ligand had a strong influence on the reaction outcome (Entries
2–10), while the amount of the ligand had only little effect (Entries
10, 11). Bis(2-diphenylphosphinophenyl) ether (DPE-Phos), a
strongly coordinating chelating phosphine, was by far the most
effective (Entry 10). This finding is particularly interesting, since
the adverse effect of phosphines in the Heck olefinations of
carboxylic acid derivatives has been suspected to be due to the
phosphines inhibiting the decarbonylation step.3,10
The Pd-precursor also had a profound influence on the catalyst
performance (Entries 10, 12–14). PdBr2 was more active than
PdCl2, but also facilitated the undesirable double bond isomeriza-
tion of the product. The isomerization step is much slower for the
PdCl2–DPE-Phos combination, and can almost completely be
avoided by stopping the reaction at a conversion around 80%. Best
results were obtained when the activating agent was applied in
excess (Entries 10, 15).
A high solvent polarity resulted in best turnovers and highest
selectivities. DMPU gave the best results, in NMP and diglyme
moderate yields were still obtained, while other solvents were not
effective (Entries 18–22). Unlike for similar transformations,1,3 the
addition of water, bases, and other additives did not enhance the
yields but facilitated the isomerization (Entries 16, 17).
In order to investigate the scope of the transformation, we
applied the best protocol to the synthesis of a variety of olefins
(Table 2).† Special emphasis was put on naturally occurring long
chain fatty acid substrates. Gratifyingly, the reaction proved to be
of reasonably broad scope. Both linear and branched carboxylic
acids were successfully converted, and even some functionalized
olefins were obtained in satisfactory yields. It is especially worth
mentioning that not only olefins, but also vinyl ethers such as 2k are
accessible through this reaction. Unfortunately, the reaction cannot
yet be extended to the even more desirable synthesis of enamides
from N-protected a-amino acids. Thus, only a small amount of 2l
was detected while mainly the corresponding oxazol-5-one was
formed.
In summary, an efficient protocol for the synthesis of olefins and
enol ethers directly from easily available carboxylic acids has been
developed. In the presence of pivalic anhydride and a palladium–
DPE-Phos catalyst, facile decarbonylation of carboxylic acids was
achieved at a temperature as low as 110 °C. Under these conditions,
double bond isomerization of the products is very slow and can thus
easily be avoided. The fact that the reaction can now be performed
at moderate temperatures without the need for special distillation
techniques makes it much more attractive for applications in
organic synthesis.
We thank Professor Dr. M. T. Reetz for generous support and
constant encouragement, and the DFG, the FCI, and the BMBF for
financial support.
Notes and references
†
Synthesis of (E)-heptadeca-1,8-diene (2f): A dried flask was charged
Table 2 Synthesis of olefins from carboxylic acids
with elaidic acid 1f (282 mg, 1.00 mmol), pivalic anhydride (3) (186 mg,
2.00 mmol), dry palladium chloride (5.3 mg, 0.03 mmol), and DPE-Phos
(48 mg, 0.09 mmol). Dry DMPU (4 mL) was added by syringe and the
reaction was stirred overnight at 110 °C. After the reaction was almost
complete (TLC), ethyl acetate was added and the organic layer was washed
consecutively with ammonium chloride solution, water and brine. The
product was filtered through a small plug of silica using hexane as eluent.
After concentrating to dryness, 2f (164 mg, 69%) was obtained as a
colorless oil. 1H-NMR (300.1 MHz, CDCl3): d = 5.92–5.71 (m, 1H),
5.49–5.32 (m, 2H), 5.06–4.88 (m, 2H), 3.13–1.85 (m, 6H), 1.48–1.31 (m,
18H), 0.87 (t, 3J = 8 Hz, 3H) ppm; 13C-NMR (75.5 MHz, CDCl3): d =
139.5, 130.8, 130.6, 114.5, 34.1, 33.0, 32.9, 32.3, 30.0, 29.9, 29.9, 29.7,
29.5, 29.2, 29.0, 23.0, 14.5 ppm; MS (EI, 70 eV): m/z (%) = 236 (3, [M]+),
207 (7), 194 (8), 123 (14), 110 (65), 96 (100), 81 (73), 68 (90), 55 (75), 41
(59), 29 (30); HRMS (EI) calcd. for C17H32 [M]+: 236.250142, found:
236.250142.
Carboxylic acid
Product
Yield (%)
66
2a
2b
2c
80
78
2d
64
2e
2f
59
69
1 A. Zapf, Angew. Chem., Int. Ed., 2003, 42, 5394.
2 R. Kakino, S. Yasumi, I. Shimizu and A. Yamamoto, Bull. Chem. Soc.
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2001, 40, 3458; L. J. Gooßen and K. Ghosh, Chem. Commun., 2001,
2084.
2g
81a
2h
23b
3 L. J. Gooßen, J. Paetzold and L. Winkel, Synlett, 2002, 1721; L. J.
Gooßen and J. Paetzold, Angew. Chem., Int. Ed., 2002, 41, 1237.
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Commun., 2002, 836.
2i
2j
65
77
5 J. Tsuji and K. Ohno, Synthesis, 1969, 157.
6 J. A. Miller, J. A. Nelson and M. P. Byrne, J. Org. Chem., 1993, 58,
18.
7 W. Boland and L. Jaenicke, Liebigs Ann. Chem., 1981, 92.
8 J. Tsuji and K. Ohno, J. Am. Chem. Soc., 1968, 90, 94; J. A. Miller and
J. A. Nelson, Organometallics, 1991, 10, 2958.
2k
2l
56
5c
9 H. Nagashima, K. Sato and J. Tsuji, Tetrahedron Lett., 1982, 23, 3085;
H. Nagashima, K. Sato and J. Tsuji, Tetrahedron, 1985, 41, 5645; G. S.
Jones and W. J. Scott, J. Am. Chem. Soc., 1992, 114, 1491.
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Angew. Chem., Int. Ed., 1998, 37, 662; A. F. Shmidt and V. V. Smirnov,
Kinet. Catal., 2000, 41, 743.
Conditions: 1.0 mmol carboxylic acid, 2.0 mmol pivalic anhydride, 3 mol%
PdCl2, 9 mol% DPE-Phos, 110 °C, DMPU, 16 h, isolated yields.a 4:1
mixture of the (E)- and (Z)-isomers. b The low yield is due to the high
volatility of the compound. c Main product: (S)-4-benzyl-2-methyl-4H-
oxazol-5-one.
C h e m . C o m m u n . , 2 0 0 4 , 7 2 4 – 7 2 5
725