Asymmetric Bronsted acid-catalyzed intramolecular aza-michael reaction - Enantioselective synthesis of dihydroquinolinones

Article abstract of DOI:10.5560/ZNB.2012-0183

The enantioselective synthesis of 2-aryl-substituted 2,3-dihydroquinolin-4- ones, a class of heterocyclic compounds with interesting biological activities, has been achieved through a Bronsted acidcatalyzed enantioselective intramolecular Michael addition. The products are available in moderate to high yields and with good enantioselectivities.

Full text of DOI:10.5560/ZNB.2012-0183

Asymmetric Brønsted Acid-catalyzed Intramolecular aza-Michael
Reaction – Enantioselective Synthesis of Dihydroquinolinones
Magnus Ruepinga, Stefan A. Moretha and Michael Bolteb
a
RWTH Aachen University, Institute of Organic Chemistry, Landoltweg 1, D-52074 Aachen,
Germany
b
Goethe University Frankfurt, Institut of Inorganic and Analytical Chemistry, Max-von-Laue-
Str. 7, D-60438 Frankfurt am Main, Germany
Reprint requests to Prof. Dr. Magnus Rueping. Fax: +49 241 8092665.
E-mail: magnus.rueping@rwth-aachen.de
Z. Naturforsch. 2012, 67b, 1021 – 1029 / DOI: 10.5560/ZNB.2012-0183
Received July 5, 2012
Dedicated to Professor Heribert Offermanns on the occasion of his 75th birthday
The enantioselective synthesis of 2-aryl-substituted 2,3-dihydroquinolin-4-ones, a class of hetero-
cyclic compounds with interesting biological activities, has been achieved through a Brønsted acid-
catalyzed enantioselective intramolecular Michael addition. The products are available in moderate
to high yields and with good enantioselectivities.
Key words: aza-Michael Addition, Brønsted Acid, N-Triflyl Phosphoramide,
Dihydroquinolin-4-ones
Introduction
group and that of Gong reported independently the
asymmetric synthesis of isoquinuclidines through
The asymmetric catalytic aza-Michael reaction of- a Brønsted acid-catalyzed Mannich/aza-Michael addi-
fers a convenient route to a wide variety of enantio- tion [18, 19].
enriched amine derivatives and N-heterocyclic com-
Herein, we describe the application of Brønsted acid
pounds [1 – 6]. In recent years efforts have been catalysis to the enantioselective synthesis of 2-aryl-
devoted in particular to the development of effi- substituted 2,3-dihydroquinolin-4-ones which repre-
cient organocatalytic approaches for both inter- and sent a class of heterocyclic compounds with interest-
intramolecular versions of the aza-Michael reac- ing biological activities [20, 21]. A similar approach
tion [3 – 6]. On the one hand progress was made was recently described by You [15]. Lu used a bifunc-
with chiral primary and secondary amine catalysts. tional thiourea catalyst for the asymmetric synthesis
On the other hand, Brønsted acid-catalyzed aza- of this class of compounds [22]. In addition, racemic
Michael reactions attracted further interest. Notably, resolution [23] and metal-catalyzed processes [24, 25]
different classes of N-heterocyclic compounds have have been applied to obtain chiral 2-aryl-substituted
been obtained in an enantioselective fashion by ei- 2,3-dihydroquinolin-4-ones.
ther amine- or Brønsted acid-catalyzed intramolecu-
lar aza-Michael reactions or domino sequences com- Results and Discussion
prising an aza-Michael addition step [3 – 6]. For ex-
ample You reported the application of Brønsted acid
We started our investigation with a study of the
catalysis [7 – 14] in the synthesis of dihydroquinoli- intramolecular reaction of the N-methyl derivative
nones [15], pyrrolidines and morpholines [16]. En- 1a. Various chiral BINOL-based N-triflyl phosphor-
ders described the synthesis of tetrahydroisoquino- amides 3a–i [26 – 44] were evaluated in the in-
lines through a Brønsted acid-catalyzed reductive tramolecular aza-Michael addition with 1a as model
amination/aza-Michael domino reaction [17]. Our substrate, and the results are summarized in Ta-
c
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M. Rueping et al. · Enantioselective Synthesis of Dihydroquinolinones
Table 1. Catalyst screening for the asymmetric intramolecular aza-Michael reaction.
O
O
Entrya
Catalyst 3
Yield (%)b
Erc
Ph
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3f
3g
3h
3i
30
82
57
–
15
3
8
32
43
50 : 50
55.5 : 44.5 (R)
50 : 50
10 mol-% 3
Me
N
Me
2a
Ph
N
H
toluene, r. t.
–
1a
56.5 : 43.5 (R)
n. d.
57 : 43 (R)
74 : 26 (S)
56.5 : 43.5 (S)
Binaphthyl
3a: Ar = Phenyl
3b: Ar = 4-NO2-C6H4
3c: Ar = 3,5-(CF3)2C6H3
3d: Ar = 2-Naphthyl
Ar
O
O
O
P
3e: Ar = 4-Biphenylyl
3f: Ar = Anthracen-9-yl
3g: Ar = 9-Phenanthryl
NHTf
a
Reaction was performed with 0.05 mmol of the chalcone and
10 mol-% of catalyst in 0.25 mL of toluene at r. t. with stirring for
40 h; b yield after column chromatography; c Er = enantiomeric ra-
tio; determined by chiral HPLC.
Ar
Octahydrobinaphthyl
3h: Ar = SiPh3
3i: Ar = SiMePh2
3
Table 2. Solvent and temperature evaluation in the asymmetric intramolecular aza-Michael reaction.
O
O
Ph
10 mol-% 3h
Me
N
Me
Ph
N
H
solvent, temp.
1a
2a
Entrya
Solvent
Temperature ( ◦C)
Yield (%)b
3
Erc
1
2
3
4
5
6
7
8
CH2Cl2
CHCl3
MeOH
MeCN
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
50
n. d.d
8
76.5 : 23.5
50 : 50
65.5 : 34.5
75.5 : 24.5
76 : 24
n. d.
33
52
29
23
4
ethyl acetate
THF
Ph2O
n-Bu2O
Et2O
9
4
n. d.
n. d.
9
10
11
12
13
14
15e
ethyl diglycol
59
51
79
10
4
71 : 29
76.5 : 23.5
72.5 : 27.5
78 : 22
80.5 : 19.5
–
dimethyl glycol
dimethyl glycol
dimethyl glycol
dimethyl glycol
dimethyl glycol
10
0
−25
–
a
Reaction was performed with 0.05 mmol of the chalcone and 10 mol-% of catalyst 3h in
b
0.25 mL solvent at the indicated temperature with stirring for 40 h; yield after column
chromatography; c Er = enantiomeric ratio; determined by chiral HPLC; d n. d. = not deter-
mined; e stirred for 4 days.
ble 1. Among the BINOL- and octahydro-BINOL-
In order to improve the enantioselectivity, vari-
triflylphosphoramides tested, a promising level of ous solvents and temperatures were tested. Chlori-
enantioselectivity was observed with the octahydro- nated solvents and acyclic ethers were less suitable,
BINOL-triflylphosphoramide 3h bearing triphenylsilyl affording only traces of the desired product 2a (Ta-
residues at the 3,3’-positions (Table 1, entry 8). The ble 2, entries 1 – 2 and 7 – 9). Ethyl acetate and THF
absolute configuration of the product 2a obtained with proved to be better in terms of selectivity, and the
the silyl derivatives 3h und 3i is opposite to the one product 2a was obtained with 75.5 : 24.5 and 76 :
of the product obtained with catalysts 3b, 3e and 3g 24 enantiomeric ratios, respectively (Table 2, entries
(Table 1, entries 8 and 9 vs. entries 2, 5 and 7) [45].
5 – 6).
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M. Rueping et al. · Enantioselective Synthesis of Dihydroquinolinones
1023
Table 3. Evaluation of different N-protecting groups in the the subsequent optimization and evaluation of the sub-
asymmetric intramolecular aza-Michael reaction.
strate scope was performed at room temperature in
dimethyl glycol as solvent.
Substrates with different N-protecting groups were
also tested. While N-Me and N-allyl groups provided
comparable results in terms of yield and selectiv-
ity (Table 3, entries 1 and 5), the use of N-Bn re-
sulted in the corresponding product with a slightly in-
creased yield but decreased selectivity (Table 3, entry
2). The use of N-acyl and N-tosyl amine derivatives
did not afford the desired products (Table 3, entries 6
and 7).
With the optimized conditions in hand, the scope
of the reaction was investigated (Table 4). Chalcones
7 bearing aryl groups with electron donating groups
(Me, MeO, PhO) afforded the corresponding products
with good to excellent yields and selectivities. The se-
lectivity was not visibly affected by the electronic na-
ture of the substituents. However, the use of chalcones
Entrya Substrat
R
Me
Bn
Product
2a
Yield (%)b Erc
1
2
3
4
5
6
7
1a
4a
5a
6a
7a
8a
9a
51
72
66
32
46
–
76 : 24
10a
11a
12a
13a
14a
15a
73.5 : 26.5
57.5 : 42.5
75 : 25
75.5 : 24.5
–
Ph
i-Pr
Allyl
Ac
Ts
–
–
a
Reaction was performed with 0.05 mmol of the chalcone and
10 mol-% of catalyst 3h in 0.25 mL of dimethyl glycol at r. t.
b
with stirring for 40 h;
yield after column chromatography;
c
Er = enantiomeric ratio; determined by chiral HPLC.
The best result with regard to both, yield and selec- with sterically more demanding substituents resulted
tivity, was obtained in dimethyl glycol at room tem- in lower yield.
perature (Table 2, entry 11). Higher temperature re-
The absolute configuration of product 10d was de-
sulted in reduced selectivity and lower temperature termined as (S) by X-ray crystal structure analysis
had a detrimental influence on the yield. Therefore, (Fig. 1).
Table 4. Substrate scope of the Brønsted acid-catalyzed aza-Michael addition reaction.
Entrya
4, 7
Ar
R
10, 13
Yield (%)b
Erc
1
2
3
4
5
6
7
8
7a
7b
7c
7d
7e
7f
7g
7h
7i
Ph
Allyl
Allyl
Allyl
Allyl
Allyl
Allyl
Allyl
Allyl
Allyl
Allyl
Allyl
Bn
13a
13b
13c
13d
13e
13f
13g
13h
13i
13j
13k
10a
10b
10c
10d
10e
10f
46
45
63
53
36
98
92
58
74
86
68
72
71
29
58
57
41
75.5 : 24.5
76 : 24
76.5 : 23.5
76 : 24
74.5 : 25.5
75 : 25
75.5 : 24.5
81.5 : 18.5
74.5 : 25.5
77 : 23
74.5 : 25.5
73.5 : 26.5
76.5 : 23.5
81.5 : 18.5
76 : 24
2-Me-C6H4
2-MeO-C6H4
3-Me-C6H4
3-PhO-C6H4
4-MeO-C6H4
4-F-C6H4
3,4,5-(MeO)3-C6H2
1-naphthyl
2-naphthyl
furan
9
10
11
12
13
14
15
16
17
7j
7k
4a
4b
4c
4d
4e
4f
Ph
2-MeO-C6H4
2-Br-C6H4
3-Br-C6H4
4-Br-C6H4
1-naphthyl
Bn
Bn
Bn
Bn
74.5 : 25.5
78 : 22
Bn
a
Reaction was performed with 0.05 mmol of the chalcone and 10 mol-% of catalyst 3h in 0.25 mL of
b
c
dimethyl glycol at r. t.; yield after column chromatography; Er = enantiomeric ratio; determined by
chiral HPLC.
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1024
M. Rueping et al. · Enantioselective Synthesis of Dihydroquinolinones
O
N
Br
10d
Fig. 1. Molecular structure of 10d
(left) in the crystal (hydrogen
atoms have been omitted for clar-
ity).
Conclusion
(cm−1). Optical rotations were measured on a Perkin Elmer
241 polarimeter. The enantiomeric excesses were determined
In conclusion we have developed a catalytic route
to various N-allyl- and N-benzyl-protected 2-aryl-
substituted dihydroquinolin-4-one derivatives. The
products have become available in moderate to high
yields and with good enantiomeric ratios. The results
reported not only demonstrate that chiral Brønsted
acids can be efficient catalysts for enantioselective in-
tramolecular Michael additions, but also show the high
potential of highly acidic N-triflyl phosphoramides in
asymmetric catalysis.
by HPLC analysis using a chiral stationary phase column
(column: Chiralcel OD-H or Chiralcel OJ-H or Chiralpak
AD-H; eluent: hexane-2-propanol). Solvent mixtures are un-
derstood as volume/volume. The HPLC spectra of enantio-
enriched compounds were calibrated with the corresponding
racemic mixtures. Chemical yields refer to pure isolated sub-
stances. The yields and enantiomeric excesses are given in
the corresponding tables.
General procedure for the enantioselective intramolecular
1,4-addition
Experimental Section
General
0.05 mmol of the chalcone and 10 mol-% of octahydro-
BINOL N-triflyl phosphoramide 3h were dissolved in
0.25 mL of DME, and the reaction mixture was stirred at r. t.
The product was directly charged on silica gel and purified
by column chromatography using hexane-ethyl acetate mix-
tures as eluents to afford the desired product.
Unless otherwise noted, all commercially available com-
pounds were used as provided without further purification.
Solvents for chromatography were technical grade and dis-
tilled prior to use. Analytical thin-layer chromatography
(TLC) was performed on Merck silica gel aluminum plates
with F-254 indicator and visualized by irradiation with UV
light. Column chromatography was performed using silica
gel Merck 60 (particle size 0.040 – 0.063 mm). 1H NMR and
1-Methyl-2-phenyl-2,3-dihydroquinolin-4(1H)-one (2a)
Synthesized according to the general procedure: 6.1 mg,
13C NMR spectra were recorded on a Bruker AM 250 or 51%, yellow oil. – 1H NMR (250 MHz, CDCl3): δ = 7.78
a Bruker AV 300 spectrometer in CDCl3. Data are reported (dd, J = 7.8, 1.6 Hz, 1H), 7.41 – 7.34 (m, 1H), 7.25 – 7.16
in the following order: chemical shift (δ) in ppm; multiplici- (m, 3H), 7.10 – 7.06 (m, 2H), 6.71 – 6.64 (m, 2H), 4.59 (t,
ties are indicated s (singlet), d (doublet), dd (doublet of dou- J = 6.2 Hz, 1H), 3.08 (dd, J = 16.1, 6.2 Hz, 1H), 2.88 – 2.79
blets), t (triplet), m (multiplet); coupling constants (J) are in (m, 4H). −13C NMR (63 MHz, CDCl3): δ = 192.4, 151.7,
Hertz (Hz). Mass spectra (MS-EI, 70 eV) were conducted on 139.9, 136.0, 128.9, 127.8, 127.6, 126.5, 119.7, 116.6, 112.9,
R
a GC-MS Shimadzu QP2010 instrument (column: Equityꢀ 64.7, 45.4, 37.8. − IR (KBr): v˜= 3061, 3027, 2921, 1759,
-5, length × I. D. 30 m × 0.25 mm, df 0.25 µm, lot # 28089- 1600, 1492, 1433, 807, 758, 718, 700. − MS-EI: m/z
U, Supelco). IR spectra were recorded on a Jasco FT/IR- (%) = 237.0 (100) [M]+, 222.9 (4), 160.0 (83), 146.0 (5),
420 spectrometer and are reported as frequency of absorption 77.0. − [α]2D5 = +141.8◦ (c = 1.0 in chloroform). − HPLC
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M. Rueping et al. · Enantioselective Synthesis of Dihydroquinolinones
1025
conditions: AD-H column, n-hexane-2-propanol = 98 : 2, [α]2D5 = +94.0◦ (c = 0.1 in chloroform). − HPLC condi-
flow rate = 0.6 mL min−1, major enantiomer: tR = 33.9 min; tions: OD-H column, n-hexane-2-propanol = 90 : 10, flow
minor enantiomer: tR = 31.6 min.
rate = 0.6 mL min−1, major enantiomer: tR = 13.9 min; mi-
nor enantiomer: tR = 20.7 min.
1-Benzyl-2-phenyl-2,3-dihydroquinolin-4(1H)-one (10a)
1-Allyl-2-phenyl-2,3-dihydroquinolin-4(1H)-one (13a)
Synthesized according to the general procedure: 11.3 mg,
72%, yellow oil. – 1H NMR (250 MHz, CDCl3): δ = 7.80
Synthesized according to the general procedure: 6.3 mg,
(dd, J = 7.7, 1.8 Hz, 1H), 7.31 – 7.04 (m, 11H), 6.69 – 6.62 46%, yellow oil. – 1H NMR (250 MHz, CDCl3): δ = 7.79
(m, 2H), 4.77 (dd, J = 6.6, 4.6 Hz, 1H), 4.70 (d, J = 17.0 Hz, (dd, J = 7.8, 1.7 Hz, 1H), 7.38 – 7.31 (m, 1H), 7.22 – 7.18 (m,
1H), 4.17 (d, J = 17.0 Hz, 1H), 3.22 (dd, J = 15.9, 6.6 Hz, 3H), 7.12 – 7.09 (m, 2H), 6.73 – 6.60 (m, 2H), 5.83 – 568 (m,
1H), 2.90 (dd, J = 15.9, 4.6 Hz, 1H). −13C NMR (63 MHz, 1H), 5,22 – 5.10 (m, 2H), 4.68 (t, J = 6.2 Hz, 1H), 4.11 – 4.01
CDCl3): δ = 191.9, 150.7, 139.3, 137.3, 135.8, 128.8, 128.7, (m, 1H), 3.63 – 3.53 (m, 1H), 3.07 (dd, J = 15.9, 6.2 Hz,
127.7, 127.6, 127.2, 126.4, 126.2, 119.8, 116.5, 112.8, 62.4, 1H), 2.87 (dd, J = 15.9, 6.2 Hz, 1H). − 13C NMR (63 MHz,
53.5, 44.8. − IR (KBr): v˜= 3027, 2924, 2849, 1673, 1602, CDCl3): δ = 192.2, 150.9, 139.9, 135.8, 132.8, 128.9, 127.9,
1491, 1450, 805, 751, 698. − MS-EI: m/z (%) = 313.1 127.7, 126.7, 119.9, 116.8, 116.6, 113.2, 62.4, 52.1, 45.2.
(44) [M]+, 236.0 (12), 222.0 (17), 91.0 (100), 77.0 (15). − IR (KBr): v˜= 3027, 2919, 1642, 1604, 1493, 752, 730,
− [α]2D5 = +43.3◦ (c = 1.0 in chloroform). − HPLC con- 698. − MS-EI: m/z (%) = 263.1 (22) [M]+, 222.0 (4), 186.1
ditions: OD-H column, n-hexane-2-propanol = 90 : 10, flow (14), 146.1 (4), 77 (100). − [α]2D5 = +139.0◦ (c = 0.2 in
rate = 0.6 mL min−1, major enantiomer: tR = 39.5 min; mi- chloroform). − HPLC conditions: OD-H column, n-hexane-
nor enantiomer: tR = 25.7 min.
2-propanol = 95 : 5, flow rate = 0.6 mL min−1, major enan-
tiomer: tR = 16.9 min; minor enantiomer: tR = 17.9 min.
1,2-Diphenyl-2,3-dihydroquinolin-4(1H)-one (11a)
1-Allyl-2-o-tolyl-2,3-dihydroquinolin-4(1H)-one (13b)
Synthesized according to the general procedure: 9.9 mg,
66%, pale-yellow solid. – 1H NMR (250 MHz, CDCl3):
Synthesized according to the general procedure: 6.3 mg,
δ = 7.89 (dd, J = 8.2, 1.7 Hz, 1H), 7.33 – 7.16 (m, 11H), 45%, yellow oil. – 1H NMR (250 MHz, CDCl3): δ = 7.86
6.81 – 6.76 (m, 2H), 5.14 (t, J = 5.6 Hz, 1H), 3.36 (dd, (dd, J = 7.8, 1.7 Hz, 1H), 7.46 – 7.39 (m, 1H), 7.17 – 7.06 (m,
J = 16.3, 5.6 Hz, 1H), 3.09 (dd, J = 16.3, 5.6 Hz, 1H). −13C 4H), 6.82 – 6.71 (m, 2H), 5.89 – 5.76 (m, 1H), 5.25 – 5.18 (m,
NMR (63 MHz, CDCl3): δ = 192.2, 150.2, 145.2, 140.0, 2H), 4.98 (t, J = 6.5 Hz, 1H), 4.13 – 4.03 (m, 1H), 3.61 – 3.51
135.2, 129.6, 128.7, 127.6, 126.9, 125.9, 125.8, 120.7, (m, 1H), 3.08 (dd, J = 15.9, 6.3 Hz, 1H), 2.86 (dd, J = 15.9,
118.2, 116.3, 64.3, 44.9. − IR (KBr): v˜= 3032, 2922, 2883, 6.6 Hz, 1H), 2.34 (s, 3H). − 13C NMR (63 MHz, CDCl3):
2832, 1716, 1596, 1490, 777, 765, 748, 701. − MS-EI: δ = 192.0, 164.3, 160.3, 150.6, 135.9, 132.7, 128.4, 128.3,
m/z (%) = 299.0 (43) [M]+, 222.0 (43), 77.0 (100). − 127.7, 119.9, 116.9, 116.7, 116.0, 115.9, 113.2, 61.7, 52.0,
[α]2D5 = −19.0◦ (c = 0.5 in chloroform). − HPLC condi- 45.3. − IR (KBr): v˜= 3059, 2922, 1676, 1601, 1493, 1463,
tions: OD-H column, n-hexane-2-propanol = 90 : 10, flow 1348, 1320, 1095, 924, 754. − MS–EI: m/z (%) = 277.0
rate = 0.6 mL min−1, major enantiomer: tR = 18.1 min; mi- (83) [M]+, 235.9 (9), 186.2 (46), 146.0 (27), 91.0 (100).
nor enantiomer: tR = 26.1 min.
− [α]2D5 = +83.5◦ (c = 0.2 in chloroform). − HPLC con-
ditions: AD-H column, n-hexane-2-propanol = 90 : 10, flow
rate = 0.6 mL min−1, major enantiomer: tR = 9.6 min; minor
enantiomer: tR = 10.6 min.
1-Isopropyl-2-phenyl-2,3-dihydroquinolin-4(1H)-one (12a)
Synthesized according to the general procedure: 4.2 mg,
32%, yellow oil.
–
1H NMR (250 MHz, CDCl3):
1-Allyl-2-(2-methoxyphenyl)-2,3-dihydroquinolin-4(1H)-
one (13c)
δ = 7.81 (dd, J = 7.8, 1.8 Hz, 1H), 7.47 – 7.40 (m, 1H),
7.21 – 7.10 (m, 5H), 6.95 (d, J = 8.7 Hz 1H), 6.69 – 6.62
(m, 1H), 4.70 (dd, J = 6.7, 2.2 Hz, 1H), 4.43 – 4.27
Synthesized according to the general procedure: 9.2 mg,
(m, 1H), 3.17 (dd, J = 15.9 Hz, 6.7 Hz, 1H), 2.84 (dd, 63%, yellow oil. – 1H NMR (250 MHz, CDCl3): δ = 7.82
J = 15.9, 2.2 Hz, 1H), 1.40 (d, J = 6.6 Hz, 3H), 1.08 (d, (dd, J = 7.8, 1.7 Hz, 1H), 7.44 – 7.37 (m, 1H), 7.24 – 7.17 (m,
J = 6.7 Hz, 3H). − 13C NMR (63 MHz, CDCl3): δ = 192.2, 1H), 6.91 – 6.84 (m, 2H), 6.79 – 6.66 (m, 3H), 5.95 – 5.81 (m,
150.4, 141.5, 135.9, 128.6, 128.1, 127.2, 126.2, 120.4, 1H), 5.36 – 5.12 (m, 3H), 4.17 – 4.07 (m, 1H), 3.83 (s, 3H),
115.6, 112.5, 54.0, 48.8, 44.6, 21.6, 19.7. − IR (KBr): 3.67 – 3.56 (m, 1H), 3.15 (dd, J = 15.9, 7.0 Hz, 1H), 2.99
v˜= 3028, 2968, 2925, 1716, 1604, 1507, 1457, 1396, (dd, J = 15.9, 3.6 Hz, 1H). −13C NMR (63 MHz, CDCl3):
1271, 1188, 752, 700. − MS-EI: m/z (%) = 265.1 (43) δ = 192.9, 156.8, 150.9, 135.7, 133.1, 128.7, 127.6, 126.8,
[M]+, 222.0 (9), 188.1 (3), 146.1 (100), 77.0 (63). − 120.4, 119.4, 116.1, 116.0, 112.3, 110.7, 56.6, 55.1, 52.5,
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1026
M. Rueping et al. · Enantioselective Synthesis of Dihydroquinolinones
42.5. − IR (KBr): v˜= 3059, 3002, 2924, 2853, 1716, 1667, (m, 2H), 6.83 – 6.69 (m, 4H), 5.89 – 5.74 (m, 1H), 5.27 – 5.16
1598, 1558, 1487, 1177, 1044, 1024, 997, 980, 907, 806, 788, (m, 2H), 4.70 (t, J = 6.4 Hz, 1H), 4.15 – 4.05 (m, 1H), 3.77
719. − MS-EI: m/z (%) = 293.2 (89) [M]+, 261.8 (9), 251.9 (s, 3H), 3.70 – 3.60 (m, 1H), 3.09 (dd, J = 15.9, 5.9 Hz,
(10), 186.0 (43), 108.1 (27). − [α]2D5 = +83.8◦ (c = 1.0 in 1H), 2.91 (dd, J = 15.9, 6.7 Hz, 1H). − 13C NMR (63 MHz,
chloroform). − HPLC conditions: AD-H column, n-hexane- CDCl3): δ = 192.5, 159.2, 150.9., 135.7, 132.9, 131.8,
2-propanol = 90 : 10, flow rate = 0.6 mL min−1, major enan- 127.9, 127.7, 119.9, 116.7, 116.5, 114.3, 113.3, 61.9, 55.2,
tiomer: tR = 13.8 min; minor enantiomer: tR = 11.9 min.
51.8, 45.5. − IR (KBr): v˜= 2929, 2834, 1675, 1604, 1510,
1490, 1107, 1031, 989, 924, 810, 799, 755, 703. − MS-EI:
m/z (%) = 293.1 (39) [M]+, 252.0 (7), 185.9 (31), 108.1
(27). − [α]2D5 = +122.6◦ (c = 1.0 in chloroform). − HPLC
conditions: AD-H column, n-hexane-2-propanol = 90 : 10,
flow rate = 0.6 mL min−1, major enantiomer: tR = 16.5 min;
minor enantiomer: tR = 17.8 min.
1-Allyl-2-m-tolyl-2,3-dihydroquinolin-4(1H)-one (13d)
Synthesized according to the general procedure: 7.3 mg,
53%, yellow oil. – 1H NMR (250 MHz, CDCl3): δ = 7.86
(dd, J = 7.8, 1.7 Hz, 1H), 7.44 – 7.37 (m, 1H), 7.20 – 6.95 (m,
4H), 6.80 – 6.70 (m, 2H), 5.92 – 5.72 (m, 1H), 5.28 – 5.17 (m,
2H), 4.71 (t, J = 6.4 Hz, 1H), 4.17 – 4.07 (m, 1H), 3.70 – 3.59
(m, 1H), 3.11 (dd, J = 15.9, 6.4 Hz, 1H), 2.93 (dd, J = 15.9,
6.4 Hz, 1H), 2.30 (s, 3H). − 13C NMR (63 MHz, CDCl3):
δ = 192.4, 150.9, 139.8, 138.6, 135.7, 132.9, 128.8, 128.7,
127.7, 127.5, 123.7, 119.9, 116.7, 116.5, 113.2, 62.4, 51.9,
45.3, 21.5. − IR (KBr): v˜= 2957, 2926, 2857, 1725, 1677,
1605, 1487, 1466, 1348, 1320, 1177, 754, 704. − MS-EI:
m/z (%) = 277.1 (72) [M]+, 263.2 (4), 236.0 (14), 186.0,
146.1 (10), 91.1 (88). − [α]2D5 = +111.6◦ (c = 0.5 in chlo-
roform). − HPLC conditions: OJ-H column, n-hexane-2-
propanol = 90 : 10, flow rate = 0.6 mL min−1, major enan-
tiomer: tR = 18.7 min; minor enantiomer: tR = 24.8 min.
1-Allyl-2-(4-fluorophenyl)-2,3-dihydroquinolin-4(1H)-
one (13g)
Synthesized according to the general procedure: 12.9 mg,
92%, yellow oil. – 1H NMR (250 MHz, CDCl3): δ = 7.86
(dd, J = 7.8, 1.7 Hz, 1H), 7.45 – 7.38 (m, 1H), 7.18 – 7.11
(m, 2H), 7.02 – 6.94 (m, 2H), 6.80 – 6.71 (m, 2H), 5.90 – 5.75
(m, 1H), 5.28 – 5.18 (m, 2H), 4.74 (t, J = 6.1 Hz, 1H),
4.17 – 4.07 (m, 1H), 3.68 – 3.58 (m, 1H), 3.13 (dd, J = 15.9,
6.1 Hz, 1H), 2.89 (dd, J = 15.9, 6.1 Hz, 1H). − 13C NMR
(63 MHz, CDCl3): δ = 192.0, 164.3, 160.3, 150.6, 135.9,
132.7, 128.4, 128.3, 127.7, 119.9, 116.9, 116.7, 116.0, 115.9,
113.2, 61.7, 52.0, 45.3. − IR (KBr): v˜= 2958, 2928, 2857,
1725, 1676, 1603, 1508, 990, 924, 839, 799, 754, 705. −
MS-EI: m/z (%) = 281.0 (33) [M]+, 239.9 (11), 186.1 (20),
145.0 (4), 96.0 (93). − [α]2D5 = +130.3◦ (c = 1.0 in chlo-
roform). – HPLC conditions: AD-H column, n-hexane-2-
propanol = 90 : 10, flow rate = 0.6 mL min−1, major enan-
tiomer: tR = 12.3 min; minor enantiomer: tR = 14.8 min.
1-Allyl-2-(3-phenoxyphenyl)-2,3-dihydroquinolin-4(1H)-
one (13e)
Synthesized according to the general procedure: 6.4 mg,
36%, yellow oil. – 1HNMR (250 MHz, CDCl3): δ = 7.84
(dd, J = 7.8, 1.4 Hz, 1H), 7.42 – 7.27 (m, 3H), 7.21 (d,
J = 7.8 Hz, 1H), 7.13 – 7.07 (m, 1H), 6.98 – 6.69 (m, 7H),
5.90 – 5.75 (m, 1H), 5.28 – 5.14 (m, 2H), 4.72 (t, J = 6.1 Hz,
1H), 4.18 – 4.08 (m, 1H), 3.70 – 3.60 (m, 1H), 3.13 (dd,
J = 15.9, 6.1 Hz, 1H), 2.90 (dd, J = 15.9, 6.1 Hz, 1H). −
13C NMR (63 MHz, CDCl3): δ = 192.0, 157.9, 156.5, 150.7,
142.0, 135.8, 132.8, 130.3, 129.8, 127.7, 123.6, 121.2, 119.9,
119.2, 117.8, 116.8, 116.7, 116.7, 113.1, 62.2, 52.2, 45.1.
− IR (KBr): v˜= 3062, 2923, 1725, 1675, 1604, 1485, 988,
916, 754, 692. − MS-EI: m/z (%) = 355.2 (100) [M]+,
314.4 (19), 186.0 (55), 168.1 (12), 145.7 (11), 76.8 (85).
− [α]2D5 = +73.4◦ (c = 0.5 in chloroform). − HPLC con-
ditions: AD-H column, n-hexane-2-propanol = 98 : 2, flow
rate = 0.6 mL min−1, major enantiomer: tR = 37.5 min; mi-
nor enantiomer: tR = 35.5 min.
1-Allyl-2-(3,4,5-trimethoxyphenyl)-2,3-dihydroquinolin-
4(1H)-one (13h)
Synthesized according to the general procedure: 10.2 mg,
58%, yellow oil. – 1H NMR (250 MHz, CDCl3): δ = 7.88
(dd, J = 7.8, 1.7 Hz, 1H), 7.45 – 7.38 (m, 1H), 6.85 – 6.69
(m, 2H), 6.41 (s, 2H), 5.92 – 5.77 (m, 1H), 5.30 – 5.19
(m, 2H), 4.66 (dd, J = 7.3, 5.8 Hz, 1H), 4.15 – 4.06 (m,
1H), 3.81 (s, 3H), 3.74 (s, 6H), 3.72 – 3.61 (m, 1H), 3.09
(dd, J = 15.9, 5.8 Hz, 1H), 2.93 (dd, J = 15.9, 7.3 Hz, 1H).
−
13C NMR (63 MHz, CDCl3): δ = 192.3, 153.5, 151.0,
137.5, 135.8, 135.5, 133.0, 127.7, 120.0, 116.8, 116.7, 113.4,
103.7, 63.0, 60.8, 56.0, 52.1, 45.6. − IR (KBr): v˜= 2926,
2852, 1725, 1675, 1601, 1489, 1008, 921, 799, 755, 687.
− MS-EI: m/z (%) = 353.1 (88) [M]+, 321.9 (4), 312.3
(8), 280.7 (3), 250.2 (4), 186.1 (63), 167.1, 146.1 (12). −
[α]2D5 = +93.4◦ (c = 0.5 in chloroform). − HPLC condi-
1-Allyl-2-(4-methoxyphenyl)-2,3-dihydroquinolin-4(1H)-
one (13f)
Synthesized according to the general procedure: 14.4 mg, tions: AD-H column, n-hexane-2-propanol = 90 : 10, flow
98%, yellow oil. – 1H NMR (250 MHz, CDCl3): δ = 7.86 rate = 0.6 mL min−1, major enantiomer: tR = 33.3 min; mi-
(dd, J = 7.8, 1.7 Hz, 1H), 7.44 – 7.37 (m, 1H), 7.13 – 7.09 nor enantiomer: tR = 51.9 min.
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M. Rueping et al. · Enantioselective Synthesis of Dihydroquinolinones
1027
1-Allyl-2-(naphthalen-1-yl)-2,3-dihydroquinolin-4(1H)-
one (13i)
116.8, 113.4, 110.1, 108.0, 56.1, 52.7, 41.9. − IR (KBr):
v˜= 2924, 1670, 1604, 1489, 1032, 911, 756. − MS-EI: m/z
(%) = 252.9 (52) [M]+, 212.1 (5), 186.3 (7), 146.3 (6), 67.1
(7). − [α]2D5 = +4.6◦ (c = 0.5 in chloroform). – HPLC con-
ditions: OD-H column, n-hexane-2-propanol = 90 : 10, flow
rate = 0.6 mL min−1, major enantiomer: tR = 15.6 min; mi-
nor enantiomer: tR = 17.7 min.
Synthesized according to the general procedure: 13.4 mg,
86%, yellow oil.
–
1H NMR (250 MHz, CDCl3):
δ = 8.04 – 8.00 (m, 1H), 7.92 – 7.85 (m, 2H), 7.77 (d, J = 8.0
Hz, 1H), 7.58 – 7.43 (m, 3H), 7.34 – 7.22 (m, 2H), 6.85 (d,
J = 8.5 Hz, 1H), 6.80 – 6.73 (m, 1H), 5.96 – 5.81 (m, 1H),
5.57 (t, J = 6.2 Hz, 1H), 5.32 – 5.19 (m, 2H), 4.25 – 4.15
(m, 1H), 3.68 – 3.58 (m, 1H), 3.31 (dd, J = 15.8, 6.8 Hz,
1H), 3.17 (dd, J = 15.9, 5.3 Hz, 1H). −13C NMR (63 MHz,
CDCl3): δ = 192.0, 151.2, 135.9, 134.4, 134.0, 132.7, 130.4,
1-Benzyl-2-(methoxyphenyl)-2,3-dihydroquinolin-4(1H)-
one (10b)
Synthesized according to the general procedure: 12.1 mg,
129.4, 128.6, 127.9, 126.4, 125.7, 125.3, 124.1, 122.4, 71%, yellow solid. – 1H NMR (250 MHz, CDCl3): δ = 7.85
119.4, 116.7, 116.5, 112.8, 59.0, 52.2, 43.6. − IR (KBr): (dd, J = 7.8, 1.6 Hz, 1H, Ar), 7.37 – 7.18 (m, 7H, Ar),
v˜= 3060, 2922, 1675, 1638, 1599, 159, 1496, 993, 957, 6.94 – 6.65 (m, 5H, Ar), 5.24 (dd, J = 7.2, 2.8 Hz, 1H, CH),
916, 868, 799, 783, 761. − MS-EI: m/z (%) = 312.9 (56) 4.74 (d, J = 17.0 Hz, 1H, NCH2), 4.22 (d, J = 17.0 Hz, 1H,
[M]+, 272.1 (10), 186.1 (37), 145.2 (6), 127.0 (92). − NCH2), 3.80 (s, 3H, OCH3), 3.28 (dd, J = 16.0, 7.2 Hz, 1H,
[α]2D5 = +24.0◦ (c = 1.0 in chloroform). – HPLC condi- CH2), 3.05 (dd, J = 16.0, 2.8 Hz, 1H, CH2). − 13C NMR
tions: OD-H column, n-hexane-2-propanol = 90 : 10, flow (63 MHz, CDCl3): δ = 192.8, 156.9, 151.0, 137.7, 135.9,
rate = 0.6 mL min−1, major enantiomer: tR = 32.2 min; mi- 128.8, 127.7, 127.3, 126.6, 126.5, 126.2, 120.4, 119.5, 116.3,
nor enantiomer: tR = 38.6 min.
112.3, 110.7, 104.9, 57.3, 55.1, 54.0, 42.4. − IR (KBr):
v˜= 3058, 3032, 2999, 2962, 2935, 2836, 1943, 1672, 1602,
1585, 1558, 1495, 1469, 1461, 1449, 1414, 1396, 1345,
1321, 1287, 1264, 1244, 1222, 1205, 1174, 1120, 1097,
1052, 1024, 1006, 970, 952, 931, 864, 808, 795, 754, 732,
719, 694, 598, 576, 553, 527, 506, 477, 458, 403. − MS-
EI (70 eV): m/z (%) = 343.2 (5) [M]+, 252.0 (3), 236.0 (4),
107.1 (2), 91.0 (100). − [α]2D5 = +1.7◦ (c = 1.0 in chlo-
roform). – HPLC conditions: OD-H column, n-hexane-2-
propanol = 90 : 10, flow rate = 0.6 mL min−1, major enan-
tiomer: tR = 15.6 min; minor enantiomer: tR = 20.0 min.
1-Allyl-2-(naphthalen-2-yl)-2,3-dihydroquinolin-4(1H)-
one (13j)
Synthesized according to the general procedure: 11.6 mg,
74%, yellow oil. – 1H NMR (250 MHz, CDCl3): δ = 7.89
(dd, J = 7.8, 1.6 Hz, 1H), 7.84 – 7.70 (m, 3H), 7.60 (d,
J = 0.9 Hz, 1H), 7.50 – 7.35 (m, 4H), 6.86 – 6.74 (m, 2H),
5.91 – 5.76 (m, 1H), 5.29 – 5.18 (m, 2H), 4.92 (t, J = 6.5 Hz,
1H), 4.24 – 4.13 (m, 1H), 3.75 – 3.64 (m, 1H), 3.17 (dd,
J = 15.9, 6.0 Hz, 1H), 3.05 (dd, J = 15.9, 7.0 Hz, 1H).
−
13C NMR (63 MHz, CDCl3): δ = 192.2, 151.0, 137.3,
1-Benzyl-2-(2-bromophenyl)-2,3-dihydroquinolin-4(1H)-
135.8, 133.3, 133.0, 132.8, 129.0, 127.9, 127.8, 127.7,
126.4, 126.2, 125.9, 124.4, 120.0, 116.9, 116.7, 113.4, 62.7,
51.9, 45.2. − IR (KBr): v˜=3057, 2925, 1719, 1671, 1600,
1561, 1490, 987, 919, 859, 821, 799, 750. − MS-EI: m/z
(%) = 313.0 (63) [M]+, 272.2 (14), 186.0 (43), 127.0 (89).
− [α]2D5 = +121.3◦ (c = 1.0 in chloroform). – HPLC con-
ditions: AD-H column, n-hexane-2-propanol = 90 : 10, flow
rate = 0.6 mL min−1, major enantiomer: tR = 16.9 min; mi-
nor enantiomer: tR = 19.0 min.
one (10c)
Synthesized according to the general procedure: 11.5 mg,
29%, yellow solid. – 1H NMR (250 MHz, CDCl3): δ = 7.87
(dd, J = 7.8, 1.6 Hz, 1H, Ar), 7.59 – 7.52 (m, 1H, Ar),
7.41 – 7.30 (m, 6H, Ar), 7.15 – 7.07 (m, 3H, Ar), 6.79 – 6.69
(m, 2H, Ar), 5.24 (dd, J = 7.4, 3.0 Hz, 1H, CH), 4.73
(d, J = 17.0 Hz, 1H, NCH2), 4.17 (d, J = 17.0 Hz, 1H,
NCH2), 3.33 (dd, J = 16.0, 7.4 Hz, 1H, CH2), 3.07 (dd,
J = 16.0, 3.0 Hz, 1H, CH2). − 13C NMR (63 MHz, CDCl3):
δ = 191.7, 150.8, 137.9, 137.0, 136.1, 133.8, 129.4, 128.9,
1-Allyl-2-(furan-2-yl)-2,3-dihydroquinolin-4(1H)-one (13k)
Synthesized according to the general procedure: 8.6 mg, 127.9, 127.7, 127.5, 127.4, 126.3, 122.8, 119.7, 116.8, 112.5,
68%, yellow oil.
–
1H NMR (250 MHz, CDCl3): 61.7, 54.0, 42.3. − IR (KBr): v˜= 3075, 3020, 2962, 2921,
δ = 7.90 – 7.86 (m, 1H), 7.40 – 7.30 (m, 2H), 6.75 – 6.68 1739, 1669, 1602, 1559, 1493, 1471, 1449, 1422,1410,
(m, 2H), 6.23 (dd, J = 3.3, 1.8 Hz, 1H), 6.09 – 6.08 (m, 1396, 1351, 1324, 1222, 1173, 1114, 1055, 1006, 966, 935,
1H), 5.96 – 5.81 (m, 1H), 5.35 – 5.20 (m, 2H), 4.79 (dd, 885, 807, 764, 728, 691, 671. − MS-ESI (+): m/z = 392.1
J = 5.9, 4.3 Hz, 1H), 4.23 – 4.13 (m, 1H), 3.93 – 3.83 (m, (Br79), 394.1 (Br81). − [α]D25 = +9.1◦ (c = 1.0 in chlo-
1H), 3.13 (dd, J = 16.2, 5.9 Hz, 1H), 3.01 (dd, J = 16.2, roform). – HPLC conditions: AS-H column, n-hexane-2-
4.3 Hz, 1H). − 13C NMR (63 MHz, CDCl3): δ = 192.3, propanol = 90 : 10, flow rate = 0.6 mL min−1, major enan-
152.5, 149.5, 142.4, 135.6, 133.2, 127.7, 119.6, 116.9, tiomer: tR = 30.8 min; minor enantiomer: tR = 57.9 min.
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Download Date | 6/15/15 11:23 AM

1028
M. Rueping et al. · Enantioselective Synthesis of Dihydroquinolinones
1-Benzyl-2-(3-bromophenyl)-2,3-dihydroquinolin-4(1H)-
one (10d)
Table 5. Crystal structure data and numbers pertinent to data
collection and structure refinement for 10d.
10d
C22H18BrNO
392.28
Synthesized according to the general procedure: 22.8 mg,
58%, yellow solid. – 1H NMR (250 MHz, CDCl3): δ = 7.87
(dd, J = 7.8, 1.6 Hz, 1H, Ar), 7.41 – 7.27 (m, 8H, Ar),
7.16 – 7.04 (m, 2H, Ar), 6.79 – 6.72 (m, 2H, Ar), 4.84 – 4.77
(m, 2H, CH, NCH2), 4.22 (d, J = 17.0 Hz, 1H, NCH2),
3.28 (dd, J = 16.0, 6.6 Hz, 1H, CH2), 2.93 (dd, J = 16.0,
4.4 Hz, 1H, CH2). −13C NMR (63 MHz, CDCl3): δ = 191.5,
150.5, 142.0, 137.1, 136.2, 131.1, 130.6, 129.9, 128.9,
127.8, 127.5, 126.4, 125.1, 123.0, 119.9, 117.0, 112.9, 62.0,
53.7, 44.7. − IR (KBr): v˜= 3063, 3030, 2924, 2854, 1722,
1673, 1599, 1560, 1485, 1452, 1391, 1347, 1294, 1217,
1172, 1072, 1027, 1008, 963, 946, 887, 834, 791, 754,
696. − MS-ESI (+): m/z = 392.1 (Br79), 394,1 (Br81). −
[α]2D5 = +30.3◦ (c = 1.0 in chloroform). – HPLC condi-
tions: AS-H column, n-hexane-2-propanol = 90 : 10, flow
rate = 0.6 mL min−1, major enantiomer: tR = 37.8 min; mi-
nor enantiomer: tR = 54.8 min.
Formula
Mr
Crystal size, mm3
Crystal system
Space group
0.37 × 0.31 × 0.29
orthorhombic
P212121
9.0521(4)
13.4433(4)
15.0807(5)
1835.17(12)
4
˚
a, A
˚
b, A
˚
c, A
3
˚
V, A
Z
Dcalcd, g cm−3
µ(MoKα ), cm−1
F(000), e
1.42
2.2
800
hkl range
((sinθ)/λ)max, A
±12, −18→16, ± 20
−1
˚
0.6757
Refl. measured / unique / Rint
Param. refined
64986 / 4729 / 0.0722
226
0.0471 / 0.1012
0.023(9)
1.124
0.59/−0.914
R(F) / wR(F2)a (all refls.)
x (Flack)
GoF (F2)b
1-Benzyl-2-(4-bromophenyl)-2,3-dihydroquinolin-4(1H)-
one (10e)
−3
˚
∆ρfin (max/min), e A
R = Σ||Fo| − |F ||/Σ|Fo|, wR = [Σw(F2 − F2)2/Σw(Fo2)2]1/2
,
a
c
w = [σ2(Fo2) + (AP)2 + BP]−1, where P =o(Max(Fo2,0) + 2F2)/3;
c
Synthesized according to the general procedure: 22.5 mg,
57%, yellow solid. – 1H NMR (250 MHz, CDCl3): δ = 7.87
(dd, J = 7.8, 1.6 Hz, 1H, Ar), 7.41 – 7.27 (m, 8H, Ar), 7.01
(d, J = 8.4 Hz, 2H, Ar), 7.15 – 7.07 (m, 3H, Ar), 6.78 – 6.71
(m, 2H, Ar), 4.82 – 4.75 (m, 2H, CH, NCH2), 4.21 (d,
J = 17.0 Hz, 1H, NCH2), 3.28 (dd, J = 16.0, 6.6 Hz, 1H,
CH2), 2.91 (dd, J = 16.0, 4.5 Hz, 1H, CH2). −13C NMR
(63 MHz, CDCl3): δ = 191.5, 150.6, 138.6, 137.2, 136.1,
132.1, 128.9, 128.3, 127.8, 127.5, 126.4, 121.8, 119.9, 116.9,
112.9, 61.9, 53.6, 44.8. − IR (KBr): v˜= 3064, 3014, 2921,
2852, 1724, 1675, 1604, 1565, 1491, 1466, 1347, 1293,
1271, 1173, 1126, 1024, 803, 754, 698, 666. − MS-ESI
(+): m/z = 391.7 (Br79), 394,1 (Br81). − [α]D25 = +15.3◦
(c = 1.0 in chloroform). − HPLC conditions: AS-H col-
umn, n-hexane-2-propanol = 90 : 10, flow rate = 0.6 mL
min−1, major enantiomer: tR = 46.1 min; minor enantiomer:
tR = 54.9 min.
c
GoF = [Σw(Fo2 −F2)2/(nobs −nparam)]1/2
.
b
c
126.5, 126.3, 125.7, 125.3, 123.6, 122.2, 119.4, 116.6, 112.5,
59.1, 53.8, 43.4. − IR (KBr): v˜= 3054, 3016, 2864, 1671,
1625, 1601, 1560, 1491, 1469, 1448, 1404, 1348, 1321,
1291, 1259, 1223, 1193, 1172, 1116, 1054, 1025, 1008,
943, 907, 862, 811, 798, 767, 727, 693, 638, 583, 562,
546, 534, 517, 501, 484, 471, 458, 420. − MS-EI (70 eV):
m/z (%) = 363.2 (4) [M]+, 272.1 (2), 127.0 (4), 91.0 (100).
− [α]2D5 = +49.3◦ (c = 0.5 in chloroform). – HPLC condi-
tions: OD-H column, n-hexane-2-propanol = 90 : 10, flow
rate = 0.6 mL min−1, major enantiomer: tR = 40.2 min; mi-
nor enantiomer: tR = 72.0 min.
Crystal structure determination
Crystallographic data were collected with a Stoe IPDS
1-Benzyl-2-(naphthalen-1-yl)-2,3-dihydroquinolin-4(1H)-
one (10f)
II two-circle-diffractometer with monochromatic MoKα ra-
˚
diation (λ = 0.71073 A). The structure was solved by Di-
rect Methods using SHELXS-97 and refined against F2 on
all data by full-matrix least-squares methods using SHELXL-
97 [46, 47]. Details regarding the crystal structure determi-
nation are summarized in Table 5.
Synthesized according to the general procedure: 7.4 mg,
41%, yellow solid. – 1H NMR (250 MHz, CDCl3):
δ = 7.91 – 7.86 (m, 3H, Ar), 7.69 (dd, J = 7.7, 1.8 Hz, 1H,
Ar), 7.55 – 7.21 (m, 10H, Ar), 6.80 – 6.74 (m, 2H, Ar),
5.60 (dd, J = 7.2, 3.3 Hz, 1H, CH), 4.76 (d, J = 17.0 Hz,
1H, NCH2), 4.15 (d, J = 17.0 Hz, 1H, NCH2), 3.39 (dd,
J = 15.7, 7.2 Hz, 1H, CH2), 3.10 (dd, J = 15.7, 3.3 Hz, 1H,
CH2). −13C NMR (63 MHz, CDCl3):128.9, 127.9, 127.4,
CCDC 897124 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data request/cif.
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M. Rueping et al. · Enantioselective Synthesis of Dihydroquinolinones
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