Efficient synthesis and X-ray structures of new α-quinolin-3-yl- α-aminonitriles and derivatives

Article abstract of DOI:10.1016/j.tetlet.2012.11.032

This study describes the synthesis of novel α-aminonitrile derivatives possessing a quinoline subunit via a Strecker reaction. Chiral α-methylbenzylamines were used to carry out the diastereoselective version of this sequence. Conversion of an enantiopure 2-chloroquinolin-3-yl derivative into the corresponding α-aminoester resulted in the concomitant formation of a 2(1H)-quinolinone moiety and a partial racemization. Single crystal X-ray structures are reported for three compounds.

Full text of DOI:10.1016/j.tetlet.2012.11.032

Accepted Manuscript
Efficient synthesis and X-ray structures of new α-quinolin-3-yl-α-aminonitriles
and derivatives
Souheila Ladraa, Fabienne Berrée, Abdelmalek Bouraiou, Sofiane Bouacida,
Thierry Roisnel, Bertrand Carboni, Ali Belfaitah
PII:
S0040-4039(12)01962-4
DOI:
http://dx.doi.org/10.1016/j.tetlet.2012.11.032
TETL 42124
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
3 September 2012
18 October 2012
6 November 2012
Please cite this article as: Ladraa, S., Berrée, F., Bouraiou, A., Bouacida, S., Roisnel, T., Carboni, B., Belfaitah, A.,
Efficient synthesis and X-ray structures of new α-quinolin-3-yl-α-aminonitriles and derivatives, Tetrahedron
Letters (2012), doi: http://dx.doi.org/10.1016/j.tetlet.2012.11.032
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Efficient synthesisand X-ray structures
ofnew-quinolin-3-yl--aminonitriles and derivatives 
S. Ladraa, F. Berrée, A. Bouraiou, S. Bouacida, T. Roisnel, B. Carboni, A. Belfaitah
CN
COOCH3
+
CHO
NH3 Cl -
NHR'
R
R
R
N
O
N
Cl
N
Cl
H

1
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/ locate/tetlet
Efficient synthesisand X-ray structures ofnew-quinolin-3-yl--aminonitriles and
derivatives.
Souheila Ladraa,a Fabienne Berrée,b Abdelmalek Bouraiou,a Sofiane Bouacida,c Thierry Roisnel,d
Bertrand Carboni,b Ali Belfaitah*a
a Laboratoire des Produits Naturels d’Origine Végétale et de Synthèse Organique, Faculté des Sciences Exactes, Campus de Chaabat Ersas, Université Mentouri-
Constantine, 25000, Algeria.
b Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS-Université de Rennes 1, Campus de Beaulieu, 35042 Rennes CEDEX, France.
cUnité de Recherche de Chimie de l’Environnement et Moléculaire Structurale, Université Mentouri-Constantine, 25000, Algérie.
d Centre de Diffractométrie X, Sciences Chimiques de Rennes, UMR 6226 CNRS, Université de Rennes I, 35042 Rennes CEDEX, France
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
This study describes the synthesis of novel -aminonitrile derivatives possessing a quinoline
subunit via a Strecker reaction. Chiral -methylbenzylamines were used to carry out the
diastereoselective version of this sequence. Conversion of an enantiopure 2-chloroquinolin-3-yl
derivative into the corresponding -aminoester resulted in the concomitant formation of a
2(1H)-quinolinone moiety and a partial racemisation. Single crystal X-ray structures are reported
for three compounds.
Available online
2012 Elsevier Ltd. All rights reserved
Keywords:
-Amino acid
-Aminonitrile
Asymmetric Synthesis
Quinoline
.
Strecker Reaction
Amino acids are very important in biochemical, nutritional
and biological research. In particular, the incorporation of non-
proteinogenic -amino acids into key positions of peptide chains
has played a major role in drug discovery processes and
constitutes one of the most effective methods to confer higher
biological activity, as well as increasing biostability. These
compounds have also been widely used as intermediates in the
synthesis of drug candidates, natural products and ligands for
asymmetric catalysis.1 The three-component Strecker synthesis
is one of the simplest methods for preparing -amino acids and
a great deal of effort has been devoted to the asymmetric version
of this reaction. Enantioselective protocols have been reported in
our preliminary results concerning the synthesis of new -
aminonitriles possessing quinoline unit using
diastereoselective Strecker reaction and their conversion into the
a
a
corresponding -amino esters (Scheme 1).
CN
NHR'
COOMe
CHO
Cl
+
NH3
R
R
R
-
N
Cl
O
N
Cl
N
H
Scheme 1. Access to -(quinolin-3-yl)-aminonitriles and their derivatives.
Initially, aldimines 2a-2i were easily prepared in good yields
from the corresponding 2-chloroquinolin-3-carboxaldehydes 1
in methanol in the presence of an amine (1.0 equiv).7 Their
conversion into the corresponding -aminonitriles 3 proceeded
cleanly in 83-96% yields by treatment with 1.2 eq. of t-
BuMe2SiCN and a few drops of water in acetonitrile (Table 1).8
Both the 1H and 13C NMR spectra of compounds 2 and 3 were in
full agreement with the proposed structures.
The hydrolysis of the nitrile group was then studied under
various conditions. No desired product was obtained from 3h,
selected as a model compound, either with aqueous KOH,
NaOH in methanol/water, or t-BuOK at various temperatures (0
2
the case of chiral organo- or metal-based catalysts, while, in
alternative approaches, optically pure amines were successfully
used as chiral auxiliaries in diastereoselective processes.3
On the other hand, quinoline derivatives have also received
considerable interest due to the presence of this skeleton in a
large number of bioactive compounds and natural products.4 The
introduction of a quinoline nucleus has been used successfully
in a number of pharmacomodulations.5 However, to our
knowledge, no investigations involving the combination of a
quinolinyl moiety and an -amino acid unit have been reported.
In previous work, we reported that substituted 2-chloro-3-
formylquinolines were key building blocks in the synthesis of
various quinoline-containing heterocycles.6 We describe herein
°C, r.t. or 60 °C).
.

2
Tetrahedron Letters
Table 1: Synthesis of quinolin-3-yl imines 2 and α-aminonitriles 3.
R1
R1
R1
CN
R2
R3
CHO
Cl
R2
R3
R2
R3
R'
R'NH2
N
NR'
t-BuMe2SiCN,
H
MeOH, r.t.
N
N
Cl
CH3CN, r.t.
N
Cl
R4
R4
R4
3
1
2
R1
R2
R3
H
R4
R′
i-Pr
Product
Mp (°C)
63-65
Yielda (%)
Product
Mp (°C)
91-93
Yielda (%)
H
OMe
H
H
H
H
OMe
H
90
77
98
97
78
76
60
93
87
83
96
90
89
93
88
92
87
91
2a
2b
2c
2d
2e
2f
3a
3b
3c
3d
3e
3f
H
CH2Ph
CH2Ph
CH2Ph
CH2Ph
120-121
55-57
112-113
63-65
H
H
H
OMe
H
H
H
60-61
87
H
H
Me
H
101-103
201-202
101-103
68-70
120-122
166-168
134-136
103-106
107-109
H
H
OMe
H
3,5-Me2C6H3
4-MeC6H4
CH2Ph
H
H
H
2g
2h
2i
3g
3h
3i
H
Me
H
H
H
H
H
H
4-MeOC6H4
102-105
a Yield of isolated pure products.
Table 2: Synthesis of quinolin-3-ylcarboxamides 6.
Acid-catalysed hydrolysis of 3h with concentrated sulfuric acid
in methanol or in AcOH furnished 2-oxoquinolin-3-carbaldehyde
4h as the major product which resulted from simultaneous
hydrolysis of the -aminonitrile and 2-chloroquinoline moieties.
At 0 °C, concentrated hydrochloric acid led to the N-benzyl -
amino acid hydrochloride 5h as a white solid in a 93% yield
(Scheme 2). Their structures were respectively established by
comparison with NMR data from the literature for 4h 9 and by 1H,
13C and IR spectroscopy and mass spectrometry for 5h.10
Unfortunately, attempted hydrogenolysis of -amino acid 5h
using H2/Pd-C mainly led to its decomposition (Scheme 2).
CN
CONH2
R2
R'
R2
R'
N
Conc. H2SO4
N
H
H
CH2Cl2, 0 °C to r.t.
N
Cl
N
Cl
R4
R4
6
3
Entry
Product
6c
R2
H
R4
R′
Yield a (%)
1
2
3
4
H
Me
H
CH2Ph
CH2Ph
CH2Ph
67
75
70
73
H
6e
Me
CHO
O
i or ii
Me
H
6h
N
CN
H
H
4-MeOC6H4
6i
Me
4h
N
a Yield of isolated pure products.
H
CO2H
N
Cl
Me
iii
N
With these -amino amides in hand, we next investigated the
transformation of 6e, chosen as model compound, into the
corresponding -amino ester. Treatment with methanol catalyzed
by Amberlyst 15,12 followed by hydrogenolysis with H2 in the
presence of Pd(OH)2 and HCl yielded the racemic derivative 8e
in a 55% overall yield (Scheme 3).
3h
H
H
O
N
H
Cl
5h
Scheme 2. Hydrolysis of aminonitrile 3h. i. H2SO4/MeOH, reflux. ii. H2SO4
(80%)/AcOH, 75-80 °C. iii. Conc. HCl, 0 °C to rt, 93%.
CO2CH3
NH3 Cl
O
CO2CH3
Under slightly modified conditions [addition of concentrated
H2SO4 to a pre-cooled (0 °C) solution of  in CH2Cl2],11 -
aminonitriles 3c, 3e, 3h and 3i were readily hydrolysed to give
aminocarboxamides 6 after standard work-up with NH4OH
(pH=8-9) (Table 2). The 1H and 13C NMR spectra exhibited
signals that confirmed these transformations, respectively, at 4.58
to 4.71 ppm for ArCH(CONH2)NHBn, instead of 5.13 to 5.20
ppm for the ArCH(CN)NHBn protons, and 173.2 to 173.4 ppm
for the ArCH(CONH2)NHBn carbons, instead of 117.6 to 117.8
ppm for ArCH(CN)NHBn.
ii
i
N
H
6e
N
H
N
O
H
CH3
CH3
7e
8e
Scheme 3. Synthesis of -amino ester 8e. i. MeOH, Amberlyst 15, reflux,
58%. ii. H2, Pd(OH)2 (0.1 eq.), HCl 1M (2 eq.), 95%.
To extend this work to the preparation of optically active
derivatives containing a quinolin-3-yl moiety, we applied the
Strecker reaction to enantiomerically pure amines. Chiral -
methylbenzylamines are commonly used as chiral auxilliaries in
such processes 3a,c,d,e,g which led us to synthesise the aldimine (+)

3
2j in 94% yield from 2-chloroquinolin-3-carboxaldehyde and (S-
-methylbenzylamine [[]D20= +179.1 (c 1.02, CH2Cl2)].
Me
N
Figure 4: ORTEP plot of the X-ray crystal structure of (2R,3S)-6j.
N
Cl
2j
Displacement ellipsoids are drawn at the 50% probability level.13
H2N
O
MeO
O
Me
Me
Figure 1: ORTEP plot of the X-ray crystal structure of 2j. Displacement
ellipsoids are drawn at the 50% probability level.13
R N
ii
i
S
R N S
(R, S)-3j
H
H
N
Cl
N
H
O
Conversion into the corresponding -aminonitrile 3j was
achieved in 84% yield with a 7/3 diastereoselectivity according to
the previously described protocol (Scheme 4).
(R, S)-6j
(R, S)-7j
iii
COOCH3
+
NH3 Cl -
CN Me
CHO
i.
N
N
O
H
H
ii.
N
Cl
N
Cl
8j
ee : 40%
3j
de : 40%
Scheme 5. Synthesis of enantioenriched -amino ester 8j. 18 i. Conc. H2SO4
(33 eq.), CH2Cl2, 0 °C to r.t, NH4OH, 65%. ii. MeOH, Amberlyst 15, reflux,
62%. iii. H2, Pd(OH)2 (0.1 eq.), HCl 1M (2 eq.), 92%.
Scheme 4. Diastereoselective synthesis of α-aminonitrile 3j. i. 1 eq. (S)--
methylbenzylamine, MeOH, r.t. 94%. ii. 1.2 eq. t-BuMe2SiCN, CH3CN, H2O,
r.t. 84%.
In a parallel approach, to try to circumvent epimerization,
imine 2k derived from 1-(R)-4-methoxyphenyl)ethanamine was
similarly prepared in a 95% yield.19 The Strecker reaction easily
afforded the aminonitrile 3k, albeit in a lower diastereomeric
ratio (55/45) when compared with 3j. After separation by
crystallization, the major (S,R) isomer was directly treated with
cerium ammonium nitrate to cleave the chiral auxiliary.
Unfortunately, 2-chloroquinolin-3-ylcarboxylic acid was the only
isolated product as a white solid in 93% yield,20 which was
attributed to decomposition of -aminonitrile 3k into the starting
aldehyde and its further oxidation (Scheme 6).21
While the separation of the two diastereomers failed using
standard chromatographic methods, fractional crystallization
from
a CH2Cl2/petroleum ether (1:9) solution at room
temperature afforded needles of the major isomer. Single-crystal
X-ray analysis showed the major isomer to possess (S)
configurations for the two stereocenters (Figure 3).14 The
15
structure of the minor diastereomer (2R,3S)-3j was secured by
X-ray crystallographic analysis (Figure 4).
CN Me
i
CO2H
N
H
N
Cl
N
Cl
3k
OMe
Scheme 6. Oxidation of -aminonitrile (S,R)3k. i. CAN, CH3CN/H2O (4:1),
45 min, 0 °C-r.t., 93%.
Figure 2: ORTEP plot of the X-ray crystal structure of (2S,3S)-3j.
Displacement ellipsoids are drawn at the 50% probability level.14
In summary, we have described an easy access to new non-
natural -amino acid derivatives by cyanation of the
corresponding quinolin-3-ylimines using t-BuMe2SiCN as the
cyanide source. In most cases, quantitative yields and pure
products were obtained without the need for chromatographic
separation. When the asymmetric synthesis of an -amino amide
bearing a quinoline unit was successfully achieved from (S)--
methylbenzylamine as the chiral auxiliary, partial epimerization
occurred during the methanolysis and the N-deprotection steps.
Figure 3: ORTEP plot of the X-ray crystal structure of (2R,3S)-3j.
Displacement ellipsoids are drawn at the 50% probability level.13
Finally, the minor (R,S) derivative was converted into the
corresponding amide 6j16 and methanolyzed before N-
deprotection by hydrogenolysis (Scheme 5). Derivatization with
O-acetyl-(R)-mandelic acid gave two diastereomers (ratio: 70/30)
that revealed partial racemization. 17
Acknowledgements
We thank MESRS (Ministère de l’Enseignement Supérieur et
de la Recherche Scientifique) Algeria, for financial support.

4
Tetrahedron Letters
a = 5.9047(2)Å, b = 2.5394(6)Å, c = 21.3951(9)Å, V = 1584.12(11)Å3, Z
References and notes
= 4, c= 1.349 g.cm3, F(0 0 0) = 672, crystal size: 0.52 x 0.18 x 0.14 mm.
Crystal structure analysis: for (R)-2-(2-chloroquinolin-3-yl)-2-[N-(S)--
methylbenzylamino]carboxamide (6j): C19H18ClN3O, Mr = 339.81 g.
mol-1, monoclinic, space group P21(4), a = 9.2574(2) Å, b = 6.6265(2) Å,
c = 14.2529(4) Å,  = 104.0370(10)°, V = 848.22(4) Å3, Z = 2, ρc=1.33
1. (a) Amino Acids, Peptides and Proteins in Organic Chemistry, Hughes,
A.B. Ed., Wiley-VCH, Weinheim, 2011. (b) Asymmetric Synthesis and
Application of -Amino Acids; Soloshonok, K.; Izawa, V. A. Eds., ACS.
Symposium series 1009, ACS: Washington DC, 2009. (c) Najera, C.;
Sansano, J. M. Chem. Rev. 2007, 107, 4584-4671.
g.cm3, F(0
0 0) = 356, crystal size: 0.51 x 0.13 x 0.12 mm.
Crystallographic data (excluding structure factors) for these compounds
have been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication numbers CCDC 898280 for 2j, CCDC
898281 for 3j and CCDC 898282 for 6j. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif./cif.
2. (a) Wang, J.; Liu, X.; Feng, X. Chem. Rev. 2011, 111, 6947-6983. (b)
Merino, P.; Marques-Lopez, E.; Tejero, T.; Herrera, R. P. Tetrahedron,
2009, 65, 1219-1234. (c) Gawronski, J.; Wascinska, N.; Gajewy, J.
Chem. Rev. 2008, 108, 5227-5252.
3. For some recent references, see: (a) Rajabi, F.; Nourian, S.; Ghiassian,
S.; Balu, A. M.; Saidi, M. R.; Serrano-Ruiz, J. C.; Luque, R. Green
Chem. 2011, 13, 3282-3289. (b) Cherian, J.; Choi, I.-H.; Nayyar, A.;
Manjunatha, U. H.; Mukherjee, T.; Lee, Y-S.; Boshoff, H. I.; Singh, R.;
Ha, Y-H; Goodwin, M.; Lakshminarayana, S. B.; Niyomrattanakit, P.;
Jiricek, J.; Ravindran, S.; Dick, T.; Keller, T. H.; Dartois, V.; Barry, C.
E. J. Med. Chem. 2011, 54, 5639-5659. (c) Ouizem, S.; Cheramy, S.;
Botuha, C.; Chemla, F.; Ferreira, F.; Perez-Luna, A. Chem. Eur. J. 2010,
16, 12668-12677. (d) Reddy, B. M.; Thirupathi, B.; Patil, M. K. J. Mol.
Catal. A: Chem. 2009, 307, 154-159. (e) Filosa, R.; Fulco, M. C.;
Marinozzi, M.; Giacche, N.; Macchiarulo, A.; Peduto, A.; Massa, A.; de
Caprariis, P.; Thomsen, C.; Christoffersen, C. T.; Pellicciari, R. Bioorg.
Med. Chem. 2009, 17, 242-250. (f) Mojtahedi, M. M.; Abaee, M. S.;
Alishiri, T. Tetrahedron Lett. 2009, 50, 2322-2325.
4. (a) Montalban, A. G. Heterocycles in Natural Product Synthesis Ed.,
Wiley-VCH., New York, 2011, pp 299-339. (b) Wang, X.-J.; Gong, D.-
L.; Wang, J.-D.; Zhang, J.; Liu, C.-X.; Xiang, W.-S. Bioorg. Med. Chem.
Lett. 2011, 21, 2313-2315. (c) Michael, J. P. Nat. Prod. Rep. 2007, 24,
223-246. (d) Kumar A.; Katiyar S.B.; Agarwal A.; Chauhan P.M.S. Curr.
Med. Chem. 2003, 10, 1137-1150.
5. (a) Alajarin, R.; Burgos, C. J. Modern Heterocyclic Chemistry, Ed.,
Wiley-VCH., New York, 2011, pp 1527-1629. (b) Dietrich, S. A.;
Lindauer, R.; Stierlin, C.; Gertsch, J.; Matesanz, R.; Notararigo, S.; Diaz,
J. F.; Altmann, K.-H. Chem. Eur. J. 2009, 15, 10144-10157. (c)
Rodriguez Sarmiento, R. M.; Nettekoven, M. H.; Taylor, S.; Plancher, J.-
M.; Richter, H.; Roche, O. Bioorg. Med. Chem. Lett. 2009, 19, 4495-
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Chem. Biol. Drug Des. 2009, 74, 80-86. (e) Kouznetsov, V. V.; Gomez-
Barrio, A. Eur. J. Med. Chem. 2009, 44, 3091-3113. (f) Wu, D.
Tetrahedron, 2003, 59, 8649-8687.
6. a) Hayour, H.; Bouraiou, A.; Bouacida S.; Berrée, F.; Carboni, B.; Roisnel,
T.; Belfaitah, A. Tetrahedron Lett. 2011, 52, 4868-4871. (b) Bouraiou,
A.; Berrée, F.; Bouacida, S.; Carboni, B.; Debache, A.; Roisnel, T.;
Belfaitah, A. Lett. Org. Chem. 2011, 8, 374-377. (c) Bouraiou, A.;
Debache, A.; Rhouati, S.; Benali-Cherif, N.; Carboni, B.; Belfaitah, A.
Open Org. Chem. J. 2010, 4, 1-7. (d) Bouraiou, A.; Debache, A.;
Rhouati, S.; Carboni, B.; Belfaitah, A. J. Heterocycl. Chem. 2008, 45,
329-333. (e) Menasra, H.; Kedjadja, A.; Rhouati, S.; Carboni, B.;
Belfaitah, A. Synth. Commun. 2005, 35, 2779-2788.
14. Belfaitah, A.; Ladraa, S.; Bouraiou, A.; Benali-Cherif, N.; Debache, A.;
Rhouati, S. Acta Cryst. 2006, E62, o1355.
15. Selected properties and spectral data for (R)-2-(2-chloroquinolin-3-yl)-2-
[N-[(S)--methylbenzylamino]acetonitrile (+)-3j: White crystals; mp.
1
145-146 °C. []D20= + 9.6 (c=1.0, CH2Cl2). H (300 MHz, CDCl3): 8.31
(s, 1H), 8.05 (d, J =8.4 Hz, 1H), 7.95-7.75 (m, 2H), 7.71 (d, J =8.0 Hz,
1H), 7.45-7.20 (m, 5H), 5.25 (d, J =9.6 Hz, 1H), 4.12 (q, J =6.4 Hz, 1H),
2.08 (d, J =9.6 Hz, 1H), 1.51 (d, J =6.4 Hz, 3H). 13C NMR (75.4 MHz,
CDCl3): 148.9, 147.4, 143.5, 141.9, 137.9, 131.4, 128.7, 128.3, 127.8,
127.7, 126.8, 126.7, 126.6, 117.7, 56.6, 49.9, 22.7. Anal. Calcd for
C19H16ClN3: C, 70.91; H, 5.01; N, 13.06. Found: C, 71.17; H, 4.99; N,
13.22.
16. Selected properties and spectral data for (R)-2-(2-chloroquinolin-3-yl)-2-
20
[N-(S)--methylbenzylamino]carboxamide (-)-6j: 65% yield. []D = -
139.5 (c 1.08, CH2Cl2). IR max (KBr) 3344, 1508 cm-1. 1H NMR (300
MHz, CDCl3): 7.89 (d, J = 8.5 Hz, 1H), 7.82 (s, 1H), 7.66 (d, J = 8.2 Hz,
1H), 7.60 (td, J =8.4, 1.5 Hz, 1H), 7.43 (td, J =8.4, 1.1 Hz, 1H), 7.25-715
(m, 5H), 6.74 (br s, 1H), 4.23 (s, 1H), 3.50 (q, J = 6.5 Hz, 1H), 1.21 (d, J
= 6.5 Hz, 3H). 13C NMR (75.47 MHz, CDCl3): 173.2, 149.3, 147.0,
143.2, 140.0, 130.7, 130.0, 128.9, 128.2, 127.7, 127.5, 126.9, 62.3, 55.9,
24.1. HRMS : m/z [M+Na]+ Calcd. for C19H18N3OClNa: 362.1036;
found: 362.1035.
17. Procedure for derivatization of 8j with O-acetyl-(R)-mandelic acid.
To a solution of O-acetyl-(R)-mandelic acid (7 mg, 0.037 mmol) in dry
CH2Cl2 (1 mL), were added, at 0 °C, EDCI (9 mg, 0.048 mml), HOBT (6
mg, 0.045 mmol) and N-methylmorpholine (16 mL, 0.14 mmol). After
30 min at 0 °C, a solution of 8j (10 mg, 0.037 mmol) in dry CH2Cl2 (1
mL) was added to the reaction mixture. The reaction was stirred at rt
overnight then Et2O (3 mL) was added. The organic phase was washed
with 0.1 M HCl (3x1 mL), H2O (2x1 mL), brine (1 mL) then dried,
filtered and concentrated under reduced pressure to give the
corresponding product as a mixture of two diastereomers (ratio: 70/30).
Characteristic signals for the major diastereomer : 1H NMR (500 MHz,
CDCl3): 6.20 (s, 1H), 5.58 (d, J = 8.4 Hz, 1H), 3.73 (s, 3H).
Characteristic signals for the minor diastereomer : 1H NMR (500 MHz,
CDCl3): 6.15 (s, 1H), 5.71 (d, J = 8.5 Hz, 1H), 3.76 (s, 3H).
18. Selected properties and spectral data for (R)-2-(1,2-dihydro-2-
20
7. Datta, N. J.; Khunt, R. C.; Parikh, A. R. Ind. J. Chem. 2002, 41B, 433-
435.
8. Atherton, J. H.; Blacker, J.; Crampton, M. R.; Grosjean, C. Org. Biomol.
Chem. 2004, 2, 2567-2571.
oxoquinolin-3-yl)-2-aminomethyl acetate (-)-8j. 92% yield. []D = -
52.8 (c 0.75, MeOH). IR max (KBr) 1749, 1652 cm-1. 1H NMR (400
MHz, MeOD): 8.28 (s, 1H), 7.80 (d, J = 7.8 Hz, 1H), 7.67 (t, J = 7.7 Hz,
1H), 7.44 (d, J = 7.9 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H), 5.29 (s, 1H), 3.86
(s, 3H). 13C NMR (100 MHz, MeOD): 170.1, 163.7, 145.3, 141.1, 134.1,
130.8, 125.9, 125.3, 121.4, 117.6, 55.6, 55.0. HRMS : m/z [M+H]+
Calcd. for C12H13N2O3: 233.0926; found: 233.0927.
9. Curreli, F.; Zhang, H.; Zhang, X.; Pyatkin, I.; Victor, Z.; Altieri, A.;
Debnath, A. K. Bioorg. Med. Chem. 2011, 19, 77-90.
10. Selected spectral data for 2-benzylamino-2-(1,2-dihydro-6-methyl-2-
oxoquinolin-3-yl)acetic acid hydrochloride 5h. White solid. mp 218 °C.
IR max (KBr) 3421, 1743, 1651 cm-1. 1H NMR (250 MHz, DMSO-d6):
12.20 (br s, 1H), 9.60-10.00 (br s, 2H), 8.06 (s, 1H), 7.65-7.20 (m, 8H),
5.14 (s, 1H), 4.17 (s, 2H), 2.34 (s, 3H). 13C NMR (62.9 MHz, DMSO-d6):
 168.6, 161.0, 142.4, 137.2, 133.3, 132.1, 131.7, 130.7, 130.7, 129.4,
128.9, 128.9, 128.2, 123.6, 118.7, 115.7, 58.2, 49.8, 20.7. HRMS (ESI):
m/z [M – HCl + Na]+ Calcd for C19H18N2O3Na: 345.1215. Found:
345.1212.
11. Truong, M.; Lecornué, F.; Fadel, A. Tetrahedron: Asymmetry 2003, 14,
1063-1072.
12. Katritzky, A. R.: Latif, M.; Noble, G.; Harris, P. Synthesis 1990, 999-
1001.
19. Ladraa, S.; Bouraiou, A.; Bouacida, S.; Roisnel T.; Belfaitah, A. Acta
Cryst. 2009, C65, o475-o478.
20. (a) Ladraa, S.; Bouraiou, A.; Bouacida, S.; Roisnel T.; Belfaitah, A. Acta
Cryst. 2010, E66, o693. (b) Leleu, S.; Papamicael, C.; Marsais, F.;
Dupas, G. Levacher, V. Tetrahedron: Asymmetry, 2004, 15, 3919-3928.
21. While this work was in progress, it was shown that treatment of (S,S)-α-
aminonitriles derived from (S)-1-(4-methoxyphenyl)ethylamine and
arylaldehydes in 6 M aqueous HCl at reflux resulted in cleavage of their
chiral auxiliary fragments and concomitant hydrolysis of their nitrile
groups. Perez-Fuertes, Y.; Taylor, J. E.; Tickell, D. A.; Mahon, M. F.;
Bull, S. D.; James, T. D. J. Org. Chem. 2011, 76, 6038-6047.
13. Crystal structure analysis for 2-chloro-3-[(S)--methylbenzylimino]
methylquinoline (2j): C18H15ClN2, Mr = 294,7 g.mol-1, monoclinic, space
group P21(4), a = 8.0353 (3) Ǻ, b = 13.7059 (6) Ǻ, c = 13.4665 (6) Ǻ,  =
94.717 (2)°, V = 1478.06 (11) Å3, Z = 4, c= 1.325 g.cm3, F(0 0 0) = 616,
crystal size: 0.24 x 0.13 x 0.03 mm. Crystal structure analysis for (R)-2-
(2-chloroquinolin-3-yl)-2-[N-[(S)--methylbenzylamino]acetonitrile (3j):
C19H16ClN3, Mr = 321.8 g.mol-1, orthorhombic, space group P212121(19),