Palladium-catalyzed conjugate addition of organosiloxanes to α,β-unsaturated carbonyl compounds and nitroalkenes

Article abstract of DOI:10.1021/jo034763r

The addition of aryltrialkoxysilanes to α,β-unsaturated carbonyl compounds (ketones, aldehydes) and nitroalkenes in the presence of SbCl₃, TBAF, AcOH, and a catalytic amount of Pd(OAc)₂, in CH₃CN at 60 °C, provides the corresponding conjugate addition products in moderate to good yields. The addition of equimolar amounts of SbCl₃ and TBAF is necessary for this reaction to proceed smoothly. The arylpalladium complex, which is generated by the transmetalation from a putative hypercoordinate silicon compound, is considered to be the catalytically active species.

Full text of DOI:10.1021/jo034763r

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P a lla d iu m -Ca ta lyzed Con ju ga te Ad d ition of Or ga n osiloxa n es to
r,â-Un sa tu r a ted Ca r bon yl Com p ou n d s a n d Nitr oa lk en es
Scott E. Denmark* and Nobuyoshi Amishiro
Department of Chemistry, Roger Adams Laboratory, University of Illinois, Urbana, Illinois 61801
denmark@scs.uiuc.edu
Received J une 4, 2003
The addition of aryltrialkoxysilanes to R,â-unsaturated carbonyl compounds (ketones, aldehydes)
and nitroalkenes in the presence of SbCl3, TBAF, AcOH, and a catalytic amount of Pd(OAc)2, in
CH3CN at 60 °C, provides the corresponding conjugate addition products in moderate to good yields.
The addition of equimolar amounts of SbCl3 and TBAF is necessary for this reaction to proceed
smoothly. The arylpalladium complex, which is generated by the transmetalation from a putative
hypercoordinate silicon compound, is considered to be the catalytically active species.
SCHEME 1
In tr od u ction
The 1,4-conjugate addition of organometallic reagents
to R,â-unsaturated carbonyl compounds is an important
process for carbon-carbon bond formation.1,2 Recently,
Hayashi and Miyaura have described a general and
selective rhodium-catalyzed, asymmetric 1,4-addition of
organoboron reagents to R,â-unsaturated ketones (Scheme
1), esters, amides, phosphonates and nitroalkenes.3
Furthermore, Inoue and Oi have reported the rhodium-
catalyzed conjugate addition of organostannanes4a and
organosiloxanes4b,c to R,â-unsaturated carbonyl com-
pounds. In these catalytic reactions, the aryl- or alkenyl-
rhodium complex, which is generated by the transmet-
alation from the organometallic precursors, is considered
to be the catalytically active species.
In 1995, Uemura reported the palladium-catalyzed
conjugate addition of organoboron reagents to R,â-
unsaturated ketones and aldehydes (Scheme 2).5a In this
reaction, the addition of a catalytic amount of SbCl3
resulted in the formation of the corresponding conjugate
addition products in high yield from enones and enals
with a variety of arylboron compounds. The key step of
this reaction is believed to be the formation of an
antimony enolate derived from the initial coordination
of SbCl3 to the carbonyl oxygen of an organopalladium
intermediate. Furthermore, these authors reported a
palladium-catalyzed conjugate addition of organostan-
nanes5b and organoantimony reagents5c to R,â-unsatur-
ated carbonyl compounds and Pd-catalyzed Michael-type
hydroarylation of nitroalkenes with aryltin compounds.5d
The palladium-catalyzed cross-coupling reactions of
organosilicon reagents with organic halides in the pres-
(1) For reviews on 1,4-addition reactions, see: (a) Perlmutter, P.
Conjugate Addition Reactions in Organic Synthesis; Pergamon Press:
Oxford, 1992. (b) Schmalz, H.-G. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 4,
Chapter 1.5. (c) Rossiter, B. E.; Swingle, N. M. Chem. Rev. 1992, 92,
771.
(2) For reviews on enantioselective 1,4-addition reactions, see: (a)
Krause, N.; Hoffmann-Ro¨der, A. Synthesis 2001, 171. (b) Tomioka, K.;
Nagaoka, Y. In Comprehensive Asymmetric Catalysis; J acobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999; Vol. 3, Chapter
31.1. (c) Noyori, R. Asymmetric Catalysis in Organic Synthesis; J ohn
Wiley and Sons: New York, 1994; pp 207-212. (d) No´gra´di, M.
Stereoselective Synthesis; VCH Publishers: New York, 1995; pp 213-
224. (e) Seyden-Penne, J . Chiral Auxiliaries and Ligands in Asymm-
metric Synthesis; J ohn Wiley and Sons: New York, 1995. (f) Feringa,
B. Acc. Chem. Res. 2000, 35, 346.
(3) (a) Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.; Miyaura,
N. J . Am. Chem. Soc. 1998, 120, 5579. (b) Takaya, Y.; Ogasawara, M.;
Hayashi, T. Tetrahedron Lett. 1998, 39, 8479. (c) Takaya, Y.; Ogasawara,
M.; Hayashi, T. Tetrahedron Lett. 1999, 40, 6957. (d) Hayashi, T.;
Senda, T.; Takaya, Y.; Ogasawara, M. J . Am. Chem. Soc. 1999, 121,
11591. (e) Takaya, Y.; Senda, T.; Kurushima, H.; Ogasawara, M.;
Hayashi, T. Tetrahedron: Asymmetry 1999, 10, 4047. (f) Sakuma, S.;
Sakai, M.; Itooka, R.; Miyaura, N. J . Org. Chem. 2000, 65, 5951. (g)
Takaya, Y.; Ogasawara, M.; Hayashi, T. Chirality 2000, 12, 469. (h)
Hayashi, T.; Senda, T.; Ogasawara, M. J . Am. Chem. Soc. 2000, 122,
10716. (i) Kuriyama, M.; Tomioka, K. Tetrahedron Lett. 2001, 42, 921.
(j) Reetz, M. T.; Moulin, D.; Gosberg, A. Org. Lett. 2001, 3, 4083. (k)
Sakuma, S.; Miyaura, N. J . Org. Chem. 2001, 66, 8944. (l) Hayashi,
T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J . Am. Chem. Soc. 2002,
124, 5052. (m) Hayashi, T. Synlett 2001, 879. (n) Kuriyama, M.; Nagai,
K.; Yamada, K.; Miwa, Y.; Taga, T.; Tomioka, K. J . Am. Chem. Soc.
2002, 124, 8932. (o) Boiteau, J .-G.; Imbos, R.; Minnaard, A. J .; Feringa,
B. L. Org. Lett. 2003, 5, 681.
(4) (a) Oi, S.; Moro, M.; Ito, H.; Honma, Y.; Miyano, S.; Inoue, Y.
Tetrahedron 2002, 58, 91. (b) Oi, S.; Honma, Y.; Inoue, Y. Org. Lett.
2002, 4, 667. (c) Oi, S.; Taira, A.; Honma, Y.; Inoue, Y. Org. Lett. 2003,
5, 97. For other examples of Rh-catalyzed conjugated addition, see:
(d) Venkatraman, S.; Li, C.-J . Tetrahedron Lett. 2001, 42, 781. (e)
Venkatraman, S.; Meng, Y.; Li, C.-J . Tetrahedron Lett. 2001, 42, 4459.
(f) Huang, T.-S.; Li, C.-J . Chem. Commun. 2001, 2348. (g) Kabalka,
G. W.; Das, B. C.; Das, S. Tetrahedron Lett. 2002, 43, 2323. (h)
Amengual, R.; Michelet, V.; Genet, J .-P. Tetrahedron Lett. 2002, 43,
5905. (i) Murata, M.; Shimazaki, R.; Ishikura, M.; Watanabe, S.;
Masuda, Y. Synthesis 2002, 717.
(5) (a) Cho, C. S.; Motofusa, S.; Ohe, K.; Uemura, S.; Shim, S. C. J .
Org. Chem. 1995, 60, 883. (b) Ohe, T.; Wakita, T.; Motofusa, S.; Cho,
C. S. Ohe, K.; Uemura, S. Bull. Chem. Soc. J pn. 2000, 73, 2149. (c)
Cho, C. S.; Motofusa, S.; Ohe, K.; Uemura, S. Bull. Chem. Soc. J pn.
1996, 69, 2341. (d) Ohe, T.; Uemura, S. Tetrahedron Lett. 2002, 43,
1269.
10.1021/jo034763r CCC: $25.00 © 2003 American Chemical Society
Published on Web 08/09/2003
J . Org. Chem. 2003, 68, 6997-7003
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Denmark and Amishiro
SCHEME 2
SCHEME 4
in high yield, we undertook an extensive optimization
study by GC analysis using naphthalene as an internal
standard.
ence of fluoride ion (pioneered by Hiyama) has emerged
as a viable and powerful alternative to the conventional
boron and tin-based reagents.6 Recent reports from these
and other laboratories have demonstrated that simple
organosilicon compounds bearing a single oxygen sub-
stituent can serve effectively as the donor in palladium-
catalyzed cross-coupling reactions.7-9 Compared to the
other organometallic reagents, silicon compounds have
the advantages of (1) low molecular weight, (2) higher
stability, (3) ease of activation, and (4) conversion to
harmless byproducts. In view of the strong similarities
between boron and silicon chemistry, we naturally con-
sidered the possibility of effecting the Hayashi/Miyaura
addition with silicon reagents under palladium catalysis.
Herein, we report the palladium-catalyzed conjugate
addition of organosiloxanes to R,â-unsaturated carbonyl
compounds and nitroalkenes (Scheme 3).
2. Op tim iza tion Exp er im en ts. 2.1. Su r vey of F lu o-
r id e Sou r ces in th e Rea ction w ith ou t SbCl3. At first,
several fluoride sources were surveyed in this reaction
in absence of SbCl3 (Table 1). These reactions were
carried out in AcOH as the solvent at room temperature
for 2 h. Of the fluoride sources tested, tris(dimethylami-
no)sulfur (trimethylsilyl)difluoride (TASF) provided the
best result (entry 4). However, all of the reactions did
not proceed to completion and often gave a black pre-
cipitate, most likely Pd(0) from reduction of the Pd(II)
catalyst. To establish the nature of the reducing agent,
pairwise combinations of the reagents (2-cyclohexenone
(1a ), phenyltriethoxysilane (2a ), TBAF‚3H2O were added
to Pd(OAc)2 in AcOH. When 2a and TBAF were added
to the reaction together in the absence of 1a , the reaction
became a black heterogeneous suspension, presumably
from formation of Pd(0). Subsequently, we found that
TASF was not the best promoter, but that under condi-
tions that suppressed the formation of Pd(0), TBAF was
superior (vide infra).
SCHEME 3
TABLE 1. Su r vey of F lu or id e Sou r ces in th e Rea ction
Resu lts
a
w ith ou t SbCl3
1. Ap p lica tion of Uem u r a ’s Meth od . First, the
conditions described by Uemura5a for the conjugate
addition of phenyltriethoxysilane were tested. Treatment
of 2-cyclohexenone (1a , 0.5 mmol) with phenyltriethox-
ysilane (2a , 0.6 mmol) in the presence of TBAF‚3 H2O
(0.6 mmol) and catalytic amounts of Pd(OAc)2 and SbCl3
in AcOH at 60 °C afforded 3-phenylcyclohexanone (3a a )
in 11% yield (GC yield) along with 3-phenylcyclohexenone
(4a a ) in 5% yield (GC yield) (Scheme 4). The formation
of the Heck-type product 4a a indicated the intervention
of an undesirable oxidative pathway.
GC yield,b %
entry
fluoride source
time, h
1a
3a a
4a a
1
2
3
4
TBAF‚3H2O
KF
CsF
TASF
2
2
2
2
75
75
43
30
12
0
2
0
8
trace
4
Although the desired product could be obtained, the
yield of 3a a was low and formation of the Heck-type
product 4a a remained problematic. To suppress the
formation of the 4a a and to obtain the addition product
30
a
Reaction conditions: 1a (0.5 mmol), 2a (1.0 mmol), fluoride
source (3.0 mmol), Pd(OAc)2 (0.05 mmol), AcOH (1 mL), rt, Ar
atmosphere. Determined by GC analysis using naphthalene as
b
an internal standard.
(6) (a) Hiyama, T. In Metal-Catalyzed Cross-Coupling Reactions;
Diederich, F., Stang, P., J ., Eds.; Wiley-VCH: Weinheim, 1998; Chapter
10. (b) Hiyama, T.; Hatanaka, Y. Pure Appl. Chem. 1994, 66, 1471.
(7) (a) Denmark, S. E.; Sweis, R. F. Acc. Chem. Res. 2002, 35, 835.
(b) Denmark, S. E.; Sweis, R. F. Chem. Pharm. Bull. 2002, 50, 1531.
(c) Denmark, S. E.; Yang, S.-M. J . Am. Chem. Soc. 2002, 124, 2102.
(d) Denmark, S. E.; Sweis, R. F. Org. Lett. 2002, 4, 3771.
(8) (a) Hirabayashi, K.; Kawashima, J .; Nishihara, Y.; Mori, A.;
Hiyama. T. Org. Lett. 1999, 1, 299. (b) Hirabayashi, K.; Mori, A.;
Kawashima, J .; Suguro, M.; Nishihara, Y.; Hiyama. T. J . Org. Chem.
2000, 65, 5342. (c) Chang, S.; Yang, S. H.; Lee, P. H. Tetrahedron Lett.
2001, 42, 4833.
(9) Polyalkoxysilanes have also been reported as viable agents for
fluoride-activated cross-coupling reactions: (a) Tamao, K.; Kobayashi,
K.; Ito, Y. Tetrahedron Lett. 1989, 30, 6051. (b) Mowery, M. E.;
DeShong, P. Org. Lett. 1999, 1, 2137. (c) Lee, H. M.; Nolan, S. P. Org.
Lett. 2000, 2, 2053. (d) Mowery, M. E.; DeShong, P. J . Org. Chem. 1999,
64, 1684. (e) Shibata, K.; Miyazawa, K.; Goto, Y. Chem. Commun. 1997,
1309.
2.2. Op tim iza tion of th e P h Si(OEt)3/TBAF /SbCl3/
AcOH Ra tio. The next optimization studies focused on
identification of the appropriate ratio of the arylsilicon
agent, TBAF, SbCl3, and AcOH (Table 2). Preliminary
results indicated that the reaction could be run in
CH3CN without adverse effects on the rate or yield.
Therefore, in this study, all of the reactions were con-
ducted in CH3CN. The reaction without SbCl3 quickly
stalled and gave a black precipitate (entry 1). However,
the reactions with SbCl3 did not give the black precipi-
tate. In the reaction with equimolar amounts of SbCl3
and TBAF, 3a a was formed in 42% yield (entry 2). Treat-
ment of the silane 2a with 2 equiv each of TBAF and
6998 J . Org. Chem., Vol. 68, No. 18, 2003

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Palladium-Catalyzed Conjugate Addition of Organosiloxanes
TABLE 2. Op tim iza tion of th e P h Si(OEt)3/TBAF /SbCl3/
AcOH Ra tioa
TABLE 4. Su r vey of P a lla d iu m Ca ta lystsa
GC yield,b %
GC yield,c %
ratiob of
entry PhSi(OEt)3/TBAF/SbCl3/AcOH time, h 1a 3a a 4a a
entry
Pd catalyst
time, h
1a
3a a
4a a
1
2
3
4
5
6
Pd(OAc)2
PdCl2
Pd(TFA)2
(CH3CN)2PdCl2
(PPh3)2PdCl2
PdBr2
48
43
43
43
46
46
0
4
0
0
69
2
82
82
85
86
6
5
6
4
6
0
5
1
2
3
4
5
6
7
8
9
1.2/1.2/0/5.0
2
67
93
50
92
48
48
44
67
66 17
32 42
10 76
8
5
5
8
9
12
5
6
1.2/1.2/1.2/5.0
1.2/2.4/2.4/5.0
2.0/3.0/3.0/5.0
2.0/3.0/3.0/0
2.0/4.0/2.0/5.0
2.0/4.0/4.0/5.0
3.0/3.0/3.0/5.0
3.0/4.0/4.0/5.0
4
7
9
0
0
84
68
73
82
77
86
a
Reaction conditions: 1a (0.5 mmol), 2a (1.0 mmol), TBAF‚3
H2O (2.0 mmol), SbCl3 (2.0 mmol), AcOH (2.5 mmol), Pd cat. (0.05
b
mmol), CH3CN (1 mL), 60 °C, Ar atmosphere. Determined by
10 67
4
GC analysis using naphthalene as an internal standard.
a
Reaction conditions: 1a (0.5 mmol), Pd(OAc)2 (0.05 mmol),
b
CH3CN (1 mL), 60 °C, Ar atmosphere. Based on 1a . c Deter-
TABLE 5. Su r vey of Solven tsa
mined by GC analysis using naphthalene as an internal standard
TABLE 3. Su r vey of Lew is Acid sa
GC yield,b %
entry
solvent
time, h
1a
3a a
4a a
1
2
3
4
5
6
7
THF
26
26
42
29
23
48
67
6
0
24
0
24
0
2
78
79
47
78
51
82
79
7
6
GC yield,b %
toluene
MeOH
dioxane
DMF
4
entry
Lewis acid
time, h
1a
3a a
4a a
8
11
5
1
2
3
4
5
6
7
8
SbCl3
ZnCl2
BiCl3
48
45
45
43
43
21
19
20
0
82
32
57
94
65
83
55
82
5
45
0
3
0
5
5
6
0
0
0
0
0
CH3CN
AcOH
6
a
AlCl3
Reaction conditions: 1a (0.5 mmol), 2a (1.0 mmol),
TBAF‚3 H2O (2.0 mmol), SbCl3 (2.0 mmol), AcOH (2.5 mmol),
Pd(OAc)2 (0.05 mmol), solvent (1 mL), 60 °C, Ar atmosphere.
Determined by GC analysis using naphthalene as an internal
standard.
FeCl3
SnCl4
BF3‚Et2O
CeCl3
b
0
0
a
Reaction conditions: 1a (0.5 mmol), 2a (1.0 mmol), TBAF‚3
H2O (2.0 mmol), Lewis acid (2.0 mmol), AcOH (2.5 mmol), Pd(OAc)2
(0.05 mmol), CH3CN (1 mL), 60 °C, Ar atmosphere. Determined
acids afford moderate yields of the desired product. This
suggested that the role of SbCl3 in our studies may be
different from its role in Uemura’s work.
b
by GC analysis using naphthalene as an internal standard.
2.4. Su r vey of P d (II) Ca ta lysts. The conjugate ad-
dition reaction was examined using other Pd(II) catalysts
such as PdCl2, Pd(TFA)2, (CH3CN)2PdCl2, (PPh3)2PdCl2,
and PdBr2 in place of Pd(OAc)2 (Table 4). Remarkably,
all Pd(II) catalysts except (PPh3)2PdCl2 afforded similarly
high yields as Pd(OAc)2. Presumably, the presence of the
phosphine in (PPh3)2PdCl2 inhibited this reaction (entry
5).
2.5. Effect of th e Solven t. The next stage in the
optimization focused on the effect of the solvent (Table
5). The yield of 3a a was found to be greater than 70% in
THF, toluene, dioxane, and AcOH (entries 1, 2, 4, and
7). Although the reaction in AcOH gave 3a a in 79% yield,
the rate was slower than that in other solvents (entry
7). Thus, CH3CN was selected to be optimal for this
reaction.
2.6. Su r vey of Br on sted Acid s a n d th e Am ou n t of
th e P a lla d iu m Ca ta lyst. Several Bronsted acids were
examined in addition to AcOH (Table 6). With trifluoro-
acetic acid, the most acidic additive in this study, 3a a
was obtained in 78% yield (entry 9). However, the
reaction rate was lower than that with other acids.
Several acids showed results similar to those with AcOH.
SbCl3 further increased the yield of 3a a (entry 3). More-
over, the use of 2 equiv of silane 2a per enone 1a ,
produced 3a a in still higher yield (entry 3 vs 4, 7).
If the ratio of SbCl3 to TBAF was decreased to 0.5, the
amount of the Heck-type product 4a a increased (entry 6
vs 7). A reaction without AcOH led to a decrease in the
yield of 3a a and a slower reaction rate (entry 4 vs 5).
Further increasing the loading of 2a did not have a
beneficial effect (entries 8, 9). From these studies, we
concluded that the optimal ratio of 2a /SbCl3/TBAF/AcOH
was 2.0/4.0/4.0/5.0 in CH3CN solvent. Although TASF
was examined instead of TBAF using these conditions,
the reaction did not proceed as well.
2.3. Su r vey of Lew is Acid s. The effect of a wide
range of Lewis acids (other than SbCl3) on the rate and
yield of the conjugate addition was examined next (Table
3). Whereas almost all of the Lewis acids surveyed were
ineffective for formation of 3a a , SbCl3 was clearly the
Lewis acid of choice. BiCl3 gave a modest yield of the
desired product (entry 3) whereas ZnCl2 and FeCl3
(entries 2 and 5, respectively) afforded only a trace of the
product. This is in sharp contrast to Uemura’s studies
with arylboronic acids,5a wherein almost all of the Lewis
J . Org. Chem, Vol. 68, No. 18, 2003 6999

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Denmark and Amishiro
TABLE 6. Su r vey of Br on sted Acid s a n d th e Am ou n t of
th e P a lla d iu m Ca ta lysta
Next, several R,â-unsaturated aldehydes were sur-
veyed. Gratifyingly, the conjugate addition product
from (E)-cinnamaldehyde (1k ) was obtained in excellent
yield (93%) (entry 11). With R,â-unsaturated aldehydes
bearing alkyl groups in the â-position (1j, 1m , 1o), the
corresponding products were obtained in moderate to
good yield (entries 10, 13, 15). Unfortunately, in reactions
of 1-cyclohexene-1-carboxyaldehyde (1l) and 3-methy-2-
butenal (1n ), the yields of the desired products were
quite low. With methyl (E)-cinnamate (1p ), the con-
jugate addition product was not obtained at all (entry
16).
Finally, to expand the scope of synthetically useful
substrates, nitroalkenes were investigated. The addition
of phenyltriethoxysilane was successful for linear ni-
troalkenes, 2-nitrostyrene (1q), 1-nitropropene (1r ), 2-ni-
trovinylcyclohexane (1s), which gave the corresponding
phenylation products with moderate to good yield (entries
17, 18, 19). In contrast, no reaction occurred in the case
of cyclic nitroalkenes, such as 1-nitro-1-cyclohexene (1t)
(entry 20).
GC yield,d
%
Pd(OAc)2,c
mol %
b
entry
acid
AcOH
pKa
4.76
time, h 1a 3a a 4a a
1
2
10
5
10
5
10
5
10
10
10
10
10
30
30
27
68
28
46
47
47
70
47
28
5
6
2
9
0
2
0
5
7
3
0
80
83
85
80
84
82
82
84
78
81
82
5
5
5
4
5
5
4
5
3
4
5
3
MeOCH2CO2H 3.57
4
5
ClCH2CO2H
2.86
6
7
8
9
10
11
F2HCO2H
PhCO2H
F3CCO2H
Cl3CCO2H
t-BuCO2H
-
4.20
0.2
0.7
5.04
a
Reaction conditions: 1a (0.5 mmol), 2a (1.0 mmol), TBAF‚3H2O
(2.0 mmol), SbCl3 (2.0 mmol), acid (2.5 mmol), Pd(OAc)2, CH3CN
(1 mL), 60 °C, Ar atmosphere. Reference 10. c Based on 1a .
b
d
Determined by GC analysis using naphthalene as an internal
4. Con ju ga te Ad d ition of Va r iou s Ar yltr ia lk oxy-
sila n es to r,â-Un sa tu r a ted Ca r bon yl Com p ou n d s
a n d Nitr oa lk en es. In addition to phenyltriethoxysilane,
other aryltrialkoxysilanes could be used for this trans-
formation under the same conditions. The aryltrialkoxy-
silanes investigated were 4-methoxyphenyltriethoxysi-
lane (2b), 4-chlorophenyltriethoxysilane (2c) and 4-tolyl-
trimethoxysilane (2d ). These silicon compounds were
commercially available or easily prepared by Pd-11 or Rh-
catalyzed12 silylation of aryl halides.
Treatment of ketone 1i, aldehyde 1k , and nitroalkene
1q with various aryltrialkoxysilanes (2b-d ) under the
optimized condition afforded the corresponding products
in moderate to high yields, respectively (Table 8). In the
case of 4-chlorophenyltriethoxysilane (2c), the yields of
the desired products from substrates 1k and 1q were
lower than those with 4-methoxyphenyltriethoxysilane
(2b) and 4-tolyltrimethoxysilane (2d ) (entries 2, 3, 8, 9
vs 5, 6). In entries 5 and 6, the conjugate addition
reactions were not complete, and the starting material
remained.
standard.
The difference in pKa of the acids did not seem to
influence the yield of the reaction.
Next, the effect of lowering the Pd catalyst loading was
examined (entries 2, 4, 6). Interestingly, the results were
dependent on the nature of the acid additive. For
example, with AcOH, lowering the catalyst loading to 5
mol % had no effect on the yield or rate of the reaction
(entry 1 vs 2). However, with MeOCH2CO2H and ClCH2-
CO2H as the additives, the reaction rates were signifi-
cantly lowered (entry 3 vs 4, 5 vs 6). From these studies,
the conditions found in entry 2 were considered to be
optimal.
3. Con ju ga te Ad d ition of P h en yltr ieth oxysila n e
(2a ) to R,â-Un sa tu r a ted Ca r bon yl Com p ou n d s a n d
Nitr oa lk en es. With an optimal set of reaction conditions
established, the scope of the reaction components could
be surveyed. Various R,â-unsaturated carbonyl com-
pounds (ketones, aldehydes, and ester) and nitroalkenes,
were subjected to the conjugate addition process and the
results are summarized in Table 7. These reactions were
examined with both 5 and 10 mol % of the Pd catalyst
(based on 1), both of which showed good results. In all
cases, biphenyl was formed in less than 5% yield as a
side product.
Discu ssion
The palladium-catalyzed conjugate addition of 2a to
ketones, aldehydes, and nitro compounds showed modest
structural generality. Among the cyclic ketones exam-
ined, 2-cyclohexenone (1a ) showed higher reactivity than
2-cyclopentenone (1b) and 2-cycloheptenone (1c) (Table
7, entry 1 vs 2 and 3). With linear ketones, aldehydes,
and nitroalkenes, the reactivity of the substrates bearing
a phenyl group at the R1 position was higher than that
of the substrates bearing an alkyl group at the R1 position
(Table 7, entry 5 vs 8, 9, entry 11 vs 10, 13, 15, entry 17
vs 18, 19).
First, both cyclic and acyclic enones were examined.
With 2-cyclohexenone (1a ) and 2-cyclopentenone (1b), the
reaction was accompanied by the formation of an ap-
preciable amount the Heck-type products, but in other
cases the Heck-type product was scarcely formed. From
various ketones, such as 2-cyclohexenone (1a ), chalcone
(1e), and 1-phenyl-2-buten-1-one (1h ), the corresponding
phenylation products were produced in good to excellent
yield (entries 1, 5, 8). However, with other ketones (1b,
1c, 1f, 1g, 1i), the corresponding addition products were
obtained in moderate yield (entries 2, 3, 6, 7, 9). The
formation of phenylated products was not observed from
3-methyl-2-cyclohexenone (1d ) (entry 4), even with 10
mol % of Pd, most likely due to the steric inhibition
provided by the methyl group.
Inspection of the results reported with a variety of R,â-
unsaturated carbonyl compounds (Table 7, entries 5, 11,
(10) Wronski, M. J . Chromatogr. A 1997, 772, 19.
(11) (a) Murata, M.; Suzuki, K.; Watanabe, S.; Masuda, Y. J . Org.
Chem. 1997, 62, 8569. (b) Manoso, A. S.; DeShong, P. J . Org. Chem.
2001, 66, 7449.
(12) Murata, M.; Ishikura, M.; Nagata, M.; Watanabe, S.; Masuda,
Y. Org. Lett. 2002, 4, 1843.
7000 J . Org. Chem., Vol. 68, No. 18, 2003