Function of an N-heterocyclic carbene ligand based on concept of chiral mimetic

Article abstract of DOI:10.1248/cpb.54.1576

Function of a new N-heterocyclic carbene ligand based on the concept of a chiral mimetic is described. With (4R,5R)-4,5-diphenyl-1,3-dialkyl-4,5-dihydro- 3H-imidazol-1-ium tetrafluoroborates as N-heterocyclic carbene precursors, Rh-catalyzed enantioselect

Full text of DOI:10.1248/cpb.54.1576

1576
Chem. Pharm. Bull. 54(11) 1576—1581 (2006)
Vol. 54, No. 11
Function of an N-Heterocyclic Carbene Ligand Based on Concept of
Chiral Mimetic
Takafumi ARAO, Kei SATO, Kazuhiro KONDO,* and Toyohiko AOYAMA*
Graduate School of Pharmaceutical Sciences, Nagoya City University; 3–1 Tanabe-dori, Mizuho-ku, Nagoya 467–8603,
Japan. Received July 12, 2006; accepted August 9, 2006; published online August 16, 2006
Function of a new N-heterocyclic carbene ligand based on the concept of a chiral mimetic is described. With
(4R,5R)-4,5-diphenyl-1,3-dialkyl-4,5-dihydro-3H-imidazol-1-ium tetrafluoroborates as N-heterocyclic carbene
precursors, Rh-catalyzed enantioselective arylation (up to 27% ee) of aromatic aldehydes with arylboronic acids
and Pd-catalyzed enantioselective intramolecular a-arylation (up to 66% ee) of N-(2-bromoaryl)-N-alkyl-2-aryl-
propanamides are investigated.
Key words optically active N-heterocyclic carbene ligand; chiral mimetic; imidazolium salt; asymmetric arylation
We have been developing a novel chiral phosphine ligand tion of aromatic aldehydes with arylboronic acids was re-
1 mimicking axial chirality, in which a chiral carbon center ported by Miyaura in 1998.11) The corresponding diaryl-
induces a preferred conformation 2a by rotation around an methanols were obtained in good yields, and with MeO-
N–Ar bond which is fixed by formation of a chelate structure MOP12) as a chiral ligand, a product with 41% ee was formed
with metal (Fig. 1).1—6) In order to expand the scope of our in enantioselective Rh-catalyzed phenylation4,6,13—17) of 1-
chiral mimetic concept, we planned to develop a novel N-het- naphthaldehyde with PhB(OH)2. A recent attempt by Bolm
erocyclic carbene ligand7—9) 3. The substituent R on the sp2 using planar chiral imidazolium salts as NHC ligand precur-
N group in the carbene ligand 3 may be conformationally sors attained moderate enantioselectivity (up to 38% ee).14)
flexible, but if the complexation of 3 and metal is reflected by Bolm’s results using NHC ligands prompted us to investigate
the asymmetric center in 3, a more stable complex 4a, in the applicability of NHCs to the rather unexplored enantiose-
which the substituent R on the sp2 N group is fixed, is ex- lective arylation of aromatic aldehyde with arylboronic acids.
pected to be selectively formed (Fig. 2).10) Herein we would
We began to screen imidazolium salts as NHC ligand pre-
like to report our investigations5) on Rh-catalyzed enantiose- cursors 9a—d in enantioselective phenylation of 1-naph-
lective arylation of aromatic aldehydes 5 with arylboronic thaldehyde (5a) with PhB(OH)2 (14a). The results are shown
acids and enantioselective intramolecular a-arylation of in Table 1. At first, reactions were carried out with the use of
amides 7 with the novel N-heterocyclic carbene (NHC) lig- RhCl3·3H2O in DME/H2O (5 : 1) according to Fürstner’s pro-
and 3 (Chart 1).
cedure18) (entries 1—4). Among the imidazolium salts
Rh-Catalyzed Enantioselective Arylation of Aromatic screened, 9c possessing a t-butyl group as R substituent gave
Aldehydes with Arylboronic Acids Rh-catalyzed aryla- 20% enantioselectivity. The use of toluene/H2O (5 : 1) as sol-
vent gave the same results. In place of NaOt-Bu, KOt-Bu,
LiOt-Bu and LiOH gave same results, and use of KHMDS
and NaHMDS decreased reaction rates but ee’s were unaf-
fected. With 9c, further screening (entries 5, 6) of other
rhodium complexes was perforemed, and [RhCl(CH2ꢀ
CH2)2]2 as a Rh source was chosen from the viewpoint of
Table 1. Catalyst Screeninga)
Fig. 1
Imidazolium
salt
Yield (%) of
eeb) (%) of
Fig. 2
Entry
Rh complex
RhCl3·3H2O
6aa
6aa
1
2
3
4
9a
9b
9c
9d
9c
9c
9c
77
3 (S)
7 (S)
RhCl3·3H2O
RhCl3·3H2O
RhCl3·3H2O
[RhCl(coe)2]2
10c)
80
20 (S)
11 (S)
20 (S)
21 (S)
21 (S)
81
d)
5
59c)
93
6
[RhCl(CH2ꢀCH2)2]2
[RhCl(CH2ꢀCH2)2]2
7e)
81
a) For detailed reaction conditions, see experimental section. b) Determined by
HPLC analysis (Daicel Chiralcel OD-H). c) Remainder of mass balance was the un-
reacted 1-naphthaldehyde 5a. d) coeꢀcyclooctene. e) 6 mol% of 9c was used.
Chart 1. Enantioselective Arylation of Aldehyde and Intramolecular a-
Arylation of Amide 7
∗
To whom correspondence should be addressed.
e-mail: kazuk@phar.nagoya-cu.ac.jp; aoyama@phar.nagoya-cu.ac.jp © 2006 Pharmaceutical Society of Japan

November 2006
1577
a)
Table 2. Arylation of Aromatic Aldehydes with Ar’B(OH)2
Entry
Aromatic aldehyde
Ar’B(OH)2
Yield (%) of 6
eeb) (%) of 6
1
2
3
4
5
6
1-Naphthaldehyde (5a)
1-Naphthaldehyde (5a)
2-Naphthaldehyde (5b)
4-CF3–C6H4–CHO (5c)
2-Me–C6H4–CHO (5d)
2-MeO–C6H4–CHO (5e)
4-F–C6H4–B(OH)2 (11b)
2-Me–C6H4B(OH)2 (11c)
PhB(OH)2 (11a)
PhB(OH)2 (11a)
PhB(OH)2 (11a)
90 (6ab)
91 (6ac)
66d) (6ba)
80 (6ca)
61d) (6da)
82 (6ea)
20 (NDc))
18 (NDc))
10 (S)
11 (S)
27 (S)
PhB(OH)2 (11a)
23 (S)
a) The reactions were performed using aromatic aldehyde 5, 1.5 mol% of [RhCl(CH2ꢀCH2)2]2, 3 mol% of imidazolium salt 9c, and 2 mol equiv of Ar’B(OH)2 11 and
NaOt-Bu in DME/H2O (5 : 1) at 100 °C for 24 h. b) Determined by HPLC analysis. For detailed conditions, see experimental section. c) Not determined. d) Remainder of
mass balance was the unreacted aromatic aldehyde 5.
Table 3. Effects of Metal Sources, Ligands and Solventsa)
Fig. 3
Yield of
8a (%)
eeb) of
Entry
Metal sources Ligand
Solvent
8a (%)
Table 4. Effects of Basesa)
c)
1
2
3
4
5
6
7
8
9
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
NiCl2
9a
9b
9c
9d
DME
DME
DME
DME
DME
DME
DME
DME
14d)
16d)
8d)
67 (S)
45 (S)
41 (S)
36 (S)
23 (S)
—
—
—
50 (S)
46 (S)
—
Entry
Base
Yield of 8a (%)
eeb) of 8a (%)
13d)
7d)
1
NaOt-Bu
LiOt-Bu
LiOt-Bu
LHMDS
LiOH
KOt-Bu
KOH
NaOH
14c)
62c)
19c)
14c)
NRe)
5c)
67 (S)
61 (S)
61 (S)
6 (S)
2
10
3d)
4
9a
9a
9a
9a
9a
9a
NRe)
NRe)
NRe)
17d)
8d)
RhCl3
5
6
7
8
—
[RhCl(coe)2]2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
41 (S)
51 (S)
62 (S)
1,4-Dioxane
Toluene
DMF
25c)
16c)
10
11
0 f)
a) The reactions of 7a were performed using 10 mol% of Pd(OAc)2, 20 mol% of
imidazolium salt 9a and 2 mol equiv of the shown base in DME at 100 °C for 12 h. b)
Determined by HPLC analysis. c) Remainder of mass balance was the unreacted
starting amide 7a. d) The reaction was performed at 80 °C. e) No reaction oc-
curred.
a) The reactions of 7a were performed using 10 mol% of metal, 20 mol% of the imi-
dazolium salts and 2 mol equiv of NaOt-Bu in the shown solvent at 100 °C for 12 h.
b) Determined by HPLC analysis. c) The use of Pd2(dba)3·CHCl3 gave less satisfac-
tory results. d) Remainder of mass balance was the unreacted starting amide 5a. e)
No reaction occurred. f) The debrominated product, N-methyl-2,N-diphenyl-propi-
onamide, was obtained in 90% yield.
possessing a 1-adamantanyl group as R substituent gave bet-
chemical yield. When compared to Bolm’s data (38% ee), we ter asymmetric induction (67% ee, entry 1), although reac-
considered that our results (21% ee) might be promising. tion conversion was quite low. Other metal sources such as
Hence, we tested the ability of imidazolium salt 9c to serve Ni and Rh resulted in no reaction (entries 6—8). With 9a as
as ligand precursor in enantioselective arylation of aromatic an NHC ligand precursor, the use of other solvents such as
aldehydes with arylboronic acids. The results are shown in 1,4-dioxane, toluene and DMF gave less satisfactory results
Table 2. As can be seen, the presence of an ortho-substituent (entries 9—11).
in aromatic aldehydes resulted in slightly better asymmetric
induction, and the best enantioselectivity was obtained start- various bases as shown in Table 4. As can be seen, the choice
ing from 2-tolualdehyde (5d) (27% ee, entry 5). of base played an important role in the reaction conversion.
Using the best Pd(OAc)2-9a catalyst in DME, we screened
Enantioselective Intramolecular a-Arylation of N-(2- The use of LiOt-Bu gave the best reaction conversion with
Bromophenyl)-N-alkyl-2-arylpropanamides We chose 61% enantioselectivity (entry 2). Lowering the temperature
7a as a substrate and screened imidazolium salts 9a—d and from 100 °C to 80 °C decreased reaction rate (yield 19%),
10 as an NHC ligand precursor (Table 3), because Hartwig19) and ee was unaffected (entry 3).
and Glorius20) have reported the enantioselective a-aryla-
Finally, we examined the enantioselective a-arylation with
tion21—24) of amide 7a using carbene ligands, giving oxindole several amides 7b—j under the optimized conditions as
8a in 57% ee and 43% ee, respectively. As shown in entries shown in Fig. 4. Amides 7b—f possessing various sub-
1—5, reactions were carried out with amide 7a as a sub- stituents on the Ar group were found to be employable, ex-
strate, 10 mol% of Pd(OAc)2, 20 mol% of imidazolium salts hibiting 53—66% enantioselectivity. The substituents on the
9a—d and 10, and 2 mol equiv of NaOt-Bu in DME at N group and a-position of carbonyl group affected some-
100 °C for 12 h. Among the imidazolium salts screened, 9a what enantioselectivity (7a vs. 7g, 7h). The substraes 7i and

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Vol. 54, No. 11
Fig. 4. Enantioselective Intramolecular a-Arylation of Several Amides 7b—j
7j bearing chloro and iodo groups in place of bromo group
resulted in no reaction.
Conclusion
In summary, we have reported development of a new lig-
and based on the concept of a chiral mimetic, which opens
the possibility of synthesizing a new class of N-heterocyclic
carbenes for asymmetric catalysis. Currently, we are investi-
gating structural modifications of the imidazolum salts in
order to improve the catalyst performance in terms of activity
and enantioselectivity.
Chart 2. Representative Synthesis of Imidazolium Salt 9a
Experimental
(2 steps). colorless plates of mp 105 °C (CHCl3–hexane). [a]D24ꢀꢁ13°
1H-NMR (CDCl3): dꢀ1.10—
General IR spectra were measured on a SHIMADZU FTIR-8100 dif- (cꢀ1.25, THF). IR (nujol): nꢀ3369 cmꢁ1
.
fraction grating IR spectrophotometer. 1H- and 13C-NMR spectra were meas- 1.43 (m, 16H), 1.46—1.71 (m, 12H), 1.78—1.92 (br, 8H), 2.25—2.50 (m,
ured on a JEOL JNM-EX-270 NMR spectrometer, operating at 270 MHz for
4H), 3.59 (s, 2H), 6.95—7.04 (m, 4H), 7.05—7.18 (m, 6H). 13C-NMR
1H-NMR and at 68 MHz for 13C-NMR. H- and 13C-NMR spectra were re- (CDCl3): dꢀ28.73, 31.95, 31.78, 42.15, 42.66, 44.89, 69.58, 126.51,
ported in d units, parts per million (ppm) downfield from tetramethylsilane 127.66, 127.72, 141.53. FAB-MS: m/zꢀ537 (Mꢃꢃ1). Anal. Calcd for
(dꢀ0). EI- and FAB-MS spectra were measured on a JEOL JMS-SX-102A C38H52N2: C, 85.02, H, 9.76, N, 5.22, Found: C, 84.80, H, 9.74, N, 5.22.
1
instrument. Specific rotations (in deg cm3 gꢁ1 lꢁ1) were determined on a
JASCO DIP-1000 digital polarimeter.
(1R,2R)-N,Nꢀ-Bis-(3,3-dimethylbutyl)-1,2-diphenylethane-1,2-diamine
Representative procedure afforded the title compound in 84% yield (2
All aromatic aldehydes, arylboronic acids, and reagents were available steps). A colorless oil. [a]D24ꢀꢃ4.0° (cꢀ1.13, THF). IR (neat): nꢀ3312
1
from commercial sources and used without further purification. In general,
cmꢁ1. H-NMR (CDCl3): dꢀ0.81 (s, 18H), 1.24—1.48 (m, 4H), 2.01 (br s,
all reactions were performed under an argon atmosphere. H2O was used 2H), 2.29—2.49 (m, 4H), 3.61 (s, 2H), 6.93—7.04 (m, 4H), 7.06—7.17 (m,
without purification. DME, 1,4-dioxane and toluene were distilled from 6H). 13C-NMR (CDCl3): dꢀ29.68, 29.93, 43.91, 44.28, 69.51, 126.57,
Na/benzophenone ketyl under a nitrogen atmosphere. DMF was distilled 127.69, 127.74, 141.46. FAB-MS: m/zꢀ381 (Mꢃꢃ1). Anal. Calcd for
from CaH2. Silica gel column chromatography was performed on Fuji silysia C26H40N2: C, 82.05, H, 10.59, N, 7.36, Found: C, 82.23, H, 10.65, N, 7.01.
BW200.
Representative Procedure for the Synthesis of (1R,2R)-N,Nꢀ-bis-(1-
Adamantanylmethyl)-1,2-diphenylethane-1,2-diamine (Chart 2) To a
(1R,2R)-N,Nꢀ-Bis-(1-adamantanylmethyl)-cyclohexane-1,2-diamine
Representative procedure afforded the title compound in 29% yield (2
steps). A white solid of mp 151 °C (CHCl3–hexane). [a]D25ꢀꢃ74° (cꢀ1.05,
stirred solution of (1R,2R)-1,2-diphenyl-1,2-ethanediamine (1.50 g, THF). IR (nujol): nꢀ3313 cmꢁ1. 1H-NMR (CDCl3): dꢀ0.81—1.06 (m, 2H),
7.07 mmol) in THF (30.0 ml) were added 1-adamantanecarboxylic acid 1.08—1.32 (m, 2H), 1.36—1.80 (m, 28H), 1.87—2.14 (m, 12H), 2.46 (d,
(3.18 g, 17.7 mmol), DMAP (173 mg, 1.41 mmol), Et3N (2.46 ml, 1.79 g, Jꢀ11.3 Hz, 2H). 13C-NMR (CDCl3): dꢀ25.19, 28.50, 32.08, 33.70, 37.28,
17.7 mmol) and EDCI (3.39 g, 17.7 mmol) at 0 °C. The reaction mixture was
stirred for 2 h at 60 °C, diluted with water, and extracted with EtOAc. The C28H46N2: C, 81.89, H, 11.29, N, 6.82, Found: C, 81.66, H, 11.54, N, 6.83.
organic extracts were successively washed with 10% HCl, water, saturated
Representative Procedure for the Synthesis of (4R,5R)-4,5-Diphenyl-
40.91, 60.28, 63.43. EI-MS: m/zꢀ410 (Mꢃ), 275 (bp). Anal. Calcd for
aq. NaHCO3, water and brine, dried (Na2SO4) and concentrated. Purification 1,3-bis-(1-adamantanylmethyl)-4,5-dihydro-3H-imidazol-1-ium Tetra-
by silica gel column (CHCl3/hexane, 1 : 2) gave a mixture (2.86 g) of cou- fluoroborate (9a) (Chart 2) A suspension of (1R,2R)-N,Nꢂ-di-(1-adaman-
pling product and small amounts of impurities. This mixture was used for tanylmethyl)-1,2-diphenylethane-1,2-diamine (965 mg, 1.90 mmol) and
the next step without further separation. This mixture was dissolved in THF NH4BF4 (239 mg, 2.28 mmol) in (EtO)3CH (2.0 ml) was refluxed over night.
(20.0 ml), and to this mixture BH3 (26.7 ml, 26.7 mmol, 1.0 M solution in
The suspension was cooled to rt and concentrated. Purification by silica
THF) was added at 0 °C. The reaction mixture was heated under reflux for gel column (MeOH/CHCl3, 1 : 30) gave (4R,5R)-4,5-diphenyl-1,3-bis-(1-
4 h. After being cooled to 0 °C, MeOH was carefully poured into the reac-
adamantanylmethyl)-4,5-dihydro-3H-imidazol-1-ium tetrafluoroborate (9a)
tion mixture. The whole mixture was heated under reflux over night and con- (1.13 g, 98%) as a white amorphous solid. [a]D24ꢀꢃ127° (cꢀ1.21, THF). IR
centrated. The residue was dissolved in water and extracted with EtOAc. (nujol): nꢀ1634 cmꢁ1. 1H-NMR (CDCl3): dꢀ1.42—1.84 (m, 12H), 1.58 (d,
The organic extracts were washed with brine, dried (Na2SO4) and concen-
trated. Purification by silica gel column (CHCl3) gave (1R,2R)-N,Nꢂ-bis-(1-
Jꢀ12.7 Hz, 6H), 1.70 (d, Jꢀ12.7 Hz, 6H), 1.99 (s, 6H), 2.78 (d, Jꢀ14.7 Hz,
2H), 3.54 (d, Jꢀ14.7 Hz, 2H), 5.02 (s, 2H), 7.23—7.32 (m, 4H), 7.48—7.58
(m, 6H), 8.86 (s, 1H). 13C-NMR (CDCl3): dꢀ27.96, 34.98, 36.41, 40.25,
adamantanylmethyl)-1,2-diphenylethane-1,2-diamine (1.96 g, 54% in
2
steps) as colorless needles of mp 146 °C (CHCl3–hexane). [a]D23ꢀꢁ5° 57.53, 75.90, 126.2, 130.1, 130.2, 135.1, 160.1. FAB-MS: m/zꢀ520 (Mꢃꢁ
(cꢀ3.30, THF). IR (nujol): nꢀ3315 cmꢁ1
.
1H-NMR (CDCl3): dꢀ1.44—
BF4ꢁꢃ1). Anal. Calcd for C37H47N2BF4: C, 73.26, H, 7.81, N, 4.62, Found:
2.16 (m, 36H), 3.47 (s, 2H), 6.92—7.02 (m, 4H), 7.04—7.16 (m, 6H). 13C- C, 73.31, H, 7.56, N, 4.51.
NMR (CDCl3): dꢀ28.64, 33.85, 37.40, 40.95, 60.44, 70.67, 126.39, 127.53,
127.75, 142.03. EI-MS m/zꢀ508 (Mꢃ), 373, 254 (bp). Anal. Calcd for
C36H48N2: C, 84.98, H, 9.51, N, 5.51, Found: C, 85.05, H, 9.50, N, 5.26.
(4R,5R)-1,3-Bis-(1-adamantanylethyl)-4,5-diphenyl-4,5-dihydro-3H-
imidazol-1-ium Tetrafluoroborate (9b) Representative procedure af-
forded 9b in 94% yield. Colorless needles of mp 189 °C (CHCl3–hexane).
(1R,2R)-N,Nꢀ-Bis-(1-adamantanylethyl)-1,2-diphenylethane-1,2-di- [a]D24ꢀꢃ115° (cꢀ1.26, THF). IR (nujol) nꢀ1651, 1645 cmꢁ1
.
1H-NMR
amine Representative procedure afforded the title compound in 66% yield (CDCl3) dꢀ1.33—1.69 (m, 28H), 1.82—1.94 (br, 6H), 3.09—3.23 (m, 2H),

November 2006
1579
3.61—3.76 (m, 2H), 4.93 (s, 2H), 7.21—7.32 (m, 4H), 7.46—7.53 (m, 6H), (1S)-(1-naphthyl)phenylmethanol (6aa) (40.1 mg, 93%, 21% ee) as a color-
8.69 (s, 1H). 13C-NMR (CDCl3) dꢀ28.38, 31.72, 36.78, 41.03, 41.80, 42.01,
73.11, 127.02, 129.85, 130.04, 134.64, 157.57. FAB-MS m/zꢀ548 (Mꢃꢁ
less oil. The ee was determined by HPLC analysis with Daicel Chiralcel
OD-H (eluent: hexane/i-PrOH, flow: 1.0 ml/min). The physical data were
BF4ꢁꢃ1). Anal. Calcd for C39H51N2BF4: C, 73.81, H, 8.10, N, 4.41, Found: comparable to those reported.13) The absolute configuration was determined
C, 73.70, H, 8.16, N, 4.18.
by comparison of the reported specific rotation.4)
(4R,5R)-1,3-Bis-(2,2-dimethylpropyl)-4,5-diphenyl-4,5-dihydro-3H-
imidazol-1-ium Tetrafluoroborate (9c) To a stirred solution of (1R,2R)-
1,2-diphenyl-1,2-ethanediamine (1.50 g, 7.07 mmol) in THF (24.0 ml) were (CDCl3): dꢀ2.53 (s, 1H), 6.43 (s, 1H), 6.95 (d, Jꢀ8.6 Hz, 1H), 6.98 (d, Jꢀ
added Et3N (2.46 ml, 17.7 mmol), DMAP (173 mg, 1.41 mmol) and pivaloyl 8.6 Hz, 1H), 7.30 (d, Jꢀ5.4 Hz, 1H), 7.33 (d, Jꢀ5.4 Hz, 1H), 7.36—7.52 (m,
(ꢁ)-4-Fluorophenyl-(1-naphthyl)methanol (6ab) A white solid of mp
127 °C. [a]D24ꢀꢁ13° (cꢀ1.39, THF). IR (nujol): nꢀ3290 cmꢁ1 1H-NMR
.
chloride (7.03 ml, 56.5 mmol) at 0 °C. The reaction mixture was stirred for
3H), 7.57 (d, Jꢀ6.9 Hz, 1H), 7.73—7.89 (m, 2H), 7.89—7.99 (m, 1H). 13C-
3 h at rt, diluted with water, and extracted with EtOAc. The organic extracts NMR (CDCl3): dꢀ72.98, 115.23 (d, Jꢀ21.2 Hz), 123.72, 124.39, 124.85,
were successively washed with 10% NaOH aq., 10% HCl aq. and brine, 125.19, 125.57, 126.10, 128.51, 128.61 (d, Jꢀ7.8 Hz), 128.70, 130.36,
dried (Na2SO4) and concentrated. Purification by silica gel column 133.79, 138.40, 138.66 (d, Jꢀ3.4 Hz), 161.97 (d, Jꢀ245.4 Hz). EI-MS:
(hexane/EtOAc/CHCl3, 3 : 1 : 1) gave (1R,2R)-N,Nꢂ-bis-(2,2-dimethylpropi- m/zꢀ252 (Mꢃ), 129 (base peak), 123. Anal. Calcd for C17H13FO: C, 80.93,
onyl)-1,2-diphenylethane-1,2-diamine (2.51 g, 70%) as a white solid. [a]D24ꢀ H, 5.19, Found: C, 81.17, H, 5.49. The ee was determined by HPLC analysis
ꢁ30° (cꢀ1.15, THF). IR (nujol): nꢀ3391, 1651, 1643, 1634 cmꢁ1
NMR (CDCl3): dꢀ1.17 (s, 18H), 5.10—5.19 (m, 2H), 6.97 (br s, 2H),
7.04—7.17 (m, 10H). 13C-NMR (CDCl3): dꢀ27.42, 38.61, 59.79, 127.01,
127.39, 128.27, 138.99, 179.04. EI-MS: m/zꢀ380 (Mꢃ), 190 (bp), 57. Anal.
Calcd for C24H32N2O2: C, 75.75, H, 8.48, N, 7.36, Found: C, 75.52, H, 8.42, (m, 3H), 7.40—7.56 (m, 2H), 7.76 (d, Jꢀ7.9 Hz, 1H), 7.80—7.90 (m, 1H),
N, 7.11.
.
1H-
with Daicel chiral OD-H (eluent: hexane/i-PrOH, flow: 1.0 ml/min).
(ꢂ)-1-Naphthyl-(2-tolyl)methanol (6ac) A white solid of mp 119 °C.
[a]D24ꢀꢃ1.2° (cꢀ1.40, THF). IR (nujol): nꢀ3272 cmꢁ1. H-NMR (CDCl3):
1
dꢀ2.22 (s, 3H), 2.46 (s, 1H), 6.58 (s, 1H), 7.08—7.25 (m, 3H), 7.25—7.40
7.90—8.00 (m, 1H). 13C-NMR (CDCl3): dꢀ19.21, 69.78, 123.45, 124.42,
(1R,2R)-N,Nꢂ-Bis-(2,2-dimethylpropionyl)-1,2-diphenylethane-1,2-di- 125.19, 125.50, 125.97, 126.19, 126.56, 127.51, 128.31, 128.62, 130.34,
amine (1.83 g, 4.82 mmol) was dissolved in THF (12.0 ml), and to this mix-
ture BH3 (19.3 ml, 19.3 mmol, 1.0 M solution in THF) was added at 0 °C.
The reaction mixture was heated under reflux for 1.5 h. And to the reaction
mixture BH3 (9.65 ml, 9.65 mmol, 1.0 M solution in THF) was added at 0 °C.
The reaction mixture was heated under reflux for 14 h. MeOH was carefully
130.95, 133.66, 135.62, 138.03, 140.72. EI-MS: m/zꢀ248 (Mꢃ), 128, 119
(base peak). Anal. Calcd for C18H16O: C, 87.06, H, 6.49, Found: C, 86.94, H,
6.48. The ee was determined by HPLC analysis with Daicel chiral OD-H
(eluent: hexane/i-PrOH, flow: 1.0 ml/min).
(1S)-(2-Naphthyl)phenylmethanol (6ba) The spectral data were com-
added to the reaction mixture at 0 °C. The whole mixture was heated under parable to those reported.25) The ee was determined by HPLC analysis with
reflux and concentrated. The residue was dissolved in water and extracted Daicel chiralcel OD-H (eluent: hexane/i-PrOH, flow: 1.0 ml/min). The ab-
with EtOAc. The organic extracts were washed with brine, dried (Na2SO4) solute configuration was determined by comparison of the reported specific
and concentrated. Purification by silica gel column (hexane/EtOAc, 4 : 1) rotation.26)
gave a mixture (800 mg) of diamine and small amounts of impurities. This
mixture was used for the next step without further separation. A suspension
(1S)-Phenyl-(4-trifluoromethylphenyl)methanol (6ca) The physical
data were comparable to those reported.27) The ee was determined by HPLC
of this mixture and NH4BF4 (286 mg, 2.72 mmol) in (EtO)3CH (1.13 ml) was analysis with Daicel Chiralcel OB-H (eluent: hexane/i-PrOH, flow: 0.5 ml/
stirred for 5 h at 120 °C. The suspension was cooled to rt and concentrated. min). The absolute configuration was determined by comparison of the re-
Purification by silica gel column (MeOH/CHCl3, 5 : 95) gave (4R,5R)-1,3- ported specific rotation.27)
bis-(2,2-dimethylpropyl)-4,5-diphenyl-4,5-dihydro-3H-imidazol-1-ium tetra-
fluoroborate (9c) (561 mg, 26% in 2 steps) as colorless plates of mp 152 °C
(1S)-Phenyl-2-tolylmethanol (6da) The physical data were comparable
to those reported.25) The ee was determined by HPLC analysis with Daicel
(MeOH–hexane). [a]D23ꢀꢃ188° (cꢀ2.22, THF). IR (nujol) nꢀ1651, 1643, Chiralcel OB-H (eluent: hexane/i-PrOH, flow: 1.0 ml/min). The absolute
1634, 1626, 1620, 1614, 1601, 1583 cmꢁ1 1H-NMR (CDCl3) dꢀ0.98 (s, configuration was determined by comparison of the reported specific rota-
.
18H), 2.93 (d, Jꢀ14.5 Hz, 2H), 3.67 (d, Jꢀ14.5 Hz, 2H), 5.06 (s, 2H),
tion.27)
7.21—7.29 (m, 5H), 7.49—7.58 (m, 5H), 8.99 (s, 1H). 13C-NMR (CDCl3)
(1S)-(2-Methoxyphenyl)phenylmethanol (6ea) The physical data were
dꢀ27.70, 33.02, 57.17, 75.37, 126.21, 130.14, 130.18, 134.94, 160.42. comparable to those reported.28) The ee was determined by HPLC analysis
EI-MS m/zꢀ363 (MꢃꢁBF4ꢁ), 180 (bp), 57 (t-Bu). Anal. Calcd for with Daicel Chiralcel OB-H (eluent: hexane/i-PrOH, flow: 1.0 ml/min). The
C25H35N2BF4: C, 66.67, H, 7.83, N, 6.22, Found: C, 66.42, H, 7.87, N, 5.95.
(4R,5R)-1,3-Bis-(3,3-dimethylbutyl)-4,5-diphenyl-4,5-dihydro-3H-imi-
dazol-1-ium Tetrafluoroborate (9d) Representative procedure afforded
absolute configuration was determined by comparison of the reported spe-
cific rotation.27)
New N-(bromophenyl)-N-methyl-2-arylpropanamides 7b, 7c, and 7e—h
9d in 82% yield. Colorless plates of mp 166—167 °C (CHCl3–hexane). were prepared according to the same procedure reported.19)
[a]D24ꢀꢃ186° (cꢀ1.20, THF). IR (nujol) nꢀ1659, 1651, 1643 cmꢁ1
.
1H-
N-(2-Bromophenyl)-N-methyl-2-(4-methoxyphenyl)propanamide (7b)
NMR (CDCl3) dꢀ0.81 (s, 18H), 1.54 (dd, Jꢀ9.4, 7.7 Hz, 4H), 3.11—3.23 A colorless oil. IR (neat): nꢀ1667 cmꢁ1
.
1H-NMR (CDCl3): dꢀ1.38 (d,
(m, 2H), 3.61—3.75 (m, 2H), 4.95 (s, 2H), 7.24—7.30 (m, 4H), 7.44—7.53 Jꢀ6.8 Hz, 0.9H), 1.40 (d, Jꢀ6.8 Hz, 2.1H), 3.16 (s, 2.1H), 3.18 (s, 0.9H),
(m, 6H), 8.72 (s, 1H). 13C-NMR (CDCl3) dꢀ29.00, 29.71, 40.48, 43.42,
73.21, 127.13, 129.82, 130.02, 134.56, 134.58, 157.69. EI-MS m/zꢀ391
(MꢃꢁBF4ꢁ), 180 (bp), 57 (t-Bu). Anal. Calcd for C27H39N2BF4: C, 67.78, H,
8.22, N, 5.86, Found: C, 67.63, H, 8.11, N, 5.88.
3.29 (q, Jꢀ6.8 Hz, 0.7H), 3.46 (q, Jꢀ6.8 Hz, 0.3H), 3.77 (s, 3H), 6.69—
6.78 (m, 2.7H), 6.84—6.97 (m, 2H), 7.13—7.46 (m, 2.3H), 7.59 (dd, Jꢀ7.9,
1.3 Hz, 0.3H), 7.67—7.73 (m, 0.7H). 13C-NMR (CDCl3): dꢀ20.22
(mꢀminor isomer), 20.74 (MꢀMajor isomer), 36.13 (m), 36.17 (M), 42.40
(3aR,7aR)-1,3-Bis-(1-adamantanylmethyl)-3a,4,5,6,7,7a-hexahydro- (m), 43.19 (M), 55.22 (M), 55.24 (m), 113.54 (m), 113.68 (M), 123.59 (M),
3H-benzoimidazol-1-ium Tetrafluoroborate (10) Representative proce- 124.11 (m), 128.30 (m), 128.34 (M), 128.52 (m), 128.88 (M), 129.50 (M),
dure afforded 10 in 92% yield. Colorless plates of mp 248—250 °C
(CHCl3–hexane). [a]D24ꢀꢃ4.7° (cꢀ0.987, THF). IR (nujol) nꢀ1608 cmꢁ1
1H-NMR (CDCl3) dꢀ1.21—1.80 (m, 5H), 1.50 (s, 12H), 1.63 (d, Jꢀ12.2
129.54 (m), 129.94 (m), 130.78 (M), 132.76 (m), 133.41 (M), 133.72 (M),
133.89 (m), 142.24 (M), 142.51 (m), 158.22 (M), 158.32 (m), 173.83 (M),
174.06 (m). EI-MS m/zꢀ347 (Mꢃ), 268, 145, 135 (bp). Anal. Calcd for
.
Hz, 6H), 1.73 (d, Jꢀ12.2 Hz, 6H), 1.91—2.09 (m, 2H), 2.03 (br s, 6H), 2.28 C17H18BrNO2: C, 58.63, H, 5.21, N, 4.02, Found: C, 58.93, H, 5.38, N, 3.71.
(d, Jꢀ11.1 Hz, 2H), 3.11 (d, Jꢀ14.6 Hz, 2H), 3.33 (d, Jꢀ14.6 Hz, 2H),
3.45—3.54 (m, 2H), 8.06 (s, 1H). 13C-NMR (CDCl3) dꢀ23.65, 27.65, A colorless oil. IR (neat): nꢀ1666 cmꢁ1
27.91, 34.02, 36.36, 40.12, 57.38, 69.83, 161.99. FAB-MS m/zꢀ422
N-(2-Bromophenyl)-N-methyl-2-(4-fluorophenyl)propanamide
(7c)
.
1H-NMR (CDCl3): dꢀ1.38 (d,
Jꢀ7.0 Hz, 0.9H), 1.41 (d, Jꢀ7.0 Hz, 2.1H), 3.16 (s, 2.1H), 3.18 (s, 0.9H),
(Mꢃꢃ1ꢁBF4ꢁ). Anal. Calcd for C29H45N2BF4: C, 68.50, H, 8.92, N, 5.51, 3.34 (q, Jꢀ7.0 Hz, 2.1H), 3.50 (q, Jꢀ7.0 Hz, 0.9H), 6.69—6.75 (m, 0.7H),
Found: C, 68.62, H, 8.92, N, 5.34. 6.83—7.01 (m, 4H), 7.15—7.46 (m, 2.3H), 7.60 (dd, Jꢀ8.1, 1.4 Hz, 0.3H),
Representative Procedure for the Rh(I)-Catalyzed Asymmetric Aryla- 7.69—7.74 (m, 0.7H). 13C-NMR (CDCl3): dꢀ20.30 (mꢀminor isomer),
tion of 1-Naphthaldehyde (5a) with Phenylboronic Acid (11a) To a
stirred solution of [RhCl(CH2ꢀCH2)2]2 (1.1 mg, 0.027 mmol) in DME (0.30
20.79 (MꢀMajor isomer), 36.20 (m), 36.24 (M), 42.54 (m), 43.31 (M),
114.69 (m), 114.92 (M), 115.00 (m), 115.23 (M), 128.38 (M), 128.63 (m),
ml) and H2O (0.060 ml) were added imidazolium salt 9c (2.5 mg, 0.0055 128.78 (M), 128.89 (M), 129.34 (m), 129.46 (m), 129.65 (M), 129.70 (m),
mmol), NaOt-Bu (35.4 mg, 0.368 mmol), PhB(OH)2 (11a) (44.9 mg, 0.368 129.95 (m), 130.61 (M), 133.55 (M), 133.95 (m), 136.28 (d, Jꢀ2.7 Hz) (m),
mmol), and 1-naphthaldehyde (5a) (28.8 mg, 0.184 mmol). The reaction
137.29 (d, Jꢀ3.4 Hz) (M), 142.12 (M), 142.36 (m), 159.75 (M), 159.89 (m),
mixture was stirred for 8 h at 100 °C and allowed to cool. After usual work- 163.36 (M), 163.49 (m), 173.41 (M), 173.58 (m). FAB-MS m/zꢀ336
up, purification by silica gel column (hexane : EtOAcꢀ19/1 to 9/1) afforded (Mꢃꢃ1). Anal. Calcd for C16H15BrFNO: C, 57.16, H, 4.50, N, 4.17, Found:

1580
Vol. 54, No. 11
7.16 (dd, Jꢀ7.3, 8.9 Hz, 1H), 7.22—7.38 (m, 3H). 13C-NMR (CDCl3): dꢀ
24.15, 26.57, 51.59, 108.36, 115.04, 115.35, 122.77, 128.17, 128.23,
128.35, 134.35, 136.38 (d, Jꢀ3.3 Hz), 143.03, 160.03, 163.64, 179.06. EI-
MS m/zꢀ255 (Mꢃ), 240 (bp). HR-MS (EI): Calcd for C16H14FNO, [Mꢃ]:
255.1059. Found: 255.10559.
C, 56.89, H, 4.73, N, 3.91.
N-(2-Bromophenyl)-N-methyl-2-(3-tolyl)propanamide (7e) A yellow
oil. IR (neat): nꢀ1666, 1661 cmꢁ1
.
1H-NMR (CDCl3): dꢀ1.40 (d,
Jꢀ6.9 Hz, 0.9H), 1.42 (d, Jꢀ6.9 Hz, 2.1H), 2.25 (s, 3H), 3.16 (s, 2.1H), 3.18
(s, 0.9H), 3.30 (q, Jꢀ6.9 Hz, 0.7H), 3.50 (q, Jꢀ6.9 Hz, 0.3H), 6.61—6.83
(m, 2.7H), 6.91—7.46 (m, 4.3H), 7.56 (br d, Jꢀ7.9 Hz, 0.3H), 7.70 (dd,
Jꢀ1.6, 7.7 Hz, 0.7H). 13C-NMR (CDCl3): dꢀ19.91, 20.52, 21.32, 21.34,
36.10, 36.13, 43.21, 44.00, 123.48, 124.06, 124.33, 124.81, 127.19, 127.23,
127.82, 127.92, 127.97, 128.07, 128.38, 128.53, 129.38, 129.40, 129.89,
130.80, 133.27, 133.72, 137.40, 137.70, 140.15, 141.33, 142.04, 142.31,
173.49, 173.69. EI-MS: m/zꢀ252 (MꢃꢁBr), 119 (bp). FAB-MS: m/zꢀ334
(Mꢃꢃ1), 332 (Mꢃꢃ1). HR-MS (MꢃꢁBr) Calcd for C17H18NO: 252.1388,
Found: 252.1384.
(3S)-1,3-Dimethyl-3-(3-tolyl)-1,3-dihydro-indol-2-one (8e)
A
color-
.
less oil. [a]D29ꢀꢃ68° (cꢀ1.19, THF). IR (neat): nꢀ1720, 1715 cmꢁ1
1H-
NMR (CDCl3): dꢀ1.77 (s, 3H), 2.30 (s, 3H), 3.24 (s, 3H), 6.90 (d, Jꢀ7.6
Hz, 1H), 7.00—7.20 (m, 6H), 7.31 (ddd, Jꢀ1.3, 7.6, 7.6 Hz, 1H). 13C-NMR
(CDCl3): dꢀ21.64, 23.78, 26.53, 52.11, 108.17, 122.65, 123.54, 124.04,
127.16, 127.90, 128.26, 134.91, 137.98, 140.56, 143.07, 179.36. EI-MS:
m/zꢀ251 (Mꢃ), 236 (bp, MꢃꢁMe). HR-MS (Mꢃ) Calcd for C17H17NO:
251.1310, Found: 251.1312.
N-(2-Bromophenyl)-N-methyl-2-(2-naphthyl)propanamide
(7f) A
(3S)-1,3-Dimethyl-3-(2-naphthyl)-1,3-dihydro-indol-2-one (8f) A col-
yellow oil. IR (neat): nꢀ1666, 1661 cmꢁ1 1H-NMR (CDCl3): dꢀ1.49 (d,
.
orless solid of mp 125 °C. [a]D29ꢀꢃ37° (cꢀ0.91, THF). IR (neat): nꢀ1728,
1715, 1693, 1682 cmꢁ1 1H-NMR (CDCl3): dꢀ1.89 (s, 3H), 3.27 (s, 3H),
.
Jꢀ6.9 Hz, 0.9H), 1.51 (d, Jꢀ6.9 Hz, 0.9H), 3.16 (s, 2.1H), 3.18 (s, 0.9H),
3.51 (q, Jꢀ6.9 Hz, 0.7H), 3.70 (q, Jꢀ6.9 Hz, 0.3H), 6.59 (dd, Jꢀ1.6, 7.7 Hz,
0.7H), 7.03 (ddd, Jꢀ1.3, 7.6, 7.6 Hz, 0.7H), 7.09—7.29 (m, 2H), 7.30—7.55
(m, 3.8H), 7.60—7.88 (m, 3.8H). 13C-NMR (CDCl3): dꢀ19.98, 20.54,
36.08, 36.10, 43.33, 44.16, 123.42, 124.05, 125.14, 125.32, 125.44, 125.55,
125.68, 125.81, 126.00, 126.54, 127.23, 127.28, 127.42, 127.46, 127.56,
127.83, 128.11, 128.45, 129.46, 129.84, 130.68, 132.12, 132.24, 133.11,
133.30, 133.70, 137.75, 138.84, 141.92, 142.22, 173.25, 173.45. EI-MS:
m/zꢀ369 (Mꢃ), 367 (Mꢃ), 288, 155 (bp). HR-MS (Mꢃ) Calcd for
C20H1879BrNO: 367.0572, Found 367.0576, Calcd for C20H1881BrNO:
369.0551, Found: 369.0590.
6.94 (d, Jꢀ7.7 Hz, 1H), 7.10 (ddd, Jꢀ0.8, 7.4, 7.4 Hz, 1H), 7.20 (dd, Jꢀ0.8,
7.4 Hz, 1H), 7.30—7.38 (m, 2H), 7.38—7.48 (m, 2H), 7.70—7.83 (m, 4H).
13C-NMR (CDCl3): dꢀ23.69, 26.58, 52.33, 108.28, 122.75, 124.14, 124.78,
125.19, 125.86, 125.95, 127.30, 127.96, 128.09, 128.20, 132.37, 133.09,
134.75, 138.01, 143.15, 179.20. EI-MS: m/zꢀ287 (Mꢃ), 272 (bp, MꢃꢁMe).
HR-MS (Mꢃ) Calcd for C17H17NO: 287.1310, Found: 251.1308.
(3S)-1-Ethyl-3-methyl-3-phenyl-1,3-dihydro-indol-2-one (8g) A yel-
low oil. [a]D29ꢀꢃ34° (cꢀ0.60, THF). IR (neat): nꢀ1713 cmꢁ1 1H-NMR
.
(CDCl3): dꢀ1.28 (dd, Jꢀ7.1, 7.3 Hz, 3H), 1.78 (s, 3H), 3.76 (dq, Jꢀ7.1,
14.2 Hz, 1H), 3.82 (dq, Jꢀ7.3, 14.2 Hz, 1H), 6.93 (d, Jꢀ7.7 Hz, 1H), 7.06
(ddd, Jꢀ0.8, 7.4, 7.4 Hz, 1H), 7.14—7.35 (m, 7H). 13C-NMR (CDCl3): dꢀ
12.76, 23.67, 34.87, 52.08, 108.36, 122.43, 124.21, 126.45, 127.04, 127.88,
128.42, 135.16, 140.76, 142.13, 178.85. EI-MS: m/zꢀ251 (bp, Mꢃ), 236
(MꢃꢁMe). HR-MS (Mꢃ) Calcd for C17H17NO: 251.1310, Found: 251.1313.
(3S)-3-Ethyl-1-methyl-3-phenyl-1,3-dihydro-indol-2-one (8h) A col-
orless solid of mp 82 °C. [a]D29ꢀꢃ55° (cꢀ0.75, THF). IR (nujol): nꢀ
N-(2-Bromophenyl)-N-ethtyl-2-phenylpropanamide (7g)
A yellow
oil. IR (neat): nꢀ1664 cmꢁ1 1H-NMR (CDCl3): dꢀ1.06 (t, Jꢀ7.2 Hz,
.
2.1H), 1.10 (t, Jꢀ7.2 Hz, 0.9H), 3.30 (q, Jꢀ6.9 Hz, 1.4H), 3.46 (q,
Jꢀ6.9 Hz, 0.6H), 4.04 (q, Jꢀ6.9 Hz, 0.7H), 4.27 (q, Jꢀ6.9 Hz, 0.3H), 6.60
(dd, Jꢀ1.7, 7.7 Hz, 0.7H), 6.89—7.46 (m, 7.3H), 7.59 (dd, Jꢀ1.4, 7.9 Hz,
0.3H), 7.71 (dd, Jꢀ1.4, 7.9 Hz, 0.7H). 13C-NMR (CDCl3): dꢀ12.70, 12.80,
20.21, 20.64, 42.92, 43.39, 43.50, 44.43, 124.23, 124.62, 126.37, 126.48,
127.17, 127.76, 127.86, 127.93, 127.96, 128.15, 129.28, 129.40, 131.27,
131.69, 133.31, 133.84, 140.43, 141.49, 141.62, 172.90, 173.11. EI-MS:
m/zꢀ252 (MꢃꢁBr), 105 (bp). FAB-MS: m/zꢀ334 (Mꢃꢃ1), 332 (Mꢃꢃ1).
HR-MS (MꢃꢁBr) Calcd for C17H18NO: 252.1388, Found: 252.1386.
1711 cmꢁ1 1H-NMR (CDCl3): dꢀ0.68 (dd, Jꢀ7.3, 7.4 Hz, 3H), 2.23 (dq,
.
Jꢀ7.4, 13.5 Hz, 1H), 2.43 (dq, Jꢀ7.3, 13.5 Hz, 1H), 6.90 (d, Jꢀ7.7 Hz, 1H),
7.11 (ddd, Jꢀ1.0, 7.4, 7.4 Hz, 1H), 7.16—7.40 (m, 7H). 13C-NMR (CDCl3):
dꢀ9.12, 26.37, 30.93, 57.32, 108.08, 122.44, 124.66, 126.84, 127.07,
127.95, 127.98, 128.35, 131.95, 140.11, 143.98, 178.37. EI-MS: m/zꢀ251
(Mꢃ), 222 (bp, MꢃꢁEt). HR-MS (Mꢃ) Calcd for C17H17NO: 251.1310,
Found: 251.1310.
N-(2-Bromophenyl)-N-methyl-2-phenylbutanamide (7h)
A yellow
oil. IR (neat): nꢀ1666 cmꢁ1 1H-NMR (CDCl3): dꢀ0.78 (t, Jꢀ7.3 Hz,
.
0.9H), 0.82 (t, Jꢀ7.3 Hz, 2.1H), 1.67 (dq, Jꢀ7.4, 28.7 Hz, 1.4H), 2.09 (dq,
Jꢀ7.4, 28.7 Hz, 0.6H), 3.02 (t, Jꢀ7.4 Hz, 0.7H), 3.15 (s, 2.1H), 3.18 (s,
0.9H), 3.23 (t, Jꢀ7.4 Hz, 0.3H), 6.59 (dd, Jꢀ1.7, 7.8 Hz, 0.7H), 6.90—7.46
(m, 7.3H), 7.57 (dd, Jꢀ1.5, 8.0 Hz, 0.3H), 7.70 (dd, Jꢀ1.5, 8.0 Hz, 0.7H).
13C-NMR (CDCl3): dꢀ12.43, 12.66, 28.23, 28.47, 36.07, 36.08, 51.04,
52.05, 123.33, 124.29, 126.55, 126.60, 127.82, 127.98, 128.14, 128.16,
128.32, 128.46, 129.54, 130.33, 131.00, 133.39, 133.85, 138.97, 140.08,
141.99, 142.39, 172.79, 172.97. EI-MS: m/zꢀ252 (MꢃꢁBr, bp). FAB-MS:
m/zꢀ334 (Mꢃꢃ1), 332 (Mꢃꢃ1). HR-MS (MꢃꢁBr) Calcd for C17H18NO:
252.1388, Found: 252.1366.
Reresentative Procedure for the Enantioselective Intramolecular a-
Arylation of Amide 7a with Imidazolium Salt 9a (Entry 2, Table 4) To
a stirred solution of N-(2-bromophenyl)-N-methyl-2-phenylpropanamide19)
(7a) (63.6 mg, 0.200 mmol) in DME (1.0 ml) were added imidazolium salts
9a (24.3 mg, 0.0400 mmol), Pd(OAc)2 (4.5 mg, 0.0200 mmol) and LiOt-Bu
(48.0 mg, 0.600 mmol) at rt and the mixture was stirred for 12 h at 100 °C.
After being cooled to rt, the mixture was filtered through a layer of silica gel
and evaporated. Purification by silica gel column (EtOAc/hexane, 1 : 8) gave
(3S)-1,3-dimethyl-3-phenyl-1,3-dihydro-indol-2-one (8a) (29.3 mg, 62%,
61% ee). The spectral data of 8a were comparable to those reported.19)
The spectral data of the oxindole 8d were comparable to those reported.19)
The physical data of new oxindoles 8b, 8c and 8e—h were shown as fol-
lows.
(3S)-1,3-Dimethyl-3-propyl-1,3-dihydro-indol-2-one (13) A solution
of 10% Pd/C (10 mg) and (3S)-3-allyl-1,3-dimethyl-1,3-dihydro-indol-2-one
(12) (95.6 mg, 0.363 mmol) was stirred at rt for 3 h under H2 atmosphere.
The mixture was filtered and evaporated. Purification by silica gel column
(EtOAc/hexane, 1 : 8) gave (3S)-1,3-dimethyl-3-phenyl-1,3-dihydro-indol-2-
one (13) (64.3 mg, 67%) as a colorless oil. [a]D19ꢀꢃ153° (cꢀ1.56, THF). IR
(neat): nꢀ1720, 1717, 1714 cmꢁ1. 1H-NMR (CDCl3, 50 °C): dꢀ0.75—1.02
(m, 1H), 0.84 (t, Jꢀ6.6 Hz, 3H), 1.04—1.22 (m, 1H), 2.04—2.22 (m, 1H),
2.24—2.42 (m, 1H), 3.21 (s, 3H), 6.88 (d, Jꢀ7.6 Hz, 1H), 7.09 (dd, Jꢀ7.6,
7.6 Hz, 1H), 7.16—7.39 (m, 7H). 13C-NMR (CDCl3): dꢀ14.27, 18.06,
26.39, 40.23, 56.85, 108.08, 122.43, 124.67, 126.77, 127.07, 127.95,
128.36, 132.37, 140.30, 143.86, 178.51. EI-MS m/zꢀ265 (Mꢃ), 222 (bp).
Anal. Calcd for C18H19NO: C, 81.47, H, 7.22, N, 5.28, Found: C, 81.33, H,
7.25, N, 5.32.
The absolute configurations of oxindoles 8a—h were determined by com-
parison with the CD spectrum of 13 (Chart 3), whose absolute configuration
was known.29)
(3S)-3-(4-Methoxyphenyl)-1,3-dimethyl-1,3-dihydro-indol-2-one (8b)
A colorless oil. [a]D24ꢀꢃ57° (cꢀ0.83, THF). IR (neat): nꢀ1717 cmꢁ1. H-
1
Chart 3
NMR (CDCl3): dꢀ1.75 (s, 3H), 3.23 (s, 3H), 3.76 (s, 3H), 6.81 (d, Jꢀ
8.6 Hz, 2H), 6.90 (d, Jꢀ8.1 Hz, 1H), 7.43—7.37 (m, 5H). 13C-NMR
(CDCl3): dꢀ23.97, 26.50, 51.49, 55.25, 108.17, 113.78, 122.61, 124.02,
127.64, 127.91, 132.73, 134.81, 143.06, 158.54, 179.48. EI-MS m/zꢀ267
(Mꢃ), 252 (bp). HR-MS (EI): Calcd for C17H17NO2, [Mꢃ]: 267.1259. Found:
267.1260.
Acknowledgements We thank the Ministry of Education, Culture,
Sports, Science and Technology, Japan for support. K. K. was financially
supported by Takeda Science Foundation.
(3S)-3-(4-Fluorophenyl)-1,3-dimethyl-1,3-dihydro-indol-2-one (8c)
A
colorless oil. [a]D24 ꢃ68° (cꢀ1.30, THF). IR (neat): nꢀ1717 cmꢁ1. 1H-NMR
(CDCl3): dꢀ1.76 (s, 3H), 3.24 (s, 3H), 6.89—7.02 (m, 1H), 6.93 (dd, Jꢀ
7.5, 8.6 Hz, 1H), 6.96 (dd, Jꢀ8.4, 8.6 Hz, 1H), 7.10 (dd, Jꢀ7.3, 7.6 Hz, 1H),
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