2,2′-Isopropylidenebis[(4S,5R)-4,5-di(2-naphthyl)-2-oxazoline] ligand for asymmetric cyclization-carbonylation of meso-2-alkyl-2-propargylcyclohexane-1,3-diols

Article abstract of DOI:10.1016/j.tet.2006.08.004

The oxidative cyclization-carbonylation of meso-2-alkyl-2-propargylcyclohexane-1,3-diols mediated by Pd(II) with chiral bisoxazoline (box ligand) afforded bicyclic-β-alkoxyacrylates. Based on a ligand screening, 2,2′-isopropylidenebis[(4S,5R)-4,5-di(2-nap

Full text of DOI:10.1016/j.tet.2006.08.004

Tetrahedron 62 (2006) 9988–9999
2,20-Isopropylidenebis[(4S,5R)-4,5-di(2-naphthyl)-2-oxazoline]
ligand for asymmetric cyclization–carbonylation of
meso-2-alkyl-2-propargylcyclohexane-1,3-diols
a
a
a
Keisuke Kato,a, Chie Matsuba, Taichi Kusakabe, Hiroyuki Takayama,
*
Shigeo Yamamura,a Tomoyuki Mochida,b Hiroyuki Akita,a,
*
Tat’yana A. Peganova,c Nikolai V. Vologdinc and Oleg V. Gusevc
aFaculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
bDepartment of Chemistry, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
cN. Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences, Vavilov St. 28, 119991 Moscow, Russia
Received 3 July 2006; revised 1 August 2006; accepted 1 August 2006
Available online 24 August 2006
Abstract—The oxidative cyclization–carbonylation of meso-2-alkyl-2-propargylcyclohexane-1,3-diols mediated by Pd(II) with chiral bisox-
azoline (box ligand) afforded bicyclic-b-alkoxyacrylates. Based on a ligand screening, 2,20-isopropylidenebis[(4S,5R)-4,5-di(2-naphthyl)-2-
oxazoline] ligand has been developed. The products with a chiral quaternary carbon were obtained in 71–100% yields with 85–95% ee.
Ó 2006 Elsevier Ltd. All rights reserved.
Pd(OCOCF3)2 (5 mol %)/
OH
S
1. Introduction
OH
OH
ligand (10 mol %)
O
CO2R
p-benzoquinone (1.1 equiv.)
CO balloon, ROH
Palladium(II)-catalyzed reactions are fundamentally impor-
tant in organic transformations.1 Compared with the impres-
sive evolution of oxidative asymmetric reactions of alkene
catalyzed by Pd(II),2 that of alkyne has received only scant
attention.3 Previously, we have reported the cyclization–
carbonylation of 4-yne-1-ols,3a,4 4-yne-1-ones,5 and prop-
argyl acetates.6 Based on the reaction of 4-yne-1-ols, the
total synthesis of antibiotics, such as cystothiazoles and
melithazoles, has been achieved.7 As the first example of
an asymmetric version of this reaction, we have also re-
ported the cyclization–carbonylation of meso-2-methyl-2-
propargylcyclohexane-1,3-diol 1 catalyzed by palladium(II)
with chiral-box (bisoxazoline) ligands3a (Scheme 1).
Although the product was obtained in good yield, the ee
value was moderate (up to 65% ee). In this paper, we have
investigated a box-ligand structure–enantioselectivity rela-
tionship, and found that cis-4,5-di(2-naphthyl)-box ligand
34 was useful for the present reaction.
2a : R = Me
3 : R = i-Pr
1
Scheme 1.
2. Results and discussion
2.1. Synthesis of the substrates 1a–c
The substrates 1a–c were synthesized from the correspond-
ing cyclohexane-1,3-dione derivatives 8a–c8 (Scheme 2).
Monoketalization of 8a–c according to Pancrazi’s proce-
dure9 gave 9a–c. Reduction of 9a–c followed by acid
hydrolysis gave ca. 1:1 mixture of ketols 10a–c and its dia-
stereomers, which were separated by column chromato-
graphy. After protection of the hydroxyl group in 10a–c
with a tert-butyldimethylsilyl (TBDMS) group, TBDMS
ethers 11a–c were reduced with NaBH4 to afford 12a–c,
which were treated with TBAF to provide the substrates
1a–c.
2.2. Cyclization–carbonylation of 1
Keywords: Palladium; Bisoxazoline; Asymmetric cyclization–carbonyla-
tion.
* Corresponding authors. Tel./fax: +81 474 72 1825; e-mail: kkk@phar.
toho-u.ac.jp
2.2.1. Preliminary experiments. As a preliminary experi-
ment, we investigated the box-ligands 4–710 having four
kinds of substituents at the C4 position of the bisoxazoline
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.08.004

K. Kato et al. / Tetrahedron 62 (2006) 9988–9999
9989
O
OTBDMS
R
OH
O
OTBDMS
R
OH
R
R
R
R
a
b
c
d
e
O
O
O
O
OH
OH
O
8a : R = Me
8b : R = Propyl
8c : R = Allyl
9a : R = Me
9b : R = Propyl
9c : R = Allyl
10a : R = Me
10b : R = Propyl
10c : R = Allyl
11a : R = Me
11b : R = Propyl
11c : R = Allyl
12a : R = Me
12b : R = Propyl
12c : R = Allyl
1a : R = Me
1b : R = Propyl
1c : R = Allyl
Scheme 2. Reagents: (a) 2,2-Dimethyl-1,3-propandiol, BF3/OEt2 in CH2Cl2, single operation, 34–51% (recovery 40–56%); (b) LiAlH4 in THF, 70 ꢀC then 10%
HCl/MeOH 46–56% (diastereomers 31–42%); (c) TBDMSCl, imidazole in DMF 82–95%; (d) NaBH4 in MeOH 78–99%; (e) TBAF in THF 72–90%.
rings; among them, only ph-box ligand 4 was effective,
65% ee of bicyclic-b-alkoxyacrylate 2a was obtained in
98% yield (Table 1, entries 1–4; Scheme 1). When the
same reaction of 1a was carried out at 0 ꢀC, significant
rate acceleration was noted with accompanying slight
decrease in the enantioselection to 57% (entry 5). In the
absence of a ligand, the reaction proceeded at room temper-
ature to afford racemic-2a in 85% yield (entry 6). Although
Pd(CH3CN)4(BF4)2 was also effective for this reaction, the
ee of the product was slightly lower than that obtained on
using Pd(CF3CO2)2 (entries 1 and 7). When we examined
the use of CH2Cl2/MeOH¼10/1 or i-PrOH as solvents,
the product 2a was obtained in good yield with moderate
enantioselectivity (entries 8 and 9). The reaction in THF/
MeOH¼10/1 was very slow to give low yield of 2a with
low enantioselectivity (entry 10). The phosphine ligand
seems to be not effective for this type of reactions;4,11 the
use of (S)-BINAP 1310 and bis(phosphino)ferrocene com-
plexes of DPPFA 1410 gave poor results (entries 11–13).
bearing an aromatic substituent at the C4 position on the
oxazoline ring in MeOH. At first, we examined the spacer of
two oxazoline rings (Fig. 1, Part A), such as one or two car-
bon atoms (4, 15–18), pyridine ring (19 and 20), binaphthyl
skeleton (21), and cyclohexane ring (22 and 23) (entries 1–
10). Among them, ligand 4 gave the best result (entry 1). Al-
though ligands 4, 15, and 16 all contain one carbon spacer,
enantioselectivity of the reactions was different. We could
prepare palladium complexes of ligands 4 and 16 as a single
crystal, and X-ray structures of [Pd(TFA)2((S,S)-4)] and
[Pd(TFA)2((R,R)-16)] are shown in Figure 2. Although the
[Pd(TFA)2((S,S)-4)] has a rigid square plane structure and
all elements related to palladium existed on the same plane,
that of the [Pd(TFA)2((R,R)-16)] was slightly distorted. This
difference might be a cause of the difference in the selectiv-
ity. Next, we examined the substituent effect of the C5 posi-
tion on the bisoxazoline ring (Fig. 1, Part B; Table 2, entries
11–15; Scheme 1). Although the trans-phenyl group at the
C5 position (24) lowered enantioselectivity (entry 11), it
was improved by the use of ligand 25 bearing a cis-phenyl
group on the C5 position (entry 12). The use of ligand 26
lacking dimethyl groups in the spacer part and ligand 27 hav-
ing dimethyl groups on the C5 position resulted in decreased
selectivity (entries 13 and 14). Ligand 28 with the phenyl
group fixed to the oxazoline ring in parallel showed poor
2.2.2. Screening of ligands. In the next step, several kinds of
box ligands12 were tested in the present reaction as shown in
Figure 1 and Table 2 (Scheme 1). Based on the preliminary
results (Table 1), the following reactions were performed
with 5 mol % of Pd(TFA)2 and 10 mol % of a box ligand
Table 1. Cyclization–carbonylation of 1: preliminary experiments (Scheme 1)a
Entry
Catalyst
Ligand
Condition
Yield (%)
% ee (config.)
1
2
3
4
5
6
7
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(CH3CN)4(BF4)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
[PdCl2-14] 5 mol %
[PdH2O(TFA)2-14] 5 mol %
4
5
6
7
ꢁ30 ꢀC, 20 h
ꢁ15 ꢀC, 20 h
ꢁ30 to ꢁ10 ꢀC, 60 h
rt, 72 h
98
99
81
15
90
85
94
86
90e
26
35
82
81
65 (S)
0
0
0
4
None
4
4
4
0 ꢀC, 2.5 h
57 (S)
0
rt, 24 h
ꢁ30 to ꢁ10 ꢀC, 48 h
ꢁ10 ꢀC, 48 h
ꢁ15 ꢀC, 20 h
rt, 48 h
63 (S)
52 (S)
60 (S)
35 (S)
0
8b
9c
10d
11
12
13
4
13
ꢁ10 ꢀC, 40 h
ꢁ30 ꢀC, 41 h
rt, 48 h
2 (S)
11 (S)
a
Reactions were performed with 5 mol % of Pd-cat. and 10 mol % of ligand in MeOH.
CH2Cl2/MeOH¼10/1 was used as a solvent.
i-PrOH was used as a solvent.
b
c
d
e
THF/MeOH¼10/1 was used as a solvent.
i-Pr ester 3 was obtained.
O
PPh2
PPh2
O
4 : R = Ph
5 : R = i-Pr
6 : R = Bn
7 : R = t-Bu
NMe2
Me
5
PPh2
PPh2
5
Fe
N
N
4
4
R
R
Ligands
(S)-(R)-DPPFA 14
13

9990
K. Kato et al. / Tetrahedron 62 (2006) 9988–9999
(Part A)
R
O
R
O
O
O
S
O
O
S
S
S
O
O
N
N
N
O
O
O
O
N
R
N
R
Ph
Ph
N
N
N
N
4 : R = Me
15 : R = H
16 : R = Et
S
R
R
S
Ph
Ph
Ph
Ph
Ph
Ph
17
18
19
O
O
O
S
S
Ph
Ph
Ph
Ph
O
N
N
N
N
N
S
R
S
O
O
N
Ph
R
S
N
Ph
S
N
N
S
O
S
S
S
O
i-Pr
i-Pr
20
21
22
23
(Part B)
1
R1
R
R1
R3
R2
R2
O
O
O
5
R2
R3
O
5
O
O
S
5
S
5
R2
N
N
R1
N
N
S
S
N
N
R
R
R
4
4
4
4
Ph
Ph
R
Ph
Ph
24 : R1 = Ph, R2 = H
26 : R1 = H, R2 = H, R3 = Ph
28
25 : R1 = H, R2 = Ph
27 : R1 = Me, R2 = R3 = Me
(Part C)
29 : Ar = 4-MeOPh
30 : Ar = 4-CF3Ph
31 : Ar = 1-naphthyl
33 : Ar = 2-naphthyl
O
O
O
O
32 : Ar = 4-tert-BuPh
N
N
N
N
R
R
S
S
Ar
Ar
Ar
Ar
Figure 1. Screening of ligands. (Part A): spacers of two bisoxazoline rings; (Part B): substituents of C5 position on bisoxazoline rings; and (Part C): aromatic
substituents at the C4 position of the bisoxazoline rings.
selectivity (entry 15). Next, the aromatic substituent at the
C4 position of the bisoxazoline ring was investigated
(Fig. 1, Part C; Table 2, entries 16–21; Scheme 1). The selec-
tivity was slightly decreased by replacing the phenyl group
of 4 with a 4-methoxyphenyl, 4-trifluoromethylphenyl, and
4-tert-butylphenyl group (entries 16, 17, and 19). Remark-
able electronic or steric effects on the phenyl ring were not
observed. 2-Naphthyl ligand 33 clearly resulted in the best
enantioselectivity, whereas in the presence of 1-naphthyl li-
gand 31, the product was formed with good yield but a slight
decrease in enantioselectivity (entries 18, 20, and 21).
2.3. Design and synthesis of 2,20-isopropylidene-
bis[(4S,5R)-4,5-di(2-naphthyl)-2-oxazoline] 34
Table 2. Cyclization–carbonylation of 1: ligand screening (Scheme 1;
Fig. 1)a
Entry Ligand Condition
Yield (%) % ee (config.)
In recent years, many kinds of complex box ligands bearing
an additional substituent at the C5 position of both oxazoline
rings have been investigated.13 Based on ligand screening
experiments (Fig. 1, Parts A–C), a new class of substituted
aryl box ligand was designed and synthesized. As a spacer
of two box rings, the dimethylmethylene group seems to
be appropriate (Part A). As an aromatic substituent on the
C4 and C5 positions with cis relationship (Part B), the
2-naphthyl group seems to be effective for the present
reaction (Part C). As a hybrid of ligands 4, 25, and 33, cis-
4,5-di(2-naphthyl)-box ligand 34 was designed and synthe-
sized (Fig. 3). Optically active diol 35 prepared by the
known method14 was treated with thionyl chloride to form
a cyclic sulfite, which was subsequently opened by the
azide ion to afford 36.13a The ee of 36 could be fortified to
>99% ee by a single recrystallization. Reduction of 36
followed by condensation with dimethylmalonyl dichloride
afforded the corresponding diamide, which was subjected
to dehydrative cyclization to afford desired ligand 34
(Scheme 3).
1
2
3
4
5
6
7
8
4
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
33
ꢁ30 ꢀC, 20 h
0 ꢀC–rt, 48 h
ꢁ30 ꢀC, 66 h
ꢁ10 ꢀC, 24 h
rt, 24 h
98
48
72
8
65 (S)
29 (S)
31 (S)
34 (S)
17 (R)
33 (R)
5 (S)
56 (S)
26 (R)
0
12 (S)
72 (S)
52 (R)
43 (R)
9 (S)
62 (R)
57 (R)
55 (R)
64 (S)
77 (R)
85 (R)
7
rt, 48 h
rt, 24 h
88
88
67
93
93
93
99
30
72
75
98
99
ꢁ10 ꢀC, 40 h
ꢁ30 ꢀC, 68 h
ꢁ30 ꢀC, 68 h
ꢁ30 ꢀC, 30 h
ꢁ30 ꢀC, 72 h
0 ꢀC–rt, 24 h
ꢁ30 ꢀC, 96 h
ꢁ30 ꢀC, 48 h
ꢁ30 ꢀC, 43 h
ꢁ30 ꢀC, 16 h
9
10
11
12
13
14
15
16
17
18
19
20
21
ꢁ30 to ꢁ20 ꢀC, 96 h 99
ꢁ30 ꢀC, 48 h
ꢁ30 ꢀC, 19 h
ꢁ50 ꢀC, 5 days
99
99
68
a
All reactions were performed with 5 mol % of Pd(TFA)2 and 10 mol % of
ligand in MeOH.

K. Kato et al. / Tetrahedron 62 (2006) 9988–9999
9991
Figure 2. X-ray structure of [Pd(TFA)2((S,S)-4)] (up) and [Pd(TFA)2((R,R)-16)] (down).
2.4. Cyclization–carbonylation of 1a–c using 2,20-iso-
propylidenebis[(4S,5R)-4,5-di(2-naphthyl)-2-oxazoline]
ligand 34
use of cis-4,5-di(2-naphthyl)-box ligand 34 resulted in in-
creased yield (entries 1 and 2). The selectivity was slightly
increased by replacing the methyl group of the substrate
Next, we applied 34 in the cyclization–carbonylation of
1a–c (Table 3; Scheme 4). Compared with the reaction using
mono-2-naphthyl ligand 33 (Table 2, entries 20 and 21), the
Table 3. Cyclization–carbonylation of 1, 12, and 13 using 2,20-isopropyl-
idenebis[(4S,5R)-4,5-di(2-naphthyl)-2-oxazoline] ligand 34
Entry R
Product Condition
Yield (%) % ee (config.)
1
Me 2a
Me 2a
ꢁ50 to ꢁ30 ꢀC, 4 days 94
85 (S)
86 (S)
92 (S)
91 (S)
95 (S)
O
O
O
O
R
2a
3b
4
ꢁ55 to ꢁ50 ꢀC, 6 days 100
O
O
R
R
R
Ar
Ph
+
Ar
Ph
ꢁ50 to ꢁ40 ꢀC, 5 days 71
N
N
N
N
N
N
S
Pr
Pr
2b
2b
R
R
S
ꢁ40 ꢀC, 3 days
79
S
S
Ar
33
34
Ar
25
Ar
Ar
Ar = 2-Naphthyl
Ph
Ph
5
Allyl 2c
ꢁ50 to ꢁ40 ꢀC, 5 days 81
Ph-box 4
a
Pd(TFA)2/34¼10 mol %/15 mol %.
b
Pd(TFA)2/34¼5 mol %/5 mol %.
Figure 3. Design of cis-di-2-napthyl ligand.
LiAlH4 in THF
1) SOCl2, Et3N in CH2Cl2
2) NaN3 in DMF
35
H2N
OH
OH
OH
N3
HO
37
36
98%
67%(>99% ee)
O
O
O
O
HO
OH
R
R
Cl
Cl
N
N
Bu2SnCl2
xylene
refluxed for 3d
N
O O
Et3N
CH2Cl2
N
S
S
34
72%
Scheme 3.

9992
K. Kato et al. / Tetrahedron 62 (2006) 9988–9999
Pd(OCOCF3)2 (5 mol %)
HO
OH
R
Ligand 34 (10 mol %)
R
CO2Me
p-benzoquinone (1.1equiv.)
CO balloon, MeOH
S
O
OH
1a : R = Me, 1b : R = Propyl, 1c : R = Allyl
2a : R = Me, 2b : R = Propyl
2c : R = Allyl
H2 / Pd-ene, 97%
Scheme 4.
1a with a propyl and an allyl group (entries 3–5). The equi-
molar mixture of Pd(TFA)2 and 34 gave almost the same re-
sult with the use of 1:2 ratio (entries 3 and 4). The structure
of the products 2a and 2b was determined by X-ray crystal-
lographic analysis and modified Mosher’s method.15 The
structure of the product 2c was determined by conversion
of 2c to 2b.
gel. The fraction eluted with hexane/ethyl acetate (9/1)
afforded 8a–c.
4.2.1.1.
2-Methyl-2-(2-propynyl)-1,3-cyclohexane-
dione (8a). Yield (86%).8
4.2.1.2.
2-Propyl-2-(2-propynyl)-1,3-cyclohexane-
1
dione (8b). Colorless oil. Yield (86%). H NMR (CDCl3)
d 0.86 (3H, t, J¼7.2 Hz), 1.10–1.19 (2H, m), 1.73–1.77
(2H, m), 1.90–2.10 (2H, m), 1.96 (1H, t, J¼2.8 Hz), 2.61–
2.75 (4H, m), 2.61 (2H, d, J¼2.8 Hz); 13C NMR (CDCl3)
d 14.3, 16.9, 18.2, 23.5, 39.4, 39.6, 68.1, 70.4, 80.0, 209.4;
IR (KBr)¼3282, 2964, 2120, 1697 cmꢁ1; HRMS-EI m/z:
[M+] calcd for C12H16O2 192.1150; found 192.1153.
3. Conclusion
The oxidative cyclization–carbonylation of meso-2-alkyl-2-
propargylcyclohexane-1,3-diols mediated by Pd(II) with
chiral bisoxazoline (box ligands) afforded bicyclic-b-alkoxy-
acrylates. Based on a ligand screening, 2,20-isopropylidene-
bis[(4S,5R)-4,5-di(2-naphthyl)-2-oxazoline] ligand 34 has
been developed. The products with a chiral quaternary car-
bon were obtained in 71–100% yields with 85–95% ee.
4.2.1.3. 2-(2-Propenyl)-2-(2-propynyl)-1,3-cyclohex-
anedione (8c). Colorless oil. Yield (74%). 1H NMR
(CDCl3) d 1.86–2.04 (2H, m), 1.92 (1H, t, J¼2.8 Hz), 2.45
(2H, d, J¼7.6 Hz), 2.55–2.67 (4H, m), 2.57 (2H, d,
J¼2.8 Hz), 5.00–5.06 (2H, m), 5.43–5.53 (1H, m); 13C
NMR (CDCl3) d 16.5, 23.9, 39.6, 41.4, 67.4, 70.7, 80.4,
120.2, 131.3, 208.9; IR (KBr)¼3282, 2925, 2120,
1698 cmꢁ1. Anal. calcd for C12H14O2: C, 75.76; H, 7.42.
Found: C, 75.35; H, 7.46; HRMS-EI m/z: [M+] calcd for
C12H14O2 190.0994; found 190.0991.
4. Experimental
4.1. General experimental methods
All melting points were measured on a Yanaco MP-3S micro
melting point apparatus and are uncorrected. 1H, 13C NMR,
COSY, HMQC, and HMBC spectra were recorded on JEOL
AL 400 and JEOL Lambda 500 spectrometers in CDCl3 with
Me4Si as an internal reference. In the case of acetone-d6, sol-
vent peak was used as a reference (d 2.04 for 1H and d 29.8
for 13C). High-resolution mass spectra (HRMS) and the fast
atom bombardment mass spectra (FABMS) were obtained
with a JEOL JMS 600 H (HRMS), a JMS-SX102 (HRMS)
and a JEOL GC mate II (FABMS), respectively. IR spectra
were recorded with a JASCO FT/IR-300 spectrometer. All
reagents were purchased from commercial sources and
used without purification. All evaporations were performed
under reduced pressure. For column chromatography, silica
gel (Kieselgel 60) was employed.
4.2.2. Preparation of 9a–c. Compounds 9a–c was prepared
according to reported procedure. Bourgeois et al. reported
that 9a crystallized out of the reaction mixture, and it was
obtained in 84% yield by recycling the mother liquors (three
cycles).9 We performed only one cycle of the reaction. The
crude product was purified by column chromatography on
silica gel. The fraction eluted with hexane/ethyl acetate
(20/1) afforded 9a–c together with recovered 8a–c (40–56%).
4.2.2.1. 3,3,7-Trimethyl-7-(2-propynyl)-1,5-dioxaspiro-
[5.5]undecan-8-one (9a). Yield (51%).9
4.2.2.2. 3,3-Dimethyl-7-(2-propyl)-7-(2-propynyl)-1,5-
dioxaspiro[5.5]undecan-8-one (9b). Colorless needles.
Mp 103 ꢀC (hexane), 44% yield. 1H NMR (CDCl3) d
0.73 (3H, s), 0.86–1.01 (4H, m), 1.23 (3H, s), 1.44–1.59
(2H, m), 1.71–1.93 (3H, m), 1.89 (1H, t, J¼2.4 Hz), 2.10–
2.18 (1H, m), 2.28–2.33 (1H, m), 2.42–2.51 (1H, m), 2.61–
2.71 (1H, m), 2.87 (2H, d, J¼2.4 Hz), 3.33 (1H, dd, J¼2.4,
11.2 Hz), 3.40 (1H, dd, J¼2.4, 11.6 Hz), 3.55 (1H, d,
J¼11.6 Hz), 3.70 (1H, d, J¼11.2 Hz); 13C NMR (CDCl3)
d 14.8, 16.2, 17.3, 18.8, 21.0, 22.5, 23.5, 29.7, 34.1, 37.3,
61.1, 68.6, 69.9, 70.3, 83.6, 102.8, 209.9; IR (KBr)¼3276,
2960, 2871, 2120, 1713 cmꢁ1; HRMS-EI m/z: [M+] calcd
for C17H26O3 278.1882; found 278.1874.
4.2. Preparation of substrates
4.2.1. Preparation of 8a–c. Compounds 8a–c were
prepared from the corresponding 2-alkyl-1,3-cyclohexane-
diones. (8a8 from commercially available 2-methyl-1,3-
cyclohexanedione, 8b and 8c from 2-allyl-1,3-cyclohexane-
dione16 and 2-propyl-1,3-cyclohexanedione16).
To a solution of 2-alkyl-1,3-cyclohexanedione (100 mmol)
and t-BuOK (100 mmol) in DMSO (250 mL) was added
propargyl bromide (100 mmol) at 0 ꢀC. After being stirred
at room temperature for 12 h, the reaction mixture was
diluted with water and extracted with EtOAc. The organic
solution was dried (MgSO4) and concentrated. The crude
product was purified by column chromatography on silica
4.2.2.3. 3,3-Dimethyl-7-(2-propenyl)-7-(2-propynyl)-
1,5-dioxaspiro[5.5]undecan-8-one (9c). Colorless needles.

K. Kato et al. / Tetrahedron 62 (2006) 9988–9999
9993
1
Mp 62 ꢀC (hexane), 34% yield. H NMR (CDCl3) d 0.73
(5H, m), 4.10 (1H, dd, J¼4.0, 9.6 Hz), 5.04–5.14 (2H, m),
5.49–5.60 (1H, m); 13C NMR (CDCl3) d 20.3, 22.2, 28.7,
33.8, 38.0, 57.6, 71.9, 75.4, 81.5, 119.0, 132.2, 210.2; IR
(KBr)¼3517, 3291, 2120, 1701 cmꢁ1; HRMS-EI m/z:
[M+] calcd for C12H16O2 192.1150; found 192.1155.
(3H, s), 1.22 (3H, s), 1.53–1.81 (2H, m), 1.93 (1H, t, J¼
2.8 Hz), 1.98–2.06 (1H, m), 2.33–2.63 (4H, m), 2.81 (2H,
d, J¼2.8 Hz), 2.92 (1H, dd, J¼6.8, 14.4 Hz), 3.34 (1H, dd,
J¼2.4, 11.2 Hz), 3.39 (1H, dd, J¼2.4, 11.2 Hz), 3.59 (1H,
d, J¼11.2 Hz), 3.69 (1H, d, J¼11.2 Hz), 5.02–5.05 (1H,
m), 5.13–5.17 (1H, m), 5.73–5.84 (1H, m); 13C NMR
(CDCl3) d 17.7, 18.8, 21.1, 22.4, 23.6, 29.7, 35.6, 37.7,
60.9, 69.5, 70.0, 70.2, 82.9, 102.5, 118.0, 133.6, 208.9; IR
(KBr)¼3270, 2964, 2872, 2120, 1713 cmꢁ1; HRMS-EI
m/z: [M+] calcd for C17H24O3 276.1726; found 276.1723.
4.2.3.5. (2SR,3SR)-3-Hydroxy-2-(2-propenyl)-(2-pro-
pynyl)cyclohexanone (diastereomer of 10c). Colorless
oil. Yield (37%). H NMR (CDCl3) d 1.84–1.92 (3H, m),
1
2.02 (1H, t, J¼2.8 Hz), 2.08–2.16 (2H, m), 2.32–2.38 (1H,
m), 2.44–2.59 (4H, m), 2.62–2.68 (1H, m), 4.28 (1H, br s),
5.07–5.17 (2H, m), 5.49–5.59 (1H, m); 13C NMR (CDCl3)
d 19.4, 20.7, 27.8, 37.4, 38.4, 56.1, 71.2, 74.0, 80.7, 118.9,
4.2.3. Preparation of 10a–c. To a suspension of LiAlH4
(6 mmol) in toluene (50 mL) was added ketone 9 (3 mmol)
at 0 ꢀC. The mixture was heated for 4 h and then cooled
to 0 ꢀC, and treated with MeOH (4 mL, added carefully).
The mixture was diluted with water (10 mL) and EtOAc
(50 mL). After being stirred for 3 h, the mixture was
filtered through a pad of Celite and concentrated in vacuo.
A solution of the crude product in MeOH (15 mL) and
aqueous 10% HCl (8 mL) was stirred for 3 h, and diluted
with brine (40 mL) and EtOAc (50 mL). The organic layers
were separated, the aqueous layer was extracted with EtOAc
(40 mL), and the combined organic layers were washed with
brine (50 mL), then concentrated in vacuo and dried with
MgSO4. The crude product was purified by column chroma-
tography on silica gel. The fraction eluted with hexane/ethyl
acetate (13/1 to 10/1) afforded 10a–c (more polar) and dia-
stereomers (less polar).
131.9, 211.6; IR (KBr)¼3518, 3292, 2120, 1701 cmꢁ1
;
HRMS-EI m/z: [M+] calcd for C12H16O2 192.1150; found
192.1163.
4.2.4. Preparation of 11a–c. To a solution of 10a–c
(30 mmol) in DMF (15 mL) was added imidazole
(30 mmol) and TBDMSCl (35 mmol), and the mixture was
stirred for 24 h. The mixture was diluted with water
(100 mL) and EtOAc (50 mL). The organic layers were
separated, the aqueous layer was extracted with EtOAc
(40 mL), and the combined organic layers were washed
with brine (50 mL), then dried with MgSO4, and concen-
trated in vacuo. The crude product was purified by column
chromatography on silica gel. The fraction eluted with
hexane/ethyl acetate (80/1) afforded 11a–c.
4.2.4.1. (2RS,3SR)-3-[(1,1-Dimethylethyl)dimethyl-
silyl]oxy-2-methyl-2-(2-propynyl)cyclohexanone (11a).
Colorless oil. Yield (95%). H NMR (CDCl3) d 0.09 (3H,
4.2.3.1. (2SR,3SR)-3-Hydroxy-2-methyl-2-(2-propy-
nyl)cyclohexanone (10a) and (2SR,3RS)-3-hydroxy-2-
methyl-2-(2-propynyl)cyclohexanone (diastereomer of
10a). Compound 10a and its diastereomer were obtained
in 56 and 42% yields, respectively.9
1
s), 0.10 (3H, s), 0.89 (9H, s), 1.12 (3H, s), 1.53–1.63 (1H,
m), 1.75–1.85 (1H, m), 1.90–1.97 (2H, m), 1.98 (1H, t,
J¼2.6 Hz), 2.29 (1H, dd, J¼2.6, 16.4 Hz), 2.29–2.35 (1H,
m), 2.38–2.46 (1H, m), 2.57 (1H, dd, J¼2.6, 16.4 Hz),
4.09 (1H, dd, J¼3.8, 9.4 Hz); 13C NMR (CDCl3) d ꢁ5.0,
ꢁ4.2, 18.0, 18.3, 19.8, 24.7, 25.8, 29.6, 37.3, 55.2, 70.5,
73.9, 81.4, 211.9; IR (neat)¼3305, 2947, 2118,
1712 cmꢁ1; FABMS m/z: 281 (M++H); HRMS-CI m/z:
[M++H] calcd for C16H29O2Si 281.1937; found 281.1911.
4.2.3.2. (2RS,3SR)-3-Hydroxy-2-propyl-2-(2-propy-
nyl)cyclohexanone (10b). Colorless needles. Mp 68 ꢀC
(hexane/EtOAc), 46% yield. 1H NMR (CDCl3) d 0.87–
0.99 (4H, m), 1.15–1.29 (1H, m), 1.47–1.60 (1H, m),
1.72–1.99 (5H, m), 2.10 (1H, t, J¼2.8 Hz), 2.27–2.46 (3H,
m), 2.57 (1H, dd, J¼2.8, 17.2 Hz), 2.62 (1H, dd, J¼2.8,
17.2 Hz), 4.09 (1H, t, J¼8.0 Hz); 13C NMR (CDCl3)
d 14.7, 16.5, 20.4, 21.9, 28.8, 31.2, 37.9, 58.0, 71.8, 76.2,
82.2, 211.0; IR (KBr)¼3392, 3271, 2958, 2120,
1699 cmꢁ1; HRMS-EI m/z: [M+] calcd for C12H18O2
194.1307; found 194.1317.
4.2.4.2. (2RS,3SR)-3-[(1,1-Dimethylethyl)dimethyl-
silyl]oxy-2-propyl-2-(2-propynyl)cyclohexanone (11b).
Colorless oil. Yield (82%). H NMR (CDCl3) d 0.11 (3H,
1
s), 0.12 (3H, s), 0.86–0.98 (12H, m), 1.14–1.22 (1H, m),
1.47–1.73 (4H, m), 1.87–1.94 (3H, m), 1.97 (1H, t,
J¼2.8 Hz), 2.17 (1H, dd, J¼2.8, 16.4 Hz), 2.29–2.33 (2H,
m), 2.78 (1H, dd, J¼2.8, 16.4 Hz), 4.18–4.21 (1H, m); 13C
NMR (CDCl3) d ꢁ5.0, ꢁ4.2, 14.8, 16.5, 18.1, 19.8, 21.5,
25.8, 29.6, 32.9, 38.0, 58.9, 70.5, 73.7, 82.1, 210.8; IR
(KBr)¼3311, 2956, 2120, 1711; HRMS-EI m/z: [M+] calcd
for C18H32O2Si 308.2172; found 308.2177.
4.2.3.3. (2SR,3SR)-3-Hydroxy-2-propyl-2-(2-propy-
nyl)cyclohexanone (diastereomer of 10b). Colorless oil.
Yield (31%). 1H NMR (CDCl3) d 0.89–0.96 (4H, m),
1.24–1.34 (1H, m), 1.64–1.91 (6H, m), 1.99 (1H, t,
J¼2.8 Hz), 2.07–2.32 (3H, m), 2.43–2.52 (1H, m), 2.55–
2.69 (2H, m), 4.27 (1H, br s); 13C NMR (CDCl3) d 14.6,
17.0, 18.9, 21.0, 27.8, 35.4, 38.4, 56.2, 70.9, 74.4, 81.1,
4.2.4.3.
(2RS,3SR)-3-[(1,1-Dimethylethyl)dimethyl-
212.8; IR (KBr)¼3506, 3285, 2967, 2120, 1695 cmꢁ1
;
silyl]oxy-2-(2-propenyl)-2-(2-propynyl)cyclohexanone
(11c). Colorless oil. Yield (91%). 1H NMR (CDCl3) d 0.11
(3H, s), 0.13 (3H, s), 0.90 (9H, s), 1.51–1.62 (1H, m),
1.84–1.98 (3H, m), 2.00 (1H, t, J¼2.8 Hz), 2.21 (1H, dd,
J¼2.8, 16.4 Hz), 2.32–2.39 (3H, m), 2.49–2.55 (1H, m),
2.72 (1H, dd, J¼2.8, 16.4 Hz), 4.23 (1H, dd, J¼4.6,
9.6 Hz), 5.03–5.15 (2H, m), 5.51–5.63 (1H, m); 13C NMR
(CDCl3) d ꢁ5.0, ꢁ4.2, 18.1, 19.8, 21.9, 25.8, 29.6, 35.5,
HRMS-EI m/z: [M+] calcd for C12H18O2 194.1307; found
194.1304.
4.2.3.4. (2RS,3SR)-3-Hydroxy-2-(2-propenyl)-(2-pro-
pynyl)cyclohexanone (10c). Colorless oil. Yield (37%).
1H NMR (CDCl3) d 1.51–1.62 (1H, m), 1.85–2.00 (3H,
m), 2.07 (1H, t, J¼2.8 Hz), 2.28–2.44 (2H, m), 2.51–2.64

9994
K. Kato et al. / Tetrahedron 62 (2006) 9988–9999
38.2, 58.6, 70.7, 73.6, 81.6, 118.6, 132.8, 209.9; IR
(KBr)¼3259, 2959, 1704 cmꢁ1; HRMS-FAB m/z: [M++H]
calcd for C18H31O2 307.2093; found 307.2114.
4.2.6.1. (1a,2b,3a)-2-Methyl-2-(2-propynyl)-1,3-cyclo-
hexanediol (1a). Colorless needles. Mp 111 ꢀC (hexane/
EtOAc), 83% yield. H NMR (CDCl3+D2O) d 0.96 (3H,
1
s), 1.26–1.36 (1H, m), 1.44–1.54 (2H, m), 1.68–1.76 (3H,
m), 2.06 (1H, t, J¼2.8 Hz), 2.43 (2H, d, J¼2.8 Hz), 3.67
(2H, dd, J¼3.8, 10.6 Hz); 13C NMR (CDCl3) d 12.2, 19.2,
25.8, 29.5, 43.7, 71.1, 72.8, 81.8; IR (KBr)¼3303, 2938,
2112 cmꢁ1; FABMS m/z: 169 (M++H). Anal. calcd for
C10H16O2: C, 71.39; H, 9.59. Found: C, 71.44; H, 9.62.
4.2.5. Preparation of 12a–c. To a solution of 11a–c
(1.34 mmol) at ꢁ30 ꢀC in MeOH (15 mL) was added
NaBH4 (2.69 mmol), and the mixture was stirred for 1 h at
the same temperature. The mixture was diluted with water
(50 mL) and EtOAc (30 mL). The organic layers were sepa-
rated, the aqueous layer was extracted with EtOAc (30 mL),
and the combined organic layers were dried with MgSO4 and
concentrated in vacuo. The crude product was purified by
column chromatography on silica gel. The fraction eluted
with hexane/ethyl acetate (60/1 to 50/1) afforded 12a–c.
4.2.6.2. (1a,2b,3a)-2-Propyl-2-(2-propynyl)-1,3-cyclo-
hexanediol (1b). Colorless oil. Yield (90%). 1H NMR
(CDCl3) d 0.95 (3H, t, J¼7.2 Hz), 1.31–1.41 (3H, m),
1.62–1.73 (6H, m), 1.83–1.92 (1H, m), 1.98 (1H, t,
J¼2.8 Hz), 2.28 (2H, d, J¼2.8 Hz), 2.54 (2H, br), 3.75
(2H, br); 13C NMR (CDCl3) d 15.0, 16.1, 22.5, 28.5, 32.2,
42.5, 70.8, 72.6, 80.7; IR (KBr)¼3359, 3305, 2947,
2115 cmꢁ1; HRMS-FAB m/z: [M++H] calcd for C12H21O2
197.1542; found 197.1530.
4.2.5.1. (1a,2b,3a)-3-(1,1-Dimethylethyl)dimethylsilyl-
oxy-2-methyl-2-(2-propynyl)cyclohexanol (12a). Color-
less needles. Mp 66 ꢀC (hexane), 91% yield. 1H NMR
(CDCl3) d 0.06 (3H, s), 0.10 (3H, s), 0.90 (9H, s), 0.95
(3H, s), 1.24–1.33 (1H, m), 1.42–1.75 (5H, m), 2.02 (1H,
t, J¼2.8 Hz), 2.29 (1H, dd, J¼2.8, 16.8 Hz), 2.38 (1H, dd,
J¼2.8, 16.8 Hz), 3.65–3.72 (2H, m); 13C NMR (CDCl3)
d ꢁ5.0, ꢁ4.2, 13.8, 18.0, 18.5, 25.8, 25.9, 29.4, 29.7, 43.7,
70.8, 72.7, 73.1, 81.8; IR (neat)¼3307, 2938, 2862,
2115 cmꢁ1; HRMS-EI m/z: [M+] calcd for C16H30O2Si
282.2015; found 282.2003.
4.2.6.3. (1a,2b,3a)-2-(2-Propenyl)-2-(2-propynyl)-1,3-
cyclohexanediol (1c). Colorless needles. Mp 101 ꢀC
(hexane/EtOAc), 72% yield. 1H NMR (CDCl3) d 1.24–
1.44 (1H, m), 1.63–1.77 (4H, m), 1.84–1.95 (1H, m), 2.04
(1H, t, J¼2.8 Hz), 2.36 (2H, d, J¼2.8 Hz), 2.55 (2H, d,
J¼7.2 Hz), 2.71 (2H, br), 3.75 (2H, br), 5.11–5.25 (2H,
m), 5.94–6.04 (1H, m); 13C NMR (CDCl3) d 16.0, 22.7,
28.8, 33.8, 44.0, 71.3, 72.7, 80.8, 118.2, 135.1; IR
(KBr)¼3389, 3080, 2944, 2112 cmꢁ1; FABMS m/z: 195
(M++H). Anal. calcd for C12H18O2: C, 74.19; H, 9.34.
Found: C, 74.19; H, 9.38.
4.2.5.2. (1a,2b,3a)-3-(1,1-Dimethylethyl)dimethyl-
silyloxy-2-(2-propyl)-2-(2-propynyl)cyclohexanol (12b).
Colorless oil. Yield (78%). H NMR (CDCl3) d 0.09 (3H,
1
s), 0.10 (3H, s), 0.92 (9H, s), 0.95 (3H, t, J¼7.2 Hz), 1.26–
1.43 (3H, m), 1.53–1.94 (7H, m), 1.99 (1H, t, J¼2.4 Hz),
2.23 (1H, dd, J¼2.4, 13.2 Hz), 2.29 (1H, dd, J¼2.8,
13.2 Hz), 3.65 (1H, br), 3.86 (1H, br); 13C NMR (CDCl3)
d ꢁ5.2, ꢁ4.5, 15.0, 16.0, 18.0, 22.6, 25.8, 28.5, 28.6, 33.1,
42.7, 70.7, 72.1, 74.3, 80.8; IR (KBr)¼3420, 3310, 2935,
4.3. General procedure for the cyclization–
carbonylation of 1a–c
A 30 mL two-necked round-bottomed flask, containing
a magnetic stirring bar, Pd(TFA)2 (0.015 mmol), ligand
(0.03 mmol), p-benzoquinone (0.33 mmol), and MeOH
(5 mL) was fitted with a rubber septum and a three-way
stopcock connected to a balloon filled with carbon monoxide.
The apparatus was purged with carbon monoxide by pump-
filling via the three-way stopcock. The substrates 1a–c
(0.3 mmol) were added dropwise using MeOH (1 mLꢂ3)
to the stirred mixture via a syringe at ꢁ50 ꢀC. After being
stirred for the period of time at appropriate temperature,
the mixture was diluted with CH2Cl2 (30 mL), washed with
5% NaOH aq (40 mL), and dried over MgSO4. The organic
layers were separated, the aqueous layer was extracted with
CH2Cl2 (30 mL), and the combined organic layers were dried
with MgSO4 and concentrated in vacuo. The crude product
was purified by column chromatography on silica gel. The
fraction eluted with hexane/ethyl acetate (6/1 to 4/1) afforded
2a–c. Enantiomeric excess was determined by HPLC using
Chiralcel OC and OD.
2118 cmꢁ1
;
HRMS-FAB m/z: [M++H] calcd for
C18H35O2Si 311.2406; found 311.2399. Anal. calcd for
C18H34O2Si: C, 69.62; H, 11.04. Found: C, 69.24; H, 10.92.
4.2.5.3. (1a,2b,3a)-3-(1,1-Dimethylethyl)dimethylsilyl-
(12c).
oxy-2-(2-propenyl)-2-(2-propynyl)cyclohexanol
1
Colorless oil. Yield (99%). H NMR (CDCl3) d 0.10 (3H,
s), 0.11 (3H, s), 0.92 (9H, s), 1.33–1.41 (1H, m), 1.60–
1.73 (5H, m), 1.84–1.90 (1H, m), 2.02 (1H, t, J¼2.8 Hz),
2.21–2.34 (3H, m), 2.61–2.66 (1H, m), 3.62 (1H, br), 3.90
(1H, br), 5.09–5.21 (2H, m), 5.90–6.00 (1H, m); 13C NMR
(CDCl3) d ꢁ5.1, ꢁ4.4, 15.6, 18.0, 22.5, 25.9, 28.7, 28.8,
34.6, 43.9, 71.1, 71.9, 73.8, 80.9, 118.0, 135.0; IR
(KBr)¼3450, 3310, 2936, 2119 cmꢁ1; HRMS-FAB m/z:
[M++H] calcd for C18H33O2Si 309.2250; found 309.2266.
4.2.6. Preparation of the substrates 1a–c. To a solution of
12a–c (0.9 mmol) in THF (15 mL) was added TBAF (1 M
in THF, 1.87 mL, 1.87 mmol) and the mixture was stirred
for 2 h at room temperature. The mixture was diluted with
brine (40 mL) and EtOAc (50 mL). The organic layers
were separated, the aqueous layer was extracted with EtOAc
(40 mLꢂ3), and the combined organic layers were dried
with MgSO4 and concentrated in vacuo. The crude product
was purified by column chromatography on silica gel. The
fraction eluted with hexane/ethyl acetate (5/1) afforded
1a–c.
4.3.1. Methyl (2E)-[(3aS,4R,7aS)-hexahydro-4-hydroxy-
3a-methyl-2(3H)-benzofuranylidene]acetate (2a). Color-
less needles. Mp 95 ꢀC (hexane/EtOAc), [a]2D8 ꢁ155.5
(c 0.86, CHCl3, 100% ee) (Chiralcel OC, hexane/EtOH¼
20/1, FL¼1 mL minꢁ1
,
tR¼23, 27 min). 1H NMR
(CD3COCD3) d 0.82 (3H, s), 1.28–1.62 (3H, m), 1.67–
1.73 (1H, m), 1.79–1.86 (2H, m), 2.51 (1H, dd, J¼1.2,
16.8 Hz), 3.37 (1H, d, J¼16.8 Hz), 3.59 (3H, s), 3.62–3.68

K. Kato et al. / Tetrahedron 62 (2006) 9988–9999
9995
(2H, m), 5.25 (1H, dd, J¼1.2, 2.4 Hz); 13C NMR
(CD3COCD3) d 11.7, 21.5, 23.5, 30.2, 45.1, 47.0, 50.7,
74.6, 87.0, 91.7, 168.9, 177.0; IR (KBr)¼3464, 1685,
1635 cmꢁ1; FABMS m/z: 227 (M++H). Anal. calcd for
C12H18O4: C, 63.70; H, 8.02. Found: C, 63.55; H, 8.02;
X-ray crystallographic analysis (Fig. 4): X-ray diffraction
data for 2a were collected on a Rigaku AFC-5S four-circle
diffractometer equipped with a graphite crystal and inci-
dent beam monochromator using Mo Ka radiation (l¼
method17 and expanded using Fourier techniques. The non-
hydrogen atoms were refined anisotropically. The unit cell
contains two crystallographically independent molecules.
Crystallographic parameters: C24H36F6O8, MW¼452.54,
orthorhombic, space group P212121, with unit cell
5.08 (1H, dd, J¼4.8, 11.2 Hz), 5.39 (1H, dd, J¼1.2,
2.0 Hz), 7.41–7.45 (3H, m), 7.53–7.55 (2H, m) (Fig. 5).
4.3.2. i-Propyl (2E)-[(3aS,4R,7aS)-hexahydro-4-hydroxy-
3a-methyl-2(3H)-benzofuranylidene]acetate (3). Color-
less needles. Mp 103 ꢀC (hexane/EtOAc), [a]2D6 ꢁ84.6
(c 0.63, CHCl3, 60% ee) (Chiralcel OC, hexane/EtOH¼
30/1, FL¼1 mL minꢁ1, tR¼8.1, 11.4 min). 1H NMR
(CD3COCD3) d 0.81 (3H, s), 1.17 (6H, d, J¼6.0 Hz),
1.27–1.61 (3H, m), 1.65–1.85 (3H, m), 2.49 (1H, br d,
J¼17.0 Hz), 3.37 (1H, d, J¼17.0 Hz), 3.62 (1H, dd,
J¼4.0, 12.8 Hz), 3.64 (1H, dd, J¼4.8, 10.8 Hz), 4.93 (1H,
m), 5.16–5.23 (1H, m); 13C NMR (CD3COCD3) d 11.7,
21.5, 22.2, 23.6, 30.3, 45.2, 47.0, 66.5, 74.6, 86.8, 92.6,
168.0, 176.5; IR (KBr)¼3422, 1680, 1629 cmꢁ1; FABMS
m/z: 255 (M++H). Anal. calcd for C14H22O4: C, 66.12; H,
8.72. Found: C, 65.81; H, 8.67.
˚
0.71073 A). The structures were solved by the direct
˚
˚
˚
a¼14.928(6) A, b¼22.930(4) A, c¼7.111(3) A, and
V¼2434(1) A . Z¼4, Dcalcd¼1.606 g cmꢁ3
,
T¼223 K.
3
˚
R1(I>2s(I))¼0.0772, wR2¼0.2553. Refinement using
2260 reflections with F2>ꢁ10.0s(F2), 1028 independent
reflections (R(int)¼0.018), 290 parameters refined on F2.
Crystallographic data (excluding structure factors) for the
structures reported in this paper have been deposited at the
Cambridge Crystallographic Data Centre as supplementary
publication no. 601912.
4.3.3. Methyl (2E)-[(3aS,4R,7aS)-hexahydro-4-hydroxy-
3a-propyl-2(3H)-benzofuranylidene]acetate (2b). Color-
less needles. Mp 139 ꢀC (hexane/EtOAc), [a]2D7 ꢁ182.4
(c 0.98, CHCl3, 92% ee) (Chiralcel OD, hexane/EtOH¼
1
70/1, FL¼1 mL minꢁ1, tR¼26, 30 min). H NMR (CDCl3)
d 0.84 (3H, t, J¼6.8 Hz), 1.19–1.76 (8H, m), 1.85–1.89
(2H, m), 1.95 (1H, br), 2.44 (1H, dd, J¼2.4, 17.2 Hz), 3.52
(1H, dd, J¼3.8, 12.8 Hz), 3.64 (1H, dd, J¼5.4, 10.8 Hz),
3.65 (3H, s), 3.71 (1H, d, J¼17.2 Hz), 5.29 (1H, dd,
J¼1.2, 2.4 Hz); 13C NMR (CDCl3) d 15.5, 18.0, 21.2,
22.3, 29.2, 29.4, 41.3, 48.1, 50.8, 76.9, 87.3, 91.0, 168.9,
(S)-MTPA ester of (3aR,4S,7aR)-2a: 1H NMR (CDCl3) d 0.86
(3H, s), 1.42 (1H, m), 1.54 (1H, m), 1.62 (1H, m), 1.92–1.96
(3H, m), 2.63 (1H, d, J¼17.2 Hz), 3.38 (1H, d, J¼17.2 Hz),
3.54 (3H, d, J¼0.8 Hz), 3.67 (1H, dd, J¼4.0, 11.2 Hz), 3.68
(3H, s), 5.02 (1H, dd, J¼5.6, 11.2 Hz), 5.41 (1H, d,
J¼1.6 Hz), 7.43–7.46 (3H, m), 7.50–7.53 (2H, m). (R)-
175.7; IR (KBr)¼3655, 3468, 2961, 1697, 1633 cmꢁ1
;
HRMS-EI m/z: [M+] calcd for C14H22O4 254.1518; found
254.1521; X-ray crystallographic analysis (Fig. 6): X-ray
diffraction data for 2b were collected on a Bruker SMART
APEX CCD diffractometer equipped with a graphite crystal
and incident beam monochromator using Mo Ka radiation
1
MTPA ester of (3aR,4S,7aR)-2a: H NMR (CDCl3) d 0.81
(3H, s), 1.44 (1H, m), 1.63 (1H, m), 1.69 (1H, m), 1.95–1.99
(3H, m), 2.62 (1H, d, J¼16.8 Hz), 3.29 (1H, d, J¼16.8 Hz),
3.56 (3H, s), 3.67 (1H, dd, J¼4.4, 12.0 Hz), 3.68 (3H, s),
˚
(l¼0.71073 A). The structures were solved by the direct
method (SHELXS 9718) and expanded using Fourier
techniques. The non-hydrogen atoms were refined aniso-
tropically. The unit cell contains two crystallographically
independent molecules. Crystallographic parameters:
C28H44O8, MW¼508.63, monoclinic, space group P21,
˚
˚
with unit cell a¼10.3363(7) A, b¼12.3660(8) A, c¼
ꢀ
ꢀ
ꢀ
˚
10.7419(7) A, a¼90 , b¼102.630(2) , g¼90 , and V¼
1339.79(15) A . Z¼2, Dcalcd¼1.261 g cmꢁ3, T¼223 K.
3
˚
R1(I>2s(I))¼0.0413, wR2¼0.0934, R1(all data)¼0.0554,
wR2¼0.1008, 5292 independent reflections (R(int)¼
0.0222), 331 parameters refined on F2. Crystallographic
data (excluding structure factors) for the structures reported
in this paper have been deposited at the Cambridge Crystal-
lographic Data Centre as supplementary publication no.
601871.
Figure 4. X-ray structure of 2a.
5.41
5.39
H
H
3.68
OMe
3.68
0.86
OMe
0.81
O
1.62
O
Me
1.63
Me
2.62
H
2.63
H
H
3.38
O
1.54
H
O
1.69
R
H
H
R
H
H
H 3.29
3.67
H
Ph
OMe
3.67
H
MeO
Ph
O
H
H
O
H
H
S
H
CF3
R
CF3
H
H
H
H
1.44
O
1.42
O
Figure 5. 1H NMR spectra of MTPA esters of 2a.

9996
K. Kato et al. / Tetrahedron 62 (2006) 9988–9999
diffraction data for [Pd(TFA)2((S,S)-4)] were collected on
a Bruker SMART APEX CCD diffractometer equipped
with a graphite crystal and incident beam monochromator
˚
using Mo Ka radiation (l¼0.71073 A). The structures
were solved by the Patterson method19 and expanded using
Fourier techniques.20 The non-hydrogen atoms were refined
anisotropically. The trifluoromethyl groups were disordered.
Crystallographic parameters: C25H22F6N2O6Pd, MW¼
665.85, trigonal, space group P3121, with unit cell
˚
ꢀ
˚
˚
a¼11.9135(3) A, b¼1ꢀ1.9135(3) A, c¼16.8243(10) A,
3
ꢀ
˚
a¼90 , b¼90 , g¼120 , and V¼2067.98(14) A . Z¼3,
Dcalcd¼1.606 g cmꢁ3
,
T¼223 K.
R1(I>2s(I))¼0.022,
Figure 6. X-ray structure of 2b.
wR2¼0.052, R1(all data)¼0.0360, wR2¼0.1025, 3444 inde-
pendent reflections (R(int)¼0.018), 183 parameters refined
on F2. The flack parameter21 was ꢁ0.01 (2).
4.3.4. Methyl (2E)-[(3aS,4R,7aS)-hexahydro-4-hydroxy-
3a-2-(2-propenyl)-2(3H)-benzofuranylidene]acetate
(2c). Colorless syrup. [a]2D7 ꢁ207.2 (c 0.46, CHCl3, 95% ee)
1
[Pd(TFA)2((R,R)-16)]: H NMR (CD2Cl2) d 1.17 (6H, t,
(Chiralcel OD, hexane/EtOH¼70/1, FL¼0.5 mL minꢁ1
,
J¼7.6 Hz), 2.17–2.31 (4H, m), 4.52 (2H, dd, J¼4.4,
8.8 Hz), 4.87 (2H, dd, J¼8.8, 10.0 Hz), 5.34 (2H, dd,
J¼4.4, 10.0 Hz), 7.24 (4H, d-like), 7.35–7.46 (6H, m);
X-ray crystallographic analysis: X-ray diffraction data for
[Pd(TFA)2((R,R)-16)] were collected on a Rigaku Texsan
CCD diffractometer equipped with a graphite crystal and
incident beam monochromator using Mo Ka radiation
1
tR¼57, 68 min). H NMR (CDCl3) d 1.24–1.44 (1H, m),
1.57–2.05 (7H, m), 2.42–2.52 (2H, m), 3.60 (1H, dd,
J¼3.6, 12.8 Hz), 3.67 (1H, dd, J¼5.2, 10.4 Hz), 3.68 (3H,
s), 3.82 (1H, d, J¼17.2 Hz), 5.05–5.13 (2H, m), 5.36 (1H,
dd, J¼1.2, 2.0 Hz), 5.96–6.06 (1H, m); 13C NMR (CDCl3)
d 21.1, 22.3, 30.0, 31.2, 40.9, 48.7, 50.8, 76.9, 86.8, 92.1,
118.0, 135.4, 168.6, 174.6; IR (KBr)¼3472, 2955, 1688,
1635 cmꢁ1; HRMS-EI m/z: [M+] calcd for C14H20O4
252.1362; found 252.1361. (S)-MTPA ester of 2c: 1H
NMR (CDCl3) d 1.41–1.54 (1H, m), 1.65–1.84 (3H, m),
1.93–2.00 (4H, m), 2.22 (1H, dd, J¼5.2, 14.4 Hz), 2.48
(1H, d, J¼17.2 Hz), 3.47 (1H, d, J¼17.2 Hz), 3.56 (3H, d,
J¼1.2 Hz), 3.67 (3H, s), 3.72 (1H, dd, J¼3.6, 12.8 Hz),
4.66–4.87 (2H, m), 5.10 (1H, dd, J¼5.2, 11.6 Hz), 5.32–
5.42 (2H, m), 7.40–7.55 (5H, m). (R)-MTPA ester of 2c:
1H NMR (CDCl3) d 1.43–1.73 (3H, m), 1.92–1.97 (4H,
m), 2.27 (1H, dd, J¼6.0, 14.4 Hz), 2.48 (1H, d,
J¼17.2 Hz), 3.53 (3H, br s), 3.67 (1H, d, J¼17.2 Hz), 3.67
(3H, s), 3.73 (1H, dd, J¼3.3, 12.8 Hz), 4.84–4.88 (2H, m),
5.04 (1H, dd, J¼4.8, 10.8 Hz), 5.36 (1H, d, J¼2.0 Hz),
5.53–5.63 (1H, m), 7.42–7.52 (6H, m).
˚
(l¼0.71073 A). Measurement was carried out at a liquid ni-
trogen temperature. The structures were solved by the direct
method (SIR92) and DIRDIF94. The non-hydrogen atoms
were refined isotropically. The crystal contains four crystal-
lographically independent molecules and one of CF3
exhibited to be disordered. An ORTEP diagram is shown in
Figure 2. Crystallographic parameters: C27H26F6N2O6Pd,
MW¼694.92, orthorhombic, space group P21P21P21,
˚
˚
with unit cell a¼11.1799(4) A, b¼11.8974(5) A,
3
˚
˚
c¼20.6063(9) A, and V¼2740.9(2) A . Z¼4, Dcalcd
¼
1.684 g cmꢁ3, T¼93 K, l (Mo Ka)¼0.71073 A. R¼0.062,
wR¼0.109, R1¼0.037 for I>2s, 27,325 independent reflec-
tions, 379 parameters refined on F2.
˚
4.5. Synthesis of [((S,R)-BPPFA)Pd(H2O)]2D(OTf)2
4.3.5. Hydrogenation of 2c (95% ee). To a solution of
2c (27 mg, 0.108 mmol) in MeOH (3 mL) was added Pd/C
ethylenediamine complex (20 mg). The apparatus was
purged with hydrogen. After being stirred for 48 h, the mix-
ture was filtered through a pad of Celite and concentrated
in vacuo. The crude product was purified by column chroma-
tography on silica gel. The fraction eluted with hexane/ethyl
acetate (5/1) afforded 2b in 97% yield. Compound 2b (95%
ee): [a]2D6 ꢁ192.2 (c 0.84, CHCl3).
To
a
solution of 0.44 g (0.55 mmol) of [((S,R)-
BPPFA)PdCl2]10 in 20 mL CH2Cl2 was added 0.29 g
(1.1 mmol) of AgOTf. The reaction mixture was stirred at
room temperature for 3 h. The precipitate of AgCl was fil-
tered off, the filtrate was concentrated to w3 mL, and then
treated with 20 mL of CHCl3. The dark brown crystals
were filtered off to give 0.48 g (83%) of [((S,R)-BPPFA)Pd-
(H2O)]2+(OTf)2 as two isomers. 31P NMR (CD2Cl2) shows
broad signals for two isomers at d 43.5 and 49.7, 45.9 and
1
49.7. H NMR (CD2Cl2) d 1.62 and 1.68 (3H, d, J¼8 Hz,
4.4. Preparation of [Pd(TFA)2((S,S)-4)]
CH3), 1.91 and 2.03 (3H, br s, NCH3), 2.36 (3H, br s,
NCH3), 4.05, 4.11, 4.72, 4.81, 4.94, 5.13 (7H, all br s, Cp),
5.82 and 6.28 (1H, br m, CH), 7.25–7.90 (20H, m, Ph).
Anal. calcd for C40H39F6FeNO7P2S2: C, 43.36; H, 3.65; N,
1.24; F, 10.06. Found: C, 43.56; H, 3.50; N, 1.37; F, 9.87.
A solution of (S,S)-4 (92 mg, 0.28 mmol) and Pd(TFA)2
(92.2 mg, 0.28 mmol) in CH2Cl2 (15 mL) was stirred at
room temperature for 12 h and concentrated in vacuo to
give an orange powder. The powder was recrystallized
from CH2Cl2/hexane to give [Pd(TFA)2((S,S)-4)].
4.6. Synthesis of cis-4,5-di(2-naphthyl)-box ligand 34
1H NMR (CD2Cl2) d 1.91 (6H, s), 4.48 (2H, dd, J¼4.4,
9.6 Hz), 4.85 (2H, t, J¼9.6 Hz), 5.23 (2H, dd, J¼4.4,
9.6 Hz), 7.13 (4H, d-like), 7.37–7.46 (6H, m); 13C NMR
(CDCl3) d 25.5, 41.7, 68.0, 77.7, 125.7, 129.2, 129.7,
138.8, 173.0; X-ray crystallographic analysis: X-ray
4.6.1. Preparation of 37. Compound 37 was prepared from
3514 according to the published procedure.13a
4.6.1.1. (1R,2S)-2-Azido-1,2-di(2-naphthyl)ethan-1-ol
(36). Colorless needles. Mp 157 ꢀC (hexane/EtOAc), [a]2D4

K. Kato et al. / Tetrahedron 62 (2006) 9988–9999
9997
+44.0 (c 0.6, CHCl3); 1H NMR (CDCl3) d 2.22 (1H, br), 4.92
(1H, d, J¼6.8 Hz), 5.02 (1H, d, J¼6.8 Hz), 7.35–7.51 (6H,
m), 7.76–7.83 (8H, m); 13C NMR (CDCl3) d 71.4, 77.0,
124.6, 125.1, 126.2, 126.2, 126.5, 126.5, 126.5, 127.7, 127.7,
127.9, 128.1, 128.1, 128.6, 133.0, 133.0, 133.3, 133.4, 133.4,
137.2; IR (KBr)¼3400, 2202, 2098 cmꢁ1. Anal. calcd for
C22H17N3O: C, 77.86; H, 5.05; N, 12.38. Found: C, 78.06;
H, 5.28; N, 12.28; FABMS m/z: 340 (M++H).
4.7.1. (4R,40R)-2,20-(1-Methylethylidene)bis[4,5-dihydro-
4-(p-trifluoromethyl)phenyl] oxazole (30). Colorless
needles. Mp 71 ꢀC (hexane/EtOAc), [a]2D6 +104.5 (c 0.6,
1
CHCl3); H NMR (CDCl3) d 1.69 (6H, s), 4.15 (2H, dd,
J¼7.6, 8.4 Hz), 4.71 (2H, dd, J¼8.4, 10.2 Hz), 5.30
(2H, dd, J¼7.6, 10.2 Hz), 7.39 (4H, d, J¼8.2 Hz), 7.58
(4H, d, J¼8.2 Hz); IR (KBr)¼3410, 2919, 1658, 1330,
1121 cmꢁ1; HRMS-EI m/z: [M+] calcd for C23H20N2O2F6
470.1429; found 470.1428.
4.6.1.2.
(1R,2S)-2-Amino-1,2-di(2-naphthyl)ethan-
1-ol (37). Colorless needles. Mp 216 ꢀC (hexane/EtOAc),
4.7.2. (4S,40S)-2,20-(1-Methylethylidene)bis[4,5-dihydro-
4-(p-tert-butylphenyl)] oxazole (32). Colorless needles.
Mp 140 ꢀC (hexane/EtOAc), [a]D26 +183.4 (c 0.39, CHCl3);
1H NMR (CDCl3) d 1.30 (18H, s), 1.67 (6H, s), 4.18 (2H,
t, J¼8.0 Hz), 4.65 (2H, dd, J¼8.0, 9.6 Hz), 5.20 (2H, dd, J¼
8.0, 9.6 Hz), 7.20 (4H, d, J¼8.4 Hz), 7.35 (4H, d, J¼8.4 Hz);
13C NMR (CDCl3) d 24.5, 31.4, 34.5, 38.9, 69.2, 75.5,
125.6, 126.4, 139.5, 150.5, 170.2; IR (KBr)¼3395, 2957,
1
[a]2D8 ꢁ8.0 (c 0.15, THF); H NMR (DMSO) d 4.25 (1H,
d, J¼6.4 Hz), 4.89 (1H, dd, J¼4.4, 6.4 Hz), 5.47 (1H, d,
J¼4.4 Hz), 7.36–7.49 (6H, m), 7.74–7.86 (8H, m); 13C
NMR (DMSO) d 61.4, 77.6, 125.1, 125.4, 125.5, 125.6,
125.7, 126.0, 126.5, 126.6, 126.8, 127.3, 127.3, 127.4,
127.5, 127.6, 132.0, 132.2, 132.5, 132.6, 140.8, 141.5; IR
(KBr)¼3327, 3268, 3155, 2924, 1591, 1458 cmꢁ1; FABMS
m/z: 314 (M++H). Anal. calcd for C22H19O: C, 84.31; H,
6.11; N, 4.47. Found: C, 81.34; H, 6.19; N, 4.48.
2101, 1648 cmꢁ1
;
HRMS-EI m/z: [M+] calcd for
C29H38N2O2 446.2933; found 446.2944. Anal. calcd for
C29H38N2O2: C, 77.99; H, 8.58; N, 6.27. Found: C, 77.96;
H, 8.62; N, 6.24.
4.6.2. Preparation of (4S,40S,5R,50R)-2,20-(1-methylethyl-
idene)bis[4,5-dihydro-4,5-di-b-naphthyl] oxazole (34).
To a stirred solution of 37 (1 g, 3.19 mmol) and Et3N
(806 mg, 7.98 mmol) in CH2Cl2 (40 mL) at 0 ꢀC under Ar
was slowly added dimethylmalonyl dichloride (263.6 mg,
1.56 mmol), and the mixture was stirred for 2 h at the
same temperature. Volatiles were removed in vacuo and
the resulting solid was washed with water (50 mL). The solid
was collected by filtration and dried in vacuo. The suspen-
sion of the solid in EtOAc (15 mL) was heated, and then
cooled. The crude diamide was collected by filtration and
dried in vacuo. The ligand 34 was prepared according to
the reported procedure.22 The crude diamide dissolved in an-
hydrous xylene (50 mL) was refluxed in a Dean–Stark appa-
ratus with dibutyl tin dichloride (83.0 mg, 0.28 mmol) for 3
days. The solution was washed with satd NaHCO3 aq
(40 mL). The organic layers were separated, the aqueous
layer was extracted with EtOAc (30 mL), and the combined
organic layers were dried with MgSO4 and concentrated in
vacuo. The crude product was purified by column chromato-
graphy on silica gel. The fraction eluted with hexane/ethyl
acetate (3/1) afforded 34 in 74% yield. Colorless needles.
Mp 108 ꢀC (hexane/EtOAc), [a]2D3 ꢁ344.7 (c 1.02,
4.8. NMR experiments for the palladium complexes of
33 and 34
To a stirred solution of 33 or 34 (0.022 mmol) in CD2Cl2
(0.5 mL) was added Pd(TFA)2 (7.3 mg, 0.022 mmol). After
Pd(TFA)2 dissolved completely (ca. 10 h), the NMR spectra
were measured.
[Pd(TFA)2-33]: 1H NMR (CD2Cl2) d 2.00 (6H, s), 4.56 (2H,
dd, J¼4.4, 9.6 Hz), 4.92 (2H, t, J¼9.6 Hz), 5.40 (2H, dd,
J¼4.4, 9.6 Hz), 7.19 (2H, dd, J¼2.0, 8.4 Hz), 7.53–7.58
(4H, m), 7.62 (2H, s), 7.87–7.94 (4H, m), 7.95 (2H, d,
J¼8.4 Hz).
[Pd(TFA)2-34]: 1H NMR (CD2Cl2) d 2.30 (6H, s), 5.79 (2H,
d, J¼9.6 Hz), 6.49 (2H, d, J¼9.6 Hz), 6.86 (2H, dd, J¼1.7,
8.4 Hz), 6.94 (2H, dd, J¼1.6, 8.4 Hz), 7.40–7.49 (10H, m),
7.51 (2H, br s), 7.56 (2H, d, J¼8.4 Hz), 7.63–7.73 (6H,
m), 7.65 (2H, br s), 7.80 (2H, d, J¼7.6 Hz); 13C NMR
(400 MHz, CD2Cl) d 25.9, 42.7, 72.2, 88.8, 123.5, 124.4,
126.8, 126.8, 126.9, 127.0, 127.2, 128.0, 128.1, 128.2,
128.3, 128.7, 129.5, 130.9, 132.7, 133.0, 133.3, 133.4, 173.1.
1
CHCl3); H NMR (CDCl3) d 2.04 (6H, s), 5.86 (2H, d,
J¼7.6 Hz), 6.25 (2H, d, J¼10.0 Hz), 6.99–7.34 (20H, m),
7.41 (2H, d, J¼8.4 Hz), 7.51 (2H, d, J¼7.6 Hz), 7.52 (2H,
d, J¼7.6 Hz), 7.77 (2H, s); 13C NMR (400 MHz, CDCl3)
d 24.8, 39.8, 73.8, 86.8, 124.3, 125.4, 125.4, 125.6, 125.8,
126.0, 126.9, 127.2, 127.4, 127.4, 127.6, 127.8, 127.9,
132.5, 132.6, 132.6, 132.8, 133.5, 135.1, 170.6; IR
(KBr)¼3424, 2927, 1658 cmꢁ1; HRMS-EI m/z: [M+] calcd
for C49H38N2O2 686.2933; found 686.2936.
Acknowledgements
We would like to thank Professor Hiroaki Sasai (ISIR Osaka
University) for helpful discussions. We are grateful for the
financial support of the Eisai Award in Synthetic Organic
Chemistry Japan (2002), Takeda Science Foundation
(2003), and The Research Foundation for Pharmaceutical
Sciences (2002).
4.7. Preparation of 30 and 32
In a similar manner to that described for the preparation of
34. Treatment of (R)-(ꢁ)-2-amino-[p-(trifluoromethyl)phe-
nyl]ethanol23,24a or (S)-(+)-2-amino-(p-tert-butylphenyl)-
ethanol23b with dimethylmalonyl dichloride and Et3N in
CH2Cl2 gave the corresponding diamide. The ligands 30
and 32 were prepared from the corresponding diamide
according to the reported procedure.24
References and notes
1. (a) Tsuji, J. Palladium Reagents and Catalysts; Wiley:
Chichester, UK, 1995; p 19; (b) Stille, J. K. Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon:
Oxford, UK, 1991; Vol. 4, p 913; for recent reviews,

9998
K. Kato et al. / Tetrahedron 62 (2006) 9988–9999
see: (c) Nakamura, I.; Yamamoto, Y. Chem. Rev. 2004,
104, 2127; (d) Zeni, G.; Larock, R. C. Chem. Rev. 2004,
219; (e) Takayama, H.; Kato, K.; Akita, H. Eur. J. Org.
Chem. 2006, 644.
104, 2285; (e) Alonso, F.; Beletskaya, I. P.; Yus, M. Chem.
Rev. 2004, 104, 3079; (f) Tietze, L. F.; Ila, H.; Bell, H. P.
Chem. Rev. 2004, 104, 3453; (g) Soderberg, B. C. G.
Coord. Chem. Rev. 2004, 248, 1085; (h) Vizer, S. A.;
Yerzhanov, K. B.; Quntar, A. A. A. A.; Dembitsky, V. M.
Tetrahedron 2004, 60, 5499; (i) Muzart, J. Tetrahedron
2005, 61, 5955.
8. For 8a, see: Brooks, D. W. J. Org. Chem. 1987, 52, 3223; for
8b and 8c, see: Section 4.
ꢀ
9. Bourgeois, D.; Prunet, J.; Pancrazi, A.; Prange, T.; Lallemand,
J.-Y. Eur. J. Org. Chem. 2000, 4029.
10. Compounds 4, 6, 7, and 13: commercially available. For 5,
see: Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul,
M. M. J. Am. Chem. Soc. 1991, 113, 726; for 14, see:
Hayashi, T.; Konishi, M.; Fukushima, M.; Mise, T.;
Kagotani, M.; Tajika, M.; Kumada, M. J. Am. Chem. Soc.
1982, 104, 180.
2. (a) Hosokawa, T.; Uno, T.; Inui, S.; Murahashi, S.-I. J. Am.
Chem. Soc. 1981, 103, 2318; (b) Hosokawa, T.; Yamanaka,
T.; Itotani, M.; Murahashi, S.-I. J. Org. Chem. 1995, 60,
6159; (c) Ukaji, Y.; Miyamoto, M.; Mikuni, M.; Takeuchi, S.;
Inomata, K. Bull. Chem. Soc. Jpn. 1996, 69, 735; (d) Imada,
Y.; Fujii, M.; Kubota, Y.; Murahashi, S.-I. Tetrahedron Lett.
1997, 38, 8227; (e) Uozumi, Y.; Kato, K.; Hayashi, T. J. Am.
Chem. Soc. 1997, 119, 5063; (f) Okuro, K.; Kai, H.; Alper,
H. Tetrahedron: Asymmetry 1997, 8, 2307; (g) El-qisairi, A.;
Hamed, O.; Henry, P.-M. J. Org. Chem. 1998, 63, 2790; (h)
Arai, M. A.; Kuraishi, M.; Arai, T.; Sasai, H. J. Am. Chem.
Soc. 2001, 123, 2907; (i) El-qisairi, A.; Qaseer, A.-H.; Henry,
M.-P. Tetrahedron Lett. 2002, 43, 4231; (j) Overman, L. E.;
Remarchuk, T. P. J. Am. Chem. Soc. 2002, 124, 12; (k)
Yokota, T.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2002, 67,
5005; (l) Girones, J.; Duran, J.; Polo, A.; Real, J. Chem.
Commun. 2003, 1776; (m) Shinohara, T.; Arai, M. A.;
Wakita, K.; Arai, T.; Sasai, H. Tetrahedron Lett. 2003, 44,
711; (n) Muthiah, C.; Arai, M. A.; Shinohara, T.; Arai, T.;
Takizawa, S.; Sasai, H. Tetrahedron Lett. 2003, 44, 5201; (o)
Trend, R. M.; Ramtohul, Y. K.; Ferreira, E. M.; Stoltz, B. M.
Angew. Chem., Int. Ed. 2003, 42, 2892; (p) Takizawa, S.;
Honda, Y.; Arai, M. A.; Kato, T.; Sasai, H. Heterocycles
2003, 60, 2551; (q) Wakita, K.; Arai, M. A.; Kato, T.;
Shinohara, T.; Sasai, H. Heterocycles 2004, 62, 831; (r) Stahl,
S. S. Angew. Chem., Int. Ed. 2004, 43, 3400; (s) Alper, H.;
Dong, C. Tetrahedron: Asymmetry 2004, 15, 35; (t) Stoltz,
B. M. Chem. Lett. 2004, 33, 362; (u) Hayashi, T.; Yamasaki,
K.; Mimura, M.; Uozumi, Y. J. Am. Chem. Soc. 2004, 126,
3036; (v) Trend, R. M.; Ramtohul, Y. K.; Stoltz, B. M. J. Am.
Chem. Soc. 2005, 127, 17778; (w) Tietze, L. F.; Sommer,
K. M.; Zinngrebe, J.; Stecker, F. Angew. Chem., Int. Ed.
2005, 44, 257.
11. Ozawa, F.; Kubo, A.; Hayashi, T. Chem. Lett. 1992, 2177.
12. (a) Compounds 15, 19, 20, and 26: commercially available; (b)
For 16, see: Sibi, M. P.; Ji, J. J. Org. Chem. 1997, 62, 3800; (c)
For 17 and 18, see: Imai, Y.; Zhang, W.; Nakatsuji, Y.; Ikeda, I.
Tetrahedron: Asymmetry 1996, 7, 2453; Harm, A. M.; Knight,
J. G.; Stemp, G. Synlett 1996, 677; (d) For 21, see: Ref. 2e; for
22 and 23, see: Ref. 3b and Ma, L.; Du, D.-M.; Xu, J. J. Org.
Chem. 2005, 70, 10155; (e) For 24 and 25, see: Desimoni,
G.; Faita, G.; Righetti, P.; Sardone, N. Tetrahedron 1996, 52,
12019; (f) For 27, see: Corey, E. J.; Ishihara, K. Tetrahedron
Lett. 1992, 33, 6807; (g) For 28, see: Davies, I. W.;
Senanayake, C. H.; Larsen, R. D.; Verhoeven, T. R.; Reider,
P. J. Tetrahedron Lett. 1996, 37, 813; (h) For 29, see: Evans,
D. A.; Johnson, J. S.; Olhava, E. J. J. Am. Chem. Soc. 2000,
122, 1635; (i) For 30 and 32, see: Section 4; (j) For 31, see:
Evans, D. A.; Miller, S. J.; Lectka, T.; Von-Matt, P. J. Am.
Chem. Soc. 1999, 121, 7559; (k) For 33, see: Crosignani, S.;
Desimoni, G.; Faita, G.; Righetti, P. P. Tetrahedron 1998, 54,
15721.
13. (a) For 4,5-di(1-naphthyl)-box ligand, see: Hong, S.; Tian, S.;
Metz, M. V.; Marks, T. J. J. Am. Chem. Soc. 2003, 125,
14768; (b) See Ref. 12e; (c) See Ref. 12f; (d) See Ref. 12g;
(e) van Lingen, H. L.; van Delft, F. L.; Storcken, R. P. M.;
Hekking, K. F. W.; Klaassen, A.; Smits, J. J. M.; Ruskowska,
P.; Frelek, J.; Rutjes, F. P. J. T. Eur. J. Org. Chem. 2005,
4975; (f) Le, J. C. D.; Pagenkopf, B. L. Org. Lett. 2004, 6,
4097; (g) Pericas, M. A.; Puigjaner, C.; Riera, A.; Vidal-
Ferran, A.; Gomez, M.; Jimenez, F.; Muller, G.; Rocamora,
M. Chem.—Eur. J. 2002, 8, 4164.
14. Rosini, C.; Scamuzzi, S.; Uccello-Barretta, G.; Salvadori, P.
J. Org. Chem. 1994, 59, 7395.
15. Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. J. Am.
Chem. Soc. 1991, 113, 4092.
16. Stealey, M. A.; Shone, R. L.; Miyano, M. Synth. Commun.
1990, 20, 1869.
17. Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, M.;
Giacovazzo, C.; Guagliardi, A.; Polidori, G. J. Appl.
Crystallogr. 1994, 27, 435.
3. (a) Kato, K.; Tanaka, M.; Yamamoto, Y.; Akita, H. Tetrahedron
Lett. 2002, 43, 1511; (b) Kato, K.; Tanaka, M.; Yamamura, S.;
Yamamoto, Y.; Akita, H. Tetrahedron Lett. 2003, 44, 3089;
Pd(0) catalyzed intramolecular asymmetric hydroamination
of alkynes. Lutete, L. M.; Kadota, I.; Yamamoto, Y. J. Am.
Chem. Soc. 2004, 126, 1622.
4. (a) Kato, K.; Nishimura, A.; Yamamoto, Y.; Akita, H.
Tetrahedron Lett. 2001, 42, 4203; (b) See Ref. 3a.
5. (a) Kato, K.; Yamamoto, Y.; Akita, H. Tetrahedron Lett. 2002,
43, 4915; (b) See Ref. 3b.
18. Sheldrick, G. M. SHELXL97. Program for the Solution for
€
Crystal Structures; University of Gottingen: Gottingen,
€
6. (a) Kato, K.; Yamamoto, Y.; Akita, H. Tetrahedron Lett. 2002,
43, 6587; (b) Kato, K.; Nouchi, H.; Ishikura, K.; Takaishi, S.;
Motodate, S.; Tanaka, H.; Okudaira, K.; Mochida, T.;
Nishigaki, R.; Shigenobu, K.; Akita, H. Tetrahedron 2006, 62,
2545.
7. (a) Kato, K.; Sasaki, T.; Takayama, H.; Akita, H. Tetrahedron
2003, 59, 2679; (b) Sasaki, T.; Kato, K.; Akita, H. Chem.
Pharm. Bull. 2004, 52, 770; (c) Akita, H.; Sasaki, T.; Kato,
K.; Suzuki, Y.; Kondo, K.; Sakagami, Y.; Ojika, M.; Fudou,
R.; Yamanaka, S. Tetrahedron 2004, 60, 4735; (d) Akita, H.;
Sasaki, T.; Takayama, H.; Kato, K. Heterocycles 2005, 66,
Germany, 1997.
19. Beurskens, P. T.; Admiraal, G.; Beurskens, G.; Bosman, W. P.;
Garcia-Granda, S.; Gould, R. O.; Smits, J. M. M.; Smykalla, C.
PATTY. The DIRDIF Program System, Technical Report of
the Crystallography Laboratory; University of Nijmegen:
Nijmegen, The Netherlands, 1992.
20. Beurskens, P. T.; Admiraal, G.; Beurskens, G.; Bosman, W. P.;
de Gelder, R.; Israel, R.; Smits, J. M. M. DIRDIF99. The
DIRDIF-99 Program System, Technical Report of the
Crystallography Laboratory; University of Nijmegen:
Nijmegen, The Netherlands, 1999.

K. Kato et al. / Tetrahedron 62 (2006) 9988–9999
9999
21. Flack, H. D. Acta Crystallogr., Sect. A 1983, 39, 876.
22. Desimoni, G.; Faita, G.; Mella, M. Tetrahedron 1996, 52,
13649.
23. (a) Hirose, K.; Ogasahara, K.; Nishioka, K.; Tobe, Y.;
Naemura, K. J. Chem. Soc., Perkin Trans. 2 2000, 1984;
(b) Kawasaki, K.; Katsuki, T. Tetrahedron 1997, 53,
6337.
24. (a) Kohmura, Y.; Katsuki, T. Tetrahedron Lett. 2000, 41, 3941;
(b) Vorbruggen, H.; Krolikiewicz, K. Tetrahedron Lett. 1981,
22, 4471.