the same conditions, in the presence of 5 mol%
Scheme 3.

W. Zhang et al. / Tetrahedron Letters 43 (2002) 6575–6578
6577
3
4
5
6
. Trost, B. M.; Schmidt, T. J. Am. Chem. Soc. 1988, 110,
2301–2303.
. Kadota, I.; Shibuya, A.; Gyoung, Y. S.; Yamamoto, Y.
J. Am. Chem. Soc. 1998, 120, 10262–10263.
. Kadota, I.; Shibuya, A.; Lutete, L. M.; Yamamoto, Y. J.
Org. Chem. 1999, 64, 4570–4571.
. All the compounds prepared by the coupling reaction are
+
1
literature known. 6a: Oil; MS m/z 238 (M ); H NMR
CDCl ) l 7.15–7.40 (m, 10H), 6.56 (d, J=16 Hz, 1H),
(
3
6
3
.27 (dt, J=16, 7 Hz, 1H), 4.14 (dd, J=6.8, 2 Hz, 2H),
13
.69 (t, J=7.1 Hz, 2H), 2.93 (t, J=7.1 Hz, 2H);
C
NMR (CDCl ) l 138.87, 136.68, 132.16, 128.88, 128.48,
3
1
28.33, 127.59, 126.42, 126.18, 126.10, 71.44, 71.21, 36.39.
+
1
6b: Oil; MS m/z 176 (M ); H NMR (CDCl ) l 7.15–7.40
3
(
m, 5H), 6.58 (d, J=16 Hz, 1H), 6.28 (dt, J=16, 7 Hz,
1
1
1
6
H), 4.12 (dd, J=6.8, 2 Hz, 2H), 3.66 (hept, J=6.8 Hz,
1
3
H), 1.19 (d, J=6.8 Hz, 6H); C NMR (CDCl ) l
3
36.77, 131.60, 128.44, 127.39, 126.76, 126.34, 70.84,
+
1
8.61, 22.06. 6c: Oil; MS m/z 300 (M ); H NMR
Scheme 4.
(CDCl ) l 7.42–7.20 (m, 10H), 6.6 (d, J=16 Hz, 1H),
3
6
.34 (dt, J=16, 7 Hz, 1H), 5.49 (s, 1H), 4.18 (dd, J=7, 2
13
Hz, 2H); C NMR (CDCl ) l 142.11, 136.72, 132.26,
3
Pd(PPh ) , phenol 10 was isolated in 55% yield without
3
4
1
8
28.49, 128.40, 127.59, 127.42, 127.00, 126.44, 126.13,
2.58, 69.33. 6d: Oil; MS m/z 190 (M ); H NMR
9
any detectable trace of the Claisen product 15. The
involvement of the phenoxide in a palladium-catalyzed
alkylation can be implied by the failed reactions of
anisole and N,N-dimethylaniline under identical
+
1
(
CDCl ) l 7.20–7.40 (m, 5H), 6.60 (d, J=16 Hz, 1H),
3
6
1
1
.29 (dt, J=16, 7 Hz, 1H), 4.18 (dd, J=7, 2 Hz, 2H),
.26 (s, 9H); C NMR (CDCl ) l 137.03, 131.06, 128.38,
13
3
1
0
conditions.
27.65, 127.30, 126.37, 73.26, 62.77, 27.61. 6e: Oil; MS
+
1
m/z 176 (M ); H NMR (CDCl ) l 7.20–7.42 (m, 5H),
In summary, a method for the efficient synthesis of
allylic ethers and esters from 1-arylpropynes has been
developed. With phenols, the method gives C-alkyla-
tion products in moderate yields. Due to the readily
available nature of alkynes, this chemistry offers
another alternative towards the synthesis of allylic
ethers and esters.
3
6.66 (d, J=16 Hz, 1H), 6.28 (dt, J=16, 7 Hz, 1H), 4.72
13
(
dd, J=7, 2 Hz, 2H), 2.1 (s, 3H); C NMR (CDCl ) l
3
1
6
70.78, 136.14, 134.15, 128.56, 128.02, 126.55, 123.11,
+
1
5.03, 20.96. 6f: Oil; MS m/z 204 (M ); H NMR
(
CDCl ) l 7.22–7.44 (m, 5H), 6.66 (d, J=16 Hz, 1H),
3
6
2
.29 (dt, J=16, 7 Hz, 1H), 4.72 (dd, J=7, 2 Hz, 2H),
.59 (hept, J=7 Hz, 1H), 1.20 (d, J=7 Hz, 6H);
13
C
NMR (CDCl ) l 176.82, 136.25, 133.88, 128.57, 127.99,
3
Representative experimental procedures
1
26.57, 123.41, 64.85, 34.03, 19.01. 6g: Oil; MS m/z 218
+
1
(
M ); H NMR (CDCl ) l 7.22–7.43 (m, 5H), 6.64 (d,
3
For alcohols and phenols: A mixture of 2 mmol 1-
phenylpropyne 1, 4 mmol alcohol, 0.1 mol tetra-
kis(triphenylphosphine) palladium(0), and 0.2 mmol
benzoic acid in 3 ml 1,4-dioxane was heated to 100°C
for 16–20 h.
J=16 Hz, 1H), 6.28 (dt, J=16, 7 Hz, 1H), 4.73 (dd, J=7,
1
3
2
1
3
Hz, 2H), 1.23 (s, 9H); C NMR (CDCl ) l 178.30,
3
36.32, 133.57, 128.57, 127.94, 126.55, 123.56, 64.90,
8.80, 27.22. 6h: Oil; MS m/z 238 (M ); H NMR
+
1
(
CDCl ) l 8.08 (m, 2H), 7.20–7.60 (m, 8H), 6.73 (d,
3
J=16 Hz, 1H), 6.39 (dt, J=16, 7 Hz, 1H), 4.96 (dd, J=7,
For acids: A mixture of 2 mmol of 1-phenylpropyne 1,
13
2
1
1
Hz, 2H); C NMR (CDCl ) l 166.25, 136.11, 134.15,
3
3
mmol acid, 0.1 mmol tetrakis(triphenylphosphine)
32.89, 130.09, 129.56, 128.51, 128.28, 127.99, 126.55,
palladium(0), and 0.2 mmol triethylamine in 3 ml 1,4-
dioxane was heated to 100°C for 10–16 h.
1
23.16, 65.44. 6i: Oil; H NMR (CDCl ) l 8.59 (d, J=2
3
Hz, 1H), 8.45 (dd, J=5, 2 Hz, 1H), 7.69 (ddd, J=8, 2, 2
Hz, 1H), 7.23 (dd, J=8, 5 Hz, 1H), 6.59 (d, J=16 Hz,
1
2
0
H), 6.36 (ddd, J=16, 6, 6 Hz, 1H), 4.14 (dd, J=6, 2 Hz,
References
H), 3.50 (t, J=7 Hz, 2H), 1.62 (m, 2H), 1.42 (m, 2H),
+
1
.94 (t, J=7 Hz, 3H). 10: Oil; MS m/z 224 (M );
H
1
. (a) Trost, B. M.; Brieden, W.; Baringhaus, K. H. Angew.
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1
6.46 (d, J=16 Hz, 1H), 6.35 (dt, J=16, 7 Hz, 1H), 4.96
(s, 1H), 3.49 (d, J=7 Hz, 2H), 2.25 (s, 3H); C NMR
(CDCl ) l 151.52, 137.08, 131.21, 130.90, 130.11, 128.43,
128.14, 128.04, 127.17, 126.11, 125.44, 115.52, 33.93,
20.45. 11: Oil; MS m/z 240 (M ); H NMR (CDCl ) l
3
H), 6.89 (dd, J=7, 2 Hz, 1H), 6.68 (d, J=7 Hz, 1H),
13
1
3
2
(
+
1
3
A. Chem. Rev. 2000, 100, 3067–3125.
7.15–7.40 (m, 5H), 6.65–6.80 (m, 3H), 6.48 (d, J=16 Hz,
2
. (a) Trost, B. M.; Rise, F. J. Am. Chem. Soc. 1987, 109,
1H), 6.35 (dt, J=16, 7 Hz, 1H), 4.89 (s, 1H), 3.66 (s, 3H),
+
1
3
161–3163; (b) Trost, B. M.; Vercauteren, J. Tetrahedron
3.52 (d, J=7 Hz, 2H). 12: Oil; MS m/z 244 (M );
H
Lett. 1985, 26, 131–134.
NMR (CDCl ) l 7.15–7.37 (m, 5H), 7.15 (d, J=2 Hz,
3

6
578
W. Zhang et al. / Tetrahedron Letters 43 (2002) 6575–6578
1
6
H), 7.08 (dd, J=7, 2 Hz, 1H), 6.73 (d, J=7 Hz, 1H),
.50 (d, J=16 Hz, 1H), 6.32 (dt, J=16, 7 Hz, 1H), 4.98
J=2 Hz, 1H), 6.70 (d, J=7 Hz, 1H), 6.33 (m, 1H), 5.28
(dt, J=7, 1 Hz, 1H), 5.02 (dt, J=16, 1 Hz, 1H), 4.91 (d,
J=7 Hz, 1H), 4.63 (s, 1H), 2.25 (s, 3H).
(s, 1H), 3.51 (dd, J=7, 1 Hz, 2H), 2.25 (s, 3H). 13:
Colorless crystals, mp: 77–79°C (Heptane); MS m/z 224
7. Goux, C.; Massacret, M.; Lhoste, P.; Sinou, D.
Organometallics 1995, 14, 4585–4593.
+
1
(
M ); H NMR (CDCl ) l 7.20–7.45 (m, 5H), 7.09 (d,
3
J=7 Hz, 2H), 6.86 (d, J=7 Hz, 2H), 6.72 (d, J=16 Hz,
8. White, W. N.; Fife, W. K. J. Am. Chem. Soc. 1961, 83,
3846–3853. Claisen rearrangement product 15 was
detected when heating 13 to 200°C for 20 h.
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Chem. 1999, 2231–2234; (b) Organ, M. G.; Miller, M.;
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1
2
1
1
1
6
H), 6.41 (dt, J=16, 7 Hz, 1H), 4.67 (dd, J=7, 2 Hz,
13
H), 2.29 (s, 3H); C NMR (CDCl ) l 156.47, 136.47,
3
32.79, 130.09, 129.90, 128.54, 127.81, 126.54, 124.69,
14.62, 68.70, 20.48. 14: Colorless crystals, mp: 107–
1
09°C (Heptane); H NMR (CDCl ) l 7.25–7.45 (m, 5H),
3
.91 (d, J=7 Hz, 2H), 6.84 (d, J=7 Hz, 2H), 6.73 (d,
J=16 Hz, 1H), 6.41 (dt, J=16, 7 Hz, 1H), 4.66 (dd, J=7,
1
2
7
Hz, 2H), 3.78 (s, 3H). 15: Oil; H NMR (CDCl ) l
10. Malkov, A. V.; Davis, S. L.; Baxendale, I. R.; Mitchell,
3
.20–7.35 (m, 5H), 6.95 (dd, J=7, 2 Hz, 1H), 6.88 (d,
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