Kinetic resolution of allylic esters in palladium-catalyzed asymmetric allylic alkylations using C-N bond axially chiral aminophosphine ligands

Article abstract of DOI:10.1016/j.tetasy.2008.11.026

Chiral allylic esters, such as (R)-1,3-diphenyl-2-propenyl acetate (R)-2a, were synthesized by kinetic resolution in a palladium-catalyzed asymmetric allylic alkylation using N-aryl indoline type C-N bond axially chiral aminophosphines (S)-1 as ligands.

Full text of DOI:10.1016/j.tetasy.2008.11.026

Tetrahedron: Asymmetry 19 (2008) 2711–2716
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Tetrahedron: Asymmetry
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Kinetic resolution of allylic esters in palladium-catalyzed asymmetric allylic
alkylations using C–N bond axially chiral aminophosphine ligands
*
Takashi Mino , Kazuya Wakui, Shunsuke Oishi, Youtaro Hattori, Masami Sakamoto, Tsutomu Fujita
Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Chiral allylic esters, such as (R)-1,3-diphenyl-2-propenyl acetate (R)-2a, were synthesized by kinetic
resolution in a palladium-catalyzed asymmetric allylic alkylation using N-aryl indoline type C–N bond
axially chiral aminophosphines (S)-1 as ligands.
Received 4 November 2008
Accepted 28 November 2008
Available online 10 January 2009
Ó 2008 Elsevier Ltd. All rights reserved.
2. Results and discussion
1. Introduction
Although we had already reported the synthesis of chiral 3a by
palladium-catalyzed asymmetric allylic alkylation of racemic 1,3-
diphenyl-2-propenyl acetate ( )-2a using chiral aminophosphines
1a–d for 24 h,9a we investigated the kinetic resolution of the
starting material in this reaction. At first, we examined the palla-
dium-catalyzed asymmetric allylic alkylation of racemic 1,3-diphe-
nyl-2-propenyl acetate ( )-2a with 3.0 equiv of dimethyl malonate
(DMM) using chiral aminophosphines (S)-1a in THF for 4 h at 25 °C
(Table 1, entry 1). In this case, the reaction conversion was 19% and
the chiral unreacted allylic acetate (R)-2a was recovered in 17% ee
with the corresponding product (R)-3a (89% ee). A difference in the
rate of reaction for the two enantiomers of the starting material
was observed. The (S)-enantiomer of 2a reacted significantly faster
than the (R)-enantiomer. Next, we investigated the ability of li-
gands (S)-1b–d (entries 3, 5, and 6). Using aminophosphine ligand
(S)-1c, the reaction proceeded in 52% conversion while the unre-
acted chiral allylic acetate (R)-2a was recovered in 69% ee. In this
case, the selectivity factor (S value) was 8.9 (entry 5). Conversely,
(S)-1b and 1d were not effective ligands for this kinetic resolution
(entries 3 and 6). We investigated the effect of reaction time in this
kinetic resolution using aminophosphine ligand (S)-1b (entries 2–
4). The reaction conversion and ee of 2a were increased with long-
er reaction times. On the other hand, the S value decreased while
the ee of product 3a increased. When the reaction conversion
reached 94%, product (R)-3a was obtained in 86% ee and the unre-
acted acetate (R)-2a was recovered in 98% ee, although the S value
was low (entry 4). Next, the effect of the amount of nucleophile
was investigated (entry 5 vs 7). The reaction with 0.6 equiv of
DMM gave (R)-3a in good enantioselectivity (97% ee) with 52%
conversion after 8 h. In this case, the S value was 11.7 and the
enantioselectivity of unreacted acetate (R)-2a was 75% ee. The con-
centration of reaction solvent was also investigated (entries 7, 8,
and 10). The diluted reaction conditions caused the reaction rate
to slow and S value to increase. Changing the amount of catalyst
to 4 mol %, the reactivity and S value were decreased (entry 8 vs
In recent years, palladium-catalyzed allylic alkylation has been
extended to catalytic asymmetric synthesis as a versatile C–C bond
forming tool.1 Among the many chiral ligands designed for this
reaction, chiral P,N-ligands have played an important role owing
to their steric and electronic asymmetry,2,3 such as PHOX ligands,4
binaphthyl-based ligands,5 and the QUINAP-type ligand.6 We re-
cently reported a palladium-catalyzed asymmetric allylic alkyl-
ation using chiral phosphinohydrazones,7 pyrrolidinyl-containing
chiral aminophosphines,8 and N-aryl indoline type C–N bond axi-
ally chiral aminophosphines.9
Although the usual synthetic target is the product from a nucle-
ophilic addition, several reports have recently appeared document-
ing the kinetic resolution of allylic acetates and carbonates over the
course of these reactions.10 Herein, we report the synthesis of chi-
ral allylic esters by the kinetic resolution of racemic allylic esters in
palladium-catalyzed asymmetric allylic alkylation using N-aryl
indoline type C–N bond axially chiral aminophosphines 1.
N
N
R1
R2
PPh2
R1
R2
PPh2
(S)-1
(R)-1
a: R1 = CH2OAc, R2 = H
b: R1 = Me, R2 = H
c: R1 = CF3, R2 = H
d: R1 -R2 = -(CH)4-
* Corresponding author. Tel.: +81 43 290 3385; fax: +81 43 290 3401.
E-mail address: tmino@faculty.chiba-u.jp
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.11.026

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T. Mino et al. / Tetrahedron: Asymmetry 19 (2008) 2711–2716
Table 1
Kinetic resolution in palladium-catalyzed asymmetric allylic alkylation using (S)-1a
DMM
O
O
chiral ligand (S)-1
[Pd(η
3-C3H5)Cl]2
OAc
Ph
OAc
MeO
OMe
+
Ph
Ph
Ph Ph
Ph
BSA, LiOAc
25 °C
( )-2a
(R)-2a
(R)-3a
Entry
Ligand
Time (h)
DMM (equiv)
Solv.
Concn (M)
Convb (%)
ee of (R)-2ac (%)
ee of (R)-3ac (%)
Sd
1
2
3
4
5
6
7
8
(S)-1a
(S)-1b
(S)-1b
(S)-1b
(S)-1c
(S)-1d
(S)-1c
(S)-1c
(S)-1c
(S)-1c
(S)-1c
(S)-1c
(S)-1c
(S)-1c
(S)-1c
(S)-1c
(S)-1c
(S)-1c
(S)-1c
(S)-1c
4
2
4
6
4
4
8
18
24
24
18
18
18
18
18
18
18
48
40
40
3.0
3.0
3.0
3.0
3.0
3.0
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.65
0.7
THF
THF
THF
THF
THF
THF
THF
THF
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.25
0.25
0.125
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
19
26
76
94
52
23
52
54
17
37
60
60
56
54
Trace
Trace
55
17
20
79
98
69
9
75
82
16
48
96
98
89
92
—
—
81
89
73
83
86
94
55
97
96
86
94
86
93
91
95
—
—
89
7.2
4.3
3.5
3.2
8.9
2.0
11.7
13.5
11.3
15.8
17.2
21.4
16.1
23.9
—
9e
10
11
12
13
14
15f
16g
17h
18i
19
20
THF
THF
Et2O
DCM
PhCF3
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
THF
—
12.7
107
14.8
11.2
22
60
71
27
96
95(37)j
99(24)j
95(59)k
94(66)k
a
The reactions were carried out in various solvents at 25 °C with DMM and BSA (3.0 equiv), in the presence of LiOAc (2 mol %) and ligand (S)-1 (10 mol %) and [Pd(g3
-
C3H5)Cl]2 (5 mol %).
b
Determined by 1H NMR.
c
Determined by HPLC analysis using a chiral column (Daicel CHIRALCELÒ OD-H).
d
S = ln[(1 ꢀ C/100)(1 ꢀ ee/100)]/ln[(1 ꢀ C/100)(1 + ee/100)] (C = conversion; ee = ee of 2a).
e
This reaction was carried out using 4 mol % of ligand (S)-1c and 2 mol % of [Pd(g
3-C3H5)Cl]2.
f
g
h
i
This reaction was carried out using 5 mol % of [IrCl(C8H12)]2 instead of [Pd(
This reaction was carried out using 10 mol % of (C7H8)Mo(CO)3 instead of [Pd(
This reaction was carried out at 35 °C.
This reaction was carried out at 5 °C.
Values in parentheses are isolated yields of 2a.
Values in parentheses are isolated yields of 3a.
g
3-C3H5)Cl]2.
3-C3H5)Cl]2.
g
j
k
9). We examined the effect of reaction solvents using chiral amino-
phosphines (S)-1c for 18 h at 25 °C (entries 8, 11–14). When the
reaction was carried out in diethyl ether instead of THF, the S value
was increased to 17.2, but the enantioselectivity of (R)-3a de-
creased to 86% ee (entry 11). When PhMe was used as a solvent,
the reaction conversion was 56% and the chiral unreacted allylic
acetate (R)-2a was recovered in 92% ee (S value = 23.9) with the
corresponding product (R)-3a in 95% ee. We investigated the ki-
netic resolution in iridium and molybdenum-catalyzed asymmet-
ric allylic alkylation. Unfortunately neither reaction proceeded
(entries 15 and 16). We also investigated the effect of reaction tem-
perature. The reaction conversion was increased slightly to 35 °C,
but the S value and the enantioselectivity of (R)-3a decreased (entry
14 vs 17). On the other hand, the reaction was carried out at 5 °C, and
the reaction rate was very slow (entry 18). Using 0.65 equiv of di-
methyl malonate in PhMe, the reaction gave 59% of (R)-3a in 95%
ee and 37% of unreacted (R)-2a in good enantioselectivity (95% ee)
for 40 h (entry 19). Furthermore, when using 0.7 equiv of dimethyl
malonate in THF, unreacted acetate (R)-2a was obtained in 24% with
high enantioselectivity (99% ee) (entry 20).
resolution (S value = 3.8) (entry 3), but the selectivity was low
when using (S)-4 as a ligand (entry 2).
We next attempted the reaction of various allylic esters such as
racemic 1,3-diphenyl-2-propenyl pivalate ( )-2b11 and benzoate
( )-2c12 with DMM and acetate ( )-2a with diethyl malonate in
PhMe for 18 h at 25 °C (Table 3). As shown in entries 2 and 3, the
unreacted chiral pivalate (R)-2b and benzoate (R)-2c10a were recov-
ered with moderate enantioselectivities, and the corresponding
products (R)-3 were obtained with good enantioselectivity. The
reaction with diethyl malonate gave (R)-3b in good enantioselectiv-
ity (94% ee) at 53% conversion. In this case, the S value was 13.8 while
the enantioselectivity of unreacted acetate (R)-2a was 78% ee.
Finally, we suggested the plausible asymmetric induction pro-
cess of the kinetic resolution in palladium-catalyzed asymmetric
allylic alkylation of ( )-2a with DMM using chiral aminophos-
phines (S)-1c as shown in Scheme 1. There are two candidates, A
and B, which are considerable reaction intermediates formed from
palladium complex with chiral ligands (S)-1c. According to the re-
sult, (S)-2a reacted with the chiral palladium complex significantly
faster than (R)-2a. Thus, C was easily formed from A due to the ste-
ric hindrance of the phenyl rings between the allylic substrate and
the ligand. In addition, the nucleophilic attack to C occurs predom-
Under the reaction conditions of 4 mol % of catalyst in THF (Ta-
ble 1, entry 9), we examined the kinetic resolution of ( )-2a in the
palladium-catalyzed asymmetric allylic alkylation using pyrrolidi-
nyl-containing chiral aminophosphine (S)-48 and chiral phos-
phinohydrazone (S)-57 instead of (S)-1c. As shown in Table 2,
chiral hydrazone (S)-5 was a slightly effective ligand for kinetic
inantly at the allyl terminus, trans to the better
p–acceptor
(P > N).13 As a result, the (R)-product 3a was obtained mainly from
(S)-2a, while (R)-2a was recovered in this reaction using the chiral
aminophosphine (S)-1c as a ligand.

T. Mino et al. / Tetrahedron: Asymmetry 19 (2008) 2711–2716
2713
Table 2
The kinetic resolution in palladium-catalyzed asymmetric allylic alkylation using various chiral ligandsa
DMM (0.6 eq.)
chiral ligand
O
O
[Pd( 3-C3H5)Cl]2
OAc
Ph
( )-2a
OAc
MeO
OMe
+
Ph
Ph
Ph Ph
Ph
BSA, LiOAc
THF (0.25 M)
25 °C, 24 h
(R)-2a
(R)-3a
Entry
Ligand
Conv.b (%)
ee of (R)-2ac (%)
ee of (R)-3ac (%)
Sd
N
1
17
16
86
ꢀ89
74
11.3
F3C
PPh2
(S)-1c
OTMS
PPh2
N
MeO
2
58
2.6
1.1
(S)-4
OMe
N
N
3
29
21
3.8
PPh2
(S)-5
a
The reactions were carried with DMM (0.6 equiv) and BSA (3.0 equiv), in the presence of LiOAc (2 mol %) and ligand (S)-1 (4 mol %) and [Pd(
(0.25 M) at 25 °C for 24 h.
g
3-C3H5)Cl]2 (2 mol %) in THF
b
Determined by 1H NMR.
Determined by HPLC analysis using a chiral column (Daicel CHIRALCELÒ OD-H).
S = ln[(1 ꢀ C/100)(1 ꢀ ee/100)]/ln[(1 ꢀ C/100)(1 + ee/100)] (C = conversion; ee = ee of 2a).
c
d
atmosphere. After 30 min, BSA (0.6 mmol, 0.15 mL) and dimethyl
malonate (0.12 mmol) in PhMe (1.2 M, 0.1 mL) was added at
25 °C. After 18 h, the reaction mixture was diluted with diethyl
ether and water. The organic layer was washed with brine and
dried over MgSO4. The filtrate was concentrated with a rotary
evaporator and the residue was passed through a pipette plug of
silica gel (diethyl ether) to give a mixture of 2a and 3a. The reaction
conversion was determined by 1H NMR. The ee of 2a and 3a was
determined by HPLC analysis using a chiral column (Daicel CHI-
RALCELÒ OD-H, flow rate = 0.2 mL/min, hexane/iPrOH = 99:1,
detection at 254 nm: tR 32.3 min ((S)-2a), tR 36.6 min ((R)-2a), tR
41.4 min [(R)-3a], tR 44.5 min [(S)-3a)].
3. Conclusions
In conclusion, we found that C–N bond axially chiral amino-
phosphine (S)-1c was an effective ligand for the kinetic resolution
in the palladium-catalyzed asymmetric allylic alkylation. Chiral
allylic esters, such as (R)-1,3-diphenyl-2-propenyl acetate (R)-2a,
were obtained by kinetic resolution with good enantioselectivities.
4. Experimental
4.1. General procedure for the kinetic resolution in palladium-
catalyzed allylic alkylation: optimization of reaction conditions
(Table 1, entry 14)
4.2. General procedure for kinetic resolution in palladium-
catalyzed allylic alkylation in PhMe (Table 1, entry 19)
To a mixture of [Pd(g
3-C3H5)Cl]2 (0.01 mmol, 3.9 mg), chiral
aminophosphine ligand (S)-1c (0.02 mmol, 9.0 mg), and LiOAc
(0.004 mmol, 0.3 mg) in PhMe (0.7 mL) was added racemic allylic
ester 2a (0.2 mmol, 50.5 mg) at room temperature under an Ar
To a mixture of [Pd(
aminophosphine ligand (S)-1c (0.02 mmol, 9.0 mg), and LiOAc
g
3-C3H5)Cl]2 (0.01 mmol, 3.9 mg), chiral

2714
T. Mino et al. / Tetrahedron: Asymmetry 19 (2008) 2711–2716
Table 3
Kinetic resolution in palladium-catalyzed asymmetric allylic alkylation of various allylic esters using (S)-1ca
Malonate (0.6 eq.)
O
O
O
O
chiral ligand (S)-1c
O
R1
O
R1 R2O
OR2
[Pd(η
3-C3H5)Cl]2
+
Ph
Ph
Ph
Ph
Ph
Ph
BSA, LiOAc
PhMe (0.25 M)
25 °C, 18 h
( )-2
(R)-2
(R)-3
Entry
R1
R2
Conv.b (%)
ee of recovered allylic esterc (%)
ee of productc (%)
Sd
1
2
3
4
Me
t-Bu
Ph
Me
Me
Me
Et
54
44
56
53
92 (R)-2a
95 (R)-3a
23.9
9.7
5.0
55e(49)f (R)-2b
59(42)f (R)-2c
78(43)f (R)-2a
94(43)f (R)-3a
94(55)f (R)-3a
94 g(49)f (R)-3b
Me
13.8
a
The reactions were carried with malonate (0.6 equiv) and BSA (3.0 equiv), in the presence of LiOAc (2 mol %) and ligand (S)-1c (10 mol %) and [Pd(
g
3-C3H5)Cl]2 (5 mol %)
in PhMe (0.25 M) at 25 °C for 18 h.
b
Determined by 1H NMR.
c
Determined by HPLC analysis using a chiral column (Daicel CHIRALCELÒ OD-H).
d
S = ln[(1 ꢀ C/100)(1 ꢀ ee/100)]/ln[(1 ꢀ C/100)(1 + ee/100)] (C = conversion; ee = ee of 2).
e
Determined by HPLC analysis using a chiral column (Daicel CHIRALPAKÒ AS-H).
f
Values in parentheses are isolated yields.
g
Determined by HPLC analysis using a chiral column (Daicel CHIRALCELÒ OJ).
F3C
+
matched
OAc
N
P
Pd0
Ph
Ph
kfast
F3C
S
N
P
OAc
PdII
Ph
Ph
mismatched
Ph
Ph
A
kslow
MeOOHC
COOMe
F3C
OAc
C
N
P
Pd0
Ph
Ph
R
AcO
Ph
O
O
Ph
B
MeO
Ph
OMe
Ph
R
Scheme 1. Plausible asymmetric induction process during kinetic resolution in palladium-catalyzed asymmetric allylic alkylation using chiral ligands (S)-1c.
(0.004 mmol, 0.3 mg) in PhMe (0.7 mL) was added racemic allylic
ester 2a (0.2 mmol, 50.5 mg) at room temperature under an Ar
atmosphere. After 30 min, BSA (0.6 mmol, 0.15 mL) and dimethyl
malonate (0.13 mmol) in PhMe (1.3 M, 0.1 mL) were added at
25 °C. After 40 h, the reaction mixture was diluted with diethyl
ether and water. The organic layer was washed with brine and
dried over MgSO4. The filtrate was concentrated with a rotary
evaporator and the reaction conversion was determined by 1H
NMR. The residue was purified by column chromatography (hex-
ane/ethyl acetate/triethylamine = 34:1:6) to give (R)-2a (19 mg,
0.07 mmol) and (R)-3a (38 mg, 0.12 mmol).
4.2.1. Compound (R)-2a10e
37% yield; 95% ee; ½a D20
ꢁ
¼ ꢀ4:9 (c 0.30, CHCl3); 1H NMR
(300 MHz, CDCl3) d 2.14 (s, 3H), 6.35 (dd, J= 6.9 and 15.7 Hz, 1H),
6.44 (d, J= 6.9 Hz, 1H), 6.64 (d, J= 15.7 Hz, 1H), 7.21-7.43 (m,
10H); 13C NMR (75 MHz, CDCl3) d 21.3, 76.1, 126.7, 127.0, 127.5,
128.0, 128.1, 128.6, 128.6, 132.6, 136.2, 139.2, 170.0; EI-MS m/z
(rel intensity) 252 (M+, 9).
4.2.2. Compound (R)-3a9a
59% yield; 95% ee; ½a D20
ꢁ
¼ þ11:8 (c 0.20, CHCl3); 1H NMR
(300 MHz, CDCl3) d 3.51 (s, 3H), 3.70 (s, 3H), 3.95 (d, J = 10.9 Hz,

T. Mino et al. / Tetrahedron: Asymmetry 19 (2008) 2711–2716
2715
1H), 4.27 (dd, J = 8.5 and 10.9 Hz, 1H), 6.33 (dd, J = 8.5 and 15.8 Hz,
4.4. Determination of absolute configuration of 2b
4.4.1. Resolution of 1,3-diphenyl-2-propene-1-ol
The resolution was carried out by the use of a chiral stationary
phase column [Chiralcel OD-H (1.0 / ꢂ 25 cm), flow rate = 0.5 mL/
min, hexane/iPrOH = 95:5] to give both enantiomers. A 0.25 mL of
solution was injected for each batch using 110 mg of ( )-1,3-diphe-
nyl-2-propene-1-ol in EtOH (4.25 mL). Enantiomers were eluted at
38 min for (S)-isomer and 48 min for (R)-isomer.14
1H), 6.48 (d, J = 15.8 Hz, 1H), 7.17–7.34 (m, 10H); 13C NMR
(75 MHz, CDCl3) d 49.2, 52.4, 52.6, 57.6, 126.4, 127.1, 127.5,
127.8, 128.5, 128.7, 129.1, 131.8, 136.8, 140.1, 167.8, 168.2; EI-
MS m/z (rel intensity) 324 (M+, 13).
4.3. General procedure for the kinetic resolution of various
allylic esters 2 in palladium-catalyzed allylic alkylation (Table 3)
To a mixture of [Pd(g
3-C3H5)Cl]2 (0.01 mmol, 3.9 mg), chiral
aminophosphine ligand (S)-1c (0.02 mmol, 9.0 mg), and LiOAc
(0.004 mmol, 0.3 mg) in PhMe (0.7 mL) was added racemic allylic
ester 2 (0.2 mmol) at room temperature under an Ar atmosphere.
After 30 min, BSA (0.6 mmol, 0.15 mL) and malonate (0.12 mmol)
in PhMe (1.2 M, 0.1 mL) were added at 25 °C. After 18 h, the reac-
tion mixture was diluted with diethyl ether and water. The organic
layer was washed with brine and dried over MgSO4. The filtrate
was concentrated with a rotary evaporator and the reaction con-
version was determined by 1H NMR. The residue was purified by
4.4.2. (S)-1,3-Diphenyl-2-propene-1-ol
38 mg, 68%; >99% ee; ½a D20
¼ ꢀ31:9 (c 0.29, CHCl3); HPLC (Daicel
ꢁ
CHIRALCELÒ OD-H, 0.46 / ꢂ 25 cm, flow rate = 0.5 mL/min, hex-
ane/iPrOH = 90:10, detection at 254 nm) tR = 33.1 min; 1H NMR
(300 MHz, CDCl3) d 2.03 (s, br, 1H), 5.40 (d, J = 4.6 Hz, 1H), 6.39
(dd, J = 6.5 and 15.8 Hz, 1H), 6.70 (d, J = 15.8 Hz, 1H), 7.21–7.46
(m, 10H); 13C NMR (75 MHz, CDCl3) d 75.1, 126.3, 126.6, 127.8,
127.8, 128.6, 128.6, 130.6, 131.5, 136.5, 142.7; EI-MS m/z (rel
intensity) 210 (M+, 34).
column
chromatography
(hexane/ethyl
acetate/triethyl-
amine = 34:1:6) to give (R)-2 and (R)-3.
4.4.3. (R)-1,3-Diphenyl-2-propene-1-ol
38 mg, 68%; >99% ee; ½a D20
¼ þ34:8 (c 0.30, CHCl3); HPLC (Daicel
ꢁ
4.3.1. Compound (R)-2b11
CHIRALCELÒ OD-H, 0.46 / ꢂ 25 cm, flow rate = 0.5 mL/min, hex-
ane/iPrOH = 90:10, detection at 254 nm) tR = 43.0 min; 1H NMR
(300 MHz, CDCl3) d 2.03 (s, br, 1H), 5.40 (d, J = 4.6 Hz, 1H), 6.39
(dd, J = 6.5 and 15.8 Hz, 1H), 6.70 (d, J = 15.8 Hz, 1H), 7.24–7.46
(m, 10H); 13C NMR (75 MHz, CDCl3) d 75.1, 126.3, 126.6, 127.8,
127.8, 128.6, 128.6, 130.6, 131.5, 136.5, 142.7; EI-MS m/z (rel
intensity) 210 (M+, 30).
(Table 3, entry 2) 29 mg, 0.10 mmol, 49% yield; 55% ee (Daicel
CHIRALPAKÒ AS-H, flow rate = 0.25 mL/min, hexane/iPrOH = 99:1,
detection at 254 nm: tR 17.0 min ((R)-2b), tR 18.8 min ((S)-2b));
½
a 2D0
ꢁ
¼ þ3:4 (c 0.35, CHCl3); 1H NMR (300 MHz, CDCl3) d 1.25 (s,
9H), 6.32 (dd, J = 6.8 and 15.6 Hz, 1H), 6.41 (d, J = 6.9 Hz, 1H),
6.63 (d, J = 15.6 Hz, 1H), 7.23–7.41 (m, 10H); 13C NMR (75 MHz,
CDCl3) d 27.1, 38.9, 75.7, 126.67, 126.72, 127.8, 127.9, 128.0,
128.5, 128.5, 132.2, 136.3, 139.6, 177.3; EI-MS m/z (rel intensity)
294 (M+, 4).
4.4.4. Preparation of (R)-2b
To a mixture of (R)-1,3-diphenyl-2-propene-1-ol (0.179 mmol,
38 mg), triethylamine (0.9 mL), and DMAP (0.04 mmol, 4 mg) was
4.3.2. Compound (R)-3a
added pivaloyl chloride (0.179 mmol, 23 lL) at room temperature.
(Table 3, entry 2) 28 mg, 0.09 mmol, 43% yield; 94% ee.
After 21 h, the reaction mixture was diluted with 2 M HCl aq and
diethyl ether. The organic layer was washed with water, brine,
and dried over MgSO4. The filtrate was concentrated with a rotary
evaporator and the residue was purified by column chromatogra-
phy (hexane/ethyl acetate = 100:1) to give (R)-2b (16 mg,
0.054 mmol).
4.3.3. Compound (R)-2c10a,12
(Table 3, entry 3) 26 mg, 0.08 mmol, 42% yield; 59% ee (Daicel
CHIRALCELÒ OD-H + OD-H, flow rate = 0.30 mL/min, hex-
ane/iPrOH = 99:1, detection at 254 nm: tR 49.1 min (CD: kext
(De)
254 (ꢀ)) ((S)-2c), tR 55.0 min (CD: kext
(De) 254 (+)) ((R)-2c));
½
a 2D0
ꢁ
¼ þ8:0 (c 0.30, CHCl3); 1H NMR (300 MHz, CDCl3) d 6.47 (dd,
4.4.5. Compound (R)-2b
30% yield; 97% ee (Daicel CHIRALPAKÒ AS-H, flow rate = 0.25 mL/
min, hexane/iPrOH = 99:1, detection at 254 nm): tR 20.2 min (major,
J = 6.8 and 15.9 Hz, 1H), 6.69–6.76 (m, 2H), 7.21–7.59 (m, 13H),
8.13 (d, J = 8.3 Hz, 2H); 13C NMR (75 MHz, CDCl3) d 76.6, 126.7,
127.0, 127.5, 128.0, 128.2, 128.4, 128.6, 128.6, 129.7, 130.3,
132.8, 133.1, 136.1, 139.3, 165.6; EI-MS m/z (rel intensity) 314
(M+, 3).
(R)-2b), tR 23.0 min (minor, (S)-2b)); ½a D20
ꢁ
¼ þ4:1 (c 0.30, CHCl3); 1H
NMR (300 MHz, CDCl3) d 1.25 (s, 9H), 6.32 (dd, J = 6.7 and 15.6 Hz,
1H), 6.41 (d, J = 7.0 Hz, 1H), 6.63 (d, J = 15.5 Hz, 1H), 7.24–7.41 (m,
10H); 13C NMR (75 MHz, CDCl3) d 27.1, 38.9, 75.7, 126.67, 126.72,
127.8, 127.9, 128.0, 128.5, 128.5, 132.2, 136.3, 139.6, 177.3; EI-MS
m/z (rel intensity) 294 (M+, 4).
4.3.4. Compound (R)-3a
(Table 3, entry 3) 35 mg, 0.11 mmol, 55% yield; 94% ee.
4.3.5. Compound (R)-2a
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(Table 3, entry 4) 22 mg, 0.09 mmol, 43% yield; 78% ee.
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