Asymmetric 1,4-addition of triarylbismuths to enones catalyzed by dicationic palladium(II) complexes

Article abstract of DOI:10.1039/b407272c

A 1,4-addition of triarylbismuths to cyclic and acyclic enones was carried out in aqueous methanol in the presence of a chiral phosphine-dicationic palladium(II) complex. Palladium complexes of (S,S)-chiraphos or (S,S)-dipamp gave optically active β-arylketones of up to 95% ee.

Full text of DOI:10.1039/b407272c

Asymmetric 1,4-addition of triarylbismuths to enones catalyzed by
dicationic palladium(II) complexes
Takashi Nishikata, Yasunori Yamamoto and Norio Miyaura*
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628,
Japan. E-mail: miyaura@org-mc.eng.hokudai.ac.jp; Fax: 81 11 706 6561
Received (in Cambridge, UK) 13th May 2004, Accepted 3rd June 2004
First published as an Advance Article on the web 20th July 2004
A 1,4-addition of triarylbismuths to cyclic and acyclic enones
was carried out in aqueous methanol in the presence of a chiral
phosphine–dicationic palladium(II) complex. Palladium com-
plexes of (S,S)-chiraphos or (S,S)-dipamp gave optically active
b-arylketones of up to 95% ee.
In recent years we have been exploring metal-catalyzed 1,4-addi-
tion reactions of organoboron compounds, and in the process we
have reported a very general catalytic cycle for 1,4-addition of aryl-
and 1-alkenylboronic acids to a,b-unsaturated carbonyl com-
pounds with rhodium(
) complexes.1,2 The protocol has a quite high
I
level of generality, enabling exploration of analogous addition
reactions of organosilicon,3 -bismuth,4 -tin,5 -titanium,6 -zirco-
nium,7 and -zinc8 compounds and their asymmetric versions using
chiral phosphine–rhodium( )
) complexes.9 Dicationic palladium(II
I
complexes also are excellent catalysts for 1,4-additions of ar-
ylboronic acids10 and arylsiloxanes11 to enones in aqueous media
via a catalytic cycle analogous to that of rhodium complexes.
Although the use of arylbismuths in such metal-catalyzed reactions
is rare, they have promising potential due to the simplicity of their
preparation, isolation and handling as well as their functional group
compatibility.12 In this report, we describe an asymmetric palladiu-
m(II)-catalyzed 1,4-addition reaction of triarylbismuths to enones
(Scheme 1). The reaction provided optically active b-arylketones
(4) of up to 95% ee in the presence of a chiraphos- or dipamp–
cationic palladium(II) catalyst (3).
At the outset, dicationic palladium(II) catalysts were screened to
carry out 1,4-addition of Ph3Bi to 2-cyclohexenone in MeOH–H2O
(6 : 1) (Table 1). [Pd(dppe)(PhCN)2](BF4)2 stabilized by two
benzonitriles resulted in 27% yield with an accompanying biphenyl
derived by double transmetalation to the catalyst (entry 1). Addition
of Cu(BF4)2 to [Pd(dppe)(PhCN)2](BF4)2 or PdCl2(dppe) provided
an active catalyst, resulting in 90% yields at room temperature via
in situ generation of a highly electrophilic nitrile-free complex
(entries 2 and 3). Another role of the copper salt is reoxidation of
palladium(0) species by double transmetalation giving biphenyl.
Under the conditions used, 2–2.8 of the three phenyl groups on the
bismuth atom were added to the enone without any difficulty. Such
high catalyst efficiency is specific for bisphosphines bridged by two
carbon atoms since the catalysts possessing a dppm (0%), dppp
(27%), dppb (0%) or binap (0%) ligand resulted in almost no
product, as was observed in related reactions of arylboronic acids
and arylsiloxanes. Thus, palladium complexes of dipamp (3a, 3b),
chiraphos (3c), norphos (3d), and 1,1A-binaphthol-based diph-
osphonite (3e) are catalysts that meet this requirement (entries
4–10). Of the two methods for in situ preparation of nitrile-free
catalysts, the ligand exchange between 3b and Cu(BF4)2 was more
favorable for the asymmetric version than that between 3a and
Cu(BF4)2 because the former easily takes place at temperatures
lower than 0 °C (entries 4–7). The absolute configuration of
3-phenylcyclohexanone obtained from an (S,S)-dipamp complex
(3b) was R, and enantioselectivity was increased by decreasing the
reaction temperature. An (S,S)-chiraphos catalyst (3c) resulted in an
S isomer with 12% ee (entry 8), though it is an excellent catalyst for
2-cyclopentenone and acyclic enones, as shown in Table 2.
Palladium complexes of rigid norphos (3d) did not catalyze the
reaction, presumably due to its large bite angle compared to that of
Scheme 1 Asymmetric addition of Ar3Bi to enones catalyzed by dicationic
palladium(II) catalysts.
Table 1 Effect of catalysts in the addition of Ar3Bi to 2-cyclohexenonea
Temp./
°C
Yield
(%)
Entry Catalyst
% ee
1
2
3
4
5
6
7
8
9
[Pd(dppe)(PhCN)2](BF4)2
[Pd(dppe)(PhCN)2](BF4)2/Cu(BF4)2 20
20
27b
90b
90b
99
trace
94
92
89
trace
trace
—
—
—
86 (R)
—
89 (R)
92 (R)
12 (S)
PdCl2(dppe)/Cu(BF4)2
3a/Cu(BF4)2
3a/Cu(BF4)2
3b/Cu(BF4)2
3b/Cu(BF4)2
3c/Cu(BF4)2
20
20
0
0
25
25
20
20
3d/Cu(BF4)2
3e/Cu(BF4)2
10
a A mixture of 2-cyclohexenone (1 mmol), Ph3Bi (0.6 mmol) in MeOH (6
ml) and H2O (1 ml) was stirred at room temperature for 21 h in the presence
of a palladium complex (4 mol%) and Cu(BF4)2·6H2O (if used, 0.76 mmol).
b Reactions were accompanied by biphenyl (18–24%).
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C h e m . C o m m u n . , 2 0 0 4 , 1 8 2 2 – 1 8 2 3
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

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flexible dppe analogues (entry 9). The reaction also failed when
bisphosphonite (R,R-5)2f was used (entry 10).
yields,10,11 the rate of transmetalation was in the order of Ph3Bi (25
°C) > ArB(OH)2 (20 °C) > ArSi(OMe)3 (75 °C). Work aimed at
characterization of the chiral phosphine–arylpalladium(II) inter-
mediate obtained by transmetalation is in progress to elucidate the
asymmetric induction mechanism.
Asymmetric 1,4-additions of representative triarylbismuths to
enones in aqueous methanol are summarized in Table 2.† The
enantioselectivity depends on the combination between a chiral
ligand and a carbonyl compound. Chiraphos was found to be the
best ligand for 2-cyclopentenone (1a), resulting in 90–95% ee for
Ph3Bi (2a), (3-MeOPh)3Bi (2b), and (3-MePh)3Bi (2d) (entries
1–4). In contrast, dipamp gave much better selectivities than those
of chiraphos for 2-cyclohexenone (1b) (entries 5 and 6), giving
74–94% ee for Ph3Bi (2a), (4-MePh)3Bi (2c), (3-MeOPh)3Bi (2b),
(3-MePh)3Bi (2d), (4-FPh)3Bi (2e), (3-FPh)3Bi (2f), and
(4-CF3Ph)3Bi (2g) (entries 6–12). Among them, two para-
substituted derivatives (2c and 2g) unexpectedly resulted in 74% ee
and 84% ee for an unknown reason, whereas other para- and meta-
substituted arylbismuths easily resulted in over 90% ee. 2-Cyclo-
heptenone (1c) resulted in 76% ee with dipamp and 51% ee with
chiraphos, but all attempts at selective addition achieving more than
90% ee were unsuccessful (entries 13 and 14). Chiraphos was a
better ligand than dipamp for acyclic enones or enals that have a
trans olefin geometry. The steric bulkiness of a b-substituent of
5-methyl-3-hexen-2-one (1e, 81–89% ee) afforded slightly better
enantioselectivities than those of 3-nonen-2-one (1d, 80–84% ee)
(entries 16–21). Addition to enals such as 2-hexenal (1f) was very
slow due to formation of hemiacetal in aqueous solution and
resulted in a moderate range of enantioselectivities (entry 22).
The reaction may proceed through transmetalation of Ar3Bi to a
dicationic palladium(II) complex giving Ar–[Pd]+, insertion of an
enone into the C–Pd bond, and hydrolysis of the resulting palladium
enolate with water. Judging from the reaction temperatures
employed as reaction conditions to achieve more than 90%
Notes and references
† Typical experimental procedure (Table 2, entry 6). Ph3Bi (0.6 mmol),
Cu(BF4)2·6H2O (0.76 mmol), methanol (6 ml), 2-cyclohexenone (1 mmol)
and water (1 ml) were added to a flask under nitrogen. Finally, [Pd(S,S-
dipamp)(PhCN)2](SbF6)2 (0.04 mmol) was added at 25 °C. After being
stirred for 21 h, chromatography on silica gel gave (R)-3-phenyl-
cyclohexanone in 92% yield. The enantiomer excess (92% ee) was
determined by HPLC analysis using Daicel Chiralpak AD (hexane/
2-propanol = 98 : 2).
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Table 2 Asymmetric addition of Ar3Bi to enonesa
Temp./
Catalyst °C
Yield
(%)b
Entry
Enone
Ar3Bi
% eec
1
2
3
4
5
6
7
8
9
10
11
12d
13
14
15
16
17
18
19
20
21
22
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
1b
1b
1c
1c
1d
1d
1d
1d
1e
1e
1e
1f
2a
2a
2b
2d
2a
2a
2b
2c
2d
2e
2f
2g
2a
2a
2a
2a
2b
2f
3b
3c
3c
3c
3c
3b
3b
3b
3b
3b
3b
3b
3b
3c
3b
3c
3c
3c
3c
3c
3c
3c
25
25
5
25
25
25
10
25
25
10
49
85
84
94
62
92
92
64
98
93
93
66
89
89
72
99
85
76
63
70
31
55
42
95
92
92
12
92
93
74
92
90
94
84
76
51
26
83
84
80
85
89
81
68
10
10
25
25
25
25
5
25
25
10
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2a
2b
2f
10
25
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2a
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a A mixture of enone (1 mmol), Ar3Bi (0.6 mmol) in MeOH (6 ml) and H2O
(1 ml) was stirred for 21 h in the presence of a palladium catalyst (3, 4
mol%) and Cu(BF4)2·6H2O (0.76 mmol). b Isolated yields by column
chromatography. c Enantiomeric excess was determined by a chiral
stationary column. d The reaction was conducted in MeOH without using
water.
C h e m . C o m m u n . , 2 0 0 4 , 1 8 2 2 – 1 8 2 3
1823