Facile and efficient enantioselective strecker reaction of ketimines by chiral sodium phosphate

Article abstract of DOI:10.1002/chem.200900210

A facile and efficient enantioselective Strecker reaction of ketimines catalyzed by a chiral alkali-metal salt has been developed. When 10 mol% BNPNa (BNP=1,1'-binaphthyl-2,2'-diylphosphate) prepared in situ and 10 mol% para-tert-butylortho-adamantylphenol (PBAP) were introduced into the reaction, up to 96% yield and up to 95% ee (ee=enantiomeric excess) were obtained. Both aliphatic and aromatic ketimines, especially sterically bulky cyclic ketimines derived from β-acetonaphthone, α-indanone, and α-tetralone were found suitable for this reaction. On the basis of the experimental results and previous reports, trimethylsilyl cyanide (TMSCN) was indicated to be the real reactive nucleophile despite the existence of PBAP, and a possible working model was proposed to explain the origin of the asymmetric induction. The facile availability of 1,1'-binaphthyl-2,2'-diylphosphoric acid (BNPH) and the simplicity of the procedure are beneficial for practical applications.

Full text of DOI:10.1002/chem.200900210

DOI: 10.1002/chem.200900210
Facile and Efficient Enantioselective Strecker Reaction of Ketimines by
Chiral Sodium Phosphate
Ke Shen, Xiaohua Liu, Yunfei Cai, Lili Lin, and Xiaoming Feng*[a]
Abstract: A facile and efficient enan-
tioselective Strecker reaction of keti-
mines catalyzed by a chiral alkali-metal
salt has been developed. When
aliphatic and aromatic ketimines, espe-
cially sterically bulky cyclic ketimines
derived from b-acetonaphthone, a-in-
danone, and a-tetralone were found
suitable for this reaction. On the basis
of the experimental results and previ-
ous reports, trimethylsilyl cyanide
(TMSCN) was indicated to be the real
reactive nucleophile despite the exis-
tence of PBAP, and a possible working
model was proposed to explain the
origin of the asymmetric induction.
The facile availability of 1,1’-binaphth-
yl-2,2’-diylphosphoric acid (BNPH)
and the simplicity of the procedure are
beneficial for practical applications.
10 mol%
BNPNa
(BNP=1,1’-bi-
naphthyl-2,2’-diylphosphate) prepared
in situ and 10 mol% para-tert-butyl-
ortho-adamantylphenol (PBAP) were
introduced into the reaction, up to
96% yield and up to 95% ee (ee=en-
antiomeric excess) were obtained. Both
Keywords: asymmetric catalysis
enantioselectivity ketimines
sodium · Strecker reaction
·
·
·
Among them, lithium salts were the most-studied catalysts
through the understanding of the nature of chiral organo-
lithium aggregates.[3] Meanwhile, there are comparatively
few reports about chiral sodium salts and other alkali-metal
salts in asymmetric synthesis.[4] In our earlier work in devel-
oping chiral alkali-metal salts, bifunctional sodium phenyl-
glycinate was developed for the enantioselective cyanosilyla-
tion of ketones (Scheme 1; 1).[4a] Subsequently, potassium 4-
chlorophenylglycinate was applied in the asymmetric Mi-
chael addition of ketones to nitroolefins (Scheme 1; 2).[4c]
Herein, our ongoing interest was extended to a Strecker re-
action of ketimines catalyzed by a chiral salt.
Introduction
The enantioselective Strecker reaction of ketimines is one
of the most direct methods to afford the precursors of phar-
maceutically important quaternary a-amino acids.[1,2] Since
the first effective catalytic system of asymmetric cyanation
of ketimines reported in 2000,[2a,b] a number of successful
protocols have been disclosed. In general, catalysts involving
chiral metal complexes such as Ti[2b,g] and Gd,[2c–f] chiral
Brønsted acid organocatalysts,[2a,h,i] and chiral N,N’-dioxides
as neutral Lewis base organocatalysts[2j–l] have been devel-
oped for this reaction. However, to the best of our knowl-
edge, a direct catalytic asymmetric Strecker reaction cata-
lyzed by a chiral alkali-metal salt has not yet been de-
scribed. Recently, a chiral alkali-metal salt,[3,4] a sort of
anionic Lewis base,[5,6] has been uncovered as a potential
means for catalytic asymmetric reactions. Remarkable prog-
ress has been made in the asymmetric additions of trime-
thylsilyl nucleophiles with such anionic Lewis bases.[6b]
A possible working model of the salt catalysis was pro-
posed, which was different from that of the hydrocyanation
[a] K. Shen, X. Liu, Y. Cai, L. Lin, Prof. Dr. X. Feng
Key Laboratory of Green Chemistry & Technology
Ministry of Education, College of Chemistry
Sichuan University
Chengdu 610064 (P.R. China)
Fax : (+86)28-8541-8249
E-mail: xmfeng@scu.edu.cn
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200900210.
Scheme 1. Chiral alkali-metal salts developed by our group.
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FULL PAPER
of imines catalyzed by Brønsted acids.[2a,h,i,m] (Scheme 2).
When HCN was used in most Strecker variants, the imine
was activated by Brønsted acids through a hydrogen bond
as illustrated in model A. As an alternative strategy, the ac-
tries 2 and 4). As binaphthyl phosphate (BNPÀ) is often
used in asymmetric processes,[6e,7–9] sodium phosphate 3e
was prepared and promoted the reaction in good yield and
50% ee (Table 1, entry 5). In contrast, the reaction could
not proceed in the presence of BNPH using either HCN or
TMSCN as the cyanation nucleophile (Table 1, entry 6),[10]
which indicated a different working pathway with a salt cat-
alyst.
Then a series of metal salts of BNPH were examined. The
catalyst screening revealed that lithium phosphate gave
Scheme 2. Different working models of a Strecker reaction (PG=pro-
tecting group; BÉ =chiral anion; MÈ =metal cation): A) chiral Brønsted
acid catalysis; B) chiral alkali-metal-salt catalysis.
tivation of trimethylsilyl cyanide (TMSCN) by the chiral salt
was achieved by means of a reactive hypervalent silicon in-
termediate (Scheme 2, model B).[6b] Further work has been
directed toward a detailed examination of this interesting
model of salt activation.
Results and Discussion
Our work commenced with a preliminary survey of the reac-
tion conditions using N-diphenylphosphinoyl (Dpp)-protect-
ed ketimine 1a and TMSCN as reagents in the presence of
sodium salts 3a–e, which were prepared in situ by mixing
equimolar amounts of chiral acids with sodium hydroxide in
toluene at 358C for 1 h (Table 1). Initial catalyst screening
revealed that sodium phenylglycine 3a was active, but ex-
hibited poor asymmetric inducibility (Table 1, entry 1). Simi-
larly, sodium salt prepared from chiral mandelic acid or 1,1’-
bi-2-naphthol (BINOL) gave racemic products (Table 1, en-
good reactivity, but afforded a racemic product (Table 2, en-
tries 1 and 2). To our delight, enantioselectivity was im-
proved to 70% ee by the use of sodium phosphate 3e gener-
Table 2. The effect of metal salts on the Strecker reaction of ketimine
1a.
Table 1. Initial screening of typical sodium salts for a Strecker reaction
of ketimine 1a.
Entry[a]
Metal source
Time [d]
Conversion [%][b]
ee [%][c]
1
2
3
4
nBuLi
LiOH·H2O
NaH
NaOMe
Na2CO3
KOtBu
CsOH·H2O
CaH2
1.0
1.5
1.5
3.0
3.0
1.0
1.0
1.5
100
100
100
54
0
0
70
35
0
Entry[a]
Catalyst
Conversion [%][b]
ee [%][c]
1
2
3
3a
3b
3c
3d
90
80
10
15
100
8
0
10
0
50
–
5[d]
6
15
4[d]
5
100
100
80
12
3e
7
8
17
6[e]
(S)-BNPH
no reaction
À17[e]
[a] Reaction conditions: After stirring a mixture of chiral acid (20 mol%)
and NaOH (20 mol%) in toluene (0.3 mL) at 358C for 1 h, 1a
(0.125 mmol) in toluene (0.2 mL) was added at room temperature, fol-
lowed by TMSCN (1.5 equiv) at À208C. [b] Determined by chiral HPLC
analysis. [c] Determined by HPLC analysis on Chiralcel AD-H. The ab-
solute configuration was determined to be R by comparison with litera-
ture data.[2c] [d] 20 mol% (S)-BINOL and 40 mol% NaOH were used.
[e] The reaction was catalyzed by 20 mol% (S)-BNPH using either
TMSCN or HCN as cyanation reagents.
[a] Reaction conditions: After stirring
a
mixture of (S)-BNPH
(20 mol%) and metal salt (20 mol%) in toluene (0.3 mL) at 358C for
1 h, 1a (0.125 mmol) in toluene (0.2 mL) was added at room tempera-
ture, followed by TMSCN (1.5 equiv) at À208C. [b] Determined by chiral
HPLC analysis. [c] Determined by HPLC analysis on Chiralcel AD-H.
The absolute configuration was determined to be R by comparison with
literature data.[2c] [d] 20 mol% (S)-BNPH and 10 mol% Na2CO3 were
used. [e] 20 mol% (S)-BNPH and 10 mol% CaH2 were used, and the ab-
solute configuration was determined to be S.
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X. Feng et al.
ated prior from equimolar amounts of BNPH and NaH
(Table 2, entry 3). Other sodium salts only led to inferior
outcomes (Table 2, entry 3 vs. 4 or 5).[11] Other alkaline
metal salts such as KOtBu and CsOH·H2O were not effec-
tive (Table 2, entries 6 and 7). Surprisingly, changing the
cation to Ca2+ caused a reversion of the absolute configura-
tion of 2a (Table 2, entry 8). The cation effect shown in
Table 2 might be related to the effective size of the metal
cation in the solvent.[4f] The lithium cation was prone to
form aggregation of the catalyst,[3] while potassium and
cesium cations might cause different ion pairs.[4d–f] Hence,
NaH was considered as the best metal source.
enced by the solvent, temperature, and additives. At À208C,
a routine solvent screening established that toluene was the
best choice in terms of the reactivity and enantioselectivity
(Table 4, entry 1). The use of CH2Cl2 gave trace product
Table 4. Optimization of reaction conditions for the asymmetric Strecker
reaction.
Entry[a]
Additives
Solvent
Conversion [%][b]
ee [%][c]
Subsequently, various BINOL-derived sodium phosphate
compounds (3e–m) prepared by using NaH were investigat-
ed (Table 3). Sodium phosphates with sterically congested
1
2
3
–
–
–
toluene
CH2Cl2
THF
100
8
75
70
5
0
4
–
Et2O
39
0
5
6
7
8
9
10
–
CH3CN
toluene
toluene
toluene
toluene
toluene
25
32
60
100
100
100
0
Table 3. The influence of the skeleton of chiral phosphates on a Strecker
reaction of ketimine 1a.
3 ꢁ MS
iPrOH
PhOH
2-bromophenol
2-nitrophenol
63
10
65
61
72
Entry[a]
Sodium phosphate 3e–m
Conversion [%][b]
ee [%][c]
11
toluene
100
77
1
2
3
4
5
6
7
8
9
3e
3 f
3g
3h
3i
3j
3k
3l
100
100
100
100
100
85
80
100
100
70
5
10
30
À40[d]
À35[d]
À18[d]
7
12
toluene
toluene
100
100
85
88
À8[d]
13[d]
PBAP
3m
[a] Reaction conditions: After stirring a mixture of phosphoric acid
(20 mol%) and NaH (20 mol%) in toluene (0.3 mL) at 358C for 1 h, 1a
(0.125 mmol) in toluene (0.2 mL) was added at room temperature, fol-
lowed by TMSCN (1.5 equiv) at À208C. [b] Determined by chiral HPLC
analysis. [c] Determined by HPLC analysis on Chiralcel AD-H. The ab-
solute configuration was determined to be R by comparison with litera-
ture data.[2c] [d] The absolute configuration was determined to be S.
[a] Reaction conditions: After stirring (S)-BNPH (20 mol%) and NaH
(20 mol%) in toluene (0.3 mL) at 358C for 1 h, 1a (0.125 mmol), additive
(20 mol%), and toluene (0.2 mL) were added at room temperature, fol-
lowed by TMSCN (1.5 equiv) at À208C. [b] Determined by chiral HPLC
analysis. [c] Determined by HPLC analysis on Chiralcel AD-H. The ab-
solute configuration was determined to be R by comparison with litera-
ture data.[2c] [d] 10 mol% (BNPH/NaH/PBAP 1:1:1) were used; see Ex-
perimental Section.
3,3’-disubstituents on the BINOL skeleton, however, gave
non-ideal chiral induction in the asymmetric amino nitrile
synthesis (Table 3, entries 2–7), despite their excellent per-
formance in other asymmetric transformations.[7–9,12] For ex-
ample, 3,3’-dibiphenyl-, 3,3’-di-1-naphthyl-, and 3,3’-di-2-
naphthyl-BINOL-phosphoric acid combined with NaH all
provided much lower ee values (Table 3, entries 4, 6, and 7).
It was noted that stereochemical inversion of the product
occurred when 4-biphenyl was replaced by 4-chlorophenyl
(Table 3, entry 5 vs. 4).[13] Inferior asymmetric induction was
observed using 3l (Table 3, entry 8). If the BINOL frame-
work was replaced by H8-BINOL, poor ee value was ob-
tained (Table 3, entry 9), which suggested that a proper di-
hedral angle be of great importance for chiral induction.
Therefore, simple (S)-BNPH and NaH were chosen for the
following optimization.
with only 5% ee (Table 4, entry 2). Other solvents such as
THF, Et2O, and CH3CN gave racemic products with low to
moderate conversion (Table 4, entries 3–5). Next some addi-
tives were investigated. Molecular sieves were not effective
in promoting this reaction (Table 4, entry 6). Due to the sig-
nificant improvement by protic additives in the enantiose-
lective Strecker reaction of ketimines in recent
years,[2d–g,j–l,14] iPrOH and phenol derivatives were investigat-
ed. However, introduction of iPrOH sharply diminished
enantioselectivity with incompletion of the reaction
(Table 4, entry 7). The reaction maintained high reactivity
when phenol was employed, but the ee decreased to 65%
(Table 4, entry 8). Neither 2-bromophenol nor 2-nitrophenol
could improve the enantioselectivity (Table 4, entries 9 and
10). The sterically hindered 2,5-di-(1-adamantyl)hydroqui-
none (DAHQ), an additive in the Strecker reaction of N-Ts-
protected (Ts=p-toluenesulfonyl) ketimines,[2j] slightly in-
Other reaction parameters were optimized. The results
showed that the Strecker reaction was significantly influ-
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Strecker Reaction of Ketimines
FULL PAPER
Table 5. Substrate generality for the Strecker reaction of ketimine 1.
creased the ee from 70 to 77%
(Table 4, entry 11 vs. 1). To our
delight, employment of para-
butyl-ortho-adamantyl phenol
(PBAP) gave superior results
(Table 4, entry 12). Further ad-
justing the catalyst loading and
concentration enhanced the ee
value up to 88% without any
Entry[a]
Ketimine 1
Time [d]
Product 2
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
R=H
R=p-F
R=o-Cl
R=m-Cl
R=p-Cl
R=2,4-Cl2
R=3,4-Cl2
R=p-Br
R=m-NO2
R=p-NO2
R=m-Me
R=p-Me
R=m-OMe
R=p-OMe
2.0
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
3.0
3.0
3.5
3.5
2a
2b
2c
2d
2e
2 f
2g
2h
2i
2j
2k
2l
2m
2n
93
95
94
93
95
93
94
96
94
92
92
92
88
90
88 (R)
89 (R)
95
87 (R)
88 (R)
94
loss
of
yield
(Table 4,
entry 13). In addition, the reac-
tion temperature had a signifi-
cant effect on the yield, but
the enantioselectivity of the
adduct was not very sensitive
to temperature. The amount of
TMSCN was tested, but the
enantioselectivity could not be
further improved (see the Sup-
porting Information). Accord-
85
88 (R)
86 (R)
85
82
92 (R)
87
9
10
11
12
13
14
91 (R)
15
3.5
2o
90
90
ingly,
showed that the optimized re-
action conditions were
0.25 mmol ketimine, 10 mol%
catalyst (BNPH/NaH/PBAP
1:1:1), and 1.5 equiv TMSCN
in 1.0 mL toluene at À208C. It
should be noted that the reac-
tion mixture was heterogene-
ous under the optimized reac-
tion conditions.
extensive
screening
16
17
18
2.0
3.0
3.0
2p
2q
2r
95
93
92
90 (R)
94 (R)
90
19
20
21
22
2.0
3.5
1.5
1.5
2s
2t
92
90
95
94
82
79
80
82
Under the optimal reaction
conditions, a variety of Dpp-
protected ketimines were ex-
amined.
A
wide substrate
scope was evidenced with this
sodium salt catalyst. Different
2u
2v
aryl
ketimines
proceeded
smoothly to produce the corre-
sponding amino nitriles in high
yields with good to excellent
enantioselectivities
(82–
[a] For reaction conditions, see Experimental Section. [b] Isolated yield. [c] Determined by chiral HPLC analy-
sis. The absolute configuration was determined by comparison with literature data.[2c,k]
95% ee) (Table 5, entries 1–
16). Ketimines containing elec-
tron-withdrawing groups had
relatively higher reactivities
than those bearing electron-donating groups (Table 5, en-
tries 2–10 vs. 11–15). Notably, the ortho-chloro substituent,
compared with the meta or para one on the phenyl ring, af-
forded excellent ee (Table 5, entries 3 and 6 vs. 4, 5, and 7).
Most excitingly, the current catalyst system could also be ap-
plied to the sterically bulky cyclic ketimines, giving excellent
results with 94 and 90% ee, respectively (Table 5, entries 17
and 18). In addition, a,b-unsaturated ketimine 1s could be
transformed to the synthetically important product 2s with
82% ee (Table 5, entry 19). In the case of the heterocyclic
ketimine of furyl and aliphatic ketimines 1u and 1v, good
enantioselectivities were observed as well (Table 5, en-
tries 20–22).
Mechanism studies: To shed some light on the possible
origin of the remarkable performance of the Strecker reac-
tion catalyzed with sodium phosphate, a series of control ex-
periments were performed (Table 6). To determine whether
TMSCN and sodium phosphate took part in the enantiose-
lectivity-determining step, HCN was investigated as another
cyanide nucleophile. As expected, the reaction rate was con-
siderably lower and only racemic products were obtained
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X. Feng et al.
Table 6. Control experiment for mechanistic study.
(Scheme 3, step I). PBAP might not only favor the forma-
tion of a hydrogen bond with a sodium salt, but might also
serve to activate ketimine 1 and participate in the asymmet-
ric induction of the reaction (Scheme 3, step II).[16] The acti-
vated nucleophile would attack the highly polarized C=N of
ketimine 1 from a less stereohindered direction to give the
desired product. Subsequently, elimination of the catalyst
furnished the corresponding adduct 2[17] and regenerated 3e
and PBAP (Scheme 3, step III).
Entry[a] (S)-
BNPH
NaH PBAP Cyanide
source
Time Conv.
[d]
ee
[%][b]
[%][c]
ACHTUNGTRENNUNG[mol%]
1
2
3
4
10
10
10
10
10
–
10
–
HCN[d]
HCN[d]
TMSCN
TMSCN
4.0
4.0
1.5
2.0
25
29
100
100
0
3
72
88
10
10
10
10
Conclusion
[a] Reaction conditions: After stirring the corresponding catalyst in tolu-
ene (1.0 mL) at 358C for 1 h, 1a (0.25 mmol) was added, followed by the
corresponding cyanide source (1.5 equiv) at À208C. [b] Conversion deter-
mined by chiral HPLC analysis. [c] Determined by HPLC analysis on
Chiralcel AD-H. The absolute configuration was determined to be R by
comparison with literature data.[2c] [d] HCN solution was generated prior
to the reaction from equimolar amounts of TMSCN and methanol.
In summary, a successful chiral alkali-metal-salt-catalyzed
enantioselective Strecker reaction of ketimines with
TMSCN was developed by employing chiral (S)-BNPNa
(3e; 10 mol%) and PBAP. The simplicity and facile availa-
bility of the catalyst and high enantioselectivities of the re-
action make it potentially applicable in synthesis. Control
experiments have suggested that TMSCN is likely the actual
nucleophile. Detailed mechanism studies and further investi-
gations into other versions of asymmetric catalysis are cur-
rently underway.
(Table 6, entries 1 and 2). However, high ee values could be
obtained when TMSCN was employed (Table 6, entries 3
and 4). So the key role of PBAP was deduced not to gener-
ate HCN as it does in most Strecker reactions involving
TMSCN.[2e,g] These phenomena also demonstrated that
TMSCN was likely to be the real cyanating agent (Table 6,
entry 3 vs. 1; entry 4 vs. 2).
Experimental Section
In this manner, we speculated that the formation of a re-
active hexacoordinate silicon intermediate should be crucial
for the asymmetric induction,[6b] and clearly the Strecker re-
action catalyzed by the sodium salt was mechanistically dis-
tinct from the reaction catalyzed with a chiral Brønsted
acid, in which a prochiral ketimine was activated by an
acid.[2i] While more detailed investigations of the reaction
mechanism are currently underway, a possible asymmetric
induction pathway was proposed (Scheme 3). By taking ad-
vantage of the detailed studies on hypervalent silicon inter-
mediates[6b] and ion pairs,[15] compound 4 was formed
Typical procedure for the enantioselective Strecker reaction of ketimines:
(S)-1,1’-Binaphthyl-2,2’-diylphosphoric acid (8.7 mg, 0.025 mmol) and
sodium hydride (1 mg, 0.025 mmol) were placed in a tube under an argon
atmosphere. Toluene (0.5 mL) was added and the mixture was stirred at
308C for 1 h. Then PBAP (7.1 mg, 0.025 mmol) and ketimine 1a (80 mg,
0.25 mmol) were added, followed by additional toluene (0.5 mL) at room
temperature. To this mixture trimethylsilyl cyanide (50 mL, 0.375 mmol)
was added under À208C. The reaction was vigorously stirred at À208C
and monitored by HPLC. After two days, the residue was purified by
flash silica gel chromatography to obtain the corresponding Dpp-protect-
ed a-amino nitrile 2a in 93% yield with 88% ee. HPLC (DAICEL
CHIRALCEL AD-H, 210 nm, hexane/2-propanol 80:20, 1.0 mLminÀ1):
tR =9.01 min (major), tR =10.14 min (minor); [a]2D0 =+13.87 (c=0.20 in
1
CHCl3), (ref. [2c]: [a]2D3 =À19.1 (c=1.00 in CHCl3) (>99% ee)); H NMR
(400 Hz, CDCl3): d=8.01–8.07 (m, 2H), 7.81–7.86 (m, 2H), 7.73–7.76 (m,
2H), 7.33–7.60 (m, 9H), 3.68 (d, J=7.6 Hz, 1H), 2.29 ppm (s, 3H).
Typical procedure for the synthesis of (S)-BNPH ((S)-1,1’-binaphthyl-
2,2’-diylphosphoric acid): (S)-BINOL (572 mg, 2 mmol) was dissolved in
pyridine (4.5 mL). Phosphorous oxychloride (0.75 mL, 4 mmol) was
added dropwise at room temperature with rapid stirring and the resulting
solution was stirred at 608C for 12 h. Water (4.0 mL) was added and the
resulting biphasic suspension was stirred at 508C for a further 2 h. The
reaction mixture was diluted with CH2Cl2 and pyridine was extracted by
washing with aqueous 1n HCl. The combined organic phase was dried
over Na2SO4 and concentrated. The crude solid was purified by flash
silica gel chromatography (5% MeOH in CH2Cl2) to yield 7e as an
ivory-white solid (626 mg, 90% yield). 1H NMR (400 MHz, (CD3)2SO):
d=8.11 (d, J=8.0 Hz, 2H), 8.06 (d, J=8.8 Hz, 2H), 7.46–7.50 (m, 4H),
7.32–7.36 (m, 2H), 7.22 ppm (d, J=8.8 Hz, 2H).
Typical procedure for the synthesis of PBAP (para-tert-butyl-ortho-ada-
mantylphenol): To a stirred solution of para-tert-butylphenol (2.253 g,
15 mmol) and 1-adamantanol (2.283 g, 15 mmol) in CH2Cl2 (25 mL), con-
centrated H2SO4 (0.9 mL) was added dropwise at 08C over 10 min. The
suspension was stirred at room temperature for a further 2 h before 5%
aqueous NaOH was added to neutralize H2SO4. The resulting biphasic
suspension was extracted by CH2Cl2 twice. The combined organic phase
Scheme 3. Proposed catalytic cycle.
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Strecker Reaction of Ketimines
FULL PAPER
was dried over Na2SO4 and concentrated. The crude solid was purified by
silica gel chromatography using AcOEt/petroleum ether (1:25) as eluent
to yield PBAP as a pale white solid (2.773 g, 65% yield). 1H NMR
(400 MHz, CDCl3): d=7.24 (d, J=2.4 Hz, 1H), 7.05–7.08 (m, 1H), 6.58
(d, J=8.0 Hz, 1H), 4.56 (s, 1H), 2.08–2.14 (m, 9H), 1.78–1.79 (t, 6H),
1.29 ppm (s, 9H).
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Acknowledgements
We thank the National Natural Science Foundation of China (nos.
20732003 and 20602025) for financial support. We also thank Sichuan
University Analytical & Testing Center for NMR analysis and the State
Key Laboratory of Biotherapy for HRMS analysis.
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1a should be involved.
ˇ
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Chem. Eur. J. 2009, 15, 6008 – 6014
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6013

X. Feng et al.
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1H NMR spectroscopic data suggested that the N atom of the imine
probably coordinated to the silicon atom of the hypervalent silicate
À
and ultimately formed an N Si bond (see the following ref.: Z. G.
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PBAP and a proposed dimer species is described in the Supporting
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was hydrolyzed during the aqueous workup or direct silica gel chro-
matography.
Received: January 23, 2009
Revised: March 30, 2009
Published online: May 5, 2009
6014
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ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 6008 – 6014