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Chemistry Letters Vol.34, No.5 (2005)
Asymmetric 1,4-Addition of Potassium Aryltrifluoroborates [ArBF3]K to Enones
Catalyzed by Dicationic Palladium(II) Complexes
Takashi Nishikata, Yasunori Yamamoto, and Norio Miyauraꢀ
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628
(Received March 10, 2005; CL-050326)
Asymmetric 1,4-addition of [ArBF3]K to cyclic and acyclic
enones was carried out in aqueous methanol in the presence of a
chiral phosphine-dicationic palladium(II) catalyst. A palladium
complex of (S,S)-dipamp gave optically active ꢀ-arylketones
of up to 96 % ee for 2-cyclohexenone and 2-cycloheptenone. A
palladium-(S,S)-chiraphos complex resulted in 82–97 % ee for
2-cyclopentenone and acyclic enones.
BF3K
R1
R2
FG
FG
R1
O
Pd2+ catalyst (2)
R2
O
R3
1
R3
3
MeOH−H2O (10/1)
Since metal-catalyzed 1,4-addition of organometallic re-
agents to ꢁ,ꢀ-unsaturated carbonyl compounds yields a stereo-
genic center at the ꢀ-carbon, considerable efforts have been de-
voted to the development to asymmetric syntheses. Among these
studies for asymmetric C–C bond formation, the reactions cata-
lyzed by copper,1 rhodium,2 and palladium3 complexes are of
great value because of the availability of chiral ligands for these
transition metals. We have reported a rhodium(I)–binap catalyst
for achieving over 90 % ee in 1,4-addition reactions of aryl- and
1-alkenylboronic acids to cyclic and acyclic enones, esters and
amides.2a,4 Other catalysts that are effective for arylboronic acids
are rhodium(I) complexes of chiral bisphosphine ligands such as
chiraphos5 and diphosphonites,6 P–N ligands of amidomono-
phosphines,7 and bis(alkene) ligands based on a norbornadiene
skeleton.8 Although the corresponding reactions of palladium
catalysts are rare, we recently reported that dicationic palladium-
(II) complexes such as [Pd(dppe)(S)2]2þ catalyze 1,4-addition of
ArB(OH)2,9 ArSi(OMe)3,10 and Ar3Bi3 to enones via a transme-
talation–insertion-hydrolysis sequence11 analogous to the cata-
lytic cycle of rhodium(I)-catalyzed reactions. Recently, 1,4-ad-
dition of Ar3Bi was extended to an asymmetric version3 because
this reaction smoothly took place at lower temperatures
(ꢁ5{0 ꢂC) than that used ArB(OH)2 and ArSi(OMe)3 (20–
75 ꢂC). In this paper, we report 1,4-addition reaction of potassi-
um aryltrifluoroborates (Scheme 1). Air- and water-stable
[ArBF3]K, obtained by treatment of ArB(OH)2 with KHF2,12
is advantageous over ArB(OH)2 in preparation and handling of
pure and stable crystalline materials. Although these Kþ salts
are highly insoluble in common organic solvents, the reaction
worked well at temperatures lower than 0 ꢂC when using fine
powder suspended in aqueous MeOH.13
Ph
Ph
Pd
Ph
Me
Me
P
P
Ph
NCPh
NCPh
(SbF6)2
(SbF6)2
MeO
P
P
NCPh
Pd
NCPh
Ph
Ph
2b
MeO
[Pd(S,S-chiraphos)(PhCN)2]
(SbF6)2
2a
[Pd(S,S-dipamp)(PhCN)2](SbF6)2
Figure 1.
benzonitrile complexes of 2 at ꢁ15{0 ꢂC, very different from the
corresponding reaction of Ar3Bi conducted in the presence of
Cu(BF4)2 for Pd(2+)–benzonitrile catalysts.3 The copper salt
was used for in situ generation of a highly electrophilic nitrile-
free catalyst active for transmetalation via ligand exchange of
benzonitrile between the palladium complex and copper(2+)
salts.11 In contrast, [ArBF3]K could be smoothly added to repre-
sentative enones in the absence of such an activator because the
reaction yields BF3, which is also effective for in situ generation
of a nitrile-free catalyst such as [Pd(P–P)(solvent)2]2þ. High cat-
alyst efficiency specific for bisphosphines bridged by two carbon
atoms was the same as in other 1,4-addition reactions catalyzed
by dicationic palladium(II) complexes.11 Thus, palladium(2+)
complexes of dipamp and chiraphos were catalysts that meet this
requirement. The dipamp complex (2a) gave the best enantiose-
lectivities for 2-cyclohexenone (Entries 2–10) and 2-cyclohep-
tenone (Entry 11), and the chiraphos complex (2b) afforded
much higher selectivities than 2a for 2-cyclopentenone (Entry 1)
and acyclic enones (Entries 12–20). These effect of catalyst for
enones were analogous to that of previous asymmetric reaction
of Ar3Bi.3 Acyclic enones catalyzed by 2b resulted in relatively
low enantioselectivities of around 82–83 % ee (Entries 12 and
16). The selectivities increased to 89 % ee by increasing the
bulkiness of substituents of the ketone carbonyl group (R3)
which would sterically interact with one of four P-bound phenyl
groups of chiraphos ligand in coordination of an enone to the
metal center (Entries 12–15). On the other hand, the bulkiness
of aliphatic ꢀ-substituent (R1) of acyclic enones did not effect
to increase the enantioselectivities (Entries 12, 16, and 17), but
Asymmetric additions of [ArBF3]K to representative enones
in aqueous MeOH are summarized in Table 1. The reaction was
carried out by the following general procedure. To a flask charg-
ed with [ArBF3]K (1.5 mmol) was successively added MeOH
(6 mL), water (0.6 mL), enone (1 mmol), and a Pd(2+) catalyst
(2, 0.03 mmol, 3 mol %) under argon. After stirring for 21 h at
the temperature shown in Table 1, the product was isolated by
chromatography over silica gel. Enantiomer excess was deter-
mined by a chiral stationary column in comparison with a race-
mic authentic sample. The reaction was efficiently catalyzed by
Copyright Ó 2005 The Chemical Society of Japan
Nishikata, Takashi
