Addition of aldehydes with allyltrichlorosilane catalyzed by chiral bis-N-O secondary amides

Article abstract of DOI:10.1016/j.tet.2013.09.088

New axially N-oxide amides derived from l-tryptophan were prepared and used as organocatalysts in enantioselective allylation of aromatic aldehydes with allyltrichlorosilanes. The corresponding addition adducts homoallylic chiral alcohols obtained high en

Full text of DOI:10.1016/j.tet.2013.09.088

Tetrahedron 69 (2013) 10431e10437
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Addition of aldehydes with allyltrichlorosilane catalyzed by chiral
bis-NeO secondary amides
,
,
,b,
*
Yu Deng a b, Wei Pan a b, Yu-Ning Pei a, Jin-Liang Li a, Bing Bai c, Hua-Jie Zhu a
a Chinese Centre for Chirality, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, and Department of Chemistry
and Chemical Engineering of Hebei University, Baoding 071002, Hebei, PR China
b State key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, CAS, Kunming 650204, Yunnan, PR China
c School of Food & Biological Engineering, Zhengzhou University of Light Industry, Zhengzhou 450002, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 15 July 2013
Received in revised form 20 September 2013
Accepted 30 September 2013
Available online 5 October 2013
New axially N-oxide amides derived from L-tryptophan were prepared and used as organocatalysts in
enantioselective allylation of aromatic aldehydes with allyltrichlorosilanes. The corresponding addition
adducts homoallylic chiral alcohols obtained high enantioselectivities (up to 96% ee) when 1 mol % of
catalyst was used. The unexpected result is the addition product’s absolute configuration is R when
(R)-chiral amides was used, in contrast, it was (S) when (R)-chiral methyl ester were used in allylation. It
exhibited that the N atoms of amides take part in the transition state procedure.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Bis-NeO amides
Allylation
L-Tryptophan
Axial ligand
1. Introduction
moiety were developed for enantioselective allylation in our study
recently.11 We have found that 1,10-biscarboline-N,N0-dioxide was
Asymmetric additions of aldehydes with allylic reagents
represent an important method to prepare highly useful chiral
building blocks in organic synthesis due to synthetic versatility of
propylene unit.1 In 1994, Denmark reported the first example of
asymmetric allylation utilizing chiral phosphoramides as chiral
Lewis basic ligands.2 Following this report, a series of chiral Lewis
bases have been designed and investigated in the asymmetric
allylation with allytrichlorosilanes.3e6 Among these Lewis bases, N-
oxide compounds, for their strong dipole and high nucleophilicity,
serving as organocatalysts to catalyze asymmetric allylations have
attracted considerable attention in the past two decades.7 Since
Nakajima first reported the axially chiral biquinoline N,N0-dioxide
was an excellent catalyst for SakuraieHosomi reaction in 1998,5a
several kinds of N-oxides derivatives from pyridines and tertiary
amines have been synthesized and used for the asymmetric ally-
lation by Malkov and Kocovsky,8 Hayashi,9 Kotora,10 Zhu,11 and
others.12 Some axially chiral N,N0-dioxide have shown modest to
good enantioselectivities, and these catalysts were effective for
aromatic aldehydes but stranded in aliphatic aldehydes.7 On basis
of aforementioned results and intrigued by the unique properties of
N-oxides, a type of new axial Lewis bases embracing biscarboline
useful for allylation of aldehydes. Inexpensive material, low cata-
lytic amount (1 mol %) and convenient to manipulate of this cata-
lysts promote us to study it profoundly and we continued to
synthesize axial amides using the similar methods.
The unexpected result reported in this study is the addition
products had (R) configuration using (R)-axially chiral 1,10-biscar-
boline N,N0-dioxide amides (e.g., (R)-(þ)-5a). In contrast, the ab-
solute configuration of addition product was all (S) configuration
when (R)-axially chiral 1,10-biscarboline N,N0-dioxide methyl ester
(like (R)-(þ)-9) was used.
2. Results and discussion
Tryptophan 1 was converted to the corresponding methyl ester
using SOCl2 in methanol. After PicteteSpengler reactions and hy-
drolysis, 1 was transferred to 2 based on our recent report. Seven
secondary amines (3aeg) and carboxylic acid 2 were condensed to
form the corresponding amides, which were further oxidized by
MCPBA or UHP. The specific route to amides 5aeg is illustrated in
Scheme 1.
The chiral separation of (þ)-5 from (ꢀ)-5 was performed via
chiral column with the eluent DCM/MeOH (v/v¼90/10 to 95/5) at
a rate of 2 or 2.5 mL/min. Optical rotation of (R)-5g was computed
using density functional theory (DFT) at the B3LYP/6-311þG(d)
* Corresponding author. Tel./fax: þ86 312 5994812; e-mail addresses: zhuhua-
jie@hotmail.com, hjzhu@mail.kib.ac.cn (H.-J. Zhu).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.09.088

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Y. Deng et al. / Tetrahedron 69 (2013) 10431e10437
Scheme 1. Preparation of axially chiral catalysts (R)-5aeg. Reaction conditions: (a) (i) 2, isobutyl-chloroformate (2.2 equiv), Et3N (4 equiv), DCM, 0 ꢁC, 15e20 min; (ii) amine
(2.2 equiv), rt, 10 h. (b) (i) Unless otherwise noted, the reaction was carried out in DCM and MCPBA (6 equiv) at rt for 12 h; (ii) 5f was oxidized by UHP (6 equiv) and TFA (6 equiv) in
DCM at rt for 12 h. (iii) The racemic products were resolutioned by chiral HPLC on a CHIRALPAK ID column.
level in the gas phase.13 The predicted optical rotation for (R)-5g
should have positive optical rotations. The experimental data was
þ697.0 in CHCl3. Obviously, (þ)-5g owns (R) configuration.
The enantioselectivity of the catalysts is listed in Table 1. It was
found that the higher ee% values were obtained by catalyst (R)-5f,g
the enantioselectivity was not improved with lower catalytic
amount (0.5 mol % and 0.1 mol %) of (R)-5g and the conversion was
poor in the reactions. The catalysts with aliphatic amides did ex-
hibit low ee% values in the reaction.14 The unexpected discovery is
that the obtained addition products had (R) configuration using
axially chiral 1,10-biscarboline N,N0-dioxide amide, (R)-5g. This is
different from what we obtained recently. In our recent report, it
was found that the addition product had the (S)-configuration
when using axially chiral (R)-1,10-biscarboline N,N0-dioxide methyl
ester. The problem of reverse configuration of product would be
discussed later according to mechanism analysis.
Table 1
Enantioselectivity of ligands (R)-5aeg in addition of aldehydes with
allytrichlorosilanea
Entry
Cat.*
Amount (mol %)
eeb,c (%)
1
2
3
4
5
6
7
8
5a
5a
5b
5b
5c
5c
5d
5e
5e
5f
5g
5g
5g
5g
5g
1
10
1
10
1
10
10
1
10
1
0.1
0.5
1
5
10
17
24
22
40
11
28
31
16
19
84
78
84
87
77
69
Effects from solvent and temperature on the enantioselectivity
were investigated. DCM, CH3CN, toluene, THF, and other aprotic
solvent were employed.1,2 It was found that DCM was the suitable
solvent. The results are summarized in Table 2. Temperature had
great effect on ee% values, e.g., the 87% of ee% observed at ꢀ80 ꢁC
decreased to 56% while the temperature increased to ꢀ60 ꢁC, and
this magnitude decreased to 30% once the temperature raised to
ꢀ40 ꢁC (Table 2, entries 1e3).
9
10
11
12
13
14
15
a
Reaction condition: 6a, 7 (1.5 equiv), i-Pr2NEt (3 equiv), 20 h.
b
Determined by chiral HPLC on a CHIRAPAK IB column, see Experimental section
for details.
It was found that (R)-5g could catalyze the reaction in a high
enantioselectivity. Therefore, catalyst (R)-5g was used in the addi-
tions for other aldehydes (Table 3). Aldehydes with electron-
donating groups, e.g., MeO at C-3 and C-4 catalyzed by (R)-5g
exhibited good enantioselectivity (entries 3 and 4). Those aldehydes
with strong electron-withdrawing group, e.g., 4-cyanobenzaldehyde,
3-nitrobenzaldehyde, and 4-nitrobenzaldehyde were catalyzed to
give good enantioselectivities (entries 8,11, and 12). Some aldehydes
with electron-donating group, for example, 2-methoxyben
zaldehyde present unsatisfied ee% value (67%ee, entry 2). The ali-
phatic aldehydes, e.g., cyclohexanecarboxaldehyde andphenylpropyl
aldehyde were investigated to test the catalytic activity of (R)-5g.
However, the resolution result showed that (R)-5g was not very ef-
fective for aliphatic aldehydes. The ee% value of the above two ali-
phatic aldehydes was 40% and 41%, respectively.
c
The absolute configuration of the major product was (R), which was determined
by comparison with the reported value of optical rotation, see Ref. 11.
with cyclic amides (entries 10e15) at the C-3 and C-30 positions.
Among these ligands, (R)-5g with pyrrolidine moiety (entry 13)
presented the best result (100% conv., 87%ee). N,N0-Dioxide cata-
lysts with aliphatic amides (entries 1e9) at the C-3 and C-30 posi-
tions (R)-5aee were found to possess high conversion but low
enantioselectivity. As illustrated in entries 1e9, a change in the
amide substituent resulted in little or no difference in enantiose-
lectivity. An interesting phenomenon was that the enantiose-
lectivity was higher in the presence of 1 mol % of catalyst (R)-5g
than using 10 mol % and 5 mol % in the catalytic reaction. However,

Y. Deng et al. / Tetrahedron 69 (2013) 10431e10437
10433
Table 2
Theoretically, the fundamental reason is that the transition state
barriers using the (R)-5 and (R)-9 are different. However, to in-
vestigate such a big chiral catalyst to explore their barriers is cur-
rently out of our expectation due to the huge computational time.
Based on the distribution of free ligand in solution has a large effect
on the enantioselectivity,15 we carefully investigated the structures
of (R)-(þ)-5g and (R)-(þ)-9 at the B3LYP/6-311þþG(2d,p) level,
respectively. It is unexpected that the two catalysts had total dif-
ferent stable conformations. For example, in (R)-(þ)-9, the eOMe
toward the outside resulted in the two O atoms of NeO in a close
distance; thus leading to the normal bis-NeO structure TS structure
formation (Fig. 1, up). However, it could not form the similar
structure in (R)-(þ)-5g. The two pC]O(NC4H8) tended to be close
each other, which isolated the two O atoms of NeO groups (Fig. 1).
Hence, two molecules of SiCl3CH2CH]CH2 easily chelated with the
two O atom of NeO groups in (R)-(þ)-5g. Therefore, it formed two
catalytic centers other than one. Once two Si atoms chelated with
two O of NeO groups, the amide group may change their confor-
mation, the O of C]O may chelate with the Si atom again. This new
conformation may be kept until the reaction finished. Finally it
catalyzed the addition to give the (S)-product.
Investigation of effects from solvents and temperatures on the allylationa
Entry
Solvent
T (ꢁC)
eeb,c (%)
1
2
3
4
5
6
7
8
9
10
DCM
DCM
DCM
DCM
DCM/CHCl3 (1:10)
CHCl3
CH3CN
THF
Toluene
(CH2)2Cl2
ꢀ80
ꢀ60
ꢀ40
20
ꢀ80
ꢀ60
ꢀ45
ꢀ80
ꢀ80
ꢀ40
87
56
30
17
68
42
34
33
31
29
a
Reaction condition: 6a, 7 (1.5 equiv), i-Pr2NEt (3 equiv), 20 h.
Determined by chiral HPLC on a CHIRAPAK IB column.
The absolute configuration of the major product was R, which was determined
b
c
by comparison with the reported value of optical rotation, see Ref. 11.
Since bis NeO (R)-(þ)-9 catalyzed the addition to afford product
(ꢀ)-8a and if the hypothesis above is correct, mono NeO catalyst like
(R)-(þ)-10 should catalyze the addition to afford (þ)-8a. To confirm
the hypothesis, a mono NeO catalyst (R)-(þ)-10 was synthesized
and used in the addition reactions. The product 8a obtained had
optical rotation of þ15ꢁ in chloroform, the ee% was 33%. This addi-
tion product 8a has (R)-configuration. Now, the whole mechanism
for (R)-(þ)-5g catalyzing the addition to afford (þ)-8a is clear.
Table 3
Asymmetric addition of aldehydes 6 with allytrichlorosilane catalyzed by (R)-5ga
Entry
R
Yieldb (%)
eec (%)
Config.d
[a]
D
e
1
2
3
4
5
6
7
8
H
85
86
90
88
90
80
85
80
86
88
97
95
87
87
67
83
94
76
82
76
82
81
73
96
86
76
R
R
R
R
R
R
R
R
R
R
R
R
R
þ45.6
þ63.0
þ56.1
þ69.1
þ54.6
þ58.3
þ48.6
2-OMe
3-OMe
4-OMe
4-Me
3-Cl
4-Cl
4-CN
3-F
þ101.5
þ45.6
þ57.6
þ57.9
þ80.0
þ178.6
9
10
11
12
13
4-F
3-NO2
4-NO2
2-Naphth
a
Reaction condition: 6, 7 (1.5 equiv), i-Pr2NEt (3 equiv), 20 h.
Isolated yield.
Determined by HPLC using chiral column.
b
c
3. Conclusion
d
The configuration was determined by comparing the recorded optical rotation
In summary, new axially chiral N,N0-dioxide catalysts bearing
secondary amides at the C-3 and C-30 positions were developed.
The preliminary study of structureeactivity indicated that catalysts
possessing cyclic amides were more effective than the catalysts
bearing acyclic amides for the asymmetric allylation of aromatic
and aliphatic aldehydes. One unexpected and interesting result was
the absolute configuration of the products provided by the catalyst
(þ)-(R)-5g were (R), which were reverse to the outcomes offered by
(þ)-(R)-9. The mechanism for the difference was well investigated
using quantum methods and experimental results. Investigation of
more reaction scope and better catalyst is in progress and will be
reported in future.
with the reported data.
Determined using enantiomeric pure enantiomer (100%ee), see Experimental
section for details.
e
As mentioned above, the unexpected results are the obtained
addition products had (R) configuration based on its positive optical
rotation value. The absolute configuration of addition product is all
(S) configuration with negative optical rotation values when axially
chiral 1,10-biscarboline N,N0-dioxide methyl ester (R)-9 were used.
The interesting result is exhibited here: why did (R)-5g give (R)
configuration for the product in this report while (R)-9 displayed (S)
configuration in our previous study?
4. Experimental section
4.1. General methods
GF254 thin layer chromatography was used. Flash column chro-
matography was performed with silica gel (200e300 mesh). Enan-
tiomeric excess was determined by HPLC using chiral column and
also compared with the corresponding pure enantiomers’ optical
rotation values, respectively. Optical rotations were performed on an

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Y. Deng et al. / Tetrahedron 69 (2013) 10431e10437
Fig. 1. The proposed TS structure for the procedure using (R)-(þ)-5g (down) and the normal TS structure for bis-NeO catalyst (R)-(þ)-9 (up).
Optical Activity AA-55 polarimeter using a 10 cm cell with a Na
589 nm filter. IR spectra were obtained with an FT-IR spectrometer
(Bruker Tensor 27). 1H NMR and C NMR were recorded on a Bruker
AV-400 spectrometer. The mass spectra were measured on an API
QSTAR Pulsar. All solvents for the reactions were of reagent grade
and were dried and distilled before used. Compound 2 was syn-
thesized according to our former reported method.11
NMR (100 MHz, CDCl3) d 162.99, 143.50, 138.25, 128.35, 124.75,
121.23, 120.86, 115.58, 109.77, 42.66, 39.43, 29.58, 14.18, 12.61.
4.2.2. 9,90-Dimethyl-N,N,N0,N0-tetrapropyl-9H,90H-1,10-bipyrido[3,4-
b]indole-3,30-dicarboxamide (4b). Following the general procedure,
4b was obtained as yellow solid, yield of 70%. IR (KBr)
n
¼3436, 2962,
1619, 1408, 1254, 1130, 1039, 743 cmꢀ1. MS-ESI, m/z 617[MþH]þ.
HRMS m/z calcd for C34H44N6O2 616.3526, Found 616.3530. 1H NMR
4.2. General procedure for preparation of 4aeg
(400 MHz, CDCl3)
d
8.56 (s, 1Hꢂ2), 8.33e8.13 (d, 1Hꢂ2), 7.49 (ddd,
J¼28.1, 14.8, 7.4 Hz, 3Hꢂ2), 3.66e3.12 (m, 4Hꢂ2), 3.35 (s, 3Hꢂ2),
To a dried DCM (50 mL) solution of 2 (0.45 g,1 mmol) were added
drop-wise isobutyl-chloroformate (2.2 equiv) and Et3N (4 equiv) at
ice-bath stirred. The mixture was kept at this temperature for
15 min. Then amines (2.2 equiv) were added and the mixture was
stirred at rt for 12 h. The reaction was quenched by dilute HCl (1 mol/
L), and the pH of the solution was adjusted to 7e8 by using saturated
NaHCO3. The solution was washed with saturated brine two times
and was dried over anhydrous Na2SO4. The solvents were evapo-
rated under reduced pressure. The residue was purified by chro-
matography (silica gel) eluting with petroleum ether/EtOAc.
1.86e1.16 (m, 4Hꢂ2), 1.11e0.82 (m, 3Hꢂ2). 13C NMR (100 MHz,
CDCl3) d168.57, 143.11, 135.81, 130.98, 129.38, 121.97, 120.98, 120.59,
115.77, 109.92, 51.21, 48.26, 32.24, 22.26, 20.82, 11.58, 10.82.
4.2.3. N,N,N0,N0-Tetrabutyl-9,90-dimethyl-9H,90H-1,10-bipyrido[3,4-b]
indole-3,30-dicarboxamide (4c). Following the general procedure,
4c was obtained as yellow solid, yield of 80%. IR (KBr)
n
¼3425, 2954,
1614, 1450, 1409, 1287, 1245, 1131, 1040, 745 cmꢀ1. MS-ESI, m/z 672
[MþH]þ. HRMS m/z calcd for C42H52N6O2 672.4152, Found
672.4156. 1H NMR (400 MHz, CDCl3)
d
8.57 (s, 1Hꢂ2), 8.25
(d, J¼7.8 Hz, 1Hꢂ2), 7.50 (ddd, J¼31.1, 14.9, 7.5 Hz, 3Hꢂ2), 3.45 (m,
4.2.1. N,N,N0,N0-Tetraethyl-9,90-dimethyl-9H,90H-1,10-bipyrido[3,4-b]
indole-3,30-dicarboxamide (4a). Following the general procedure
mentioned above, 4a was obtained as yellow solid, yield 75%. IR
4Hꢂ2), 3.40 (s, 3Hꢂ2), 1.69e1.41 (m, 8Hꢂ2), 0.94 (dd, J¼24.2,
17.0 Hz, 4Hꢂ2). 13C NMR (100 MHz, CDCl3)
d168.25, 143.14, 135.83,
131.10, 129.40, 121.98, 121.03, 120.63, 115.98, 109.95, 49.53, 46.50,
31.28, 29.76, 20.44, 19.75, 13.94, 13.55.
(KBr)
n
¼3431, 2961, 1639, 1450, 1391, 1336, 1235, 1132, 1008,
747 cmꢀ1. MS-ESI, m/z 560 [MþH]þ. HRMS m/z calcd for C34H36N6O2
560.2900, Found 560.2899. 1H NMR (400 MHz, CDCl3)
d
8.17 (s,
4.2.4. N,N,N0,N0-Tetrabenzyl-9,90-dimethyl-9H,90H-1,10-bipyrido[3,4-
b]indole-3,30-dicarboxamide (4d). Following the general procedure,
4d was obtained as yellow solid, yield of 74%. IR (KBr)
1Hꢂ2), 8.07 (d, J¼7.2 Hz, 1Hꢂ2), 7.58 (d, J¼7.2 Hz, 1Hꢂ2), 7.36 (d,
J¼5.3 Hz, 2Hꢂ2), 3.39 (d, J¼50.7 Hz, 7Hꢂ2), 1.30e1.15 (m, 6Hꢂ2). 13
C
n¼3430, 1627,

Y. Deng et al. / Tetrahedron 69 (2013) 10431e10437
10435
1544, 1492, 1472, 1445, 1407, 1325, 1251, 1154, 1041, 745 cmꢀ1. MS-
1456, 1392, 1314, 1234, 1131, 1007, 749 cmꢀ1. MS-ESI, m/z 649
[MþH]þ. HRMS m/z calcd for C38H44N6O4 648.3424, Found
ESI, m/z 808[MþH]þ. HRMS m/z calcd for C54H44N6O2 808.3526,
Found 808.3514. 1H NMR (400 MHz, CDCl3)
d
8.68 (s, 1Hꢂ2), 8.25 (d,
648.3444. 1H NMR (400 MHz, CDCl3)
d
8.18 (s, 1Hꢂ2), 8.08 (d,
J¼12.6 Hz,1Hꢂ2), 7.66 (m,1Hꢂ2), 7.28 (m, 6Hꢂ2), 6.92 (d, J¼3.9 Hz,
J¼7.7 Hz, 1Hꢂ2), 7.59 (t, J¼7.3 Hz, 1Hꢂ2), 7.37 (t, J¼7.5 Hz, 2Hꢂ2),
3.41 (s, 3Hꢂ2), 3.39e3.11 (m, 4Hꢂ2), 1.69 (m, 4Hꢂ2), 0.99 (t,
J¼7.4 Hz, 3Hꢂ2), 0.81 (t, J¼7.3 Hz, 3Hꢂ2). 13C NMR (100 MHz, CDCl3)
2Hꢂ2), 6.72 (d, J¼3.2 Hz, 2Hꢂ2), 4.76 (dd, J¼198.6, 64.4 Hz, 1Hꢂ2),
3.26 (s, 1Hꢂ2). 13C NMR (100 MHz, CDCl3)
d 169.16, 142.95, 137.05,
135.75, 130.93, 129.30, 128.47, 127.76, 127.28, 126.72, 121.90, 120.65,
116.38, 109.90, 51.72. 48.66, 32.09.
d 163.46, 143.57, 138.22, 128.45, 121.26, 120.93, 115.99, 109.76, 49.89,
46.63, 21.86, 20.45, 11.49, 11.23. [a]D þ459 (c 0.255, CHCl3).
4.2.5. N,N0-Dibenzyl-N,N0,9,90-tetramethyl-9H,90H-1,10-bipyrido[3,4-
b]indole-3,30-dicarboxamide (4e). Following the general procedure,
4.3.3. 3,30-Bis(dibutylcarbamoyl)-9,90-dimethyl-9H,90H-1,10-bipyrido
[3,4-b]indole 2,20-dioxide (5c). Following the general procedure, 5c
4e was obtained as yellow solid, yield of 76%. IR (KBr)
n
¼3425, 2922,
was obtained as yellow solid, yield 60%. IR (KBr)
n
¼3432, 2956,
1620,1544,1488, 1443,1393,1247,1131,1041, 745 cmꢀ1. MS-ESI, m/z
1640, 1491, 1454, 1391, 1336, 1233, 1132, 1008, 748 cmꢀ1. MS-ESI, m/
z705 [MþH]þ. HRMS m/z calcd for C42H52N6O4 704.4050, Found
656[MþH]þ. HRMS m/z calcd for C42H36N6O2 656.2900, Found
656.2894. 1H NMR (400 MHz, CDCl3)
d
8.59 (s, 1Hꢂ2), 8.18 (d,
704.4056. 1H NMR (400 MHz, CDCl3)
d
8.17 (s, 1Hꢂ2), 8.07 (d,
J¼7.7 Hz, 1Hꢂ2), 7.58e7.25 (m, 3Hꢂ2), 7.20e6.79 (m, 5Hꢂ2), 4.25
J¼7.8 Hz, 1Hꢂ2), 7.58 (t, J¼7.6 Hz, 1Hꢂ2), 7.35 (m, 2Hꢂ2), 3.42 (s,
3Hꢂ2), 3.25 (m, 4Hꢂ2), 1.74e1.40 (m, 2Hꢂ2), 1.39e1.10 (m, 2Hꢂ2),
0.93 (t, J¼7.3 Hz, 3Hꢂ2), 0.80 (t, J¼7.3 Hz, 3Hꢂ2). 13C NMR
(m, 2Hꢂ2), 3.31e2.72 (m, 6Hꢂ2). 13C NMR (100 MHz, CDCl3)
d
166.55,142.90,137.20,129.57,128.57,128.12,127.98,127.38,126.94,
122.04, 121.93, 120.79, 116.36, 109.87, 55.13, 51.61, 34.19, 31.95.
(100 MHz, CDCl3) d 163.16, 143.67, 138.16, 128.62, 121.34, 121.01,
120.80, 116.01, 109.82, 47.98, 44.79, 30.75, 29.86, 29.21, 20.26, 19.91,
13.96. [
þ377 (c 0.215, CHCl3).
4.2.6. (9,90-Dimethyl-9H,90H-1,10-bipyrido[3,4-b]indole-3,30-diyl)bi-
s(azetidin-1-ylmethanone) (4f). Following the general procedure, 4f
a]
D
was obtained as yellow solid, yield of 85%. IR (KBr)
n
¼3430, 2946,
4.3.4. 3,30-Bis(dibenzylcarbamoyl)-9,90-dimethyl-9H,90H-1,10-bipyr-
ido[3,4-b]indole 2,20-dioxide (5d). Following the general procedure,
1617, 1542, 1469, 1434, 1399, 1243, 1129, 1039, 734 cmꢀ1. MS-ESI, m/
z 528[MþH]þ. HRMS m/z calcd for C32H28N6O2 528.2274, Found
5d was obtained as yellow solid, yield 56%. IR (KBr)
n
¼3432, 1643,
528.2278. 1H NMR (400 MHz, CDCl3)
d
9.02 (s, 1Hꢂ2), 8.30 (d,
1603, 1493, 1449, 1391, 1315, 1234, 1019, 746 cmꢀ1. MS-ESI, m/z 841
J¼13.5 Hz, 1Hꢂ2), 7.83e6.99 (m, 3Hꢂ2), 4.76e3.98 (t, 4Hꢂ2), 3.30
[MþH]þ. HRMS m/z calcd for C54H54N6O4 840.3424, Found 840.3425.
(s, 3Hꢂ2), 2.53e1.88 (m, 3Hꢂ2). 13C NMR (100 MHz, CDCl3)
1H NMR (400 MHz, CDCl3)
d
8.10 (s, 1Hꢂ2), 8.01 (d, J¼7.7 Hz, 1Hꢂ2),
d
165.67, 142.73, 138.43, 129.16, 122.02, 121.36, 120.83, 116.07,
7.58 (t, J¼7.6 Hz,1Hꢂ2), 7.37e7.37 (m, 2Hꢂ2), 7.25e7.15 (m,10Hꢂ2),
109.85, 55.29, 49.19, 31.87, 16.44.
4.56 (d, 2Hꢂ2), 4.25 (d, 2Hꢂ2), 3.44 (s, 3Hꢂ2). 13C NMR (100 MHz,
CDCl3) d164.27, 143.69, 137.69, 135.90, 128.81, 128.62, 128.52, 127.79,
4.2.7. (9,90-Dimethyl-9H,90H-1,10-bipyrido[3,4-b]indole-3,30-diyl)
bis(pyrrolidin-1-ylmethanone) (4g). Following the general pro-
cedure, 4g was obtained as yellow solid, yield of 78%. IR (KBr)
127.72, 127.41, 127.12, 121.56, 121.12, 120.82, 116.48, 109.86, 50.81,
47.94, 30.52. [
D þ269 (c 0.275, CHCl3).
a]
n
¼3431, 2870, 1612, 1544, 1437, 1400, 1244, 1044, 747 cmꢀ1. MS-ESI,
4.3.5. 9,90-Dimethyl-3,30-bis(2-methyl-3-phenylpropanoyl)-9H,90H-
1,10-bipyrido[3,4-b]indole 2,20-dioxide (5e). Following the general
procedure, 5e was obtained as yellow solid, yield 60%. IR (KBr)
m/z 556[MþH]þ. HRMS m/z calcd for C34H32N6O2 556.2587, Found
556.2578. 1H NMR (400 MHz, CDCl3)
d
8.83 (s, 1Hꢂ2), 8.25 (t,
J¼13.0 Hz, 1Hꢂ2), 7.65 (t, J¼7.6 Hz, 1Hꢂ2), 7.38 (t, J¼7.9 Hz, 2Hꢂ2),
n
¼3440,2992,1640,1491,1454,1391,1336,1233,1132,1008, 748cmꢀ1
.
4.03e3.58 (m, 4Hꢂ2), 3.19 (s, 3Hꢂ2), 1.86 (m, 4Hꢂ2). 13C NMR
MS-ESI, m/z689 [MþH]þ. HRMS m/z calcd for C42H36N6O4 688.2769,
(100 MHz, CDCl3)
d
166.58, 142.97, 136.09, 129.40, 122.11, 121.16,
Found688.2769.1HNMR(400MHz, CDCl3)
d
8.25(s,1Hꢂ2), 8.08(ddd,
120.75, 116.52, 109.86, 49.54, 47.15, 31.56, 26.66, 24.02.
J¼29.1, 14.3, 8.6 Hz, 1Hꢂ2), 7.59 (m, 1Hꢂ2), 7.36e7.40 (m, 2Hꢂ2),
7.33e7.23 (m, 5Hꢂ2), 4.73 (m, 2Hꢂ2), 3.45 (s, 3Hꢂ2), 3.01 (m, 3Hꢂ2).
4.3. General procedure for preparation of 5aee, g
13C NMR (100 MHz, CDCl3)
d163.70, 143.66, 138.37,136.22,128.70,
127.90, 127.82, 127.34, 121.52, 121.09, 116.32, 109.86, 54.33, 50.75,
35.09, 33.05, 29.98, 29.92. [
D þ447 (c 0.275, CHCl3).
To a stirring solution of 4aee and 4g (0.5 mmol) in DCM (25 mL)
was added MCPBA (85%, 6 equiv), the reaction mixture was stirred at
rt for 12 h. Then reaction was quenched by saturated NaHCO3 and the
pH was adjusted to 7e8. Then the solution was washed with satu-
rated brine three times and was dried over anhydrous Na2SO4. The
solvents were evaporated under reduced pressure. The residue was
purified by chromatography (silica gel) eluting with DCM/MeOH.
a]
4.3.6. 9,90-Dimethyl-3,30-di(pyrrolidine-1-carbonyl)-9H,90H-1,10-bi-
pyrido[3,4-b]indole 2,20-dioxide (5g). Following the general pro-
cedure, 5g was obtained as yellow solid, yield 70%. IR (KBr)
n
¼3440,
2874, 1635, 1490, 1443, 1334, 1234, 1007, 749 cmꢀ1. MS-ESI, m/z 589
[MþH]þ. HRMS m/z calcd for C34H32N6O4 588.2485, Found
588.2479. 1H NMR (400 MHz, CDCl3)
d
8.26 (s, 1Hꢂ2), 8.07 (d,
4.3.1. 3,30-Bis(diethylcarbamoyl)-9,90-dimethyl-9H,90H-1,10-bipyrido
[3,4-b]indole 2,20-dioxide (5a). Following the general procedure, 5a
J¼7.8 Hz, 1Hꢂ2), 7.58 (t, J¼7.7 Hz, 1Hꢂ2), 7.37 (dd, J¼12.7, 5.3 Hz,
2Hꢂ2), 3.84e3.58 (m, 4Hꢂ2), 3.43 (s, 3Hꢂ2), 1.93 (m, 4Hꢂ2). 13
C
was obtained as brown solid, yield 60%. IR (KBr)
n
¼3426, 2961, 1639,
NMR (101 MHz, CDCl3) d 161.61, 143.66, 138.37, 128.71, 124.78,
1450, 1391, 1336, 1235, 1132, 1008, 747 cmꢀ1. MS-ESI, m/z 593
[MþH]þ. HRMS m/z calcd for C34H36N6O4 592.2798, Found 592.2796.
121.98, 121.50, 121.05, 120.81, 116.25, 109.88, 46.69, 46.08, 29.81,
25.74, 24.42. [
þ697 (c 0.185, CHCl3).
a
]
D
1H NMR (400 MHz, CDCl3)
d
8.08 (s, 1Hꢂ2), 7.99 (d, J¼7.4 Hz, 1Hꢂ2),
7.50 (t, J¼7.3 Hz, 1Hꢂ2), 7.35e7.22 (m, 3Hꢂ2), 3.76e3.01 (m,11Hꢂ2),
4.4. Procedure for preparation of 5f
1.30e1.13 (m, 6Hꢂ2). 13C NMR (100 MHz, CDCl3)
d 162.82, 143.61,
138.19, 128.58, 124.70, 121.33, 120.98, 120.79, 115.66, 109.87, 42.92,
UHP (6 equiv) was added portion-wise to the stirred solution of 4
(0.5 mmol) in DCM (25 mL) at ice-bath, stirring for 15 min and to the
mixture was added TFA (6 equiv). The reaction was then transferred
to rt for 10 h. After finished, the mixture was washed with water,
dried over anhydrous Na2SO4. The solvents were evaporated under
reduced pressure. The residue was purified by chromatography
39.45, 14.23, 12.60, 11.81. [a]D þ435 (c 0.31, CHCl3).
4.3.2. 3,30-Bis(dipropylcarbamoyl)-9,90-dimethyl-9H,90H-1,10-bipyr-
ido[3,4-b]indole 2,20-dioxide (5b). Following the general procedure,
5b was obtained as yellow solid, yield 65%. IR (KBr)
n¼3431, 1636,

10436
Y. Deng et al. / Tetrahedron 69 (2013) 10431e10437
(silica gel) eluting with DCM/MeOH¼70:1 to give N,N0-dioxides as
yellow solid 182 mg, yield 37%. The racemic mixtures of 5f were
resolved by HPLC on a Chiral-park ID column (250ꢂ10 mm, DCM/
MeOH¼90:10) and (þ)-5f, (ꢀ)-5f yields 45%, 43%, respectively.
determination. [
S-enantiomer (92% ee) is [
a
]
D þ69.1 (c 0.66, CHCl3). The reported value for the
a]
D ꢀ48.0 (c 1.0, CHCl3).16
4.5.5. (R)-1-p-Tolylbut-3-en-1-ol (8e). 1H NMR (400 MHz, CDCl3)
d
2.05 (d, J¼2.6 Hz, 1H), 2.36 (s, 3H), 2.49e2.53 (m, 2H), 4.72 (m, 1H),
4.4.1. 3,30-Di(azetidine-1-carbonyl)-9,90-dimethyl-9H,90H-1,10-bipyr-
ido[3,4-b]indole 2,20-dioxide (5f). Following the general procedure,
5.14e5.19 (m, 2H), 5.77e5.87 (m, 1H), 7.18 (d, J¼7.9 Hz, 2H), 7.26 (d,
J¼7.9 Hz, 2H). Enantiomeric excess was determined by HPLC with
5fwas obtained asyellowsolid,yield65%.IR(KBr)
n
¼3441,1633,1442,
a
Chiralpark ID column (hexane/2-propanol¼95:5,
2 mL/min),
1449,1198,1020, 749 cmꢀ1. MS-ESI, m/z [MþH]þ. HRMS m/z calcd for
t1¼16.0 min (R); t2¼17.3 min (S), ee¼76%. Pure R-enantiomer (100%)
C
32H28N6O4 560.2172, Found 560.2155. 1H NMR (400 MHz, CDCl3)
was used for [
a]
D
determination. [
a]
D
þ54.6 (c 0.48, CHCl3). The re-
d
8.31 (s,1Hꢂ2), 8.03 (d, J¼7.9 Hz, 1Hꢂ2), 7.53 (t, J¼7.6 Hz, 1Hꢂ2), 7.31
ported value for the S-enantiomer(89% ee) is [
a
]D ꢀ43.4 (c1.1, CHCl3).9a
(t, J¼7.2 Hz, 2Hꢂ2), 4.48e4.17 (d, 2Hꢂ2), 4.16e4.05 (d, J¼59.5 Hz,
2Hꢂ2), 3.31 (s, 3Hꢂ2), 2.37 (m, 2Hꢂ2). 13C NMR (100 MHz, CDCl3)
4.5.6. (R)-1-(3-Chlorophenyl)but-3-en-1-ol (8f). 1H NMR (400 MHz,
CDCl3) 2.17 (s, 1H), 2.41e2.55 (m, 2H), 4.71 (m, 1H), 5.15e5.20 (m,
d
162.90, 143.57, 138.68, 128.58, 124.96, 121.58, 121.37, 121.05, 120.93,
d
117.70, 109.81, 50.70, 48.98, 29.68, 16.04. [
a
]
D þ657 (c 0.20, CHCl3).
2H), 5.73e5.84 (m, 1H), 7.21e7.30 (m, 3H), 7.37 (s, 1H). Enantio-
meric excess was determined by HPLC with a Chiralpark ID column
(hexane/2-propanol¼95:5, 3 mL/min), t1¼9.7 min (R); t2¼10.3 min
4.5. General procedure for reaction of allyltrichlorosilane
with aldehydes
(S), ee¼82%. Pure R-enantiomer (100%) was used for [
a
]
D
de-
termination. [
a
]
D
þ58.3 (c 0.60, CHCl3).
Allyltrichlorosilane 7 (0.3 mmol) was added to a solution of the
catalyst 5 (1 mol %), diisopropylethylamine (0.6 mmol), and alde-
hyde 6 (0.2 mmol) in dichloromethane (1 mL) under nitrogen at
ꢀ80 ꢁC. The mixture was stirred at the same temperature for 20 h
and then quenched with aqueous saturated NaHCO3 (0.5 mL). The
aqueous layer was extracted with dichloromethane. The combined
organic layer was washed with saturated sodium chloride, dried
over Na2SO4, and evaporated under reduced pressure. The residue
was purified by flash chromatography on silica gel (petroleum
ether/EtOAc) to give alcohol 8.
4.5.7. (R)-1-(4-Chlorophenyl)but-3-en-1-ol (8g). 1H NMR (400 MHz,
CDCl3)
d
2.13 (d, J¼2.7 Hz, 1H), 2.41e2.54 (m, 2H), 4.71 (m, 1H),
5.14e5.18 (m, 2H), 5.74e5.81 (m, 1H), 7.26e7.33 (m, 4H). Enantio-
meric excess was determined by HPLC with a Chiralpark IA column
(hexane/2-propanol¼95:5, 1.5 mL/min), t1¼26.1 min (R);
t2¼27.5 min (S), ee¼76%. Pure R-enantiomer (100%) was used for
[a]D determination. [
a]
D þ48.6 (c 0.70, CHCl3). The reported value for
the S-enantiomer (89% ee) is [
a]
D ꢀ60.6 (c 1.5, CHCl3).16
4.5.8. (R)-4-(1-Hydroxybut-30-enyl)benzonitrile
(8h). 1H
NMR
(400 MHz, CDCl3) 2.23 (br s, 1H), 2.31e2.53 (m, 2H), 4.54 (m, 1H),
5.07e5.21 (m, 2m), 5.82 (m, 1H), 7.44e7.54 (m, 4H) Enantiomeric
excess was determined by HPLC with a Chiralpark ID column
4.5.1. (R)-1-Phenylbut-3-en-1-ol (8a). 1H NMR (400 MHz, CDCl3)
d
2.09 (br s, 1H), 2.45e2.56 (m, 2H), 4.74 (dd, J¼7.3, 5.5 Hz, 1H),
5.13e5.19 (m, 2H), 5.76e5.86 (m, 1H), 7.28e7.36 (m, 5H). Enantio-
meric excess was determined by HPLC with a Chiralpark IB column
(hexane/2-propanol¼95:5, 1.5 mL/min), t1¼20.7 min (R);
t2¼22.8 min (S), ee¼87%. Pure R-enantiomer (100%) was used for
(hexane/2-propanol¼95:5,
t2¼20.7 min (S), ee¼82%. Pure R-enantiomer (100%) was used for
D determination. [
D þ101.5 (c 0.34, CHCl3).
3
mL/min), t1¼19.9 min (R);
[a
]
a]
[
a
]
determination. [
a]
þ45.6 (c 0.56, CHCl3). The reported value
4.5.9. (R)-1-(3-Fluorophenyl)but-3-en-1-ol (8i). 1H NMR (400 MHz,
CDCl3)
D
D
for the S-enantiomer (92% ee) is [
a]
ꢀ61.2 (c 1.05, CHCl3).16
d
2.13 (d, J¼3.0 Hz, 1H), 2.45e2.56 (m, 2H), 4.75 (m, 1H),
D
5.16e5.21 (m, 2H), 5.76e5.82 (m, 1H), 6.95e6.99 (m, 1H), 7.08e7.14
(m, 2H), 7.30e7.34 (m, 1H). Enantiomeric excess was determined by
HPLC with a Chiralpark IA column (hexane/2-propanol¼95:5,
1.5 mL/min), t1¼24.0 min (R); t2¼25.8 min (S), ee¼81%. Pure R-
4.5.2. (R)-1-(2-Methoxyphenyl)proene-2-en-1-ol (8b). 1H NMR
(400 MHz, CDCl3) 2.55 (m, 2H), 2.70 (br s, 1H), 3.84 (s, 3H), 4.98
d
(m, 1H), 5.14 (m, 2H), 5.85 (m, 1H), 6.88 (d, J¼8.2 Hz, 1H), 6.97 (m,
1H), 7.25 (m, 1H), 7.34 (m, 1H). Enantiomeric excess was de-
enantiomer (100%) was used for [
a
]
D
determination. [
a
]
D
þ45.6 (c
termined by HPLC with
propanol¼95:5, 2.5 mL/min), t1¼15.6 min (S); t2¼16.7 min (R),
ee¼67%. Pure R-enantiomer (100%) was used for de-
termination. [
D þ63 (c 0.86, CHCl3).
a
Chiralpark IB column (hexane/2-
0.50, CHCl3). The reported value for the S-enantiomer (99% ee) is
[a
]
D ꢀ14.1 (c 3.58, CHCl3).16
[a]
D
a
]
4.5.10. (R)-1-(4-Fluorophenyl)but-3-en-1-ol (8j). 1H NMR (400 MHz,
CDCl3)
d
¼2.13 (s, 1H), 2.43e2.55 (m, 2H), 4.73 (m, 1H), 5.15e5.19 (m,
4.5.3. (R)-1-(3-Methoxyphenyl)proene-2-en-1-ol (8c). 1H NMR
(400 MHz, CDCl3)
2H), 5.74e5.83 (m, 1H), 7.02e7.06 (m, 2H), 7.27e7.35 (m, 2H). En-
antiomeric excess was determined by HPLC with a Chiralpark IA
column (hexane/2-propanol¼95:5, 1.5 mL/min), t1¼22.6 min (R);
t2¼23.5 min (S), ee¼73%. Pure R-enantiomer (100%) was used for
d
2.09 (d, J¼3.0 Hz, 1H), 2.52 (m, 2H), 3.82 (s, 3H),
4.71 (m, 1H), 5.13e5.19 (m, 2H), 5.76e5.86 (m, 1H), 6.82 (ddd, J¼8.0,
2.4, 0.8 Hz, 1H), 6.93 (m, 2H), 7.26 (dd, J¼9.1, 7.1 Hz, 1H). Enantio-
meric excess was determined by HPLC with a Chiralpark IA col-
[a]
D determination. [
a]D þ57.6 (c 0.58, CHCl3).
umn (hexane/2-propanol¼96:4,
t2¼24.5 min (S), ee¼83%. Pure R-enantiomer (100%) was used for
determination. [
þ56.1 (c 0.76, CHCl3). The reported value
3
mL/min), t1¼23.3 min (R);
4.5.11. (R)-1-(3-Nitrophenyl)but-3-en-1-ol (8k). 1H NMR (400 MHz,
CDCl3)
[
a]
a
]
d
2.33 (d, J¼3.1 Hz, 1H), 2.43e2.52 (m, 1H), 2.53e2.62 (m,
D
D
for the R-enantiomer (97% ee) is [
a]
þ53.8 (c 0.9,benzene).
1H), 4.87 (m, 1H), 5.18e5.22 (m, 2H), 5.75e5.85 (m, 1H), 7.53 (t,
J¼7.9 Hz, 1H), 7.71 (d, J¼7.6 Hz, 1H), 8.14 (d, J¼8.0 Hz, 1H), 8.25 (s,
1H). Enantiomeric excess was determined by HPLC with a Chir-
D
4.5.4. (R)-1-(4-Methoxyphenyl)proene-2-en-1-ol (8d). 1H NMR
(400 MHz, CDCl3)
d
2.04 (br s, 1H), 2.50 (t, J¼6.8 Hz, 2H), 3.80 (s,
alpark IB column (hexane/2-propanol¼95:5,
t1¼27.3 min (S); t2¼27.8 min (R), ee¼96%. Pure R-enantiomer
(100%) was used for [ D determination. [
D þ57.9 (c 0.38, CHCl3).
2
mL/min),
3H), 4.68 (t, J¼6.4 Hz, 1H), 5.11e5.18 (m, 2H), 5.76e5.83 (m, 1H),
6.88 (d, J¼8.6 Hz, 2H), 7.28 (d, J¼8.6 Hz, 2H). Enantiomeric excess
was determined by HPLC with a Chiralpark ID column (hexane/2-
propanol¼95:5, 3 mL/min), t1¼18.4 min (R); t2¼17.6 min (S),
a
]
a]
4.5.12. (R)-1-(4-Nitrophenyl)but-3-en-1-ol (8l). 1H NMR (400 MHz,
CDCl3)
2.30 (d, J¼3.2 Hz, 1H), 2.44e2.49 (m, 1H), 2.54e2.60 (m,
ee¼93%. Pure R-enantiomer (100%) was used for
[a
]
d
D

Y. Deng et al. / Tetrahedron 69 (2013) 10431e10437
10437
4. (a) Iseki, K.; Kuroki, Y.; Takahashi, M.; Kishimoto, S.; Kobayashi, Y. Tetrahedron
1997, 53, 3513e3526; (b) Iseki, K.; Kuroki, Y.; Takahashi, M.; Kobayashi, Y.
Tetrahedron Lett. 1996, 37, 5149e5150; (c) Iseki, K.; Mizuno, S.; Kuroki, Y.; Ko-
bayashi, Y. Tetrahedron 1999, 55, 977e988; (d) Iseki, K.; Mizuno, S.; Kuroki, Y.;
Kobayashi, Y. Tetrahedron Lett. 1998, 39, 2767e2770.
5. (a) Nakajima, M.; Saito, M.; Shiro, M.; Hashimoto, S. J. Am. Chem. Soc. 1998, 120,
6419e6420; (b) Nakajima, M.; Sasaki, Y.; Shiro, M.; Hashimoto, S. Tetrahedron:
Asymmetry 1997, 8, 341e344.
1H), 4.87 (m, 1H), 5.17e5.22 (m, 2H), 5.76e5.80 (m, 1H), 7.53 (d,
J¼10.7 Hz, 2H), 8.22 (d, J¼10.4 Hz, 2H). Enantiomeric excess was
determined by HPLC with a Chiralpark IA column (hexane/2-
propanol¼95:5, 2 mL/min), t1¼25.8 min (R); t2¼27.0 min (S),
ee¼85%. Pure R-enantiomer (100%) was used for
[
a]
de-
D
termination. [
a
]
þ80.0 (c 0.25, CHCl3). The reported value for the
D
S-enantiomer (65% ee) is [
a
]
D
ꢀ33.2 (c 0.50, CHCl3).9b
6. (a) Chataigner, I.; Piarulli, U.; Gennari, C. Tetrahedron Lett. 1999, 40, 3633e3634;
€
(b) Hellwig, J.; Belser, T.; Muller, J. F. K. Tetrahedron Lett. 2001, 42, 5417e5419;
(c) Kobayashi, S.; Nishio, K. J. Org. Chem. 1994, 59, 6620e6628; (d) Kobayashi, S.;
Nishio, K. Synthesis 1994, 1994, 457e459; (e) Tanimura, Y.; Ishimaru, K. Tetra-
hedron: Asymmetry 2012, 23, 345e349.
4.5.13. (R)-1-(Naphthalen-2-yl)but-3-en-1-ol
(400 MHz, CDCl3)
(8m). 1H
NMR
d
2.24 (br s, 1H), 2.57e2.66 (m, 2H), 4.92 (m, 1H),
7. Kocovsky, P.; Malkov, A. V. In Enantioselective Organocatalysis e Reactions and
Experimental Procedures; Dalko, P. I., Ed.; Wiley-VCH: Weinheim, 2007; p 255.
8. (a) Malkov, A. V.; Barlog, M.; Jewkes, Y.; Mikusek, J.; Kocovsky, P. J. Org. Chem.
2011, 76, 4800e4804; (b) Malkov, A. V.; Bell, M.; Castelluzzo, F.; Kocovsky, P.
Org. Lett. 2005, 7, 3219e3222; (c) Malkov, A. V.; Bell, M.; Orsini, M.; Pernazza,
D.; Massa, A.; Herrmann, P.; Meghani, P.; Kocovsky, P. J. Org. Chem. 2003, 68,
5.15e5.23 (2H,m), 5.79e5.90 (1H, m), 7.48e7.51 (3H, m), 7.82e7.86
(4H, m). Enantiomeric excess was determined by HPLC with a Chir-
alpark ID column (hexane/2-propanol¼95:5, 3 mL/min), t1¼14.1 min
(R); t2¼15.1 min (S), ee¼76%. Pure R-enantiomer (100%) was used for
[a]
determination. [
a
]
þ178.6 (c 0.14, CHCl3). The reported value
D
D
ꢀ
ꢁ
9659e9668; (d) Malkov, A. V.; Dufkova, L.; Farrugia, L.; Kocovsky, P. Angew.
for the S-enantiomer (81% ee) is [
a]
D ꢀ84.1 (c 1.0, CHCl3).9a
Chem. 2003, 115, 3802e3805; (e) Malkov, A. V.; Orsini, M.; Pernazza, D.; Muir,
ꢁ
K. W.; Langer, V.; Meghani, P.; Kocovsky, P. Org. Lett. 2002, 4, 1047e1049; (f)
ꢁ
ꢁ
ꢀ
ꢁ
Malkov, A. V.; Ramírez-Lopez, P.; Biedermannova, L.; Rulísek, L.; Dufkova, L.;
4.5.14. 3,30-Bis(methoxycarbonyl)-9,90-dimethyl-9H,90H-[1,10-bipyr-
ꢁ
Kotora, M.; Zhu, F.; Kocovsky, P. J. Am. Chem. Soc. 2008, 130, 5341e5348.
ido[3,4-b]indole] 2-oxide (10). IR (KBr)
n
¼3440, 1729, 1251,
9. (a) Shimada, T.; Kina, A.; Hayashi, T. J. Org. Chem. 2003, 68, 6329e6337; (b)
Shimada, T.; Kina, A.; Ikeda, S.; Hayashi, T. Org. Lett. 2002, 4, 2799e2801.
10. (a) Hrdina, R.; Dracinsky, M.; Valterova, I.; Hodacova, J.; Cisarova, I.; Kotora, M.
Adv. Synth. Catal. 2008, 350, 1449e1456; (b) Hrdina, R.; Kadlcikova, A.; Valter-
ova, I.; Hodacova, J.; Kotora, M. Tetrahedron: Asymmetry 2006, 17, 3185e3191;
(c) Hrdina, R.; Valterova, I.; Hodacova, J.; Cisarova, I.; Kotora, M. Adv. Synth.
Catal. 2007, 349, 822e826; (d) Kadlcikova, A.; Hrdina, R.; Valterova, I.; Kotora,
M. Adv. Synth. Catal. 2009, 351, 1279e1283; (e) Vlasana, K.; Hrdina, R.; Valter-
ova, I.; Kotora, M. Eur. J. Org. Chem. 2010, 36, 7040e7044.
748 cmꢀ1
.
MS-ESI, m/z 507 [MþNa]þ. HRMS m/z calcd for
C
28H22N4O5Na [MþNa]þ 511.1487, found 517.1479. 1H NMR
(400 MHz, CDCl3) d 3.16 (3H, s, NCH3), 3.62 (3H, s, NCH3), 4.00 (3H, s,
COOCH3), 4.03 (3H, s, COOCH3), 7.34e7.47 (4H, m), 7.57 (1H, t,
J¼7.4 Hz), 7.68 (1H, t, J¼7.4 Hz), 8.11 (1H, d, J¼7.8 Hz), 8.28 (1H, d,
J¼7.8 Hz), 8.49 (1H, s), 9.08 (1H, s). 13C NMR (100 MHz, CDCl3)
d
29.5, 31.9, 52.8, 53.1, 109.8, 110.1, 118.2, 118.9, 120.8, 120.9, 121.1,
11. (a) Bai, B.; Shen, L.; Ren, J.; Zhu, H. J. Adv. Synth. Catal. 2012, 354, 354e358; (b)
Bai, B.; Zhu, H. J.; Pan, W. Tetrahedron 2012, 68, 6829e6836.
121.1,121.6,121.8,128.4,129.3,129.8,132.1,133.0,133.2,136.9,136.9,
12. (a) Adachi, S.; Harada, T. Eur. J. Org. Chem. 2009, 22, 3661e3671; (b) Chen, J. S.;
Captain, B.; Takenaka, N. Org. Lett. 2011, 13, 1654e1657; (c) Naicker, T.; Ar-
vidsson, P. I.; Kruger, H. G.; Maguire, G. E. M.; Govender, T. Eur. J. Org. Chem.
2011, 34, 6923e6932; (d) Pignataro, L.; Benaglia, M.; Annunziata, R.; Cinquini,
M.; Cozzi, F. J. Org. Chem. 2006, 71, 1458e1463; (e) Traverse, J. F.; Zhao, Y.;
Hoveyda, A. H.; Marc, L. Org. Lett. 2005, 7, 3151e3154; (f) Wong, W. L.; Lee, C. S.;
Leung, H. K.; Kwong, H. L. Org. Biomol. Chem. 2004, 2, 1967e1969.
138.1, 138.8, 142.7, 143.6, 163.3, 166.4. [
a
]
D þ605.3 (c 0.25, CHCl3).
Acknowledgements
H.J.Z. thanks the supports from Hebei University.
13. (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648e5652; (b) Lee, C.; Yang, W.; Parr, R.
G. Phys. Rev. B 1988, 37, 785e789; (c) Hehre, W. J.; Radom, L.; Schleyer, P. v. R.;
Pople, J. A. Ab Initio Molecular Orbital Theory; Wiley: New York, NY, 1986; (d)
Liu, D. Z.; Wang, F.; Liao, T. G.; Tang, J. G.; Steglich, W.; Zhu, H. J.; Liu, J. K. Org.
Lett. 2006, 8, 5749e5752; (e) Wolinski, K.; Hilton, J. F.; Pulay, P. J. Am. Chem. Soc.
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