Chiral Bronsted acid catalyzed asymmetric Friedel-Crafts alkylation reaction of indoles with α,β-unsaturated ketones: Short access to optically active 2- and 3-substituted indole derivatives

Article abstract of DOI:10.1039/c0ob00197j

The asymmetric Friedel-Crafts alkylation reaction of indoles with α,β-unsaturated ketones catalyzed by chiral phosphoric acid is reported. A wide range of indoles and 4,7-dihydroindoles were allowed to react with α,β-unsaturated ketones to give the corres

Full text of DOI:10.1039/c0ob00197j

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Chiral Brønsted acid catalyzed asymmetric Friedel–Crafts alkylation reaction
of indoles with a,b-unsaturated ketones: short access to optically active 2- and
3-substituted indole derivatives
Tsubasa Sakamoto, Junji Itoh, Keiji Mori and Takahiko Akiyama*
Received 2nd June 2010, Accepted 6th August 2010
DOI: 10.1039/c0ob00197j
The asymmetric Friedel–Crafts alkylation reaction of indoles with a,b-unsaturated ketones catalyzed
by chiral phosphoric acid is reported. A wide range of indoles and 4,7-dihydroindoles were allowed to
react with a,b-unsaturated ketones to give the corresponding 1,4-adducts in good to high chemical
yields and with excellent enantioselectivities.
imines (Fig. 2).6 Since then, phosphoric acid chemistry has been
extensively studied with its main focus being on the reaction with
imines.7,8 Recent studies have shown that aziridine, enecarbamate,
nitroalkene, and carbonyl compounds are also suitable substrates.9
Introduction
The indole skeleton is frequently encountered in biologically
active compounds and pharmaceuticals, such as rhazinoline,
(-)-eudistomin C, scholarisine A, and (+)-vinblastine (Fig. 1).1
Because of their important biological activities, the development
of new approaches for the synthesis of enantio-enriched indole
derivatives has been emphasized.2 The enantioselective Friedel–
Crafts alkylation reaction of indole constitutes an important
method for the preparation of optically active 3-substituted indole
derivatives.3 Recently, the asymmetric Friedel–Crafts reaction of
indole with a,b-unsaturated carbonyl compounds, in particular,
has attracted much attention and a range of reactions exploit-
ing transition metal catalysts and organocatalysts have been
developed.4,5
Fig. 2 Chiral phosphoric acid catalysts.
Encouraged by our success in the Friedel–Crafts reaction of
indoles with nitroalkenes,9g we envisioned that 1,3-diaryl a,b-
unsaturated ketone would be a promising carbonyl reaction
partner (Scheme 1).5
Scheme 1 This work.
Although Zhou and co-workers already reported the asymmet-
ric Friedel–Crafts alkylation reaction of indole derivatives with
1,3-diaryl a,b-unsaturated ketones catalyzed by 3, the yields and
enantiomeric excess (ee) were not satisfactory (up to 56% ee).5a,5b
Rueping and co-workers also achieved a highly enantioselective
Friedel–Crafts reaction. However, a b,g-unsaturated a-ketoester
possessing high electrophilic activity had to be employed as
a reaction partner.5c We describe herein a chiral phosphoric
acid catalyzed highly enantioselective Friedel–Crafts alkylation
reaction of indoles with simple a,b-unsaturated ketones.
Fig. 1 Bioactive molecules bearing indole skeleton.
We found that chiral phosphoric acids 3 synthesized from (R)-
BINOL worked as efficient chiral catalysts for the reaction with
imines, thereby demonstrating that 3 are efficient activators of
Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1
Mejiro, Toshima-ku, Tokyo 171-8588, Japan. E-mail: takahiko.akiyama@
gakushuin.ac.jp; Fax: (+81) 3 5992 1029; Tel: (+81) 3 3986 0221
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Table 1 Effect of phosphoric acid
Table 3 Friedel–Crafts alkylation reaction to give 3-substituted indole
analogues
Entry
Catalyst
Time/h
Yield (%)a
ee (%)b
Entry X
R1
R2
4
Time/h Yield (%)a ee (%)b
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3f
3g
3h
3i
7
36
31.5
49.5
22.5
46.5
26
76
23
47
19
quant.
70
quant.
quant.
quant.
30
49
-16
20
50
55
58
67
76
1
2
3
4
5
6
7
H(1a)
Ph
5-MeO(1b) Ph
5-BnO(1c) Ph
Ph(2a) 4a 48
87
98
94
53
42
97
90
79
74
67
94
37
94
92
91
91
90
89
88
86
90
90
91
90
91
58
Ph
Ph
Ph
Ph
Ph
4b 48
4c 34
4d 167
4e 167
4f 40
5-Cl(1d)
Ph
Ph
Ph
5-Br(1e)
7-Me(1f)
35
22
H
H
H
H
H
H
H
2-ClC6H4 Ph(2b) 4g 48
3-ClC6H4 Ph(2c) 4h 48
4-ClC6H4 Ph(2d) 4i 48
4-BrC6H4 Ph(2e) 4j 48
4-FC6H4 Ph(2f) 4k 96
8
a Isolated yield. b Determined by HPLC on a chiral stationary phase using
Daicel Chiralpak AD-H column.
9c
10c
11
12
13
Ph
Me
Me(2g) 4l 48
Ph(2h) 4m 15
Table 2 Optimization of the reaction conditions
a Isolated yield. b Determined by HPLC on a chiral stationary phase using
Daicel Chiralpak AD-H, AS-H column, and Daicel Chiralcel OD-H
column. c Mesitylene/ClCH2CH2Cl = 3/5, 0.25 mol L-1, -20 ◦C.
experiment (-40 ◦C) in mesitylene improved the enantioselectivity
to 87% ee, but this was accompanied by a decrease of the chemical
yield and a long reaction time (entry 7, 137 h). The ee could be
further enhanced to 91% by employing the mixed solvent system of
mesitylene and dichloroethane (entry 8). We were pleased to find
Entry Solvent
Temp./◦CTime/hYield (%)a ee (%)b
1
2
3
4
5
6
7
8
9c
Toluene
THF
CH2Cl2
rt
rt
22
48
quant.
4
76
40
rt
rt
39
34
84
96
73
75
ClCH2CH2Cl
Benzene
Mesitylene
Mesitylene
Mesitylene/(CH2Cl)2 = 1/1 -40
Mesitylene/(CH2Cl)2 = 1/1 -40
˚
that the addition of MS 3 A accelerated the reaction, affording 4a
rt
rt
-40
18
18
137
137
48
quant.
quant.
69
79
87(61)
72
77
87
in 87% yield within 48 h (entry 9). Enantiomerically pure adduct
4a could be obtained by single recrystallization from ethanol.
The absolute configuration of 4a was determined to be R by
comparison of the optical rotation with that of the reported data.10
Under the optimized conditions, the scope of the reaction was
examined (Table 3). In all cases of indole derivatives, excellent
ees were achieved while the chemical yields dramatically changed
depending on the substituent on the indoles. Electron-rich indoles
were obtained in excellent yields (entries 2 and 3). Indoles bearing
electron-withdrawing substituents (Cl, Br) had moderate chemical
yields and the reaction time was long (entries 4, 5, 167 h). It
should be noted that 7-methylindole adduct 4f had excellent ee
(88% ee) although 7-methylindole had low ee in the asymmetric
Friedel–Crafts reaction with a,b-unsaturated acyl phosphonates
(19% ee).5f
The substituents on a,b-unsaturated ketones were well toler-
ated. 2-Chloro-, 3-chloro-, and 4-fluorochalcone gave adducts
4 in high yields with high enantioselectivities (entries 7, 8,
and 11). On the other hand, 4-chloro- and 4-bromochalcone
exhibited low reactivities (20%) under the same conditions. By
tuning the reaction conditions (concentration, solvent ratio, and
temperature), the chemical yields were improved to 74% and 67%,
respectively, and the ees remained high (entries 9 and 10). While
the chemical yield of alkyl-substituted adduct 4l (R2 = Me) was
moderate due to the low reactivity, its ee was excellent (entry 12).
1-Phenylbut-2-en-1-one gave the corresponding adduct 4m with
91
92(>99)d
a Isolated yield. b Determined by HPLC on a chiral stationary phase
using Daicel Chiralpak AD-H column. MS 3 A was employed. d After
c
˚
recrystallization.
Results and discussion
At the outset, we studied the effects of chiral phosphoric acid
catalysts 3 on the reaction of indole 1 with chalcone 2 (Table 1).
Adduct 4 was obtained in good yield with moderate ee using
catalyst 3a bearing a phenyl group at 3,3¢-position (entry 1, 76%,
30% ee). Further screening of the catalysts revealed that the
catalysts with electron-withdrawing groups gave better results in
term of chemical yield and enantioselectivity (entries 2–5). Of
note was that phosphoric acid 3i (Ar = 2,4-(CF3)2C6H3) gave
4a in excellent yield and high enantioselectivity (entry 9, quant.,
76% ee).
Table 2 lists the results of investigation of the reaction conditions
for the further enhancement of enantioselectivity. Although the
reaction was sluggish in THF (entry 2), non-polar solvents,
such as CH2Cl2, ClCH2CH2Cl, and benzene, gave 4a in almost
quantitative yields with high ee (entries 3–5). Mesitylene turned
out to be the solvent of choice (entry 6). Low-temperature
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lower enantioselectivity (entry 13). The absolute configurations of
the adducts (4b–4l) were surmised by analogy with 4a.
Although You and co-workers reported the successful oxidation
of dihydroindole by employing benzoquinone as an oxidant,12
the oxidation of 6a by benzoquinone or DDQ gave 7a in
only 50% yield, accompanied by the formation of byproduct
8 (Scheme 2). The dihydroquinone that was produced after
oxidation induced dehydrative condensation followed by double
bond isomerization14 to afford 8. We found that treatment with
We also studied the utility of the enantioselective Friedel–
Crafts reaction for the construction of the optically active 2-
substituted indole skeleton. Recently, the asymmetric syntheses
of 2-substituted indole were developed by taking advantage of the
pyrrole-like reactivity of 4,7-dihydroindole (Fig. 3).11 Wang and
You explored the organocatalytic enantioselective reactions of 4,7-
dihydroindole.12 Although You and co-workers thoroughly studied
the chiral phosphoric acid catalyzed asymmetric Friedel–Crafts
alkylation reaction of 4,7-dihydroindole with imine, nitroalkene,
b,g-unsaturated a-ketoester, and a,b-unsaturated aldehyde,12b–d
the reaction with a,b-unsaturated ketone remains to be investi-
gated.
R
5 mol% of RuZrPꢀ15 at molecular oxygen atmosphere gave 7a in
quantitative yield.
Scheme 2 Oxidation to 2-substituted indole 7a.
This method could also be applied to various a,b-unsaturated
ketones (Table 5). The asymmetric Friedel–Crafts alkylation
reaction and the subsequent oxidation afforded 7 with high
enantioselectivities regardless of the substituent on the phenyl
group at the 3-position of 2 (entries 2–5, 82–85% ee).
Interestingly, although the same (R)-phosphoric acid catalysts
were employed in both Friedel–Crafts reactions, the absolute
configuration of the corresponding adducts was switched. In
the case of dihydroindole, the enriched enantiomer was the (S)-
enantiomer,16 while the (R)-isomer was the major indole in the
Friedel–Crafts reaction.
To gain insight into the reaction mechanism we examined the
reaction of N-Me indole with chalcone under the optimized
reaction conditions. As expected, both the chemical yield and
enantioselectivity diminished (25%, 56% ee).9g The plausible
transition states of these reactions are illustrated in Fig. 4.17 The
Fig. 3 Reactivity of 4,7-dihydroindole.
First, we studied the Friedel–Crafts reaction of 5 under the
optimized conditions (Table 3) to give corresponding 2-adduct 6a
with moderate enantioselectivity (quant., 50% ee). The search for
the most effective catalyst yielded fascinating knowledge: while the
electronic factor of a catalyst is important for the Friedel–Crafts
reaction of an indole, the steric factor governs the selectivity in this
case. Both the reaction temperature and some additives turned out
to be critical factors affecting ee, as in the case of indole: when the
◦
˚
reaction was performed at -78 C in the presence of MS 4 A,
enantioselectivity was improved to 85% ee (Table 4,13 entry 6).
Table 5 Friedel–Crafts alkylation reaction to give 2-substituted indole
analogues
Table 4 Screening for catalysts for the reaction of 4,7-dihydroindole
R1
7
Yield (%)a
ee (%)b
Entry
Catalyst
Time/h
Yield (%)a
ee (%)b
Entry
1
2
3
4
5
6c
3b
3c
3d
3e
3i
2
1
3.5
3
1
91
93
86
77
80
79
10
56
42
23
53
85
1
2
3
4
5
6
Ph
7a
7b
7c
7d
7e
7f
90
51
65
69
58
79c
87
84
85
82
85
79d
4-ClC6H4
4-BrC6H4
4-FC6H4
4-MeOC6H4
Me
3c
48
a NMR yield of a mixture of 6a and corresponding indole 7a. b Determined
a Isolated yield. b Determined by HPLC on a chiral stationary phase
using Daicel Chiralpak AS-H and AD-H column. c 10 h. d S-isomer was
obtained.
by HPLC on a chiral stationary phase using Daicel Chiralpak AS-H
◦
c
˚
column. The reaction was performed in the presence of MS 4 A at -78 C.
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Fig. 4 Plausible transition states.
reversal of facial selectivity is ascribed to the difference in the
direction of the a,b-unsaturated ketone. In the case of indole, TS
A was preferred over TS B because of the p,p-stacking between
the indole benzene ring and the benzene ring at the 3-position
of the chalcone moiety. On the other hand, in the case of 4,7-
dihydroindole, the collapse of aromaticity brought about severe
steric repulsion (Fig. 4), which led to TS D being the predominant
transition state.
In summary, we have developed the phosphoric acid catalyzed
asymmetric Friedel–Crafts alkylation reaction of indole with a,b-
unsaturated ketone. Futhermore, we have established an effective
method for the synthesis of 2-substituted indole analogues using
4,7-dihydroindole.
(0.5 mL). The solution was cooled to -40 ◦C, and indole 1a
(23.4 mg, 0.2 mmol) was added. After completion of the reaction,
the mixture was purified directly by flash silica gel chromatography
(hexane–ethyl acetate = 20/1, and then hexane–ethyl acetate–
dichloromethane = 1/1/8) to afford adduct 4a as a white solid.
Solid, mp 159–160 ◦C (EtOH); [a]D27 -47 (c 1.0, CHCl3, 91% ee),
[a]2D6 -57 (c 1.0, CHCl3, 100% ee (EtOH)); Rf 0.10 (hexane: ethyl
acetate = 5 : 1), 1H NMR (400 MHz, CDCl3) d = 7.97 (brs, 1 H),
7.93–7.91 (m, 2 H), 7.53 (dddd, 1 H, J = 7.5, 7.3, 1.3, 1.3 Hz),
7.44–7.40 (m, 3 H), 7.34 (d, 2 H, J = 7.7 Hz), 7.30 (ddd, 1 H, J =
8.2, 0.9, 0.7 Hz), 7.24 (dd, 2 H, J = 7.3, 6.6 Hz), 7.17–7.11 (m, 2 H),
7.01 (ddd, 1 H, J = 7.1, 7.0, 1.1 Hz), 6.97 (dd, 1 H, J = 2.4, 0.7 Hz),
5.06 (dd, 1 H, J = 7.0, 7.7 Hz), 3.81 (dd, 1 H, J = 16.7, 7.0 Hz), 3.72
(dd, 1 H, J = 16.7, 7.7 Hz); 13C NMR (100 MHz, CDCl3) d = 198.6,
144.2, 137.2, 136.6, 133.0, 128.6, 128.4, 128.1, 127.8, 126.6, 126.3,
122.1, 121.4, 119.6, 119.4, 119.3, 111.1, 45.2, 38.3; HPLC: Daicel
Chiralpak AD-H, Hexane/iPrOH = 5/1, Flow rate = 0.5 mL min-1,
UV = 254 nm, tR = 40.6 min (major), tR = 47.1 min (minor).
Experimental
1. General details
NMR spectra were recorded on Unity Inova 400 instrument
1
(Varian Inc., 400 MHz for H, 100 MHz for 13C, 376 MHz for
(R)-3-(5-Benzy◦loxy-1H-indol-3-yl)-1,3-diphenylpropan-1-one
(4c). Mp 61–62 C; [a]D25 -4.6 (c 1.0, CHCl3, 91% ee); Rf 0.10
19F, 189 MHz for 31P) using CDCl3 as a solvent. Tetramethylsilane
(TMS) (d = 0) or CHCl3 (d = 7.27) served as an internal standard
for 1H NMR spectroscopy. H3PO4 was used as an external
standard (d = 0) for 31P NMR. C6F6 was used as an internal
standard (d = 0) for 19F NMR. IR spectra were recorded on
a Shimadzu FT-IR 8600 spectrometer. EI Mass spectra were
measured by JMS-AX505HA (JEOL) at an ionizing voltage of
70 eV. Purification of the products was performed by column
chromatography on silica gel (Fuji sylisia D60L or PSQ-60B).
All solvents were purified according to the standard procedures.
Elemental analysis (EA) was carried out on EA1110 instrument
(Amco Inc.).
1
(hexane: ethyl acetate = 5 : 1), H NMR (400 MHz, CDCl3) d =
7.93–7.90 (m, 2 H), 7.90 (brs, 1 H), 7.52 (dddd, 1 H, J = 7.5, 7.3,
1.3, 1.3 Hz), 7.43–7.39 (m, 4 H), 7.35–7.32 (m, 4 H), 7.29–7.22 (m,
3 H), 7.18–7.14 (m, 1 H), 7.15 (d, 1 H, J = 8.8 Hz), 6.93 (d, 1 H, J =
2.4 Hz), 6.89 (d, 1 H, J = 2.2 Hz), 6.86 (dd, 1 H, J = 8.8, 2.4 Hz),
4.99 (dd, 1 H, J = 7.7, 7.0 Hz), 4.96 (s, 2 H), 3.75 (dd, 1 H, J = 16.8,
7.0 Hz), 3.68 (dd, 1 H, J = 16.8, 7.7 Hz); 13C NMR (100 MHz,
CDCl3) d = 198.6, 152.9, 144.1, 137.6, 137.1, 135.0, 133.0, 132.5,
131.9, 128.5, 128.4, 128.1, 127.8, 127.7, 127.6, 126.9, 126.3, 122.2,
119.0, 113.0, 111.8, 103.1, 70.8, 45.0, 38.1; IR (CHCl3) 3479, 3012,
1685, 1582, 1481, 1452, 1288, 1267, 1222, 1184, 1080, 1022 cm-1;
MS (EI) m/z 431 (M++1, 24), 431 (M+, 71), 340 (23), 312 (53), 220
(100), 192 (30), 165 (9), 105 (37), 91 (31), 77 (14), 69 (8); Found: C,
83.55; H, 5.72; N, 3.30%. Calcd for C30H25NO2: C, 83.50; H, 5.84;
N, 3.25%; HPLC: Daicel Chiralcel OD-H, Hexane/EtOH = 9/1.
Flow rate = 1.0 mL min-1, UV = 254 nm, tR = 26.1 min (major),
tR = 30.7 min (minor).
2. Friedel–Crafts alkylation
(R)-3-(1H-Indol-3-yl)-1,3-diphenylpropan-1-one (4a)5a. To a
˚
dry 20 mL flask with activated MS 3 A (20 mg) under nitrogen
were added phosphoric acid 3e (15.5 mg, 0.02 mmol), chalcone 2a
(62.5 mg, 0.3 mmol), mesitylene (0.5 mL), and 1,2-dichloroethane
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(R)-3-(5-C◦hloro-1H-indol-3-yl)-1,3-diphenylpropan-1-one (4d).
Mp 165–166 C; [a]2D4 -35 (c 0.50, CHCl3, 90% ee); Rf 0.15 (hexane:
ethyl acetate = 5 : 1) 1H NMR (400 MHz, CDCl3) d = 8.00 (brs, 1
H), 7.94–7.92 (m, 2 H), 7.55 (dddd, 1 H, J = 7.5, 7.3, 1.3, 1.3 Hz),
7.44 (dd, 2 H, J = 7.7, 7.5 Hz), 7.38 (d, 1 H, J = 2.0 Hz), 7.33 (m, 2
H), 7.29–7.25 (m, 2 H), 7.23 (d, 1 H, J = 8.6 Hz), 7.18 (dddd, 1 H,
J = 7.3, 7.1, 1.3, 1.3 Hz), 7.09 (dd, 1 H, J = 8.6, 2.0 Hz), 7.04 (d, 1
H, J = 2.4 Hz), 5.00 (dd, 1 H, J = 7.3, 7.1 Hz), 3.78 (dd, 1 H, J =
16.7, 7.3 Hz), 3.70 (dd, 1 H, J = 16.7, 7.1 Hz). 13C NMR (100 MHz,
CDCl3) d = 198.3, 143.8, 137.0, 134.9, 133.1, 128.6, 128.6, 128.1,
127.8, 127.7, 126.5, 125.2, 122.7, 122.5, 119.1, 119.0, 112.1, 45.2,
38.0. IR (CHCl3) 3477, 1686, 1599, 1464, 1448, 1377, 1362, 1223,
1209, 1101 cm-1; MS (EI) m/z 361 (M++1, 8), 359 (M+-1, 26), 284
(2), 254 (18), 242 (32), 240 (100), 204 (17), 176 (5), 151 (3), 105
(17), 77 (16), 69 (9).; Found: C, 76.87; H, 4.82; N, 3.87%. Calcd for
C23H18ClNO: C, 76.77; H, 5.04; N, 3.89%; HPLC: Daicel Chiralcel
OD-H, Hexane/EtOH = 10/1. Flow rate = 1.0 mL min-1, UV =
254 nm, tR = 19.5 min (major), tR = 24.4 min (minor).
dihydroindole 5 (23.8 mg, 0.2 mmol) was added. After being
stirred at the temperature for 48 h, the mixture was quenched with
NaHCO3, and extracted with AcOEt(¥3). The combined organic
layers were washed with brine, dried over anhydrous Na2SO4, and
concentrated under vacuo to dryness. The residue was purified by
p-TLC (hexane–ethyl acetate = 5/1) to obtain 6a as yellow solid.
This material was subjected to RuZrP oxidation (25 mg, 5 mol%
against 5) under O2 at 80 ◦C in toluene. As a result, corresponding
adduct 7a was obtained with high yield and good ee.
Mp 136–137 ◦C (i-PrOH); [a]D26 -50 (c 1.0, CHCl3, 87% ee); Rf
1
0.40 (hexane: ethyl acetate = 5 : 1), H NMR(400 MHz, CDCl3)
d = 8.23 (brs, 1 H), 7.99–7.97 (m, 2 H), 7.58 (dddd, 1 H, J = 7.5,
7.3, 1.8, 1.3 Hz), 7.50–7.45 (m, 3 H), 7.36–7.31 (m, 4 H), 7.29–
7.24 (m, 2 H), 7.10 (ddd, 1 H, J = 7.1, 7.1, 1.1 Hz), 7.03 (ddd,
1 H, J = 7.1, 7.1, 1.1 Hz), 6.19 (m, 1 H), 4.95 (dd, 1 H, J = 8.2,
5.3 Hz), 3.93 (dd, 1 H, J = 17.6, 8.2 Hz), 3.68 (dd, 1 H, J = 17.6,
8.2 Hz). 13C NMR (100 MHz, CDCl3) d = 198.5, 142.2, 141.5,
136.6, 136.0, 133.3, 128.6, 128.6, 128.1, 128.0, 128.0, 127.0, 121.3,
119.9, 119.5, 110.6, 99.7, 44.7, 39.6. HPLC: Daicel Chiralpak AS-
H, Hexane/iPrOH = 9/1. Flow rate = 1.0 mL min-1, UV = 254 nm,
tR = 13.9 min (major), tR = 16.3 min (minor).
(R)-3-(4-Fluorophenyl)-3-(1H-indol-3-yl)-1-phenylpropan-1-one
(4k). Mp 149–150 ◦C; [a]D27 -43 (c 1.0, CHCl3, 90% ee); Rf 0.10
1
(hexane: ethyl acetate = 5 : 1), H NMR (400 MHz, CDCl3) d =
7.99 (brs, 1 H), 7.94–7.91 (m, 2 H), 7.55 (dddd, 1 H, J = 7.5, 7.3,
1.3, 1.3 Hz), 7.44 (dd, 2 H, J = 7.9, 7.3 Hz), 7.40 (d, 1 H, J =
7.9 Hz), 7.34 (ddd, 1 H, J = 8.2, 0.9, 0.7 Hz), 7.30 (dd, 2 H, J =
8.6 Hz, JH–F = 5.5 Hz), 7.16 (ddd, 1 H, J = 7.1, 6.9, 1.1 Hz), 7.03
(ddd, 1 H, J = 7.1, 7.0, 1.1 Hz), 7.00 (d, 1 H, J = 2.2 Hz), 6.93
(dd, 2 H, JH–F = 8.8, 8.6 Hz), 5.05 (dd, 1 H, J = 6.4, 8.1 Hz), 3.80
(dd, 1 H, J = 16.7, 6.4 Hz), 3.70 (dd, 1 H, J = 16.7, 8.1 Hz).;
19F-NMR (376 MHz, CDCl3) d = 44.8 (m).; 13C NMR (100 MHz,
CDCl3) d = 198.4, 161.3 (d, J = 244.4 Hz), 139.9, 139.8, 137.0,
136.6, 133.1, 129.2 (d, J = 7.7 Hz), 128.6, 128.0, 126.4, 122.2,
121.3, 119.4 (d, J = 4.6 Hz), 119.2, 115.1 (d, J = 21.1 Hz), 111.2,
45.2, 37.5. IR (CHCl3) 3479, 3010, 1684, 1599, 1508, 1456, 1448,
1337, 1229, 1157, 1096, 1014 cm-1; MS (EI) m/z 343 (M+, 18),
238 (13), 224 (100), 97 (11), 83 (18), 69 (23).; Found: C, 80.23;
H, 5.36; N, 3.81%. Calcd for C23H18FNO: C, 80.45; H, 5.28; N,
4.08%; HPLC: Daicel Chiralpak AD-H, Hexane/EtOH = 1/1.
Flow rate = 0.5 mL min-1, UV = 254 nm, tR = 12.4 min (major), tR =
13.8 min (minor).
(S)-3-(4-Chloroph◦enyl)-3-(1H-indol-2-yl)-1-phenylpropan-1-one
(7b). Mp 122–123 C; [a]D25 -8.0 (c 1.0, CHCl3, 84% ee); Rf 0.25
(hexane: ethyl acetate = 5 : 1), H NMR (400 MHz, CDCl3) d =
1
8.22 (brs, 1 H), 7.99–7.96 (m, 2 H), 7.59 (dddd, 1 H, J = 7.3, 7.3,
1.3, 1.1 Hz), 7.50–7.45 (m, 3 H), 7.32–7.25 (m, 5 H), 7.11 (ddd, 1 H,
J = 8.1, 7.1, 1.3 Hz), 7.04 (ddd, 1 H, J = 8.1, 7.0, 1.1 Hz), 6.18–6.18
(m, 1 H), 4.92 (dd, 1 H, J = 7.9, 5.7 Hz), 3.90 (dd, 1 H, J = 17.6,
7.9 Hz), 3.65 (dd, 1 H, J = 17.6, 5.7 Hz). 13C NMR (100 MHz,
CDCl3) d = 198.3, 141.0, 140.2, 136.5, 136.1, 133.5, 132.8, 129.5,
128.8, 128.7, 128.1, 128.0, 121.6, 120.1, 119.7, 110.7, 100.0, 44.6,
39.0.; IR (CHCl3) 3464, 3020, 2401, 1686, 1597, 1521, 1490, 1456,
1418, 1340, 1300, 1209, 1092, 1015, 928, 731, 669 cm-1; MS (EI)
m/z 361 (M++2, 10), 359 (M+, 29), 256 (38), 255 (26), 254 (100),
237 (10), 236 (25), 111 (16), 105 (21), 77 (16); Found: C, 76.77;
H, 5.04; N, 3.89%. Calcd for C23H18ClNO: C, 76.94; H, 5.12; N,
3.85%; HPLC: Daicel Chiralpak AD-H, Hexane/iPrOH = 1/1.
Flow rate = 0.5 mL min-1, UV = 254 nm, tR = 14.1 min (minor),
tR = 17.7 min (major).
(S)-3-(1H-Indol-3-yl)-1-phenylbutan-1-one
(4m)18. Amor-
(S)-3-(4-Bromophenyl)-3-(1H-indol-2-yl)-1-phenylpropan-1-one
(7c). Mp 170–171 ◦C; [a]D26 -9.1 (c 0.99, CHCl3, 85% ee); Rf 0.35
(hexane: ethyl acetate = 5 : 1), H NMR (400 MHz, CDCl3) d =
phous, [a]2D6 -8.1 (c 1.2, CHCl3, 58% ee) (lit. (R)-isomer, [a]D25
+24.2 (c 0.4, CHCl3));18 Rf 0.20 (hexane: ethyl acetate = 5 : 1),
1H NMR (400 MHz, CDCl3) d = 7.97–7.94 (m, 3 H), 7.68 (dd,
1 H, J = 7.8, 1.0 Hz), 7.54 (dddd, 1 H, J = 7.4, 7.2, 1.4, 1.4 Hz),
7.46–7.41 (m, 2 H), 7.36 (ddd, 1 H, J = 8.0, 1.0, 1.0 Hz), 7.19
(ddd, 1 H, J = 8.0, 7.0, 1.2 Hz), 7.12 (ddd, 1 H, J = 7.0, 7.0,
1.0 Hz), 7.04–7.03 (m, 1 H), 3.83 (ddq, 1 H, J = 8.8, 4.9, 6.9 Hz),
3.48 (dd, 1 H, J = 16.4, 4.9 Hz), 3.24 (dd, 1 H, J = 16.4, 8.8 Hz),
1.45 (d, 3 H, J = 6.9 Hz); 13C NMR (100 MHz, CDCl3) d = 199.7,
137.3, 136.5, 132.9, 128.5, 128.1, 126.3, 122.0, 121.6, 120.2, 119.3,
119.2, 111.2, 46.4, 27.1, 21.0; HPLC: Daicel Chiralcel OD-H,
Hexane/EtOH = 5/1, Flow rate = 1.0 mL min-1, UV = 254 nm,
tR = 9.3 min (major), tR = 11.8 min (minor).
1
8.22 (brs, 1 H), 7.99–7.96 (m, 2 H), 7.59 (dddd, 1 H, J = 7.5, 7.3,
1.3, 1.3 Hz), 7.50–7.44 (m, 5 H), 7.27–7.22 (m, 3 H), 7.12 (ddd, 1 H,
J = 8.2, 7.0, 1.3 Hz), 7.05 (ddd, 1 H, J = 8.1, 7.0, 1.1 Hz), 6.18–6.18
(m, 1 H), 4.91 (dd, 1 H, J = 7.9, 5.7 Hz), 3.90 (dd, 1 H, J = 17.6,
7.9 Hz), 3.65 (dd, 1 H, J = 17.6, 5.7 Hz); 13C NMR (100 MHz,
CDCl3) d = 198.2, 141.3, 141.0, 136.6, 136.1, 133.6, 131.9, 129.9,
128.7, 128.1, 128.1, 121.7, 121.0, 120.1, 119.8, 110.7, 110.1, 44.7,
39.1; IR (CHCl3) 3686, 3618, 3464, 3020, 2401, 1684, 1597, 1521,
1489, 1420, 1340, 1217, 1074, 1045, 1013, 930, 731, 669 cm-1; MS
(EI) m/z 404 (M+, 25), 402 (M+, 27), 300 (18), 299 (98), 298 (100),
285 (17), 283 (19), 183 (13), 181 (13), 105 (16) 77 (15); Found:
C, 68.33; H, 4.49; N, 3.46%. Calcd for C23H18BrNO: C, 68.39; H,
4.31; N, 3.45%; Daicel Chiralpak AD-H, Hexane/iPrOH = 1/1.
Flow rate = 0.5 mL min-1, UV = 254 nm, tR = 15.5 min (minor),
tR = 20.6 min (major).
(S)-3-(1H-Indol-2-yl)-1,3-diphenylpropan-1-one (7a)11. To a
dry 20 mL flask under nitrogen were added phosphoric acid 3c
(14.0 mg, 0.02 mmol), chalcone 2a (62.5 mg, 0.3 mmol), and
toluene (1.0 mL). The solution was cooled to -78 ◦C, and 4,7-
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(S)-3-(4-Fluorophenyl)-3-(1H-indol-2-yl)-1-phenylpropan-1-one
NMR (100 MHz, CDCl3) d = 141.2, 135.3, 134.9, 133.2, 132.8,
130.9, 129.0, 128.7, 128.3, 127.5, 127.1, 125.7, 125.2, 125.1, 123.1,
117.5, 111.9, 111.8, 30.2.; Found: C, 89.74; H, 5.30; N, 4.55%.
Calcd for C23H17N: C, 89.87; H, 5.57; N, 4.56%.
◦
(7d). Mp 75–77 C; [a]D25 -39 (c 1.0, CHCl3, 82% ee); Rf 0.30
1
(hexane: ethyl acetate = 5 : 1), H NMR (400 MHz, CDCl3) d =
8.21 (brs, 1 H), 7.99–7.96 (m, 2 H), 7.59 (dddd, 1 H, J = 7.4, 7.4,
1.4, 1.0 Hz), 7.52–7.45 (m, 3 H), 7.32 (dd, 2 H, J = 8.6 Hz, JH–F
=
3. Preparation of phosphoric acid
5.3 Hz), 7.27–7.25 (m, 1 H), 7.11 (ddd, 1 H, J = 8.2, 7.0, 1.0 Hz),
7.06–7.00 (m, 3 H), 6.18 (m, 1 H), 4.94 (dd, 1 H, J = 7.8, 5.7 Hz),
3.90 (dd, 1 H, J = 17.6, 7.8 Hz), 3.66 (dd, 1 H, J = 17.6, 5.7 Hz);
19F-NMR (376 MHz, CDCl3) d = 46.2 (m).; 13C NMR (100 MHz,
CDCl3) d = 198.4, 161.7 (d, J = 245.3 Hz), 141.4, 138.0 (d, J =
3.0 Hz), 136.6, 136.1, 133.5, 129.6 (d, J = 7.5 Hz), 128.7, 128.5,
128.1, 121.6, 120.0, 119.7, 115.5 (d, J = 21.7 Hz), 110.6, 99.9, 44.8,
38.9. IR (CHCl3) 3464, 3032, 3009, 2928, 2855, 1686, 1601, 1508,
1458, 1412, 1342, 1296, 1219, 1180, 1157, 1099, 980, 918, 837, 787,
760, 729, 691, 667, 548, 436 cm-1; MS (EI) m/z 343 (M+, 18), 325
(35), 324 (17), 239 (18), 238 (100), 224 (22), 222 (15), 121 (29), 77
(14).; Found: C, 80.45; H, 5.11; N, 4.05%. Calcd for C23H18FNO:
C, 80.45; H, 5.28; N, 4.08%; HPLC: Daicel Chiralpak AD-H,
Hexane/iPrOH = 1/1. Flow rate = 0.5 mL min-1, UV = 254 nm,
tR = 13.0 min (minor), tR = 14.7 min (major).
(R)-3,3¢-Bis(2,4-bis(trifluoromethyl)phenyl)-1,1¢-binaphth-2,2¢-
diol (precursor of 3i). To a three-necked round flask with a
condenser were added barium hydroxide octahydrate (15 mmol),
tetrakis(triphenylphosphine)palladium(0) (0.25 mmol), a 1,4-
dioxane/H2O solution (3/1, 75 mL), 2,2¢-(2,2¢-bis(methoxy-
methoxy)-1,1¢-binaphthyl-3,3¢-diyl)bis(4,4,5,5-tetramethyl-1,3,2-
dioxaborolane),
and
2,4-bis(trifluoromethyl)bromobenzene
(11 mmol). The mixture was refluxed for 24 h and quenched with
1 M aq. HCl. After extraction of this solution with CH2Cl2(¥3),
the combined organic layers were successively washed 1 N aq.
HCl, brine, sat. NaHCO3 aq., and brine. The organic layers
were dried over Na2SO4, and concentrated in vacuo to give crude
product.
A 1,4-dioxane/conc. HCl (= 3/1) solution of the crude mixture
in a flask with a condenser was stirred for 5 h at 70 ◦C. After
cooling down to room temperature, the solution was extracted
with CH2Cl2(¥3). The organic layers were combined, dried over
Na2SO4, and concentrated to give a crude product, which was
purified by column chromatography (hexane–ethyl acetate = 20/1)
to give the precursor of 3i.
(S)-3-(1H-Indol-2-yl)-3-(4-methoxyphenyl)-1-phenylpropan-1-
one (7e). Mp 48–49 ◦C; [a]D28 -54 (c 1.0, CHCl3, 85% ee); Rf 0.30
1
(hexane: ethyl acetate = 5 : 1), H NMR (400 MHz, CDCl3) d =
8.20 (brs, 1 H), 7.99–7.97 (m, 2 H), 7.59 (dddd, 1 H, J = 7.5, 7.3,
1.3, 1.3 Hz), 7.50–7.45 (m, 3 H), 7.27–7.23 (m, 3 H), 7.10 (ddd, 1
H, J = 8.1, 7.1, 1.3 Hz), 7.03 (ddd, 1 H, J = 7.9, 7.1, 1.1 Hz), 6.87
(dd, 2 H, J = 9.5, 2.2 Hz), 6.19–6.18 (m, 1 H), 4.90 (dd, 1 H, J =
8.1, 5.7 Hz), 3.89 (dd, 1 H, J = 17.6, 8.1 Hz), 3.80 (s, 3 H), 3.65 (dd,
1 H, J = 17.6, 5.7 Hz); 13C NMR (100 MHz, CDCl3) d = 198.7,
158.6, 142.0, 136.8, 136.1, 134.3, 133.4, 129.1, 128.7, 128.2, 128.1,
121.4, 120.0, 119.6, 114.1, 110.6, 99.7, 55.2, 45.0, 38.9. IR (CHCl3)
3684, 3618, 3462, 3020, 2401, 1684, 1611, 1599, 1582, 1512, 1458,
1420, 1302, 1209, 1180, 1036, 928, 731, 669 cm-1; MS (EI) m/z 356
(M++1, 12), 355 (M+, 45), 251 (21), 250 (100), 237 (21), 236 (73),
135 (15), 133 (58), 107 (12), 105 (32), 77 (24).; Found: C, 81.10;
H, 5.96; N, 3.94%. Calcd for C24H21NO2: C, 80.15; H, 5.84; N,
4.00%; HPLC: Daicel Chiralpak AD-H, Hexane/iPrOH = 1/1.
Flow rate = 0.5 mL min-1, UV = 254 nm, tR = 20.3 min (minor),
tR = 23.9 min (major).
◦
Mp 122–123 C, [a]2D4 +50 (c 1.0, CHCl3, 100% ee); H NMR
(400 MHz, CDCl3) d = 8.06 (d, 2 H, J = 8.2 Hz), 7.93–7.88 (m, 6 H),
7.72–7.62 (m, 2 H), 7.47–7.41 (m, 4 H), 7.27–7.19 (m, 2 H), 5.13–
5.09 (m, 2 H); 13C NMR (75 MHz, CDCl3) d = 150.5, 150.3, 150.2,
140.3, 135.8, 133.7, 133.5, 133.4, 133.3, 133.2, 133.1, 131.9, 131.4,
131.3, 131.2, 130.9, 130.8, 130.8, 130.7, 130.5, 130.4, 130.4, 130.3,
130.0, 130.0, 129.9, 128.9, 128.8, 128.7, 128.5, 128.5, 128.3, 128.2,
128.1, 127.5, 127.3, 127.1, 125.3, 125.0, 124.9, 24.1, 124.0, 123.9,
123.6, 121.7, 121.6, 118.1, 118.0, 118.0, 111.2, 111.0, 110.9, 110.8;
19F-NMR (376 MHz, CDCl3) d = 102.58, 102.57, 102.5, 102.4,
98.94, 98.92; IR (CHCl3) 3531, 3020,1710, 1628, 1603, 1578, 1501,
1439, 1346, 1298, 1279, 1267, 1220, 1209, 1180, 1140, 1084, 1063,
912, 862, 847 cm-1; MS (EI) m/z 711 (M++1, 10), 709 (M+-1, 100),
670 (35), 669 (70), 347 (24), 149 (31); Found: C, 60.86; H, 2.55%.
Calcd for C36H18F12O2: C, 60.62; H, 2.68%.
1
(S)-3-(1H-Indol-2-yl)-1-phenylbutan-1-one
(7f)14. Amor-
phous, [a]2D7 +31 (c 1.0, CH2Cl2, 79% ee) (lit. (R)-isomer, [a]D25
-16.7 (c 0.87, CH2Cl2, 71% ee));14 Rf 0.40 (hexane: ethyl acetate =
5 : 1), 1H NMR (400 MHz, CDCl3) d = 8.62 (brs, 1 H), 7.97–7.94
(m, 2 H), 7.57 (dddd, 1 H, J = 7.4, 7.4, 1.4, 1.2 Hz), 7.52 (dd, 1 H,
J = 7.0, 0.8 Hz), 7.48–7.44 (m, 2 H), 7.31 (dd, 1 H, J = 8.0, 0.8 Hz),
7.11 (ddd, 1 H, J = 8.0, 7.2, 1.4 Hz), 7.04 (ddd, 1 H, J = 8.2, 7.2,
1.2 Hz), 6.28 (m, 1 H), 3.74 (ddq, 1 H, J = 8.0, 4.7, 7.1 Hz), 3.41
(dd, 1 H, J = 18.0, 8.0 Hz), 3.31 (dd, 1 H, J = 18.0, 4.7 Hz), 1.52
(d, 3 H, J = 7.1 Hz); 13C NMR (100 MHz, CDCl3) d = 200.1,
144.2, 136.7, 135.7, 133.4, 128.6, 128.2, 128.0, 121.2, 119.8, 119.4,
110.6, 97.5, 47.0, 27.9, 19.9; HPLC: Daicel Chiralpak AS-H,
Hexane/iPrOH = 10/1, Flow rate = 0.5 mL min-1, UV = 254 nm,
tR = 23.0 min (major), tR = 24.9 min (minor).
(R)-3,3¢-Bis(2,4-bis(trifluoromethyl)phenyl)-1,1¢-binaphth-2,2¢-
yl phosphate (3i). Phosphoryl chloride (2.8 mmol) was
added to a pyridine (20 mL) solution of (R)-3,3¢-bis(2,4-
bis(trifluoromethyl)phen-yl)-1,1¢-binaphth-2,2¢-diol (2 mmol) in a
dry flask equipped with a condenser under nitrogen at 0 ◦C. After
being refluxed for 3 h, the reaction mixture was cooled to 0 ◦C and
excess pure water was added, and then the mixture was warmed to
room temperature. After being stirred at the temperature for 1 h,
the reaction mixture was quenched with 6 N HCl and CH2Cl2,
and extracted with CH2Cl2 (¥3). The combined organic layers
were washed with 6 N HCl, dried over Na2SO4, and concentrated
in vacuo to give crude product. Reprecipitation with MeOH/6N
◦
HCl gave phosphoric acid 3i, which was dried in vacuo at 50 C
1,3-Diphenyl-9H-pyrrolo[1,2-a]indole (8). Amorphous, Rf 0.40
(hexane: ethyl acetate = 10 : 1), 1H NMR (400 MHz, CDCl3) d =
7.63–7.59 (m, 4 H), 7.50–7.45 (m, 3 H), 7.44–7.38 (m, 3 H), 7.23–
with P2O5 in another flask to remove water.
Amorphous, [a]2D4 +17 (c 1.0, CHCl3, 100% ee); 1H NMR
(400 MHz, CDCl3) d = 8.00–7.88 (m, 6 H), 7.64–7.54 (m, 6 H),
7.48–7.34 (m, 4 H), 6.93 (brs, 1 H); 13C NMR (75 MHz, CDCl3)
7.19 (m, 1 H), 7.15–7.07 (m, 3 H), 6.68 (s, 1 H), 4.15 (s, 2 H); 13
C
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d = 176.9, 149.5, 144.1, 144.0, 143.9, 143.8, 143.4, 143.3, 143.2,
143.1, 138.6, 138.2, 138.1, 133.7, 133.6, 132.6, 132.6, 132.4, 132.3,
132.2, 132.0, 131.9, 131.8, 131.4, 131.3, 131.0, 131.0, 130.9, 130.8,
130.6, 130.6, 130.5, 130.4, 130.2, 130.2, 130.1, 129.8, 129.7, 129.6,
129.4, 129.4, 129.2, 129.1, 128.8, 128.8, 128.6, 128.5, 128.0, 127.9,
127.7, 127.5, 127.3, 127.2, 127.1, 127.0, 126.7, 126.6, 125.7, 125.6,
125.1, 125.0, 124.9, 124.5, 124.3, 122.9, 122.9, 122.8, 122.4, 122.4,
122.2, 122.2, 121.7, 121.6, 121.6, 121.6, 121.5, 121.5, 121.4, 121.4,
121.4, 121.3, 121.3, 117.8, 117.7; 19F-NMR (376 MHz, CDCl3) d =
105.6, 105.4, 102.4, 102.3, 98.5, 98.4, 98.3; 31P NMR (189 MHz,
CDCl3) d = 5.67, 4.76, 4.17. IR (CHCl3) 3649, 3063, 2253, 1711,
1628, 1499, 1418, 1346, 1298, 1281, 1269, 1221, 1180, 1140, 1082,
1063, 1020, 999, 970, 908, 847, 822 cm-1; MS (EI) m/z 772 (M+,
69), 771 (100), 770 (55), 691 (46), 369 (45), 368 (78), 129 (46), 111
(48), 97 (69), 83 (85), 77 (43), 69 (95).; Found: C, 55.97; H, 2.22%.
Calcd for C36H17F12O4P: C, 55.98; H, 2.49%.
6 (a) T. Akiyama, J. Itoh, K. Yokota and K. Fuchibe, Angew. Chem.,
Int. Ed., 2004, 43, 1566–1568; (b) D. Uraguchi and M. Terada, J. Am.
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7 For selected examples, see: (a) M. Yamanaka, J. Itoh, K. Fuchibe and
T. Akiyama, J. Am. Chem. Soc., 2007, 129, 6756–6764; (b) J. Itoh, K.
Fuchibe and T. Akiyama, Angew. Chem., Int. Ed., 2006, 45, 4796–4798;
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128, 13070–13071; (d) T. Akiyama, Y. Tamura, J. Itoh, H. Morita and
K. Fuchibe, Synlett, 2006, 141–143; (e) M. Terada, S. Yokoyama, K.
Sorimachi and D. Uraguchi, Adv. Synth. Catal., 2007, 349, 1863–1867;
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Antilla, Org. Lett., 2007, 9, 2609–2611; (g) Q. Kang, Z.-A. Zhao and
S.-L. You, J. Am. Chem. Soc., 2007, 129, 1484–1485.
8 For reviews, see: (a) T. Akiyama, J. Itoh and K. Fuchibe, Adv. Synth.
Catal., 2006, 348, 999–1010; (b) T. Akiyama, Chem. Rev., 2007, 107,
5744–5758; (c) M. Terada, Chem. Commun., 2008, 4097–4112.
9 (a) M. Terada, K. Soga and N. Momiyama, Angew. Chem., Int. Ed.,
2008, 47, 4122–4125; (b) N. Momiyama, H. Tabuse and M. Terada,
J. Am. Chem. Soc., 2009, 131, 12882–12883; (c) J. Lv, X. Li, L. Zhong,
S. Luo and J.-P. Cheng, Org. Lett., 2010, 12, 1096–1099; (d) K. Mori,
T. Katoh, T. Suzuki, T. Noji, M. Yamanaka and T. Akiyama, Angew.
Chem., Int. Ed., 2009, 48, 9652–9654; (e) S. E. Larson, J. C. Baso, G.
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47, 4016–4018.
Notes and references
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T.-S. Kam, J. Nat. Prod., 2007, 70, 1302–1307; (b) T. Yamashita, N.
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W.-Q. Li and X.-D. Luo, Org. Lett., 2008, 10, 577–580; (d) S.
Yokoshima, T. Ueda, S. Kobayashi, A. Sato, T. Kuboyama, H.
Tokuyama and T. Fukuyama, J. Am. Chem. Soc., 2002, 124, 2137–
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2911; (b) T. Ohshima, Chem. Pharm. Bull., 2004, 52, 1031–1052; (c) M.
Bandini and A. Eichholzer, Angew. Chem., Int. Ed., 2009, 48, 9608–
9644.
10 [a]2D0 -33 (c 0.1, CHCl3, 92% ee);Q.-X. Guo, Y.-G. Peng, J.-W. Zhang,
L. Song, Z. Feng and L.-Z. Gong, Org. Lett., 2009, 11, 4620–4623.
11 H. C¸ avdar and N. Sarac¸og˘lu, Tetrahedron, 2005, 61, 2401–
2405.
12 (a) L. Hong, C. Liu, W. Sun, L. Wang, K. Wong and R. Wang, Org.
Lett., 2009, 11, 2177–2180; (b) Q. Kang, X.-J. Zheng and S.-L. You,
Chem.–Eur. J., 2008, 14, 3539–3542;(c) M. Zeng, Q. Kang, Q.-L. He and
S.-L. You, Adv. Synth. Catal., 2008, 350, 2169–2173; (d) Y.-F. Sheng,
G.-Q. Li, Q. Kang, A.-J. Zhang and S.-L. You, Chem.–Eur. J., 2009, 15,
3351–3354.
13 Adduct 6a was partially oxidized to 7a during purification. All yields
shown in Table 4 are the mixture of 6a and 7a (6a: 7a = 6 : 1 ~ 17:
1). Therefore 4 peaks were detected through HPLC, and major peaks
indicated that of 6a: Daicel Chiralcel AD-H, Hexane/EtOH = 9/1.
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Flow rate = 1.0 mL min-1, UV = 254 nm, tR = 17.8 min (minor), tR
=
19.9 min (major).
14 G. Blay, I. Fernndez, J. R. Pedro and C. Vila, Tetrahedron Lett., 2007,
48, 6731–6734.
15 This catalyst is available from Kanto Chemical Co., Inc. (Tokyo,
Japan). Ruthenium is supported on zirconium phosphate: K. Fuchibe,
T. Kaneko, K. Mori and T. Akiyama, Angew. Chem., Int. Ed., 2009, 48,
8070–8073.
16 HPLC: Daicel Chiralcel AD, Hexane/EtOH = 9/1. Flow rate =
1.0 mL min-1, tR = 17.2 min (major), tR = 20.5 min (minor); L. Hong,
W. Sun, C. Liu, L. Wang, K. Wong and R. Wang, Chem.–Eur. J., 2009,
15, 11105–11108.
17 C. Zheng, Y.-F. Sheng, Y.-X. Li and S.-L. You, Tetrahedron, 2010, 66,
2875–2880.
18 G. Blay, I. Ferna´ndez, J. R. Pedro and C. Vila, Org. Lett., 2007, 9,
2601–2604.
5454 | Org. Biomol. Chem., 2010, 8, 5448–5454
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