Regio- and enantioselective allylic substitution with less active N- or O-nucleophiles catalyzed by iridium-complex of bis(oxazolinyl)pyridine

Article abstract of DOI:10.1248/cpb.59.714

The utility of hydroxylamines as nitrogen nucleophiles was investigated in the iridium-catalyzed regio- and enantioselective allylic substitution. Allylic substitution with hydroxylamines proceeded with good enantioselectivities by using the iridium-complex of bis(oxazolinyl)pyridine ligand. The good regio- and enantioselectivities were also achieved in the reaction with alkylamines, p-anisidine, and 4-methoxyphenol.

Full text of DOI:10.1248/cpb.59.714

714
Regular Article
Chem. Pharm. Bull. 59(6) 714—720 (2011)
Vol. 59, No. 6
Regio- and Enantioselective Allylic Substitution with Less Active N- or
O-Nucleophiles Catalyzed by Iridium-Complex of Bis(oxazolinyl)pyridine
Hideto MIYABE,*,a,b Katsuhiko MORIYAMA,a and Yoshiji TAKEMOTO*,a
a Graduate School of Pharmaceutical Sciences, Kyoto University; Yoshida, Sakyo-ku, Kyoto 606–8501, Japan: and b School
of Pharmacy, Hyogo University of Health Sciences; Minatojima, Chuo-ku, Kobe 650–8530, Japan.
Received January 27, 2011; accepted February 28, 2011
The utility of hydroxylamines as nitrogen nucleophiles was investigated in the iridium-catalyzed regio- and
enantioselective allylic substitution. Allylic substitution with hydroxylamines proceeded with good enantioselec-
tivities by using the iridium-complex of bis(oxazolinyl)pyridine ligand. The good regio- and enantioselectivities
were also achieved in the reaction with alkylamines, p-anisidine, and 4-methoxyphenol.
Key words allylic substitution; catalytic; enantioselective; iridium
Enantioselective transition metal-catalyzed allylic substitu- zoyl and O-benzyl groups (Chart 1). Although the reaction of
tions have been developed as fundamentally important cross- 4A with carbonate 7 was less effective in the absence of a
coupling reactions.1—8) In general, the heteroatom nucleo- base, the reaction of 4A with acetate 8 proceeded smoothly
philes in these reactions have been largely limited to alkyl- by employing Et2Zn as a base to give the branched product
amines, anilines, carboxylates and phenols. Our laboratory is 9Aa in 60% yield without formation of the linear product.
interested in searching the synthetically useful heteroatom
Based on these results, we next investigated iridium-cata-
nucleophiles for the synthesis of functionalized allylic com- lyzed asymmetric allylic substitution with hydroxylamine 4A
pounds (Fig. 1).9) As our successful examples, we have re- under basic conditions (Chart 2). In this study, phosphate 10a
cently reported the utility of oximes 1 and guanidines 5 and 6 was employed as an unsymmetrical substrate to prove the ef-
as nucleophiles in the transition metal-catalyzed allylic sub- ficiency of iridium complex of pybox ligand 12. In our pre-
stitution.10—14)
liminary communication,19) we reported that the base drama
Hydroxylamines are also attractive synthetic reagents for tically influenced the regio- and enantioselectivities. Here
allylic substitution, since they have nitrogen and oxygen
atoms as nucleophiles. However, the allylic substitution with
hydroxylamines has not been studied well and is limited to a
simple palladium-catalyzed amination15,16); thus, there are no
reports on asymmetric reactions. We have recently reported
that hydroxylamines 2 and 3 having an N-electron-withdraw-
ing substituent, also known as hydroxamic acids, act as reac-
tive oxygen nucleophiles in the enantioselective allylic sub-
stitution (Fig. 1).17,18) As a part of our program directed to-
ward searching the synthetically useful heteroatom nucleo-
philes, we describe in detail the study of hydroxylamines 4 as
Fig. 1. Heteroatom Nucleophiles in Transition Metal-Catalyzed Allylic
Substitution
nitrogen nucleophiles in the regio- and enantioselective irid-
ium-catalyzed allylic substitutions.19) In this study, we also
expected that comparison with alkylamines, p-anisidine, and
4-methoxyphenol would lead to informative suggestions re-
garding the asymmetric reaction using the iridium complex
of pybox (bis(oxazolinyl)pyridine) ligand.
Chart 1. Iridium-Catalyzed Allylic Substitution of Hydroxylamine 4A
Results and Discussion
Controlling both regio- and enantioselectivities has been
of great importance in the allylic substitution of unsymmetri-
cal substrates with heteroatom nucleophiles.20—24) The regio-
selectivities in reactions using rhodium,25—33) iridium,34—38)
and ruthenium39—41) complexes are quite different from those
of palladium-catalyzed reaction. Therefore, chiral iridium
complexes controlling regio- and enantioselectivities have
been a subject of current interest.42—84) Recently, we reported
that the iridium-complex of pybox catalyzed allylic substitu-
tion of unsymmetrical substrates to form branched products
with good enantioselectivities.13,14,17,19)
Prior to exploring the enantioselective reaction, we first in-
vestigated the viability of hydroxylamine 4A having N-ben-
Chart 2. Regio- and Enantioselective Iridium-Catalyzed Allylic Substitu-
tion
© 2011 Pharmaceutical Society of Japan
∗ To whom correspondence should be addressed. e-mail: miyabe@huhs.ac.jp; takemoto@pharm.kyoto-u.ac.jp

June 2011
715
Table 1. Enantioselective Reaction of Hydroxylamine 4A with 10aa)
T
(°C)
Time
(h)
% Yieldb)
(Ratio)c)
Ee
Entry
Catalyst
CsOH·H2O
(%)d)
1
2
3
4
5
6
7
8
9
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrOMe(cod)]2
[IrOMe(cod)]2
[IrCl(coe)]2
1.0 eq
1.0 eq
1.0 eq
1.0 eq
0.5 eq
none
1.0 eq
none
1.0 eq
ꢂ20
ꢀ20
ꢀ40
ꢀ60
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
1
8
94 (76 : 24)
89 (86 : 14)
86 (90 : 10)
45 (87 : 13)
45 (76 : 24)
NR
79
92
92
87
79
17
40
18
50
3
94 (86 : 14)
NR
95
50
50
trace
a) Reactions were carried out with 4A and 10a in CH2Cl2 in the presence of catalyst (4 mol%) and pybox 12 (8 mol%). b) Combined yields. c) Ratio for 9Aa : 11Aa. d)
Enantioselectivities were determined by HPLC analysis.
Chart 3. Regio- and Enantioselective Amination Using 4A—D
too, good yields of 9Aa were obtained with reasonable regio-
Chart 4. Conversion into Functionalized Compounds
and enantioselectivities by employing CsOH·H2O or
Ba(OH)2·H2O as a base. The results using Ba(OH)2·H2O
have been described in our report19); thus, Table 1 outlines the reaction did not proceed effectively when [IrCl(coe)]2
the optimization of reaction conditions using CsOH·H2O. To was employed (entry 9).
a solution of hydroxylamine 4A and CsOH·H2O in CH2Cl2
To gain further insight into the reactivity of hydroxyl-
was added a solution of the phosphate 10a, [IrCl(cod)]2 amines, several hydroxylamines 4A—D and allylic substrates
(4 mol%) and ligand 12 (8 mol%) in CH2Cl2, and then the re- 10a—d were tested under the reaction conditions using
action mixture was stirred at 20 °C for 1 h (entry 1). The re- [IrCl(cod)]2 (Chart 3). The nitrogen atom of hydroxylamine
action proceeded smoothly to give the branched product 9Aa 4B having two electron-withdrawing substituents acted as a
and the linear product 11Aa in 94% combined yield although reactive nucleophile in allylic substitution (Table 2, entries 1
low regioselectivity was observed. Enantiomeric excess of and 2). The reaction at ꢀ20 °C gave the branched product
9Aa was determined to be 79% by high performance liquid 9Ba with 87% ee in a 73 : 23 regioselectivity (entry 1). When
chromatography analysis using Chiralcel OD-H. The degree the reaction was carried out at ꢀ40 °C, the product 9Ba was
of regio- and enantioselectivities was shown to be dependent obtained with 85% ee (entry 2). The hydroxylamine 4C hav-
on the reaction temperature (entries 2—4). Thus, changing ing N-benzoyl and O-allyl groups worked well as a nitrogen
the temperature from 20 to ꢀ20 °C led to an increase in re- nucleophile (entries 3 and 4). Changing the temperature from
gioselectivity to 86 : 14 and enantioselectivity to 92% ee ꢀ20 to ꢀ40 °C led to a decrease in regio- and enantioselec-
(entry 2). The branched product 9Aa was also obtained with tivity (entry 4). In contrast, moderate enantioselectivities
92% ee, after being stirred at ꢀ40 °C for 17 h (entry 3). In were observed in the reaction with hydroxylamine 4D having
the absence of ligand 12, the iridium-catalyzed reaction of N-acetyl and O-benzyl groups (entries 5 and 6). Phosphates
4A with phosphate 10a did not occur. This result indicates 10b—d worked well, allowing facile incorporation of struc-
the remarkable background reaction did not proceed under tural variety (entries 7—11). The use of phosphate 10d hav-
the present mild conditions using CsOH·H2O. The reaction ing 1-naphthyl group led to an increase in regioselectivity to
proceeded slowly at ꢀ60 °C to afford 9Aa with 87% ee in ꢁ95 : 5 and enantioselectivity to 96% ee (entries 10 and 11).
87 : 13 ratio (entry 4). The reaction did not proceed effec-
The branched products can be converted into functional-
tively when 0.5 eq of CsOH·H2O was employed (entry 5). In ized allylic compounds (Chart 4). The branched product 9Aa
the absence of CsOH·H2O, practically no reaction occurred was easily converted into 13. The absolute configuration of
(entry 6). The use of [IrOMe(cod)]2 led to an increase in product 13 was determined to be S upon comparison with au-
enantioselectivity to 95% ee (entry 7). However, in the ab- thentic compound (R)-13.85) The combination of intermolecu-
sence of base, the reaction using [IrOMe(cod)]2 did not pro- lar allylic substitution with metathesis is a useful method for
ceed (entry 8). In contrast to [IrCl(cod)]2 and [IrOMe(cod)]2, the synthesis of heterocycles as demonstrated by Evans.25,26,86)

716
Vol. 59, No. 6
Table 2. Reaction of Hydroxylamines 4A—D with 10a—da)
Hydroxyl-
amine
T
(°C)
Time
(h)
% Yieldb)
(ratio)
Ee
Entry
Phosphate
(%)c)
1
2
3
4
5
6
7
8
9
4B
4B
4C
4C
4D
4D
4A
4A
4A
4A
4A
10a
10a
10a
10a
10a
10a
10b
10c
10c
10d
10d
ꢀ20
ꢀ40
ꢀ20
ꢀ40
ꢂ20
ꢀ20
ꢀ20
ꢀ20
ꢀ40
ꢀ20
ꢀ40
12
12
8
73 (9Ba : 11Baꢃ73 : 27)
44 (9Ba : 11Baꢃ72 : 28)
88 (9Ca : 11Caꢃ89 : 11)
47 (9Ca : 11Caꢃ87 : 13)
84 (9Da : 11Daꢃ89 : 11)
69 (9Da : 11Daꢃ90 : 10)
75 (9Ab : 11Abꢃ70 : 30)
67 (9Ac : 11Acꢃ71 : 29)
45 (9Ac : 11Acꢃ80 : 20)
95 (9Ad : 11Adꢃꢁ95 : 5)
56 (9Ad : 11Adꢃꢁ95 : 5)
87
85
94
89
33
65
87
83
82
96
96
50
12
65
20
30
65
30
65
10
11
a) Reactions were carried out with 4A—D and 10a—d in CH2Cl2 in the presence of [IrCl(cod)]2 (4 mol%) and pybox 12 (8 mol%). b) Combined yields. c) Enantioselec-
tivities were determined by HPLC analysis.
Table 3. Reaction of Amines 17A—C with 10aa)
T
(°C)
Time
(h)
% Yieldb)
(ratio)c)
Ee
Entry
Amine
Base
(%)d)
1
2
3
4
5
6
17A
17A
17A
17B
17C
17C
CsOH·H2O
CsOH·H2O
none
CsOH·H2O
CsOH·H2O
CsOH·H2O
ꢀ20
ꢀ40
ꢀ20
ꢀ20
ꢂ20
ꢀ20
1
2
24
20
5
91 (71 : 29)
86 (70 : 30)
53 (67 : 33)
66 (78 : 22)e)
87 (71 : 29)
67 (68 : 32)
95
87
76
94
56
71
65
a) Reactions were carried out with 17A—C and phosphate 10a in CH2Cl2 in the presence of [IrCl(cod)]2 (4 mol%) and pybox 12 (8 mol%). b) Combined yields. c) Ratio
for 18A—C : 19A—C. d) Enantioselectivities were determined by HPLC analysis. e) A small amount of dicinnamylated product was obtained.
Chart 5. Regio- and Enantioselective Amination Using Other Amines
Chart 6. Regio- and Enantioselective Amination Using 20
Cyclic compound 14 was obtained by ring-closing metathesis
(RCM) reaction of 9Ca using Grubbs’ 2nd gen. catalyst 15.
The cleavage of N–O bond of 14 was achieved by reduction
Table 4. Reaction of 20 with 10aa)
using Zn and AcOH to give the aminoalcohol 16 in 80%
yield.
T
(°C)
Time
(h)
% Yieldb)
(ratio)c)
Ee
Entry
Base
(%)d)
We next studied the asymmetric reaction with alkylamines
as compared with hydroxylamines (Chart 5). Although N,N-
dibenzylamine 17A has nucleophilic property even in the ab-
sence of a base, excellent enantioselectivity and chemical ef-
ficiency were obtained when CsOH·H2O was employed
(Table 3, entries 1—3). In the presence of CsOH·H2O, the
reaction proceeded smoothly at ꢀ20 °C to give the branched
product 18A with 95% ee within 1 h (entry 1). The reaction
at ꢀ40 °C afforded the product 18A with 87% ee (entry 2).
1
2
3
CsOH·H2O
CsOH·H2O
none
ꢀ20
ꢀ40
ꢀ40
3
24
24
95 (81 : 9 : 10)
86 (80 : 10 : 10)
55 (71 : 15 : 14)
88
87
72
a) Reactions were carried out with 20 and phospate 10a in CH2Cl2 in the presence of
[IrCl(cod)]2 (4 mol%) and pybox 12 (8 mol%). b) Combined yields. c) Ratio for
21 : 22 : 22. d) Enantioselectivities were determined by HPLC analysis.
Next, the asymmetric reaction with less reactive aniline
In the absence of CsOH·H2O, the reaction with 17A was less derivative was investigated (Chart 6). Although p-anisidine
effective (entry 3). Similar trend was observed in the reaction 20 participated in the present reaction, formation of branched
with N-benzylamine 17B. The product 18B was obtained product 21, linear product 22 and diallylated product 23 were
with 94% ee under the reaction conditions using CsOH·H2O observed. The use of CsOH·H2O as a base led to an increase
(entry 4). N,O-Dibenzylhydroxylamine 17C worked well (en- in regioselectivity and enantioselectivity (Table 4). p-Ani-
tries 5 and 6). Treatment of phosphate 10a with 17C at sidine 20 worked well at ꢀ20 °C to give the branched prod-
ꢀ20 °C gave the branched product 18C with 71% ee (entry uct 21 with 88% ee in 81 : 9 : 10 ratio (entry 1). The product
6).
21 was also obtained with 87% ee after being stirred at

June 2011
717
Table 5. Reaction of 24 with 10aa)
[IrCl(cod)]2 (26.9 mg, 0.040 mmol) in CH2Cl2 (2.0 ml) at temperature indi-
cated in Tables 2—4. After the reaction was completed, the reaction mixture
was diluted with saturated NH4Cl and then extracted with AcOEt. The or-
ganic phase was dried over MgSO4 and concentrated at reduced pressure.
T
Time
(h)
% Yieldb)
(ratio)c)
ee
Entry
Base
(°C)
(%)d)
1
The ratio of products was determined by H-NMR analysis of crude prod-
1
2
3
4
5
CsOH·H2O
Ba(OH)2·H2O
Ba(OH)2·H2O
K2CO3
ꢂ20
ꢂ20
ꢀ20
ꢂ20
ꢀ20
48
1
48
3
61 (78 : 22)
84 (87 : 13)
65 (98 : 2)
86 (83 : 17)
88 (92 : 8)
24
45
51
58
72
ucts. Purification of the residue by preparative TLC (hexane : AcOEtꢃ
5 : 1—25 : 1, 2-fold development) afforded the products 9Aa—Ad, 11Aa—
Ad, 18A—C, and 19A—C.
N-(Benzyloxy)-N-((S)-1-phenylallyl)benzamide (9Aa) As a colorless
1
oil: IR (CHCl3) cmꢀ1: 1635, 1495, 1451. H-NMR (CDCl3) d: 7.70 (2H, d,
K2CO3
48
Jꢃ7.0 Hz), 7.60—7.15 (11H, m), 6.83 (2H, d, Jꢃ7.0 Hz), 6.32 (1H, ddd,
Jꢃ17.7, 11.0, 6.1 Hz), 6.15 (1H, d, Jꢃ6.1 Hz), 5.39 (1H, d, Jꢃ17.7 Hz),
5.38 (1H, d, Jꢃ11.0 Hz), 4.48 (1H, d, Jꢃ8.5 Hz), 4.11 (1H, d, Jꢃ8.5 Hz).
13C-NMR (CDCl3) d: 170.6, 138.1, 134.9, 134.2, 134.1, 130.6, 129.5, 128.8,
128.6 (2C), 128.3, 128.3, 128.1, 118.6, 78.5, 64.1. One carbon peak was
missing due to overlapping. MS (EIꢂ) m/z: 343 (Mꢂ, 11), 115 (100). HR-MS
m/z: 343.1570 (Calcd for C23H21NO2: 343.1572). HPLC (Chiralcel OD-H,
hexane/2-propanolꢃ95/5, 0.5 ml/min, 254 nm) tR (S)ꢃ15.8 min, tR (R)ꢃ18.1
min. A sample of 92% ee (S) by HPLC analysis gave [a]D29 ꢀ33.8 (cꢃ1.02,
CHCl3).
a) Reactions were carried out with 24 and phosphate 10a in CH2Cl2 in the presence
of [IrCl(cod)]2 (4 mol%) and pybox 12 (8 mol%). b) Combined yields. c) Ratio for
25 : 26. d) Enantioselectivities were determined by HPLC analysis.
N-(Benzoyloxy)-N-((S)-1-phenylallyl)benzamide (9Ba) As a colorless
1
oil: IR (CHCl3) cmꢀ1: 1767, 1665, 1495, 1451. H-NMR (CDCl3) d: 7.84
(2H, d, Jꢃ7.6 Hz), 7.68 (2H, d, Jꢃ7.3 Hz), 7.55 (1H, t, Jꢃ7.6 Hz), 7.45—
7.22 (10H, m), 6.22 (1H, ddd, Jꢃ17.1, 8.9, 6.1 Hz), 6.11 (1H, d, Jꢃ6.1 Hz),
5.40 (1H, d, Jꢃ8.9 Hz), 5.37 (1H, d, Jꢃ17.1 Hz). 13C-NMR (CDCl3) d:
170.6, 164.0, 134.0, 133.9, 133.8, 131.1, 129.8, 128.6, 128.4, 128.1, 127.8,
127.2, 119.4, 66.1. Two carbon peaks were missing due to overlapping. MS
(EIꢂ) m/z: 357 (Mꢂ, 7), 116 (100). HR-MS m/z: 357.1371 (Calcd for
C23H19NO3: 357.1365). HPLC (Chiralcel AD-H, hexane/2-propanolꢃ90/10,
1.0 ml/min, 254 nm) tR (S)ꢃ19.7 min, tR (R)ꢃ15.1 min. A sample of 87% ee
(S) by HPLC analysis gave [a]D31 ꢂ2.6 (cꢃ0.96, CHCl3).
Chart 7. Regio- and Enantioselective Amination Using 24
ꢀ40 °C for 24 h (entry 2). In the absence of CsOH·H2O,
treatment of phosphate 10a with 20 gave 21 with 72% ee
(entry 3). Although the effect of base on these enantioselec-
tivities was questioned, we assume that one role would in-
volve the activation of catalyst.
We finally investigated the asymmetric reaction with 4-
methoxyphenol 24 (Chart 7). In the presence of CsOH·H2O,
the reaction of 10a with 4-methoxyphenol 24 proceeded
slowly to afford the branched product 25 with poor enantio-
selectivity (Table 5, entry 1). To improve the reactivity and
N-(Allyloxy)-N-((S)-1-phenylallyl)benzamide (9Ca) As
a colorless
1
oil: IR (CHCl3) cmꢀ1: 1767, 1665, 1495, 1451. H-NMR (CDCl3) d: 7.68
(2H, d, Jꢃ7.0 Hz), 7.46—7.30 (8H, m), 6.30 (1H, ddd, Jꢃ17.2, 10.4,
6.4 Hz), 6.03 (1H, d, Jꢃ6.4 Hz), 5.51 (1H, m), 5.39 (1H, d, Jꢃ10.4 Hz), 5.38
(1H, d, Jꢃ17.2 Hz), 5.06 (1H, d, Jꢃ10.4 Hz), 4.98 (1H, d, Jꢃ17.2 Hz), 4.03
(1H, m), 3.75 (1H, m). 13C-NMR (CDCl3) d: 170.5, 138.1, 134.8, 134.3,
131.2, 130.6, 128.6, 128.5, 128.1, 128.0 (2C), 119.9, 118.6, 77.6, 64.4. MS
(EIꢂ) m/z: 293 (Mꢂ, 3), 77 (100). HR-MS m/z: 293.1412 (Calcd for
C19H19NO2: 293.1416). HPLC (Chiralcel AD-H, hexane/2-propanolꢃ90/10,
selectivities, the effect of bases was next studied (entries 2— 0.5 ml/min, 254 nm) tR (S)ꢃ19.2 min, tR (R)ꢃ14.2 min. A sample of 94% ee
(S) by HPLC analysis gave [a]D25 ꢂ50.1 (cꢃ1.3, CHCl3).
5). Although Ba(OH)2·H2O was less effective for the present
reaction, improved selectivities and chemical efficiencies
were observed when K2CO3 was employed. The reaction
N-(Benzoyloxy)-N-((S)-1-phenylallyl)acetamide (9Da) As a colorless
1
oil: IR (CHCl3) cmꢀ1: 1767, 1665, 1495, 1451. H-NMR (CDCl3) d: 7.46
(2H, d, Jꢃ7.0 Hz), 7.42—7.30 (6H, m), 7.19—7.13 (2H, m), 6.26 (1H, ddd,
using K2CO3 at ꢀ20 °C gave the 72% ee of the branched
product 25 with a 92 : 8 regioselectivity (entry 5). Results
from this study show that the iridium complex of pybox lig-
and is able to catalyze the allylic substitution with less reac-
tive O-nucleophiles such as phenols.
In conclusion, we have demonstrated that the iridium-
complex of pybox catalyzed the allylic substitution with
hydroxylamines in good enantioselectivities. Good regio- and
enantioselectivities were also achieved in allylic substitution
with alkylamines, p-anisidine, and 4-methoxyphenol.
Jꢃ17.1, 10.4, 5.5 Hz), 6.12 (1H, d, Jꢃ5.5 Hz), 5.35 (1H, d, Jꢃ10.4 Hz),
5.31 (1H, d, Jꢃ17.1 Hz), 4.67 (1H, d, Jꢃ9.8 Hz), 4.27 (1H, d, Jꢃ9.8 Hz),
2.22 (3H, s). 13C-NMR (CDCl3) d: 173.6, 138.2, 134.4, 134.0, 129.0, 128.8
(2C), 128.5 (2C), 128.0, 118.5, 78.7, 63.2, 21.0. MS (EIꢂ) m/z: 281 (Mꢂ,
15), 91 (100). HR-MS m/z: 281.1410 (Calcd for C18H19NO2: 281.1416).
HPLC (Chiralcel OD-H, hexane/2-propanolꢃ95/5, 0.5 ml/min, 254 nm) tR
(S)ꢃ18.9 min, tR (R)ꢃ20.5 min. A sample of 65% ee (S) by HPLC analysis
gave [a]D29 ꢀ13.1 (cꢃ1.03, CHCl3).
N-(Benzyloxy)-N-((S)-1-(4-chlorophenyl)allyl)benzamide (9Ab) As a
colorless oil: IR (CHCl3) cmꢀ1: 1639, 1492, 1449. 1H-NMR (CDCl3) d: 7.67
(2H, d, Jꢃ7.0 Hz), 7.52—7.19 (10H, m), 6.87 (2H, d, Jꢃ7.3 Hz), 6.29 (1H,
ddd, Jꢃ15.9, 9.5, 6.7 Hz), 6.09 (1H, d, Jꢃ6.7 Hz), 5.40 (1H, d, Jꢃ9.5 Hz),
5.37 (1H, d, Jꢃ15.9 Hz), 4.54 (1H, br d, Jꢃ8.9 Hz), 4.22 (1H, br d,
Jꢃ8.9 Hz). 13C-NMR (CDCl3) d: 170.7, 136.8, 134.7, 133.9 (2C), 130.7,
Experimental
General Melting points are uncorrected. 1H- and 13C-NMR spectra 130.0, 129.4, 128.8, 128.4, 128.2, 128.1, 119.2, 78.7, 63.7. Two carbon
were recorded at 500 MHz, and at 125 MHz, respectively. IR spectra were
recorded using Fourier transform (FT)-IR apparatus. Mass spectra were ob- (100). HR-MS m/z: 377.1187 (Calcd for C23H20ClNO2: 377.1188). HPLC
tained by EI or FAB methods. Preparative TLC separations were carried out
(Chiralcel AD-H, hexane/2-propanolꢃ90/10, 0.5 ml/min, 254 nm) tR
peaks were missing due to overlapping. MS (EIꢂ) m/z: 377 (Mꢂ, 2), 91
on precoated silica gel plates (E. Merck 60F254). Flash column chromatogra- (S)ꢃ28.0 min, tR (R)ꢃ21.9 min. A sample of 87% ee (S) by HPLC analysis
phy was performed using E. Merck Kieselgel 60 (230—400 mesh). [a]D val-
ues are measured in 10ꢀ1 deg cm2 gꢀ1. The ratios of products were deter-
mined by 1H-NMR analysis. Enantiomeric excess was determined by high
gave [a]D26 ꢀ3.7 (cꢃ1.15, CHCl3).
N-(Benzyloxy)-N-((S)-1-(4-fluorophenyl)allyl)benzamide (9Ac) As a
colorless oil: IR (CHCl3) cmꢀ1: 1637, 1510, 1449. 1H-NMR (CDCl3) d: 7.68
performance liquid chromatography (HPLC) analysis. Products 19A,87) (2H, d, Jꢃ7.0 Hz), 7.52—7.38 (5H, m), 7.30—7.20 (3H, m), 7.07 (2H, t,
19B,88) 22,89) 23,89) and 2690) are the known compounds.
Jꢃ8.5 Hz), 6.86 (2H, d, Jꢃ7.3 Hz), 6.29 (1H, ddd, Jꢃ17.1, 10.4, 6.4 Hz),
6.11 (1H, d, Jꢃ6.4 Hz), 5.39 (1H, d, Jꢃ10.4 Hz), 5.37 (1H, d, Jꢃ17.1 Hz),
4.52 (1H, br d, Jꢃ8.9 Hz), 4.16 (1H, br d, Jꢃ8.9 Hz). 13C-NMR (CDCl3) d:
170.7, 162.6 (d, Jꢃ247 Hz), 134.8, 134.2, 134.0, 130.7, 130.5, 130.4, 129.4,
128.7, 128.3, 128.2, 128.1, 118.9, 115.5 (d, Jꢃ21 Hz), 78.6, 63.5. Two car-
bon peaks were missing due to overlapping. MS (EIꢂ) m/z: 361 (Mꢂ, 3), 91
General Procedure for Enantioselective Allylic Substitution of
Amines A mixture of amine 4A—D or 17A—C (1.0 mmol) and CsOH·
H2O (168 mg, 1.0 mmol) in CH2Cl2 (4.0 ml) was stirred under argon atmo-
sphere at 20 °C for 10 min. To the reaction mixture was added a solution of
allylic phosphate 10a—d (1.5 mmol), pybox 12 (29.6 mg, 0.080 mmol) and

718
Vol. 59, No. 6
(100). HR-MS m/z: 361.1476 (Calcd for C23H20FNO2: 361.1478). HPLC
(S)-N,N-Dibenzyl-1-phenylprop-2-en-1-amine (18A) A colorless oil:
(Chiralcel AD-H, hexane/2-propanolꢃ90/10, 0.5 ml/min, 254 nm) tR (S)ꢃ IR (CHCl3) cmꢀ1: 1493, 1451. 1H-NMR (CDCl3) d: 7.48 (2H, d, Jꢃ7.6 Hz),
23.9 min, tR (R)ꢃ20.6 min. A sample of 83% ee (S) by HPLC analysis gave
7.40 (4H, d, Jꢃ7.3 Hz), 7.35—7.15 (9H, m), 6.08 (1H, ddd, Jꢃ17.1, 10.1,
8.5 Hz), 5.44 (1H, d, Jꢃ10.1 Hz), 5.20 (1H, d, Jꢃ17.1 Hz), 4.27 (1H, d,
Jꢃ8.5 Hz), 3.66 (2H, d, Jꢃ14.0 Hz), 3.53 (2H, d, Jꢃ14.0 Hz). 13C-NMR
(CDCl3) d: 141.5, 140.1, 135.4, 128.7, 128.3, 128.2 (2C), 127.0, 126.8,
[a]D26 ꢀ22.7 (cꢃ1.30, CHCl3).
N-(Benzyloxy)-N-((S)-1-(naphthalen-1-yl)allyl)benzamide (9Ad) As
a colorless oil: IR (CHCl3) cmꢀ1: 1632, 1511, 1495, 1449. 1H-NMR
(CDCl3) d: 8.37 (1H, d, Jꢃ8.5 Hz), 7.90 (2H, d, Jꢃ8.2 Hz), 7.76 (3H, d, 119.4, 65.2, 53.6. MS (EIꢂ) m/z: 313 (Mꢂ, 22), 117 (100). HR-MS m/z:
Jꢃ7.9 Hz), 7.65 (1H, t, Jꢃ7.0 Hz), 7.57—7.35 (5H, m), 7.20—7.05 (4H, 313.1824 (Calcd for C23H23N: 313.1830). HPLC (Chiralcel OJ-H, hexane/2-
m), 6.50—6.40 (3H, m), 5.59 (1H, d, Jꢃ17.1 Hz), 5.48 (1H, d, Jꢃ10.7 Hz), propanolꢃ95/5, 0.5 ml/min 254 nm) tR (S)ꢃ10.8 min, tR (R)ꢃ14.0 min. A
3.94 (1H, br s), 3.36 (1H, br s). 13C-NMR (CDCl3) d: 170.1, 134.8, 134.1, sample of 95% ee (S) by HPLC analysis gave [a]D31 ꢀ111.0 (cꢃ1.06,
133.7, 133.6, 133.4, 132.0, 130.5, 129.5, 129.3, 128.9, 128.5, 128.3, 128.1,
CHCl3).
128.0, 127.8, 127.1, 126.1, 125.1, 123.5, 117.8, 78.4, 58.7. MS (EIꢂ) m/z:
(S)-N-Benzyl-1-phenylprop-2-en-1-amine (18B)42) A colorless oil: IR
393 (Mꢂ, 6), 167 (100). HR-MS m/z: 393.1727 (Calcd for C27H23NO2: (CHCl3) cmꢀ1: 3330, 1493, 1453. 1H-NMR (CDCl3) d: 7.38—7.22 (10H,
393.1729). HPLC (Chiralcel AD-H, hexane/2-propanolꢃ90/10, 0.5 ml/min, m), 5.95 (1H, ddd, Jꢃ17.4, 10.1, 7.0 Hz), 5.22 (1H, d, Jꢃ17.4 Hz), 5.12
254 nm) tR (S)ꢃ17.4 min, tR (R)ꢃ14.9 min. A sample of 96% ee (S) by
(1H, d, Jꢃ10.1 Hz), 4.22 (1H, d, Jꢃ7.0 Hz), 3.74 (1H, d, Jꢃ13.1 Hz), 3.71
HPLC analysis gave [a]D28 ꢀ20.6 (cꢃ1.07, CHCl3).
(1H, d, Jꢃ13.1 Hz), 1.66 (1H, br s). 13C-NMR (CDCl3) d: 142.8, 141.0,
N-(Benzyloxy)-N-cinnamylbenzamide (11Aa) As a colorless oil: IR 140.4, 128.6, 128.4, 128.2, 127.4, 127.2, 126.9, 115.2, 65.1, 51.2. MS
(CHCl3) cmꢀ1: 1635, 1496, 1450. 1H-NMR (CDCl3) d: 7.67 (2H, d, Jꢃ (FABꢂ) m/z: 224 (M+Hꢂ, 81), 117 (100). HR-MS m/z: 224.1443 (Calcd for
7.3 Hz), 7.49—7.22 (11H, m), 7.07 (2H, d, Jꢃ6.7 Hz), 6.61 (1H, d, Jꢃ
C16H18N: 224.1439). HPLC (Chiralcel OD-H, hexane/2-propanolꢃ99/1,
15.9 Hz), 6.31 (1H, dt, Jꢃ15.9, 6.1 Hz), 4.72 (2H, s), 4.49 (2H, d, 0.3 ml/min 254 nm) tR (S)ꢃ25.5 min, tR (R)ꢃ21.7 min. A sample of 94% ee
Jꢃ6.1 Hz). 13C-NMR (CDCl3) d: 170.3, 136.5, 134.5, 134.3, 134.0, 130.6, (S) by HPLC analysis gave [a]D29 ꢂ5.0 (cꢃ 1.0, CHCl3).
129.5, 128.8, 128.6, 128.5, 128.3, 128.1, 127.9, 126.6, 123.4, 77.1, 50.5.
(S)-N-Benzyl-N-(benzyloxy)-1-phenylprop-2-en-1-amine (18C) A colorless
One carbon peak was missing due to overlapping. MS (FABꢂ) m/z: 344 oil: IR (CHCl3) cmꢀ1: 1494, 1454. 1H-NMR (CDCl3) d: 7.48 (2H, d,
(MꢂHꢂ, 64), 117 (100). HR-MS m/z: 344.1656 (Calcd for C23H22NO2: Jꢃ7.3 Hz), 7.43—7.13 (11H, m), 6.79 (2H, br m), 6.27 (1H, m), 5.26 (1H, d,
344.1651).
Jꢃ17.4 Hz), 5.23 (1H, d, Jꢃ10.1 Hz), 4.29 (1H, d, Jꢃ8.5 Hz), 4.15 (1H,
N-(Benzoyloxy)-N-cinnamylbenzamide (11Ba) As a colorless oil: IR br m), 4.00 (1H, br d, Jꢃ9.2 Hz), 3.89 (1H, br m), 3.77 (1H, br d,
1
(CHCl3) cmꢀ1: 1764, 1663, 1495, 1449. H-NMR (CDCl3) d: 7.91 (2H, d, Jꢃ12.5 Hz). 13C-NMR (CDCl3) d: 141.4, 138.3, 138.0, 136.7, 130.1, 129.2,
Jꢃ7.6 Hz), 7.65 (2H, d, Jꢃ7.0 Hz), 7.56 (1H, d, Jꢃ7.3 Hz), 7.44—7.21 128.5, 128.4, 128.1, 127.8, 127.4, 127.2, 117.6, 76.8, 75.5, 60.8. One carbon
(10H, m), 6.61 (1H, d, Jꢃ15.9 Hz), 6.31 (1H, dt, Jꢃ15.9, 6.4 Hz), 4.67 (2H,
peak was missing due to overlapping. MS (EIꢂ) m/z: 329 (Mꢂ, 3), 117 (100).
HR-MS m/z: 329.1782 (Calcd for C23H23NO: 329.1780). HPLC (Chiralcel
d, Jꢃ6.4 Hz). 13C-NMR (CDCl3) d: 170.8, 164.6, 136.3, 134.4, 134.1,
133.5, 131.1, 129.9, 128.7, 128.6, 128.3, 128.0, 127.9, 127.0, 126.6, 122.6, AD-H, hexane/2-propanolꢃ95/5, 0.5 ml/min, 254 nm) tR (S)ꢃ7.1 min, tR
52.3. MS (EIꢂ) m/z: 357 (Mꢂ, 3), 116 (100). HR-MS m/z: 357.1369 (Calcd
for C23H19NO3: 357.1365).
(R)ꢃ7.6 min. A sample of 71% ee (S) by HPLC analysis gave [a]D28 ꢂ15.2
(cꢃ0.82, CHCl3).
N-(Allyloxy)-N-cinnamylbenzamide (11Ca) As a colorless oil: IR
(E)-N-Benzyl-N-(benzyloxy)-3-phenylprop-2-en-1-amine (19C)
A
1
(CHCl3) cmꢀ1: 1634, 1495, 1449, 1427. H-NMR (CDCl3) d: 7.70 (2H, d,
colorless oil: IR (CHCl3) cmꢀ1: 1495, 1452. 1H-NMR (CDCl3) d: 7.43—
7.08 (15H, m), 6.56 (1H, d, Jꢃ16.2 Hz), 6.36 (1H, dt, Jꢃ16.2, 7.0 Hz), 4.44
(2H, br s), 3.89 (2H. s), 3.56 (2H, d, Jꢃ7.0 Hz). 13C-NMR (CDCl3) d: 137.7,
137.1 (2C), 133.6, 129.9, 129.1, 128.6, 128.2 (2C), 127.8, 127.5, 127.3,
Jꢃ7.0 Hz), 7.46—7.23 (8H, m), 6.63 (1H, d, Jꢃ15.9 Hz), 6.34 (1H, dt,
Jꢃ15.9, 6.4 Hz), 5.71 (1H, m), 5.19 (1H, d, Jꢃ16.2 Hz), 5.18 (1H, d,
Jꢃ11.0 Hz), 4.50 (2H, d, Jꢃ6.4 Hz), 4.26 (2H, d, Jꢃ6.4 Hz). 13C-NMR
(CDCl3) d: 170.1, 136.5, 134.4, 133.8, 131.5, 130.6, 128.6, 128.3, 128.0, 126.4, 125.8, 76.0, 62.8, 60.9. MS (EIꢂ) m/z: 329 (Mꢂ, 5), 117 (100). HR-
127.9, 126.5, 123.4, 120.5, 76.0, 50.6. MS (EIꢂ) m/z: 293 (Mꢂ, 2), 77 (100). MS m/z: 329.1773 (Calcd for C23H23NO: 329.1780).
HR-MS m/z: 293.1419 (Calcd for C19H19NO2: 293.1416).
Enantioselective Allylic Substitution with p-Anisidine A mixture of
N-(Benzyloxy)-N-cinnamylacetamide (11Da) As a colorless oil: IR 20 (40.0 mg, 0.325 mmol) and CsOH·H2O (54.5 mg, 0.325 mmol) in CH2Cl2
(CHCl3) cmꢀ1: 1655, 1496, 1434. 1H-NMR (CDCl3) d: 7.40—7.21 (10H, (1.0 ml) was stirred under argon atmosphere at 20 °C for 10 min. To the reac-
m), 6.55 (1H, d, Jꢃ15.9 Hz), 6.25 (1H, dt, Jꢃ15.9, 5.8 Hz), 4.87 (2H, s),
tion mixture was added a solution of allylic phosphate 10a (132 mg,
4.39 (2H, d, Jꢃ5.8 Hz), 2.13 (3H, s). 13C-NMR (CDCl3) d: 172.6, 136.5, 0.487 mmol), pybox 12 (9.60 mg, 0.0260 mmol) and [IrCl(cod)]2 (8.73 mg,
134.6, 133.7, 129.2, 129.0, 128.7, 128.6, 127.8, 126.5, 123.5, 77.0, 48.7, 0.0130 mmol) in CH2Cl2 (1.0 ml) at ꢀ20 °C. After the reaction was com-
20.5. MS (EIꢂ) m/z: 281 (Mꢂ, 7), 91 (100). HR-MS m/z: 281.1417 (Calcd pleted, the reaction mixture was diluted with water and then extracted with
for C18H19NO2: 281.1416). AcOEt. The organic phase was dried over MgSO4 and concentrated at re-
1
N-(4-Chlorocinnamyl)-N-(benzyloxy)benzamide (11Ab) As a color- duced pressure. The ratio of products was determined by H-NMR analysis
less oil: IR (CHCl3) cmꢀ1: 1637, 1492, 1450. 1H-NMR (CDCl3) d: 7.67 (2H, of crude products. Purification of the residue by preparative TLC
d, Jꢃ7.0 Hz), 7.48 (1H, t, Jꢃ7.3 Hz), 7.44—7.20 (9H, m), 7.07 (2H, d, (hexane : AcOEtꢃ10 : 1, 2-fold development) afforded the products 21
Jꢃ6.7 Hz), 6.54 (1H, d, Jꢃ15.9 Hz), 6.28 (1H, dt, Jꢃ15.9, 6.1 Hz), 4.71 (64.8 mg, 84%), 2289) (7.3 mg, 9%) and 2389) (8.1 mg, 10%).
(2H, s), 4.48 (2H, d, Jꢃ6.1 Hz). 13C-NMR (CDCl3) d: 170.2, 134.9, 134.3,
4-Methoxy-N-((S)-1-phenylallyl)benzenamine (21)91) A colorless oil:
134.2, 133.5, 132.6, 130.6, 129.5, 128.8, 128.7, 128.5, 128.3, 128.1, 127.7, IR (CHCl3) cmꢀ1: 1512, 1457. 1H-NMR (CDCl3) d: 7.42—7.21 (5H, m),
124.1, 76.9, 50.3. MS (EIꢂ) m/z: 377 (Mꢂ, 0.5), 105 (100). HR-MS m/z: 6.72 (2H, d, Jꢃ8.9 Hz), 6.55 (2H, d, Jꢃ8.9 Hz), 6.02 (1H, ddd, Jꢃ17.1,
377.1184 (Calcd for C23H20ClNO2: 377.1188).
N-(4-Fluorocinnamyl)-N-(benzyloxy)benzamide (11Ac) As a color-
10.1, 5.8 Hz), 5.25 (1H, d, Jꢃ17.1 Hz), 5.19 (1H, d, Jꢃ10.1 Hz), 4.85 (1H,
d, Jꢃ5.8 Hz), 3.70 (3H, s). 13C-NMR (CDCl3) d: 152.3, 142.1, 141.3, 139.5,
less oil: IR (CHCl3) cmꢀ1: 1636, 1508, 1450. 1H-NMR (CDCl3) d: 7.67 (2H, 128.7, 127.4, 127.2, 115.9, 115.0, 114.7, 61.8, 55.6. MS (EIꢂ) m/z: 239
d, Jꢃ7.0 Hz), 7.50—7.22 (8H, m), 7.11—6.97 (4H, m), 6.56 (1H, d, Jꢃ15.9 (Mꢂ, 58), 115 (100). HR-MS m/z: 239.1303 (Calcd for C16H17NO:
Hz), 6.21 (1H, dt, Jꢃ15.9, 6.1 Hz), 4.71 (2H, s), 4.47 (2H, d, Jꢃ6.1 Hz). 239.1310). HPLC (Chiralcel AD-H, hexane/2-propanolꢃ90/10, 0.5 ml/min
13C-NMR (CDCl3) d: 170.3, 162.5 (d, Jꢃ247 Hz), 134.4, 134.2, 132.7, 254 nm) tR (S)ꢃ15.8 min, tR (R)ꢃ13.8 min. A sample of 88% ee (S) by
132.6, 130.6, 129.5, 128.8, 128.5, 128.3, 128.1 (2C), 123.1, 115.5 (d,
Jꢃ22 Hz), 77.0, 50.3. MS (EIꢂ) m/z: 361 (Mꢂ, 0.5), 105 (100). HR-MS m/z:
361.1477 (Calcd for C23H20FNO2: 361.1478).
N-(Benzyloxy)-N-((E)-3-(naphthalen-1-yl)allyl)benzamide (11Ad) As a
colorless oil: IR (CHCl3) cmꢀ1: 1637, 1496, 1450. 1H-NMR (CDCl3) d: 8.06
(1H, d, Jꢃ8.9 Hz), 7.84 (1H, d, Jꢃ9.2 Hz), 7.78 (1H, d, Jꢃ7.9 Hz), 7.70
HPLC analysis gave [a]D28 ꢀ12.1 (cꢃ0.95, CHCl3).
Enantioselective Allylic Substitution with 4-Methoxyphenol A mix-
ture of 24 (40.0 mg, 0.322 mmol) and K2CO3 (44.5 mg, 0.322 mmol) in
CH2Cl2 (1.0 ml) was stirred under argon atmosphere at 20 °C for 10 min. To
the reaction mixture was added a solution of allylic phosphate 10a (131 mg,
0.483 mmol), pybox 12 (9.52 mg, 0.0258 mmol) and [IrCl(cod)]2 (8.66 mg,
(2H, d, Jꢃ7.0 Hz), 7.58 (1H, d, Jꢃ7.0 Hz), 7.53—7.32 (7H, m), 7.30—7.20 0.0129 mmol) in CH2Cl2 (1.0 ml) at ꢀ20 °C. After the reaction was com-
(3H, m), 7.10 (2H, d, Jꢃ7.0 Hz), 6.34 (1H, dt, Jꢃ15.6, 6.1 Hz), 4.76 (2H, s),
pleted, the reaction mixture was diluted with water and then extracted with
4.61 (2H, d, Jꢃ6.1 Hz). 13C-NMR (CDCl3) d: 170.3, 134.5, 134.3, 134.2, AcOEt. The organic phase was dried over MgSO4 and concentrated at re-
1
133.6, 131.3, 131.1, 130.6, 129.4, 128.8, 128.5 (2C), 128.3, 128.2, 128.1, duced pressure. The ratio of products was determined by H-NMR analysis
126.6, 126.1, 125.8, 125.6, 124.1, 123.7, 77.1, 50.7. MS (EIꢂ) m/z: 393 of crude products. Purification of the residue by preparative TLC
(Mꢂ, 0.7), 105 (100). HR-MS m/z: 393.1734 (Calcd for C27H23NO2: (hexane : AcOEtꢃ15 : 1, 2-fold development) afforded the products 25
393.1729).
(62.4 mg, 81%) and 2690) (5.5 mg, 7%).

June 2011
719
(S)-1-Phenyl-1-(4-methoxyphenoxy)-2-propene (25)43) A colorless oil:
IR (CHCl3) cmꢀ1: 1505, 1458. 1H-NMR (CDCl3) d: 7.42—7.25 (5H, m),
6.86 (2H, d, Jꢃ9.2 Hz), 6.76 (2H, d, Jꢃ9.2 Hz), 6.09 (1H, ddd, Jꢃ17.1,
10.4, 5.8 Hz), 5.52 (1H, d, Jꢃ5.8 Hz), 5.32 (1H, d, Jꢃ17.1 Hz), 5.24 (1H, d,
Jꢃ10.4 Hz), 3.73 (3H, s). 13C-NMR (CDCl3) d: 154.1, 152.1, 140.3, 138.2,
128.6, 127.8, 126.7, 117.5, 116.5, 114.5, 81.9, 55.6. MS (EIꢂ) m/z: 240
(Mꢂ, 87), 136 (100). HR-MS m/z: 240.1154 (Calcd for C16H16O2:
240.1150). HPLC (Chiralcel OD-H, hexane/2-propanolꢃ95/5, 0.5 ml/min
254 nm) tR (S)ꢃ21.6 min, tR (R)ꢃ19.2 min. A sample of 72% ee (S) by
HPLC analysis gave [a]D31 ꢀ5.8 (cꢃ1.4, CHCl3).
Synlett, 2004, 2123—2126 (2004).
11) Miyabe H., Yoshida K., Reddy V. K., Matsumura A., Takemoto Y., J.
Org. Chem., 70, 5630—5635 (2005).
12) Reddy V. K., Miyabe H., Yamauchi M., Takemoto Y., Tetrahedron, 64,
1040—1048 (2008).
13) Miyabe H., Yoshida K., Reddy V. K., Takemoto Y., J. Org. Chem., 74,
305—311 (2009).
14) Miyabe H., Matsumura A., Yoshida K., Takemoto Y., Tetrahedron, 65,
4464—4470 (2009).
15) Murahashi S., Imada Y., Taniguchi Y., Kodera Y., Tetrahedron Lett.,
29, 2973—2976 (1988).
16) Genet J.-P., Thorimbert S., Touzin A.-M., Tetrahedron Lett., 34,
1159—1162 (1993).
17) Miyabe H., Yoshida K., Yamauchi M., Takemoto Y., J. Org. Chem., 70,
2148—2153 (2005).
Reduction of 9Aa into 13 To a solution of 9Aa (40.0 mg, 0.116 mmol)
in AcOH–H2O (1.0 ml, 1 : 1, v/v) was added Zn powder (305 mg, 4.66
mmol) at 20 °C. After being stirred at 60 °C for 20 h, the reaction mixture
was diluted with saturated NaHCO3 and then extracted with CHCl3. The or-
ganic phase was dried over MgSO4 and concentrated at reduced pressure.
Purification of the residue by preparative TLC (hexane : AcOEtꢃ8 : 1) af-
18) Miyabe H., Yoshida K., Matsumura A., Yamauchi M., Takemoto Y.,
Synlett, 2003, 567—569 (2003).
forded the product 1385) (21.6 mg, 78%) as a white solid. IR (CHCl3) cmꢀ1
:
3445, 1662, 1510, 1482. 1H-NMR (CDCl3) d: 7.79 (2H, d, Jꢃ7.0 Hz),
7.51—7.27 (8H, m), 6.44 (1H, br d, Jꢃ6.7 Hz), 6.11 (1H, ddd, Jꢃ17.4, 10.2,
5.5 Hz), 5.85 (1H, br m), 5.32 (1H, d, Jꢃ10.2 Hz), 5.29 (1H, d, Jꢃ17.4 Hz).
13C-NMR (CDCl3) d: 166.6, 140.6, 137.2, 134.4, 131.6, 128.9, 128.6, 127.8,
127.3, 127.0, 116.2, 55.5. MS (EIꢂ) m/z: 237 (Mꢂ, 35), 105 (100). HR-MS
m/z: 237.1160 (Calcd for C16H15NO: 237.1154). [a]D29 ꢀ70.6 (cꢃ1.0,
CHCl3).
Conversion of 9Ca into 14 A mixture of 9Ca (40.0 mg, 0.136 mmol)
and 2nd Grubbs’ Ru-catalyst 15 (11.6 mg, 0.0136 mmol) in CH2Cl2 (8 ml)
was stirred under argon atmosphere at reflux for 12 h. After the reaction was
completed, the reaction mixture was diluted with water and then extracted
with CH2Cl2. The organic phase was dried over MgSO4 and concentrated at
reduced pressure. Purification of the residue by preparative TLC
(hexane : AcOEtꢃ7 : 1) afforded the product 14 (31.2 mg, 87%) as colorless
oil. IR (CHCl3) cmꢀ1: 1634, 1494, 1449, 1410. 1H-NMR (CDCl3) d: 7.67
(2H, d, Jꢃ7.3 Hz), 7.51 (2H, d, Jꢃ7.3 Hz), 7.45—7.30 (6H, m), 6.07—6.01
(3H, m), 4.52 (1H, br d, Jꢃ15.6 Hz), 4.29 (1H, dd, Jꢃ15.6, 3.0 Hz). 13C-
NMR (CDCl3) d: 168.8, 138.5, 133.8, 130.8, 128.6, 128.5, 128.0, 127.9,
125.7, 123.6, 69.6, 55.1. One carbon peak was missing due to overlapping.
MS (EIꢂ) m/z: 265 (Mꢂ, 2), 105 (100). HR-MS m/z: 265.1095 (Calcd for
C17H15NO2: 265.1103). [a]D30 ꢂ405 (cꢃ1.08, CHCl3).
19) Preliminary communication, see: Miyabe H., Matsumura A.,
Moriyama K., Takemoto Y., Org. Lett., 6, 4631—4634 (2004).
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Reduction of 14 into 16 To a solution of 14 (47.0 mg, 0.177 mmol) in
AcOH–H2O (1.6 ml, 1 : 1, v/v) was added Zn powder (463 mg, 7.09 mmol) at
20 °C. After being stirred at 60 °C for 20 h, the reaction mixture was diluted
with saturated NaHCO3 and then extracted with CHCl3. The organic phase
was dried over MgSO4 and concentrated at reduced pressure. Purification of
the residue by preparative TLC (hexane : AcOEtꢃ2 : 1) afforded the product
16 (37.7 mg, 80%) as colorless crystal. mp 128—130 °C (AcOEt/hexane).
1
IR (CHCl3) cmꢀ1: 3438, 1652, 1512, 1481. H-NMR (CDCl3) d: 7.77 (2H,
d, Jꢃ7.3 Hz), 7.50 (1H, t, Jꢃ7.3 Hz), 7.45—7.31 (7H, m), 6.73 (1H, br s),
6.15 (1H, br t, Jꢃ8.6 Hz), 5.99 (1H, br m), 5.74 (1H, t, Jꢃ10.4 Hz), 4.55
(1H, dd, Jꢃ13.0, 8.1 Hz), 4.05 (1H, dd, Jꢃ13.0, 6.0 Hz), 3.82 (1H, br s).
13C-NMR (CDCl3) d: 167.2, 140.1, 134.0, 131.9, 131.6, 130.6, 129.0, 128.6,
128.0, 127.0, 126.7, 57.9, 50.5. MS (FABꢂ) 268 (MꢂHꢂ, 94), 105 (100).
HR-MS m/z: 268.1332 (Calcd for C17H18NO2: 268.1337). [a]D23 ꢂ3.7
(cꢃ0.7, CHCl3). Anal. Calcd for C17H18NO2: C, 76.38; H, 6.41; N, 5.24.
Found: C, 76.30; H, 6.60; N, 5.14.
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Acknowledgements This work was supported in part by a Grant-in-Aid
for Scientific Research (C) (H.M.) from the Ministry of Education, Culture,
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