Enantioselective Strecker reactions between aldimines and trimethylsilyl cyanide promoted by chiral N,N′-dioxides

Article abstract of DOI:10.1002/ejoc.200300319

Axially chiral N,N′-dioxide Lewis base promoters have been developed and have for the first time been applied to the asymmetric synthesis of α-amino nitriles through cyanide addition to aldimines. The chiral 3,3′-dimethyl-2,2′-biquinoline N,N′-dioxide 2 exhibited high enantioselectivity for asymmetric Strecker reactions between N-benzhydrylimines and trimethylsilyl cyanide. In the presence of 1 equiv. of chiral promoter 2, the cyanosilylation of aldimines afforded the corresponding α-amino nitriles with ee values of up to 95%. Optically pure products (99% ee) were obtained simply by recrystallization in the cases of some of the products. Moreover, the promoter 2 could be recovered and reused at least four times without any loss of enantioselectivity and reactivity. A putative mechanism for the enantioselective Strecker reactions is also discussed. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200300319

FULL PAPER
Enantioselective Strecker Reactions between Aldimines and Trimethylsilyl
Cyanide Promoted by Chiral N,NЈ-Dioxides
[b]
[a]
[b]
[b]
[c]
Zhigang Jiao, Xiaoming Feng,* Bo Liu, Fuxue Chen, Guolin Zhang, and
Yaozhong Jiang[
b]
Keywords: Amino acids /Asymmetric synthesis / Enantioselectivity / Lewis bases / Nitrogen oxides
Axially chiral N,NЈ-dioxide Lewis base promoters have been
developed and have for the first time been applied to the
asymmetric synthesis of α-amino nitriles through cyanide ad-
dition to aldimines. The chiral 3,3Ј-dimethyl-2,2Ј-biquinoline
tically pure products (99% ee) were obtained simply by
recrystallization in the cases of some of the products. More-
over, the promoter 2 could be recovered and reused at least
four times without any loss of enantioselectivity and reactiv-
N,NЈ-dioxide 2 exhibited high enantioselectivity for asym- ity. A putative mechanism for the enantioselective Strecker
metric Strecker reactions between N-benzhydrylimines and
trimethylsilyl cyanide. In the presence of 1 equiv. of chiral
promoter 2, the cyanosilylation of aldimines afforded the cor-
responding α-amino nitriles with ee values of up to 95%. Op-
reactions is also discussed.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
Because of the significance of α-amino acids in chemistry
and biology, the development of efficient synthetic methods
for the preparation of various α-amino acids has attracted
considerable attention. Recently, the ever-increasing de-
mand for the non-proteinogenic α-amino acids in a variety
Scheme 1. Cyanation of imines
Because chiral molecules play key roles in asymmetric
of scientific disciplines has promoted the development of synthesis, the rational design and synthesis of new chiral
novel methods for the asymmetric syntheses of α-amino ac- molecules have currently become the focus of attention.[
8]
ids.[ Together with the classic Strecker reaction, one of In this context, a great number of homochiral molecules
the most important reactions for the production of α-amino containing amines, ethers, and phosphanes as electron-pair
nitriles Ϫ key intermediates for the synthesis of α-amino donors have been employed as asymmetric controllers in
1]
[2]
[
3]
[9]
acids Ϫ is asymmetric cyanation of imines (Scheme 1).
many enantioselective reactions. It is well known that am-
Several procedures requiring the use of chiral auxiliaries ine N-oxides possess a notable electron-pair donor property,
have been reported to afford α-amino nitriles with high sel- which allows them to form different complexes with a vari-
[
4]
[10]
ectivity. However, the enantioselective addition of cyanide ety of metal ions,
but few reports have dealt with the
[
5,6]
[11]
to imine through the employment of chiral ligands
chiral promoters can be regarded as one of the most attract- ral promoters.
ive strategies. Despite the progress achieved, a more gen- ide 2, one of the chiral N-oxides, attracted our attention
and application of chiral N-oxides as chiral ligands or as chi-
[
12]
The axially chiral biquinoline N,NЈ-diox-
[
7]
eral and practical procedure for its application to a wide because of its highly skewed chiral environment. Nakajima
range of imines is still highly desirable.
and co-workers have employed the chiral biquinoline N,NЈ-
[
12b][12c,13]
dioxide in asymmetric reactions.
Intrigued by the
feasibility of these catalytic asymmetric processes based on
the chiral biquinoline N,NЈ-dioxide 2, we surmised that it
may also have a positive effect on promoting asymmetric
[
a]
Sichuan Key Laboratory of Green Chemistry and Technology,
College of Chemistry, Sichuan University
Jiuyan Bridge, Chengdu 610064, China
Fax: (internat.) ϩ 86-28/85412907
cyanosilylation of aldimines. We have recently reported our
E-mail: xmfeng@pridns.scu.edu.cn
[
[
b]
c]
[14]
Chengdu Institute of Organic Chemistry, Chinese Academy of preliminary studies,
and detailed investigations into the
Sciences
enantioselective Strecker reaction with the use of the axially
chiral biquinoline N,NЈ-dioxide 2 as a promoter are re-
ported here.
9
Rennan Road 4 Duan, Chengdu 610041, China
Chengdu Institute of Biology, Chinese Academy of Sciences
9
Rennan Road 4 Duan, Chengdu 610041, China
3818
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200300319
Eur. J. Org. Chem. 2003, 3818Ϫ3826

Enantioselective Strecker Reactions between Aldimines and Trimethylsilyl Cyanide
FULL PAPER
Results and Discussion
Table 1. Effects of chiral promoters on the enantioselective Strecker
reaction between benzaldehyde N-benzhydrylimine and HCN
Promoter Survey
A series of axially chiral N,NЈ-dioxides 1Ϫ5 (Scheme 2)
were examined as promoters for the enantioselective
Strecker reaction. The racemic N,NЈ-dioxides 1Ϫ4 were pre-
pared by reported procedures.[
15,16]
Racemates rac-1 and
Entry[a]
Yield[b] [%]
ee[c] [%]
Config.[d]
Promoter
rac-2 were resolved by Nakajima’s method,[
17,18]
while (ϩ)-
3
and (Ϫ)-4 were obtained by resolution of rac-3 and rac-4
1
2
3
4
5
(R)-1
(R)-2
(ϩ)-3
(Ϫ)-4
(R)-5
7
13
62
20
Ϫ
(S)
(S)
(R)
Ϫ
20
31
NR
with -dibenzoyltartaric acid (-DBTA) and -DBTA,
respectively. The absolute configuration of (ϩ)-3 was deter-
mined to be (S) by crystal X-ray analysis of its complex
[e]
17
53
(S)
[
19]
with -DBTA.
Compound (R)-5 was prepared in excel-
[a]
Conditions: 1 equiv. of chiral N,NЈ-dioxide, concentration of im-
lent yield by hydrogenation of (R)-2 in the presence of PtO2
[
b]
ine ϭ 0.05  in CH
Isolated yield. Determined by HPLC analysis on Daicel Chiral-
pak AD.
2
Cl
2
, Ϫ25 °C, 24 h, ratio imine/HCN ϭ 1:1.
in CF COOH (Scheme 3). To investigate the effects of chi-
3
[c]
ral N,NЈ-dioxides on the Strecker reaction, the compounds
[d]
The configuration was determined by comparison of
[
7a]
1
Ϫ5 were evaluated by the addition of benzaldehyde N- the elution order of the chiral HPLC assay with literature values.
[20]
[e]
benzhydrylimine 6a to HCN. The results listed in Table 1
indicated that the chiral promoters 1Ϫ5 showed surprising
differences in chiral induction, although each of them pos-
NR ϭ no reaction.
Optimization of the Reaction Conditions
sesses a C -symmetric axis. (R)-BINOL has been found to
2
Since we had found that the N,NЈ-dioxide (R)-2 was the
best promoter among the screened N,NЈ-dioxides under the
employed conditions, the solvent effects on the reaction be-
tween 6a and TMSCN in the presence of (R)-2 were studied
be an excellent chiral inducer in many asymmetric reac-
tions, but the similar molecule (R)-1 exhibited poor asym-
metric inductive abilities in the Strecker reaction (Table 1,
Entry 1). The highest ee value (62%) was recorded on em-
ployment of (R)-2, whereas its analogues (ϩ)-3 and (Ϫ)-4
gave no meaningful enantioselectivities (Table 1, Entries
[
22]
(
Table 2).
when the reaction was run in diethyl ether (Table 2, Entry
). With THF and CH CN as solvents, the reaction pro-
Only traces of product were detected by TLC
1
2
Ϫ4). H -BINOL, a hydrogenation product of BINOL, has
3
8
[
21]
vided the product with poor enantioselectivity and in low
to moderate yields. Moreover, (R)-2 was found to be insol-
proven to be a ligand superior to BINOL in some cases.
However, (R)-5 showed poorer abilities than the unsatu-
rated dioxide (R)-2 in promoting the asymmetric Strecker
reaction (Table 1, Entry 5).
uble in Et O, THF, and CH CN during the course of the
2
3
experiments. Toluene and benzene were also found to afford
results as poor as those obtained with ether-type solvents
(Table 2, Entries 4, 5). When DMF and MeOH were em-
ployed, the reaction proceeded smoothly, and afforded the
racemic product. Although the yields in CH Cl and CHCl
3
2
2
were relatively low, the cyanosilylation of imine afforded
moderate ee values (Table 2, Entries 8, 9). In terms of en-
antioselectivity, CH Cl2 appeared to be the best solvent
2
among the solvents tested, affording the product with 61%
ee.
Table 2. Solvent effects on the enantioselective Strecker reaction
between benzaldehyde N-benzhydrylimine and TMSCN
Entry[a]
Solvent
Yield[b] [%]
ee[c] [%]
1
2
3
4
5
6
7
8
9
Et
THF
CH CN
2
O
trace
30
57
10
10
78
94
64
60
Ϫ
6
7
18
12
0
0
61
59
Scheme 2. Chiral N,NЈ-dioxides investigated in this study
3
toluene
benzene
DMF
MeOH[
d]
CH
2
Cl
2
CHCl
3
[
a]
Conditions: 1 equiv. of chiral N,NЈ-dioxide 2, concentration of
[
b]
imine ϭ 0.2 , 0 °C, 24 h, ratio imine/TMSCN ϭ 1:2.
Isolated
[c]
yield. Determined by HPLC analysis on Daicel Chiralpak AD-
d]
Scheme 3. Synthesis of (R)-5
H. [ Carried out at Ϫ25 °C.
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Z. Jiao, X. Feng, B. Liu, F. Chen, G. Zhang, Y. Jiang
FULL PAPER
To improve the enantioselectivity, the effect of promoter enantioselectivity (Table 5, Entries 1Ϫ3). When, however,
loading was investigated in detail. The results, described in the reaction was carried out below 0 °C, α-amino nitrile
Table 3, indicated that the enantioselectivity and yield were was obtained with low conversion and enantioselectivity
influenced by the amount of the chiral N,NЈ-dioxide 2. On (Table 5, Entries 4, 5). The highest ee value was obtained at
increasing of the promoter loading from 5 to 50 mol %, the 0 °C. It should be noted that enantiomeric excesses similar
ee value was sharply enhanced from 14 to 58% (Table 3, (60%) to those obtained at 0 °C were also observed at
Entries 1Ϫ4). The highest ee value (61%) was obtained 19Ϫ25 °C, which made the procedure more attractive, since
when stoichiometric amounts of the promoter were used most previous enantioselective Strecker reactions required
(Table 3, Entry 5), suggesting that the background reaction, rather low temperatures (Ϫ78 to Ϫ20 °C) in order to pro-
which would be able to take in the process, could have led vide good levels of enantioselectivity.
to the diminution in the ee value. When over 1 equiv. of
promoter was used, the yield increased significantly but
Table 5. Effects of temperature on the enantioselective Strecker re-
action between benzaldehyde N-benzhydrylimine and TMSCN
without any improvement in the observed enantioselectivity
Table 3, Entry 6).
(
Entry[a]
Temperature [°C]
Time [h]
Yield[b] [%]
ee[c] [%]
Table 3. Effect of the amount of promoter on the enantioselective
Strecker reaction between benzaldehyde N-benzhydrylimine and
TMSCN
1
2
3
4
5
23Ϫ27
19Ϫ25
0
Ϫ25
Ϫ78
48
24
24
48
96
85
80
64
77
80
56
60
61
57
59
Entry[a] Promoter loading [mol %] Time [h] Yield[b] [%] ee[c] [%]
1
2
3
4
5
6
5
10
20
50
100
120
39
39
39
24
24
24
79
73
81
54
64
84
14
39
42
58
61
60
[
a]
Conditions: 1 equiv. of chiral N,NЈ-dioxide 2, concentration of
2 2
imine ϭ 0.2  in CH Cl
, ratio imine/TMSCN ϭ 1:2. [ Isolated
b]
yield. [ Determined by HPLC analysis on Daicel Chiralpak AD-
c]
H.
[
a]
In order to find the optimal reaction conditions, the ef-
2 2
Conditions: concentration of imine ϭ 0.2  in CH Cl , 0 °C,
4 h, ratio imine/TMSCN ϭ 1:2. [ Isolated yield. Determined fects of the molar ratio of 6a to TMSCN were investigated
b]
[c]
2
by HPLC analysis on Daicel Chiralpak AD-H.
(
Table 6). The reaction between 6a and 1 equiv. of TMSCN
gave a low yield and moderate enantioselectivity (Table 6,
Entry 1). With molar ratios of 1:1.2 or 1:1.5 the reaction
gave better ee values (65 and 66% ee, respectively) than seen
with the higher molar ratio of 1:2 (Table 6, Entries 2Ϫ4),
The concentration of substrate was also found to be an-
other important factor for yield and enantioselectivity. The
results, listed in Table 4, indicated that the enantioselectivity
increased rapidly from 45 to 59% with a change of the con-
centration of the imine 6a from 0.025 to 0.05  (Table 4,
Entries 1, 2). The highest enantioselectivity was observed
when the reaction was carried out at 0.2 . When the con-
centration of substrate and promoter was changed from 0.2
[
6,7]
which was not consistent with reported results.
A further
increase in the molar ratio to 1:3 disrupted the reaction
enantioselectivity (Table 6, Entry 5).
to 0.1 , both yield and ee decreased (Table 4, Entries 3, 4). Table 6. Effects of the ratio of imine to TMSCN on the enantiose-
lective Strecker reaction between benzaldehyde N-benzhydrylimine
and TMSCN
At a higher concentration, the yield was improved, but the
ee value was lowered (Table 4, Entry 5).
Entry[a] Ratio imine/TMSCN Time [h] Yield[b] [%] ee[c] [%]
Table 4. Effects of the concentration of substrate on the enantiose-
lective Strecker reaction between benzaldehyde N-benzhydrylimine
and TMSCN
1
2
3
4
5
1:1
36
24
24
24
36
43
67
67
64
64
58
65
66
61
35
1:1.2
1:1.5
1:2
Entry[a] Concentration of substrate [mol·LϪ1] Yield[b] [%] ee[c] [%]
1:3
1
2
3
4
5
0.025
0.05
0.1
0.2
0.4
60
41
52
64
75
45
59
52
61
56
[a]
Conditions: 1 equiv. of chiral N,NЈ-dioxide 2, concentration of
[b]
[c]
2 2
imine ϭ 0.2  in CH Cl , 0 °C. Isolated yield. Determined by
HPLC analysis on Daicel Chiralpak AD-H.
[
a]
Conditions: 1 equiv. of chiral N,NЈ-dioxide 2, CH
2
Cl
2
, 0 °C, 24 h,
ratio imine/TMSCN ϭ 1:2. [ Isolated yield.
b]
[c]
Determined by
The effects of potential recycling of the promoter were
also studied. The chiral N,NЈ-dioxide 2 could be recovered
HPLC analysis on Daicel Chiralpak AD-H.
An examination of the temperature effects, shown in quantitative by chromatography. Furthermore, the results
Table 5, revealed that the temperature clearly affected the in Table 7 showed that the chiral N,NЈ-dioxide 2 could be
yield, but not the enantioselectivity. At slightly higher tem- reused at least four times without any loss of enantioselec-
peratures, the yield increased without significant impact on tivity and reactivity.
3820
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Enantioselective Strecker Reactions between Aldimines and Trimethylsilyl Cyanide
FULL PAPER
Table 7. Effects of recovery of promoter on the enantioselective o-methyl- and o-methoxy-substituted substrates provided
Strecker reaction between benzaldehyde N-benzhydrylimine and the Strecker products with 71 and 12% ee, respectively
TMSCN
(Table 8, Entries 2, 4). On the whole, the electron-deficient
imines were able to provide higher enantioselectivity than
the electron-rich imines, and the electronic effects of sub-
strates were more significant than steric effects in terms of
enantioselectivity.
Entry[a]
Recovery
Yield[b] [%]
ee[c] [%]
1
2
3
4
5
0
1
2
3
4
64
71
71
67
60
61
62
57
64
61
As illustrated in Entries 6Ϫ9 in Table 8, the electron-do-
nating m-methyl- and m-methoxy-substituted imines also
participated in the chiral N-oxide-promoted addition reac-
tion, albeit with lower enantioselectivities (66 and 71% ee,
respectively). The electron-withdrawing m-chloro and m-
nitro derivatives were more suitable for asymmetric cyanide
addition to imines to afford α-amino nitriles with high ee
values and excellent yields. It could be concluded that the
electronic effects were still the most important factors on
enantioselectivity. It is worthwhile to mention that the
asymmetric reaction of the m-nitro-substituted substrate 6i
gave an 88% ee and an 87% yield (Table 8, Entry 9), while
an essentially racemic product was obtained on employ-
[
a]
Conditions: 1 equiv. of chiral N,NЈ-dioxide 2, concentration of
imine ϭ 0.2  in CH Cl , 24 h, 0 °C, ratio imine/TMSCN ϭ 1:2.
Isolated yield. Determined by HPLC analysis on Daicel Chir-
2
2
[
b]
[c]
alpak AD-H.
Substrate Generality
A series of N-benzhydrylimines was tested under the opti-
mal conditions. As shown in Table 8, aromatic, heteroarom-
atic, and conjugated aldimines afforded the corresponding
α-amino nitriles with moderate to excellent ee values and in
considerable yields. The results suggested that there was a
positive ortho-substitution effect on enantioselectivity ex-
cept in the case of an o-methoxy substituent (Table 8, En-
tries 1Ϫ5). The electron-withdrawing o-nitro- and o-chloro-
substituted imines underwent the enantioselective cyanide
addition to afford α-amino nitriles with excellent enantiose-
lectivities. The o-chlorobenzaldehyde derivative 6c provided
[
7a]
ment of a cyclic dipeptide catalyst.
All para-substituted N-benzhydrylimines gave moderate
to good enantioselectivities, indicating little influence deriv-
ing from electronic effects (Table 8, Entries 10Ϫ14). The p-
cyano-substituted Strecker product 7n could be isolated in
only 30% yield, however.
Chiral promoter 2 was adapted to promote the reaction
the highest enantioselectivity and yield (95% ee, 96% yield) of the heteroaromatic and conjugated aromatic aldimines
Table 8, Entry 3). Notably, the o-nitro-substituted substrate under general reaction conditions. In contrast with the pre-
e first afforded the Strecker adduct in 85% yield with 89% vious examples, a low enantioselectivity (49% ee) was ob-
(
6
ee in the molar ratio of imine to TMSCN ϭ 1:2 (Table 8, served for the o-furyl derivative 7o, showing poor compati-
Entry 5). On the other hand, the electron-donating bility of the asymmetric reaction with a heteroaromatic im-
Table 8. Enantioselective Strecker reactions between aldimines and TMSCN
Entry[a]
Ar in imine 6
a: Ph
Aldimine/TMSCN
Time [h]
Yield[b] [%]
ee[c] [%]
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1:1.5
1:1.5
1:1.5
1:2
24
72
96
94
96
72
96
94
96
72
96
96
96
72
72
96
67
70
96
67
85
83
90
69
87
72
93
90
95
30
86
88
66
71 (99)
95 (99)
[
[
c]
b: o-MeC
c: o-ClC
d: o-MeOC
e: o-O NC
f: m-MeC
g: m-ClC
h: m-MeOC
6
H
4
H
4
d]
6
[
[
e]
e]
6
H
H
4
12
1:2
89 (99)[d]
2
6
4
6
H
4
1:1.5
1:1.5
1:2
66
81
71
88
6
H
4
[
[
e]
e]
6
H
4
i: m-O
j: p-MeC
k: p-ClC
l: p-MeOC
m: p-FC
2
NC
6
H
H
4
H
4
1:2
[
[
d]
d]
0
1
2
3
4
5
6
6
4
1.1.5
1:1.5
1:2
1:1.5
1:1.5
1:1.5
1:1.5
75 (99)
78 (99)
62
72 (99)
61
6
[
e]
6
H
H
4
4
[
d]
6
n: p-NCC
6 4
H
o: o-furyl
49
67
p: PhCHϭCH
[
a]
2 2
Conditions: 1 equiv. of chiral N,NЈ-dioxide 2, concentration of imine ϭ 0.2  in CH Cl
, 0 °C. [b] Isolated yield. [c] Determined by
HPLC analysis on Daicel Chiralpak AD-H/AS-H and Chiralcel OD. [ Purified by recrystallization. Nitro- and methoxy-substituted
d]
[e]
imines gave better results under the molar ratio of imine to TMSCN ϭ 1:2.
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Z. Jiao, X. Feng, B. Liu, F. Chen, G. Zhang, Y. Jiang
FULL PAPER
ine (Table 8, Entry 15). Nevertheless, aromatic α,β-unsatu- effects of the strong donor (NϪO) and the weak donor (N)
rated imine 6p underwent asymmetric cyanosilylation to on TMSCN in the process. When imine is added to the
provide the corresponding α-amino nitrile with moderate solution of rac-2 and TMSCN, an almost identical spec-
enantioselectivity (67% ee) and in 88% yield (Table 8, En- trum is observed (Table 9, Entry 4). The spectra suggest
try 16).
that a six-coordinate hypervalent silicate also exists after
Furthermore, some of the Strecker products, such as the imine has been added, but there is a small difference be-
o-methyl-, o-chloro-, o-nitro-, p-methyl-, p-chloro-, and p- tween its transition state and that of Entry 2 according to
fluoro-substituted α-amino nitriles, could be recrystallized the chemical shift.
from n-hexane to afford optically pure materials (99% ee).
To elucidate the significant nucleophilic effect of the N-
Table 9. 29Si NMR chemical shifts of several systems
oxides on the silicon atoms and their potential role in the
Entry[a]
Components
δ [ppm]
reaction, rac-2, rac-3,3Ј-dimethyl-2,2Ј-biquinoline N-oxide
N-monoxide), and 3,3Ј-dimethyl-2,2Ј-biquinoline were
(
1
2
3
4
TMSCN
TMSCNϩ rac-2
TMSCNϩ rac-N-monoxide
TMSCNϩ rac-2ϩimine
Ϫ11.5
chosen for investigation of the promotion of the Strecker
reaction between benzaldehyde N-benzhydrylimine and
TMSCN under the general reaction conditions, affording
7.1, Ϫ11.5
7.1, Ϫ11.5
7.2, Ϫ11.5
8
8, 76, and 60% yields, respectively. The different yields
[
a]
Conditions: CDCl
3
, 25 °C. Imine/rac-2/TMSCN ϭ 1:1:1.5. TMS
indicated that the strong donor (NϪO) could play the most
important role in enhancing reactivity and nucleophilicity
of TMSCN, but that the weak donor (N) could have only
(
δ ϭ 0.1 ppm) as internal standard.
1H NMR (600 MHz) analysis in CDCl
at 25 °C was also
3
1
a small effect on the silicon atom in the process. This is carried out to support the hypothesis further. The H NMR
in agreement with Feng’s reports that TMSCN could be spectrum of Entry 4 in Table 9 shows that the representative
[
11f][11g]
activated by an achiral N-oxide.
sumed that the transition states of the chiral N-oxide-pro- (HCCN) ppm are observed, but that there is no corre-
We therefore as- signals of the Strecker adduct at δ ϭ 5.28 (HCPh ) and 4.64
2
[
23]
1
moted Strecker reactions should be hypervalent silicates.
In order to confirm the hypothesis, Si NMR (300 MHz) troscopic data suggest that the N atom of the imine prob-
sponding signal at δ ϭ 2.18 (NH) ppm. The H NMR spec-
2
9
analyses were carried out at 25 °C in CDCl . Firstly, all ably coordinates to the silicon atom of the hypervalent sili-
3
experiments were performed in CDCl , as detailed in the cate and ultimately forms an NϪSi bond.
3
2
9
Exp. Sect. The Si NMR spectra were then recorded and
On the basis of these observations, it is possible to pro-
scaled from tetramethylsilane (TMS). As illustrated in En- pose reaction transition states to account for the observed
try 1 in Table 9, TMSCN affords a signal at δ ϭ Ϫ11.5 asymmetric induction of (S)-2, as shown in Figure 1. The
ppm. When TMSCN is added to the solution of rac-2, an- mechanistic hypothesis suggests that when TMSCN is ad-
other strong signal is found at δ ϭ 7.1 ppm (Table 9, Entry ded to the solution of (S)-2 and CH
Cl , the strong electron
2
2
2
). The spectral changes strongly indicate that the environ- donors (NϪO) of (S)-2 coordinate to the silicon atom of
ments around the silicon atoms of some TMSCN species TMSCN to form hexacoordinate hypervalent silicate A, so
are changed when rac-2 is present. It is very possible that the nucleophilicity of the cyano group of A is enhanced.
these silicon atoms of TMSCN could form five- or six-coor- The highly reactive cyano group then attacks the imine
dinate hypervalent silicate species by coordination to N-ox- from the Re face, and the nitrogen atom simultaneously co-
ides. Furthermore, when rac-N-monoxide, possessing only ordinates to the silicon atom to produce another hexacoor-
one NϪO dipolar moiety, is employed instead of rac-2, the dinate hypervalent silicate B, which ultimately forms the de-
2
9
same Si NMR spectroscopic data are recorded, but the sired Strecker adduct with (R) configuration.
signal at δ ϭ 7.1 ppm is weakened and that at δ ϭ Ϫ11.5
2
9
ppm strengthened. The similar Si spectra of rac-2 and rac- Conclusion
N-monoxide suggest that it is easier for the silicon atom
of TMSCN to form a six-coordinate silicate because the
In conclusion, efficient, enantioselective Strecker reac-
hexacoordinate silicate is more stable than pentacoordinate tions between aromatic aldimines and TMSCN promoted
silicate. The different results are also consistent with the by 1 equiv. of axially chiral promoter 2 are documented. A
Figure 1. Proposed transition states
3822
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 3818Ϫ3826

Enantioselective Strecker Reactions between Aldimines and Trimethylsilyl Cyanide
FULL PAPER
wide range of aromatic N-benzhydrylimines can be em- of (ϩ)-3, as a yellow solid with 97% ee; m.p. 205Ϫ207 °C. [α]2
0
ϭ
D
Ϫ1247 (c ϭ 0.22 in CHCl
column (Daicel Chiralcel OJ, n-hexane/iPrOH, 65:35, 1.0 mL/min,
3
); ee was determined by chiral HPLC
ployed to obtain the corresponding α-amino nitriles in high
yields and with moderate to excellent enantioselectivities
1
UV: 254 nm). H NMR (400 MHz, CDCl
3
): δ ϭ 8.82 (d, J ϭ
.8 Hz, 2 H, H-8 and H-8Ј), 7.87 (d, J ϭ 8.0 Hz, 2 H; H-5 and H-
Ј), 7.73 (m, 2 H, H-7 and H-7Ј), 7.68 (s, 2 H, H-4 and H-4Ј), 7.67
),
), 2.26 (t, J ϭ 8.8 Hz, 2 H;
(
up to 95% ee) under mild and practical conditions. In ad-
dition, some of the products can be obtained with up to
9% ee after recrystallization. Future efforts will be directed
8
5
9
(
m, 2 H, H-6 and H-6Ј), 3.01 (dd, J ϭ 8.0, 13.6 Hz, 2 H; CH
2
towards the design and syntheses of novel chiral ligands
and chiral molecules for enantioselective Strecker reactions
of aldimines and ketoimines.
2.35 (dd, J ϭ 11.6, 14.0 Hz, 2 H; CH
2
CH
2
),1.64 (m, 2 H, CH ) ppm.
2
(
R)-3,3Ј-Dimethyl-5,5Ј,6,6Ј,7,7Ј,8,8Ј-octahydro-2,2Ј-biquinoline N,NЈ-
Dioxide [(R)-5]: Compound (R)-2 (100 mg, 0.32 mmol) was dis-
solved in CF COOH (2 mL), PtO (12 mg) was added, the solution
3
2
Experimental Section
was connected to the hydrogenator, the air was removed, 0.34 MPa
pressure was applied, and the mixture was hydrogenated for 4 h. It
General: Analytical TLC was carried out with 0.25 mm precoated
was then diluted with H
extracted with CH Cl (3 ϫ 10 mL) and brine (10 mL), and dried
with anhydrous Na SO . After filtration and removal of solvent,
the residue was chromatographed on silica gel. Compound (R)-5
96 mg, 94%) was obtained as a colorless solid; m.p. 190Ϫ192 °C.
2
O (10 mL), neutralized with 10% NaOH,
plates from Yan-Tai (SIL G-60 UV254 60-F), and spots were
1
13
29
2
2
viewed by use of UV light. H NMR, C NMR, and Si NMR
spectra were recorded on 400 MHz (Inova), 600 MHz (Bruker), or
2
4
3
300 MHz. (Bruker) spectrometers with CDCl as standard; Chemi-
(
cal shifts (δ) are reported in ppm, and coupling constants (J) are
reported in Hz. Melting points are uncorrected. Elemental analyses
were performed with a Carlo-1160 instrument. Enantiomeric ex-
cesses were determined by chiral HPLC analysis on Daicel Chiral-
cel OJ/OD and Daicel Chiralpak AD/AD-H/AS-H equipment. Op-
tical rotations were measured with a PerkinϪElmer 341 instrument.
2
0
1
D 3 3
[α] ϭ ϩ41.3 (c ϭ 0.54 in CHCl ). H NMR (400 MHz, CDCl ):
δ ϭ 6.94 (s, 2 H, H-4 and H-4Ј), 2.99 (tt, J ϭ 6.0, 19.2 Hz, 2 H;
H-8 or H-8Ј), 2.84 (tt, J ϭ 6.4, 19.2 Hz, 2 H; H-8Ј or H-8), 2.76
(
t, J ϭ 6.0 Hz, 4 H; H-5 and H-5Ј), 2.03 (s, 6 H, CH
m, 8 H, H-6 and H-6Ј and H-7 and H-7Ј) ppm. C NMR
): δ ϭ 146.1, 140.1, 135.4, 132.4, 127.0, 28.5,
4.3, 21.9, 21.7, 17.4 ppm. ESI-HRMS for C20 ϩNa:
calcd. 325.1915; found 325.1909.
3
), 1.91Ϫ1.73
1
3
(
ϩ
(100 MHz, CDCl
3
HRMS data were measured with a Finnigan MA mass spec-
2
24 2 2
H N O
trometer. The Strecker reactions were performed under nitrogen
with the use of oven-dried glassware (at 140 °C for at least 4 h,
then stored in the drybox) and magnetic stirring. Reaction solvents
were distilled under nitrogen from appropriate agents immediately
rac-3,3Ј-Dimethyl-2, 2Ј-biquinoline N-Oxide: A solution of m-chlor-
operbenzoic acid (m-CPBA, 130 mg, 0.75 mmol) in CH Cl
10 mL) was slowly added at 0 °C to a stirred solution of 3,3Ј-
dimethyl-2,2Ј-biquinoline (210 mg, 0.75 mmol) in CH Cl (10 mL).
The resulting yellow solution was stirred at room temperature for
h and was then diluted with CH Cl (20 mL), washed with 5%
Na CO (3 ϫ 20 mL), and dried with anhydrous MgSO . After
2
2
prior to use: toluene, benzene, THF, and Et
phenone, CH Cl and CHCl from CaH , and methanol from Mg/
. DMF and CH CN were distilled under nitrogen by standard
2
O from Na/benzo-
(
2
2
3
2
2
2
I
2
3
methods just prior to use. Commercially available reagents were
used without further purification. The following compounds are
6
2
2
2
3
4
[
15,17]
available by literature procedures: (R)-1,
quinoline, (R)-2,
3,3Ј-dimethyl-2,2Ј-bi-
filtration and removal of solvent, the residue was chromatographed
on silica gel, with elution by petroleum ether/ethyl acetate (1:2) to
afford the mono-N-oxide (170 mg, 77%), which was recrystallized
[
16]
[16,18]
[16]
[16]
[24]
rac-3, rac-4, and 6aϪ6p.
Preparation of (ϩ)-3, (Ϫ)-4, (R)-5, and rac-3,3Ј-Dimethyl-2,2Ј-bi-
quinoline N-Oxide
from ethyl acetate to afford thin yellow crystals: m.p. 232Ϫ234 °C.
1
3
H NMR (400 MHz, CDCl ): δ ϭ 8.73 (d, J ϭ 8.8 Hz, 1 H; aro-
(
؉)-3,3Ј-Trimethylene-2,2Ј-biquinoline N,NЈ-Dioxide [(؉)-3]:
solution of racemic 3 (81 mg, 0.25 mmol) in CH Cl (5.6 mL) was
added to a solution of -DBTA (47 mg, 0.13 mmol) in EtOH
0.28 mL). The resulting clear solution was allowed to stand at
room temp. for 30 min to afford yellow prisms. The mother liquor
was washed with CH Cl (10 mL) and a satd. solution of NaHCO
3ϫ10 mL) and dried with anhydrous Na SO . After filtration and
A
matic H), 8.11 (d, J ϭ 10.8 Hz, 2 H; aromatic H), 7.84 (d, J ϭ
2
2
8
3
.0 Hz, 2 H; aromatic H), 7.73Ϫ7.55 (m, 5 H, aromatic H), 2.35 (s,
H, CH ), 2.19 (s, 3 H,CH ) ppm. C NMR (100 MHz, CDCl ):
3 3 3
13
(
δ ϭ 153.6, 146.8, 140.2, 136.3, 131.1, 130.6, 129.7, 129.4, 129.3,
28.73, 128.66, 128.3, 127.3, 127.1, 127.0, 125.8, 119.8, 19.2, 17.6
ppm. ESI-HRMS for C20 OϩNa: calcd. 301.1335; found
01.1333.
1
2
2
3
16 2
H N
(
2
4
3
removal of solvent, the residue was chromatographed on silica gel,
with elution with ethyl acetate, to afford optically pure (ϩ)-3 (Ͼ
General Enantioselective Strecker Procedure: A mixture of (S)-2
9
9% ee) as a yellow solid (31 mg, 38%). The absolute configuration (31.6 mg, 0.1 mmol) and imine 6 (0.1 mmol) was kept in vacuo for
of (ϩ)-3 was determined to be (S) by X-ray crystal structure analy-
30 min, after which CH Cl (0.5 mL) was added. The resulting
2
2
sis of its complex with -DBTA; m.p 163Ϫ165 °C. [α]2
0
ϭ ϩ1263
); ee was determined by chiral HPLC column
Daicel Chiralcel OJ, n-hexane/iPrOH, 65:35, 1.0 mL/min, UV:
solution was then cooled to 0 °C, and TMSCN (0.15 or 0.2 mmol)
was added. When the reaction was complete (24Ϫ96 h), the solvent
was evaporated directly and the crude residue was purified by flash
D
(
(
2
c ϭ 0.24 in CHCl
3
1
54 nm). H NMR (400 MHz, CDCl
H; H-8 and H-8Ј), 7.85 (d, J ϭ 7.6 Hz, 2 H; H-5 and H-5Ј), 7.74 as white solids or oils.
td, J ϭ 1.2, 8.0 Hz, 2 H; H-7 and H-7Ј), 7.67 (td, J ϭ 1.2 Hz, 2
H; H-6 and H-6Ј), 7.56 (s, 2 H, H-4 and H-4Ј), 2.88 (dt, J ϭ 4.0,
4.0 Hz, 2 H; CH ), 2.55 (dt, J ϭ 6.0, 14.0 Hz, 2 H; CH ), 2.15
m, 2 H, CH ) ppm.
3
): δ ϭ 8.87 (d, J ϭ 8.8 Hz, 2 column chromatography on silica gel to afford compounds (R)-7
(
α-[(Diphenylmethyl)amino]-α-phenylacetonitrile (7a):[7a] The crude
material was purified by flash chromatography on silica gel (Et O/
2
1
2
2
light petroleum ether, 1:60) to afford the product in 67% yield as a
white solid. The chromatographed material was determined to be
of 66% ee by chiral HPLC analysis [Chiralpak AD-H, 80:20 n-
hexane/iPrOH, 1.0 mL/min, t(minor) ϭ 7.96 min, t(major) ϭ
(
2
(
؊)-3,3Ј-Tetramethylene-2,2Ј-biquinoline N,NЈ-Dioxide [(؊)-4]:
Compound (Ϫ)-4 was obtained with O,OЈ-dibenzoyl--tartaric acid
-DBTA) by a procedure similar to that used for the preparation
2
0
1
(
13.31 min]; m.p. 94Ϫ96 °C. [α]
D
ϭ Ϫ3.9 (c ϭ 0.36 in CHCl
3
). H
Eur. J. Org. Chem. 2003, 3818Ϫ3826
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3823

Z. Jiao, X. Feng, B. Liu, F. Chen, G. Zhang, Y. Jiang
FULL PAPER
NMR (400 MHz, CDCl
.25 (s, 1 H, HCPh
J ϭ 12.0 Hz, 1 H; NH) ppm. C NMR (100 MHz, CDCl
1
1
3
): δ ϭ 7.58Ϫ7.20 (m, 15 H, aromatic H), t(major) ϭ 13.35 min], after recrystallization from n-hexane to af-
5
2
), 4.60 (d, J ϭ 12.4 Hz, 1 H; HCCN), 2.14 (d,
ford of a colorless needle crystal (Ͼ 99% ee); m.p. 88Ϫ90 °C. [α]
13
2
0
1
3
): δ ϭ
42.7, 141.0, 134.9, 129.03, 129.00, 128.98, 128.8, 127.9, 127.7, CDCl
27.4, 127.2, 127.1, 118.7, 65.6, 52.4 ppm. 8.0 Hz, 1 H; aromatic H), 7.64 (t, J ϭ 8.0 Hz, 1 H; aromatic H),
.55 (t, J ϭ 8.0 Hz, 1 H; aromatic H), 7.47 (d, J ϭ 7.6 Hz, 2 H;
aromatic H), 7.39Ϫ7.19 (m, 8 H, aromatic H), 5.29 (d, J ϭ 12.0 Hz,
H; HCCN), 5.20 (s, 1 H, HCPh ), 2.38 (d, J ϭ 11.6 Hz, 1 H;
NH) ppm. C NMR (100 MHz, CDCl ): δ ϭ 148.4, 142.2, 140.1,
33.4, 130.2, 129.8, 129.2, 128.9, 128.7, 128.1, 127.74, 127.68,
27.0, 125.4, 117.1, 65.8, 49.6 ppm. C21 (343.1): calcd. C
3.45, H 4.99, N 12.24; found C 73.56, H 5.12, N 11.98.
D
ϭ Ϫ17.8 (c ϭ 1.1 in CHCl
3
, 99% ee). H NMR (400 MHz,
3
): δ ϭ 7.95 (d, J ϭ 8.0 Hz, 1 H; aromatic H), 7.76 (d, J ϭ
7
α-[(Diphenylmethyl)amino]-α-(2-methylphenyl)acetonitrile (7b):[7c]
The crude material was purified by flash chromatography on silica
1
2
gel (Et
2
O/light petroleum ether, 1:60) to afford the product in 70%
13
3
yield as a white solid. The chromatographed material was deter-
mined to be of 71% ee by chiral HPLC analysis [Chiralpak AD-
H, n-hexane/iPrOH, 80:20, 1.0 mL/min, t (minor) ϭ 4.80 min, t
1
1
7
17 3 2
H N O
(
major) ϭ 6.89 min], after recrystallization from n-hexane to afford
colorless needle crystals [Ͼ 99% ee by chiral HPLC analysis, Chir-
alpak AD-H, n-hexane/iPrOH, 80:20, 1.0 mL/min, t(minor) ϭ crude material was purified by flash chromatography on silica gel
α-[(Diphenylmethyl)amino]-α-(3-methylphenyl)acetonitrile (7f): The
2
0
4
.17 min, t(major) ϭ 6.32 min]; m.p. 106Ϫ108 °C. [α]
D
ϭ Ϫ11.6
, 99% ee). H NMR (400 MHz, CDCl ): δ ϭ yield as a liquid. The chromatographed material was determined
.56 (d, J ϭ 7.2 Hz, 3 H; aromatic H), 7.45 (d, J ϭ 7.2 Hz, 2 H; to be of 66% ee by chiral HPLC analysis [Chiralpak AD-H, n-
hexane/iPrOH, 95:5, 1.0 mL/min, t(minor) ϭ 6.55 min, t(major) ϭ
2
(Et O/light petroleum ether, 1:60) to afford the product in 83%
1
(c ϭ 0.53 in CHCl
3
3
7
aromatic H), 7.37 (t, J ϭ 7.2 Hz, 2 H; aromatic H), 7.31Ϫ7.20 (m,
H, aromatic H), 5.26 (s, 1 H, HCPh ), 4.60 (d, J ϭ 12.0 Hz, 1 H; 8.68 min]. [α]
HCCN), 2.27 (s, 3 H, CH ), 1. 99 (d, J ϭ 11.6 Hz, 1 H; NH) ppm. CDCl ): δ ϭ 7.61 (d, J ϭ 8.0 Hz, 2 H; aromatic H), 7.49 (d, J ϭ
C NMR (100 MHz, CDCl ): δ ϭ 142.7, 140.9, 136.4, 133.1, 8.0 Hz, 2 H; aromatic H), 7.43Ϫ7.21 (m, 10 H, aromatic H), 5.28
2
0
1
7
2
D 3
ϭ Ϫ4.1 (c ϭ 1.1 in CHCl ). H NMR (400 MHz,
3
3
13
3
1
1
31.1, 129.2, 128.9, 128.7, 128.0, 127.8, 127.6, 127.4, 126.9, 126.6,
18.7, 65.7, 50.3, 18.9 ppm.
(s, 1 H, HCPh
s, 1 H; NH) ppm. C NMR (100 MHz, CDCl
1
1
2
), 4.59 (s, 1 H, HCCN), 2.42 (s, 3 H, CH
3
), 2.15 (br.
): δ ϭ 142.8, 141.2,
38.9, 134.9, 129.8, 129.0, 128.9, 128.8, 127.90, 127.86, 127.7,
27.5, 127.2, 124.4, 118.9, 65.6, 52.4, 21.4 ppm. C22 (312.2):
1
3
3
α-(2-Chlorophenyl)-α-[(diphenylmethyl)amino]acetonitrile
The crude material was purified by flash chromatography on silica
gel (Et O/light petroleum ether, 1:30) to afford the product in 96%
yield as a white solid. The chromatographed material was deter-
mined to be of 95% ee by chiral HPLC analysis [Chiralpak AS-H, The crude material was purified by flash chromatography on silica
n-hexane/iPrOH, 90:10, 1.0 mL/min, t(minor) 10.31 min, gel (Et O/light petroleum ether, 1:30) to afford the product in 90%
t(major) ϭ 11.66 min], after recrystallization from n-hexane to af-
(7c):[6c]
20 2
H N
calcd. C 84.58, H 6.45, N 8.97; found C 84.48, H 6.36, N 8.84.
2
α-(3-Chlorophenyl)-α-[(diphenylmethyl)amino]acetonitrile
(7g):[7a]
ϭ
2
yield as a white solid. The chromatographed material was deter-
mined to be of 81% ee by chiral HPLC analysis [Chiralpak AD-H,
2
0
ford colorless crystals (99% ee); m.p. 100Ϫ102 °C. [α]
D
ϭ Ϫ10.2
1
(
(
(
1
(
c ϭ 0.56 in CHCl
m, 3 H, aromatic H), 7.45Ϫ7.42 (m, 3 H, aromatic H), 7.38Ϫ7.20
m, 8 H, aromatic H), 5.22 (s, 1 H, HCPh ), 4.89 (d, J ϭ 12.0 Hz,
H; HCCN), 2.19 (d, J ϭ 11.6 Hz, 1 H; NH) ppm. C NMR aromatic H), 7.46Ϫ7.22 (m, 11 H, aromatic H), 5.23(s, 1 H,
100 MHz, CDCl ): δ ϭ 142.5, 140.7, 133.4, 132.7, 130.5, 130.4, HCPh ), 4.58 (d, J ϭ 12.4 Hz, 1 H, HCCN), 2.16 (d, J ϭ 12.8 Hz,
3
). H NMR (400 MHz, CDCl
3
): δ ϭ 7.58Ϫ7.55 n-hexane/iPrOH, 80:20, 1.0 mL/min, t(major)
ϭ
4.96 min,
ϭ Ϫ4.1 (c ϭ 0.83 in
3 3
CHCl ). H NMR (400 MHz, CDCl ): δ ϭ 7.57Ϫ7.55 (m, 3 H,
2
0
t(minor) ϭ 5.67 min]; m.p. 101Ϫ103 °C. [α]
D
1
2
13
3
2
1
3
1
5
29.2, 128.8, 128.7, 127.9, 127.7, 127.64, 127.55, 127.1, 118.1, 65.6,
0.2 ppm.
1 H, NH) ppm. C NMR (100 MHz, CDCl
136.7, 134.9, 130.2, 129.3, 129.1, 128.8, 128.0, 127.8, 127.43,
27.39, 127.0, 125.4, 118.2, 65.6, 51.8 ppm.
3
): δ ϭ 142.4, 140.7,
1
α-[(Diphenylmethyl)amino]-α-(2-methoxyphenyl)acetonitrile
The crude material was purified by flash chromatography on silica
gel (Et O/light petroleum ether, 1:20) to afford the product in 67%
(7d):
α-[(Diphenylmethyl)amino]-α-(3-methoxyphenyl)acetonitrile
The crude material was purified by flash chromatography on silica
gel (Et O/light petroleum ether, 1:20) to afford the product in 69%
(7h):[7a]
2
yield as a white solid. The chromatographed material was deter-
2
mined to be of 12% ee by chiral HPLC analysis [Chiralpak AD-H,
yield as a white solid. The chromatographed material was deter-
n-hexane/iPrOH, 90:10, 1.0 mL/min, t(minor)
ϭ
6.57 min,
mined to be of 71% ee by chiral HPLC analysis [Chiralpak AD-H,
20
t(major) ϭ 8.14 min]; m.p. 98Ϫ100 °C. [α]
D
ϭ Ϫ0.4 (c ϭ 0.92 in n-hexane/iPrOH, 80:20, 1.0 mL/min, t(minor)
ϭ
6.16 min,
ϭ Ϫ2.8 (c ϭ 0.76 in
): δ ϭ 7.57Ϫ7.55 (m, 2 H,
aromatic H), 7.46Ϫ7.44 (m, J ϭ 8.0 Hz, 2 H, aromatic H),
), 4.66 (d, 7.38Ϫ7.21 (m, 7 H, aromatic H), 7.19 (dd, J ϭ 0.8, 7.6 Hz, 1 H,
), 2.55 (d, J ϭ aromatic H), 7.08 (d, J ϭ 2.0 Hz, 1 H, aromatic H), 6.91 (dd, J ϭ
2.0 Hz, 1 H; NH) ppm. C NMR (100 MHz, CDCl ): δ ϭ 157.0, 2.0, 8.0 Hz, 1 H, aromatic H), 5.23(s, 1 H, HCPh ), 4.56 (d, J ϭ
42.9, 141.4, 130.5, 128.9, 128.71, 128.67, 127.7, 127.5, 127.4, 12.4 Hz, 1 H, HCCN), 3.83 (s, 3 H, OCH ), 2.15 (d, J ϭ 12.4 Hz,
1 H, NH) ppm. C NMR (100 MHz, CDCl ): δ ϭ 160.0, 142.7,
1
20
CHCl
3
). H NMR (400 MHz, CDCl
3
): δ ϭ 7.52 (d, J ϭ 7.2 Hz, 2
t(major) ϭ 6.67 min]; m.p. 82Ϫ84 °C. [α]
D
1
H; aromatic H), 7.43 (d, J ϭ 7.6 Hz, 2 H; aromatic H), 7.38Ϫ7.20 CHCl
3
). H NMR (400 MHz, CDCl
3
(
(
m, 8 H, aromatic H), 6.97 (d, J ϭ 7.6 Hz, 1 H; aromatic H), 6.93
d, J ϭ 8.0 Hz, 1 H; aromatic H), 5.18 (s, 1 H, HCPh
2
J ϭ 12.0 Hz, 1 H; HCCN), 3.85 (s, 3 H, OCH
3
13
1
1
1
3
2
3
1
3
27.2, 123.3, 120.9, 119.0, 111.3, 65.3, 55.5, 48.5 ppm. C22
H
20
N
2
O
3
(
328.2): calcd. C 80.46, H 6.14, N 8.53; found C 80.56, H 6.11,
141.0, 136.3, 130.1, 129.0, 128.8, 127.9, 127.7, 127.4, 127.1, 119.4,
118.7, 114.3, 113.1, 65.5, 55.4, 52.2 ppm.
N 8.49.
α-[(Diphenylmethyl)amino]-α-(2-nitrophenyl)acetonitrile (7e): The
α-[(Diphenylmethyl)amino]-α-(3-nitrophenyl)acetonitrile (7i):[7a] The
crude material was purified by flash chromatography on silica gel
crude material was purified by flash chromatography on silica gel
(
Et
yield as a white solid. The chromatographed material was deter-
mined to be of 89% ee by chiral HPLC analysis [Chiralpak AD-H, mined to be of 88% ee by chiral HPLC analysis [Chiralpak AD-H,
n-hexane/iPrOH, 95:5, 1.0 mL/min, t(minor) 11.88 min, n-hexane/iPrOH, 80:20, 1.0 mL/min, t(minor) 6.16 min,
2
O/light petroleum ether, 1:10) to afford the product in 85%
(Et
2
O/light petroleum ether, 1:10) to afford the product in 87%
yield as a white solid. The chromatographed material was deter-
ϭ
ϭ
3824
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 3818Ϫ3826

Enantioselective Strecker Reactions between Aldimines and Trimethylsilyl Cyanide
FULL PAPER
t(major) ϭ 7.01 min]; m.p. 101Ϫ103 °C. [α]2
0
ϭ Ϫ4.1 (c ϭ 0.48 in
D
2
(m, 14 H, aromatic H), 5.22 (s, 1 H, HCPh ), 4.57 (d, J ϭ 12.4 Hz,
1
13
CHCl
H), 8.25 (dd, J ϭ 1.6, 8.0 Hz, 1 H; aromatic H), 7.92 (d, J ϭ 6.0 Hz,
H, aromatic H), 7.64Ϫ7.23 (m, 11 H, aromatic H), 5.27 (s, 1 H, 129.01, 128.8, 128.0, 127.7, 127.4, 127.0, 118.5, 116.1, 115.8, 65.6,
HCPh ), 4.72 (d, J ϭ 12.4 Hz, 1 H, HCCN), 2.27 (d, J ϭ 12.4 Hz, 51.7 ppm.
H, NH) ppm. 13C NMR (100 MHz, CDCl
): δ ϭ 148.5, 142.1,
3
). H NMR (400 MHz, CDCl
3
): δ ϭ 8.45 (s, 1 H, aromatic 1 H; HCCN), 2.13 (d, J ϭ 12.4 Hz, 1 H; NH) ppm. C NMR
(100 MHz, CDCl ): δ ϭ 142.5, 140.9, 130.74, 130.70, 129.1, 129.03,
3
1
2
1
1
1
3
α-(4-Cyanophenyl)-α-[(diphenylmethyl)amino]acetonitrile (7n): The
crude material was purified by flash chromatography on silica gel
40.4, 136.9, 133.2, 130.1, 129.2, 128.9, 128.2, 127.9, 127.4, 127.0,
24.1, 122.4, 117.7, 65.7, 51.7 ppm.
(Et
2
O/light petroleum ether, 1:8) to afford the product in 30% yield
α-[(Diphenylmethyl)amino]-α-(4-methylphenyl)acetonitrile
The crude material was purified by flash chromatography on silica
gel (Et O/light petroleum ether, 1:60) to afford the product in 72%
(7j):[7c] as a white solid. The chromatographed material was determined to
be of 61% ee by chiral HPLC analysis [Chiralcel OD, n-hexane/
iPrOH, 80:20, 1.0 mL/min, t(minor) ϭ 13.31 min, t(major) ϭ
2
2
0
yield as a white solid. The chromatographed material was deter-
mined to be of 75% ee by chiral HPLC analysis [Chiralpak AD-H,
16.34 min]; m.p. 109Ϫ110 °C. [α] ϭ Ϫ1.3 (c ϭ 0.39 in CHCl3).
H NMR (400 MHz, CDCl ): δ ϭ 7.71 (s, 3 H, aromatic H), 7.56
D
1
3
n-hexane/iPrOH, 80:20, 1.0 mL/min, t(minor)
ϭ
10.39 min,
(d, J ϭ 7.2 Hz, 2 H; aromatic H), 7.45Ϫ7.24 (m, 9 H, aromatic H),
t(major) ϭ 23.68 min], after recrystallization from n-hexane to af- 5.24 (s, 1 H, HCPh ), 4.66 (d, J ϭ 12.4 Hz, 1 H; HCCN), 2.22 (d,
2
2
0
13
ford of a colorless crystal (Ͼ 99% ee); m.p. 104Ϫ106 °C. [α]
D
ϭ
3
J ϭ 12.4 Hz, 1 H; NH) ppm. C NMR (100 MHz, CDCl ): δ ϭ
1
Ϫ2.5 (c ϭ 1.0 in CHCl
3
). H NMR (400 MHz, CDCl
3
): δ ϭ 7.55 142.2, 140.4, 139.7, 132.7, 129.2, 128.9, 128.2, 128.0, 127.9, 127.4,
(
d, J ϭ 7.6 Hz, 2 H; aromatic H), 7.45Ϫ7.19 (m, 12 H, aromatic 127.0, 118.1, 117.7, 113.1, 65.7, 52.0 ppm. C H N (323.1): calcd.
2
2
17
3
2
H), 5.22 (s, 1 H, HCPh ), 4.54 (d, J ϭ 12.0 Hz, 1 H, HCCN), 2.36 C 81.71, H 5.30, N 12.99; found C 81.76, H 5.33, N 13.16.
), 2.10 (d, J ϭ 12.4 Hz, 1 H, NH) ppm. 1 C NMR
3
(
(
1
s, 3 H, CH
100 MHz, CDCl
28.7, 127.8, 127.6, 127.4, 127.10, 127.06, 118.9, 65.5, 52.1, 21.1
ppm.
3
α-[(Diphenylmethyl)amino]-α-furylacetonitrile (7o):[7a] The crude
material was purified by flash chromatography on silica gel (Et O/
3
): δ ϭ 142.7, 141.1, 138.9, 132.0, 129.6, 128.9,
2
light petroleum ether, 1:15) to afford the product in 86% yield as a
white solid. The chromatographed material was determined to be
of 49% ee by chiral HPLC analysis [Chiralpak AS-H, n-hexane/
iPrOH, 95:5, 1.0 mL/min, t(minor) ϭ 12.18 min, t(major) ϭ
α-(4-Chlorophenyl)-α-[(diphenylmethyl)amino]acetonitrile
The crude material was purified by flash chromatography on silica
gel (Et O/light petroleum ether, 1:30) to afford the product in 93%
(7k):[7a]
2
0
1
2
13.14 min]; m.p. 99Ϫ101 °C. [α]D ϭ Ϫ1.7 (c ϭ 1.2 in CHCl ). H
3
yield as a white solid. The chromatographed material was deter-
NMR (400 MHz, CDCl ): δ ϭ 7.55Ϫ7.24 (m, 11 H, aromatic H
3
mined to be of 78% ee by chiral HPLC analysis [Chiralpak AD-H,
and furyl H), 6.47 (d, J ϭ 3.6 Hz, 1 H; furyl H), 6.40 (dd, J ϭ 1.6,
n-hexane/iPrOH, 80:20, 1.0 mL/min, t(minor)
t(major) ϭ 19.38 min], after recrystallization from n-hexane to af- 2.35 (br. s, 1 H, NH) ppm. C NMR (100 MHz, CDCl ): δ ϭ
ϭ
8.31 min,
3.2 Hz, 1 H, furyl H), 5.19 (s, 1 H, HCPh ), 4.67 (s, 1 H, HCCN),
2
1
3
3
2
0
ford of a colorless crystal (Ͼ 99% ee); m.p. 102Ϫ104 °C. [α]
D
ϭ
147.3, 143.6, 142.3, 140.9, 129.0, 128.8, 127.9, 127.7, 127.4, 127.2,
): δ ϭ 116.9, 110.6, 108.8, 65.1, 46.2 ppm.
), 4.57 (d,
J ϭ 12.4 Hz, 1 H; HCCN), 2.14 (d, J ϭ 12.8 Hz, 1 H, NH) ppm.
1
Ϫ4.5 (c ϭ 0.61 in CHCl
3 3
). H NMR (400 MHz, CDCl
7.56Ϫ7.21 (m, 14 H, aromatic H), 5.22 (s, 1 H, HCPh
2
trans-2-[(Diphenylmethyl)amino]-4-phenylbut-3-enenitrile
The crude material was purified by flash chromatography on silica
gel (Et O/light petroleum ether, 1:10) to afford the product in 88%
(7p):[6e]
13
3
C NMR (100 MHz, CDCl ): δ ϭ 142.5, 140.8, 135.0, 133.4,
1
5
29.2, 129.1, 128.8, 128.6, 128.0, 127.8, 127.4, 127.0, 118.4, 65.6,
1.8 ppm.
2
yield as a white solid. The chromatographed material was deter-
mined to be of 67% ee by chiral HPLC analysis [Chiralpak AD-H,
α-[(Diphenylmethyl)amino]-α-(4-methoxyphenyl)acetonitrile
The crude material was purified by flash chromatography on silica
gel (Et O/light petroleum ether, 1:10) to afford the product in 90%
(7l):[7a]
n-hexane/iPrOH, 80:20, 1.0 mL/min, t(minor)
ϭ
5.27 min,
2
0
t(major) ϭ 6.93 min]; m.p. 90Ϫ92 °C. [α] ϭ Ϫ1.1 (c ϭ 0.51 in
D
1
2
CHCl ). H NMR (400 MHz, CDCl ): δ ϭ 7.55 (d, J ϭ 7.6 Hz, 2
3
3
yield as a liquid. The chromatographed material was determined
to be of 62% ee by chiral HPLC analysis [Chiralpak AD-H, n-
H, aromatic H), 7.48 (d, J ϭ 7.6 Hz, 2 H; aromatic H), 7.44Ϫ7.25
(m, 11 H, aromatic H), 6.93 (d, J ϭ 16 Hz, 1 H, ϭCHPh), 6.25
hexane/iPrOH, 80:20, 1.0 mL/min, t(major)
ϭ
11.62 min,
(qd, J ϭ 1.2, 5.2, 16.0 Hz, 1 H, ϭCHϪ), 5.24 (s, 1 H, HCPh ),
2
t(minor) ϭ 30.15 min]. [α]2
400 MHz, CDCl
.48Ϫ7.22 (m, 10 H, aromatic H), 6.96Ϫ6.92 (m, 2 H, aromatic
H), 5.23 (s, 1 H, HCPh2), 4.55 (s, 1 H, HCCN), 3.83 (s, 3 H, OCH
0
1
13
D
3
ϭ Ϫ1.5 (c ϭ 1.6 in CHCl ). H NMR 4.27 (s, 1 H, HCCN), 2.02 (br. s, 1 H, NH) ppm. C NMR
(
3
): δ ϭ 7.58Ϫ7.56 (m, 2 H, aromatic H), (100 MHz, CDCl ): δ ϭ 142.8, 141.1, 135.3, 133.8, 128.9, 128.8,
3
7
128.75, 128.70, 128.55, 127.8, 127.7, 127.4, 127.1, 126.8, 122.4,
), 118.3, 65.3, 50.1 ppm.
3
1
3
2
1
1
3
.11 (br. s, 1 H, NH) ppm. C NMR (100 MHz, CDCl ): δ ϭ
60.0, 142.6, 141.1, 128.8, 128.6, 128.4, 127.7, 127.5, 127.3, 127.0,
18.8, 114.2, 65.4, 55.2, 51.7 ppm.
Acknowledgments
α-[(Diphenylmethyl)amino]-α-(4-fluorophenyl)acetonitrile (7m):[7c] We thank the National Natural Science Foundation of China (No.
The crude material was purified by flash chromatography on silica
20072037, 20390050, and 20225206) and the Ministry of Education
of the P. R. China for financial support.
gel (Et O/light petroleum ether, 1:30) to afford the product in 95%
2
yield as a white solid. The chromatographed material was deter-
mined to be of 72% ee by chiral HPLC analysis [Chiralpak AD-H,
8
0:20 n-hexane/iPrOH, 1.0 mL/min, t(major)
ϭ
6.71 min,
[
1] [1a]
R. M. Williams, Synthesis of Optically Active α-Amino Ac-
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994, 50, 1539Ϫ1650.
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0
1
0.37 min, t(minor) ϭ 13.38 min]; m.p. 84Ϫ86 °C. [α]
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[2]
(c ϭ 0.45 in CHCl
3
). H NMR (400 MHz, CDCl
3
): δ ϭ 7.57Ϫ7.07
Eur. J. Org. Chem. 2003, 3818Ϫ3826
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3825

Z. Jiao, X. Feng, B. Liu, F. Chen, G. Zhang, Y. Jiang
FULL PAPER
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CCDC-217323 contains the supplementary crystallographic
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at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; Fax: (internat.) ϩ 44-1223/336-033;
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[
7]
For asymmetric Strecker reaction catalyzed by chiral molecule,
[
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see:
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Received May 26, 2003
3826
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Eur. J. Org. Chem. 2003, 3818Ϫ3826