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Chemistry Letters Vol.37, No.8 (2008)
Platinum-catalyzed 1,4-Addition of Arylboronic Acids
to ꢀ-Substituted ꢁ,ꢀ-Unsaturated Ketones
Tamio Hayashiꢀ and Keigo Sasaki
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502
(Received May 23, 2008; CL-080522; E-mail: thayashi@kuchem.kyoto-u.ac.jp)
Platinum salts represented by K2PtCl4 were found to
Table 1. Platinum-catalyzed 1,4-addition of phenylboronic
acid (2m) to 2-cyclohexen-1-one (1a)
catalyze the 1,4-addition of arylboronic acids to ꢀ-substituted
ꢁ,ꢀ-unsaturated ketones to give high yields of ꢀ-arylated
ketones. The reaction is completed in 1 h in the presence of
1 mol % of the catalyst in dioxane/H2O at 70 ꢁC.
O
O
platinum catalyst (3 mol % Pt)
+
PhB(OH)2 (2m)
additive (1.0 equiv)
Dioxane/H2O (10/1)
(1.5 equiv)
Ph
1a
3am
Catalytic 1,4-addition of organoboronic acids to ꢁ,ꢀ-unsat-
urated ketones and other electron-deficient olefins has been at-
tracting considerable attention owing to its high utility in organic
synthesis.1 The reaction was first reported by Miyaura et al.
in 1997 to be catalyzed by a rhodium complex,2,3 and the rhodi-
um-catalyzed 1,4-addition reactions have been extended suc-
cessfully to catalytic asymmetric reactions by use of rhodium
catalysts bearing chiral phosphine or diene ligands.4,5 Palladi-
um–phosphine complexes were also found to be active catalysts
for the 1,4-addition of arylboronic acids.6 More recently, the 1,4-
addition was reported to be catalyzed by nickel7 and ruthenium8
complexes. Another new entry into the 1,4-addition catalyst
group is platinum. A platinacycle generated by ortho-platination
of tri(2,4-di-tert-butylphenyl)phosphite was reported by Bedford
et al.9 and by Hu et al.10 to catalyze the 1,4-addition of phenyl-
boronic acid to chalcone. Here, we report that the 1,4-addition
of arylboronic acids to ꢁ,ꢀ-unsaturated ketones is efficiently
catalyzed by simple platinum salts such as K2PtCl4 and PtCl2
under mild conditions without any additional ligands (eq 1).
T
Time Yield/%a
Entry
Catalyst
Additive
/ꢁC
/h
3am
1
2b
3
4
5
6
7
8
9
10
11
12
13
14
15
K2PtCl4
K2PtCl4
K2PtCl4
K2PtCl4
K2PtCl4
K2PtCl4
K2PtCl4
PtCl2
KOH
KOH
KOH
—
70
70
30
70
70
70
70
70
70
70
70
70
70
70
70
4
1
24
4
>98
>98
>98
0
NaOH
K3PO4
NEt3
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
4
4
4
>98
>98
0
4
4
4
4
>98
>98
>98
70
[PtCl2(C2H4)]2
PtCl2(cod)
PtCl2(PPh3)2
PtCl2(PEt3)2
PtCl2(dppe)
PtCl2(binap)
Pt(dba)2
4
0
4
0
4
4
0
55
aDetermined by H NMR using an internal standard (MeNO2).
bIn the presence of 1 mol % of K2PtCl4.
1
K2PtCl4 or PtCl2 (1 mol %)
O
Ar
O
+ ArB(OH)2
(1.5 equiv)
Under the conditions using K2PtCl4 as a catalyst and one
equiv (to enone 1) of potassium hydroxide in dioxane/H2O
at 70 ꢁC for 1 h, several arylboronic acids 2m–2s were found
to add to 2-cyclohexen-1-one (1a) to give the corresponding
1,4-addition products 3am–3as in high yields (Table 2,11 Entries
1–9). In addition to the unsubstituted phenyl group (2m),
those substituted with electron-donating groups, 4-methyl (2n),
3-methyl (2o), and 4-methoxy (2p), were successfully intro-
duced in the presence of 1 mol % of the K2PtCl4 catalyst (Entries
1–4). Although the yields for phenyl groups substituted with
electron-withdrawing groups, 4-trifluoromethyl (2q) and 4-
chloro (2r), are not high, owing mainly to the hydrolysis of the
arylboronic acids under the reaction conditions, the yields were
greatly improved by use of an excess amount (3 equiv to enone
1a) of the boronic acids (Entries 5–8). The addition of phenyl-
boronic acid (2m) took place in high yields under standard
conditions (1 mol % of K2PtCl4 and 1.5 equiv of 2m) for linear
ꢀ-substituted ꢁ,ꢀ-unsaturated ketones, 1d and 1e (Entries 12
and 13), as well as some other cyclic enones, 1b and 1c (Entries
10 and 11). Interestingly, the 1,4-addition catalyzed by K2PtCl4
was observed only with aromatic boronic acids, not with olefinic
boronic acids such as 1-heptenylboronic acid. This is mainly
due to the hydrolysis of the alkenylboronic acid.
KOH (1.0 equiv)
Dioxane/H2O (10/1)
70 °C, 1 h
R1
R2
R1
high yields
R2
ð1Þ
In the first set of experiments, we examined several platinum
salts and complexes (3 mol %) for their catalytic activity toward
the addition of phenylboronic acid (2m) to 2-cyclohexen-1-one
(1a) (Table 1). It was found that K2PtCl4 is an efficient catalyst,
giving a quantitative yield of 1,4-addition product 3am in the
presence of KOH (1 equiv) in dioxane/H2O (10/1) at 70 ꢁC
for 4 h (Entry 1). The catalytic activity of K2PtCl4 is so high that
the catalyst loading can be reduced to 1 mol % and the reaction
time can be shortened to 1 h while maintaining the high yield of
3am (Entry 2). The use of KOH is important for the present re-
action. It can be replaced by NaOH or K3PO4, but the 1,4-addi-
tion did not take place without base additives (Entries 4–7).
PtCl2 and platinum/olefin complexes, [PtCl2(C2H4)]2 and
PtCl2(cod), are as catalytically active as K2PtCl4 (Entries 8–
11). A lower yield (70%) of 3am was observed in the presence
of PtCl2(PPh3)2 (Entry 11). The catalytically active species
may be a phosphine-free platinum complex generated by disso-
ciation of PPh3 from PtCl2(PPh3)2, considering that the reaction
is not catalyzed by other platinum/phosphine complexes where
the phosphine dissociation is less probable (Entries 12–14).
Copyright Ó 2008 The Chemical Society of Japan
Hayashi, Tamio
