Mn(III) salen complexes-catalyzed enantioselective addition of trimethyl silylcyanide to N-benzylimines in the presence of 4-phenyl pyridine-N-oxide as an additive

Article abstract of DOI:10.1016/j.tetasy.2010.07.003

Chiral monomeric and dimeric Mn(III) salen complexes viz., [(S,S)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminato manganese(III) chloride and 5,5-methylene di-[(S,S)-{N-(3-tert-butyl salicylidine)-N′-(3′,5′-di-tert-butyl salicylidene)}-1,

Full text of DOI:10.1016/j.tetasy.2010.07.003

Tetrahedron: Asymmetry 21 (2010) 2076–2080
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Mn(III) salen complexes-catalyzed enantioselective addition of trimethyl
silylcyanide to N-benzylimines in the presence of 4-phenyl pyridine-N-oxide
as an additive
*
Noor-ul H. Khan , S. Saravanan, Rukhsana I. Kureshy, Sayed H. R. Abdi, Hari C. Bajaj
Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSMCRI), Council of Scientific and Industrial Research (CSIR), G. B.
Marg, Bhavnagar 364 002, Gujarat, India
a r t i c l e i n f o
a b s t r a c t
Chiral monomeric and dimeric Mn(III) salen complexes viz., [(S,S)-N,N0-bis(3,5-di-tert-butylsalicylidene)-
1,2-cyclohexanediaminato manganese(III) chloride and 5,5-methylene di-[(S,S)-{N-(3-tert-butyl salicyli-
dine)-N0-(30,50-di-tert-butyl salicylidene)}-1,2-cyclohexanediaminato manganese(III) chloride were used
as catalysts for the highly enantioselective Strecker reaction of various imines (derived by the condensa-
tion of aldehydes and amine) with TMSCN as a source of cyanide in toluene. Excellent yield (95%) of
Article history:
Received 17 May 2010
Accepted 1 July 2010
Available online 31 July 2010
a
-amino nitrile with ee >99% was achieved when N-(2-methoxybenzylidine)-1-phenylmethanamine
was used as a substrate and 4-phenyl pyridine-N-oxide (4-PPNO) as an additive at ꢀ55 °C in 28 h. The
dimeric catalyst was found to be more reactive and enantioselective than the monomeric catalyst. The
chiral dimeric catalyst used in the present study was recoverable and recyclable several times with reten-
tion of its performance.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
recyclable catalysts, earlier we have reported the applications of chi-
ral Mn(III) salen complexes in various organic transformations viz.,
The classical Strecker reaction is one of the simplest and most
asymmetric cyantion of ketones,42 epoxidation of non-functional-
ized alkenes,43–46 and oxidative kinetic resolution of secondary alco-
hols.47,48 Herein, we have explored the use of chiral monomeric and
dimeric Mn(III) salen complexes as efficient catalysts for the asym-
metric Strecker reaction of imines using TMSCN as cyanide source.
economical methods for the production of racemic a-amino acids
and pharmacologically useful compounds.1–3 The enantioselective
versions of this process are of great interest, due to the application
of (R)- and/or (S)-
gen-containing heterocycles such as imidazoles, thiodiazoles, and
others.8–11 To prepare
-amino nitrile (precursor to -amino acids)
a
-amino acids4–7 in the synthesis of valuable nitro-
Excellent yields (up to 95%) of
a-amino nitriles were achieved in
a
a
high ees (99%) when chiral dimeric complex 2 was used as a catalyst
in the presence of 4-phenyl pyridine-N-oxide as an additive. The
complex 2 was recycled efficiently for several times.
generally an imine is reacted with a cyanide source, notable among
them are HCN,12 KCN,13 (EtO)2P(O)CN, Et2AlCN, Bu3SnCN, and
TMSCN.14–20 Among these cyanide sources, TMSCN is relatively easy
to handle and highly soluble in organic solvents. In order to route the
Strecker reaction through an enantioselective pathway, usually a
chiral catalyst is required. In recent years, considerable efforts have
been made toward the development of chiral catalytic systems for
the Strecker reaction5 using organocatalysts,13,21–25 Jacobsen0s
Schiff base complexes,26–29 bifunctional catalyst,30 and various
metal complexes of salen ligands.31–39 Among these, Jacobsen salen
complexes have emerged as efficient catalysts for the asymmetric
Strecker reaction.31,40 Although, Jacobsen salen complexes are
highly efficient, their recyclability is an important issue from an eco-
nomical and an environmental point of view. In view of our ongoing
interest in the development of asymmetric Strecker reaction41 and
2. Results and discussion
Chiral monomeric and dimeric Mn(III) salen complexes 1 and 2
were synthesized by the reaction of (1S,2S)-N,N0-bis[3,5-di-tert-
butylsalicylidene] cyclohexane-1, 2-diamine/5,5-methylenedi-[(1S,
2S)-{N-(3-tert-butylsalicylidine)-N0-(30,50-di-tert-butylsalicylid-
ene)]-1,2-cyclohexanediamine] with manganese acetate followed
by the addition of LiCl under auto-oxidation condition (Fig. 1).46
To assess the viability of chiral monomeric Mn(III) salen com-
plex 1 as a catalyst (15 mol %) in the asymmetric Strecker reaction,
we have initiated our systematic study by taking 4-methoxy imine
7 as a model substrate with TMSCN in toluene at ꢀ20 °C. Moderate
isolated yield (65%) and enantioselectivity (ee, 52%) for the product
a
-amino nitrile were achieved in 18 h (Table 1, entry 1). It has been
* Corresponding author. Tel.: +91 0278 2567760; fax: +91 0278 2566970.
E-mail address: khan251293@yahoo.in (N.-u. H. Khan).
reported in the literature that the use of an additive affords a
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.07.003

N.-u. H. Khan et al. / Tetrahedron: Asymmetry 21 (2010) 2076–2080
2077
as in the case of (R)-Prl and (S)-Prl played no role in the enantiose-
lectivity of the reaction (entries 2 and 3). Among the various addi-
tives used, 4-PPNO was found to be the most efficient to give the
desired product in high isolated yield (80%) and ee (71%) (entry
5). Having established that 4-phenyl pyridine N-oxide 4-PPNO as
an additive is the most suitable, we next varied the loadings of
additive (4-PPNO) and catalyst 1 for this reaction. Accordingly,
we first increased the additive loading from 15 mol % to 20 mol %
at a catalyst loading of 15 mol % by keeping the other reaction con-
ditions constant. However, this change was inconsequential as
there was only a marginal increase in isolated yield with no change
in enantioselectivity (entry 7). However, on decreasing the additive
loading (10 mol %) there was a decrease in the yield and enantiose-
lectivity (yield, 71%; ee, 62%) (entry 8). Further, when the catalyst
loading was increased from 15 mol % to 20 mol % keeping the opti-
mum additive loading (15 mol %) there was only a slight increase
in the isolated yield of the product with no significant change in
the enantioselectivity of the product (entry 9). A decrease in the
catalyst loading to 10 mol % caused a decrease in the yield and
enantioselectivity (entry 10; yield, 73%; ee, 64%). Thus, the use of
4-phenyl pyridine N-oxide 4-PPNO (15 mol %) as an additive and
catalyst 1 (15 mol %) is optimum to catalyze the enantioselective
Strecker reaction of 4-methoxy imine 7 with TMSCN at ꢀ20 °C (en-
try 5). Temperature also plays a crucial role in achieving high chiral
induction in asymmetric catalysis. Therefore, we varied the reac-
tion temperature in a stepwise manner. Consequently, an increase
N
O
N
O
Mn
Cl
1
N
O
N
O
N
O
N
O
Mn
Cl
Mn
Cl
H2
C
2
Figure 1. Structure of the catalysts 1 and 2.
beneficial effect on the reaction rate and enantioselectivity.42 Thus
we have examined the role of different additives viz., (R)-proline
(R)-Prl, (S)-proline (S)-Prl, (S)-mandelic acid (S)-Mand, 4-phenyl
pyridine N-oxide 4-PPNO, and pyridine N-oxide PNO for this reac-
tion (Table 1, entries 2–6). Noticeably, the chirality of the additive
Table 1
Data for the optimization of reaction conditions for asymmetric addition of TMSCN to 4-MeO benzylimine 7 as a representative substrate in the presence of Mn(III) salen complex
1a
CN
Catalyst 1, Additive
N
H
N
TMSCN
Temperature, Solvent
MeO
MeO
7'
7
O
N
O
HO
COOH
(R)
(S)
O
(S)
O
N
N
H
N
H
OH
(R)-Prl
OH
(S)-Prl
PNO
Yieldb (%)
4-PPNO
(S)-Mand
Time (h)
Entry
Catalyst (mol %)
Additive (mol %)
Solvent
Temp (°C)
eec (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
15
15
15
15
15
15
15
15
20
10
15
15
15
15
15
15
15
15
—
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
CH2Cl2
18
12
12
15
10
8
10
10
8
12
3
6
12
16
36
28
28
28
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
rt
65
65
68
62
80
79
83
71
87
73
92
85
88
90
91
80
78
60
52
56
58
58
71
60
71
62
71
64
30
44
72
77
83
24
(R)-Prl (15)
(S)-Prl (15)
(S)-Mand (15)
4-PPNO (15)
PNO (15)
4-PPNO (20)
4-PPNO (10)
4-PPNO (15)
4-PPNO (15)
4-PPNO (15)
4-PPNO (15)
4-PPNO (15)
4-PPNO (15)
4-PPNO (15)
4-PPNO (15)
4-PPNO (15)
4-PPNO (15)
0
ꢀ30
ꢀ40
ꢀ55
ꢀ55
ꢀ55
ꢀ55
CHCl3
THF
10
Racemic
a
b
c
Strecker reaction of 4-methoxy imine 7 was carried out with 1.5 equiv of TMSCN by using catalyst 1 in the presence of various additives.
Isolated yield.
Ee were determined by using chiral OD column.

2078
N.-u. H. Khan et al. / Tetrahedron: Asymmetry 21 (2010) 2076–2080
Optimization of reaction condition
100
80
60
40
20
0
% Yield
% ee
Solvent
Additive mol%
Cat. mol%
0
15 15 15 15 15 20 10 15 15 15 15 15 15 15 15 15 15
15 15 15 15 15 15 15 15 20 10 15 15 15 15 15 15 15 15
18 12 12 15 10
8
10 10
8
12
3
6
0
10 16 36 28 28 28 Time (h)
Temp (O C)
-20 -20 -20 -20 -20 -20 -20 -20 -20 -20 RT
-30 -40 -55 -55 -55 -55
Figure 2. Optimization graph for the enantioselective addition of TMSCN to 4-MeO N-benzyl imines (e) using the catalyst 1.
in reaction temperature (from ꢀ20 °C to 27 °C) caused an increase
in the product yield (85–92%) in a shorter reaction time but there
was a significant decrease in the enantioselectivity (44–30%) (en-
tries 11 and 12). On the other hand, lowering of the reaction tem-
perature (ꢀ30 to ꢀ55 °C) caused significant improvement in
enantioselectivity (ee 83%) (entries 13–15), but the reaction took
longer time (12–36 h) for completion. Hence, ꢀ55 °C was taken
as the optimum reaction temperature for the present protocol for
the product were achieved in the case of toluene as solvent (entry,
15) (Fig. 2).
To examine the general applicability of the above optimized
reaction conditions, (Table 1, entry 15) we next carried out Strec-
ker reaction of various N-benzyl imines 3–13 with catalyst 1 and
the results are summarized in Table 2. Good to excellent isolated
yield (60–88%) and ee (60–85%) of a-aminonitriles were achieved
in most of the cases, which clearly show the usefulness of this pro-
tocol over a range of substrates synthesized from aromatic alde-
hyde and benzylamine (entries 1, 3, 5, 7, 9, 11, 13, 15, 17, 19).
Surprisingly, electronic and steric factors for different substituents
on N-benzyl imines did not have a noticeable effect on the yield
and enantioselectivity of the products. In addition to this, N-ben-
zylimine derived from aliphatic aldehydes and benzylamine gave
the synthesis of various a-amino nitriles. We next varied the reac-
tion medium bearing in mind that the reactivity and enantioselec-
tivity of the Strecker reaction are strongly dependent on the nature
of the solvent used.31,41 Therefore, the above optimized parameters
(entry 15) were then used for the asymmetric Strecker reaction of
4-methoxy imine 7 in different solvents viz., toluene, dichloro-
methane, chloroform, and THF (Table 1; entries 15–19). Among
all the solvents used the best results in terms of yield and ee of
the respective
a-aminonitriles in moderate isolated yield and ee
(Table 2, entry 21).
Table 2
Asymmetric addition of TMSCN to various N-benzyl imines 3–13 catalyzed by monomeric and dimeric Mn(III) salen complexes 1 and 2a
CN
Catalysts 1,2 (15 mol%)
R
N
TMSCN
R
N
H
Toluene, -55oC
4PPNO(15 mol%)
R = C6H5 3
R = 2-MeO-C6H4 9
R = 4-Cl-C6H4 10
R = 4-F-C6H4 11
R = C10H7 12
R = 4-Me-C6H4 4
R = 3-Me-C6H4 5
R = 2-Me-C6H4 6
R = 4-MeO-C6H4 7
R = 3-MeO-C6H4 8
3'-13'
R = (CH3)3CH 13
S. No.
Imine
C6H5CH@NHCH2C6H5
4-MeC6H4CH@NHCH2C6H5
3-MeC6H4CH@NHCH2C6H5
2-MeC6H4CH@NHCH2C6H5
4-MeOC6H4CH@NHCH2C6H5
3-MeOC6H4CH@NHCH2C6H5
2-MeOC6H4CH@NHCH2C6H5
4-ClC6H4CH@NHCH2C6H5 10
4-FC6H4CH@NHCH2C6H5 11
Time (h)
Yieldb (%)
eec (%)
1 (2)
3 (4)
5 (6)
7 (8)
9 (10)
11 (12)
13 (14)
15 (16)
17 (18)
19 (20)
21 (22)
3
36 (28)
36 (28)
36 (28)
36 (28)
36 (28)
36 (28)
36 (28)
36 (28)
36 (28)
36 (28)
36 (28)
72 (80)
75 (85)
70 (83)
72 (78)
88 (88)
71 (80)
75 (95)
64 (70)
68 (75)
60 (70)
73 (76)
64 (88)
72 (78)
63 (91)
60 (68)
83 (85)
64 (74)
85 (>99)
65 (74)
72 (80)
70 (75)
68 (73)
4
5
6
7
8
9
N-Benzyl-1-naphthylimine 12
(CH3)3CH@NHCH2C6H5 13
a
Reaction was carried out at ꢀ55 °C in toluene using 15 mol % of catalysts 1 and 2 in the presence of 4-phenyl pyridine N-oxide 4-PPNO (15 mol %) with N-benzyl imines
3–13 using 1.5 equiv of TMSCN.
b
Isolated yield.
c
Ee were determined using chiral OD and OD-H column.

N.-u. H. Khan et al. / Tetrahedron: Asymmetry 21 (2010) 2076–2080
2079
Table 3
Catalyst
in KBr window. High-resolution mass spectra were obtained with
an LC–MS (Q-TOF) LC (Waters), MS (Micromass) instruments. Opti-
cal rotation was measured witha Digipol 781 Automatic Polarimeter
Rudolph Instruments. Enantiomeric excess (ee) were determined by
HPLC (Shimadzu SCL-10AVP) using Daicel Chiralpak OD-H and OD
chiral columns with 2-propanol/hexane as the eluent. For the prod-
uct purification flash chromatography was performed using silica
gel 100–200 mesh, manganese acetate purchased from s.d. Fine-
Chem Limited Mumbai (India). TMSCN, benzaldehyde, 2-methoxy
benzaldehyde, 3-methoxybenzaldehyde, 4-methoxy benzaldehyde,
4-fluoro benzaldehyde, 4-chlorobenzaldehyde, trimethylacetalde-
hyde, 1-naphthaldehyde, (Aldrich Chemicals) 2-methyl benzaldehyde,
3-methyl benzaldehyde, 4-methyl benzaldehyde, and benzylamine
(Merck Chemicals) were used as received. The monomeric and dimeric
Mn(III) salen complexes 1 and 2 were synthesized by the interaction of
[(S,S)-N,N0-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine/
5,5-methylene di-[(S,S)-{N-(3-tert-butylsalicylidine)-N0-(30,50-di-
tert-butylsalicylidene)]-1,2-cyclohexanediamine] with manganese
acetate followed by the addition of LiCl under auto-oxidation pro-
cess by our previously reported method.46 All the solvents were dis-
tilled, dried by using standard procedures,49 and stored under
nitrogen.
2 recycling data for enantioselective asymmetric Strecker
reaction of 2-methoxy imine 9a
Run
Time (h)
Yieldb (%)
eec (%)
1
2
3
4
5
28
28
29
31
33
95
95
95
94
93
>99
99
99
97
98
a
Strecker reaction of 2-methoxy imine 9 was carried out at ꢀ55 °C
in toluene using 15 mol % of catalyst 2 in the presence of 4-phenyl
pyridine N-oxide 4-PPNO (15 mol %) and 1.5 equiv of TMSCN.
b
Isolated yield.
Ee were determined using chiral OD-H column.
c
The Strecker reaction of substrates 3–13 was also conducted
using the above optimized protocol with dimeric Mn(III) salen
complex 2 as a catalyst, which gave the product
a-amino nitrile
in a shorter reaction time and in higher isolated yield (up to 95%)
and enantioselectivity (ee, >99%) as compared to the products ob-
tained with the use of catalyst 1 (Table 2, entry 14). This remark-
able improvement in the performance of dimeric complex 2 over
monomeric complex 1 suggests that the two catalytic centers are
working in co-operation rather than in isolation.42 Remarkably,
the dimeric Mn(III) salen complex 2 as a catalyst was recoverable
and recyclable while the monomeric complex 1 was difficult to
recover due to more solubility of the catalyst in the reaction
medium.
To the best of our knowledge, the chiral dimeric Mn(III) salen
complex 2 is the most efficient recyclable catalyst reported so far
for the asymmetric Strecker reaction of 2-methoxy imine 9 to give
the corresponding chiral a-amino nitrile in quantitative yield with
>99% ee (Table 2, entry 14). In all catalytic runs the (1S,2S) chiral
4.2. Typical experimental procedure for addition of TMSCN to N-
benzylimines
To a solution of chiral monomeric and dimeric Mn(III) salen com-
plexes (10 mg, 0.009 mmol) in toluene (5 ml), 4-PPNO (0.009 mmol)
was added and the resulting solution was cooled to ꢀ55 °C under N2
atmosphere. To the cooled solution TMSCN (0.75 equiv) was added
in a dropwise manner over 15 min with stirring. Subsequently
N-benzylimine (0.06 mmol) was added to the above cooled solution
and the stirring was continued for another 15 min. This was fol-
lowed by the addition of additional quantity of TMSCN (0.75 equiv)
monomeric and dimeric Mn(III) salen complexes gave the (R)-form
of the corresponding a-amino nitrile.
In order to assess the recyclability of the dimeric complex 2, the
catalytic run for the asymmetric Strecker reaction of 2-methoxy
imine 9 as a model substrate with TMCSN in toluene was carried
out at ꢀ55 °C (Table 1, entry 15). Consequently, after the first cat-
alytic run, an excess amount of hexane was added to the reaction
mixture, and the resulting solid was collected by filtration. The
recovered solid was thoroughly washed with hexane and vacuum
dried before reuse. The recovered solid containing the catalyst 2
was used as such in the same manner as the fresh catalyst in Strec-
ker reaction, and which showed similar activity and enantioselec-
tivity in the recycle experiments (Table 3, runs 1–5), though there
was some increase in the reaction time.
over a period of 15 min. Consequently H2O (15 ll) was added to the
stirred solution and the progress of the reaction was monitored on
TLC (silica plates) using hexane/ethyl acetate (90/10) as an eluent.
After the reaction was over the solvent was removed on rotavapor
and the product was purified by flash column chromatography on
silica gel (eluted with hexane/ethyl acetate = 90:10). The purified
products were characterized by 1H NMR which was in agreement
with the reported values.31
4.3. Characterization of the products
31
4.3.1. N-Benzyl (R)-2-amino-phenylacetonitrile 30
1H NMR (500 MHz, CDCl3) d = 1.86 (br, s, 1H), 3.95 (d,
J = 13.0 Hz, 1H), 4.06 (d, J = 13.0 Hz, 1H), 4.76 (s, 1H), 7.3–7.6 (m,
3. Conclusion
10H); ½a 2D7
¼ þ71 (c 1, CHCl3); HPLC analysis: CHIRALCEL OD col-
ꢁ
umn, hexane/2-propanol = 95:5, flow rate 0.8 ml/min, tr1 (min-
or) = 19.02 min, tr2 (major) = 20.42 min.
Chiral
a-aminonitriles in high ees were obtained by the chiral
monomeric and dimeric Mn(III) salen complex-catalyzed asym-
metric Strecker reaction of various N-benzylimines using TMSCN
as a source of cyanide at ꢀ55 °C in toluene. The dimeric catalyst
2 worked better than the catalyst 1 in terms of reactivity and
31
4.3.2. N-Benzyl (R)-2-amino-(4-methylphenyl) acetonitrile 40
1H NMR (500 MHz, CDCl3) d = 1.83 (1H, br s), 2.36 (3H, s), 3.95
(d, J = 13.0 Hz, 1H), 4.06 (d, J = 13.0 Hz, 1H), 4.71 (s, 1H), 7.2–7.4
enantioselectivity. High enantiomeric purity of
a-aminonitrile
(m, 9H); ½a 2D7
¼ þ35 (c 1, CHCl3); CHIRALCEL OD column, hexane/
ꢁ
(ee, >99%) was obtained from 2-MeO-imine 9 with catalyst 2 which
was recycled several times without affecting its performance.
2-propanol = 95:5, flow rate 0.8 ml/min, tr1 (minor) = 16.28 min,
tr2 (major) = 17.61 min.
4. Experimental
31
4.3.3. N-Benzyl (R)-2-amino-(3-methylphenyl)acetonitrile 50
1H NMR (500 MHz, CDCl3) d = 1.53 (br s, 1H), 2.31 (s, 3H), 3.89
(d, J = 13.0 Hz, 1H), 4.01 (d, J = 13.0 Hz, 1H), 4.64 (s, 1H), 7.2–7.4
4.1. Materials and characterization
(m, 9H); ½a 2D7
¼ þ63:4 (c 1, CHCl3); CHIRALCEL OD column, hex-
ꢁ
NMR spectra were obtained with a Bruker F113V spectrometer
(500 MHz) and are referenced internally with TMS. FTIR spectra
were recorded on a Perkin Elmer Spectrum GX spectrophotometer
ane/2-propanol = 95:5, flow rate 0.8 ml/min, tr1 (minor) = 14.78 -
min, tr2 (major) = 15.68 min.

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N.-u. H. Khan et al. / Tetrahedron: Asymmetry 21 (2010) 2076–2080
31
4.3.4. N-Benzyl (R)-2-amino-(2-methylphenyl)acetonitrile 60
1H NMR (500 MHz, CDCl3) d = 1.6 (br s, 1H), 2.22 (s, 3H), 3.89 (d,
J = 13.0 Hz, 1H), 4.04 (d, J = 13.0 Hz, 1H), 4.69 (s, 1H), 7.1–7.5 (m,
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14. Harusawa, S.; Hamada, Y.; Shioiri, T. Tetrahedron Lett. 1979, 20, 4663.
15. Mai, K.; Patil, G. Tetrahedron Lett. 1984, 25, 4583.
16. Kobayashi, S.; Ishitani, H. Chem. Rev. 1999, 99, 1069.
17. Davis, F. A.; Lee, S.; Zhang, H.; Fanelli, D. L. J. Org. Chem. 2000, 65, 8704.
18. Mori, Y.; Kimura, M.; Seki, M. Synthesis 2003, 2311.
19. Nakamura, S.; Sato, N.; Sugimoto, M.; Toru, T. Tetrahedron: Asymmetry 2004, 15,
1513.
20. Herrera, R. P.; Sagarzani, V.; Bernardi, L.; Fini, F.; Pettersen, D.; Ricci, A. J. Org.
Chem. 2006, 71, 9869.
21. Merino, P.; Marqués-López, E.; Tejero, T.; Herrera, R. P. Tetrahedron 2009, 65,
1219.
1H NMR (500 MHz, CDCl3) d = 1.62 (br s, 1H), 3.81 (s, 3H), 3.95
(d, J = 13.0 Hz, 1H), 4.06 (d, J = 13.0 Hz, 1H), 4.69 (s, 1H), 6.92(d,
J = 8.5 Hz, 2H), 7.3–7.5 (m, 7H); ½a D27
¼ þ25 (c 0.5, CHCl3); CHIRAL-
ꢁ
CEL OD column, hexane/2-propanol = 95:5, flow rate 0.8 ml/min,
tr1 (minor) = 23.75 min, tr2 (major) = 26.48 min.
31
4.3.6. N-Benzyl (R)-2-amino-(3-methoxyphenyl)acetonitrile 80
1H NMR (500 MHz, CDCl3) d = 1.84 (br s, 1H), 3.82 (s, 3H), 3.95
(d, J = 13.0 Hz, 1H), 4.04 (d, J = 13.0 Hz, 1H), 4.72 (s, 1H), 7.3–7.5
(m, 9H); ½a 2D7
¼ þ29:1 (c 1, CHCl3); CHIRALCEL OD column, hex-
ꢁ
ane/2-propanol = 95:5, flow rate 0.8 ml/min, tr1 (minor) = 26.66 -
min, tr2 (major) = 29.40 min.
4.3.7. N-Benzyl (R)-2-amino-(2-methoxyphenyl)acetonitrile 90
1H NMR (500 MHz, CDCl3) d = 2.0 (br s, 1H), 3.77 (s, 3H), 3.86 (d,
J = 13.0 Hz, 1H), 3.99 (d, J = 13.0 Hz, 1H), 4.72 (s, 1H), 6.84(d,
J = 8 Hz, 2H) 7.2–7.4 (m, 7H); CHIRALCEL OD-H column, hexane/
2-propanol = 99:1, flow rate 0.8 ml/min, tr (major) = 49.05 min.
22. Becker, C.; Hoben, C.; Kunza, H. Adv. Synth. Catal. 2007, 349, 417.
23. Wen, Y.; Gao, B.; Fu, Y.; Dong, S.; Liu, X.; Feng, X. Chem. Eur. J. 2008, 14, 6789.
24. Hou, Z.; Wang, J.; Liu, X.; Feng, X. Chem. Eur. J. 2008, 14, 4484.
25. Shen, K.; Liu, X.; Cai, Y.; Lin, L.; Feng, X. Chem. Eur. J. 2009, 15, 6008.
26. Su, J. T.; Vachal, P.; Jacobsen, E. N. Adv. Synth. Catal. 2001, 343, 197.
27. Vachal, P.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 10012.
28. Sigman, M. S.; Vachal, P.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2000, 39, 1279.
29. Pan, S. C.; List, B. Org. Lett. 2007, 9, 1149.
31
4.3.8. N-Benzyl (R)-2-amino-(4-chlorophenyl)acetonitrile 100
1H NMR (500 MHz, CDCl3) d = 1.6 (br s, 1H), 3.95 (d, J = 13.0 Hz,
1H), 4.05 (d, J = 13.0 Hz, 1H), 4.72 (s, 1H), 7.2–7.5 (m, 9H); ½a D27
¼
ꢁ
þ36 (c 0.8, CHCl3); CHIRALCEL OD column, hexane/2-propanol =
95:5, flow rate 0.8 ml/min, tr1 (minor) = 25.90 min, tr2
(major) =29.62 min.
30. Huang, X.; Huang, J.; Wen, Y.; Feng, X. Adv. Synth. Catal. 2006, 348, 2579.
31. Blacker, J.; Clutterbuck, L. A.; Crampton, M. R.; Grosjean, C.; North, M.
Tetrahedron: Asymmetry 2006, 17, 1449.
32. Ishitani, H.; Komiyama, S.; Hasegawa, Y.; Kobayashi, S. J. Am. Chem. Soc. 2000,
762.
33. Kato, N.; Suzuki, M.; Kanai, M.; Shibasaki, M. Tetrahedron Lett. 2004, 45, 3147.
34. Byrne, J. J.; Chavarot, M.; Chavant, P. V.; Vallée, Y. Tetrahedron Lett. 2000, 41,
873.
35. Takamura, M.; Hamashima, Y.; Usuda, H.; Kanai, M.; Shibasaki, M. Angew.
Chem., Int. Ed. 2000, 39, 1650.
36. Hatano, M.; Hattori, Y.; Furuya, Y.; Ishihara, K. Org. Lett. 2009, 11, 2321.
37. Seayad, A. M.; Ramalingam, B.; Yoshinaga, K.; Nagata, T.; Chai, C. L. L. Org. Lett.
2010, 12, 264.
38. Wang, J.; Wang, W.; Li, W.; Hu, X.; Shen, K.; Tan, C.; Liu, X.; Feng, X. Chem. Eur. J.
2009, 15, 11642.
39. Karimi, B.; Maleki, A. Chem. Commun. 2009, 5180.
40. Sigman, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120, 5315.
41. Khan, N. H.; Saravanan, S.; Kureshy, R. I.; Abdi, S. H. R.; Sadhukhan, A.; Bajaj, H.
C. J. Organomet. Chem. 2010, 695, 1133.
42. Khan, N. H.; Agrawal, S.; Kureshy, R. I.; Abdi, S. H. R.; Prathap, K. J.; Jasra, R. V.
Chirality 2009, 21, 262.
43. Kureshy, R. I.; Singh, S.; Khan, N. H.; Abdi, S.; Ahmed, I.; Bhatt, A.; Jasra, R. V.
Catal. Lett. 2006, 107, 127.
31
4.3.9. N-Benzyl (R)-2-amino-(4-fluorophenyl)acetonitrile 110
1H NMR (500 MHz, CDCl3) d = 1.78 (br s, 1H), 3.88 (d, J = 13.0 Hz,
1H), 3.98 (d, J = 13.0 Hz, 1H), 4.64 (s, 1H), 6.9–7.4 (m, 9H); CHIRAL-
CEL OD column, hexane/2-propanol = 95:5, flow rate 0.8 ml/min,
tr1 (minor) = 20.71 min, tr2 (major) = 22.08 min.
31
4.3.10. N-Benzyl (R)-2-amino-(1-naphthyl)acetonitrile 120
1H NMR (500 MHz, CDCl3) d = 1.815 (br s, 1H), 3.86 (d,
J = 12.8 Hz, 1H), 3.99 (d, J = 13.0 Hz, 1H), 4.76 (s, 1H), 7.21–7.90
(m, 12H); ½a 2D7
¼ þ170:4 (c 0.5, CHCl3); CHIRALCEL OD column,
ꢁ
hexane/2-propanol = 95:5, flow rate 0.8 ml/min, tr1 (minor) =
33.20 min, tr2 (major) = 35.32 min.
31
4.3.11. N-Benzyl (R)-2-amino-3,3-dimethyl butanonitrile 130
1H NMR (500 MHz, CDCl3) d = 1.18 (s, 9H), 3.03 (s, 1H), 3.88 (d,
44. Kureshy, R. I.; Khan, N. H.; Abdi, S. H. R.; Vyas, A. P.; Singh, S.; Ahmad, I.; Jasra,
R. V. J. Catal. 2004, 224, 229.
45. Kureshy, R. I.; Khan, N. H.; Abdi, S. H. R.; Singh, S.; Ahmed, I.; Shukla, R. S.; Jasra,
R. V. J. Catal. 2003, 219, 1.
46. Kureshy, R. I.; Khan, N. H.; Abdi, S. H. R.; Patel, S. T.; Jasra, R. V. Tetrahedron Lett.
2001, 24, 1915.
J = 13.0 Hz, 1H), 4.01 (s, 1H), 7.2–7.4 (m, 5H); ½a D27
¼ þ53 (c 1,
ꢁ
CHCl3); CHIRALCEL OD column, hexane/2-propanol = 95:5, flow
rate 0.8 ml/min, tr1 (minor) = 17.54 min, tr2 (major) = 19.02 min.
47. Pathak, K.; Ahmad, I.; Abdi, S. H. R.; Kureshy, R. I.; Khan, N. H.; Jasra, R. V. J. Mol.
Catal. Chem. 2007, 294, 120.
Acknowledgments
48. Kureshy, R. I.; Ahmed, I.; Pathak, K.; Khan, N. H.; Abdi, S. H. R.; Prathap, K. J.;
Jasra, R. V. Chirality 2007, 19, 352.
49. Perrin, D. D.; Armarego, W. L. F.; Perrin, D. R. In Purification of Laboratory
Chemicals, 2nd ed.; Pergamon Press: New York, 1981.
N. H. Khan and S. Saravanan are thankful to DST and CSIR Net-
work project on catalysis for the financial assistance and Analytical
Science Discipline for providing instrumentation facility.