Enantioselective Strecker-type reaction of phosphinoyl ketimines catalyzed by a chiral Zr-bipyridyldiol catalyst

Article abstract of DOI:10.1016/j.tetasy.2008.09.011

An enantioselective Strecker reaction of N-diphenylphosphinoyl ketimines with TMSCN employing a chiral zirconium complex formed from chiral bipyridyl diol 1 as catalyst is described. The catalytic efficiency of chiral ligand 1 with other Lewis acids was also explored. Higher yields (50-85%) with moderate to good enantioselectivities (30-80%) were achieved for a variety of N-diphenylphosphinoyl ketimines.

Full text of DOI:10.1016/j.tetasy.2008.09.011

Tetrahedron: Asymmetry 19 (2008) 2201–2209
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Enantioselective Strecker-type reaction of phosphinoyl ketimines catalyzed
by a chiral Zr-bipyridyldiol catalyst
*
Yi-Jing Chen, Chinpiao Chen
Department of Chemistry, National Dong Hwa University, Shoufeng, Hualien 974, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
An enantioselective Strecker reaction of N-diphenylphosphinoyl ketimines with TMSCN employing a chi-
ral zirconium complex formed from chiral bipyridyl diol 1 as catalyst is described. The catalytic efficiency
of chiral ligand 1 with other Lewis acids was also explored. Higher yields (50–85%) with moderate to good
enantioselectivities (30–80%) were achieved for a variety of N-diphenylphosphinoyl ketimines.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 6 August 2008
Accepted 2 September 2008
Available online 9 October 2008
1. Introduction
high enantioselectivity in the asymmetric Strecker reaction of keti-
mines. The use of structurally different chiral ligands is therefore
Chiral cyanohydrins are highly versatile intermediates, which
can be converted into a wide range of pharmaceutically and indus-
trially useful chiral compounds. The catalytic asymmetric Strecker
reaction1 is one of the most convenient methods for the synthesis
of chiral amino nitriles in high yields.2 The process involves the
addition of trimethylsilyl cyanide (TMSCN) or HCN to aldimines
in the presence of a chiral catalyst. A variety of C1 or C2 symmetric
chiral diamides, TADDOLs, BINOL, salen and other ligands in com-
bination with Lewis acids such as Ti(Oi-Pr)4, TiCl4, AlCl3, Gd(Oi-
Pr)3, Et2AlCl and Zr(Ot-Bu)4 were reported to induce high enantio-
selectivity during the reaction.3 Lipton et al. investigated the
viability of the asymmetric Strecker synthesis of amino acids using
a cyclic guanidine dipeptide in the reaction of N-benzhydrylimines
essential for a broad substrate scope and in the improvement of
the enantioselectivity of ketimine substrates.
As an extension of our earlier work on the asymmetric addition
of TMSCN to aldehydes forming chiral cyanohydrins in good
enantiomeric excess using chiral Ti-1 catalyst,11a chiral ligand 1
with different Lewis acids was explored towards the enantioselec-
tive addition of TMSCN to N-diphenylphosphinoyl ketimines
(Scheme 1).
Ph
O
O
with hydrogen cyanide to N-benzhydryl-a
-aminonitriles.4 Jacob-
Ph
Zr(O
t-Bu)4 (10 mol %), 1,
PPh2
N
N
OH
PPh2
N
TMSCN, THF, -30 oC, 72 h
HN
sen et al. reported chiral 1,2-trans-diaminocyclohexanes modified
with urea and thiourea functionalities on one side, and salicylaldi-
mine on the other side5,6 to furnish efficient organocatalysts for the
cyanohydrination of imines. Although asymmetric hydrocyanation
of aldimines has been well established with high yields and enantio-
selectivity, the more related reaction of ketimines has not been
fully explored. Recently, more enantioselective catalysts have been
applied to improve the asymmetric induction of Strecker reaction
involving ketimines as substrates.7 Among the ketimines activated
with different protections at the imine, N-diphenylphosphinoyl
ketimines are reported to be better substrates for the Strecker reac-
tion which require protic additives in the reaction.8 Chiral alkyl
diphenylphosphinite in combination with two hydroxyl groups
CN
R1
R2
OH
Ph
Ph
R1
5b-25b
R2
5a-25a
1
Scheme 1. Enantioselective Strecker reaction of N-diphenylphosphinoyl ketimines
catalyzed by Zr(Ot-Bu)4-1.
2. Results and discussion
9
and Gd(Oi-Pr)3 and chiral bifunctional N,N0-dioxides derived from
As an initial effort towards the ligand synthesis, chiral N,N-diox-
ide 4 resembling Feng0s catalyst10 was synthesized from chiral
bipyridine 211c according to Scheme 2. Treatment of 2 with LDA,
followed by reaction with diphenylphosphinoyl chloride afforded
bipyridine 3 in 64% yield. Oxidation of 3 with mCPBA formed the
chiral N,N-dioxide 4 in excellent yield.
L
-prolinamide10 were the two catalyst systems reported to induce
* Corresponding author.
E-mail address: chinpiao@mail.ndhu.edu.tw (C. Chen).
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.09.011

2202
Y.-J. Chen, C. Chen / Tetrahedron: Asymmetry 19 (2008) 2201–2209
2.1. Effect of reaction solvents and Lewis acids on the
enantioselective addition of TMSCN to N-diphenylphosphinoyl
ketimines
O
O
P
Ph
P
Ph
Ph
m
CPBA
Ph
N
N
LDA, Ph2POCl
N
N
N
N
O
O
The asymmetric addition of TMSCN to 5a was screened with
catalytic species formed from chiral ligand 1 and different Lewis
acids (Table 1). Accordingly four different Lewis acids (10 mol %),
namely Ti(Oi-Pr)4, Et2AlCl, Gd(Oi-Pr)3 and Zr(Ot-Bu)4, were
employed for the reactions performed at ꢀ40 °C in toluene. The
most commonly employed titanium complex afforded only the
racemic 5b (72%) even after longer reaction times (Table 1, entry
5). In a similar way, no enantioselectivity was observed in the case
of Et2AlCl (65% of racemic 5b). The lanthanide metal complex
Gd(Oi-Pr)3, however, gave promising results, although with poor
enantioselectivity (95% yield; 3% ee). The reactions involving lan-
thanide complexes Gd(Oi-Pr)3-1 and Zr(Ot-Bu)4-1 were then per-
formed in solvents other than toluene (Table 1, entries 9–13) to
improve the enantioselectivity of the reaction. Tetrahydrofuran
was found to be better solvent for the Zr(Ot-Bu)4-1 catalyzed reac-
tion displaying higher selectivity (Table 1, entry 9). Gd(Oi-Pr)3-1,
did not exhibit any improvement in the enantioselectivity of the
reaction under the conditions screened and therefore was not ex-
plored further.
3
2
4
Scheme 2. Synthesis of the chiral ligands 3 and 4.
Chiral bipyridyldiol 1 was synthesized following the reported
protocol.11b The chiral ligands 1, 3 and 4 were screened for the
asymmetric addition of TMSCN to N-diphenylphosphinoyl keti-
mines following the protocol reported in the literature (Scheme
1). Accordingly the ligands were treated with an equal amount of
Zr(Ot-Bu)4 (10 mol %) and the in situ formed catalysts were used
for the addition of TMSCN to N,N-diphenyl-N-(1-phenylethyli-
dene)phosphinamide 5a at ꢀ40 °C. After considerably longer reac-
tion times (40 h), the Strecker product 5b (Table 1) was formed in
excellent yield, however, no chiral induction was observed with
either of the ligands 3 and 4 (Table 1, entries 1 and 2). Interestingly,
there was no reaction when ligand 4 was used in the absence of
any Lewis acid (Table 1, entry 3). On the other hand, ligand 1 under
identical reaction conditions afforded the (S)-enantiomer in 20%
enantiomeric excess and 73% isolated yield (Table 1, entry 4).
Based on this preliminary observation, ligand 1 was used for fur-
ther exploration of the reaction. A variety of reaction conditions
(temperature, reaction time and catalyst loading) and Lewis acids
were attempted to establish the optimized reaction condition.
Alternatively, the Strecker reaction of other activated ketimine
substrates with benzyl and benzhydryl protection at the imine
were subjected to reaction with TMSCN in the presence of the
zirconium catalyst (formed from 1, 3 and 4). All the catalysts
employed afforded the corresponding Strecker product in good
yields but in poor enantioselectivities under different reaction
conditions.
2.2. Effect of reaction temperature and catalyst loading on the
enantioselective addition of TMSCN to N-diphenylphosphinoyl
ketimines
The asymmetric addition of TMSCN to ketimine 5a was then
performed with different catalyst loadings of Zr(Ot-Bu)4-1
(1ꢀ20 mol %) and at different reaction temperatures in THF (Table 2).
Table 2
Effect of the reaction temperature and catalyst loading on the asymmetric Strecker
reaction of 5a
Entry
Catalyst loading (mol %)
T (°C)
Conversiona,b (%)
eec (%)
1
2
3
4
5
6
10
10
10
1
5
20
0
ꢀ20
ꢀ40
ꢀ20
ꢀ20
ꢀ20
93
84
33
—
30
98
37
74
78
—
54
63
Table 1
Asymmetric Strecker reaction of 5a catalyzed by various Lewis acid–ligand complexes
in different solvents
a,b,c
O
See Table 1.
O
PPh2
PPh2
HN
N
CN
CH3
Lewis acid (10 mol%), Ligand
TMSCN, Solvent, T oC, 72 h
CH3
-20oC
90
80
70
60
50
40
-30oC
-40oC
5b
5a
Entry
Ligand
Lewis acid
Solvent
T (°C)
Conversiona,b
(%)
eec (%)
10 mol %
1
2
3
4
5
6
7
8
9
10
11
12
13
3
4
4
1
1
1
1
1
1
1
1
1
1
Zr(Ot-Bu)4
Zr(Ot-Bu)4
None
Zr(Ot-Bu)4
Ti(Oi-Pr)4
Et2AlCl
Gd(Oi-Pr)3
Zr(Ot-Bu)4
Zr(Ot-Bu)4
Zr(Ot-Bu)4
Gd(Oi-Pr)3
Gd(Oi-Pr)3
Gd(Oi-Pr)3
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
ꢀ40
ꢀ40
ꢀ40
ꢀ40
ꢀ40
ꢀ40
ꢀ40
rt
rt
rt
rt
rt
85
97
—
2
0
—
20
0
0
3
2
17
4
73
72
65
95
90
95
96
92
90
93
CH2Cl2
Toluene
THF
0
3
2
CH2Cl2
rt
a
Conversions were determined by chiral HPLC.
t = 40 h.
Determined by HPLC on chiral OD column and the absolute configuration was
0
10
20
30
40
50
60
70
80
90
100
b
c
Conversion (%)
assigned (S) based on comparison with the literature data.7
Figure 1. Conversion and enantiomeric excess of 5a at different temperatures.

Y.-J. Chen, C. Chen / Tetrahedron: Asymmetry 19 (2008) 2201–2209
2203
Table 3
Results of the effect of aryl substituents on the asymmetric Strecker reaction of ketimines
O
O
Ph
Ph
CN
CH3
Ph
P
OH
P
N
N
HN
Ph
PPh2Cl, Et3N
Zr(Ot-Bu)4-1 (10 mol %)
CH3
CH3
R
R
R
TMSCN (1.0 equiv.), THF
-30 oC, 72 h
CH2Cl2-hexane
6-16
6a-16a
6b-16b
eeb (%)
Entry
Substrate
Product
Yielda (%)
[a
]
D
(c CH2Cl2)
1
2
3
4
5
6
7
8
9
6a; R = o-OMe
7a; R = m-OMe
8a; R = p-OMe
9a; R = o-Me
10a; R = m-Me
11a; R = p-Me
12a; R = o-Br
13a; R = m-Br
14a; R = p-Br
15a; R = m-Cl
16a; R = p-Cl
6b
7b
8b
9b
10b
11b
12b
13b
14b
15b
16b
81
86
63
87
76
63
52
67
85
78
76
64 (S)
72 (S)
34 (S)
36 (S)
68 (S)
70 (S)d
ꢀ2.15 (1.3)
ꢀ4.9 (1.6)
ꢀ2.35 (0.85)
ꢀ2.7 (2.0)
ꢀ1.7 (1.05)
ꢀ4.8 (0.9)
ꢀ1.3 (1.15)
ꢀ4.6 (1.4)
ꢀ6.4 (1.15)
ꢀ3.2 (1.25)
ꢀ5.7 (0.85)
c
—
54 (S)
44 (S)
46 (S)
60 (S)d
10
11
a
Isolated yield of a-aminonitriles.
b
c
Determined by HPLC on chiral OD column and the absolute configurations were assigned based on comparison with the literature data.
Ee could not be determined by HPLC.
Please see Ref. 9.
d
ilar manner, an increase in catalyst loading at lower temperature
improved both the yields and enantiomeric excess of 5b. The opti-
mum catalyst loading was found to be 10 mol % (Table 2, entry 2),
beyond which the enantioselectivity of the catalyst deteriorated
(Table 2, entry 6).
An increase in the reaction time generally afforded higher
conversions and better enantioselectivity as seen in Figure 1. The
reaction of 5a using 10 mol % of Zr-1 was studied at three different
temperatures in different time intervals. At temperatures beyond
ꢀ30 °C, slower reaction rates with moderate enantioselection were
observed. The optimum reaction temperature was hence assigned
as ꢀ30 °C (72 h), which afforded the highest enantioselectivity
compared to the equally efficient ꢀ20 °C.
80
70
60
50
40
30
20
10
0
m-Me
m-OMe
m-Br
m-Cl
-0.1
0
0.1
0.2
0.3
0.4
0.5
σm
80
70
60
50
40
30
20
10
0
p-Me
p-Cl
p-Br
2.3. Effect of substrate structure
p-OMe
The catalytic efficiency of Zr(Ot-Bu)4-1 towards the asymmetric
Strecker reaction of different ketimines was investigated under the
optimized reaction condition.
-0.3
-0.2
-0.1
0
0.1
0.2
0.3
σp
A series of N-diphenylphosphinoyl ketimines 6a–16a were syn-
thesized from various acetophenone oximes 6–16 and subjected to
a Strecker reaction in order to study the electronic influence of sub-
stituents on the aryl moiety on the enantioselectivity of the reac-
tion. The isolated yields and enantiomeric excess of asymmetric
Strecker reaction of ketimines 6a–16a by Zr(Ot-Bu)4-1 is shown
in Table 3.
Figure 2. The plots of the enantiomeric excess of the reaction and Hammett
substituent constants [rm (a) and rp (b)].
Lower temperatures improved the enantioselectivity of the reac-
tion drastically although the reactions were comparatively slower
and required longer reaction times for higher conversions. In a sim-
Table 4
Asymmetric Strecker reaction of phenylalkyl ketimines with TMSCN
O
Ph
O
Ph
P
OH
Zr(Ot-Bu)4-1 (10 mol %),
TMSCN (1.0 equiv.), THF,
-30 oC, 72 h
P
N
HN Ph
CN
N
Ph
Et3N, PPh2Cl,
R
CH2Cl2-hexane
R
R
17-20
17b-20b
17a-20a
Substrate
Product
Yielda (%)
eeb (%)
[a] (c CH2Cl2)
D
17a; R = Et
18a; R = nPr
19a; R = iPr
20a; R = H
17b
18b
19b
20b
68
68
73
75
10
42
35
10
+0.9 (1.2)
ꢀ3.4 (0.85)
ꢀ3.2 (1.05)
ꢀ0.6 (1.2)
a,b
See Table 3.

2204
Y.-J. Chen, C. Chen / Tetrahedron: Asymmetry 19 (2008) 2201–2209
Ketimines with electron rich methoxy and methyl groups (at
gation of the presented catalyst systems as well as broad catalytic
studies is currently underway.
the meta-position) afforded higher enantiomeric excesses com-
pared to electron deficient halogens. The substituents at the
meta-position of the aryl moiety showed higher enantioselectivi-
ties when compared to the same substituent on the other posi-
tions. The plots of the enantiomeric excess of the reaction and
4. Experimental
4.1. 8-(Diphenyl-phosphinoyl)-10,10-dimethyl-5-pyridin-2-yl-
6-aza-tricyclo[7.1.1.02,7]undeca-2(7),3,5-triene 3
Hammett substituent constants (rm and
rp) (Fig. 2a and b) are
interesting and showed the apparent substituent effect of the sub-
strates on the enantioselectivity of the reaction. Electron-with-
drawing groups and mild electron releasing groups at the para-
positions of the aryl moiety of the ketimines displayed higher ee
in comparison to the strongly electron releasing groups at the same
position (Fig. 2b). In general, the substituent effect of the sub-
strates in these reactions differs markedly to that observed in the
asymmetric TMSCN addition to aldehydes by the same chiral
ligand 1.11a
The influence of the alkyl part of the substrate on the enantio-
selectivity of the reaction was studied with ketimines possessing
alkyl groups 17a–19a larger than a methyl group. The ketimine
substrates were synthesized from the corresponding phenyl alkyl
ketoximes 17–19 and reacted with TMSCN in the presence of
Zr-1 as described earlier (Table 4). Under identical reaction condi-
tions, the yield and enantiomeric excess in the case of these sub-
strates were lower than 5a which could probably be as a result
of increase in steric crowding. The benzaldoxime derived N-diphe-
nylphosphinoyl aldimine 20a, however, formed the Strecker prod-
uct 20b in low enantiomeric excess though in good yield (Table 4,
entry 4).
A solution of 2 (2.50 g, 10.0 mmol) in THF (20 mL) was added to
a LDA solution (1.1 equiv.) in THF at ꢀ40 °C under an argon atmo-
sphere, and stirred for 2 h at the same temperature. To the result-
ing dark blue solution was added diphenylphosphinic chloride
(3.0 mL, 10.0 mmol) dropwise. The reaction mixture was warmed
to room temperature and stirred for a further 15 h. After the com-
pletion of the reaction, saturated ammonium chloride solution
(20 mL) was added, and extracted with ethyl acetate (2 ꢁ 30 mL).
The combined organic extracts were dried over anhydrous magne-
sium sulfate, filtered and the solvent was removed under reduced
pressure to yield a crude product, which was purified by flash col-
umn chromatography on silica gel using ethyl acetate/hexane gra-
dient (3:7, 1:1) as the mobile phase to afford the pure compound 3
(2.88 g, 6.4 mmol, 64%) and unreacted starting material 2 (693 mg,
2.7 mmol). 1H NMR (CDCl3, d): 8.57 (s, 1H), 8.19 (s, 1H), 7.93–7.89
(t, J = 8.9 Hz, 2H), 7.85–7.80 (t, J = 8.9 Hz, 2H), 7.58–7.34 (m, 8H),
7.19 (s, 1H), 6.83–6.81 (d, J = 8.1 Hz, 1H), 4.40–4.36 (d,
J = 13.7 Hz, 1H), 2.77 (s, 1H), 2.70–2.63 (m, 1H), 2.58–2.50 (m,
1H), 1.60–1.70 (d, J = 9.8 Hz, 1H), 1.41 (s, 3H), 0.72 (s, 3H); 13C
NMR (CDCl3, d): 156.0, 152.8, 151.8 (d, J = 6.0 Hz), 148.7, 143.0
(d, J = 6.0 Hz), 136.3, 135.2, 134.6, 133.9, 132.9, 132.1 (d,
J = 9.5 Hz), 131.4 (d, J = 9.5 Hz), 131.2, 130.9, 128.6 (d,
J = 11.1 Hz), 128.3 (d, J = 11.1 Hz), 123.1, 120.7, 118.3, 46.1 (d,
J = 20.6 Hz), 45.3, 42.1 (d, J = 10.3 Hz), 41.3, 28.5, 25.8, 21.0; 31P
NMR (CDCl3, d): 33.1; IR (KBr): 3398, 3058, 2978, 2924, 1576,
1435, 1197, 792 cmꢀ1; MS m/z: 450 (M+, 7), 435 (3), 277 (18),
249 (100), 201 (25), 77 (14); HRMS-EI m/z [M]+ calcd for
C29H27N2OP, 450.1861; found, 450.1867.
The efficiency of the new catalyst system was then explored
with ketimines 21a–25a possessing different aryl or heteroaro-
matic ring. Though a good yield of Strecker product was obtained
in all the cases (Table 5), the enantioselectivities were moderate
to low under the reaction condition employed. As expected, keti-
mine 23a with a furanyl moiety underwent the Strecker reaction
with high enantioselectivity forming 23b in 76% ee as a result of
the oxophilic nature of the zirconium catalyst (Table 5, entry 3).9
Table 5
Substrate generality of the asymmetric Strecker reaction of ketimines
4.2. 8-(Diphenyl-phosphinoyl)-10,10-dimethyl-5-(1-oxy-
pyridin-2-yl)-6-aza-tricyclo[7.1.1.02,7]undeca-2(7),3,5-triene
6-oxide 4
Zr(Ot-Bu)4-1 (10 mol %),
TMSCN (1.0 equiv.), THF,
-30 oC, 72 h
O
Ph
O
Ph
P
OH Et3N, PPh2Cl,
CH2Cl2-hexane
P
N
HN Ph
CN
N
Ph
R
21-25
R
R
To an ice-cold solution of 3 (225 mg, 0.5 mmol) in CH2Cl2
(10 mL) was added mCPBA (70%) (378 mg, 1.1 mmol) portionwise
and stirred for 30 min. It was then warmed to ambient tempera-
ture and stirred for 20 h. After the completion of reaction, satu-
rated sodium bicarbonate solution was added, and the aqueous
phase was extracted with CH2Cl2. The extracts were dried over
anhydrous magnesium sulfate, and the solvent was removed under
reduced pressure to yield a crude product which was purified by
flash column chromatography on Al2O3 using methanol/ethyl ace-
tate gradient (0:1, 1:9) to give pure 4 (204 mg, 0.42 mmol, 84%). 1H
NMR (CDCl3, d): 9.00–8.97 (d, J = 8.1 Hz, 1H), 8.19–8.17 (d,
J = 6.4 Hz, 1H), 7.89–7.82 (m, 4H), 7.54–7.44 (m, 6H), 7.37–7.34
(d, J = 8.0 Hz, 1H), 7.08–7.04 (t, J = 7.0 Hz, 1H), 6.83–6.75 (m, 2H),
4.36–4.31 (d, J = 12.7 Hz, 1H), 2.82–2.78 (t, J = 5.5 Hz, 1H), 2.58–
2.55 (m, 2H), 1.85–1.78 (d, J = 9.2 Hz, 1H), 1.40 (s, 3H), 0.70 (s,
3H); 13C NMR (CDCl3, d): 151.9 (d, J = 6.9 Hz), 146.8, 145.8, 144.0
(d, J = 4.7 Hz), 140.7, 134.7, 134.2, 134.0, 133.7, 133.2, 131.9 (d,
J = 8.9 Hz), 131.3, 131.1 (d, J = 8.6 Hz), 128.7 (d, J = 11.5 Hz), 128.4
(d, J = 1.5 Hz), 127.6, 127.4, 125.2, 124.1, 123.3, 46.1, 45.5 (d,
J = 68.6 Hz), 42.0 (d, J = 11.0 Hz), 42.1, 28.4, 25.8, 21.0; 31P NMR
(CDCl3, d): 33.0; IR (KBr): 3101, 2865, 2344, 1738, 1437, 1187,
996 cmꢀ1; MS m/z: 482 (M+, 0.2), 466 (5), 449 (26), 405 (11), 265
(14), 249 (100), 207 (39), 77 (20); HRMS-EI (m/z): [M]+ calcd for
C29H27N2O3P, 428.1759; found, 428.1762.
21b-25b
[a] (c CH2Cl2)
D
21a-25a
Entry Substrate
Product Yielda (%) eeb (%)
c
1
2
3
4
5
21a; R = 1-naphthalenyl 21b
22a; R = 2-naphthalenyl 22b
73
79
58
65
67
—
ꢀ1.2 (1.25)
ꢀ0.3 (1.9)
ꢀ2.7 (0.9)
ꢀ0.9 (1.05)
ꢀ2.4 (1.05)
10
76
3
23a; R = 2-furanyl
23b
24b
25 b
24a; R = 3-thiophenyl
25a; R = 3-pyridinyl
24
a
Isolated yield of
a
-aminonitriles.
b
Determined by HPLC on chiral OD column and the absolute configurations were
assigned based on comparison with the literature.
c
Ee could not be determined by HPLC.
3. Conclusions
In conclusion, a chiral bipyridyldiol 1 based on a zirconium
complex as a catalyst for the enantioselective Strecker reaction of
ketimines is described. Higher yields with moderate to good
enantioselectivities were achieved for a wide range of substrates
with the optimized catalyst system. The enantioselectivity of the
reaction was strongly influenced by the electronic nature of the
substrate. Other chiral phosphinite bipyridyl ligands 3 and 4, how-
ever, failed to induce enantioselectivity during the reaction under
different reaction conditions. A more detailed mechanistic investi-

Y.-J. Chen, C. Chen / Tetrahedron: Asymmetry 19 (2008) 2201–2209
2205
4.3. General procedure for the preparation of N-
diphenylphosphinoyl ketimines 5a–25a
130.1, 128.4, 128.2, 113.7, 55.5, 22.8 (d, J = 12.9 Hz); 31P NMR
(162 MHz, CDCl3, d): 18.4; IR (KBr): 3266, 3127, 1675, 1601,
1436, 1259, 1174, 915 cmꢀ1; MS m/z: 349 (M+, 9), 216 (99), 199
(100), 140 (31), 124 (35), 77 (64); HRMS-EI (m/z): [M]+ calcd for
C21H20NO2P, 349.1232; found, 349.1227.
To a solution of NH2OHꢂHCl (2.1 g, 30 mmol) and NaOAc (2.5 g,
30 mmol) in EtOH/H2O (16 mL, 1:1) was added ketones (20 mmol)
at room temperature, and then refluxed for 20 h. After cooling to
room temperature, the reaction mixture was stored at ꢀ20 °C for
24 h. The precipitated oxime 5–25 was filtered, washed with cold
aqueous ethanol, vacuum dried and used directly for further reac-
tion without purification. To a solution of oxime (10 mmol) in
dichloromethane/n-hexane (30 mL, 1:1) was added triethylamine
(1.5 mL, 10 mmol) at ꢀ40 °C, and stirred for 10 min followed by
the addition of chlorodiphenylphosphine (2 mL, 10 mmol) drop-
wise. After stirring at ꢀ40 °C for 1 h and room temperature for
15 h, the solvents were removed under reduced pressure. Water
(20 mL) was added to the residue, and then extracted with dichlo-
romethane (2 ꢁ 30 mL). The extracts were dried over anhydrous
magnesium sulfate, and the solvent was removed under reduced
pressure to yield a crude product which was purified by flash col-
umn chromatography to give pure ketimines 5a–25a.
4.3.5. N-[(E)-1-(2-Methylphenyl)ethylidene]diphenyl-
phosphinic amide 9a
1H NMR (400 MHz, CDCl3, d): 7.94–7.90 (m, 4H), 7.49–7.39 (m,
7H), 7.31–7.29 (m, 1H), 7.23–7.20 (m, 2H), 2.85 (d, J = 2.0 Hz, 3H),
2.35 (s, 3H); 13C NMR (100.6 MHz, CDCl3, d): 187 (d, J = 9.5 Hz),
142.2, 142.0, 135.2, 134.8, 133.5, 131.9, 131.8, 131.7, 131.6,
131.5, (d, J = 2.7 Hz), 131.3, 129.7, 128.8, 128.7, 128.5, 128.3,
127.2, 125.8, 27.9 (d, J = 13.6 Hz), 20.8; 31P NMR (162 MHz, CDCl3,
d): 19.1; IR (KBr): 3436, 3057, 1967, 1637, 1438, 1195, 829 cmꢀ1
;
MS m/z: 333 (M+, 8), 318 (32), 201 (76), 153 (22), 132 (100), 77
(24); HRMS-EI (m/z): [M]+ calcd for C21H20NOP, 333.1283; found,
333.1278.
4.3.6. N-[(E)-1-(3-Methylphenyl)ethylidene]diphenyl-
phosphinic amide 10a
4.3.1. Diphenyl-N-[(E)-1-phenylethylidene]phosphinic amide
5a
1H NMR (400 MHz, CDCl3, d): 8.00–7.93 (m, 4H), 7.86 (s, 1H),
7.49–7.40 (s, 1H), 7.37 (d, J = 4.8 Hz, 2H), 2.95 (d, J = 2.2 Hz, 3H),
2.44 (s, 3H); 13C NMR (100.6 MHz, CDCl3, d): 181.9 (d, J = 7.6 Hz),
138.2, 135.3, 133.2, 131.9, 131.8, 131.7, 131.6, 131.5, 131.4, 131.3
(d, J = 2.3 Hz), 128.5, 128.4, 128.3, 128.2, 128.1, 125.2, 26.7, 23.2
(d, J = 12.6 Hz); 31P NMR (162 MHz, CDCl3, d): 18.9; IR (KBr):
3228, 3054, 2919, 2322, 1978, 1680, 1634, 1438, 1282, 1106,
886 cmꢀ1; MS m/z: 333 (M+, 4), 216 (100), 199 (70), 140 (23),
124 (24), 77 (40); HRMS-EI (m/z): [M]+ calcd for C21H20NOP,
333.1283; found, 333.1291.
1H NMR (400 MHz, CDCl3, d): 8.10–8.07 (m, 2H), 8.01–7.95 (m,
4H), 7.56–7.40 (m, 9H), 2.97 (d, J = 2.0 Hz, 3H); 13C NMR (100.6
MHz, CDCl3, d): 198.2, 137.6, 137.0, 136.1, 133.1, 131.8, 131.7,
131.0, 130.9, 130.3, 128.6, 128.5, 128.4, 128.3, 128.0, 127.9, 26.6;
31P NMR (162 MHz, CDCl3, d): 18.8; IR (KBr): 3307, 3065, 2899,
1895, 1698, 1494, 1210, 951 cmꢀ1; MS m/z: 320 (M+, 5), 217
(100), 199 (68), 152 (12), 77 (47); HRMS-EI (m/z): [M]+ calcd for
C20H18NOP, 319.1126; found, 319.1126.
4.3.2. N-[(E)-1-(2-Methoxyphenyl)ethylidene]diphenyl-
phosphinic amide 6a
4.3.7. N-[(E)-1-(4-Methylphenyl)ethylidene]diphenyl-
phosphinic amide 11a
1H NMR (400 MHz, CDCl3, d): 7.98–7.93 (m, 4H), 7.64 (d,
J = 7.6 Hz, 1H), 7.46–7.38 (m, 7H), 7.01–6.98 (t, J = 7.4 Hz, 1H),
6.93 (d, J = 8.3 Hz, 1H), 3.80 (s, 3H), 2.88 (d, J = 1.9 Hz, 3H); 13C
NMR (100.6 MHz, CDCl3, d): 185.0 (d, J = 7.7 Hz), 157.9, 135.3,
134.0, 132.2, 131.9, 131.7, 131.6, 131.4, 131.3 (d, J = 2.4 Hz),
131.1, 129.8, 128.4, 128.3, 120.5, 111.4, 55.4, 28.2 (d, J = 13.0 Hz);
31P NMR (162 MHz, CDCl3, d): 18.4; IR (KBr): 3306, 3229, 3071,
2835, 2309, 1967, 1830, 1619, 1435, 1121, 827 cmꢀ1; MS m/z:
349 (M+, 1), 216 (100), 199 (89), 140 (62), 124 (67), 77 (73);
HRMS-EI (m/z): [M]+ calcd for C21H20NO2P, 349.1232; found,
349.1228.
1H NMR (400 MHz, CDCl3, d): 7.42–7.39 (m, 6H), 7.27 (d,
J = 8.1 Hz, 2H), 2.93 (d, J = 2.0 Hz, 3H), 2.40 (s, 3H); 13C NMR
(100.6 MHz, CDCl3, d): 181.4 (d, J = 7.6 Hz), 143.2, 137.0, 136.8,
135.6, 134.3, 131.6, 131.5, 131.3 (d, J = 1.6 Hz), 129.2, 128.4,
128.3, 128.0, 23.0 (d, J = 12.9 Hz), 21.5; 31P NMR (162 MHz, CDCl3,
d): 18.6; IR (KBr): 3255, 3126, 2925, 1906, 1688, 1579, 1436, 1175,
914 cmꢀ1; MS m/z: 333 (M+, 12), 216 (100), 199 (71), 140 (26), 124
(34), 77 (36); HRMS-EI (m/z): [M]+ calcd for C21H20NOP, 333.1283;
found, 333.1284.
4.3.8. N-[(E)-1-(2-Bromophenyl)ethylidene]diphenyl-
phosphinic amide 12a
4.3.3. N-[(E)-1-(3-Methoxyphenyl)ethylidene]diphenyl-
phosphinic amide 7a
1H NMR (400 MHz, CDCl3, d): 7.95–7.90 (m, 4H), 7.56–7.22 (m,
10H), 2.83 (d, J = 1.7 Hz, 3H); 13C NMR (100.6 MHz, CDCl3, d): 186
(d, J = 8.4 Hz), 143.9, 143.6, 134.3, 133.2, 133.0, 132.1, 131.7,
131.6, 131.5 (d, J = 2.0 Hz), 130.4, 128.5, 128.4, 128.3, 128.1,
127.4, 118.7, 28.3 (d, J = 14.1 Hz); 31P NMR (162 MHz, CDCl3, d):
19.6; IR (KBr): 3433, 3056, 1968, 1824, 1649, 1438, 1026,
809 cmꢀ1; MS m/z: 400 (M++2, 100), 398 (M+, 99), 318 (47), 201
(85), 154 (78), 136 (63), 89 (25), 55 (43); HRMS-FAB (m/z):
[M+1]+ calcd for C20H18BrNOP, 398.0309; found, 398.0304.
1H NMR (400 MHz, CDCl3, d): 8.00–7.94 (m, 4H), 7.65–7.63 (m,
2H), 7.47–7.37 (m, 7H), 7.10 (d, J = 8.1 Hz, 1H), 3.88 (s, 3H), 2.95 (d,
J = 2.0 Hz, 3H); 13C NMR (100.6 MHz, CDCl3, d): 181.4 (d, J = 7.7 Hz),
159.7, 140.9 (d, J = 23.9 Hz), 138.4, 135.2, 133.9, 132.6, 132.5,
132.2, 132.0, 131.8, 131.7, 131.6, 131.5, 131.4 (d, J = 2.5 Hz),
129.5, 128.5, 128.3, 121.1, 120.1, 119.6, 117.7, 113.4, 112.3, 55.4,
23.2 (d, J = 12.5 Hz); 31P NMR (162 MHz, CDCl3, d): 18.8; IR (KBr):
3342, 3235, 3058, 2940, 2346, 1975, 1824, 1682, 1637, 1437,
896 cmꢀ1; MS m/z: 349 (M+, 5), 216 (100), 199 (92), 140 (41),
124 (41), 77 (42); HRMS-EI (m/z): [M]+ calcd for C21H20NO2P,
349.1232; found, 349.1229.
4.3.9. N-[(E)-1-(3-Bromophenyl)ethylidene]diphenyl-
phosphinic amide 13a
1H NMR (400 MHz, CDCl3, d): 8.12 (s, 1H), 7.98–7.93 (m, 5H),
7.67 (d, J = 8.0 Hz, 1H), 7.50–7.42 (m, 6H), 7.37–7.33 (t, J = 8.0 Hz,
1H), 2.94 (s, 3H); 13C NMR (100.6 MHz, CDCl3, d): 180.9 (d,
J = 7.5 Hz), 141.4, 141.1, 135.2, 134.8, 135.5, 131.8, 131.7, 131.6,
131.5, 130.8, 130.1, 128.6, 128.5, 128.4, 126.5, 122.8, 23.0 (d,
J = 12.3 Hz); 31P NMR (162 MHz, CDCl3, d): 19.3; IR (KBr): 3234,
3123, 3055, 1963, 1818, 1686, 1642, 1438, 994, 834 cmꢀ1; MS
m/z: 400 (M++2, 25), 398 (M+, 24), 216 (94), 201 (100), 199 (78),
4.3.4. N-[(E)-1-(4-Methoxyphenyl)ethylidene]diphenyl-
phosphinic amide 8a
1H NMR (400 MHz, CDCl3, d): 8.09 (d, J = 8.3 Hz, 2H), 7.99–7.94
(m, 4H), 7.43–7.41 (m, 6H), 6.96 (d, J = 8.2 Hz, 2H), 3.87 (s, 3H),
2.91 (s, 3H); 13C NMR (100.6 MHz, CDCl3, d): 180.5 (d, J = 7.2 Hz),
163.2, 135.8, 134.5, 132.4, 132.1, 131.8, 131.6, 131.5, 131.2,

2206
Y.-J. Chen, C. Chen / Tetrahedron: Asymmetry 19 (2008) 2201–2209
140 (28), 125 (35), 77 (50); HRMS-EI (m/z): [M]+ calcd for
C20H17BrNOP, 397.0231; found, 397.0239.
(100.6 MHz, CDCl3, d): 193.1 (d, J = 10.1 Hz), 139.4, 139.3, 135.7,
134.4, 132.4, 132.3, 131.9, 131.7, 131.6, 131.2 (d, J = 2.5 Hz),
130.3, 128.8, 128.3, 127.8, 127.5, 39.8 (d, J = 16.6 Hz), 20.6; 31P
NMR (162 MHz, CDCl3, d): 14.9; IR (KBr): 3166, 3058, 2910, 2853,
1964, 1825, 1680, 1641, 1438, 914 cmꢀ1; MS m/z: 347 (M+, 2),
304 (0.3), 201 (100), 146 (22), 77 (21); HRMS-EI (m/z): [M]+ calcd
for C22H22NOP, 347.1439; found, 347.1431.
4.3.10. N-[(E)-1-(4-Bromophenyl)ethylidene]diphenyl-
phosphinic amide 14a
1H NMR (400 MHz, CDCl3, d): 7.97–7.92 (m, 6H), 7.61 (d,
J = 8.3 Hz, 2H), 7.47–7.44 (m, 6H), 2.93 (s, 3H); 13C NMR
(100.6 MHz, CDCl3, d): 180 (d, J = 7.2 Hz), 138.4, 138.2, 135.1,
133.8, 131.8, 131.6, 131.5, 129.4, 128.5, 128.4, 127.4, 22.9 (d,
J = 14.1 Hz); 31P NMR (162 MHz, CDCl3, d): 19.1; IR (KBr): 3255,
3126, 1673, 1617, 1579, 1436, 1175, 914 cmꢀ1; MS m/z: 400
(M++2, 35), 398 (M+, 36), 201 (100), 125 (38), 77 (24); HRMS-EI
(m/z): [M]+ calcd for C20H17BrNOP, 397.0231; found, 397.0235.
4.3.16. Diphenyl-N-[(E)-1-phenylmethylidene]phosphinic
amide 20a
1H NMR (400 MHz, CDCl3, d): 9.36 (d, J = 32.0 Hz, 1H),
8.00–7.90 (m, 6H), 7.49–7.43 (m, 9H); 13C NMR (100.6 MHz, CDCl3,
d): 173.8 (d, J = 7.7 Hz), 135.9, 135.7, 135.6, 132.4, 132.3, 132.0,
131.8 (d, J = 2.2 Hz), 131.6, 131.5, 130.1, 128.9, 128.7, 128.6,
128.5, 128.4; 31P NMR (162 MHz, CDCl3, d): 24.8; IR (KBr): 3233,
3125, 3056, 2881, 1906, 1625, 1438, 1127, 832 cmꢀ1; MS m/z:
305 (M++2, 18), 216 (100), 199 (64), 140 (26), 124 (31), 77 (33);
HRMS-EI (m/z): [M]+ calcd for C19H16NOP, 305.0970; found,
305.0974.
4.3.11. N-[(E)-1-(3-Chlorophenyl)ethylidene]diphenyl-
phosphinic amide 15a
1H NMR (400 MHz, CDCl3, d): 8.03 (s, 1H), 7.98–7.91 (m, 5H),
7.51–7.38 (m, 8H), 2.94 (d, J = 1.2 Hz, 3H); 13C NMR (100.6 MHz,
CDCl3, d): 180.1 (d, J = 7.5 Hz), 141.2, 140.9, 134.9, 133.0, 132.2,
131.8, 131.7, 131.6, 131.5, 129.8, 128.6, 128.5, 128.4, 127.9,
126.1, 23.0 (d, J = 12.2 Hz); 31P NMR (162 MHz, CDCl3, d): 19.4; IR
(KBr): 3229, 3056, 2924, 2854, 1687, 1641, 1438, 1211,
848 cmꢀ1; MS m/z: 355 (M++2, 7), 353 (M+, 19), 216 (100), 199
(61), 140 (26), 124 (29), 77 (34); HRMS-EI (m/z): [M]+ calcd for
C20H17ClNOP, 353.0736; found, 353.0737.
4.3.17. N-[(E)-1-(1-Naphthyl)ethylidene]diphenylphosphinic
amide 21a
1H NMR (400 MHz, CDCl3, d): 8.14 (d, J = 8.5 Hz, 1H), 7.99–7.87
(m, 6H), 7.62–7.38 (m, 10H), 3.03 (d, J = 2.1 Hz, 3H); 13C NMR
(100.6 MHz, CDCl3, d): 186.3 (d, J = 9.2 Hz), 140.1, 139.9, 134.7,
133.7, 133.0, 132.2, 131.9, 131.8, 131.7, 131.5, 130.7, 129.6,
128.8, 128.7, 128.5, 128.4, 126.8, 126.2, 126.1, 125.5, 28.4 (d,
J = 13.3 Hz); 31P NMR (162 MHz, CDCl3, d): 18.7; IR (KBr): 3423,
3057, 2224, 1824, 1642, 1438, 1122, 853 cmꢀ1; MS m/z: 369 (M+,
1), 216 (100), 199 (70), 155 (28), 124 (24), 77 (34); HRMS-EI
(m/z): [M]+ calcd for C24H20NOP, 369.1283; found, 369.1286.
4.3.12. N-[(E)-1-(4-Chlorophenyl)ethylidene]diphenyl-
phosphinic amide 16a
1H NMR (400 MHz, CDCl3, d): 8.02–7.93 (m, 6H), 7.49–7.43 (m,
8H), 2.94 (s, 3H); 13C NMR (100.6 MHz, CDCl3, d): 180.2 (d,
J = 7.5 Hz), 138.8, 138.0, 137.7, 135.2, 133.9, 132.1, 129.6, 129.3,
128.8, 128.5, 128.4, 22.9 (d, J = 12.9 Hz); 31P NMR (162 MHz, CDCl3,
d): 19.1; IR (KBr): 3067, 1641, 1587, 1438, 1197, 731 cmꢀ1; MS m/z:
355 (M++2, 18), 353 (M+, 52), 311 (20), 276 (11), 201 (100), 125
(51), 77 (39); HRMS-EI (m/z): [M]+ calcd for C20H17ClNOP,
353.0736; found, 353.0735.
4.3.18. N-[(E)-1-(2-Naphthyl)ethylidene]diphenylphosphinic
amide 22a
1H NMR (400 MHz, CDCl3, d): 8.45 (s, 1H), 8.29 (d, J = 8.7 Hz,
1H), 8.04–7.88 (m, 7H), 7.60–7.41 (m, 8H), 3.08 (d, J = 2.0 Hz,
3H); 13C NMR (100.6 MHz, CDCl3, d): 181.3 (d, J = 7.6 Hz), 136.9,
136.6, 135.4, 135.2, 134.1, 132.6, 131.8, 131.7, 131.6, 131.5, 131.4
(d, J = 2.3 Hz), 129.5, 129.4, 128.5, 128.4, 128.3, 127.7, 126.7,
124.1, 23.1 (d, J = 12.5 Hz); 31P NMR (162 MHz, CDCl3, d): 18.9; IR
(KBr): 3230, 3121, 3041, 2922, 1967, 1818, 1677, 1623, 1438,
1194, 994 cmꢀ1; MS m/z: 369 (M+, 69), 327 (14), 292 (18), 201
(100), 125 (23), 77 (13); HRMS-EI (m/z): [M]+ calcd for C24H20NOP,
369.1283; found, 369.1279.
4.3.13. Diphenyl-N-[(E)-1-phenylpropylidene]phosphinic
amide 17a
1H NMR (400 MHz, CDCl3, d): 8.06–7.96 (m, 6H), 7.54–7.42 (m,
9H), 3.45–3.39 (m, 2H), 1.23 (t, J = 7.8 Hz, 3H); 13C NMR
(100.6 MHz, CDCl3, d): 186.7 (d, J = 7.7 Hz), 138.2, 137.9, 135.7,
134.4, 132.2, 131.6, 131.5, 131.3, 128.6, 128.4, 128.3, 128.2, 29.8
(d, J = 12.0 Hz), 13.1; 31P NMR (162 MHz, CDCl3, d): 17.6; IR
(KBr): 3612, 3255, 3126, 1906, 1738, 1616, 1579, 1436, 1175,
914 cmꢀ1; MS m/z: 333 (M+, 23), 306 (13), 217 (41), 201 (100),
199 (45), 132 (22), 77 (56); HRMS-EI (m/z): [M]+ calcd for
C21H20NOP, 333.1283; found, 333.1286.
4.3.19. N-[(E)-1-(2-Furyl)ethylidene]diphenylphosphinic amide
23a
1H NMR (400 MHz, CDCl3, d): 7.98–7.93 (m, 4H), 7.61 (s, 1H),
7.47–7.39 (m, 6H), 7.24 (d, J = 3.4 Hz, 1H), 6.55–6.54 (m, 1H),
2.80 (d, J = 1.9 Hz, 3H); 13C NMR (100.6 MHz, CDCl3, d): 170.2 (d,
J = 10.1 Hz), 154.6, 154.3, 146.4, 135.5, 134.2, 131.6, 131.5, 131.3
(d, J = 2.3 Hz), 128.4, 128.3, 116.3, 112.5, 22.2 (d, J = 16.6 Hz); 31P
NMR (162 MHz, CDCl3, d): 19.5; IR (KBr): 3612, 3247, 3127, 1908,
1617, 1579, 1436, 1125, 915 cmꢀ1; MS m/z: 309 (M+, 0.7), 216
(100), 199 (78), 140 (35), 124 (42), 77 (41); HRMS-EI (m/z): [M]+
calcd for C18H16NO2P, 309.0919; found, 309.0923.
4.3.14. Diphenyl-N-[(E)-1-phenylbutylidene]phosphinic amide
18a
1H NMR (400 MHz, CDCl3, d): 8.06–7.96 (m, 6H), 7.56–7.40 (m,
9H), 3.42–3.37 (t, J = 8.0 Hz, 2H), 1.66–1.61 (m, 2H), 0.97 (t,
J = 7.0 Hz, 3H); 13C NMR (100.6 MHz, CDCl3, d): 185.0 (d, J = 7.0
Hz), 138.6, 138.3, 135.7, 134.4, 132.2, 132.1, 132.0, 131.6, 131.5,
131.3 (d, J = 3.0 Hz), 130.2, 128.6, 128.5, 128.4, 128.3, 128.2,
127.1, 37.7 (d, J = 11.3 Hz), 22.4, 14.2; 31P NMR (162 MHz, CDCl3,
d): 17.6; IR (KBr): 3431, 3052, 2957, 2872, 1964, 1913, 1827,
1635, 1437, 1287, 814 cmꢀ1; MS m/z: 347 (M+, 52), 319 (21), 216
(18), 201 (100), 199 (17), 146 (65), 77 (54); HRMS-EI (m/z): [M]+
calcd for C22H22NOP, 347.1439; found, 347.1433.
4.3.20. Diphenyl-N-[(E)-1-(3-thienyl)ethylidene]phosphinic
amide 24a
1H NMR (400 MHz, CDCl3, d): 7.99–7.92 (m, 5H), 7.74 (d,
J = 5.2 Hz, 1H), 7.45–7.40 (m, 6H), 7.34–7.32 (m, 1H), 2.88 (s,
3H); 13C NMR (100.6 MHz, CDCl3, d): 176.0 (d, J = 7.3 Hz), 144.6,
144.4, 135.5, 134.2, 131.6, 131.5, 131.3, 130.7, 128.4, 128.3,
127.1, 126.2, 23.8 (d, J = 12.6 Hz). 31P NMR (162 MHz, CDCl3, d):
18.9; IR (KBr): 3295, 3232, 3124, 1968, 1903, 1667, 1628, 1437,
1264, 1175, 914 cmꢀ1; MS m/z: 325 (M+, 0.5), 216 (100), 199
4.3.15. N-[(E)-2-Methyl-1-phenylpropylidene]diphenyl-
phosphinic amide 19a
1H NMR (400 MHz, CDCl3, d): 7.94–7.88 (m, 4H), 7.48–7.31 (m,
1H), 3.52–3.45 (m, 1H), 1.30 (d, J = 6.9 Hz, 6H); 13C NMR

Y.-J. Chen, C. Chen / Tetrahedron: Asymmetry 19 (2008) 2201–2209
2207
(63), 140 (19), 124 (27), 77 (26); HRMS-EI (m/z): [M]+ calcd for
C18H16NOPS, 325.0690; found, 325.0685.
(d, J = 4.1 Hz), 114.2, 56.3, 55.3, 29.6 (d, J = 3.5 Hz); 31P NMR
(162 MHz, CDCl3, d): 20.2; IR (KBr): 3160, 3077, 2873, 1738,
1609, 1510, 1253, 1192, 995 cmꢀ1; MS m/z: 376 (M+, 12), 349
(67), 307 (21), 201 (100), 125 (32), 125 (32), 77 (31); HRMS-EI
(m/z): [M]+ calcd for C22H22N2O2P, 376.1340; found, 376.1337;
HPLC (Daicel Chiralcel OJ, hexane/i-PrOH = 90:10, flow rate
0.5 mL/min) tR 33.1 and 58.9 min.
4.3.21. Diphenyl-N-[(E)-1-(3-pyridyl)ethylidene]phosphinic
amide 25a
1H NMR (400 MHz, CDCl3, d): 9.29 (d, J = 1.8 Hz, 1H), 8.75 (d,
J = 4.7 Hz, 1H), 8.32 (d, J = 7.8 Hz, 1H), 8.00–7.94 (m, 3H), 7.48–
7.39 (m, 7H), 2.98 (d, J = 2.0 Hz, 3H); 13C NMR (100.6 MHz, CDCl3,
d): 179.5 (d, J = 7.4 Hz), 152.7, 149.4, 135.0, 134.8, 133.5, 131.6,
131.5, 128.5, 123.3, 22.9 (d, J = 13.1 Hz); 31P NMR (162 MHz, CDCl3,
d): 19.3; IR (KBr): 3247, 3128, 1906, 1688, 1587, 1437, 1175,
915 cmꢀ1; MS m/z: 320 (M+, 0.3), 216 (100), 199 (67), 140 (26),
124 (29), 77 (29); HRMS-EI (m/z): [M]+ calcd for C19H17N2OP,
320.1079; found, 320.1074.
4.4.4. N-[1-Cyano-1-(2-methylphenyl)ethyl]diphenyl-
phosphinic amide 9b
½
a 2D3
ꢃ
¼ ꢀ2:7 (c 2.0, CH2Cl2); 1H NMR (400 MHz, CDCl3, d): 8.06–
8.01 (m, 2H), 7.83–7.77 (m, 2H), 7.65–7.63 (d, J = 7.6 Hz, 2H), 7.56–
7.39 (m, 6H), 7.42–7.18 (3H), 3.65 (d, J = 7.3 Hz, 1H), 2.71 (s, 3H),
2.11 (s, 3H); 13C NMR (100.6 MHz, CDCl3, d): 137.1, 135.8, 133.4,
133.1, 132.5, 132.4, 132.2, 131.4, 131.4, 131.0, 129.2, 128.7 (d,
J = 3.4 Hz), 128.6, 126.5, 126.0, 121.5, 55.6, 27.6 (d, J = 3.4 Hz),
21.3; 31P NMR (162 MHz, CDCl3, d): 19.9; IR (KBr): 3425, 3108,
2875, 1742, 1591, 1436, 1169, 988 cmꢀ1; MS m/z: 360 (M+, 0.8),
333 (16), 318 (13), 201 (100), 159 (25), 132 (73), 77 (28); HRMS-
EI (m/z): [M]+ calcd for C22H21N2OP, 360.1391; found, 360.1385;
HPLC (Daicel Chiralcel OJ, hexane/i-PrOH = 90:10, flow rate
0.5 mL/min) tR 20.4 and 26.9 min.
4.4. General procedure for the Strecker synthesis of N-
substituted a-aminonitriles (5b–25b)
To a solution of chiral ligand 1 (7.0 mg, 0.01 mmol) in THF
(1.5 mL) was added Zr(Ot-Bu)4 (4 L, 0.01 mmol) dropwise, and
l
stirred at room temperature for 1 h. Ketimines (5a–25a)
(0.1 mmol) and TMSCN (0.1 mmol) were then added successively
and the solution was stirred at ꢀ30 °C for 72 h. The reaction mix-
ture was then passed through silica gel column, and eluted with
ethyl acetate. The concentrated residues were purified by flash col-
umn chromatography on silica gel to afford pure products (5b–
25b).
4.4.5. N-[1-Cyano-1-(3-methylphenyl)ethyl]diphenyl-
phosphinic amide 10b
½
a 2D3
ꢃ
¼ ꢀ1:7 (c 1.05, CH2Cl2); 1H NMR (400 MHz, CDCl3, d): 8.06–
8.00 (m, 2H), 7.85–7.80 (m, 2H), 7.57–7.42 (m, 8H), 7.31–7.27 (t,
J = 7.6 Hz, 1H), 7.15 (d, J = 7.5 Hz, 1H), 3.69 (d, J = 7.3 Hz, 1H),
2.36 (s, 3H), 1.92 (s, 3H); 13C NMR (100.6 MHz, CDCl3, d): 141.0
(d, J = 3.8 Hz), 138.9, 133.5, 132.8, 132.4, 132.3 (d, J = 5.0 Hz),
131.5, 131.4, 131.3, 129.7, 129.0, 128.9, 128.8, 128.7, 128.6,
125.9, 122.4, 121.5, 56.8, 29.5, 21.5; 31P NMR (162 MHz, CDCl3,
4.4.1. N-[1-Cyano-1-(2-methoxyphenyl)ethyl]diphenyl-
phosphinic amide 6b
½
a 2D3
ꢃ
¼ ꢀ2:15 (c 1.3, CH2Cl2); 1H NMR (400 MHz, CDCl3, d):
7.97–7.02 (m, 2H), 7.75–7.69 (m, 2H), 7.54–7.34 (m, 8H), 7.00 (d,
J = 7.2 Hz, 2H), 4.72 (d, J = 8.4 Hz, 2H), 3.93 (s, 3H), 2.09 (s, 3H);
13C NMR (100.6 MHz, CDCl3, d): 156.8, 134.2, 133.7, 132.9, 132.4,
132.1, 132.0, 131.9, 131.4, 131.3, 130.5, 128.7, 128.6 (d,
J = 2.9 Hz), 128.4, 128.2, 125.8, 121.7 (d, J = 5.0 Hz), 121.3, 112.2,
55.9, 52.4, 24.9; 31P NMR (162 MHz, CDCl3, d): 20.4; IR (KBr):
3389, 3105, 2885, 1587, 1486, 1436, 1193, 992 cmꢀ1; MS m/z:
376 (M+, 1), 318 (62), 201 (100), 148 (18), 77 (31); HRMS-EI (m/
z): [M]+ calcd for C22H22N2O2P, 376.1340; found, 376.1348; HPLC
(Daicel Chiralcel OJ, hexane/i-PrOH = 90:10, flow rate 0.75 mL/
min) tR 16.3 and 25.7 min.
d): 20.3; IR (KBr): 3426, 3104, 2879, 1591, 1436, 1126, 993 cmꢀ1
;
MS m/z: 360 (M+, 12), 333 (25), 291 (21), 201 (100), 125 (17), 77
(28); HRMS-EI (m/z): [M]+ calcd for C22H21N2OP, 360.1391; found,
360.1397; HPLC (Daicel Chiralcel OJ, hexane/i-PrOH = 90:10, flow
rate 0.5 mL/min) tR 13.3 and 17.4 min.
4.4.6. N-[1-Cyano-1-(4-methylphenyl)ethyl]diphenyl-
phosphinic amide 11b
½
a 2D3
ꢃ
¼ ꢀ1:7 (c 1.05, CH2Cl2); 1H NMR (400 MHz, CDCl3, d): 8.06–
8.00 (m, 2H), 7.85–7.80 (m, 2H), 7.63 (d, J = 8.2 Hz, 2H), 7.57–7.42
(m, 6H), 7.20 (d, J = 8.0 Hz, 2H), 3.61 (d, J = 8.0 Hz, 1H), 2.34 (s, 3H),
1.92 (s, 3H); 13C NMR (100.6 MHz, CDCl3, d): 139.0, 138.3, 132.4,
132.3, 131.4, 131.2, 129.6, 128.9, 128.8, 128.7, 128.6, 125.2, 121.5
(d, J = 3.8 Hz), 56.7, 29.4, 21.0; 31P NMR (162 MHz, CDCl3, d):
4.4.2. N-[1-Cyano-1-(3-methoxyphenyl)ethyl]diphenyl-
phosphinic amide 7b
½
a 2D3
ꢃ
¼ ꢀ4:9 (c 1.6, CH2Cl2); 1H NMR (400 MHz, CDCl3, d): 8.04–
7.99 (m, 2H), 7.84–7.99 (m, 2H), 7.56–7.39 (m, 6H), 7.32–7.29 (m,
3H), 6.87–6.85 (m, 1H), 3.83 (s, 3H), 3.74 (br, 1H), 1.92 (s, 3H); 13C
NMR (100.6 MHz, CDCl3, d): 160.0, 142.7 (d, J = 3.3 Hz), 133.5,
132.8, 132.4, 132.3, 132.2, 131.5, 131.4, 131.3, 130.1, 128.9,
128.1, 128.7, 128.6, 121.3 (d, J = 4.4 Hz), 117.4, 114.6, 111.0, 56.9,
55.4, 29.4; 31P NMR (162 MHz, CDCl3, d): 20.5; IR (KBr): 3131,
3056, 2873, 1738, 1599, 1436, 1263, 1194, 865 cmꢀ1; MS m/z:
376 (M+, 37), 307 (49), 201 (11), 125 (11), 77 (29); HRMS-EI
(m/z): [M]+ calcd for C22H22N2O2P, 376.1340; found, 376.1337;
HPLC (Daicel Chiralcel OJ, hexane/i-PrOH = 90:10, flow rate
0.5 mL/min) tR 19.9 and 35.0 min.
20.2; IR (KBr): 3099, 2880, 1738, 1436, 1377, 1190, 995 cmꢀ1
;
MS m/z: 360 (M+, 27), 345 (7), 333 (17), 291 (66), 201 (100), 125
(28), 77 (32); HRMS-EI (m/z): [M]+ calcd for C22H21N2OP,
360.1391; found, 360.1395; HPLC (Daicel Chiralcel OJ, hexane/i-
PrOH = 100:1, flow rate 1.0 mL/min) tR 20.6 and 26.2 min.
4.4.7. N-[1-(2-Bromophenyl)-1-cyanoethyl]diphenylphosphinic
amide 12b
½
a 2D3
ꢃ
¼ ꢀ1:3 (c 1.15, CH2Cl2); 1H NMR (400 MHz, CDCl3, d):
7.99–7.94 (m, 2H), 7.80–7.75 (m, 2H), 7.66–7.63 (d, J = 7.8 Hz,
2H), 7.59–7.46 (m, 5H), 7.40–7.38 (m, 2H), 7.32 (t, J = 7.1 Hz, 1H),
4.4 (d, J = 3.6 Hz, 1H), 2.23 (s, 3H); 13C NMR (100.6 MHz, CDCl3,
d): 137.5 (d, J = 3.0 Hz), 235.5, 133.3, 132.8, 132.4, 132.1, 132.0,
131.5, 131.4, 130.6, 128.8, 128.7, 128.5, 128.1, 127.8, 121.5,
120.3 (d, J = 5.4 Hz), 55.3, 26.6 (d, J = 4.1 Hz); 31P NMR (162 MHz,
CDCl3, d): 20.5; IR (KBr): 3427, 3063, 2872, 1728, 1591, 1463,
1436, 1125, 993 cmꢀ1; MS m/z: 426 (M++2, 0.5), 424 (M+, 0.5),
345 (95), 318 (100), 277 (10), 201 (98), 183 (23), 152 (15),
77(65); HRMS-EI (m/z): [M]+ calcd for C21H18BrN2OP, 424.0340;
found, 424.0338.
4.4.3. N-[1-Cyano-1-(4-methoxyphenyl)ethyl]diphenyl-
phosphinic amide 8b
½
a 2D3
ꢃ
¼ ꢀ2:35 (c 0.85, CH2Cl2); 1H NMR (400 MHz, CDCl3, d):
8.03–7.97 (m, 2H), 7.83–7.82 (m, 2H), 6.42–6.19 (d, J = 6.7 Hz,
2H), 7.54–7.41 (m, 6H), 6.88–6.86 (d, J = 6.8 Hz, 2H), 3.79 (s, 3H),
3.69 (d, J = 7.6 Hz, 1H), 1.91 (s, 3H); 13C NMR (100.6 MHz, CDCl3,
d): 159.9, 133.6, 133.0 (d, J = 4.0 Hz), 132.3, 132.4, 132.1 (d,
J = 2.2 Hz), 131.6, 131.4, 131.3, 128.8, 128.7, 128.5, 126.4, 121.5

2208
Y.-J. Chen, C. Chen / Tetrahedron: Asymmetry 19 (2008) 2201–2209
4.4.8. N-[1-(3-Bromophenyl)-1-cyanoethyl]diphenylphosphinic
(m, 4H), 7.41–7.32 (m, 4H), 2.36–2.30 (m, 2H), 1.23 (t, J = 7.2 Hz,
3H); 13C NMR (100.6 MHz, CDCl3, d): 138.3 (d, J = 3.3 Hz), 133.4,
133.0, 132.3, 132.2, 132.1 (d, J = 2.3 Hz), 131.7, 131.5, 131.4,
128.9, 128.8, 128.7, 128.5, 126.3, 120.2 (d, J = 3.6 Hz), 62.5, 34.8
(d, J = 3.7 Hz), 9.3; 31P NMR (162 MHz, CDCl3, d): 20.3; IR (KBr):
amide 13b
½
a 2D3
ꢃ
¼ ꢀ4:6 (c 1.4, CH2Cl2); 1H NMR (400 MHz, CDCl3, d): 7.99–
7.96 (m, 2H), 7.82–7.77 (m, 2H), 7.71 (d, J = 7.8 Hz, 1H), 7.57–7.41
(m, 7H), 7.28–7.24 (m, 1H), 3.74 (d, J = 7.4 Hz, 1H), 1.93 (s, 3H); 13C
NMR (100.6 MHz, CDCl3, d): 143 (d, J = 3.1 Hz), 133.2, 132.7, 132.5,
132.4, 132.3, 132.2, 131.9, 131.4, 131.3, 130.6, 128.9, 128.8, 124.3,
122.9, 120.8 (d, J = 4.2 Hz), 56.3, 29.6 (d, J = 3.8 Hz); 31P NMR
(162 MHz, CDCl3, d): 20.7; IR (KBr): 3433, 3079, 2877, 1591,
1471, 1737, 1125, 995 cmꢀ1; MS m/z: 426 (M++2, 2.5), 424 (M+,
2.5), 399 (4), 397 (4), 201 (100), 125 (31), 77 (31); HRMS-EI
(m/z): [M]+ calcd for C21H18BrN2OP, 424.0340; found, 424.0335;
HPLC (Daicel Chiralcel OJ, hexane/i-PrOH = 90:10, flow rate
0.5 mL/min) tR 15.7 and 19.6 min.
3176, 3056, 2896, 2234, 1896, 1737, 1449, 1198, 1123, 873 cmꢀ1
;
MS m/z: 360 (M+, 4), 333 (26), 201 (100), 132 (27), 77 (24);
HRMS-EI (m/z): [M]+ calcd for C22H21N2OP, 360.1391; found,
360.1385; HPLC (Daicel Chiralcel OJ, hexane/i-PrOH = 90:10, flow
rate 0.5 mL/min) tR 12.5 and 20.1 min.
4.4.13. N-(1-Cyano-1-phenylbutyl)diphenylphosphinic amide
18b
½
a 2D3
ꢃ
¼ ꢀ3:4 (c 0.85, CH2Cl2); 1H NMR (400 MHz, CDCl3, d):
7.99–7.93 (m, 2H), 7.78–7.73 (m, 2H), 7.64 (d, J = 8.0 Hz, 1H),
7.53–7.47 (m, 4H), 7.41–7.31 (m, 5H), 3.72 (d, J = 7.3 Hz, 1H),
2.30–2.16 (m, 2H), 1.39–1.32 (m, 1H), 0.93–0.85 (m, 1H), 0.76 (t,
J = 7.2 Hz, 3H); 13C NMR (100.6 MHz, CDCl3, d): 138.6 (d,
J = 3.3 Hz), 133.2, 132.9, 132.3, 132.2, 132.1 (d, J = 2.2 Hz), 131.9,
131.6, 131.5, 131.4, 128.9, 128.8, 128.7, 128.6, 128.5, 126.2, 120.5
(d, J = 3.5 Hz), 61.5, 43.6 (d, J = 3.7 Hz), 18.4, 13.4; 31P NMR
(162 MHz, CDCl3, d): 20.2; IR (KBr): 3199, 3060, 2962, 1731,
1590, 1437, 1124, 907 cmꢀ1; MS m/z: 374 (M+, 2), 318 (12), 216
(3), 201 (100), 175 (8), 132 (8), 77 (34); HRMS-EI (m/z): [M]+ calcd
for C23H23N2OP, 374.1548; found, 374.1544; HPLC (Daicel Chiralcel
OJ, hexane/i-PrOH = 90:10, flow rate 0.75 mL/min) tR 7.2 and 10.91
min
4.4.9. N-[1-(4-Bromophenyl)-1-cyanoethyl]diphenylphosphinic
amide 14b
½
a 2D3
ꢃ
¼ ꢀ6:4 (c 1.15, CH2Cl2); 1H NMR (400 MHz, CDCl3, d):
7.98–7.94 (m, 2H), 7.79–7.74 (m, 2H), 7.59–7.41 (m, 8H), 3.90 (d,
J = 6.8 Hz, 1H), 1.89 (s, 3H); 13C NMR (100.6 MHz, CDCl3, d): 140
(d, J = 3.2 Hz), 133.2, 132.7, 132.4, 132.3, 132.2, 132.0, 131.9,
131.3, 131.2, 128.9, 128.8, 128.7, 128.6, 127.3, 123.1, 121.0,
120.9, 56.5, 29.6 (d, J = 3.9 Hz); 31P NMR (162 MHz, CDCl3, d):
20.8; IR (KBr): 3255, 3126, 1673, 1617, 1579, 1436, 1175,
914 cmꢀ1; MS m/z: 426 (M++2, 41), 424 (M+, 41), 357 (63), 355
(60), 201 (100), 125 (59), 77 (63); HRMS-EI (m/z): [M]+ calcd for
C21H18BrN2OP, 424.0340; found, 424.0337; HPLC (Daicel Chiralcel
OJ, hexane/i-PrOH = 90:10, flow rate 0.5 mL/min) tR 25.1 and
31.2 min.
4.4.14. N-(1-Cyano-2-methyl-1-phenylpropyl)diphenyl-
phosphinic amide 19b
4.4.10. N-[1-(3-Chlorophenyl)-1-cyanoethyl]diphenyl-
½
a 2D3
ꢃ
¼ ꢀ3:2 (c 1.05, CH2Cl2); 1H NMR (400 MHz, CDCl3, d): 7.80–
phosphinic amide 15b
7.75 (m, 2H), 7.58–7.53 (m, 2H), 7.48–7.45 (m, 1H), 7.40–7.36 (m,
5H), 7.28–7.24 (m, 2H), 7.22–7.18 (m, 3H), 4.08 (d, J = 5.0 Hz, 1H),
2.46–2.43 (m, 1H), 1.30 (d, J = 6.6 Hz, 3H), 0.74 (d, J = 6.7 Hz, 3H);
13C NMR (100.6 MHz, CDCl3, d): 136.5, 133.2, 132.1, 132.0, 131.9,
131.8 (d, J = 2.3 Hz), 130.5, 128.5, 128.4, 128.1, 128.0, 127.0,
118.8 (d, J = 2.6 Hz), 65.7 (d, J = 3.4 Hz), 40.6 (d, J = 5.0 Hz), 18.9,
17.7; 31P NMR (162 MHz, CDCl3, d): 20.7; IR (KBr): 3426, 3174,
3061, 2965, 1729, 1591, 1437, 1195, 1123, 857 cmꢀ1; MS m/z:
374 (M+, 13), 347 (50), 304 (18), 228 (32), 201 (100), 146 (63),
77 (63); HRMS-EI (m/z): [M]+ calcd for C23H23N2OP, 374.1548;
found, 374.1545; HPLC (Daicel Chiralcel OJ, hexane/i-PrOH = 90:10,
flow rate 0.5 mL/min) tR 10.7 and 14.9 min.
½
a 2D3
ꢃ
¼ ꢀ3:2 (c 1.25, CH2Cl2); 1H NMR (400 MHz, CDCl3, d):
7.98–7.93 (m, 2H), 7.80–7.75 (m, 2H), 7.65–7.63 (m, 2H), 7.55–
7.47 (m, 4H), 7.43–7.40 (m, 2H), 7.31–7.29 (m, 2H), 3.94 (d,
J = 1.8 Hz, 1H), 1.91 (s, 3H); 13C NMR (100.6 MHz, CDCl3, d):
142.9 (d, J = 3.4 Hz), 134.9, 133.2, 132.7, 132.4 (d, J = 2.3 Hz),
132.3, 132.2, 131.9, 131.4, 131.3, 130.3, 129.1, 128.9, 128.7 (d,
J = 1.6 Hz), 128.6, 125.7, 123.8, 120.9 (d, J = 4.0 Hz), 56.4, 29.7 (d,
J = 4.0 Hz); 31P NMR (162 MHz, CDCl3, d): 20.8; IR (KBr): 3049,
3078, 2871, 1739, 1592, 1437, 1192, 1077, 996 cmꢀ1; MS m/z:
382 (M++2, 2), 380 (M+, 7), 353 (36), 311 (18), 201 (100), 125
(33), 77 (31); HRMS-EI (m/z): [M]+ calcd for C21H18ClN2OP,
380.0845; found, 380.0849; HPLC (Daicel Chiralcel OJ, hexane/i-
PrOH = 90:10, flow rate 0.5 mL/min) tR 15.7 and 19.8 min.
4.4.15. N-Cyano(phenyl)methyl(diphenyl)phosphinic
amide 20b
4.4.11. N-[1-(4-Chlorophenyl)-1-cyanoethyl]diphenyl-
½
a 2D3
ꢃ
¼ ꢀ0:6 (c 1.2, CH2Cl2); 1H NMR (400 MHz, CDCl3, d): 8.02–
phosphinic amide 16b
7.97 (m, 2H), 7.83–7.78 (m, 2H), 7.62–7.37 (m, 6H), 5.20 (d,
J = 10.6 Hz, 1H), 4.02 (d, J = 8.7 Hz, 1H); 13C NMR (100.6 MHz,
CDCl3, d): 134.9, 132.7, 132.6, 132.5, 131.8, 131.7, 129.2, 129.0,
128.9, 128.8, 128.7, 127.1, 46.2; 31P NMR (162 MHz, CDCl3, d):
24.6; IR (KBr): 3436, 3128, 2879, 2720, 2233, 1979, 1741, 1591,
1437, 939 cmꢀ1; MS m/z: 332 (M+, 18), 305 (18), 201 (94), 155
(20), 91 (42), 77 (68); HRMS-EI (m/z): [M]+ calcd for C20H17N2OP,
332.1078; found, 332.1080; HPLC (Daicel Chiralcel OJ, hexane/i-
PrOH = 90:10, flow rate 0.5 mL/min) tR 24.3 and 27.1 min.
½
a 2D3
ꢃ
¼ ꢀ5:7 (c 0.85, CH2Cl2); 1H NMR (400 MHz, CDCl3, d): 8.00–
7.97 (m, 2 H), 7.81–7.76 (m, 2H), 6.80 (d, J = 8.6 Hz, 2H), 7.56–7.50
(m, 4H), 7.44–7.41 (m, 2H), 7.34 (d, J = 8.6 Hz, 2H), 3.72 (br, 1H),
1.91 (s, 3H); 13C NMR (100.6 MHz, CDCl3, d): 139.5 (d, J = 2.9 Hz),
135.0, 133.2, 132.7, 132.4, 132.3, 132.0, 131.5, 131.3, 131.2,
129.1, 128.9, 128.8, 128.7, 128.6, 127.0, 121.0 (d, J = 4.3 Hz), 56.4,
29.6 (d, J = 3.9 Hz); 31P NMR (162 MHz, CDCl3, d): 20.7; IR (KBr):
3421, 3109, 2875, 2232, 1905, 1736, 1592, 1490, 1437, 1188,
995 cmꢀ1; MS m/z: 382 (M++2, 2), 380 (M+, 6), 380 (6), 353 (27),
311 (19), 201 (100), 125 (28), 77 (23); HRMS-EI (m/z): [M]+ calcd
for C21H18ClN2OP, 380.0845; found, 380.0849; HPLC (Daicel Chiral-
cel OJ, hexane/i-PrOH = 90:10, flow rate 0.5 mL/min) tR 15.7 and
18.3 min.
4.4.16. N-[1-Cyano-1-(1-naphthyl)ethyl]diphenylphosphinic
amide 21b
½
a 2D3
ꢃ
¼ ꢀ1:2 (c 1.25, CH2Cl2); 1H NMR (400 MHz, CDCl3, d): 8.97
(d, J = 8.7 Hz, 1H), 8.08–8.03 (m, 2H), 7.89–7.83 (m, 3H), 7.77–7.73
(m, 2H), 7.72–7.68 (t, J = 7.7 Hz, 1H), 7.58–7.52 (m, 4H), 7.43–7.39
(m, 2H), 7.34–7.32 (m, 2H), 3.98 (d, J = 8.0 Hz, 1H), 2.33 (s, 3H); 13C
NMR (100.6 MHz, CDCl3, d): 134.8, 134.2 (d, J = 4.6 Hz), 133.3,
132.6, 132.5, 132.1 (d, J = 2.3 Hz), 131.9, 131.2, 131.1, 130.9,
130.6, 129.5, 129.0, 128.4, 128.7, 128.6, 128.4, 126.8, 126.1,
4.4.12. N-(1-Cyano-1-phenylpropyl)diphenylphosphinic amide
17b
½
a 2D3
ꢃ
¼ þ0:9 (c 1.2, CH2Cl2); 1H NMR (400 MHz, CDCl3, d): 8.00–
7.79 (m, 2H), 7.77–7.74 (m, 2H), 7.66 (d, J = 8.0 Hz, 2H), 7.55–7.45

Y.-J. Chen, C. Chen / Tetrahedron: Asymmetry 19 (2008) 2201–2209
2209
124.9, 124.7, 124.5, 121.7 (d, J = 3.0 Hz), 56.3, 27.9 (d, J = 3.0 Hz);
31P NMR (162 MHz, CDCl3, d): 20.3; IR (KBr): 3106, 2980, 2865,
1739, 1591, 1437, 1187, 981 cmꢀ1; MS m/z: 396 (M+, 3), 369
(15), 327 (59), 201 (100), 168 (89), 127 (21), 77 (28); HRMS-EI
(m/z): [M]+ calcd for C25H21N2OP, 396.1391; found, 396.1385.
(d, J = 4.6 Hz); 31P NMR (162 MHz, CDCl3, d): 21.2; IR (KBr): 3101,
2865, 2344, 1738, 1437, 1187, 996 cmꢀ1; MS m/z: 320 (M+, 0.3),
216 (100), 199 (67), 140 (26), 124 (29), 77 (29); HRMS-EI (m/z):
[M]+ calcd for C20H18N3OP, 347.1187; found, 347.1187; HPLC (Dai-
cel Chiralcel OJ, hexane/i-PrOH = 90:10, flow rate 0.5 mL/min) tR
22.9 and 25.7 min.
4.4.17. N-[1-Cyano-1-(2-naphthyl)ethyl]diphenylphosphinic
amide 22b
Acknowledgments
½
a 2D3
ꢃ
¼ ꢀ3:2 (c 1.05, CH2Cl2); 1H NMR (400 MHz, CDCl3, d): 8.13
(s, 1H), 8.08–8.02 (m, 2H), 7.90–7.80 (m, 6H), 7.55–7.39 (m, 8H),
3.75 (d, J = 7.8 Hz), 2.03 (s, 3H); 13C NMR (100.6 MHz, CDCl3, d):
138.1, 133.2, 132.7, 132.4, 132.3, 132.2, 131.3, 131.2, 129.4,
128.9, 128.8, 128.7, 128.6, 128.4, 127.5, 127.0, 126.8, 124.5,
122.7, 121.4, 57.0, 29.2 (d, J = 3.6 Hz); 31P NMR (162 MHz, CDCl3,
d): 20.4; IR (KBr): 3113, 2874, 1738, 1473, 1193, 996 cmꢀ1; MS
m/z: 396 (M+, 4), 369 (64), 327 (22), 201 (100), 125 (31), 77 (27);
HRMS-EI (m/z): [M]+ calcd for C25H21N2OP, 396.1391; found,
396.1387; HPLC (Daicel Chiralcel OD-H, hexane/i-PrOH = 90:10,
flow rate 0.3 mL/min) tR 62.1 and 65.7 min.
We thank Dr. Sankareswaran Srimurugan for his helpful discus-
sions (Postdoctoral fellowship awarded by National Science Coun-
cil of the Republic of China, under contract NSC 96-2811-M-259-
001). The authors thank Ms. L. M. Hsu, at the Instruments Center,
National Chung Hsing University, for her help in obtaining HRMS,
and the National Science Council of the Republic of China, for
financially supporting this research under contract NSC 96-2113-
M-259-001.
References
4.4.18. N-[1-Cyano-1-(2-furyl)ethyl]diphenylphosphinic amide
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7.88 (m, 2H), 7.84–7.80 (m, 2H), 7.52–7.43 (m, 6H), 7.31 (s, 1H),
6.43 (d, J = 3.3 Hz, 1H), 6.26–6.25 (m, 1H), 3.80 (d, J = 6.7 Hz, 1H),
2.04 (s, 3H); 13C NMR (100.6 MHz, CDCl3, d): 150 (d, J = 4.5 Hz),
143.4, 133.2, 132.7, 132.2 (d, J = 8.4 Hz), 132.0, 131.9, 131.7,
131.6, 131.4, 128.7, 128.6, 128.5, 119.6 (d, J = 4.0 Hz), 110.7,
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20.4; IR (KBr): 3078, 2870, 1902, 1683, 1436, 1125, 1010, 748
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4.4.19. N-[1-Cyano-1-(3-thienyl)ethyl]diphenylphosphinic
amide 24b
½
a 2D3
ꢃ
¼ ꢀ0:9 (c 1.05, CH2Cl2); 1H NMR (400 MHz, CDCl3, d): 8.00–
7.95 (m, 2H), 7.83–7.78 (m, 2H), 7.56–7.40 (m, 7H), 7.33–7.29 (m,
2H), 3.67 (d, J = 7.1 Hz, 1H), 1.97 (s, 3H); 13C NMR (100.6 MHz,
CDCl3, d): 141.8, 133.3, 132.8, 132.4, 132.2, 132.1, 132.0, 131.4,
131.3, 128.9, 128.7 (d, J = 3.3 Hz), 128.6, 127.6, 125.4, 122.9,
121.4, 53.0, 29.1; 31P NMR (162 MHz, CDCl3, d): 20.0; IR (KBr):
3103, 2917, 2867, 1738, 1592, 1435, 1191, 1009 cmꢀ1; MS m/z:
352 (M+, 33), 325 (24), 283 (23), 201 (100), 77 (30); HRMS-EI
(m/z): [M]+ calcd for C19H17N2OPS, 352.0799; found, 352.0804;
HPLC (Daicel Chiralcel OJ, hexane/i-PrOH = 90:10, flow rate 0.5
mL/min) tR 23.9 and 28.84 min.
´
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4.4.20. N-[1-Cyano-1-(3-pyridyl)ethyl]diphenylphosphinic
amide 25b
½
a 2D3
ꢃ
¼ ꢀ2:4 (c 1.05, CH2Cl2); 1H NMR (400 MHz, CDCl3, d): 8.87
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(d, J = 2.2 Hz, 1H), 8.51–8.49 (d, J = 4.7 Hz, 1H), 8.06 (d, J = 7.9 Hz,
1H), 7.95–7.90 (m, 2H), 7.79–7.74 (m, 2H), 7.54–7.39 (m, 7H),
7.29–7.27 (m, 1H), 4.23 (d, J = 7.4 Hz, 1H), 1.95 (s, 3H); 13C NMR
(100.6 MHz, CDCl3, d): 150.1, 146.9, 136.6 (d, J = 3.0 Hz), 133.6,
133.0, 132.6, 132.4 (d, J = 8.3 Hz), 132.2, 132.1, 131.8, 131.4,
131.3, 128.9, 128.7, 128.6, 123.5, 120.0 (d, J = 4.2 Hz), 54.9, 29.8
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