Asymmetric organocatalytic tandem cyclization/transfer hydrogenation: A synthetic strategy for enantioenriched nitrogen heterocycles

Article abstract of DOI:10.1002/adsc.201300576

An asymmetric organocatalytic tandem reaction comprising cyclization/transfer hydrogenation has been established in a compatible and synergistic way, leading to the step-economical synthesis of enantioenriched tetrahydroquinoxalines and dihydroquinoxalinones from readily accessible materials in excellent enantioselectivity of up to >99% ee. This protocol of a one-operation tandem reaction combines the merits of both tandem reactions and asymmetric organocatalysis, providing an efficient strategy for concisely and enantioselectively synthesizing nitrogen heterocycles with biological relevance. Copyright

Full text of DOI:10.1002/adsc.201300576

UPDATES
DOI: 10.1002/adsc.201300576
Asymmetric Organocatalytic Tandem Cyclization/Transfer
Hydrogenation: A Synthetic Strategy for Enantioenriched
Nitrogen Heterocycles
Feng Shi,a,* Wei Tan,a Hong-Hao Zhang,a Mei Li,a Qin Ye,a Guan-Hua Ma,a
Shu-Jiang Tu,a,* and Guigen Lib,c
a
School of Chemistry & Chemical Engineering, and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional
Materials, Jiangsu Normal University, Xuzhou 221116, Peopleꢀs Republic of China
E-mail: fshi@jsnu.edu.cn or laotu@jsnu.edu.cn
Institute of Chemistry & BioMedical Sciences, Nanjing University, Nanjing 210093, Peopleꢀs Republic of China
b
c
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA
Received: June 28, 2013; Revised: September 30, 2013; Published online: November 27, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300576.
Abstract: An asymmetric organocatalytic tandem
reaction comprising cyclization/transfer hydrogena-
tion has been established in a compatible and syner-
gistic way, leading to the step-economical synthesis
of enantioenriched tetrahydroquinoxalines and di-
hydroquinoxalinones from readily accessible mate-
rials in excellent enantioselectivity of up to >99%
ee. This protocol of a one-operation tandem reac-
tion combines the merits of both tandem reactions
and asymmetric organocatalysis, providing an effi-
cient strategy for concisely and enantioselectively
synthesizing nitrogen heterocycles with biological
relevance.
action step or paralleled by multi-step reactions due
to the effect of compatibility and synergy generated
in the tandem reaction.[2e]
Chiral nitrogen heterocycles constitute the core
structures of many natural alkaloids and artificial
pharmaceuticals. In particular, optically pure 1,2,3,4-
tetrahydroquinoxalines have exhibited great potential
for medicinal applications.[3] As indicated in Figure 1,
compound I is utilized as a cholesterol ester transfer
protein inhibitor,[3a] and compound II is found to be
a potent p53/Hdm2 antagonist.[3b] Besides, compound
III possesses the important activities of anti-athero-
sclerosis and anti-obesity.[3c] Therefore, the synthesis
of enantioenriched tetrahydroquinoxalines has at-
tracted intensive attention in organic and medicinal
research areas.
Keywords: asymmetric catalysis; enantioselectivity;
organic catalysis; tandem reaction; transfer hydro-
genation
The known enantioselective approaches to tetrahy-
droquinoxaline motifs are represented by the catalytic
asymmetric hydrogenation of quinoxalines.[4]
A
number of metal-catalyzed [Eq. (1)][4a–j] and one
organo-catalyzed asymmetric hydrogenation reactions
[Eq. (2)][4k] have been established by using either hy-
drogen gas or a Hantzsch ester (HEH) as hydride
Introduction
The concept of step-economy has been playing an in-
creasingly important role in chemical and pharma-
ceutical synthesis.[1] In recent years, asymmetric cata-
lytic cascade or tandem reactions have substantially
benefited from this concept and turned out to be
robust step-economical tools for an easy access to
complex chiral scaffolds using simple materials, fea-
tured by avoiding time-consuming isolation and pu-
rification procedures, which are inherently required in
stepwise synthesis.[2] More significantly, the catalytic
asymmetric tandem reaction has been proven to
enable unprecedented step-economical transforma-
tions, which can hardly be achieved by any single re- Figure 1. Some bioactive chiral tetrahydroquinoxalines.
Adv. Synth. Catal. 2013, 355, 3715 – 3726
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Feng Shi et al.
UPDATES
source. Although this strategy is elegant, it mostly re- Results and Discussion
quires pre-formed and purified quinoxalines as start-
ing materials, and thereby suffers from low step-econ- The attempt to validate our proposal commenced
omy. The development of more step-economical with the reaction of 1,2-phenylenediamine 1a with
tandem reactions for the asymmetric synthesis of opti- phenylglyoxal 2a using Hantzsch ester 3a as the hy-
cally pure tetrahydroquinoxalines from readily avail- dride source, which was performed in the presence of
able starting materials continues to be desirable and 5 mol% of chiral phosphoric acids 5 in chloroform at
challenging.
358C (Table 1). Unfortunately, the initial experiment
It has long been recognized that the condensation only gave a tiny amount of the desired product 4aa
of 1,2-phenylenediamine with phenylglyoxal would (entry 1). This implied that the way to fuse the two
give quinoxalines.[5] But the possibility of integrating steps of cyclization and transfer hydrogenation in
this process with the asymmetric organocatalytic hy- a compatible and synergistic mode was the key point
drogenation of quinoxalines into a tandem reaction is to realize this tandem reaction. After many tries, it
still unknown, since a successful tandem reaction was found that the addition of 3ꢂ MS could enable
relies on the compatibility and more importantly, on the same reaction to afford the product 4aa in
the synergy of two or more reaction processes per- a nearly quantitative yield and excellent enantioselec-
formed under the same reaction conditions. Inspired tivity (99% and 93% ee, respectively, entry 2). The
by this anticipation and our interests in enantioselec-
tive tandem reactions,[6] we proposed a phosphoric
Table 1. The optimization of the reaction conditions.[a]
acid-catalyzed[7] cascade condensation/enantioselec-
tive transfer hydrogenation, enabling the direct trans-
formation of commercially available starting materials
into optically pure 1,2,3,4-tetrahydroquinoxalines
(Scheme 1). Besides, this strategy may be employed
to synthesize other chiral heterocycles.
In this work, we present an organocatalytic asym-
metric tandem reaction comprising cyclization/trans-
fer hydrogenation in a one-pot operation by using
a bulky chiral phosphoric acid as the catalyst and
a Hantzsch ester as the hydride source, which pro-
vides a step-economical synthetic strategy for enan-
tioenriched heterocycles such as tetrahydroquinoxa-
lines and dihydroquinoxalinones in excellent enantio-
selectivity of up to >99% ee.
Entry
5
Solvent
MS
Yield [%][b]
ee [%][c]
[e]
1[d]
2
3
4
5
6
7
8
9
10
11
12
13
14[f]
5a
5a
5b
5c
5d
5e
5f
5a
5a
5a
5a
5a
5c
5c
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
DCE
toluene
EtOAc
CHCl3
CHCl3
CHCl3
CHCl3
–
<10
99
72
86
90
91
75
93
93
57
99
76
94
97
–
3ꢂ
3ꢂ
3ꢂ
3ꢂ
3ꢂ
3ꢂ
3ꢂ
3ꢂ
3ꢂ
4ꢂ
5ꢂ
4ꢂ
4 ꢂ
93
93
94
74
18
7
91
79
83
94
71
95
90
[a]
Unless indicated otherwise, the reaction was carried out
on a 0.2-mmol scale under argon in a solvent (1 mL) with
MS (100 mg) for 24 h, using 3a as hydride source, and
the ratio of 1a:2a:3a was 1:1:3.
Yields refer to isolated yields.
The ees were determined by HPLC.
Performed in the absence of MS.
Not determined.
3b was employed as hydride source instead of 3a.
Scheme 1. Proposed strategy for organocatalytic step-eco-
nomical synthesis of chiral tetrahydroquinoxalines.
[b]
[c]
[d]
[e]
[f]
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Asymmetric Organocatalytic Tandem Cyclization/Transfer Hydrogenation
Table 2. Substrate scope of the asymmetric organocatalytic
tandem reaction for the synthesis of tetrahydroquinoxa-
AHCTUNGTRENNUNG
lines.[a]
crucial role of 3ꢂ MS would be largely attributed to
its action in removing the water molecules generated
from the condensational cyclization of reactants 1a
and 2a, thus facilitating the formation of the inter-
mediate quinoxaline. The screening of chiral catalysts
(entries 2–7) revealed that phosphoric acids 5a–5c
with bulky groups at the 3,3’-positions of the BINOL
backbone were much more efficient in delivering high
enantioselectivity (entries 2–4) than other counter-
parts. We then investigated the solvent effect in the
presence of catalyst 5a. Among the solvents we uti-
lized, chloroform was proven to be the best one with
regard to enantioselectivity (entries 8–10 vs. 2). Due
to the importance of 3ꢂ MS, we further studied 4ꢂ
or 5ꢂ MS for this reaction (entries 11–12), and found
4ꢂ MS showed a slightly higher capacity than 3ꢂ
MS in controlling the enantioselectivity (entry 11 vs.
2). Under these conditions, the replacement of cata-
lyst 5a by 5c enhanced the enantioselectivity to the
highest level of 95% ee (entry 13), but the subsequent
change of Hantzsch esters from 3a to 3b did not im-
prove the enantioselectivity (entry 14).
Under the optimal reaction conditions (Table 1,
entry 13), we then examined the substrate scope of
this asymmetric organocatalytic tandem cyclization/
transfer hydrogenation sequence for the synthesis of
tetrahydroquinoxalines. As illustrated in Table 2, this
cascade reaction is amenable to a wide scope of sub-
stituted glyoxals 2 including aryl glyoxals bearing
electronically neutral, rich, or poor substituents on
their aromatic rings, and a heteroaryl-substituted
glyoxal as well, thus delivering structurally diverse 2-
substituted tetrahydroquinoxalines 4aa–4aj in excel-
lent enantioselectivities (90–97% ee) and good to
quantitative yields (57–99%). Generally, there is no
significant difference in enantioselectivity among vari-
ous 2-aryltetrahydroquinoxalines 4aa–4ai, and high ee
values ranging from 93% to 97% were achieved re-
gardless of the electronic nature and position of the
substituents. More importantly, the heteroaryl-substi-
tuted glyoxal appeared to be a suitable substrate, of-
fering 2-(thiophen-2-yl)tetrahydroquinoxaline 4aj in
high enantioselectivity of 90% ee.
[a]
Unless indicated otherwise, the reaction was carried out
on a 0.2-mmol scale under argon in CHCl3 (1 mL) with
4ꢂ MS (100 mg) for 24 h, and the ratio of 1:2:3a was
1:1:3. Yields refer to isolated yields and ees were deter-
mined by HPLC.
Moreover, as shown in Table 2, this approach is
also applicable to various symmetrical 1,2-arylenedia-
mines 1 with electron-rich, electron-neutral, or elec-
tron-withdrawing substituents on their benzene rings,
offering tetrahydroquinoxalines 4ba–4da in excellent
levels of enantioselectivities (97–99% ee) and high selective tetrahydroquinoxalines with structural diver-
yields (86–96%). Furthermore, these diamines 1 can sity.
smoothly participate in the tandem reactions with dif-
Besides, the reaction involving aliphatic glyoxals as
ferent aryl glyoxals 2 to provide a series of tetrahy- exemplified by methylglyoxal 2k was also investigat-
droquinoxalines 4cc–4dc in perfect enantioselectivities ed. The reaction afforded the desired 2-methyltetra-
of 98–>99% ee and good to excellent yields of 73– hydroquinoxaline 4ak with acceptable enantioselectiv-
90%. Therefore, this protocol has proven to be a pow- ity of 70% ee in a two-step manner [Eq. (1)]. Howev-
erful tool in the step-economical synthesis of enantio- er, the same reaction in a one-step mode only gave
product 4ak with moderate enantioselectivity of 50%
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Feng Shi et al.
UPDATES
ee [Eq. (2)]. The difference between the enantioselec- uct 4ea was identified by X-ray single crystal analysis
tivity of the two reactions might be ascribed to the of rac-4ea (Figure 2).[8] Also the structures of products
water molecules in the methylglyoxal solution 4ga and 4ga’ were determined by comparing their
(40 wt% in water), since water molecules could form NMR and HPLC spectra with those of the same
hydrogen bonds with catalyst 5c. This would disturb known compounds.[4k] The structures of other prod-
the formation of hydrogen bonds between the catalyst ucts were assigned by analogy. Interestingly, the meta-
and the substrates, which play a crucial role in enan- directing group CO2Et led to the formation of 4 as
tioselective control.
major regioselective product (entry 1), while the
Then, we studied the regioselectivity of the reaction ortho-para-directing group Br resulted in the genera-
when unsymmetrical 1,2-arylenediamines were em- tion of 4’ as major regioselective product (entry 3).
ployed for this tandem reaction. As shown in Table 3, This difference in regioselectivity might largely be at-
various unsymmetrical 1,2-arylenediamines with dif- tributed to the electronic effects of these substituents,
ferent types of orientating groups were utilized as which led to differential reactivity of the two amino
substrates in the reaction, leading to two different re- groups, thereby resulting in the formation of different
gioselective tetrahydroquinoxalines 4 and 4’ concur- regioselective products.
rently, both in good to excellent enantioselectivities.
More importantly, the strategy of asymmetric orga-
It was found that 1,2-arylenediamine 1e with a strong nocatalytic tandem cyclization/transfer hydrogenation
electron-withdrawing ester group showed the highest can be successfully employed to synthesize other
regioselectivity of 3.2:1 rr (entry 1, rr=regioselective enantioenriched heterocycles as exemplified by chiral
ratio), but 1,2-arylenediamine 1h with a strong elec- 3,4-dihydroquinoxalinones, which also possess signifi-
tron-donating group exhibited poor regioselectivity of cant bioactivities[9] but are rather limited in their
1:1 rr (entry 4). The structure of regioselective prod- enantioselective versions.[4j,10] As indicated in Table 4,
Table 3. The investigation on the regioselectivity of the reaction for the synthesis of tetrahydroquinoxalines.[a]
Entry
4 (4’)
R (1)
rr[b] (4:4’)
Yield [%] 4 (4’)[c]
ee [%] 4 (4’)[d]
1
2
3
4
4ea (4ea’)
4fa (4fa’)
4ga (4ga’)
4ha (4ha’)
CO2Et (1e)
CF3 (1f)
Br (1g)
3.2:1
1.3:1
1:1.3
1:1
42 (13)
39 (31)
37 (48)
26 (26)
79 (90)
90 (87)
97 (94)
86 (89)
OMe (1h)
[a]
Unless indicated otherwise, the reaction was carried out on a 0.2-mmol scale under argon in CHCl3 (1 mL) with 4ꢂ MS
(100 mg) for 24 h, and the ratio of 1:2a:3a was 1:1:3.
The regioselective ratio (rr) was calculated by the yields of products 4 and 4’.
Yields refer to isolated yields.
[b]
[c]
[d]
The ees were determined by HPLC.
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Asymmetric Organocatalytic Tandem Cyclization/Transfer Hydrogenation
Figure 2. X-ray single crystal structure of rac-4ea.
Table 4. Extension of the strategy to the step-economical synthesis of 3,4-dihydroquinoxalin-
ACHTUNGTRENNUNG
ones.[a]
[a]
Unless indicated otherwise, the reaction was carried out on a 0.2-mmol scale under argon
in THF (1 mL) for 24 h, and the ratio of 1:6:3a was 1:1:1.5. Yields refer to isolated yields
and ees were determined by HPLC.
the cascade cyclization/transfer hydrogenation se- a variety of 1,2-phenylenediamines 1 and ethyl 2-oxo-
quence consists of the condensation-type cyclization 2-phenylacetates 6, offering structurally diverse 3,4-di-
of 1,2-phenylenediamines 1 with ethyl 2-oxo-2-phenyl- hydroquinoxalinones 7 in excellent enantioselectivi-
acetates 6 and the subsequent enantioselective trans- ties (94–99% ee).
fer hydrogenation of the intermediate products 8
The absolute configuration of product 4aa was de-
using Hantzsch ester 3a as hydride source, giving the termined to be 2R by comparing its optical rotation
desired chiral 3,4-dihydroquinoxalinones 7 in a step- ([a]2D0: À97.0) with that of the same known compound
economical fashion. Under the similar reaction condi- ([a]rD:t:: À98.6).[4k] The absolute configurations of other
tions, the one-step, one-pot operation cascade reac- products were assigned by analogy.
tion took place smoothly and was found to tolerate
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Feng Shi et al.
UPDATES
Scheme 2. Proposed reaction pathway and transition state.
On the basis of our experimental results and previ- Experimental Section
ously reported calculations on transfer hydrogenation
of imines,[11] we proposed a possible reaction pathway General
and transition state to explain the stereochemistry of
NMR spectra were measured at 400 and 100 MHz, respec-
tively. The solvent used for NMR spectroscopy was CDCl3,
using tetramethylsilane as the internal reference. HR-MS
(ESI) were determined with a micrOTOF-QII HRMS/MS
instrument (Bruker). Enantiomeric excesses (ee) were deter-
mined by chiral high-performance liquid chromatography
(chiral HPLC). The chiral columns used for the determina-
tion of enantiomeric excesses by chiral HPLC were Chiral-
pak OD-H, AD-H and IA columns. Optical rotation values
were measured with instruments operating at l=589 nm,
corresponding to the sodium D line at the temperatures in-
dicated. Analytic grade solvents for the column chromatog-
raphy and commercially available reagents were used as re-
ceived. All commercially available starting materials were
used directly. Substrates 2 except for 2a and 2k were synthe-
sized according to the literature methods.[12]
this reaction (Scheme 2). Initially, the condensation-
type cyclization of substrates 1 and 2 or 6 in the pres-
ence of chiral phosphoric acid (B*-H) generated in-
termediate product 8 or 9. Subsequently, B*-H acted
as a bifunctional catalyst to activate both the inter-
mediate and HEH 3a by hydrogen-bonding interac-
tion, thereby facilitating the asymmetric 1,4-hydride
transfer pathway to generate the final product (R)-4
or 7. The two hydrogen bonds and the effect of steric
hindrance created by B*-H built up a “three-point
contact model”,[11a,b] which determined the excellent
enantioselectivities and (R)-configurations of the
products experimentally observed.
Conclusions
General Procedure for the Synthesis of Chiral
Tetrahydroquinoxalines 4 via Asymmetric
Organocatalytic Tandem Cyclization/Transfer
Hydrogenation
In summary, we have established an asymmetric orga-
nocatalytic tandem reaction of cyclization/transfer hy-
drogenation in a compatible and synergistic way, lead-
ing to the step-economical synthesis of enantioen-
riched tetrahydroquinoxalines and dihydroquinoxali-
nones from readily accessible materials. This protocol
of a one-operation tandem reaction combines the
merits of both tandem reactions and asymmetric orga-
nocatalysis, tolerating a wide range of simple sub-
strates to concisely furnish structurally diverse tetra-
hydroquinoxalines and dihydroquinoxalinones in ex-
cellent enantioselectivity of up to >99% ee. This
strategy not only provides an easy access to biologi-
cally significant chiral nitrogen heterocycles, but also
opens a new window towards the extension of this
strategy to other synthetically important compounds.
Under an argon atmosphere, chloroform (1 mL) was added
to the mixture of 1,2-arylenediamine 1 (0.2 mmol), substitut-
ed glyoxal 2 (0.2 mmol), Hantzsch ester 3a (0.6 mmol), the
catalyst 5c (0.01 mmol) and 4ꢂ molecular sieves (100 mg).
After being stirred at 358C for 24 h, the reaction mixture
was filtered to remove molecular sieves and the solid
powder was washed with ethyl acetate. The resultant solu-
tion was concentrated under the reduced pressure to give
the residue, which was purified through flash column chro-
matography on silica gel to afford pure products 4.
General Procedure for the Synthesis of Chiral
Dihydroquinoxalinones 7 via Asymmetric
Organocatalytic Tandem Cyclization/Transfer
Hydrogenation
Under an argon atmosphere, THF (1 mL) was added to the
mixture of 1,2-arylenediamine 1 (0.2 mmol), ethyl 2-oxo-2-
phenylacetate 6 (0.2 mmol), Hantzsch ester 3a (0.3 mmol)
and the catalyst 5a (0.01 mmol). After being stirred at 508C
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Asymmetric Organocatalytic Tandem Cyclization/Transfer Hydrogenation
for 24 h, the reaction mixture was purified through flash
column chromatography on silica gel to afford pure products
7.
H)+: 225.1392; enantiomeric excess: 96%, determined by
HPLC (Daicel Chirapak OD-H, hexane/2-propanol=80/20,
flow rate 1.0 mLminÀ1, T=308C, 254 nm): tR =11.510 min
(major), tR =16.790 min (minor).
(R)-2-Phenyl-1,2,3,4-tetrahydroquinoxaline (4aa): Flash
column chromatography eluent, toluene/ethyl acetate=80/1;
reaction time=24 h; yield: 39.4 mg (94%); yellow solid; mp
68–698C; [a]20: À97.0 (c 0.3, CHCl3); 1H NMR (400 MHz,
CDCl3): d=7D.41–7.31 (m, 5H), 6.66–6.58 (m, 4H), 4.49 (dd,
J=8.0, 2.4 Hz, 1H), 4.16–3.15 (m, 4H); 13C NMR (100 MHz,
CDCl3): d=141.8, 134.2, 132.7, 128.7, 127.9, 127.0, 119.0,
118.8, 114.8, 114.5, 54.7, 49.1; IR (KBr): n=3383, 3357,
(R)-2-(4-Fluorophenyl)-1,2,3,4-tetrahydroquinoxaline
(4ae): Flash column chromatography eluent, toluene/ethyl
acetate=90/1; reaction time=24 h; yield: 45.3 mg (99%);
yellow solid; mp 62–638C; [a]2D0: À98.8 (c 0.7, CHCl3);
1H NMR (400 MHz, CDCl3): d=7.38–7.34 (m, 2H), 7.06 (t,
J=8.8 Hz, 2H), 6.67–6.65 (m, 2H), 6.6–6.58 (m, 2H), 4.47
(dd, J=8.4, 3.2 Hz, 1H), 3.76 (s, 2H), 3.43 (dd, J=11.2,
3.2 Hz, 1H), 3.29 (dd, J=10.8, 8.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d=163.6, 161.2, 137.6, 133.9, 132.6,
128.6, 119.0, 115.6, 115.4, 114.9, 114.6, 54.0, 49.2; IR (KBr):
n=3357, 3338, 3277, 2917, 2849, 1601, 1509, 1457, 1305,
1229, 1119, 829, 751 cmÀ1; ESI-FT-MS: m/z=229.1130, exact
mass calcd. for (C14H13FN2 +H)+: 229.1141; enantiomeric
excess: 96%, determined by HPLC (Daicel Chirapak OD-
H, hexane/2-propanol=80/20, flow rate 1.0 mLminÀ1, T=
308C, 254 nm): tR =15.657 min (major), tR =24.830 min
(minor).
(R)-2-(4-Chlorophenyl)-1,2,3,4-tetrahydroquinoxaline
(4af): Flash column chromatography eluent, toluene/ethyl
acetate=90/1; reaction time=24 h; yield: 36.8 mg (75%);
yellow solid; mp 100–1018C; [a]2D0: À79.4 (c 0.3, CHCl3);
1H NMR (400 MHz, CDCl3): d=7.37–7.28 (m, 4H), 6.66–
6.63 (m, 2H), 6.60–6.57 (m, 2H), 4.47 (dd, J=7.6, 2.8 Hz,
1H), 3.83 (s, 2H), 3.44 (dd, J=11.2, 2.8 Hz, 1H), 3.28 (dd,
J=10.8, 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=
140.4, 133.8, 133.6, 132.5, 128.8, 128.4, 119.2, 119.0, 114.9,
114.6, 54.1, 48.9; IR (KBr): n=3338, 2922, 2852, 1597, 1507,
1491, 1457, 1304, 1090, 1014, 820, 741, 669 cmÀ1; ESI-FT-
MS: m/z=245.0835, exact mass calcd. for (C14H13ClN2 +
H)+: 245.0846; enantiomeric excess: 97%, determined by
HPLC (Daicel Chirapak OD-H, hexane/2-propanol=80/20,
flow rate 1.0 mLminÀ1, T=308C, 254 nm): tR =17.990 min
(major), tR =31.137 min (minor).
(R)-2-(4-Bromophenyl)-1,2,3,4-tetrahydroquinoxaline
(4ag): Flash column chromatography eluent, toluene/ethyl
acetate=90/1; reaction time=24 h; yield: 34.7 mg (60%);
yellow solid; mp 117–1188C; [a]2D0: À69.8 (c 0.4, CHCl3);
1H NMR (400 MHz, CDCl3): d=7.49 (d, J=8.0 Hz, 2H),
7.26 (d, J=8.0 Hz, 2H), 6.66–6.64 (m, 2H), 6.59–6.56 (m,
2H), 4.45 (dd, J=8.0, 2.8 Hz, 1H), 3.86 (s, 2H), 3.43 (dd,
J=11.2, 2.8 Hz, 1H), 3.27 (dd, J=10.8, 8.0 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=140.9, 133.8, 132.7, 131.8,
128.7, 121.7, 119.0, 114.8, 114.5, 54.2, 48.9; IR (KBr): n=
3367, 3335, 3046, 2917, 2850, 1596, 1517, 1488, 1464, 1338,
1304, 1119, 1010, 816, 737 cmÀ1; ESI-FT-MS: m/z=289.0328,
exact mass calcd. for (C14H13BrN2 +H)+: 289.0340; enantio-
meric excess: 93%, determined by HPLC (Daicel Chirapak
OD-H, hexane/2-propanol=80/20, flow rate 1.0 mLminÀ1,
T=308C, 254 nm): tR =20.063 min (major), tR =34.437 min
(minor).
3337, 3252, 3061, 3031, 2914, 2850, 1949, 1869, 1595 cmÀ1
;
ESI-FT-MS: m/z=211.1224, exact mass calcd. for
(C14H14N2 +H)+: 211.1235; enantiomeric excess: 95%, deter-
mined by HPLC (Daicel Chirapak OD-H, hexane/2-propa-
nol=80/20, flow rate 1.0 mLminÀ1, T=308C, 254 nm): tR =
13.457 min (major), tR =18.043 min (minor).
(R)-2-(Naphthalen-2-yl)-1,2,3,4-tetrahydroquinoxaline
(4ab): Flash column chromatography eluent, toluene/ethyl
acetate=90/1; reaction time=24 h; yield: 38.6 mg (74%);
yellow solid; mp 150–1518C; [a]2D0: À96.5 (c 0.5, CHCl3);
1H NMR (400 MHz, CDCl3): d=7.87–7.85 (m, 4H), 7.52–
7.49 (m, 3H), 6.67–6.62 (m, 4H), 4.65 (d, J=6.4 Hz, 1H),
3.94 (s, 2H), 3.52 (d, J=8.8 Hz, 1H), 3.47–3.37 (m, 1H);
13C NMR (100 MHz, CDCl3): d=139.2, 134.2, 133.4, 133.2,
132.9, 128.4, 127.9, 127.7, 126.3, 126.0, 125.8, 125.1, 119.0,
118.9, 114.8, 114.5, 54.9, 49.2; IR (KBr): n=3351, 3054,
2922, 2834, 1591, 1504, 1454, 1299, 1271, 1119 cmÀ1; ESI-FT-
MS: m/z=261.1382, exact mass calcd. for (C18H16N2 +H)+:
261.1392; enantiomeric excess: 94%, determined by HPLC
(Daicel Chirapak AD-H, hexane/2-propanol=70/30, flow
rate 1.0 mLminÀ1, T=308C, 254 nm): tR =14.307 min
(major), tR =30.943 min (minor).
(R)-2-(4-Methoxyphenyl)-1,2,3,4-tetrahydroquinoxaline
(4ac): Flash column chromatography eluent, toluene/ethyl
acetate=90/1; reaction time=24 h; yield: 47.7 mg (99%);
yellow solid; mp 83–858C; [a]2D0: À71.4 (c 0.9, CHCl3);
1H NMR (400 MHz, CDCl3): d=7.34 (d, J=8.8 Hz, 2H),
6.95 (d, J=8.4 Hz, 2H), 6.89–6.67 (m, 2H), 6.62–6.60 (m,
2H), 4.46 (dd, J=8.4, 2.8 Hz, 1H), 3.85 (s, 3H), 3.75 (s,
2H), 3.45 (dd, J=11.2, 3.2 Hz, 1H), 3.33 (dd, J=10.8,
8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=159.3, 134.3,
133.9, 132.7, 128.1, 118.9, 118.8, 114.8, 114.5, 114.0, 55.4,
54.1, 49.3; IR (KBr): n=2920, 2850, 1616, 1558, 1541, 1518,
1458, 1339, 1252, 1176, 1101 cmÀ1
;
ESI-FT-MS: m/z
241.1329, exact mass calcd. for (C15H16N2O +H)+: 241.1341;
enantiomeric excess: 96%, determined by HPLC (Daicel
Chirapak OD-H, hexane/2-propanol=80/20, flow rate
1.0 mLminÀ1, T=308C, 254 nm): tR =16.613 min (major),
tR =23.343 min (minor).
(R)-2-(p-Tolyl)-1,2,3,4-tetrahydroquinoxaline (4ad): Flash
column chromatography eluent, toluene/ethyl acetate=90/1;
reaction time=24 h; yield: 44.2 mg (99%); yellow solid; mp
93–958C; [a]20: À87.4 (c 0.7, CHCl3); 1H NMR (400 MHz,
CDCl3): d=7D.64 (d, J=8.0 Hz, 2H), 7.55 (d, J=7.6 Hz, 2H),
7.01–6.91 (m, 4H), 4.80 (dd, J=8.0, 2.8 Hz, 1H), 4.11 (s,
2H), 3.79 (dd, J=10.8, 2.8 Hz, 1H), 3.67 (dd, J=11.2,
8.4 Hz, 1H), 2.73 (s, 3H); 13C NMR (100 MHz, CDCl3): d=
138.9, 137.6, 134.3, 132.8, 129.4, 126.9, 118.8, 114.8, 114.5,
54.5, 49.2, 21.2; IR (KBr): n=3363, 3333, 3245, 3023, 2918,
2850, 1597, 1514, 1457, 1339, 1306, 1107, 814, 739 cmÀ1; ESI-
FT-MS: m/z=225.1380, exact mass calcd. for (C15H16N2 +
(R)-2-(3-Chlorophenyl)-1,2,3,4-tetrahydroquinoxaline
(4ah): Flash column chromatography eluent, toluene/ethyl
acetate=70/1; reaction time=24 h; yield: 36.8 mg (75%);
1
yellow oil; [a]2D0: À87.3 (c 0.6, CHCl3); H NMR (400 MHz,
CDCl3): d=7.37 (s, 1H), 7.29–7.24 (m, 3H), 6.65–6.55 (m,
4H), 4.44 (dd, J=8.0, 2.8 Hz, 1H), 3.75 (s, 2H), 3.43 (dd,
J=11.2, 2.8 Hz, 1H), 3.27 (dd, J=10.8, 8.4 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=143.9, 134.6, 133.8, 132.6,
Adv. Synth. Catal. 2013, 355, 3715 – 3726
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3721

Feng Shi et al.
UPDATES
129.9, 128.1, 127.2, 125.2, 119.2, 119.0, 114.9, 114.6, 54.3,
48.9; IR (KBr): n=2923, 2851, 1749, 1717, 1699, 1684, 1558,
1508, 1489, 1457 cmÀ1; ESI-FT-MS: m/z=245.0835, exact
mass calcd. for (C14H13ClN2 +H)+: 245.0846; enantiomeric
excess: 94%, determined by HPLC (Daicel Chirapak AD-
H, hexane/2-propanol=70/30, flow rate 1.0 mLminÀ1, T=
308C, 254 nm): tR =8.400 min (major), tR =10.643 min
(minor).
(R)-2-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydroquinoxaline
(4ai): Flash column chromatography eluent, toluene/ethyl
acetate=90/1; reaction time=24 h; yield: 46.2 mg (83%);
yellow solid; mp 94–958C; [a]2D0: À86.9 (c 0.5, CHCl3);
1H NMR (400 MHz, CDCl3): d=7.49 (d, J=2.0 Hz, 1H),
7.43 (d, J=8.4 Hz, 1H), 7.22 (dd, J=8.4, 2.0 Hz, 1H), 6.67–
6.64 (m, 2H), 6.61–6.57 (m, 2H), 4.45 (dd, J=7.6, 2.8 Hz,
1H), 3.86 (s, 2H), 3.44 (dd, J=10.8, 2.8 Hz, 1H), 3.26 (dd,
J=11.2, 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=
142.3, 133.4, 132.7, 131.7, 130.6, 128.9, 126.4, 119.2, 114.9,
114.6, 53.8, 48.8; IR (KBr): n=3341, 2918, 2850, 1595, 1507,
1490, 1458, 1310, 1129, 1027, 742 cmÀ1; ESI-FT-MS: m/z=
279.0445, exact mass calcd. for (C14H12Cl2N2 +H)+: 279.0456;
enantiomeric excess: 97%, determined by HPLC (Daicel
Chirapak OD-H, hexane/2-propanol=80/20, flow rate
1.0 mLminÀ1, T=308C, 254 nm): tR =21.933 min (major),
tR =43.853 min (minor).
1H NMR (400 MHz, CDCl3): d=7.40–7.32 (m, 5H), 6.59 (d,
J=3.6 Hz, 2H), 4.43 (dd, J=8.0, 2.8 Hz, 1H), 3.96 (s, 2H),
3.44 (dd, J=10.8, 2.9 Hz, 1H), 3.27 (dd, J=11.2, 8.1 Hz,
1H); 13C NMR (100 MHz, CDCl3): d=140.9, 133.7, 132.5,
128.8, 128.2, 126.9, 120.6, 114.9, 54.3, 48.4; IR (KBr): n=
3395, 3065, 3032, 2912, 2856, 1953, 1600, 1584, 1506, 1298,
1124, 1060, 849, 757, 701 cmÀ1; ESI-FT-MS: m/z=279.0447,
exact mass calcd. for (C14H12Cl2N2 +H)+: 279.0456; enantio-
meric excess: 99%, determined by HPLC (Daicel Chirapak
AD-H, hexane/2-propanol=80/20, flow rate 1.0 mLminÀ1,
T=308C, 254 nm): tR =13.497 min (minor), tR =15.583 min
(major).
(R)-6,7-Dimethyl-2-phenyl-1,2,3,4-tetrahydroquinoxaline
(4da): (Flash column chromatography eluent, toluene/ethyl
acetate=90/1); reaction time=24 h; yield: 43.9 mg (92%);
yellow solid; mp 99–1018C; [a]2D0: À33.8 (c 0.5, CHCl3);
1H NMR (400 MHz, CDCl3): d=7.40–7.26 (m, 5H), 6.41 (s,
2H), 4.45 (d, J=6.8 Hz, 1H), 3.44–2.26 (m, 4H), 2.14 (s,
6H); 13C NMR (100 MHz, CDCl3): d=142.1, 132.1, 130.4,
129.1, 128.6, 127.8, 127.4, 126.9, 126.5, 116.7, 116.2, 55.1,
49.5, 18.9; IR (KBr): n=3318, 3242, 1915, 2849, 1618, 1518,
1453, 1385, 1340, 1307, 1224, 868, 764, 701 cmÀ1; ESI-FT-
MS: m/z=239.1538, exact mass calcd. for (C16H18N2 +H)+:
239.1548; enantiomeric excess: 98%, determined by HPLC
(Daicel Chirapak AD-H, hexane/2-propanol=70/30, flow
rate 1.0 mLminÀ1, T=308C, 254 nm): tR =10.207 min
(minor), tR =11.367 min (major).
(S)-2-(Thiophen-2-yl)-1,2,3,4-tetrahydroquinoxaline (4aj):
Flash column chromatography eluent, toluene/ethyl ace-
tate=90/1; reaction time=24 h; yield: 24.6 mg (57%);
yellow solid; mp 73–748C; [a]2D0: À33.5 (c 0.2, CHCl3);
1H NMR (400 MHz, CDCl3): d=7.29 (d, J=5.2 Hz, 1H),
7.08 (d, J=3.2 Hz, 1H), 7.02 (dd, J=4.8, 3.6 Hz, 1H), 6.68–
6.65 (m, 2H), 6.61–6.58 (m, 2H), 4.86 (dd, J=7.6, 3.2 Hz,
1H), 3.98 (s, 2H), 3.58 (dd, J=10.8, 2.8 Hz, 1H), 3.45 (dd,
J=10.8, 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=
145.6, 133.2, 132.8, 126.6, 124.9, 124.2, 119.3, 119.0, 114.8,
114.8, 50.6, 49.4; IR (KBr): n=3395, 3347, 3041, 2916, 2850,
(R)-6,7-Dichloro-2-(4-methoxyphenyl)-1,2,3,4-tetrahydro-
quinoxaline (4cc): Flash column chromatography eluent, tol-
uene/ethyl acetate=90/1; reaction time=24 h; yield:
54.7 mg (89%); yellow solid; mp 91–928C; [a]2D0: À51.7 (c
1
0.2, CHCl3); H NMR (400 MHz, CDCl3): d=7.30–7.27 (m,
2H), 6.93 (d, J=8.8 Hz, 2H), 6.61 (s, 2H), 4.40 (dd, J=8.0,
3.2 Hz, 1H), 3.95 (s, 2H), 3.84 (s, 3H), 3.43 (dd, J=11.2,
3.2 Hz, 1H), 3.27 (dd, J=11.2, 8.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d=140.9, 133.8, 132.7, 131.8, 128.7,
121.7, 119.1, 118.9, 114.8, 114.5, 54.2, 48.9, 29.7; IR (KBr):
n=3395, 2968, 2843, 1717, 1507, 1295, 1253, 1175, 857,
828 cmÀ1; ESI-FT-MS: m/z=309.0552, exact mass calcd. for
(C15H14Cl2N2O+H)+: 309.0561; enantiomeric excess: 99%,
determined by HPLC (Daicel Chirapak AD-H, hexane/2-
propanol=70/30, flow rate 1.0 mLminÀ1, T=308C, 254 nm):
tR =12.580 min (minor), tR =17.543 min (major).
1869, 1600, 1516, 1508, 1463, 1311, 1298, 1037, 737 cmÀ1
;
ESI-FT-MS: m/z=217.0790, exact mass calcd. for
(C12H12N2S+H)+: 217.0799; enantiomeric excess: 90%, de-
termined by HPLC (Daicel Chirapak OD-H, hexane/2-prop-
anol=80/20, flow rate 1.0 mLminÀ1, T=308C, 254 nm): tR =
15.720 min (major), tR =22.307 min (minor).
(R)-2-Phenyl-1,2,3,4-tetrahydrobenzo[g]quinoxaline
(4ba): Flash column chromatography eluent, toluene/ethyl
acetate=90/1; reaction time=24 h; yield: 50.4 mg (96%);
gray solid; mp 168–1698C; [a]2D0: 37.8 (c 0.6, CHCl3);
1H NMR (400 MHz, CDCl3): d=7.51–7.49 (m, 2H), 7.44–
7.34 (m, 5H), 7.18–7.15 (m, 2H), 6.85 (d, J=4.0 Hz, 2H),
4.59 (dd, J=8.0, 2.8 Hz, 1H), 4.25 (s, 2H), 3.52 (dd, J=10.8,
(R)-6,7-Dichloro-2-(p-tolyl)-1,2,3,4-tetrahydroquinoxaline
(4cd): Flash column chromatography eluent, toluene/ethyl
acetate=90/1; eeaction time=24 h; yield: 42.6 mg (73%);
yellow solid; mp 145–1468C; [a]2D0: À71.3 (c 0.7, CHCl3);
1H NMR (400 MHz, CDCl3): d=7.16–7.09 (m, 4H), 6.50 (s,
2H), 4.31 (dd, J=7.6, 2.4 Hz, 1H), 3.83 (s, 2H), 3.34 (dd,
J=11.2, 2.8 Hz, 1H), 3.17 (dd, J=10.8, 8.4 Hz, 1H), 2.28 (s,
3H); 13C NMR (100 MHz, CDCl3): d=138.0, 137.9, 133.8,
132.2, 129.5, 126.8, 120.8, 120.5, 115.1, 114.8, 53.9, 48.5, 21.2;
IR (KBr): g 3394, 2923, 2856, 1599, 1579, 1509, 1475, 1347,
1291, 1220 cmÀ1; ESI-FT-MS: m/z 293.0602, exact mass calcd
for (C15H14Cl2N2 +H)+: 293.0612; enantiomeric excess: 99%,
determined by HPLC (Daicel Chirapak AD-H, hexane/2-
propanol=70/30, flow rate 1.0 mLminÀ1, T=308C, 254 nm):
tR =9.093 min (minor), tR =11.290 min (major).
3.0 Hz, 1H), 3.42–3.37ACTHNUTRGNEUNG
(m, 1H); 13C NMR (100 MHz,
CDCl3): d=141.5, 135.5, 134.2, 129.0, 128.7, 128.1, 127.0,
125.2, 122.7, 108.1, 107.8, 54.8, 48.7; IR (KBr): n=3396,
3351, 3036, 2923, 2853, 1685, 1627, 1525, 1455, 1322, 1295,
1121 cmÀ1; ESI-FT-MS: m/z=261.1380, exact mass calcd. for
(C18H16N2 +H)+: 261.1392; enantiomeric excess: 97%, deter-
mined by HPLC (Daicel Chirapak OD-H, hexane/2-propa-
nol=80/20, flow rate 1.0 mLminÀ1, T=308C, 254 nm): tR =
28.313 min (major), tR =31.450 min (minor).
(R)-6,7-Dichloro-2-phenyl-1,2,3,4-tetrahydroquinoxaline
(4ca): Flash column chromatography eluent, toluene/ethyl
acetate=90/1; reaction time=24 h; yield: 48.4 mg (86%);
yellow solid; mp 116–1178C; [a]2D0: À75.7 (c 0.6, CHCl3);
(R)-6,7-Dichloro-2-(4-fluorophenyl)-1,2,3,4-tetrahydroqui-
noxaline (4ce): Flash column chromatography eluent, tolu-
ene/ethyl acetate=90/1; reaction time=24 h; yield: 53.6 mg
(90%); yellow solid; mp 90–918C; [a]2D0: À16.4 (c 0.8,
3722
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 3715 – 3726

Asymmetric Organocatalytic Tandem Cyclization/Transfer Hydrogenation
1
CHCl3); H NMR (400 MHz, CDCl3): d=7.33–7.29 (m, 2H),
7.06 (t, J=8.8 Hz, 2H), 6.58 (d, J=4.8 Hz, 2H), 4.41 (dd,
J=8.0, 3.2 Hz, 1H), 3.93 (s, 2H), 3.42 (dd, J=11.2, 3.2 Hz,
1H), 3.23 (dd, J=11.2, 8.0 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d=163.8, 161.3, 136.6, 136.6, 133.6, 132.0, 128.6,
128.5, 120.9, 120.7, 115.8, 115.6, 115.2, 114.9, 53.5, 48.4; IR
(KBr): n=3392, 2925, 2872, 1889, 1602, 1506, 1466, 1298,
1220, 1125, 1062, 849, 834, 673 cmÀ1; ESI-FT-MS: m/z
297.0351, exact mass calcd. for (C14H11Cl2FN2 +H)+:
297.0362; enantiomeric excess: >99%, determined by
HPLC (Daicel Chirapak AD-H, hexane/2-propanol=70/30,
flow rate 1.0 mLminÀ1, T=308C, 254 nm): tR =9.130 min
(minor), tR =11.257 min (major).
(R)-Ethyl
3-phenyl-1,2,3,4-tetrahydroquinoxaline-6-car-
boxylate (4ea): Flash column chromatography eluent, tolu-
ene/ethyl acetate=120/1; reaction time=24 h; yield: 24 mg
(42%); yellow solid; mp 146–1478C; [a]2D0: À66.7 (c 0.8,
1
CHCl3); H NMR (400 MHz, CDCl3): d=7.42–7.38 (m, 2H),
7.36 (d, J=6.6 Hz, 3H), 7.33 (dd, J=4.9, 3.6 Hz, 1H), 7.28
(d, J=1.8 Hz, 1H), 6.51 (d, J=8.2 Hz, 1H), 4.43 (dd, J=8.2,
3.2 Hz, 1H), 4.30 (q, J=7.1 Hz, 2H), 3.52 (dd, J=11.2,
3.2 Hz, 1H), 3.38 (dd, J=11.2, 8.2 Hz, 1H), 1.35 (t, J=
7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=166.9, 141.1,
137.3, 132.7, 128.7, 128.1, 126.9, 121.7, 119.8, 115.3, 112.7,
60.2, 53.9, 48.8, 14.4; IR (KBr): n=2922, 2851, 1725, 1675,
1603, 1488, 1455, 1367, 1224, 1139, 1104, 1024, 765 cmÀ1
;
ESI-FT-MS: m/z= 283.1452, exact mass calcd. for
(C17H18N2O2 +H)+: 283.1447; enantiomeric excess: 79%, de-
termined by HPLC (Daicel Chirapak AD-H, hexane/2-prop-
anol=70/30, flow rate 1.0 mLminÀ1, T=308C, 254 nm): tR =
14.437 min (major), tR =16.150 min (minor).
(R)-2-(4-Bromophenyl)-6,7-dichloro-1,2,3,4-tetrahydroqui-
noxaline (4cg): Flash column chromatography eluent, tolu-
ene/ethyl acetate=100/1; reaction time=24 h; yield:
64.4 mg (90%); yellow solid; mp 146–1478C; [a]2D0: À88.1 (c
0.4, CHCl3); 1H NMR (400 MHz, CDCl3): d=7.49 (d, J=
8.0 Hz, 2H), 7.22 (d, J=8.0 Hz, 2H), 6.60 (d, J=5.2 Hz,
2H), 4.41 (dd, J=7.6, 2.8 Hz, 1H), 3.95 (s, 1H), 3.90 (s,
1H), 3.42 (dd, J=11.2, 3.2 Hz, 1H), 3.22 (dd, J=11.2,
7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=140.1, 133.3,
132.3, 131.9, 128.6, 122.0, 120.8, 115.1, 114.9, 53.7, 48.2; IR
(KBr): n=3406, 3373, 2918, 2847, 1716, 1698, 1600, 1505,
1294, 1125, 1010 cmÀ1; ESI-FT-MS: m/z=356.9551, exact
mass calcd. for (C14H11BrCl2N2 +H)+: 356.9561; enantiomer-
ic excess: >99%, determined by HPLC (Daicel Chirapak
AD-H, hexane/2-propanol=70/30, flow rate 1.0 mLminÀ1,
T=308C, 254 nm): tR =9.213 min (minor), tR =12.330 min
(major).
(R)-Ethyl
2-phenyl-1,2,3,4-tetrahydroquinoxaline-6-car-
boxylate (4ea’): Flash column chromatography eluent, tolu-
ene/ethyl acetate=120/1; reaction time=24 h; yield: 7.3 mg
(13%); yellow solid; mp 136–1378C; [a]2D0: À7.1 (c 4.2,
CHCl3); 1H NMR (400 MHz, CDCl3): d=7.39 (dd, J=8.3,
1.8 Hz, 2H), 7.36 (q, J=2.6 Hz, 3H), 7.33 (d, J=6.7 Hz,
1H), 7.27 (d, J=1.8 Hz, 1H), 6.53 (d, J=8.2 Hz, 1H), 4.57
(dd, J=7.7, 3.2 Hz,1H), 4.31 (q, J=7.1 Hz, 2H), 3.49 (dd,
J=11.1, 3.3 Hz, 1H), 3.29 (dd, J=11.1, 7.8 Hz, 1H), 1.36 (t,
J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=166.6,
140.2, 139.3, 128.8, 128.4, 126.9, 123.8, 120.1, 117.7, 113.3,
60.3, 54.3, 48.0, 14.4; IR (KBr): n=3399, 2922, 2812, 1714,
1685, 1618, 1523, 1368, 1290, 1093, 1023, 767, 682, 620 cmÀ1
;
(R)-2-(4-Methoxyphenyl)-6,7-dimethyl-1,2,3,4-tetrahydro-
quinoxaline (4dc): Flash column chromatography eluent, tol-
uene/ethyl acetate=90/1; reaction time=24 h; yield: 42 mg
(78%); yellow oil; [a]2D0: À78.3 (c 0.7, CHCl3); 1H NMR
(400 MHz, CDCl3): d=7.31 (d, J=8.4 Hz, 2H), 6.91 (d, J=
8.4 Hz, 2H), 6.40 (d, J=5.2 Hz, 2H), 4.40 (d, J=6.0 Hz,
1H), 3.82 (s, 3H), 3.64 (s, 2H), 3.39 (dd, J=10.8, 2.4 Hz,
1H), 3.29–3.24 (m, 1H), 2.14 (s, 6H); 13C NMR (100 MHz,
CDCl3): d=159.2, 134.2, 132.2, 130.5, 128.1, 126.8, 126.4,
116.7, 116.1, 113.9, 55.3, 54.5, 49.7, 18.9; IR (KBr): n=3357,
2916, 2856, 1608, 1558, 1514, 1457, 1304, 1248, 1175, 1108,
1032, 863, 832 cmÀ1; ESI-FT-MS: m/z=269.1643, exact mass
calcd. for (C17H20N2O+H)+: 269.1654; enantiomeric excess:
98%, determined by HPLC (Daicel Chirapak AD-H,
hexane/2-propanol=70/30, flow rate 1.0 mLminÀ1, T=308C,
254 nm): tR =12.863 min (minor), tR =16.490 min (major).
(R)-2-Methyl-1,2,3,4-tetrahydroquinoxaline (4ak): Flash
column chromatography eluent, petroleum ether/ethyl ace-
tate=10/1; Reaction time=24 h; yield: 25.5 mg (86%);
yellow solid; mp 42–438C; [a]2D0: 49.4 (c 2.2, CHCl3);
1H NMR (400 MHz, CDCl3): d=6.64–6.55 (m, 2H), 6.50
(dd, J=9.1, 4.2 Hz, 2H), 3.46–3.55 (m, 1H), 3.32 (d, J=
10.4 Hz, 1H), 3.09–2.99 (m, 1H), 1.19 (d, J=6.3 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=133.6, 133.2, 118.7, 118.7,
114.5, 114.5, 48.2, 5.7, 19.9; IR (KBr): n=3358, 3312, 3041,
ESI-FT-MS: m/z=283.1455, exact mass calcd. for
(C17H18N2O2 +H)+: 283.1447; enantiomeric excess: 90%, de-
termined by HPLC (Daicel Chirapak AD-H, hexane/2-prop-
anol=70/30, flow rate 1.0 mLminÀ1, T=308C, 254 nm): tR =
18.607 min (major), tR =15.643 min (minor).
(R)-2-Phenyl-7-(trifluoromethyl)-1,2,3,4-tetrahydroqui-
noxaline (4fa): Flash column chromatography eluent, tolu-
ene/ethyl acetate=120/1; reaction time=24 h; yield: 21 mg
(39%); yellow solid; mp 112–1138C; [a]2D0: À109.4 (c 0.6,
1
CHCl3); H NMR (400 MHz, CDCl3): d=7.39 (t, J=4.1 Hz,
1H), 7.37 (s, 3H), 7.35–7.30 (m, 1H), 6.91–6.84 (m, 1H),
6.77 (d, J=1.7 Hz, 1H), 6.57 (d, J=8.1 Hz, 1H), 4.52 (dd,
J=7.9, 3.2 Hz, 1H), 4.19 (s, 1H), 3.49 (dd, J=11.1, 3.2 Hz,
1H), 3.31 (dd, J=11.0, 7.9 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d=140.9, 136.9, 131.7, 129.3, 128.7, 128.2, 127.7,
126.8, 120.4, 116.4, 113.3, 111.3, 54.4, 48.4; IR (KBr): n=
3424, 3405, 2921, 2852, 1614, 1598, 1494, 1462, 1356, 1087,
864, 802, 705 cmÀ1; ESI-FT-MS: m/z=279.1121, exact mass
calcd. for (C15H13F3N2 +H)+: 279.1109; enantiomeric excess:
90%, determined by HPLC (Daicel Chirapak AD-H,
hexane/2-propanol=70/30, flow rate 1.0 mLminÀ1, T=308C,
254 nm): tR =6.983 min (major), tR =6.197 min (minor).
(R)-2-Phenyl-6-(trifluoromethyl)-1,2,3,4-tetrahydroqui-
noxaline (4fa’): Flash column chromatography eluent, tolu-
ene/ethyl acetate=120/1; reaction time=24 h; yield: 17 mg
(31%); yellow oil; [a]2D0: 181.8 (c 0.3, CHCl3); 1H NMR
(400 MHz, CDCl3): d=7.42–7.32 (m, 5H), 6.88 (d, J=
8.1 Hz, 1H), 6.78 (d, J=1.5 Hz, 1H), 6.55 (d, J=8.1 Hz,
1H), 4.46 (dd, J=8.1, 3.1 Hz, 1H), 4.13 (s, 1H), 4.04 (s,
1H), 3.50 (dd, J=11.1, 3.0 Hz, 1H), 3.35 (dd, J=11.1,
8.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=140.7, 134.6,
2956, 2924, 2848, 1602, 1516, 1343, 743, 677, 587, 559 cmÀ1
;
ESI-FT-MS: m/z 149.1092, exact mass calcd. for (C9H12N2 +
H)+: 149.1079; enantiomeric excess: 70%, determined by
HPLC (Daicel Chirapak AD-H, hexane/2-propanol=70/30,
flow rate 1.0 mLminÀ1, T=308C, 254 nm): tR =5.797 min
(major), tR =6.253 min (minor).
Adv. Synth. Catal. 2013, 355, 3715 – 3726
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3723

Feng Shi et al.
UPDATES
133.6, 128.8, 128.2, 126.9, 126.1, 123.4, 121.0, 120.7, 116.1,
J=8.4 Hz, 1H), 6.21 (t, J=7.2 Hz, 2H), 4.40 (d, J=7.1 Hz,
1H), 3.73 (s, 3H), 3.44 (d, J=9.7 Hz, 1H), 3.38–3.28 (m,
1H); 13C NMR (100 MHz, CDCl3): d=153.5, 143.2, 141.5,
133.7, 130.5, 129.7, 129.1, 128.6, 127.9, 127.0, 123.5, 115.4,
106.5, 103.8, 101.2, 55.6, 54.8, 49.1; IR (KBr): n=3522, 3445,
3298, 2922, 2850, 1730, 1600, 1518, 1455, 1320, 1213, 1124,
1027 cmÀ1; ESI-FT-MS: m/z=241.1358, exact mass calcd. for
(C15H16N2O+H)+: 241.1341; enantiomeric excess: 89%, de-
termined by HPLC (Daicel Chirapak IA-H, hexane/2-prop-
anol=70/30, flow rate 1.0 mLminÀ1, T=308C, 254 nm): tR =
11.760 min (major), tR =10.713 min (minor).
116.0, 116.0, 113.8, 111.0, 110.9, 54.1, 48.4; IR (KBr): n=
3445, 3297, 2922, 2851, 1651, 1631, 1262, 1024, 803, 549 cmÀ1
;
ESI-FT-MS: m/z 279.1116, exact mass calcd. for
(C15H13F3N2 +H)+: 279.1109; enantiomeric excess: 87%, de-
termined by HPLC (Daicel Chirapak AD-H, hexane/2-prop-
anol=70/30, flow rate 1.0 mLminÀ1, T=308C, 254 nm): tR =
7.037 min (major), tR =8.533 min (minor).
(R)-7-Bromo-2-phenyl-1,2,3,4-tetrahydroquinoxaline
(4ga): Flash column chromatography eluent, toluene/ethyl
acetate=90/1; reaction time=24 h; yield: 21.4 mg (37%);
yellow solid; mp 86–878C; [a]2D0: À95.4 (c 0.4, CHCl3);
1H NMR (400 MHz, CDCl3): d=7.40–7.32 (m, 5H), 6.72–
6.68 (m, 2H), 6.43 (d, J=8.0 Hz, 1H), 4.46 (d, J=7.6 Hz,
1H), 3.91 (s, 2H), 3.45 (d, J=11.2 Hz, 1H), 3.30–3.25 (m,
1H); 13C NMR (100 MHz, CDCl3): d=141.2, 135.6, 131.4,
128.8, 128.1, 126.9, 121.0, 116.6, 115.9, 110.7, 54.4, 48.7; IR
(KBr): n=3346, 3032, 2918, 2852, 1594, 1506, 1456, 1300,
1234, 1074, 794, 754, 698 cmÀ1; ESI-FT-MS: m/z=289.0330,
exact mass calcd. for (C14H13BrN2 +H)+: 289.0340; enantio-
meric excess: 97%, determined by HPLC (Daicel Chirapak
OD-H, hexane/2-propanol=80/20, flow rate 1.0 mLminÀ1,
T=308C, 254 nm): tR =14.403 min (major), tR =17.820 min
(minor).
(R)-3-Phenyl-3,4-dihydroquinoxalin-2(1H)-one
(7aa):
Flash column chromatography eluent, petroleum ether/ethyl
acetate=5/1; reaction time=24 h; yield: 35.3 mg (79%);
white solid; mp 145–1468C; [a]2D0: +181.0 (c 0.2, MeOH);
1H NMR (400 MHz, CDCl3): d=8.86 (s, 1H), 7.42 (d, J=
7.0 Hz, 2H), 7.34–7.31 (m, 3H), 6.92 (t, J=7.2 Hz, 1H),
6.78–6.67 (m, 3H), 5.07 (s, 1H), 4.30 (s, 1H); 13C NMR
(100 MHz, CDCl3): d=167.3, 139.0, 132.9, 128.8, 128.4,
127.2, 124.7, 124.1, 119.3, 115.6, 113.7, 60.6; IR (KBr): n=
3327, 3304, 3032, 1671, 1601, 1533, 1504, 1455, 766 cmÀ1
;
ESI-FT-MS: m/z=223.0873, exact mass calcd. for
(C14H14N2OÀH)À: 223.0872; enantiomeric excess: 94%, de-
termined by HPLC (Daicel Chirapak OD-H, hexane/2-prop-
anol=80/20, flow rate 1.0 mLminÀ1, T=308C, 254 nm): tR =
23.467 min (major), tR =14.143 min (minor).
(R)-6-Bromo-2-phenyl-1,2,3,4-tetrahydroquinoxaline
(4ga’): Flash column chromatography eluent, toluene/ethyl
acetate=90/1; reaction time=24 h; yield: 27.7 mg (48%);
yellow solid; mp 103–1048C; [a]2D0: À59.4 (c 0.3, CHCl3);
1H NMR (400 MHz, CDCl3): d=7.37–7.33 (m, 5H), 6.72–
6.60 (m, 2H), 6.43 (d, J=8.2 Hz, 1H), 4.43 (d, J=8.0 Hz,
1H), 3.88 (s, 2H), 3.45 (d, J=10.8 Hz, 1H), 3.32–3.27 (m,
1H); 13C NMR (100 MHz, CDCl3): d=141.2, 133.9, 133.0,
128.7, 128.1, 126.9, 121.2, 116.8, 115.5, 110.3, 54.4, 48.6; IR
(KBr): n=3407, 3360, 3059, 3030, 2919, 2856, 1596, 508,
1455, 1301, 1249, 1074, 791, 757 cmÀ1; ESI-FT-MS: m/z=
289.0330, exact mass calcd. for (C14H13BrN2 +H)+: 289.0340;
enantiomeric excess: 94%, determined by HPLC (Daicel
Chirapak OD-H, hexane/2-propanol=80/20, flow rate
1.0 mLminÀ1, T=308C, 254 nm): tR =13.920 min (major),
tR =17.100 min (minor).
(R)-7-Methoxy-2-phenyl-1,2,3,4-tetrahydroquinoxaline
(4ha): Flash column chromatography eluent, toluene/ethyl
acetate=120/1; reaction time=24 h; yield: 12.6 mg (26%);
yellow solid; mp 76–778C; [a]2D0: 54.1 (c 1.1, CHCl3);
1H NMR (400 MHz, CDCl3): d=7.42–7.34 (m, 4H), 7.34–
7.27 (m, 1H), 6.54 (d, J=8.3 Hz, 1H), 6.22 (dd, J=13.1,
2.4 Hz, 2H), 4.48 (dd, J=7.7, 2.5 Hz, 1H), 3.73 (s, 3H), 3.42
(dd, J=11.1, 2.4 Hz, 1H), 3.31–3.22 (m, 1H); 13C NMR
(100 MHz, CDCl3): d=154.1, 141.6, 140.7, 135.8, 130.0,
129.1, 128.6, 127.9, 127.5, 126.9, 125.3, 116.7, 106.9, 103.5,
100.8, 55.6, 54.9, 49.3; IR (KBr): n=2923, 2852, 1619, 1509,
1494, 1455, 1413, 1375, 1216, 1173, 1118, 1025, 959, 830,
689 cmÀ1; ESI-FT-MS: m/z=241.1349, exact mass calcd. for
(C15H16N2O+H)+: 241.1341; enantiomeric excess: 86%, de-
termined by HPLC (Daicel Chirapak AD-H, hexane/2-prop-
anol=70/30, flow rate 1.0 mLminÀ1, T=308C, 254 nm): tR =
13.993 min (major), tR =16.847 min (minor).
(R)-3-Phenyl-3,4-dihydrobenzo[g]quinoxalin-2(1H)-one
(7ba): Flash column chromatography eluent, petroleum
ether/ethyl acetate=5/1; reaction time=24 h; yield: 42.7 mg
(78%); white solid; mp 68–698C; [a]2D0: À105.8 (c 0.1,
1
MeOH); H NMR (400 MHz, acetone-d6): d=9.61 (s, 1H),
7.61 (dd, J=18.2, 8.1 Hz, 2H), 7.47 (d, J=7.2 Hz, 2H),
7.34–7.23 (m, 5H), 7.22–7.16 (m, 2H), 6.17 (s, 1H), 5.14 (s,
1H); 13C NMR (100 MHz, CDCl3): d=167.3, 138.9, 132.9,
131.4, 129.6, 128.9, 128.6, 128.3, 127.0, 126.7, 126.2, 125.6,
125.3, 123.6, 111.6, 108.3, 60.7; IR (KBr): n=3314, 3184,
3052, 2922, 1672, 1638, 1492, 1454, 757 cmÀ1; ESI-FT-MS: m/
z
273.1031, exact mass calcd. for (C18H14N2OÀH)À:
273.1028; enantiomeric excess: 97%, determined by HPLC
(Daicel Chirapak OD-H, hexane/2-propanol=80/20, flow
rate 1.0 mLminÀ1, T=308C, 254 nm): tR =32.813 min
(major), tR =27.367 min (minor).
(R)-6,7-Dichloro-3-phenyl-3,4-dihydroquinoxalin-2(1H)-
one (7ca): Flash column chromatography eluent, petroleum
ether/ethyl acetate=5/1; reaction time=24 h; yield: 36 mg
(64%); white solid; mp 262–2638C; [a]2D0: 190.5 (c 0.1,
1
MeOH); H NMR (400 MHz, acetone-d6): d=9.71 (s, 1H),
7.44 (dd, J=8.2, 1.3 Hz, 2H), 7.40–7.35 (m, 2H), 7.34–7.29
(m, 1H), 7.07 (d, J=4.0 Hz, 2H), 6.37 (s, 1H), 5.13 (d, J=
1.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=166.6, 138.3,
132.3, 129.0, 128.8, 128.3, 126.9, 121.8, 116.6, 114.7, 60.2; IR
(KBr): n=3340, 3064, 2922, 2851, 1660, 1558, 1506, 1450,
1457, 755 cmÀ1; ESI-FT-MS: m/z 291.0078, exact mass calcd.
for (C14H10Cl2N2OÀH)À: 291.0092; enantiomeric excess:
95%, determined by HPLC (Daicel Chirapak IA, hexane/2-
propanol=80/20, flow rate 1.0 mLminÀ1, T=308C, 254 nm):
tR =9.557 min (major), tR =11.013 min (minor).
(R)-6-Methoxy-2-phenyl-1,2,3,4-tetrahydroquinoxaline
(4ha’): Flash column chromatography eluent, toluene/ethyl
acetate=120/1; reaction time=24 h; yield: 12.5 mg (26%);
yellow solid; mp 90–918C; [a]2D0: À80.5 (c 0.9, CHCl3);
1H NMR (400 MHz, CDCl3): d=7.43–7.28 (m, 5H), 6.51 (d,
(R)-3-(4-Chlorophenyl)-3,4-dihydroquinoxalin-2(1H)-one
(7ab): Flash column chromatography eluent, petroleum
ether/ethyl acetate=5/1; reaction time=24 h; yield: 27.5 mg
(53%); white solid; mp 203–2048C; [a]2D0: À54.3 (c 0.2,
1
MeOH); H NMR (400 MHz, acetone-d6): d=9.49 (s, 1H),
3724
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 3715 – 3726

Asymmetric Organocatalytic Tandem Cyclization/Transfer Hydrogenation
7.44 (d, J=8.5 Hz, 2H), 7.38–7.29 (m, 2H), 6.92–6.79 (m,
3H), 6.76–6.64 (m, 1H), 5.96 (s, 1H), 5.04 (d, J=1.8 Hz,
1H); 13C NMR (100 MHz, CDCl3): d=166.9, 137.3, 134.4,
132.6, 130.9, 128.9, 128.6, 124.6, 124.2, 119.6, 115.7, 113.8,
60.0; IR (KBr): n=3416, 3055, 2923, 1614, 1518, 1504, 1470,
1421, 738 cmÀ1; ESI-FT-MS: m/z 257.0483, exact mass calcd.
for (C14H11ClN2OÀH)À: 257.0482; enantiomeric excess:
97%, determined by HPLC (Daicel Chirapak AD-H,
hexane/2-propanol=70/30, flow rate 1.0 mLminÀ1, T=308C,
254 nm): tR =9.170 min (major), tR =9.937 min (minor).
(R)-4-(3-Oxo-1,2,3,4-tetrahydrobenzo[g]quinoxalin-2-yl)-
benzonitrile (7ac): Flash column chromatography eluent, pe-
troleum ether/ethyl acetate=2/1; reaction time=24 h; yield:
50.4 mg (84%); white solid; mp 236–2378C; [a]2D0: À241.3 (c
0.5, MeOH); 1H NMR (400 MHz, acetone-d6): d=9.91 (s,
1H), 7.79–7.68 (m, 4H), 7.63 (dd, J=15.5, 8.1 Hz, 2H),
7.37–7.25 (m, 3H), 7.24–7.18 (m, 1H), 6.45 (s, 1H), 5.30 (d,
J=2.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=166.2,
143.8, 132.6, 132.1, 131.4, 128.4, 127.9, 126.8, 125.7, 125.5,
123.9, 118.3, 112.5, 112.1, 108.7, 60.3; IR (KBr): n=3369,
3043, 2924, 1677, 1637, 1533, 1487, 1459, 734 cmÀ1; ESI-FT-
MS: m/z 298.0981, exact mass calcd. for (C19H13N3OÀH)À:
298.0981; enantiomeric excess: 98%, determined by HPLC
(Daicel Chirapak OD-H, hexane/2-propanol=75/25, flow
rate 1.0 mLminÀ1, T=308C, 254 nm): tR =34.437 min
(major), tR =28.710 min (minor).
1H), 7.62 (dd, J=18.0, 8.1 Hz, 2H), 7.51–7.46 (m, 2H),
7.39–7.31 (m, 3H), 7.28 (ddd, J=8.2, 6.9, 1.3 Hz, 1H), 7.25–
7.17 (m, 2H), 6.36 (s, 1H), 5.19–5.14 (m, 1H); 13C NMR
(100 MHz, CDCl3): d=167.0, 137.2, 134.6, 132.6, 131.4,
129.0, 128.4, 128.4, 126.8, 126.0, 125.7, 125.4, 123.7, 111.8,
108.5, 60.1; IR (KBr): n=3355, 3300, 3047, 2924,1683, 1597,
1530, 1489, 1393, 743 cmÀ1; ESI-FT-MS: m/z=307.0635,
exact mass calcd. for (C18H13ClN2OÀH)À: m/z=307.0638;
enantiomeric excess: 99%, determined by HPLC (Daicel
Chirapak AD-H, hexane/2-propanol=75/25, flow rate
1.0 mLminÀ1, T=308C, 254 nm): tR =16.067 min (major),
tR =13.707 min (minor).
(R)-6,7-Dichloro-3-(4-chlorophenyl)-3,4-dihydroquinoxa-
lin-2(1H)-one (7cb): Flash column chromatography eluent,
petroleum ether/ethyl acetate=7/1; reaction time=24 h;
yield: 30.8 mg (47%); white solid; mp 240–2418C; [a]2D0:
1
+88.6 (c 0.2, MeOH); H NMR (400 MHz, acetone-d6): d=
9.69 (s, 1H), 7.46–7.41 (m, 2H), 7.40–7.35 (m, 2H), 7.04 (d,
J=4.6 Hz, 2H), 6.35 (s, 1H), 5.12 (d, J=2.0 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=166.1, 136.6, 134.8, 132.0,
129.1, 128.3, 127.0, 124.1, 122.1, 116.7, 114.8, 59.5; IR (KBr):
n=3303, 3130, 2923, 1734, 1666, 1594, 1494, 1464, 1403 cmÀ1
;
ESI-FT-MS: m/z 324.9692, exact mass calcd. for
(C14H19Cl3N2OÀH)À: 324.9702; enantiomeric excess: 97%,
determined by HPLC (Daicel Chirapak OD-H, hexane/2-
propanol=80/20, flow rate 1.0 mLminÀ1, T=308C, 254 nm):
tR =12.580 min (major), tR =15.173 min (minor).
(R)-3-[4-(tert-Butyl)phenyl]-3,4-dihydrobenzo[g]quinoxa-
lin-2(1H)-one (7ad): Flash column chromatography eluent,
petroleum ether/ethyl acetate=12/1; reaction time=24 h;
yield: 53.1 mg (81%); white solid; mp 238–2398C; [a]2D0:
1
À45.0 (c 0.4, MeOH); H NMR (400 MHz, CDCl3): d=9.34
Acknowledgements
(s, 1H), 7.59 (dd, J=20.5, 8.1 Hz, 2H), 7.39–7.27 (m, 5H),
7.27–7.20 (m, 1H), 7.15 (s, 1H), 7.03 (s, 1H), 5.14 (s, 1H),
1.24 (s, 9H); 13C NMR (100 MHz, CDCl3): d=167.9, 151.6,
135.9, 132.6, 131.5, 128.5, 126.9, 126.7, 126.4, 125.9, 125.7,
125.2, 123.6, 111.9, 108.6, 60.4, 34.6, 31.2; IR (KBr): n=
We are grateful for financial support from National Natural
Science Foundation of China (21372002 and 21232007),
PAPD of Jiangsu Higher Education Institutions, and the
project on Cultivating Innovative Graduate Students of Jiang-
su Province (CXLX13 973).
3376, 3049, 2959, 1679, 1638, 1530, 1488, 1393, 745 cmÀ1
;
ESI-FT-MS exact mass calcd. for (C22H22N2OÀH)À:
329.1654; enantiomeric excess: 95%, determined by HPLC
(Daicel Chirapak OD-H, hexane/2-propanol=70/30, flow
rate 1.0 mLminÀ1, T=308C, 254 nm): tR =16.703 min
(major), tR =12.500 min (minor).
References
(R)-3-(4-Methoxyphenyl)-3,4-dihydrobenzo[g]quinoxalin-
2(1H)-one (7ae): Flash column chromatography eluent, pe-
troleum ether/ethyl acetate=7/1; reaction time=24 h; yield:
28.9 mg (48%); white solid; mp 202–2038C; [a]2D0: À24.6 (c
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1
0.2, MeOH); H NMR (400 MHz, CDCl3): d=8.87 (s, 1H),
7.60 (dd, J=19.4, 8.1 Hz, 2H), 7.34–7.31 (m, 3H), 7.25 (dd,
J=8.8, 6.0 Hz, 1H), 7.13 (s, 1H), 7.02 (s, 1H), 6.83 (d, J=
8.5 Hz, 2H), 5.10 (s, 1H), 3.74 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=167.9, 159.8, 132.9, 131.5, 131.1, 128.4, 128.3,
126.8, 126.4, 125.7, 125.2, 123.6, 114.3, 111.7, 108.4, 60.2,
55.3; IR (KBr): n=3312, 3194, 3052, 2925, 2853, 1679, 1612,
1587, 1460, 1392, 745 cmÀ1; enantiomeric excess: 94%, deter-
mined by HPLC (Daicel Chirapak AD-H, hexane/2-propa-
nol=70/30, flow rate 1.0 mLminÀ1, T=308C, 254 nm): tR =
21.927 min (major), tR =17.413 min (minor).
(R)-3-(4-Chlorophenyl)-3,4-dihydrobenzo[g]quinoxalin-
2(1H)-one (7bb): Flash column chromatography eluent, pe-
troleum ether/ethyl acetate=5/1; reaction time=24 h; yield:
41.9 mg (68%); white solid; mp 93–948C; [a]2D0: À201.6 (c
0.3, MeOH); 1H NMR (400 MHz, acetone-d6): d=9.83 (s,
Adv. Synth. Catal. 2013, 355, 3715 – 3726
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asc.wiley-vch.de
3725

Feng Shi et al.
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Adv. Synth. Catal. 2013, 355, 3715 – 3726