Nickel-catalysed addition of dialkylzinc reagents to N-phosphinoyl- and N-sulfonylimines

Article abstract of DOI:10.1016/j.tet.2006.11.056

A catalytic amount of a nickel complex (0.1-5.3 mol %) extraordinarily increases the reaction rate of the addition of dialkylzinc reagents to N-(diphenylphosphinoyl)- or N-(benzenesulfonyl)imines. The reaction of imines derived from both aromatic and alip

Full text of DOI:10.1016/j.tet.2006.11.056

Tetrahedron 63 (2007) 1167–1174
Nickel-catalysed addition of dialkylzinc reagents
to N-phosphinoyl- and N-sulfonylimines
*
Raquel Almansa, David Guijarro and Miguel Yus
Departamento de Quꢀımica Orgaꢀnica, Facultad de Ciencias and Instituto de Sꢀıntesis Orgaꢀnica (ISO),
Universidad de Alicante, Apdo. 99, 03080 Alicante, Spain
Received 10 October 2006; revised 16 November 2006; accepted 20 November 2006
Available online 12 December 2006
This paper is dedicated to Professor K. P. C. Vollhardt on occasion of his 60th anniversary
Abstract—A catalytic amount of a nickel complex (0.1–5.3 mol %) extraordinarily increases the reaction rate of the addition of dialkylzinc
reagents to N-(diphenylphosphinoyl)- or N-(benzenesulfonyl)imines. The reaction of imines derived from both aromatic and aliphatic alde-
hydes with various dialkylzinc reagents in the presence of several nickel complexes gives the expected addition products in most cases in 1 h
and in very good yields. In general, the formation of reduction by-products was not an important side reaction. The process represents a great
improvement, with regard to the reaction rate and the yield of the addition products, in comparison with the reactions performed in the absence
of the nickel catalyst, and reaction times are much shorter than the ones reported so far using other catalysts.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
groups can easily be prepared,7 and can lead to polyfunction-
alised organic compounds. However, the reaction of N-phos-
phinoyl- or N-sulfonylimines with dialkylzincs is very slow,
leading to low yields of addition products in very long reac-
tion times. For N-phosphinoylimines, improved reaction
rates and much higher yields have been observed by using
some additives like b-aminoalcohols,4,8 iminoalcohols,9
hydroxyoxazolines10 and copper11 or zirconium12 com-
plexes, rendering the addition reactions into stereoselective
processes. In the case of N-sulfonylimines, b-aminoalco-
hols13 and copper14 or rhodium15 complexes have also shown
to be efficient in catalysing the addition of organozinc
reagents. We have recently started testing nickel complexes
as catalysts for several nucleophilic addition reactions and
we found that a catalytic amount of nickel acetylacetonate
greatly accelerates the addition of dialkylzinc reagents to
both aromatic and aliphatic aldehydes.16 As an extension of
that study, in this paper we report our results on the use of
several nickel complexes to catalyse the addition of dialkyl-
zincs to N-(diphenylphosphinoyl)- and N-(benzenesulfonyl)-
imines.
The addition of organometallic reagents to imines is a valu-
able method for the preparation of primary and secondary
amines,1,2 which are very interesting from both the synthetic
and the biological point of view. However, this method pres-
ents some problems due to the low electrophilic character
of the C]N bond and to the tendency of basic reagents to
abstract protons a to the imine leading to tautomerization to
the corresponding enamines. The electrophilicity of the
imine can be enhanced by introducing an electron-with-
drawing group attached to the nitrogen atom, such as the
phosphinoyl or the sulfonyl group, among others. N-Phos-
phinoylimines3 are very attractive since the phosphinoyl
group can easily be removed from the addition product under
mild reaction conditions leading to the free amines.4 N-Sul-
fonylimines5 are also very useful substrates, since they are
slightly more reactive than N-phosphinoylimines, but the
deprotection of the sulfonamide products can sometimes
be problematic. Both N-phosphinoyl- and N-sulfonylimines
have found a variety of synthetic applications, including
asymmetric processes.2,5 On the other hand, the susceptibil-
ity to a-deprotonation can be diminished by using less basic
nucleophiles, such as boranes, stannanes, cuprates or dialkyl-
zinc reagents. Among them, the latter are very useful nucleo-
philes since organozinc reagents6 bearing several functional
2. Results and discussion
Since we have demonstrated the usefulness of Ni(acac)2 to
catalyse the addition of dialkylzinc reagents to aldehydes,16
we decided to test the same complex for the addition to
activated imines. N-(diphenylphosphinoyl)benzaldimine and
diethylzinc were chosen as model substrate and nucleophilic
Keywords: N-(Diphenylphosphinoyl)imine; N-(Benzenesulfonyl)imine;
Dialkylzinc; Nickel complex; Addition.
* Corresponding author. Fax: +34 965903549; e-mail: yus@ua.es
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.11.056

1168
R. Almansa et al. / Tetrahedron 63 (2007) 1167–1174
reagent, respectively, in order to start our study. Gratifyingly,
the reaction of imine 1a with an excess of diethylzinc (1:2.2
molar ratio) and a catalytic amount of Ni(acac)2 (1:0.05 mo-
lar ratio) in acetonitrile at 0 ꢀC for 1 h led, after hydrolysis,
to the expected addition product 4aa in 81% yield (Scheme 1
and Table 1, entry 1). As a mode of comparison, the same
reaction in the absence of the nickel catalyst gave only a
11% yield of the addition product 4aa after stirring for
48 h at room temperature (Table 1, entry 15). We then
decided to test some other nickel complexes in order to
look for the best catalyst. NiCl2 and NiBr2 were as efficient
as Ni(acac)2, giving the addition product in similar yields in
1 h under the same reaction conditions (Table 1, entries 2
and 3). However, NiCO3 did not show the same acceleration
effect: after stirring the reaction between 1a and diethylzinc
in the presence of 5 mol % of NiCO3 for three days at room
temperature, only 29% of the addition product was obtained
(Table 1, entry 4), the major product being the one resulting
from reduction of the C]N bond (60% yield; Table 1,
entry 4). This reduction product was also detected in minor
amounts in the reactions with the other nickel(II) complexes
[2% with both Ni(acac)2 and NiBr2 and 13% with NiCl2] and
it is probably formed via b-hydride transfer from diethylzinc
(or a generated ethylnickel complex) to the imine.17 The
nickel(0) complex Ni(COD)2 was also tested and a 83% of
the addition product was obtained (Table 1, entry 5), the
reaction being as fast as the ones catalysed by the nickel(II)
complexes (Table 1, entries 1–3). This result suggests that
there is a mechanistic difference between this reaction and
the nickel-catalysed addition of dialkylzinc reagents to alde-
hydes,16,18 since we found that in that case Ni(COD)2 was
not acting as a catalyst.16 Although the yield obtained with
Ni(COD)2 was slightly higher than the one obtained with
Ni(acac)2, we decided to use the latter in the next experi-
ments, since it is more easily handled and inexpensive.
Next, we studied the effect of the solvent. The addition of
diethylzinc to the imine 1a in the presence of 5 mol % of
Ni(acac)2 was performed in acetonitrile, THF, dichloro-
methane and toluene. The addition product 4aa was obtained
in 81, 76, 59 and 76% yields, respectively (Table 1, entries 1
and 6–8), together with variable amounts of the correspond-
ing reduction product (2% in MeCN, 11% in THF, 32%
in CH2Cl2 and 18% in PhMe; Table 1, entries 1 and 6–8).
From these results, it is clear that acetonitrile is the solvent
of choice, since it gives the highest yield of the addition
product and the smallest amount of the reduction by-
product.
The effect of the amount of the nickel catalyst on the in-
crease of the rate of the addition reaction was also explored.
The reaction of imine 1a with diethylzinc in acetonitrile at
0 ꢀC was performed in the presence of variable amounts of
Ni(acac)2, namely 2, 1, 0.5 and 0.1 mol %. In all cases, the
reaction was finished in 1 h and the addition product 4aa
was isolated in 83, 78, 86 and 89% yield, respectively (Table
1, entries 9–12). It is remarkable that even such a low amount
of nickel catalyst as 0.1 mol % can effectively promote the
addition reaction, giving a slightly higher yield than the
reaction in the presence of 5 mol % of Ni(acac)2 (Table 1,
entry 1). The reaction in the presence of 0.1 mol % of
Ni(acac)2 was repeated at ꢁ30 ꢀC and no difference in reac-
tion rate was observed: after 1 h, the starting material had
disappeared and the addition product was obtained in
89% yield (Table 1, entry 13). In an attempt to further de-
crease the temperature, the same reaction was performed
at ꢁ78 ꢀC, but in toluene instead of acetonitrile, due to freez-
ing of the reaction medium with the latter solvent. In this
case, the reaction was much slower: after stirring for 26 h
at ꢁ78 ꢀC, the hydrolysis of the reaction gave only 20% of
the addition product (Table 1, entry 14), together with
some unreacted imine, benzaldehyde and diphenylphos-
phinic amide. The latter two products derive from the hydro-
lysis of part of the starting imine 1a.
O
O
PPh2
PPh2
N
HN
Ph
i, ii
+
R22Zn
Ph
H
R2
1a
2
4a
i
n
(R2 = Me, Et, Pr, Bu, Ph)
Scheme 1. Reagents and conditions: (i) Ni complex 3, solvent, T. (ii)
NH4Cl (aq).
Table 1. Preparation of compound 4aa (R2¼Et) by a nickel-catalysed
addition of diethylzinc to imine 1a under optimised reaction conditions
Entry
Nickel complex
Mol %
Solvent T (ꢀC) Time Product
(h)
3
Yield (%)a,b
1
2
3
4
5
6
7
8
Ni(acac)2
NiCl2
NiBr2
NiCO3
5
MeCN
MeCN
MeCN
MeCN
MeCN
THF
0
0
0
1
1
1
81 (2)
5
5
5
5
5
5
5
2
1
77 (13)
80 (2)
29 (60)
83 (7)
76 (11)
59 (32)
76 (18)
83
0–20 72
0
0
0
0
0
0
0
0
Ni(COD)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2 0.5
Ni(acac)2 0.1
Ni(acac)2 0.1
Ni(acac)2 0.1
1
1
1
1
1
1
1
1
1
26
CH2Cl2
PhMe
We then focused on the possibility of using other dialkylzinc
reagents. Commercially available Me2Zn, iPr2Zn and
nBu2Zn reacted with N-(diphenylphosphinoyl)benzaldimine
1a in the presence of 5 mol % of Ni(acac)2 at 0 ꢀC, giving the
corresponding addition products 4ab–4ad in 1 h invery good
yields (Scheme 1 and Table 2, entries 2–4). The addition of
commercially available diphenylzinc was also attempted, but
without success. However, when the phenyl transfer reaction
was tried by using a mixture of triphenylborane and diethyl-
zinc as the phenyl source,19 the expected addition product
4ae was obtained in 1 h in 58% yield (Table 2, entry 5).
9
MeCN
MeCN
MeCN
MeCN
MeCN
PhMe
10
11
12
13
14
15
78
86
89
89
ꢁ30
ꢁ78
20c
—
—
MeCN
0–20 48
11d
a
Isolated yield after column chromatography (silica gel, hexane/acetone)
based on the starting imine 1a. The isolated compound 4aa was always
ꢂ95% pure (GC and/or 300 MHz 1H NMR).
b
c
In brackets, yields of the corresponding reduction products.
The reaction was not complete. A significant amount of the starting
material was detected in the crude mixture.
d
The reaction was not complete. A significant amount of the starting
material was detected in the crude mixture, together with 37% of the
reduction product.
Next, we investigated the versatility of our procedure con-
cerning the substrate. Although imine 1a could be prepared

R. Almansa et al. / Tetrahedron 63 (2007) 1167–1174
1169
Table 2. Preparation of compounds 4 by a Ni(acac)2-catalysed addition
of dialkylzinc reagents to N-(diphenylphosphinoyl)imines 1 in acetonitrile
at 0 ꢀC
the addition reactions with diethylzinc are much higher. We
were delighted to see that our methodology was also appli-
cable to imines derived from aliphatic aldehydes. Imine 1e
was generated in situ by reaction of the corresponding
adduct 5e (obtained in pure form by a literature procedure21)
with diethylzinc and it gave the addition product in a reaction
time of only 1 h at 0 ꢀC using 5 mol % of Ni(acac)2 (Table 2,
entry 9). To the best of our knowledge, this is the fastest
addition reaction of diethylzinc to an aliphatic N-(diphenyl-
phosphinoyl)imine that has ever been reported.
Entry
Imine
Nickel complex Time
(h)
Product
No. R1
R2 Mol %
No. Yield (%)a
1
2
3
4
5
6
7
8
9
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
Et
Me
5
5
5
5
5
1
1
1
1
1
4aa 81
4ab 85
4ac 92
4ad 80
4ae 58
4b 43e
4c 50e
4d 29e
4e 80
iPr
nBu
Phb
1bc 4-ClC6H4
Et 2.6d
2
1cc 4-MeOC6H4 Et 5.3d
1dc 2-Naphthyl Et 5.3d
17
13
1
O
O
O
1ec PhCH2CH2 Et
5
PPh2
PPh2
PPh2
O
N
HN
R1
HN
R1
ii, iii
i
a
+
Isolated yield after column chromatography (silica gel, hexane/acetone)
based on the starting imine 1. All isolated compounds 4 were ꢂ95%
pure (GC and/or 300 MHz 1H NMR).
Phenylzinc species were generated in situ by reaction between triphenyl-
borane and diethylzinc.
Imine generated in situ (see text and experimental part).
The mol % of Ni(acac)2 is based on the starting amount of P,P-diphenyl-
phosphinic amide.
Isolated yield after column chromatography (silica gel, hexane/acetone)
based on the starting amount of P,P-diphenylphosphinic amide.
R1
H
R1
H
Ts
5b-5e
(not isolated)
(R1 = 4-ClC6H4, 4-MeOC6H4, 2-naphthyl, PhCH2CH2)
1b-1e
4b-4e
b
c
d
Scheme 2. Reagents and conditions: (i) Ph2P(O)NH2, p-MeC6H4SO2H,
Et2O, 20 ꢀC, then filtrate. (ii) Et2Zn (1.7–3.3 equiv), Ni(acac)2 (2.6–
5.3 mol %), MeCN, 0 ꢀC. (iii) NH4Cl (aq).
e
Unfortunately, the application of the same methodology to
ketimines was unsuccessful. The N-(diphenylphosphinoyl)-
imine derived from acetophenone was prepared and sub-
mitted to the reaction with diethylzinc in the presence of
10 mol % of Ni(acac)2. No addition product was detected
after stirring for 24 h at room temperature, the unaltered
starting imine being recovered.
by reaction of benzaldehyde with diphenylphosphinic amide
in the presence of titanium tetrachloride following the liter-
ature procedure20 and could be isolated in pure form, we
found some problems when the same method was applied
to the synthesis of imines 1b–1e. In all cases, the expected
imines were formed in very small amounts and they could
not be purified neither by recrystallisation nor by column
chromatography on deactivated silica gel. Fortunately,
imines 1b–1e could be generated in situ from their corre-
sponding sulfinic acid adducts 5 (Scheme 2), which were
readily prepared by mixing the corresponding aldehydes
with diphenylphosphinic amide and p-toluenesulfinic acid in
Et2O.21 In all of these reactions, a white precipitate was
slowly formed, which was filtered and washed with Et2O.
For the reactions with 4-chlorobenzaldehyde, 4-methoxy-
benzaldehyde and 2-naphthaldehyde, 1H NMR of the white
solid showed that it was a mixture of the expected adducts
5b–5d and the corresponding imines 1b–1d. Since both
compounds 5 and 1 were expected to yield the same addition
product by reaction with diethylzinc, the solid mixtures were
used in the addition reactions without purification. When the
mixture of 5b and 1b, derived from p-chlorobenzaldehyde,
was treated with an excess of diethylzinc in the presence
of 2.6 mol % of Ni(acac)2 (based on the starting amount of
P,P-diphenylphosphinic amide) in acetonitrile at 0 ꢀC, the
expected product 4b was obtained in 2 h in 43% yield
(Scheme 2 and Table 2, entry 6). The addition to electron-
rich imines was slower, but increasing the amount of the
nickel catalyst up to 5.3 mol % (based on the starting amount
of P,P-diphenylphosphinic amide) and stirring for a longer
time, the mixtures 5c+1c and 5d+1d gave the addition prod-
ucts 4c and 4d in 50 and 29% yields, respectively, after stir-
ring at 0 ꢀC for 17 and 13 h, respectively (Table 2, entries 7
and 8). It must be noted that the yields of products 4b–4d are
referred to the starting amounts of P,P-diphenylphosphinic
amide. Since in the formation step of the adducts the
amounts of solid that precipitated were 54% (for 5b), 78%
(for 5c) and 47% (for 5d) of the expected amounts (assuming
that only the adducts had been formed), the actual yields of
Having established the usefulness of our methodology to
the addition of dialkylzinc reagents to N-(diphenylphos-
phinoyl)imines, we decided to apply it to another type of
activated imines, N-sulfonylimines. Commercially available
N-(benzenesulfonyl)benzaldimine 6 was treated with an ex-
cess of diethylzinc (1:2.2 molar ratio) and a catalytic amount
of Ni(acac)2 (1:0.05 molar ratio) in acetonitrile at 0 ꢀC for
1 h and, after hydrolysis, the expected addition product 7a
was obtained in 80% yield (Scheme 3 and Table 3, entry
1). In order to compare with the non-catalysed reaction,
the addition of diethylzinc to 6 was repeated in the absence
of the nickel catalyst. In this case, after 24 h at room tem-
perature, 40% of the product 7a was obtained, together with
8% of the product resulting from reduction of the imine17,22
(Table 3, entry 2). Both reactions were also performed in
toluene instead of acetonitrile and a significant increase in
the amount of the reduction by-product was observed (Table
3, entries 3 and 4). The improvement in yield obtained in this
solvent was much higher than the one obtained with aceto-
nitrile: while the nickel-catalysed reaction gave a 83% yield
of the addition product 7a in 1 h (Table 3, entry 3), the non-
catalysed reaction afforded only 6% of 7a, together with
59% of the reduction product (Table 3, entry 4). As it was the
SO2Ph
H
SO2Ph
R2
N
HN
Ph
i, ii
+
R22Zn
Ph
i
n
(R2 = Me, Et, Pr, Bu)
Scheme 3. Reagents and conditions: (i) Ni complex 3, solvent, T. (ii) NH4Cl
(aq).

1170
R. Almansa et al. / Tetrahedron 63 (2007) 1167–1174
Table 3. Preparation of compounds 7 by a nickel-catalysed addition of dialkylzinc reagents to N-(benzenesulfonyl)benzaldimine 6
Entry
R2
Nickel complex
Mol %
Solvent
T (ꢀC)
Time (h)
Product
Yield (%)a,b
3
No.
1
2
3
4
5
6
7
8
9
Et
Et
Et
Et
Ni(acac)2
—
Ni(acac)2
—
Ni(COD)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
5
—
5
—
5
5
5
5
5
MeCN
MeCN
PhMe
PhMe
MeCN
PhMe
PhMe
MeCN
PhMe
0
0–20
0
0–20
0
0
0
0
0
1
24
1
24
1
1
1
1
1
7a
7a
7a
7a
7a
7b
7c
7c
7d
80 (2)
40 (8)
83 (14)
6 (59)
67 (19)
83
24 (73)
27 (31)
48 (41)
Et
Me
iPr
iPr
nBu
a
Isolated yield after column chromatography (silica gel, hexane/ethyl acetate) based on the starting imine 6. All isolated compounds 7 were ꢂ95% pure (GC
and/or 300 MHz 1H NMR).
In brackets, yields of the corresponding reduction products.
b
case with the N-(diphenylphosphinoyl)imines, the nickel(0)
observed in the reaction medium from green [corresponding
to Ni(acac)2] to black after a few drops of the dialkylzinc
reagent have been added could support this hypothesis.
Coordination of the imine to these nickel(0) species could
facilitate the attack of the dialkylzinc reagent to the imine
carbon atom, leading to a fast addition reaction.
complex Ni(COD)2 was also an efficient catalyst for the
addition reaction, although the yield of product 7a was lower
than the one obtained with Ni(acac)2 (Table 3, entry 5).
We then tested some other dialkylzinc reagents for the addi-
tion to the sulfonylimine 6 using 5 mol % of Ni(acac)2 as
catalyst. Me2Zn gave the expected addition product 7b in
83% yield after 1 h at 0 ꢀC (Table 3, entry 6). When imine
Finally, we have performed the Ni(acac)2-catalysed addition
of diethylzinc to imines 1a and 6 in the presence of several
chiral b-aminoalcohols in order to try to get some enantio-
selectivity in the process. The reaction rates were not
affected by the presence of the chiral ligands, but almost
racemic products have been obtained so far. Further efforts
to develop an asymmetric version of this addition reaction
are currently underway in our laboratories.
i
6 was treated with Pr2Zn in toluene at 0 ꢀC, after stirring
for 1 h only 24% of the addition product 7c was formed, the
major product being N-benzylbenzenesulfonamide (Table 3,
entry 7). This reaction was repeated in acetonitrile in order
to try to improve the yield of the addition product, but a dis-
appointing 27% yield of 7c was obtained (Table 3, entry 8).
nBu2Zn gave a moderate yield of 48% of 7d together with
41% of the reduction product (Table 3, entry 9). According
to these results, it seems that N-sulfonylimines are more
prone to undergo reduction than N-phosphinoylimines when
treated with the combination dialkylzinc-Ni(acac)2, espe-
cially with sterically congested dialkylzinc reagents.
3. Conclusion
In conclusion, we have reported here a very efficient proce-
dure to effect the addition of dialkylzinc reagents to both
N-(diphenylphosphinoyl)- and N-(benzenesulfonyl)imines
in short times and under mild reaction conditions. The use
of a catalytic amount of a nickel(II) or a nickel(0) complex
causes an extraordinary increase in the reaction rate and
leads to very good yields of the addition products in reaction
times as short as 1 h. The methodology is applicable to
imines derived from both aromatic and aliphatic aldehydes,
but it is not successful for ketimines. Several dialkylzinc
reagents and phenylzinc species can be employed with good
results. Ni(acac)2 has been shown to be a very convenient
catalyst, since it is inexpensive and an amount of it as low
as 0.1 mol % can be used without loosing efficiency.
It is interesting to note that, to the best of our knowledge,
although several reports have been published concerning
the addition of diethylzinc to N-tosylimines and other
arene substituted N-arenesulfonylimines, no addition to
N-(benzenesulfonyl)imines has been reported in the litera-
ture. Therefore, this is the first time that the addition of di-
alkylzinc reagents to such type of imines has been described.
AsitwasthecasewiththeN-(diphenylphosphinoyl)ketimines,
the application of our methodology to N-(benzenesulfonyl)-
ketimines was unsuccessful. The N-(benzenesulfonyl)imine
derived from acetophenone was prepared and submitted to
the reaction with diethylzinc in acetonitrile in the presence
of 10 mol % of Ni(acac)2. No addition product was detected
after stirring for 48 h at room temperature. The starting imine
was recovered unchanged.
4. Experimental
4.1. General
Concerning a possible reaction mechanism, the fact that the
addition reaction to both N-(diphenylphosphinoyl)imines
and N-(benzenesulfonyl)imines is very fast with nickel(II)
as well as nickel(0) complexes suggests that the mechanism
could be similar in both cases. We assume that a nickel(0)
species could be the real catalyst. The nickel(II) complexes
could be reduced to nickel(0) species by the action of the
dialkylzinc reagent.23 The rapid change in colour that is
All moisture sensitive reactions were carried out under an
argon atmosphere. Commercially available anhydrous MeCN
(ꢂ99.9%, water content ꢃ0.005%, Acros), THF (99.9%,
water content ꢃ0.006%, Acros), CH2Cl2 (ꢂ99.5%, water
content ꢃ0.005%, Fluka), toluene (ꢂ99.7%, water content
ꢃ0.005%, Fluka) and Et2O (ꢂ99.8%, water content
ꢃ0.005%, Fluka) were used as solvents in the reactions.
All the aldehydes needed for the synthesis of imines 1

R. Almansa et al. / Tetrahedron 63 (2007) 1167–1174
1171
were commercially available and liquid ones were distilled
before use. Solid aldehydes and commercially available
P,P-diphenylphosphinic amide, sodium p-toluenesulfinate,
N-(benzenesulfonyl)benzaldimine 6, Ni(acac)2, NiCl2,
NiBr2, NiCO3 and Ni(COD)2 were used without further
purification. Imine 1a was prepared according to a literature
procedure20 and it was obtained in pure form by column chro-
matography on silica gel previously deactivated by treatment
with triethylamine. Dialkylzinc reagents were used as their
commercially available solutions in toluene or heptane
(Aldrich, Fluka). Phenylzinc species were generated in situ
by reaction between triphenylborane and diethylzinc.19 All
glassware was dried in an oven at 100 ꢀC and cooled to
room temperature under argon before use. Column chroma-
tography was performed with Merck silica gel 60 (0.040–
0.063 mm, 240–400 mesh). Thin layer chromatography
(TLC) was performed on precoated silica gel plates (Merck
60, F254, 0.25 mm); detection was done by UV254 light; Rf
values are given under these conditions. Melting points
(mp) are uncorrected and were measured on a Reichert
thermovar apparatus. Nuclear magnetic resonance (NMR)
spectra were recorded on a Bruker AC-300 spectrometer
using CDCl3 as solvent and, as internal references, tetra-
methylsilane (TMS) for 1H NMR and CDCl3 for 13C NMR;
chemical shifts are given in d (ppm) and coupling constants
(J) in Hertz. 13C NMR assignments were made on the basis
of DEPTexperiments. Infrared (FTIR) spectra were obtained
on a Nicolet 510 P-FT spectrophotometer. Mass spectra
(EI) were obtained at 70 eV on a Hewlett Packard HP-5890
GC/MS instrument equipped with a HP-5972 selective
mass detector.
7.54, 7.59–7.73 and 7.77–7.91 (2H, 9H, 2H and 2H, respec-
tively, 4m, ArH); dC 19.2, 19.3 (2ꢄMe), 35.7 (d, J¼4.3 Hz,
CHMe), 61.3 (CN), 126.8, 126.9, 128.0, 128.1, 128.2,
128.4, 128.5, 131.7, 131.8, 131.9, 132.6, 132.7, 142.9
(d, J¼3.9 Hz) (ArC); m/z 349 (M+, <1%), 307 (22), 306
(100), 201 (50).
4.2.2. P,P-Diphenyl-N-(1-phenylpentyl)phosphinic amide
(4ad).9 White solid; Rf 0.63 (ethyl acetate); mp 167 ꢀC;
n (KBr) 3126 (NH), 3055, 3022, 3000, 1591 (HC]C),
1100 cmꢁ1 (P¼O); dH 0.79 (3H, t, J¼6.9 Hz, Me), 0.99–
1.32 [4H, m, Me(CH2)2], 1.73–1.87, 1.89–2.02 (1H each,
2m, CH2CN), 3.11–3.27 (1H, m, NH), 4.07–4.21 (1H, m,
CHN), 7.06–7.55, 7.68–7.80 and 7.81–7.91 (11H, 2H and
2H, respectively, 3m, ArH); dC 13.9 (Me), 22.4, 28.2
[Me(CH2)2], 39.5 (d, J¼3.7 Hz, CH2CN), 55.8 (CN),
126.4, 127.0, 128.2, 128.3, 128.4, 128.45, 128.5, 131.75,
131.8, 131.9, 132.5, 132.6, 143.9 (d, J¼5.4 Hz) (ArC); m/z
363 (M+, <1%), 307 (21), 306 (100), 201 (46).
4.3. Nickel-catalysed phenyl transfer reaction to imine
1a. Preparation of product 4ae
Diethylzinc (0.91 mL of a 1.1 M solution of diethylzinc in
toluene, 1.0 mmol) was dropwise added to a solution of tri-
phenylborane (66 mg, 0.25 mmol) in toluene (1 mL) at room
temperature.19 After stirring for 30 min at that temperature,
the resulting solution was dropwise transferred via syringe
during ca. 5 min to a stirred mixture of the imine 1a
(76 mg, 0.25 mmol) and Ni(acac)2 (3.3 mg, 0.013 mmol)
in toluene (1 mL) under argon at 0 ꢀC. After stirring for
1 h, the reaction was hydrolysed with an aqueous saturated
solution of NH4Cl (5 mL). Water (5 mL) was added and
the mixture was extracted with ethyl acetate (3ꢄ20 mL).
The combined organic layers were washed with brine
(5 mL), being then dried (Na2SO4). After filtration and evap-
oration of the solvents, the resulting residue was purified by
column chromatography (silica gel, hexane/acetone), afford-
ing product 4ae in 58% yield. The corresponding physical
and spectroscopic data for compound 4ae follow.
4.2. Nickel-catalysed addition of dialkylzinc reagents to
imine 1a. Preparation of products 4aa–4ad. General
procedure
The commercially available solution of the dialkylzinc
reagent in toluene (for dimethyl-, diethyl- and diisopropyl-
zinc) or heptane (for dibutylzinc) (1.1 mmol of R22Zn) was
dropwise added during ca. 5 min to a stirred mixture of the
imine 1a (153 mg, 0.5 mmol) and the corresponding amount
of the nickel complex 3 in the desired solvent (3 mL) under
argon at the required temperature (see Tables 1 and 2 for
details). After stirring for the time indicated in Tables 1
and 2, the reaction was hydrolysed with an aqueous saturated
solution of NH4Cl (5 mL). Water (5 mL) was added and the
mixture was extracted with ethyl acetate (3ꢄ20 mL). The
combined organic layers were washed with brine (5 mL),
being then dried (Na2SO4). After filtration and evaporation
of the solvents, the crude residue was purified by column
chromatography (silica gel, hexane/acetone), giving prod-
ucts 4aa–4ad in the yields indicated in Tables 1 and 2. Com-
pounds 4aa and 4ab were characterised by comparison of
their physical and spectroscopic data with the ones reported
in the literature.4 For the rest of the products, 4ac and 4ad,
their corresponding physical and spectroscopic data follow.
4.3.1. P,P-Diphenyl-N-(diphenylmethyl)phosphinic
amide (4ae).24 White solid; Rf 0.47 (ethyl acetate); mp
166 ꢀC; n (KBr) 3170 (NH), 3062, 3049, 3022, 1598
(HC]C), 1194 cmꢁ1 (P¼O); dH 3.61–3.78 (1H, m, NH),
5.44 (1H, t, J¼10.8 Hz, CHN), 7.09–7.58 and 7.67–7.98
(15H and 5H, respectively, 2m, ArH); dC 58.8 (CN), 127.4,
127.6, 127.7, 128.5, 128.6, 128.7, 132.1, 132.2, 132.3,
132.4, 134.4, 143.3 (d, J¼4.4 Hz) (ArC); m/z 383 (M+,
<1%), 307 (21), 306 (100), 201 (55).
4.4. Nickel-catalysed addition of diethylzinc to adducts
5b–5d. Preparation of products 4b–4d. General
procedure21
A representative experimental procedure for the preparation
of 4b follows. p-Toluenesulfinic acid was prepared by dis-
solving sodium p-toluenesulfinate in hot 10% (v/v) hydro-
chloric acid (the resulting pH must be lower than 3). After
cooling to 4 ꢀC, the white crystals that appeared were filtered
and dried under vacuum. 4-Chlorobenzaldehyde (0.32 mL,
2.8 mmol) was added to a suspension of P,P-diphenylphos-
phinic amide (402 mg, 1.9 mmol) and p-toluenesulfinic acid
4.2.1. N-(2-Methyl-1-phenylpropyl)-P,P-diphenylphos-
phinic amide (4ac).11c White solid; Rf 0.38 (ethyl acetate);
mp 166 ꢀC; n (KBr) 3443 (NH), 3088, 3060, 3028, 1503
(HC]C), 1165 cmꢁ1 (P¼O); dH 0.82, 1.01 (3H each, 2d,
J¼6.9 Hz each, 2ꢄMe), 1.90–2.11 (1H, m, CHMe), 3.33
(1H, m, NH), 3.80–3.99 (1H, m, CHN), 7.00–7.11, 7.15–

1172
R. Almansa et al. / Tetrahedron 63 (2007) 1167–1174
(437 mg, 2.8 mmol) in anhydrous Et2O (16 mL) at room
temperature. The mixture was stirred for 15 h, during which
time a white precipitate was slowly formed. The solution
was filtered and the white solid was washed with anhydrous
Et2O (10 mL) and dried under vacuum. The weight of this
solid was 496 mg. Its 1H NMR showed that it was a mixture
of the expected adduct 5b and the corresponding imine 1b,
which was used in the addition reaction with diethylzinc
without purification. Diethylzinc (3.0 mL of a 1.1 M solu-
tion in toluene, 3.3 mmol) was dropwise added during ca.
5 min to a stirred mixture of the white solid obtained before
(496 mg) and Ni(acac)2 (13 mg, 0.05 mmol) in MeCN
(6 mL) under argon at 0 ꢀC. After stirring for 2 h, the reac-
tion was hydrolysed with an aqueous saturated solution of
NH4Cl (5 mL). Water (5 mL) was added and the mixture
was extracted with ethyl acetate (3ꢄ20 mL). The combined
organic layers were washed with brine (5 mL), being then
dried (Na2SO4). After filtration and evaporation of the sol-
vents, the crude residue was purified by column chromato-
graphy (silica gel, hexane/acetone), giving product 4b in
43% overall yield (based on the starting P,P-diphenylphos-
phinic amide). Following a similar procedure but using
0.10 mmol of Ni(acac)2 and stirring the reactions with
diethylzinc for the time indicated in Table 2, products 4c
and 4d were isolated in 50 and 29% overall yields, respec-
tively. Compound 4b was characterised by comparison of
its physical and spectroscopic data with the ones reported
in the literature.4 For the rest of the products, 4c and 4d, their
corresponding physical and spectroscopic data follow.
solution in toluene, 3.3 mmol) was dropwise added during
ca. 5 min to a stirred mixture of the adduct 5e (490 mg,
1.0 mmol) and Ni(acac)2 (13 mg, 0.05 mmol) in MeCN
(6 mL) under argon at 0 ꢀC. After stirring for 1 h, the reac-
tion was hydrolysed with an aqueous saturated solution of
NH4Cl (5 mL). Water (5 mL) was added and the mixture
was extracted with ethyl acetate (3ꢄ20 mL). The combined
organic layers were washed with brine (5 mL), being then
dried (Na2SO4). After filtration and evaporation of the sol-
vents, the crude residue was purified by column chromato-
graphy (silica gel, hexane/acetone), affording product 4e in
80% yield. Compound 4e was characterised by comparison
of its physical and spectroscopic data with the ones reported
in the literature.21
4.6. Nickel-catalysed addition of dialkylzinc reagents to
N-sulfonyl imine 6. Preparation of products 7a–7d.
General procedure
The commercially available solution of the dialkylzinc
reagent in toluene (for dimethyl-, diethyl- and diisopropyl-
zinc) or heptane (for dibutylzinc) (2.2 mmol of R22Zn) was
dropwise added during ca. 5 min to a stirred mixture of
the imine 6 (245 mg, 1.0 mmol) and Ni(acac)2 (13 mg,
0.05 mmol) in the desired solvent (1.5 mL) (see Table 3
for details) under argon at 0 ꢀC. After stirring for 1 h, the
reaction was hydrolysed with an aqueous saturated solution
of NH4Cl (5 mL). Water (5 mL) was added and the mixture
was extracted with ethyl acetate (3ꢄ20 mL). The combined
organic layers were washed with brine (5 mL), being then
dried (Na2SO4). After filtration and evaporation of the
solvents, the crude residue was purified by column chro-
matography (silica gel, hexane/ethyl acetate), giving
products 7a–7d in the yields indicated in Table 3. The cor-
responding physical and spectroscopic data for compound
7a–7d follow.
4.4.1. N-[1-(4-Methoxyphenyl)propyl]-P,P-diphenyl-
phosphinic amide (4c).25 White solid; Rf 0.32 (ethyl ace-
tate); mp 173 ꢀC; n (KBr) 3208 (NH), 3060, 3044, 3039,
1618, 1509 (HC]C), 1105 cmꢁ1 (P¼O); dH 0.77 (3H, t,
J¼7.5 Hz, MeCH2), 1.70–2.10 (2H, m, CH2), 3.18–3.40
(1H, br s, NH), 3.79 (3H, s, MeO), 3.97–4.16 (1H, m,
CHN), 6.81, 7.08 (2H each, 2d, J¼7.6 Hz each, 4ꢄArH),
7.26–7.54 and 7.67–8.00 (6H and 4H, respectively, 2m,
10ꢄArH); dC 10.6 (MeCH2), 32.4 (d, J¼4.4 Hz, CH2),
55.2 (MeO), 56.6 (CN), 113.7, 127.6, 128.1, 128.3, 128.4,
131.6, 131.7, 131.9, 132.4, 132.6, 135.6 (d, J¼5.5 Hz),
158.5 (ArC); m/z 366 (M++1, <1%), 365 (M+, 2), 337 (22),
336 (100), 202 (14), 201 (83), 165 (10), 164 (89), 77 (18).
4.6.1. N-(1-Phenylpropyl)benzenesulfonamide (7a).26
White solid; Rf 0.30 (hexane/ethyl acetate: 4/1); mp 74 ꢀC;
n (KBr) 3246 (NH), 3066, 3028, 3006, 1503 (HC]C),
1159 cmꢁ1 (S]O); dH 0.79 (3H, t, J¼7.5 Hz, Me), 1.58–
1.91 (2H, m, CH2), 4.22 (1H, q, J¼7.4 Hz, CHN), 5.24–
5.50 (1H, m, NH), 6.91–7.05, 7.06–7.17, 7.22–7.47 and
7.59–7.72 (2H, 3H, 3H and 2H, respectively, 4m, ArH); dC
10.4 (Me), 30.6 (CH2), 59.9 (CN), 126.5 (2C), 126.9 (2C),
127.3, 128.3 (2C), 128.6 (2C), 132.1, 140.5, 140.6 (ArC);
m/z 275 (M+, <1%), 247 (16), 246 (100), 141 (25), 77 (35).
4.4.2. N-[1-(2-Naphthyl)propyl]-P,P-diphenylphosphinic
amide (4d).13b White solid; Rf 0.29 (ethyl acetate); mp
105 ꢀC; n (KBr) 3127 (NH), 3040, 3026, 3012, 1598
(HC]C), 1114 cmꢁ1 (P¼O); dH 0.81 (3H, t, J¼7.4 Hz,
Me), 1.88–2.17 (2H, m, CH2), 3.27–3.46 (1H, m, NH),
4.21–4.34 (1H, m, CHN), 7.21–7.30, 7.32–7.57 and 7.65–
7.93 (2H, 8H and 7H, respectively, 3m, ArH); dC 10.6
(Me), 32.3 (d, J¼4.0 Hz, CH2), 57.3 (CN), 124.5, 125.5,
125.7, 126.1, 127.6, 127.8, 128.2, 128.3, 128.4, 128.5,
131.65, 131.7, 131.75, 131.8, 131.9, 132.5, 132.6, 132.7,
133.2, 140.7 (d, J¼5.4 Hz) (ArC); m/z 386 (M++1, 2%),
385 (M+, 6), 357 (25), 356 (100), 202 (16), 201 (89), 185
(13), 184 (83), 154 (13), 77 (17).
4.6.2. N-(1-Phenylethyl)benzenesulfonamide (7b).27
White solid; Rf 0.20 (hexane/ethyl acetate: 4/1); mp
102 ꢀC; n (KBr) 3268 (NH), 3071, 3028, 3006, 1585
(HC]C), 1170 cmꢁ1 (S]O); dH 1.43 (3H, d, J¼7.1 Hz,
Me), 4.38–4.59 (1H, m, CHN), 4.87–5.40 (1H, m, NH),
6.96–7.23, 7.28–7.54 and 7.67–7.80 (5H, 3H and 2H,
respectively, 3m, ArH); dC 23.6 (Me), 53.7 (CN), 126.1
(2C), 127.0 (2C), 127.5, 128.5 (2C), 128.8 (2C), 132.3,
140.6, 141.8 (ArC); m/z 261 (M+, <1%), 246 (56), 141
(40), 120 (41), 105 (21), 104 (11), 78 (12), 77 (100), 51
(27), 42 (16).
4.5. Nickel-catalysed addition of diethylzinc to adduct
5e. Preparation of product 4e
4.6.3. N-(2-Methyl-1-phenylpropyl)benzenesulfonamide
(7c).28 White solid; Rf 0.33 (hexane/ethyl acetate: 4/1); mp
102 ꢀC; n (KBr) 3252 (NH), 3066, 3028, 3017, 1585
Sulfinic acid adduct 5e was prepared in pure form according
to a literature procedure.21 Diethylzinc (3.0 mL of a 1.1 M

R. Almansa et al. / Tetrahedron 63 (2007) 1167–1174
1173
(HC]C), 1159 cmꢁ1 (S]O); dH 0.71, 0.95 (3H each, 2d,
J¼7.1 Hz each, 2ꢄMe), 1.84–1.99 (1H, m, CHMe), 4.03
(1H, t, J¼8.4 Hz, CHN), 5.28 (1H, d, J¼8.4 Hz, NH),
6.84–6.97, 7.01–7.11, 7.19–7.41 and 7.53–7.67 (2H, 3H,
3H and 2H, respectively, 4m, ArH); dC 18.8, 19.4 (2ꢄMe),
34.4 (CHMe), 64.2 (CN), 126.8 (2C), 126.9 (2C), 127.1,
128.1 (2C), 128.5 (2C), 132.0, 139.7, 140.5 (ArC); m/z
289 (M+, <1%), 247 (16), 246 (100), 141 (24), 77 (33).
(d) Vettel, S.; Vaupel, A.; Knochel, P. J. Org. Chem. 1996, 61,
7473–7481; (e) Langer, F.; Schwink, L.; Devasagayaraj, A.;
Chavant, P.-Y.; Knochel, P. J. Org. Chem. 1996, 61, 8229–
8243; (f) Micouin, L.; Knochel, P. Synlett 1997, 327–328.
8. See, for instance: (a) Soai, K.; Hatanaka, T.; Miyazawa, T.
J. Chem. Soc., Chem. Commun. 1992, 1097–1098; (b)
Suzuki, T.; Narisada, N.; Shibata, T.; Soai, K. Tetrahedron:
Asymmetry 1996, 7, 2519–2522; (c) Guijarro, D.; Pinho, P.;
Andersson, P. G. J. Org. Chem. 1998, 63, 2530–2535; (d)
4.6.4. N-(1-Phenylpentyl)benzenesulfonamide (7d).29
White solid; Rf 0.40 (hexane/ethyl acetate: 4/1); mp 70 ꢀC;
n (KBr) 3257 (NH), 3066, 3017, 1585 (HC¼C), 1165 cmꢁ1
(S]O); dH 0.78 (3H, t, J¼7.0 Hz, Me), 0.97–1.32 [4H, m,
(CH2)2Me], 1.55–1.85 (2H, m, CH2CN), 4.28 (1H, q,
J¼7.2 Hz, CHN), 5.58 (1H, d, J¼7.2 Hz, NH), 6.90–7.05,
7.06–7.17, 7.22–7.46 and 7.59–7.71 (2H, 3H, 3H and 2H,
respectively, 4m, ArH); dC 13.8 (Me), 22.1, 27.9, 37.3
(3ꢄCH2), 58.4 (CN), 126.4 (2C), 126.9 (2C), 127.2, 128.3
(2C), 128.6 (2C), 132.0, 140.6, 140.8 (ArC); m/z 303 (M+,
<1%), 247 (16), 246 (100), 141 (24), 77 (35).
ꢁ
Jimeno, C.; Vidal-Ferran, A.; Moyano, A.; Pericas, M. A.;
Riera, A. Tetrahedron Lett. 1999, 40, 777–780; (e) Jimeno,
ꢁ
ꢁ
C.; Reddy, K. S.; Sola, L.; Moyano, A.; Pericas, M. A.;
Riera, A. Org. Lett. 2000, 2, 3157–3159; (f) Pinho, P.;
Andersson, P. G. Tetrahedron 2001, 57, 1615–1618; (g)
Zhang, H.-L.; Zhang, X.-M.; Gong, L.-Z.; Mi, A.-Q.; Cui,
X.; Jiang, Y.-Z.; Choi, M. C. K.; Chan, A. S. C. Org. Lett.
2002, 4, 1399–1402; (h) Beresford, K. J. M. Tetrahedron
Lett. 2002, 43, 7175–7177.
9. Zhang, H.-L.; Jiang, F.; Zhang, X.-M.; Cui, X.; Gong, L.-Z.;
Mi, A.-Q.; Jiang, Y.-Z.; Wu, Y.-D. Chem.—Eur. J. 2004, 10,
1481–1492.
10. (a) Zhang, X.; Lin, W.; Gong, L.; Mi, A.; Cui, X.; Jiang, Y.;
Choi, M. C. K.; Chan, A. S. C. Tetrahedron Lett. 2002, 43,
1535–1537; (b) Zhang, X.-M.; Zhang, H.-L.; Lin, W.-Q.;
Gong, L.-Z.; Mi, A.-Q.; Cui, X.; Jiang, Y.-Z.; Yu, K.-B.
J. Org. Chem. 2003, 68, 4322–4329.
Acknowledgements
ꢀ
This work was generously supported by the Direccion
General de Ensen˜anza Superior (DGES) of the current
ꢀ
Spanish Ministerio de Educacion y Ciencia (MEC; grant
11. (a) Shi, M.; Wang, C.-J. Adv. Synth. Catal. 2003, 345, 971–973;
(b) Boezio, A. A.; Charette, A. B. J. Am. Chem. Soc. 2003, 125,
no. CTQ2004-01261) and the Generalitat Valenciana (grant
no. GRUPOS03/135). R.A. thanks the Spanish Ministerio de
ꢀ
Educacion y Ciencia for a predoctoral fellowship. We also
thank MEDALCHEMY S.L. for a gift of chemicals.
ˆ
1692–1693; (c) Boezio, A. A.; Pytkowicz, J.; Cote, A.;
Charette, A. B. J. Am. Chem. Soc. 2003, 125, 14260–14261;
ꢀ
ˆ ꢀ
(d) Cote, A.; Boezio, A. A.; Charette, A. B. Angew. Chem.,
Int. Ed. 2004, 43, 6525–6528; (e) Wang, M.-C.; Liu, L.-T.;
Hua, Y.-Z.; Zhang, J.-S.; Shi, Y.-Y.; Wang, D.-K.
Tetrahedron: Asymmetry 2005, 16, 2531–2534.
References and notes
12. Porter, J. R.; Traverse, J. F.; Hoveyda, A. H.; Snapper, M. L.
J. Am. Chem. Soc. 2001, 123, 984–985.
13. (a) Hayase, T.; Osanai, S.; Shibata, T.; Soai, K. Heterocycles
1998, 48, 139–144; (b) Beresford, K. J. M. Tetrahedron Lett.
2004, 45, 6041–6044.
14. See, for instance: (a) Fujihara, H.; Nagai, K.; Tomioka, K.
J. Am. Chem. Soc. 2000, 122, 12055–12056; (b) Li, X.; Cun,
L.-F.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z. Tetrahedron:
Asymmetry 2003, 14, 3819–3821; (c) Wang, C.-J.; Shi, M.
J. Org. Chem. 2003, 68, 6229–6237; (d) Soeta, T.; Nagai, K.;
Fujihara, H.; Kuriyama, M.; Tomioka, K. J. Org. Chem. 2003,
68, 9723–9727; (e) Wang, M.-C.; Xu, C.-L.; Zou, Y.-X.;
Liu, H.-M.; Wang, D.-K. Tetrahedron Lett. 2005, 46, 5413–
5416.
1. (a) Volkmann, R. A. Comprehensive Organic Synthesis;
Shreiber, S. L., Ed.; Pergamon: Oxford, 1991; Vol. 1, Chapter
1.12; (b) Kleinman, E. F.; Volkmann, R. A. Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Heathcock,
C. H., Eds.; Pergamon: Oxford, 1991; Vol. 2, Chapter 4.3; (c)
Bloch, R. Chem. Rev. 1998, 98, 1407–1438.
2. For reviews on the asymmetric nucleophilic addition to imines,
see: (a) Enders, D.; Reinhold, U. Tetrahedron: Asymmetry
1997, 8, 1895–1946; (b) Kobayashi, S.; Ishitani, H. Chem.
Rev. 1999, 99, 1069–1094; (c) Charette, A. B.; Boezio, A. A.;
ˆ ꢀ
Cote, A.; Moreau, E.; Pytkowicz, J.; Desrosiers, J.-N.;
Legault, C. Pure Appl. Chem. 2005, 77, 1259–1267; (d)
Vilaivan, T.; Bhanthumnavin, W.; Sritana-Anant, Y. Curr.
Org. Chem. 2005, 9, 1315–1392.
15. Nishimura, T.; Yasuhara, Y.; Hayashi, T. Org. Lett. 2006, 8,
979–981.
3. For a review on the use of N-phosphinoylimines in stereo-
selective synthesis, see: Weinreb, S. M.; Orr, R. K. Synthesis
2005, 1205–1227.
4. See, for instance: Andersson, P. G.; Guijarro, D.; Tanner, D.
J. Org. Chem. 1997, 62, 7364–7375.
5. Weinreb, S. M. Top. Curr. Chem. 1997, 190, 131–184.
6. (a) Knochel, P. Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Shreiber, S. L., Eds.; Pergamon: Oxford,
1991; Vol. 1, Chapter 1.7; (b) Erdik, E. Organozinc Reagents
in Organic Synthesis; CRC: Boca Raton, FL, 1996.
7. (a) Rozema, M. J.; Sidduri, A.; Knochel, P. J. Org. Chem. 1992,
57, 1956–1958; (b) For a review, see: Knochel, P.; Singer,
R. D. Chem. Rev. 1993, 93, 2117–2188; (c) Vettel, S.; Vaupel,
A.; Knochel, P. Tetrahedron Lett. 1995, 36, 1023–1026;
16. Almansa, R.; Guijarro, D.; Yus, M. ARKIVOC 2006, iv, 18–28.
17. The reduction of electronically deficient imines with diethyl-
zinc in the presence of a catalytic amount of Ni(acac)2 has
recently been reported: Xiao, X.; Wang, H.; Huang, Z.; Yang,
J.; Bian, X.; Qin, Y. Org. Lett. 2006, 8, 139–142.
18. Burguete, M. I.; Collado, M.; Escorihuela, J.; Galindo, F.;
Garcia-Verdugo, E.; Luis, S. V.; Vicent, M. J. Tetrahedron
Lett. 2003, 44, 6891–6894.
19. The use of this mixture to effect the catalytic asymmetric phenyl
transfer to aldehydes has been reported: Bolm, C.; Schmidt, F.;
Zani, L. Tetrahedron: Asymmetry 2005, 16, 1367–1376.
20. Jennings, W. B.; Lovely, C. J. Tetrahedron 1991, 47, 5561–
5568.

1174
R. Almansa et al. / Tetrahedron 63 (2007) 1167–1174
ˆ ꢀ
21. Cote, A.; Boezio, A. A.; Charette, A. B. Proc. Natl. Acad. Sci.
U.S.A. 2004, 101, 5405–5410.
24. Zwierzak, A.; Slusarska, E. Synthesis 1979, 691–693.
25. Yang, W.-W.; Cun, L.-F.; Zhi, Y.-G.; Mi, A.-Q.; Jiang, Y.-Z.;
Gong, L.-Z. Lett. Org. Chem. 2005, 2, 605–607.
26. Busch, M.; Leefhelm, L. J. Physiol. (Paris) 1908, 77, 1–19;
Chem. Abstr. 1908, 2, 9973.
27. Xu, L.; Zhang, S.; Trudell, M. L. Synlett 2004, 1901–1904.
28. Stamm, H.; Onistschenko, A.; Buchholz, B.; Mall, T. J. Org.
Chem. 1989, 54, 193–199.
29. Davis, F. A.; Mancinelli, P. A.; Balasubramanian, K.; Nadir,
U. K. J. Am. Chem. Soc. 1979, 101, 1044–1045.
22. The formation of the reduction by-products in the copper-
catalysed addition of diethylzinc to N-tosylimines has also
been reported. See, for instance: Nagai, K.; Fujihara, H.;
Kuriyama, M.; Yamada, K.-I.; Tomioka, K. Chem. Lett. 2002,
8–9.
23. This reduction and the intermediacy of nickel(0) species in the
reduction of imines with diethylzinc catalysed by Ni(acac)2 has
been proposed in the literature. See Ref. 17.