Angewandte
Chemie
Table 2: 1,4-Addition of aryl boronic acids and boroxines.[a]
(Table 1, entry 1), but cationic palladium–dppe complexes of
ClO4ꢀ, OTfꢀ, BF4ꢀ, PF6ꢀ, and SbF6ꢀ catalyzed the reaction at
room temperature (Table 1, entries 1–6).Although variation
of the counteranion had no significant effect, the catalyst
efficiency was greatly dependent on the phosphane ligand.Of
the catalysts tested, the dppe complex was found to be the
best choice, as the use of dppp (1,3-bis(diphenylphosphanyl)-
propane), (S)-binap ((S)-2,2’-bis(diphenylphosphanyl)-1,1’-
binaphthyl) and PPh3 complexes resulted in no reaction.
The cationic benzonitrile complexes are bench-stable cata-
lysts that required no activation.The presence of benzonitrile
was critical: The use of a nitrile-free catalyst generated in situ
from [PdCl2(dppe)] and AgSbF6 resulted in 45% yield, and
the use of electron-poor benzonitrile complexes such as
[Pd(dppe)(4-CF3C6H4CN)2](SbF6)2 led to less than 1% yield.
Although K2CO3 was used to accelerate the reaction[8] and the
yields were indeed highly dependent on the bases employed
(K2CO3 > KHCO3 > Et3N), the use of a base always resulted
in the formation of a Heck product (4–11%), whereas Heck
products were negligible in the absence of a base (Table 1,
entry 7).The reaction proceeded smoothly in less polar
solvents, such as THF, dioxane, and cyclohexane, but was very
slow in donating solvents such as N,N-dimethylformamide
(DMF) and MeCN.
The reaction requires the presence of water, as does the
analogous rhodium-catalyzed reaction.[1] The reactions with
p-tolylboronic acid (2d, boronic acid/boroxine = 87:13) and
tris(p-tolyl)boroxine (2i) resulted in 77% and 43% yields,
respectively, in the absence of water (Table 1, entries 8 and
10).Both yields improved to 95% upon the addition of water
to the boronic acid or boroxine, which are in equilibrium in an
aqueous solution (Table 1, entries 9 and 12).[16] On the other
hand, all attempts at using boronic esters were unsuccessful.
The reactions of all five- and six-membered boronic esters
tested occurred in low yields in either the presence or the
absence of water (for example, Table 1, entries 14 and 15).
Results of the 1,4-addition of aryl boronic acids and
boroxines to representative a,b-unsaturated carbonyl com-
pounds at room temperature are summarized in Table 2.The
reaction of 2-cyclopentenone with phenylboronic acid (2a,
boronic acid/boroxine = 68:32) occurred in 63% yield in the
absence of water, in 78% yield when water was added to the
boronic acid, and in 91% yield when a mixture of the
corresponding boroxine 2g and water was used (Table 2,
entries 1–3).These reactions selectively provided 1,4-addition
products, whereas a Heck product was selectively formed in
the presence of K2CO3 (Table 2, entry 4).Although various
boronic acids gave the best yields in the presence of water in
reactions with 2-cyclohexenone or 2-cycloheptenone (Table 2,
entries 5–8 and 11), the presence of water was not critical for
reactions with p-acetyl and p-trifluoromethylphenylboronic
acid (Table 2, entries 9 and 10).An NMR spectroscopic study
indicated that these two compounds were pure boronic acid
with no accompanying boroxine.The protocol was easily
extended to acyclic a,b-unsaturated ketones and aldehydes
with a primary alkyl, secondary alkyl, or phenyl substituent on
the b carbon atom (Table 2, entries 12–21).In most reactions
5 mol% of the catalyst was used.However, the loading could
be decreased to less than 1 mol%: An almost quantitative
Entry
1
2
Product
Yield [%][b]
1
2
3
4[e]
5
6
7
8
9
10
11
12
13[g]
14
15
18
20
21
22
2-cyclopentenone
2-cyclopentenone
2-cyclopentenone
2-cyclopentenone
2-cyclohexenone
2-cyclohexenone
2-cyclohexenone
2-cyclohexenone
2-cyclohexenone
2-cyclohexenone
2-cycloheptenone
a
4a
4a
4a
5a[f]
4b
4c
4d
4e
4g
4h
4i
63
78
91
48
87
80
95
95
96
94
87
92
97
82
83
92
83
76
5[i]
a/H2O[c]
g/H2O[d]
a
a/H2O[c]
b/H2O[c]
c/H2O[c]
d/H2O[c]
e
f
a/H2O[c]
a
¼
(E)-C5H11CH CHCOCH3
4j
4j
¼
(E)-C5H11CH CHCOCH3
a
a/H2O[c]
a/H2O[c]
a
4k
4l
4m
4n
4o[h]
4p
¼
(E)-i-C3H7CH CHCOCH3
¼
(E)-PhCH CHCOCH3
¼
(E)-PhCH CHCOPh
(E)-CH3CH CHCHO
g/H2O[d]
a/H2O[c]
a
¼
¼
(E)-C3H7CH CHCHO
¼
CH2 CHCO2Et
[a]All reactions were carried out at 20 8C for 23 h in the presence of 2-
cyclohexenone (1 mmol), an aryl boron compound (1.5 mmol), and
[Pd(dppe)(PhCN)2](SbF6)2 (5 mol%) in THF (6 mL), unless otherwise
noted. The ratios of boronic acid/boroxine were: 2a: 68:32, 2b: 68:32,
2c: 100:0, 2d: 87:13, 2e: 100:0, and 2 f: 100:0. [b]Yields of isolated
products, after purification by chromatography. [c]The reaction was
conducted in THF/H2O (10:1, 6 mL). [d]An aryl boroxine (0.5 mmol)
and water (3 mmol) were used in place of the boronic acid. [e]K 2CO3
(1.2 mmol) was used. [f]3-Phenyl-2-cyclopentene was formed selectively.
[g]Catalyst used: 0.5 mol%. [h]1,3-Diphenyl-1-hexanone (1.6%) was
also obtained. [i]Ethyl cinnamate (31%) was also isolated.
yield was found in a reaction in which only 0.5 mol% of the
catalyst was used (Table 2, entry 13).In contrast to the
rhodium-catalyzed reaction, which gave a mixture of 1,4- and
1,2-addition products from enals,[17] the palladium catalysts
selectively yielded 1,4-addition products (Table 2, entries 20
and 21).On the other hand, the addition of boronic acids to
a,b-unsaturated esters was very slow, and Heck-coupling
products predominated (Table 2, entry 22).No reaction was
observed for the addition to N-benzylcrotonamide.
A proposed catalytic cycle involving transmetalation,
ꢀ
insertion, and hydrolytic C Pd-bond cleavage is shown in
Scheme 2.Organoboronic acids are inert to neutral palladi-
um(ii) halides, but they easily undergo transmetalation with
cationic platinum(ii) and palladium(ii) complexes.[8,18]
Although the mechanism has not yet been fully elucidated,
the high reactivity of the cationic species suggests that a
transmetalation occurs through a Wheland intermediate 7 to
produce a cationic aryl palladium(ii) species 8.[19] Because of
the difficulty in preventing double transmetalation to 6, which
results in the formation of a homocoupling product (Ar–Ar)
and palladium black, palladium(ii) complexes have rarely
been used in reactions that occur through such a catalytic
cycle, which starts with a transmetalation.However, the high
turnover number of the catalyst observed in entry 13 of
Table 2 indicates that the next insertion step is sufficiently fast
ꢀ
to prevent a second transmetalation to 8.Insertion of a C
C
ꢀ
double bond into a C Pd bond proceeds for electron-
deficient alkenes, and this process can be further accelerated
Angew. Chem. Int. Ed. 2003, 42, 2768 – 2770
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2769