Palladium catalyzed conjugate 1,4-addition of organoboronic acids to α,β-unsaturated ketones

Article abstract of DOI:10.1246/cl.2006.198

1,4-Addition of arylboronic acids to α,β-unsaturated ketones was smoothly catalyzed by palladium(0) phosphine complexes with chloroform in the presence of base. It is remarked that the palladium(0) complexes have no catalytic activity in the absence of chloroform. The reaction proceeded without β-hydride elimination. Copyright

Full text of DOI:10.1246/cl.2006.198

1
98
Chemistry Letters Vol.35, No.2 (2006)
Palladium Catalyzed Conjugate 1,4-Addition
of Organoboronic Acids to ꢀ,ꢁ-Unsaturated Ketones
Ã
Tetsuya Yamamoto, Michiko Iizuka, Tetsuo Ohta, and Yoshihiko Ito
Department of Molecular Science and Technology, Faculty of Engineering, Doshisha University, Kyotanabe, Kyoto 610-0394
Received December 1, 2005; CL-051489; E-mail: tota@mail.doshisha.ac.jp)
Table 1. Addition of PhB(OH)2 to 2-cyclohexenonea
(
1
,4-Addition of arylboronic acids to ꢀ,ꢁ-unsaturated
ketones was smoothly catalyzed by palladium(0) phosphine
complexes with chloroform in the presence of base. It is
remarked that the palladium(0) complexes have no catalytic
activity in the absence of chloroform. The reaction proceeded
without ꢁ-hydride elimination.
Entry
Catalyst/Phosphine (mol %)
Yield/%b
3/4b
1
2
3
4
Pd(OAc)2 (5)/PPh3 (5)
Pd(dba)2 (5)/PPh3 (5)
PdCl2(CH3CN)2 (5)/PPh3 (5)
0
0
0
—
—
—
>100:1
>100:1
>100:1
>100:1
.
Pd2(dba)3 CHCl3 (3)/PPh3 (6)
>99
>99
>99
43e
c
5
d
Pd(OAc)2 (5)/PPh3 (10)
.
6
Pd2(dba)3 CHCl3 (3)/PPh3 (6)
The transition metal-catalyzed 1,4-conjugate addition reac-
tion of organometallic reagents to ꢀ,ꢁ-unsaturated ketones is
widely used for carbon–carbon bond formation giving ꢁ-substi-
.
7
Pd2(dba)3 CHCl3 (3)/PPh3 (12)
a
ꢀ
Reactions were carried out at 60 C for 24 h in the presence of
2-cyclohexenone (1.0 mmol), phenylboronic acid (2.0 mmol),
palladium complex, phosphine, and Cs2CO3 (1.0 mmol) in
1
tuted functionalized compounds. Particularly, in various orga-
no-main group metal compounds, organoboron compounds are
non-toxic and effective for carbon–carbon bond forming reac-
tions with various electrophiles in the presence of a transition
metal.2 Recently, rhodium-catalyzed carbon–carbon coupling
reactions with organoboron reagents have remarkably been de-
veloped. Miyaura et al. found that rhodium(I) complexes cata-
lyze 1,4-addition to ꢀ,ꢁ-unsaturated carbonyl with aryl- and 1-
b
1
toluene (2 mL). Determined by H NMR spectroscopy.
CHCl3 (0.01 mL) was added. A catalytic amount of Cs2CO3
0.2 mmol) was used. Yield of product isolated by silica gel
c
d
e
(
column chromatography, and based on 2-cyclohexenone.
(
Table 1, Entries 1–3). On the other hand, phosphine–palla-
dium(0) complexes catalyzed 1,4-addition in the presence of a
catalytic amount of chloroform (Table 1, Entries 4–7). The
reaction proceeded smoothly even using a catalytic amount of
Cs2CO3 (Table 1, Entry 6). Other bases were also usable for this
reaction but the yields slightly decreased (K3PO4 99%, K2CO3
70%, Na CO 77%, and KOH 72%). The yields of the 1,4-addi-
3
alkenylboron compounds. Although, there are a few reports that
the palladium-catalyzed addition reaction of arylboron reagents.
Uemura and co-workers demonstrated the palladium(0) and
SbCl3-catalyzed conjugate addition of arylboron reagents to
4
ꢀ
al. reported the cationic palladium(II)-catalyzed 1,4-addition of
,ꢁ-unsaturated carbonyl compounds. Recently, Miyaura et
2
3
tion products decreased with the increase of triphenylphosphine
(Table 1, Entries 4 and 7), and bidentate phosphines, such as
dppe, dppp, dppb, and dppf, were less effective. In every
reaction, formation of a considerable amount of biphenyl was
observed. Addition of water slightly accelerated the reaction.
Results of the reaction of enones with arylboronic acids are
5
arylboronic acids to ꢀ,ꢁ-unsaturated enones. Very recently,
we found that palladium(0) complexes coordinated by phosphine
ligands catalytically induced 1,2-addition of arylboronic acids to
aldehydes in the presence of base and a catalytic amount of
6
chloroform. Herein, we report the 1,4-addition of arylboronic
7
summarized in Table 2. The palladium-catalyzed addition of
acids to ꢀ,ꢁ-unsaturated ketones, catalyzed by palladium(0)
phosphine complexes in the presence of a base and a catalytic
amount of chloroform (Scheme 1).
phenylboronic acid proceeded smoothly to several acyclic and
cyclic enones (Table 2, Entries 1–8). Electron-rich arylboronic
acids such as 4-tolylboronic acid and 4-methoxyphenylboronic
acid reacted smoothly as well as phenylboronic acid (Table 2,
Entries 9 and 11). On the other hand, ortho-substituted or elec-
tron-deficient arylboronic acids such as 2-tolylboronic acid, 4-
fluorophenylboronic acid, and 4-trifluoromethylphenylboronic
acid reacted slightly slow to 2-cyclohexenone (Table 2, Entries
Palladium-catalyzed addition of phenylboronic acid to 2-cy-
ꢀ
clohexenone was examined at 60 C, and the results are summa-
rized in Table 1. Palladium(0) complex precursors and neutral
palladium(II) complex, such as Pd(OAc)2, Pd(dba)2 and PdCl2-
(
CH3CN)2, had no catalytic activity in the absence of chloroform
1
arylated to give the product in good yield ((E)-2-hexenal, 16 h
0, 12, and 13). ꢀ,ꢁ-Unsaturated aldehyde and nitrile were also
O
ArB(OH)2 (2)
O
O
R2
Pd(0) / Phosphine
R2
+
R2
ꢀ
>
99% yield; (E)-2-pentenenitrile, 60 C, H2O (1.0 mmol) 79%
CHCl , Base
R1
3
R1
R1
yield). It is remarked that all reactions proceed without ꢁ-hy-
dride elimination except the reaction of 2-pentenenitrile.8
We propose the catalytic cycle of this reaction in Scheme 2.
At first, phosphine and dichloromethyl coordinating palla-
dium(II) intermediate 5 was generated by oxidative addition of
chloroform to phosphine coordinated palladium(0) complexes,9
and dichloromethyl palladium(II) intermediate 5 is converted
to a hydroxyl palladium(II) species 6 by ligand exchange. Then,
the transmetalation between arylboronic acid and the hydroxyl
Ar
Ar
4
1
3
2
2
2
a: FG = H
b: FG = 4-Me
c: FG = 2-Me
B(OH)2
FG
2d: FG = 4-MeO
2
2
e: FG = 4-F
f: FG = 4-CF
3
Scheme 1.
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.2 (2006)
199
Table 2. Addition of ArB(OH)2 to enonesa
PPh3
Cl Pd CHCl2
O
O
b
c
Entry
2
Enone
Yield/%
3/4
PPh3
9
1
2
3
4
5
6
7
8
9
0
1
2
3
2a PhCH=CHCOPh
2a PhCH=CHCOCH3
2a n-C3H7CH=CHCOCH3
2a CH3CH=CHCOC2H5
2a iso-C3H7CH=CHCOCH3
2a 2-cyclopentenone
2a 2-cycloheptenone
2a 2-cyclohexenone
2b 2-cyclohexenone
2c 2-cyclohexenone
2d 2-cyclohexenone
2e 2-cyclohexenone
2f 2-cyclohexenone
ꢀ
99
89
92
91
>100:1
>100:1
>100:1
>100:1
>100:1
>100:1
>100:1
>100:1
>100:1
>100:1
>100:1
>100:1
>100:1
PhB(OH)2
Ph
Cs CO , toluene
2
3
1
9
2% yield ( H NMR)
Scheme 3.
80
>99
>99
>99
>99
87
96
83
70
tion of H2O to the reaction improved the ratio of addition prod-
uct/Heck type product in case of 2-pentenenitrile (without H2O,
52:7; with H2O, 79:2). As Herrmann et al. reported the chloro-
(dichloromethyl)bis(triphenylphosphine)palladium(II) (9) that
was prepared from Pd(PPh3)4 with CHCl3, we used the com-
plex 9 as a catalyst for the addition of phenylboronic acid to
9
1
1
1
1
ꢀ
2-cyclohexenone at 80 C (Scheme 3), and this acted as a cata-
lyst as well.
a
In conclusion, aryl boronic acids react with ꢀ,ꢁ-unsaturated
ketones in the presence of base and a catalytic amount of a
palladium(0) complex with chloroform, affording the corre-
sponding ketones in good yields. Newly, we investigate an
asymmetric version of this reaction.
All Reactions were carried out at 80 C for 24 h in the presence
of enone (1.0 mmol), arylboronic acid (2.0 mmol), Pd(OAc)2
5 mol %), PPh3 (10 mol %), Cs2CO3 (1.0 mmol), and CHCl3
0.01 mL) in toluene (2 mL). Yield of product isolated by silica
(
(
b
c
gel column chromatography, and based on enoes. Determined
by H-NMR spectroscopy.
1
References and Notes
1
2
3
For reviews: a) P. Perlmutter, in Conjugate Addition Reac-
tions in Organic Synthesis, Pergamon Press, Oxford, 1992.
b) B. E. Rossiter, N. M. Swingle, Chem. Rev. 1992, 92, 771.
For reviews: a) A. Suzuki, Acc. Chem. Res. 1982, 15, 178.
b) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457. c)
A. Suzuki, J. Organomet. Chem. 1998, 576, 147.
a) M. Sakai, H. Hayashi, N. Miyaura, Organometallics 1997,
16, 4229. For a review: b) K. Fagonou, M. Lautens, Chem.
Rev. 2003, 103, 169.
CHCl2
CHCl3
P
Pd(0)
P Pd S
Cl
5
P = phosphine
S = H O or solvent
OH
Cl
2
Ar
R2
CHCl2
R1
Pd
P
S
O
4
5
C. S. Cho, S. Motofusa, K. Ohe, S. Uemura, J. Org. Chem.
1
3
OH
995, 60, 883.
6
a) T. Nishikata, Y. Yamamoto, N. Miyaura, Angew. Chem.,
Int. Ed. 2003, 42, 2768. b) T. Nishikata, Y. Yamamoto, N.
Miyaura, Organometallics 2004, 23, 4317. c) Recently,
another cationic catalysis was published: F. Gini, B. Hessen,
A. J. Minnaard, Org. Lett. 2005, 7, 5309.
H O
ArB(OH)2
2
B(OH)3
CHCl2
P Pd S
P
CHCl2
Pd
R2
Ar
enone (1)
6
7
T. Yamamoto, T. Ohta, Y. Ito, Org. Lett. 2005, 7, 4153.
General procedure (Table 2). Pd(OAc)2 (0.05 mmol, 5
mol %) and PPh3 (0.1 mmol, 10 mol %), arylboronic acid
(2.0 mmol), aldehyde (1.0 mmol), and Cs2CO3 (1.0 mmol)
were dissolved in toluene (2 mL) and chloroform (0.01 mL,
R1
O
Ar
7
8
Scheme 2.
ꢀ
palladium(II) species 6 occurs to generate an arylpalladium(II)
intermediate 7, and the insertion of the enone into carbon–palla-
dium bond affords a C-bound enolate 8. The palladium enolate 8
was hydrolyzed to give the corresponding ketone and the hy-
droxyl palladium(II) species 6 was reproduced. Espinet et al.
demonstrated that C-bound palladium enolate is very easy to
12 mol %). After the mixture was stirred at 80 C for 24 h.
The analytically pure ketone was obtained by chromato-
graphy on silica gel.
H. A. Dieck, R. F. Heck, J. Org. Chem. 1975, 40, 1083.
¨
W. A. Herrmann, W. R. Thiel, C. Broßmer, K. Ofele, T.
Priermeier, W. Scherer, J. Organomet. Chem. 1993, 461, 51.
8
9
1
0
suffer hydrolytic carbon–palladium bond cleavage. A small
amount of water might be present in our reaction system. Addi-
10 A. C. Alb e´ niz, N. M. Catalina, P. Espinet, R. Red o´ n,
Organometallics 1999, 18, 4317.
Published on the web (Advance View) January 14, 2006; DOI 10.1246/cl.2006.198