Stepwise palladium-catalyzed 1,4-addition of arylboronic acids to enones and regioselective Baeyer-Villiger oxidation for enantioselective synthesis of β-diaryl esters and (+)-(R)-tolterodine

Article abstract of DOI:10.1246/bcsj.81.1019

Baeyer-Villiger oxidation of chiral β-diaryl ketones synthesized by 1,4-addition of arylboronic acids to β-arylα,β-unsaturated ketones catalyzed by a palladium(2+)-chiraphos complex provided optically active β-diaryl esters up to 98% ee. The protocol was

Full text of DOI:10.1246/bcsj.81.1019

Ó 2008 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 81, No. 8, 1019–1025 (2008) 1019
Stepwise Palladium-Catalyzed 1,4-Addition of Arylboronic Acids
to Enones and Regioselective Baeyer–Villiger Oxidation for
Enantioselective Synthesis of ꢀ-Diaryl Esters and (+)-(R)-Tolterodine
ꢀ1
Kenya Kobayashi,1 Takashi Nishikata,2 Yasunori Yamamoto,1 and Norio Miyaura
1Division of Chemical Process Engineering, Graduate School of Engineering,
Hokkaido University, Sapporo 060-8628
2Innovation Plaza Hokkaido, Japan Science and Technology Agency, Sapporo 060-0819
Received March 12, 2008; E-mail: miyaura@eng.hokudai.ac.jp
Baeyer–Villiger oxidation of chiral ꢀ-diaryl ketones synthesized by 1,4-addition of arylboronic acids to ꢀ-aryl-
ꢁ,ꢀ-unsaturated ketones catalyzed by a palladium(2+)–chiraphos complex provided optically active ꢀ-diaryl esters
up to 98% ee. The protocol was applied to the synthesis of a potent competitive muscarinic receptor antagonist, (R)-tol-
terodine (21), which has a chiral center consisting of two aryl rings.
Enantioselective conjugate additions of nucleophiles to ꢁ,ꢀ-
unsaturated carbonyl compounds are a versatile methodology
for forming chiral carbon–carbon bonds.1 We have reported
that aryl- and 1-alkenylboronic acids undergo 1,4-addition to
ꢁ,ꢀ-unsaturated carbonyl compounds in the presence of a rho-
dium(I) catalyst.2 The protocol has been proved to be a general
reaction for a wide range of selective carbon–carbon bond
formations including enantioselective reactions using chiral
rhodium–phosphine catalysts.3 We have also reported that di-
cationic palladium(II) complexes are excellent catalysts that
allow 1,4-additions of organoboron,4 -silicon,5 and -bismuth6
compounds at temperatures lower than room temperature.
Palladium(2+) complexes possessing bisphosphines bridged
by two carbons, such as chiraphos (2,3-bis(diphenylphosphino)-
butane),6,7 dipamp (1,2-bis[(2-methoxyphenyl)(phenyl)phos-
phino]ethane),7 and Me-Duphos (1,2-bis(2,5-dimethylphos-
pholano)benzene),8 were found to be effective for asymmetric
versions of compounds of those elements. Among these three
catalysts, the palladium–chiraphos complex exhibited high
enantioselectivities for 1,4-additions of arylboronic acids to un-
saturated ketones,7a,7b,7d,7f aldehydes,7c and N-acyl amides7e
having an aryl ring at the ꢀ-carbon. Chiral ꢀ-diaryl carbonyl
compounds thus obtained are key intermediates in the synthe-
ses of a potent competitive muscarinic receptor antagonist
(R)-tolterodine,9 a potential therapeutic agent (+)-(R)-CDP
840,7c,10 and endothelin receptor antagonist.11 Although chiral
ꢀ-diaryl esters are often desirable for syntheses of those biolog-
ically active compounds, this protocol effective for ketones,
aldehydes, and N-acyl amides does not work for unsaturated
esters. The corresponding rhodium catalysts such as [Rh-
(nbd)2]BF4/chiraphos and [Rh(binap)(nbd)]BF4 meet this
purpose; however, enantioselectivities raging from 89 to 90%
ee can be improved to 95–98% ee by the use of palladium–
chiraphos complex.7d Another advantage of palladium(2+) cat-
alysts is higher turnover number (TON) than those of rhodium
complexes.7d,12 The palladium complexes achieved quantita-
tive yields with a less than 0.1 mol % catalyst loading in the
presence of less than 1.5 equivalents of arylboronic acids.7d
A difficulty in using palladium(2+) catalysts for unsaturated
esters is the high stability of palladium(+) C-enolate compared
to that of O-enolate. A proposed catalytic cycle shown in
Figure 1 involves an equilibrium formation of C-enolate 4
and O-enolate 5 as the key intermediates for giving 1,4-addi-
tion products 6 via hydrolysis with water. Although ketone
substrates selectively produced 6, the ester derivatives resulted
in Heck coupling 7, thus suggesting slow formation of water-
sensitive 5. Thus, all attempts at using acrylates as the sub-
strates of palladium-catalyzed 1,4-addition failed to give 1,4-
addition products 6.
ArB(OH)2
[Pd]2+
Ar [Pd]+
1
2
Ar'
R
Ar'
R
Ar
O
6
O
3
H2O
R
[Pd]+
R
Ar'
Ar'
Ar
O[Pd]+
Ar
O
5
4
β-elimination
Ar'
Ar
R
O
7
Figure 1. Catalytic cycle.
Published on the web August 11, 2008; doi:10.1246/bcsj.81.1019

1020 Bull. Chem. Soc. Jpn. Vol. 81, No. 8 (2008)
Enantioselective Synthesis of ꢀ-Diaryl Esters
Table 1. Enantioselective Synthesis of ꢀ-Diaryl Ketones and Esters (Scheme 1)a)
10
11
No Yield/%b) % ee No Yield/%b) % ee
Entry
1
Enone 8
Arylboronic acid
Product
O
OMe
MeO
PMP
O
B(OH)2
10a
10b
99
86
95 11a
73
72
95
97
PMP
8a
OMe
O
OMe
O
MeO
PMP
MeO
B(OH)2
2
95 11b
MeO
8b
PMP
MeO
OMe
O
OMe
O
MeO
MeO
O
O
PMP
PMP
B(OH)2
3
4
10c
10d
74c)
97 11c
67
95
8c
O
O
PMP
OMe
O
O
MeO
B(OH)2
90
95 11d
0
PMP
8d
a) All reactions were carried out at room temperature for 6 h in aqueous acetone in the presence of enone (1 mmol), ArB(OH)2
(1.2 mmol), and [Pd(S,S-chiraphos)(PhCN)2](SbF6)2 (S,S-chiraphos = (2S,3S)-(ꢁ)-bis(diphenylphosphino)butane) (9, 0.5 mol %).
Chromatographic isolation of 10 was followed by Baeyer–Villiger oxidation with NaBO3 in acetic acid at 30–50 ꢂC. b) Isolated yields
by chromatography. c) In MeOH–water (10/1).
arylpropanates and 4-aryldihydrocoumarins which provided a
simple access to (R)-tolterodine (21) with high enantioselectivity.
B(OH)2
FG
FG'
Results and Discussion
FG
PMP
PMP
Synthesis of Optically Active 3,3-Diarylpropanoic
Esters. Traditional methods for conversion of ketones to
the corresponding acids or esters are haloform reaction of
methyl ketones or trihalomethyl ketones,13 oxidative cleavage
of ꢀ-hydroxy ketones with (NH4)2Ce(NO3)6,14 and Baeyer–
Villiger oxidation of unsymmetrical ketones.15 Thus, PhCH=
CHCOR (R ¼ Me, CF3, C(OH)Me2, CMe3, and Ph) are potent
substrates that can be finally transformed into desired acids or
esters. However, palladium(2+) complex 9 failed to catalyze
the additions of phenylboronic acid for trifluoromethyl,
dimethyl(hydroxy)methyl, and t-butyl ketones, whereas meth-
yl and phenyl ketones afforded excellent yields of 1,4-addition
products. Thus, p-methoxyphenyl (PMP) enones 8 were finally
chosen as the substrates for stepwise 1,4-addition and Baeyer–
Villiger oxidation, giving 11 because of higher enantioselec-
tivities of the palladium(2+)/chiraphos catalyst for aryl-
ketones than for methyl ketones.7b Regioselective cleavage
of the PMP ring rather than the primary alkyl group was pre-
Pd catalyst (9)
O
O
H2O
8
FG'
10
FG
[O]
OPMP
O
FG'
11
Ph
Ph
Ph
Pd
Ph
(SbF6)2
Me
Me
P
P
NCPh
NCPh
PMP=
OMe
9
[Pd(S,S-chiraphos)(PhCN)2](SbF6)2
S,S-chiraphos = (2S,3S)-(-)-bis(diphenylphosphino)butane
Scheme 1. Stepwise 1,4-addition and Baeyer–Villiger oxi-
dation for synthesis of optically active ꢀ-diaryl esters.
viously reported by Ruedi and Hansen (Scheme 1).15b
¨
Asymmetric addition of arylboronic acids to four ꢀ-aryl
ketones and oxidation of 10 to 11 with NaBO3 are summarized
in Table 1. Arylboronic acids possessing one or two alkoxy
groups at para or meta carbons were smoothly added to ꢀ-aryl
enones 8 at room temperature in the presence of 1.2 equiva-
lents of arylboronic acids and 0.5 mol % of dicationic palla-
As a means to overcome this limitation of the palladium-
catalyzed protocol, we report here stepwise 1,4-addition and
Baeyer–Villiger oxidation for the synthesis of optically active
ꢀ-diaryl esters (Scheme 1). We developed two selective meth-
ods for Baeyer–Villiger oxidation of p-methoxyphenyl 3,3-di-

K. Kobayashi et al.
Bull. Chem. Soc. Jpn. Vol. 81, No. 8 (2008) 1021
Table 2. Enantioselective Synthesis of 4-Aryldihydrocou-
marins (Scheme 2)a)
B(OH)2
OH
FG'
PMP
Arylboronic
acid
Yield
/%b)
Entry
1
Product 15
% ee
96
Pd catalyst (9)
acetone-H2O, rt
O
12
O
O
O
OH
PMP
B(OH)2
O
OH
15a 83
PMP
+
O
O
O
FG'
FG'
MeO
B(OH)2
2
3
15b 75
98
97
13
14
O
O
[O]
O
O
FG'
O
B(OH)2
15c 70
15
O
O
Scheme 2. Synthesis of optically active 4-aryldihydrocoumarins.
O
O
dium(II) catalyst 9 in aqueous acetone. The reaction easily
achieved 74–99% yields with 95–97% ee. The efficiency of
a rhodium–chiraphos catalyst for chalcone derivatives and
the enantioselection mechanism proposed on the basis of the-
oretical calculation of the transition state have been previously
reported.11 Baeyer–Villiger oxidation of 10 suffered from low
yields, resulting in complex mixtures. This is mainly due to
steric hindrance of substituents on aryl groups around the car-
bonyl group because unsubstituted Ph2CHCH2COPMP result-
ed in 99% yield by traditional MCPBA oxidation. Oxidation of
10 with NaBO3 resulted in the best yields among the represen-
tative methods reported for Baeyer–Villiger oxidation. Oxida-
tion of 10a–10c with 3 equivalents of NaBO3 at 30–50 ꢂC gave
11a–11c in 67–73% yields, whereas MCPBA (5 equivalents)
and trifluoroacetic acid (TFA) resulted in 38–48% yields
(Entries 1–3). A combination of H2O2 and TFA or bis(tri-
methylsilyl)peroxide (TMSO)2 and SnCl4 gave a complex
mixture from which it was difficult to isolate pure 11. All
attempts at oxidation of 10d with these oxidants failed
(Entry 4). The enantioselectivities of 10a–10c remained per-
fectly intact during the NaBO3 oxidation (Entries 1–3).
MeO
B(OH)2
4
15d 74
97
OMe
a) All reactions were carried out at 10 ꢂC for 24 h in aqueous
acetone in the presence of enone (0.5 mmol), ArB(OH)2
(0.75 mmol), and [Pd(S,S-chiraphos)(PhCN)2](SbF6)2 (9, 0.5
mol %). The crude product 13/14 thus obtained was directly
treated with (TMSO)2 (1 mmol) and SnCl4 (0.5 mmol) in
CH2Cl2. b) Isolated yields by chromatography.
The synthesis of 13/14 via asymmetric addition of arylbo-
ronic acids to 12 was followed by oxidation with (TMSO)2
at room temperature in the presence of SnCl4 to give optically
active 4-aryldihydrocoumarins (Table 2). Total yields of this
two-step synthesis of 15 were 70–83%, which were higher
than those obtained by an analogous procedure described for
the synthesis of 3,3-diarylpropanoic esters (Table 1). Palla-
dium(2+)–chiraphos catalyst 9 again achieved high enantio-
selectivities in a range of 96 to 98% ee.
Synthesis of Optically Active 4-Aryldihydrocoumarins.
In a previous study on the synthesis of optically active 4-
aryl-4H-chromenes, 1,4-addition of arylboronic acids to ꢀ-
(2-hydroxyaryl)enones 12 provided chromanol 14 accompa-
nied by a small amount of 13, which were then led to single
chromenes via acid-catalyzed dehydration.7d Baeyer–Villiger
oxidation of these intermediates 13 and 14 provided 4-aryldi-
hydrocoumarins, which were previously synthesized by rhodi-
um-catalyzed 1,4-addition of arylboronic acids to coumarins3o
(Scheme 2). Oxidation with MCPBA and NaBO3 resulted in
low yields, but (TMSO)2 and SnCl4 were found to be an excel-
lent combination for selective Baeyer–Villiger oxidation. A
one-pot two-step procedure without isolation of 1,4-addition
intermediates afforded good yields of desired dihydrocouma-
rins 15 as the sole products with excellent enantioselectivities.
Enantioselective synthesis of a potent competitive musca-
rinic receptor antagonist, (R)-tolterodine (21), has attracted
much attention as a target for enantioselective synthesis of a
chiral center consisting of two aryl rings. The synthesis has
been achieved by diastereoselective cycloaddition of o-qui-
none methide with a chiral enol ether,16 1,4-addition of aryl-
copper reagent to cinnamic amide of chiral oxazolidinone,17
catalytic 1,4-addition of arylboronic acids to coumarins3o and
hydrogenation of 4-arylcoumarin.18 The present method pro-
vided an alternative convenient and practical access to (R)-tol-
terodine (21) with high enantioselectivity (Scheme 3). The de-
sired enone 17 synthesized from 16 was subjected to 1,4-addi-
tion of phenylboronic acid (1.2 equiv) with the (S,S)-chiraphos
complex 9 (0.5 mol %). Chromatographic separation of 18 re-
sulted in 95% ee, but crystallization from THF furnished enan-

1022 Bull. Chem. Soc. Jpn. Vol. 81, No. 8 (2008)
Enantioselective Synthesis of ꢀ-Diaryl Esters
OMe
4-MeOC6H4COCH3
1. MCPBA, TFA
PMP
PhB(OH)2
2. NaOH, MeOH
NaOH, EtOH-H2O
CHO
[Pd(S,S-chiraphos)
(PhCN)2](SbF6)2 (9)
acetone-H2O, rt
BnO
O
OBn
OBn
O
(PMP)
18
16
17 (99%)
91%, 95% ee
83%, 99% ee by crystallization
1. LiAlH4
1. SOCl2
N
N
CO2H
2. H2, Pd/C
2. i-Pr2NH
BnO
BnO
O
HO
21
19 (74%)
20 (81%)
(R)-tolterodine (74%)
OH
PMP
OH
O
OH
PMP
PhB(OH)2
[Pd(S,S-chiraphos)
(TMSO)2
+
PMP
O
SnCl4, CH2Cl2
(PhCN)2](SbF6)2 (9)
acetone-H2O, 10 °C
O
12
13a (FG'=H)
14a (FG'=H)
O
O
1. DIBAH
2. iPr2NH, H2, Pd/C
(R)-tolterodine (21)
15a (83%, 96%ee)
Scheme 3. Synthesis of (R)-tolterodine.
AD-H, OJ-H, and OB-H purchased from Daicel Co., Ltd. Phen-
yl-, 3,5-dimethyl-4-methoxyphenyl-, and 3,4-dimethoxyphenyl-
boronic acid were purchased from Wako Chemical Co., Ltd.
and Lancaster Co., Ltd.
Preparation of Enones (8 and 12). 8a was commercially
available. Other ꢀ-arylenones were synthesized by reported proce-
dures.19 To a solution of ArCHO (30 mmol) and p-methoxyaceto-
phenone (30 mmol) in ethanol (15 mL) was slowly added aqueous
NaOH (39 mmol for 8 or 90 mmol for 12) in water (30 mL). The
resulting mixture was stirred overnight at 40 ꢂC. The mixture was
acidified with aqueous HCl and extracted with diethyl ether. The
product was isolated by crystallization.
8b: 89% yield; 1H NMR (400 MHz, CDCl3) ꢂ 8.03 (d, J ¼
8:8 Hz, 2H), 7.78 (d, J ¼ 15:6 Hz, 1H), 7.60 (d, J ¼ 8:8 Hz,
2H), 7.43 (d, J ¼ 15:6 Hz, 1H), 6.98 (d, J ¼ 8:8 Hz, 2H), 6.93
(d, J ¼ 8:8 Hz, 2H), 3.89 (s, 3H), 3.86 (s, 3H); 13C NMR
(100 MHz, CDCl3) ꢂ 188.67, 163.20, 161.44, 143.73, 131.27,
130.63, 130.48, 127.73, 119.45, 114.31, 113.72, 55.41, 55.33;
MS (m=z) 77 (18.5), 92 (14.4), 133 (10.6), 135 (30.6), 225
(20.0), 237 (17.8), 253 (33.7), 268 (Mþ, 100.0); Exact mass calcd
for C17H16O3: 268.1100. Found: 268.1082.
tiomerically pure 18 in 83% yield. Baeyer–Villiger oxidation
of 18 with MCPBA and TFA in toluene followed by saponifi-
cation of the ester group afforded an acid 19 which was previ-
ously led to (R)-tolterodine (21) in two steps. Conversion into
an N,N-diisopropylamide 20 in 81% yield was followed by re-
duction of the carbonyl group and deprotection of the benzyl
group to furnish optically pure tolterodine (21) in 74% yield.17
The formation of (R)-18 from the (S,S)-chiraphos complex 9
was finally established by the specific rotation reported
23
for 21 (½ꢁꢃD +23.9ꢂ (c 0.58, MeOH)).3o,9b Thus, the product
was produced by the same mode of face selection as that
proposed on the basis of theoretical calculation.7b
The alternative protocol provides a simpler access to (R)-
tolterodine. A one-pot, two-step procedure of stepwise 1,4-ad-
dition and Baeyer–Villiger oxidation directly gave a key inter-
mediate 15a in 96% ee, which has been previously converted
into (R)-tolterodine (21) in two steps.3o
Conclusion
8c: 91% yield; 1H NMR (400 MHz, CDCl3) ꢂ 8.02 (d, J ¼
9:1 Hz, 2H), 7.73 (d, J ¼ 15:6 Hz, 1H), 7.38 (d, J ¼ 15:6 Hz,
1H), 7.17 (s, 1H), 7.12 (d, J ¼ 8:1 Hz, 1H), 6.98 (d, J ¼ 9:1 Hz,
2H), 6.84 (d, J ¼ 8:1 Hz, 1H), 6.03 (s, 2H), 3.89 (s, 3H); 13C NMR
(100 MHz, CDCl3) ꢂ 188.58, 163.32, 149.71, 148.36, 143.80,
131.25, 130.70, 129.55, 125.00, 119.90, 113.80, 108.64, 106.62,
101.58, 55.48; MS (m=z) 77 (11.8), 89 (12.3), 122 (13.0), 135
(31.2), 145 (11.9), 175 (10.2), 251 (10.5), 267 (13.1), 282 (Mþ,
100); Exact mass calcd for C17H14O4: 282.0892. Found: 282.0901.
In conclusion, we have demonstrated the efficiency of a
Pd(2+)–chiraphos complex for the synthesis of ꢀ-diaryl
ketones and esters that provides a simple access to (R)-
tolterodine.
Experimental
General. All experiments were carried out under nitrogen
atmosphere. HPLC analysis was directly performed with chiral
stationary phase columns using Chiralcel IA, IB, OD-H, AD,

K. Kobayashi et al.
Bull. Chem. Soc. Jpn. Vol. 81, No. 8 (2008) 1023
8d: 52% yield; 1H NMR (400 MHz, CDCl3) ꢂ 8.03 (d, J ¼
8:8 Hz, 2H), 7.80 (d, J ¼ 15:6 Hz, 1H), 7.58 (d, J ¼ 8:1 Hz,
2H), 7.51 (d, J ¼ 15:6 Hz, 1H), 7.27 (d, J ¼ 8:1 Hz, 2H), 6.95
(d, J ¼ 8:8 Hz, 2H), 3.89 (s, 3H), 2.95 (sept, J ¼ 6:8 Hz, 1H),
1.27 (d, J ¼ 6:8 Hz, 6H); 13C NMR (100 MHz, CDCl3) ꢂ
188.36, 162.85, 151.23, 143.58, 132.25, 130.77, 130.29, 128.01,
126.57, 120.49, 113.32, 54.50, 33.64, 23.30; MS (m=z) 77
(10.7), 135 (28.2), 237 (100.0), 238 (19.2), 265 (35.0), 280
(Mþ, 56.6); Exact mass calcd for C19H20O2: 280.1463. Found:
280.146.
12: 63% yield; 1H NMR (400 MHz, CDCl3) ꢂ 8.16 (d, J ¼
16:1 Hz, 1H), 8.06 (d, J ¼ 8:7 Hz, 2H), 7.68 (d, J ¼ 16:1 Hz,
1H), 7.39 (s, 1H), 7.07 (d, J ¼ 8:5 Hz, 1H), 6.98 (d, J ¼ 8:7 Hz,
2H), 6.82 (d, J ¼ 8:5 Hz, 1H), 6.60 (s, 1H), 3.89 (s, 3H), 2.30
(s, 3H); 13C NMR (100 MHz, CDCl3) ꢂ 190.09, 163.39, 153.68,
140.24, 132.34, 131.23, 130.99, 129.91, 129.40, 122.20, 122.03,
116.54, 113.79, 55.49, 20.46; MS (m=z) 77 (22.3), 92 (12.5),
108 (22.9), 135 (100.0), 161 (10.7), 251 (47.4), 268 (Mþ, 31.7);
Exact mass calcd for C17H16O3: 268.1010. Found: 268.1088.
General Procedure for 1,4-Addition (Table 1). A solution
of [Pd((S,S)-chiraphos)(PhCN)2](SbF6)2 (9, 0.5 mol %), enone
substrate (0.5 mmol) and ArB(OH)2 (0.6 mmol) in acetone
(3.0 mL) and H2O (0.3 mL) was stirred at room temperature for
6–12 h. The product was extracted with diethyl ether and the ex-
tract was then concentrated in vacuo. Chromatography on silica
gel with hexane/EtOAc afforded the desired 10.
8:3 Hz, 2H), 7.22–7.12 (m, 3H), 7.10 (d, J ¼ 7:8 Hz, 2H), 6.90–
6.85 (m, 3H), 6.81 (s, 1H), 6.69 (d, J ¼ 7:8 Hz, 1H), 4.75 (t,
J ¼ 6:8 Hz, 1H), 3.83 (s, 3H), 3.73 (s, 3H), 3.65 (dd, J ¼ 6:8,
2.9 Hz, 2H), 2.85 (sept, J ¼ 6:8 Hz, 1H), 1.19 (d, J ¼ 6:8 Hz,
6H); 13C NMR (100 MHz, CDCl3) ꢂ 196.12, 162.94, 159.11,
146.25, 145.68, 140.98, 129.87, 129.71, 128.95, 127.13, 126.09,
119.76, 113.60, 113.21, 110.67, 54.98, 54.63, 45.19, 43.93,
33.13, 23.49; IR (neat) 1675, 1598, 1253, 1167, 1130, 984, 830,
780, 703, 580 cmꢁ1; MS (m=z) 135 (100), 145 (15.6), 211
(11.1), 239 (52.7), 240 (10.0), 253 (16.1), 388 (Mþ, 50.9); Exact
mass calcd for C26H28O3: 388.2038. Found: 388.2032.
Baeyer–Villiger Oxidation (Table 1). Baeyer–Villiger oxi-
dation of 10 was carried out by a modified procedure.20 A solution
of 1,4-adduct 10 (0.5 mmol) and NaBO3 4H2O (2.5 mmol) in
ꢄ
acetic acid (3 mL) was stirred at 30–50 ꢂC to room temperature
for 24 h. The product was extracted with diethyl ether, washed
with brine and concentrated in vacuo. Chromatography on silica
gel with hexane/EtOAc afforded 11.
23
11a: 73% yield, 95% ee; ½ꢁꢃD +6.3ꢂ (c 0.10, CDCl3), Daicel
Chiralcel IB with hexane/2-propanol = 19/1, flow = 1.0
mL minꢁ1, wavelength = 254 nm, tR ¼ 15:4 min (minor) and
16.5 min (major); 1H NMR (400 MHz, CDCl3) ꢂ 7.33–7.29 (m,
4H), 7.27–7.20 (m, 2H), 6.90 (d, J ¼ 8:0 Hz, 1H), 6.86–6.74 (m,
4H), 6.73–6.66 (m, 2H), 4.62 (t, J ¼ 8:3 Hz, 1H), 3.77 (s, 3H),
3.75 (s, 3H), 3.26 (d, J ¼ 8:3 Hz, 2H); 13C NMR (100 MHz,
CDCl3) ꢂ 170.79, 159.73, 157.19, 144.68, 143.99, 142.90,
129.61, 128.65, 127.73, 126.77, 122.16, 120.04, 114.34, 113.84,
111.77, 55.54, 55.17, 47.32, 40.81; IR (neat) 1752, 1503, 1236,
1191, 1128, 1033, 842, 768, 743, 699 cmꢁ1; MS (m=z): 124
(100.0), 165 (13.2), 197 (30.3), 239 (15.3), 362 (Mþ, 4.3); Exact
mass calcd for C23H22O4: 362.1518. Found: 362.1502.
10a: 99% yield, 95% ee; Daicel Chiralcel IB with hexane/
2-propanol = 9/1, flow = 1.0 mL minꢁ1, wavelength = 254 nm,
tR ¼ 13:9 min (minor) and 15.5 min (major). The spectral data
have been previously reported.11
23
10b: 86% yield, 95% ee; ½ꢁꢃD +2.1ꢂ (c 0.33, CDCl3), Daicel
23
Chiralcel IA with hexane/2-propanol/dichloromethane = 4/2/1,
11b: 72% yield, 97% ee; ½ꢁꢃD +2.4ꢂ (c 0.10, CDCl3), Daicel
flow = 0.5 mL minꢁ1
,
wavelength = 254 nm, tR ¼ 13:8 min
Chiralcel AD-H with hexane/2-propanol = 9/1, flow = 0.5
(minor) and 15.6 min (major); 1H NMR (400 MHz, CDCl3)
ꢂ 7.92 (d, J ¼ 8:8 Hz, 2H), 7.17 (d, J ¼ 8:8 Hz, 2H), 6.90 (d,
J ¼ 8:8 Hz, 2H), 6.81 (d, J ¼ 8:8 Hz, 2H), 6.77–6.75 (m, 3H),
4.72 (t, J ¼ 7:3 Hz, 1H), 3.84 (s, 3H), 3.81 (s, 3H), 3.79 (s, 3H),
3.75 (s, 3H), 3.61 (t, J ¼ 6:6 Hz, 2H); 13C NMR (100 MHz,
CDCl3) ꢂ 196.35, 162.97, 157.49, 148.34, 146.93, 136.75,
136.15, 129.87, 129.73, 128.18, 117.78, 113.39, 113.23, 111.03,
110.61, 55.35, 55.32, 54.98, 54.72, 44.45, 44.25; IR (neat) 1598,
1509, 1244, 1169, 1141, 1025, 986, 831, 807, 545 cmꢁ1; MS
(m=z) 135 (12.9), 257 (100), 406 (Mþ, 18.7); Exact mass calcd
for C25H26O5: 406.1780. Found: 406.1283.
mL minꢁ1
,
wavelength = 254 nm, tR ¼ 70 min (major) and
79 min (minor); 1H NMR (400 MHz, CDCl3) ꢂ 7.14 (d, J ¼
8:0 Hz, 2H), 6.81–6.70 (m, 7H), 6.66–6.61 (m, 2H), 4.48 (t,
J ¼ 8:3 Hz, 1H), 3.79 (s, 3H), 3.76 (s, 3H), 3.72 (s, 3H), 3.69
(s, 3H), 3.14 (d, J ¼ 8:3 Hz, 2H); 13C NMR (100 MHz, CDCl3)
ꢂ 170.90, 158.26, 157.19, 148.90, 147.68, 143.99, 136.02,
135.44, 128.58, 122.16, 119.31, 114.36, 113.97, 111.18, 111.13,
55.86, 55.82, 55.53, 55.24, 46.14, 41.32; IR (neat) 1751, 1505,
1243, 1190, 1127, 1027, 838, 810, 760, 539 cmꢁ1; MS (m=z):
124 (25.9), 257 (100.0), 258 (17.8), 270 (31.0), 298 (35.0), 422
(Mþ, 23.6); Exact mass calcd for C25H26O6: 422.1729. Found:
22
10c: 74% yield, 97% ee; ½ꢁꢃD +4.8ꢂ (c 0.17, CDCl3), Daicel
422.1747.
11c:
23
Chiralcel IA with hexane/2-propanol/dichloromethane = 4/2/1,
flow = 0.5 mL minꢁ1
67% yield, 95% ee; ½ꢁꢃD : +3.6ꢂ (c 0.19, CDCl3),
,
wavelength = 254 nm,
tR ¼ 15 min
Daicel Chiralcel IA with hexane/2-propanol = 9/1, flow = 1.0
mL minꢁ1, wavelength = 254 nm, tR ¼ 46:5 min (major) and
53.2 min (minor); 1H NMR (400 MHz, CDCl3) ꢂ 6.86–6.71 (m,
10H), 5.91 (s, 2H), 4.52 (t, J ¼ 8:3 Hz, 1H), 3.86 (s, 3H), 3.84
(s, 3H), 3.76 (s, 3H), 3.19 (d, J ¼ 8:3 Hz, 2H); 13C NMR
(100 MHz, CDCl3) ꢂ 170.75, 157.21, 148.94, 147.83, 147.78,
146.24, 143.96, 137.34, 135.68, 122.14, 120.44, 119.21, 114.38,
111.13, 111.12, 108.19, 108.16, 100.97, 55.86, 55.84, 55.53,
46.58, 41.20; IR (neat) 1503, 1481, 1237, 1191, 1127, 1029,
910, 811, 761, 728 cmꢁ1; MS (m=z) 124 (31.7), 271 (100), 284
(29.9), 312 (53.3), 436 (31.2); Exact mass calcd for C25H24O7:
436.1522. Found: 436.1535.
1
(minor) and 19 min (major); H NMR (400 MHz, CDCl3) ꢂ 7.92
(d, J ¼ 8:9 Hz, 2H), 6.91 (d, J ¼ 8:9 Hz, 2H), 6.82–6.67 (m,
6H), 5.88 (s, 2H), 4.68 (t, J ¼ 7:3 Hz, 1H), 3.85 (s, 3H), 3.82 (s,
3H), 3.80 (s, 3H), 3.60 (d, J ¼ 7:3 Hz, 1H), 3.59 (d, J ¼ 7:3 Hz,
1H); 13C NMR (100 MHz, CDCl3) ꢂ 196.14, 163.00, 148.38,
147.22, 147.02, 145.44, 138.03, 136.45, 129.87, 129.66, 120.03,
118.66, 113.25, 110.95, 110.61, 107.85, 107.68, 100.40, 55.35,
55.34, 54.99, 44.92, 44.11; IR (neat) 1598, 1509, 1486, 1235,
1169, 1141, 1027, 930, 832, 809 cmꢁ1; MS (m=z) 135 (15.6),
271 (100), 420 (Mþ, 20.7); Exact mass calcd for C25H24O6:
420.1573. Found: 420.1579.
22
10d: 90% yield, 95% ee; ½ꢁꢃD +3.4ꢂ (c 0.22, CDCl3), Daicel
General Procedure for Synthesis of 4-Aryldihydrocouma-
Chiralcel OD-H with hexane/2-propanol = 9/1, flow = 0.7
mL minꢁ1, wavelength = 254 nm, tR ¼ 19:6 min (minor) and
27.9 min (major); 1H NMR (400 MHz, CDCl3) ꢂ 7.91 (d, J ¼
rins (Table 2). A solution of [Pd((S,S)-chiraphos)(PhCN)2]-
(SbF6)2 (9, 0.5 mol %), enone 12 (0.5 mmol), and ArB(OH)2
(0.75 mmol) in acetone (3.0 mL) and H2O (0.3 mL) was stirred

1024 Bull. Chem. Soc. Jpn. Vol. 81, No. 8 (2008)
Enantioselective Synthesis of ꢀ-Diaryl Esters
at 10 ꢂC for 24 h. The mixture was passed through a short pad of
silica gel with diethyl ether as eluent. The filtrate was concentrat-
ed in vacuo to give crude 13/14.
(s, 2H), 3.88 (s, 3H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3)
ꢂ 162.63, 155.69, 139.65, 136.20, 131.35, 130.89, 130.29,
129.78, 128.23, 127.63, 127.36, 123.52, 122.68, 113.26, 111.96,
70.15, 54.95, 31.10, 22.17, 19.93; MS (m=z) 77 (11.2), 91 (100),
135 (89.0), 160 (16.0), 251 (47.3), 358 (Mþ, 12.5); Exact mass
calcd for C24H22O3: 358.1569. Found: 358.1581.
Baeyer–Villiger oxidation of crude 13/14 was carried out by a
reported procedure.21 The residue thus obtained was dissolved in
CH2Cl2 (5 mL) and treated with (TMSO)2 (0.5 mmol). To this
mixture was slowly added SnCl4 (0.5 mmol) (1.0 M solution in
heptane) at 0 ꢂC and the mixture was stirred for 15 min at 0 ꢂC
and at room temperature for 1 h. Additional (TMSO)2 (0.5 mmol)
was then added and stirred for 3 h. The product was extracted with
diethyl ether, washed with saturated K2CO3 in water and concen-
trated in vacuo. Chromatography on silica gel with hexane/EtOAc
afforded 15.
Synthesis of 18. The procedure shown in general for 1,4-
23
addition (Table 1) gave 18. 91% yield; 95% ee. ½ꢁꢃD +13.3ꢂ (c
0.28, CDCl3), Daicel Chiralcel AD with hexane/2-propanol =
9/1, flow = 1.0 mL minꢁ1, wavelength = 254 nm, tR ¼ 17 min
(minor) and 205 min (major); 1H NMR (400 MHz, CDCl3)
ꢂ 7.89 (d, J ¼ 8:0 Hz, 2H), 7.31–7.12 (m, 10H), 6.98 (s, 1H),
6.93 (d, J ¼ 8:3 Hz, 1H), 6.82 (d, J ¼ 7:3 Hz, 2H), 6.77 (d, J ¼
8:3 Hz, 1H), 5.16 (t, J ¼ 7:3 Hz, 1H), 5.01 (d, J ¼ 14:6 Hz, 1H),
4.98 (d, J ¼ 14:6 Hz, 1H), 3.83 (s, 3H), 3.65 (d, J ¼ 7:3 Hz,
2H), 2.23 (s, 3H); 13C NMR (100 MHz, CDCl3) ꢂ 196.98,
163.19, 153.81, 143.74, 137.26, 132.60, 130.32, 130.17, 129.84,
129.04, 128.38, 128.18, 128.14, 127.68, 127.62, 127.36, 125.94,
113.54, 112.05, 70.14, 55.39, 43.38, 40.40, 20.72; IR (neat)
1659, 1598, 1571, 1501, 1450, 1312, 1263, 1238, 1178, 1120,
1044, 1022, 994 cmꢁ1; MS (m=z) 91 (30.7), 135 (100), 241
(11.7), 345 (18.6), 345 (18.6), 436 (Mþ, 1.8); Exact mass calcd
for C30H28O3: 436.2038. Found: 436.2059.
15a and 15b have been previously reported.3o
23
15c:
Daicel Chiralcel IB with hexane/2-propanol/dichloromethane =
50/1/3, flow = 0.5 mL minꢁ1
wavelength = 254 nm, tR
70% yield, 97% ee; ½ꢁꢃD +9.4ꢂ (c 0.9, CDCl3),
,
¼
1
29 min (minor) and 33 min (major); H NMR (400 MHz, CDCl3)
ꢂ 7.09 (d, J ¼ 8:3 Hz, 1H), 7.01 (d, J ¼ 8:3 Hz, 1H), 6.80 (s,
1H), 6.76 (d, J ¼ 8:8 Hz, 1H), 6.65–6.55 (m, 2H), 5.95 (s, 2H),
4.22 (t, J ¼ 6:6 Hz, 1H), 3.02 (dd, J ¼ 16, 5.9 Hz, 1H), 2.94
(dd, J ¼ 16, 7.6 Hz, 1H), 2.27 (s, 3H); 13C NMR (100 MHz,
CDCl3) ꢂ 167.79, 149.52, 148.21, 146.96, 134.33, 134.29,
129.31, 128.58, 125.33, 120.80, 116.84, 108.61, 107.70, 101.18,
40.41, 37.36, 20.74; IR (neat) 1487, 1443, 1239, 1198, 1164,
1150, 1118, 1036, 927, 812 cmꢁ1; MS (m=z): 152 (12.6), 182
(15.6), 210 (19.6), 239 (81.7), 264 (41.8), 282 (Mþ, 100); Exact
Syntheses and spectral data of 19, 20, and (R)-tolterodine (21)
have been previously reported.17
This work was supported by Grant-in-Aid from Innovation
Plaza Hokkaido in Japan Science and Technology Agency.
mass calcd for C17H14O4: 282.08921. Found: 282.08827.
23
15d:
74% yield, 97% ee; ½ꢁꢃD +2.6ꢂ (c 0.45, CDCl3),
Daicel Chiralcel IA with hexane/2-propanol = 9/1, flow =
0.5 mL minꢁ1, wavelength = 254 nm, tR ¼ 12 min (minor) and
14 min (major); 1H NMR (400 MHz, CDCl3) ꢂ 6.99 (d, J ¼
8:3 Hz, 1H), 6.92 (d, J ¼ 8:3 Hz, 1H), 6.72 (s, 1H), 6.68 (s,
2H), 4.09 (t, J ¼ 6:8 Hz, 1H), 3.62 (s, 3H), 2.92 (dd, J ¼ 16,
6.1 Hz, 1H), 2.86 (dd, J ¼ 16, 7.1 Hz, 1H), 2.18 (s, 3H), 2.16
(s, 6H); 13C NMR (100 MHz, CDCl3) ꢂ 167.98, 156.17, 149.47,
135.67, 134.19, 131.41, 129.11, 128.64, 127.68, 125.47, 116.07,
59.56, 40.08, 37.16, 20.69, 16.11; IR (neat) 1764, 1488, 1223,
1200, 1154, 1128, 1010, 924, 894, 815 cmꢁ1; MS (m=z) 195
(10.3), 223 (37.0), 239 (81.1), 253 (19.1), 263 (28.0), 278
(31.8), 296 (Mþ, 100); Exact mass calcd for C19H20O3:
296.1413. Found: 296.1400.
Synthesis of 16. To a mixture of 5-methylsalicylaldehyde
(50 mmol) and K2CO3 (55 mmol) in ethanol (100 mL) and water
(50 mL) was slowly added benzyl chloride (55 mmol) and the mix-
ture was then stirred overnight at reflux. The product was obtained
by crystallization. 77% yield; 1H NMR (400 MHz, CDCl3) ꢂ 10.53
(s, 1H), 7.66 (s, 1H), 7.46–7.30 (m, 6H), 6.95 (d, J ¼ 8:4 Hz, 1H),
5.17 (s, 2H), 2.31 (s, 3H); 13C NMR (100 MHz, CDCl3) ꢂ 189.93,
159.15, 136.54, 136.24, 130.44, 128.68, 128.42, 128.19, 127.25,
124.84, 113.08, 70.54, 20.26; MS (m=z) 65 (10.3), 91 (100.0),
135 (8.2), 226 (Mþ, 7.5); Exact mass calcd for C15H14O2:
226.0994. Found: 226.0987.
References
1
For reviews, see: a) B. E. Rossiter, N. M. Swingle, Chem.
Rev. 1992, 92, 771. b) K. Tomioka, Y. Nagaoka, in Comprehen-
sive Asymmetric Catalysis, ed. by E. N. Jacobsen, A. E. Pfalts,
H. Yamamoto, S.-V. Berlin, 1999, Chap. 31.1. c) M. P. Sibi,
S. Manyem, Tetrahedron 2000, 56, 8033. d) N. Krause, A.
Hoffmann-Roder, Synthesis 2001, 171. e) J. Christoffers, G.
¨
M. Sakai, H. Hayashi, N. Miyaura, Organometallics 1997,
¨
Koripelly, A. Rosiak, M. Rossle, Synthesis 2007, 1279.
2
16, 4229.
3
a) Y. Takaya, M. Ogasawara, T. Hayashi, M. Sakai, N.
Miyaura, J. Am. Chem. Soc. 1998, 120, 5579. b) R. A. Batey,
A. N. Thadani, D. V. Smil, Org. Lett. 1999, 1, 1683. c) T.
Hayashi, T. Senda, Y. Takaya, M. Ogasawara, J. Am. Chem.
Soc. 1999, 121, 11591. d) S. Sakuma, M. Sakai, R. Itooka,
N. Miyaura, J. Org. Chem. 2000, 65, 5951. e) M. T. Reetz, D.
Moulin, A. Gosberg, Org. Lett. 2001, 3, 4083. f) J. Ramnauth,
O. Poulin, S. Bratovanov, S. S. Rakhit, S. P. Maddaford, Org. Lett.
2001, 3, 2571. g) R. Itooka, Y. Iguchi, N. Miyaura, Chem. Lett.
ˆ
2001, 722. h) R. Amengual, V. Michelet, J.-P. Genet, Tetrahedron
Lett. 2002, 43, 5905. i) M. Pucheault, S. Darses, J.-P. Genet,
ˆ
Tetrahedron Lett. 2002, 43, 6155. j) T. Hayashi, M. Takahashi,
Y. Takaya, M. Ogasawara, J. Am. Chem. Soc. 2002, 124, 5052.
k) R. Itooka, Y. Iguchi, N. Miyaura, J. Org. Chem. 2003, 68,
6000. l) Y. Ma, C. Song, C. Ma, Z. Sun, Q. Chai, M. B. Andrus,
Angew. Chem., Int. Ed. 2003, 42, 5871. m) D. F. Cauble, J. D.
Gipson, M. J. Krische, J. Am. Chem. Soc. 2003, 125, 1110. n)
Synthesis of 17. To a solution of 16 (77 mmol) and p-me-
thoxyacetophenone (77 mmol) in ethanol (18 mL) was slowly add-
ed aqueous NaOH (100 mmol, 36 mL). The mixture was stirred
overnight at 40 ꢂC and then acidified with hydrochloric acid at
room temperature. The product was obtained by crystallization.
99% yield; 1H NMR (400 MHz, CDCl3) ꢂ 8.00 (d, J ¼ 15:6 Hz,
1H), 7.85 (d, J ¼ 8:8 Hz, 2H), 7.74 (d, J ¼ 15:6 Hz, 1H), 7.49
(d, J ¼ 6:3 Hz, 2H), 7.45–7.35 (m, 4H), 7.14 (d, J ¼ 8:3 Hz,
1H), 6.91 (d, J ¼ 8:3 Hz, 1H), 6.88 (d, J ¼ 8:8 Hz, 2H), 5.14
ˆ
L. Navarre, M. Pucheault, S. Darses, J.-P. Genet, Tetrahedron
Lett. 2005, 46, 4247. o) G. Chen, N. Tokunaga, T. Hayashi,
Org. Lett. 2005, 7, 2285. p) Y. Yamamoto, K. Kurihara, N.
Sugishita, K. Oshita, D. Piao, N. Miyaura, Chem. Lett. 2005, 34,
1224. q) R. T. Stemmler, C. Bolm, J. Org. Chem. 2005, 70,

K. Kobayashi et al.
Bull. Chem. Soc. Jpn. Vol. 81, No. 8 (2008) 1025
9925. r) K. Vandyck, B. Matthys, M. Willen, K. Robeyns, L. van
Meervelt, J. van der Eycken, Org. Lett. 2006, 8, 363. s) K.
Kurihara, N. Sugishita, K. Oshita, D. Piao, Y. Yamamoto, N.
Miyaura, J. Organomet. Chem. 2007, 692, 428. For reviews,
see: t) Y. Yamamoto, T. Nishikata, N. Miyaura, J. Synth. Org.
Chem., Jpn. 2006, 64, 1112. u) T. Hayashi, K. Yamasaki, Chem.
Rev. 2003, 103, 2829.
E. C. Boyd, J. C. Head, J. R. Porter, J. A. Brown, J. T. Reuberson,
B. Hutchinson, P. Turner, B. Boyce, D. Barnes, B. Mason, A.
Cannell, R. J. Taylor, A. Zomaya, A. Millican, J. Leonard, R.
Morphy, M. Wales, M. Perry, R. A. Allen, N. Gozzard, B.
Hughes, G. Higgs, Bioorg. Med. Chem. Lett. 2002, 12, 1451.
c) V. K. Aggarwal, I. Bae, H.-Y. Lee, J. Richardson, D. T.
Williams, Angew. Chem., Int. Ed. 2003, 42, 3274.
4
a) T. Nishikata, Y. Yamamoto, N. Miyaura, Angew. Chem.,
11 T. Itoh, T. Mase, T. Nishikata, T. Iyama, H. Tachikawa,
Y. Kobayashi, Y. Yamamoto, N. Miyaura, Tetrahedron 2006,
62, 9610.
Int. Ed. 2003, 42, 2768. b) T. Nishikata, Y. Yamamoto, N.
Miyaura, Organometallics 2004, 23, 4317.
5
32, 752.
T. Nishikata, Y. Yamamoto, N. Miyaura, Chem. Lett. 2003,
12 a) R. Amengual, V. Michelet, J.-P. Genet, Synlett 2002,
1791. b) F.-X. Chen, A. Kina, T. Hayashi, Org. Lett. 2006, 8, 341.
13 a) R. C. Fuson, B. A. Bull, Chem. Rev. 1934, 15, 275.
b) P. Kaszynski, J. Michel, J. Org. Chem. 1988, 53, 4593.
6 T. Nishikata, Y. Yamamoto, N. Miyaura, Chem. Commun.
2004, 1822.
´
´
7
a) T. Nishikata, Y. Yamamoto, N. Miyaura, Chem. Lett.
14 C. Palomo, M. Oiarbide, J. M. Garcla, A. Gonzalez,
E. Arceo, J. Am. Chem. Soc. 2003, 125, 13942.
15 a) S. Kobayashi, H. Tanaka, H. Amii, K. Uneyama, Tetra-
2005, 34, 720. b) T. Nishikata, Y. Yamamoto, I. D. Gridnev,
N. Miyaura, Organometallics 2005, 24, 5025. c) T. Nishikata,
Y. Yamamoto, N. Miyaura, Tetrahedron Lett. 2007, 48, 4007.
d) T. Nishikata, Y. Yamamoto, N. Miyaura, Adv. Synth. Catal.
2007, 349, 1759. e) T. Nishikata, Y. Yamamoto, N. Miyaura,
Chem. Lett. 2007, 36, 1442. f) T. Nishikata, Y. Kobayashi, K.
Kobayashi, Y. Yamamoto, N. Miyaura, Synlett 2007, 3055.
hedron 2003, 59, 1547. b) G. Ruedi, H.-J. Hansen, Helv. Chim.
Acta 2004, 87, 1968.
16 C. Selenski, T. R. R. Pettus, J. Org. Chem. 2004, 69, 9196.
¨
¨
17 P. G. Andersson, H. E. Schink, K. Osterlund, J. Org.
Chem. 1998, 63, 8067.
18 F. Ulgheri, M. Marchetti, O. Piccolo, J. Org. Chem. 2007,
72, 6056.
19 R. M. Kellogg, J. W. Nieuwenhuijzen, K. Pouwer, T. R.
Vries, Q. B. Broxterman, R. F. P. Grimbergen, B. Kaptein,
R. M. L. Crois, E. de Wever, K. Zwaagstra, A. C. van der Laan,
Synthesis 2003, 1626.
20 A. McKillop, J. A. Tarbin, Tetrahedron 1987, 43, 1753.
21 S. Matsubara, K. Takai, H. Nozaki, Bull. Chem. Soc. Jpn.
1983, 56, 2029.
8
a) F. Gini, B. Hessen, A. J. Minnaard, Org. Lett. 2005, 7,
5309. b) F. Gini, B. Hessen, B. L. Feringa, A. J. Minnaard, Chem.
Commun. 2007, 710.
9
Stahl, B. Sparf, Eur. J. Pharmacol. 1997, 327, 195. b) S. Sorgel,
N. Tokunaga, K. Sasaki, K. Okamoto, T. Hayashi, Org. Lett. 2008,
10, 589.
10 a) J. E. Lynch, W.-B. Choi, H. R. O. Churchill, R. P.
Volante, R. A. Reamer, R. G. Ball, J. Org. Chem. 1997, 62,
9223. b) R. P. Alexander, G. J. Warrellow, M. A. W. Eaton,
a) L. Nilvebrant, K.-E. Andersson, P.-G. Gillberg, M.
¨