COMMUNICATION
to be a viable approach for the rapid construction of com-
plex molecules from simple starting materials.
vephos (Davephos=2-Dicyclohexylphosphino-2’-(N,N-dime-
thylamino)biphenyl) and Xphos (Xphos=2-Dicyclohexyl-
phosphino-2’,4’,6’-triisopropylbiphenyl), and sterically bulky
tBu3P, were used as supporting ligands, no reaction occurred
(entries 17–21). Less sterically hindered phosphines, such as
PCp3·HBF4 (Cp=cyclopentyl) and iPr3P·HBF4, were ob-
served to be as efficient as PCy3 (Cy=cyclohexyl; entries 22
and 23).
We initiated our investigation by studying the reaction of
propiophenone (1a) with 2-nitrobenzoic acid (2a) under
a variety of reaction parameters (Table 1). In the presence
of Ag2CO3, additional bases were observed to have an effect
on the reaction outcome depending on the nature of the
base (entries 4–10), presumably, because bases play a key
role in the formation of the Pd-enolate intermediate that is
supposed to be the precursor to enones. Relatively weak
bases, such as carboxylate salts, facilitated this reaction and
the effect of the bases was a function of their solubility (en-
tries 4–7), while strong bases, such as K3PO4 and K2CO3,
shut down the reaction completely. The simultaneous use of
carboxylate salts (2 equiv) and equimolar carboxylic acids
significantly improved the yield of 3a (entry 11 vs. 5 and
entry 13 vs. 7), although the use of acetic acid alone was in-
effective for the reaction. The complex of tetrabutylammo-
nium acetate and acetic acid gave a similar result (entry 16).
The beneficial effect of acetic acid may stem from the acid-
After identifying the factors influencing the reaction out-
come, we next evaluated the substrate scope of this reaction
with respect to aromatic carboxylic acids by using the reac-
tion conditions of entry 16 in Table 1 (PdACTHNURTGNENG(U OAc)2 (15 mol%),
PCy3 (30 mol%), Ag2CO3 (2.5 equiv), nBu4NOAc·HOAc
(1.7 equiv), DMF, 908C, 24 h). Considering that the elec-
tronic nature of substituents on the benzene ring have a re-
markable influence on the acidity and decarboxylation rate
of benzoic acids, we reasoned that the reaction conditions
needed to be adjusted for different benzoic acids to achieve
efficient transformation. We were pleased to find that slight
modifications of the standard reaction conditions enabled
the use of a variety of benzoic acids to produce chalcones
(Table 2). 2-Nitrobenzoic acids bearing a variety of addition-
promoted separation of the ion pair [nBu4N] CTHNUGTRNENUG
+A[OAc]À[14] and
the acid-promoted enolization of ketones. The choice of
phosphine ligands was also crucial for achieving this reac-
tion. When phenyl-substituted phosphines, such as PPh3, Da-
Table 2. Scope of aryl carboxylic acids.[a,f,g]
Table 1. Optimization studies for the decarboxylative olefination
reaction.[a,d]
Entry Ligand
Base ([equiv])
Acid ([equiv]) Yield of 3a
[b]
[%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
–
–
–
–
–
–
–
–
–
–
–
6
10
12
31
49
66
44
0
PCy3
–
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PPh3
KOAc (2)
KOAc (2)
PivOk (2)
Me4NOAc (2)
nBu4NOAc
K2CO3 (2)
K3PO4 (2)
Ph3N (2)
PivOk (2)
Me4NOAc (2)
nBu4NOAc (2)
–
nBu4NOAc (1.7) HOAc (1.7)
nBu4NOAc·HOAc (1.7)
nBu4NOAc·HOAc (1.7)
nBu4NOAc·HOAc (1.7)
nBu4NOAc·HOAc (1.7)
nBu4NOAc·HOAc (1.7)
nBu4NOAc·HOAc (1.7)
nBu4NOAc·HOAc (1.7)
nBu4NOAc·HOAc (1.7)
–
–
0
0
PivOH (2)
HOAc (2)
HOAc (2)
HOAc (2)
67
69
73
12
76
75[c]
0
0
0
0
0
[a] Reaction conditions: 1a (0.2 mmol, 1 equiv), 2 (3.0 equiv), Pd
(15 mol%), PCy3 (30 mol%), Ag2CO3 (2.5 equiv), nBu4OAc·HOAc
(1.7 equiv), DMF (1 mL), 908C, 24 h. [b] Cu(OAc)2 (2.5 equiv), DME
ACHTUNGTRENNUNG(OAc)2
AHCTUNGTRENNUNG
(DME=dimethyl ether; 1 mL), 90–1408C. [c] 5-Methyl-2-nitrobenzoic
acid (4 equiv) was used. [d] 808C. [e] CuF2 (2.5 equiv) was used. [f] Isolat-
ed yield. [g] When non-ortho-substituted benzoic acids were used, the
final chalcones were not obtained.
dppe
Davephos
Xphos
tBu3P
PCp3·HBF4
iPrP3·HBF4
al substituents afforded generally good yields. In some cases,
CuACTHNUTRGNE(NUG OAc)2 or CuF2 was found to be more efficient than
79
76
54
Ag2CO3 for the decarboxylative cross-coupling process, es-
pecially, when electron-rich and heterocyclic carboxylic
acids were used.
We further investigated the compatibility of functional
groups on the propiophenones (Table 3). Under the stan-
tBu2MeP·HBF4 nBu4NOAc·HOAc (1.7)
[a] Reaction conditions: 1a (0.2 mmol, 1 equiv), 2a (3.0 equiv), PdACTHNUTRGNE(NUG OAc)2
(15 mol%), ligand (30 mol%), Ag2CO3 (2.5 equiv), DMF (1 mL), 908C,
24 h. [b] GC yield. [c] 71% isolated yield. [d] The a-arylated product was
not detected. dppe=1,2-Bis(diphenylphosphino)ethane.
Chem. Eur. J. 2012, 18, 8032 – 8036
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
8033