Addition of trialkylalanes to imines under zirconium catalysis

Article abstract of DOI:10.1055/s-2005-870028

Trialkylalanes, which are inert toward imines, undergo addition to them in the presence of a catalytic amount of dichlorodicyclopentadienylzirconium(IV) (Cp₂ZrCl₂). The reaction tolerates the presence of several functional groups in the starting imine such as halo, amide, nitrile, and hydroxy groups. A possible reaction pathway is proposed involving metallacyclic intermediates. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-870028

SPECIAL TOPIC
2075
Addition of Trialkylalanes to Imines under Zirconium Catalysis
A
ddition of Trial
l
n
é
es to Imine
m
s
unde
r
Zirconium
C
e
atalysis nt Denhez, Jean-Luc Vasse, Jan Szymoniak*
Réactions Sélectives et Applications, CNRS and Université de Reims, 51687 Reims Cedex 2, France
Fax +33(3)26913166; E-mail: jan.szymoniak@univ-reims.fr
Received 15 February 2005
Ph
1) 5 mol% Cp2ZrCl2
Et3Al (1.5 equiv)
CH2Cl2, 20 °C, 3 h
Ph
N
Abstract: Trialkylalanes, which are inert toward imines, undergo
addition to them in the presence of a catalytic amount of dichloro-
dicyclopentadienylzirconium(IV) (Cp2ZrCl2). The reaction toler-
ates the presence of several functional groups in the starting imine
such as halo, amide, nitrile, and hydroxy groups. A possible reac-
tion pathway is proposed involving metallacyclic intermediates.
HN
Ph
Ph
2a (91%)
H
2) DCl/D2O
1
Scheme 1
Key words: zirconium, catalysis, trialkylalanes, amine synthesis,
imines
romethane at 20 °C for three hours produced, after hydro-
lysis, amine 2a in 91% isolated yield (Scheme 1).
In contrast to the catalytic ethylalumination of alkenes,7
no deuterium incorporation at the b-carbon atom was ob-
served after deuterolysis with deuterium chloride–deuteri-
um oxide (DCl–D2O), irrespective of the conditions
employed. This result indicates a different mechanism oc-
curring with imines than those postulated with alkenes
(see below).
Recently, we1 and others2 reported that ketimines can un-
dergo zirconium-catalyzed addition with ethylmagnesium
reagents. This reaction has been demonstrated to be simi-
lar to the zirconium-catalyzed ethylmagnesation of
alkenes3 from both a mechanistic and synthetic point of
view. In fact, as in the case of alkenes, zirconacycles have
also been shown to be intermediates in the reaction with
imines.1a The same synthetic limitation has been encoun-
tered in both reactions, i.e. alkylmagnesium halides higher
than EtMgX appeared to be unreactive.4
Various imines underwent the zirconium-catalyzed addi-
tion with Et3Al.10 The results are shown in Table 1.
The reactions proceeded smoothly with aromatic imines
bearing N-aryl or N-alkyl groups (Table 1, entries 1–4).
Interestingly, using a chiral imine, amine 2e was isolated
as a single diastereomer (Table 1, entry 5). To further ex-
plore the reaction, we next used a higher trialkylalane and
noticed that, in contrast to the ethylmagnesation of
imines,1,2 the alkylalumination reaction is not limited to
the use of Et3Al. Thus, treatment of imine 1 with 1.5
equivalents of tributylalane (n-Bu3Al) in the presence 5
mol% Cp2ZrCl2 gave amine 2f (Table 1, entry 6). Similar
to the reaction with Et3Al, no deuterium incorporation
was observed in this reaction after deuterolysis with DCl–
D2O. Compound 2f was accompanied by the reduction
side product, i.e. N-benzylaniline (28%). Contrary to the
zirconium-catalyzed hydroalumination of alkenes,5,7 the
competing reduction of imine 1 by n-Bu3Al proved to oc-
cur without adding Cp2ZrCl2. This side reaction could be
slightly limited by lowering the reaction temperature to 10
°C (Table 1, entries 7 and 8). When using an imine
derived from an aliphatic aldehyde, lower yields of the
alkylation products 2h and 2i were obtained, probably due
to a slower zirconium-mediated alkylalumination reaction
with respect to the direct side reduction reaction (Table 1,
entries 9 and 10).
Zirconium-catalyzed carboalumination of alkynes5,6 and
alkenes5,7 has been shown to smoothly occur through mul-
tiple mechanistic pathways, depending upon the reaction
conditions and substrates. Furthermore, in the absence of
additives, trialkylalanes proved to be inert toward imines.8
Based on these literature data, we focused on the possibil-
ity of performing zirconium-catalyzed addition of
trialkylalanes to imines. We thought that such reactions
could broaden the scope of the alkyl groups added while
offering mild reaction conditions and selectivity. The zir-
conium-catalyzed reactions might then be a prerequisite
for developing a new catalytic asymmetric synthesis of
amines.9
At the outset of our study, we examined the reaction of tri-
ethylalane (Et3Al) with N-phenylbenzaldimine (1). The
reactions were carried out in hexane or chlorinated hydro-
carbon solvents (CH2Cl2, DCE) in the presence of 5–20
mol% of Cp2ZrCl2 at 0–20 °C. In all cases, amine 2a was
obtained after hydrolysis in good to excellent yields. In
contrast, in the absence of the zirconium catalyst, no
alkylation occurred after a long reaction period (24 h). A
particularly clean alkylation reaction took place in the
chlorinated solvents. Thus, treatment of imine 1 with
Et3Al (1.5 equiv) and Cp2ZrCl2 (5 mol%) in dichlo-
The alkylation reactions involving main-group organome-
tallics frequently exhibit poor chemoselectivity. In con-
trast, the described reaction was found to be compatible
with the presence of several groups (Table 2). Thus, halo,
amide, nitrile, and hydroxy groups can be present in the
substrate and tolerated by the reaction conditions
SYNTHESIS 2005, No. 12, pp 2075–2079
x
x.
x
x
.
2
0
0
5
Advanced online publication: 14.07.2005
DOI: 10.1055/s-2005-870028; Art ID: C03905SS
© Georg Thieme Verlag Stuttgart · New York

2076
C. Denhez et al.
SPECIAL TOPIC
Table 2 Chemoselective Zirconium-Catalyzed Alkylation of Aldi-
Table 1 Zirconium-Catalyzed Alkylation of Aldimines by Trialkyl-
mines by Triethylalanea
alanesa
R2
R2
R2
R2
Cp2ZrCl2 cat.
R3Al
Cp2ZrCl2 cat.
Et3Al
HN
R1
HN
N
N
R1
2a–i
R
R1
R1
3a–g
Productb (%)
3a (89)
R1
R2
R
Time (h) Productb
(%)
Entry
R1
R2
Entry
1
2
3
4
5
6
7
2-BrC6H4
Ph
Ph
1
2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Et
Ph
Et
3
3
2a (91)
2b (86)
2c (88)
2d (85)
2e (92)e
2f (67)f
2f (75)f
2g (71)f
2h (32)f,g
2i (24)f,g
2-IC6H4
Ph
3b (88)
3c (88)
PMP
Bn
Et
4-MeCONHC6H4
4-NCC6H4
3-MeO-4-HOC6H3
2-pyridyl
3-pyridyl
3
Et
6
Ph
3d (88)
3e (89)
4
n-Pr
R*
Et
8
Ph
5c,d
6
Et
3
Ph
3f (95)
Ph
n-Bu
n-Bu
n-Bu
Et
12
24
24
24
24
Ph
3g (95)
7
Ph
a The reactions were run using Cp2ZrCl2 (5 mol%) and Et3Al (1.5
equiv, except entries 3 and 5 where 2.5 equiv were used) in CH2Cl2
at 20 °C for 3 hours.
8
PMP
Ph
b Isolated yields.
9
10
Et
Ph
n-Bu
a The reactions were run using Cp2ZrCl2 (5 mol%) and R3Al (1.5
equiv) in CH2Cl2 at 20 °C, except for entries 7 and 8 (10 °C).
b Isolated yields.
CH activation process and formation of metallacyclic in-
termediates (cyclic mechanism).6c
c R* = (R)-2-hydroxy-1-phenylethyl.
Within this context, the lack of reactivity of Me3Al toward
imines together with the efficient catalyzed addition of
higher alanes is mechanistically relevant. It indicates that
a direct acyclic addition mechanism does not operate with
Me3Al and, accordingly, such a mechanism should also be
ruled out with higher alanes. A cyclic mechanism could be
envisaged in the latter case, irrespective of the conditions
and solvent.11 However, if a cyclic mechanism is invari-
ably involved with imines, then no deuterium incorpora-
tion in the product might be questionable. To rationalize
this, we tentatively assumed a cyclic mechanism in which
a second b-CH activation would remove the metal (Zr)
from the carbon (Scheme 2).
d 2.5 equivalents of Et3Al.
e de >95% determined by 1H NMR on the crude product.
f Accompanied by the reduction product: entry 6 (28%), entry 7
(20%), entry 8 (22%), entry 9 (65%), entry 10 (73%).
g NMR yields.
(Table 2, entries 1–5). In addition, amines 3f and 3g were
obtained both in 95% yield starting from 2- and 3-py-
ridylimines (Table 2, entries 6 and 7). The wide chemose-
lectivity of the reaction and the mild reaction conditions
should be synthetically useful.
Surprisingly, the protocol employed for the zirconium-
catalyzed addition of trialkylalanes (R = Et, n-Bu) to
imines appeared inefficient when using trimethylalane
(Me3Al). We found that the reaction of 1 with Me3Al did
not give the expected amine in detectable yields with ei-
ther catalytic or stoichiometric amounts of Cp2ZrCl2. The
use of hexane or chlorinated solvents, an excess of Me3Al
(>2 equiv), and a temperature increase up to 40 °C had no
effect on the reaction. The imine was almost entirely re-
covered in these cases. Other imines from Table 1 also did
not react with Me3Al.
The catalytic process is initiated by the reaction of
Cp2ZrCl2 with two equivalents of Et3Al to afford the bi-
metallic complex A. The formation of A from Cp2ZrCl2
and two equivalents of Et3Al has been reported12 and is
postulated to proceed via a bimetallic b-CH activation
process.6c Subsequent reaction of imine 1 with A gives
azametallacycle B, which would exist as a chlorine-
bridged species. In the next step, Et3Al reacts with B to
produce the zirconium-ethylated complex C. The b-CH
activation from C completes the catalytic cycle by regen-
erating A and by affording the final product in which no
metal atom is attached to the b-carbon of the alkyl group.
Methylalumination of alkynes and alkenes with Me3Al
and Cp2ZrCl2 has been postulated to proceed by direct
C—M bond addition via a four-centered concerted pro-
cess involving bimetallic polarization (acyclic mecha-
nism).7 In sharp contrast, zirconium-catalyzed carbo-
alumination of alkynes with higher alanes involves a b-
In support of the mechanism proposed, we independently
prepared a catalytic quantity (0.1 equiv) of the azazircon-
acyclopentane corresponding to complex B in Scheme 2,1
and subjected it to 0.1 equivalents of diethylaluminum
chloride (Et2AlCl), imine 1 (1 equiv), and Et3Al (1.5
equiv) (Scheme 3).
Synthesis 2005, No. 12, 2075–2079 © Thieme Stuttgart · New York

SPECIAL TOPIC
Addition of Trialkylalanes to Imines under Zirconium Catalysis
2077
satisfactory analysis. Unless otherwise stated, H and 13C NMR
spectra were recorded in CDCl3 on a Brucker AC-250. Mass spectra
were recorded on a Micromass Q-TOF micro MS spectrometer. El-
emental analyses were carried out on a Perkin-Elmer 2400 CHN el-
emental analyzer.
1
Et2Al
Ph
Ph
N
Cp2ZrCl2 + 2 Et3Al
H
ref. 12
Preparation of Tributylalane13
AlEt2
Cp2Zr
Cl
To a refluxing suspension of Al (2.7 g, 100 mmol) and Mg (3.6 g,
150 mmol) in heptane (120 mL) was added n-BuI (55.2 g, 300
mmol) over 45 min. The mixture was stirred for 2 h under reflux.
The reaction was cooled to r.t. and the solid was filtered off under
an argon atmosphere. The solvent was removed by distillation, and
the residue was distilled under vacuum to give n-Bu3Al in 58%
yield.
H
Cp2Zr
Cl
Ph
AlEt2
Cp2Zr
AlEt2
Cl
N
Al
Et2
A
Ph
C
Preparation of Amines 2; General Procedure
1
In an oven-dried Schlenk tube and under an argon atmosphere, the
trialkylalane (1.5 mmol) was added to a solution of imine (1 mmol)
and Cp2ZrCl2 (14.5 mg, 0.05 mmol) in CH2Cl2 (5 mL). The mixture
was stirred at 20 °C for the time specified in Tables 1 and 2 (devia-
tions from the above conditions are listed in the Tables). The reac-
tion was then quenched at 0 °C with 15% aq NaOH and the aqueous
phase was extracted with CH2Cl2 (2 × 10 mL). The organic layers
were combined, dried (MgSO4), filtered, and concentrated under
vacuum. The residue was purified by column chromatography (sil-
ica gel, petroleum ether–Et2O, 20:1) as eluent to give the corre-
sponding amine 2.
Ph
Et3Al
Ph
N
Cp2Zr
AlEt2
Cl
B
Scheme 2
Phenyl(1-phenylpropyl)amine (2a)14
Cp2ZrCl2 (0.1 equiv)
Yellow oil; yield: 91%.
+
1H NMR (250 MHz, CDCl3): d = 0.97 (t, J = 6.8 Hz, 3 H), 1.85 (m,
2 H), 4.07 (br s, 1 H), 4.24 (t, J = 6.8 Hz, 1 H), 6.52 (d, J = 7.7 Hz,
2 H), 6.64 (t, J = 7.4 Hz, 1 H), 7.04–7.11 (m, 2 H), 7.21–7.25 (m, 1
H), 7.30–7.35 (m, 4 H).
13C NMR (62.5 MHz, CDCl3): d = 11.0, 31.8, 59.9, 113.4, 117.3,
126.7, 127.0, 128.7, 129.2, 144.1, 147.7.
EtMgBr (0.2 equiv)
1 (0.1 equiv)
THF, 20 °C, 2 h
ref. 1
Ph
4-Methoxyphenyl(1-phenylpropyl)amine (2b)15
Yellow oil; yield: 86%.
1H NMR (250 MHz, CDCl3): d = 0.94 (t, J = 7.4 Hz, 3 H), 1.80 (m,
2 H), 3.68 (s, 3 H), 3.81 (br s, 1 H), 4.15 (dd, J = 12.1, 6.3 Hz, 1 H),
6.47 (d, J = 8.8 Hz, 2 H), 6.68 (d, J = 8.8 Hz, 2 H), 7.32 (m, 5 H).
Ph
Ph
a
HN
b
HN
A
Ph
Zr
Ph
H
Ph
2–D (ref.1)
D
Cp2
2a (90%)
13C NMR (62.5 MHz, CDCl3): d = 11.0, 31.8, 55.9, 60.7, 114.6,
114.9, 126.7, 127.0, 128.6, 142.0, 144.3, 152.0.
Scheme 3 (a) Et2AlCl (0.1 equiv), 1 (1 equiv), Et3Al (1.5 equiv),
CH2Cl2, 20 °C, 3 h, then DCl–D2O; (b) DCl–D2O
Benzyl(1-phenylpropyl)amine (2c)1a
Yellow oil; yield: 88%.
1H NMR (250 MHz, CDCl3): d = 0.95 (t, J = 7.4 Hz, 3 H), 1.67–1.95
(m, 2 H), 3.63 (dd, J = 7.5, 5.9 Hz, 1 H), 3.64 (d, J = 13.2 Hz, 1 H),
3.77 (d, J = 13.2 Hz, 1 H), 7.28–7.50 (m, 10 H).
13C NMR (62.5 MHz, CDCl3): d = 10.8, 11.7, 23.3, 30.9, 19.7, 65.1,
126.7, 127.3, 128.2, 144.3.
The intermediate thus formed was demonstrated to be cat-
alytically active in these conditions, since 2a was obtained
in 90% yield. Significantly, no deuterium incorporation in
the product was observed in this case. The above results
are in accordance with the mechanistic proposal in
Scheme 2. Nevertheless, further studies are clearly desir-
able to fully elucidate the mechanism of the reaction.
In conclusion, we have described a new method for the (1-Phenylpropyl)propylamine (2d)
Yellow oil; yield: 85%.
IR (film): 3421, 2963, 1582, 1459, 764, 701 cm–1.
1H NMR (250 MHz, CDCl3): d = 0.81 (t, J = 7.7 Hz, 3 H), 0.87 (t,
J = 7.2 Hz, 3 H), 1.39–1.84 (m, 4 H), 2.31–2.50 (m, 2 H), 3.48 (dd,
J = 8.0, 5.7 Hz, 1 H), 7.20–7.40 (m, 5 H).
13C NMR (62.5 MHz, CDCl3): d = 10.7, 31.0, 51.4, 64.1, 126.7,
126.8, 127.4, 128.0, 128.2, 140.6, 143.9.
HRMS-ESI: m/z [M + H]+ calcd for C12H20N: 178.1596; found:
178.1600.
alkylation of imines using trialkylalanes under zirconium
catalysis. Further developments of this new reaction will
be reported in due course.
All reactions were conducted under an atmosphere of argon using
standard Schlenk techniques. Prior to use, tetrahydrofuran and hep-
tane were distilled under argon from sodium benzophenone ketyl,
CH2Cl2 was distilled under argon from CaH2, Cp2ZrCl2 (Strem),
Et3Al, and Grignard reagents (Aldrich) were used as received. All
imines were prepared according to known procedures12 and gave
Synthesis 2005, No. 12, 2075–2079 © Thieme Stuttgart · New York

2078
C. Denhez et al.
SPECIAL TOPIC
Anal. Calcd for C12H19N·HCl: C, 67.73; N, 6.55; H, 9.43. Found: C,
67.57; N, 6.55; H, 9.66.
HRMS-ESI: m/z [M + H]+ calcd for C15H17NI: 338.0406; found:
338.0398.
(2R)-2-(1-Phenylpropylamino)-2-phenylethanol (2e)16
Yellow oil; yield: 92%.
N-{4-[(1-Phenylamino)propyl]phenyl}acetamide (3c)
Red solid; yield: 88%.
[a]D24 –37.5 (c 0.8, CHCl3).
IR (KBr): 3321, 2965, 1661, 1604, 749 cm–1.
1H NMR (250 MHz, CDCl3): d = 0.76 (t, J = 7.4 Hz, 3 H), 1.66 (m,
1 H), 1.86 (m, 1 H), 1.92 (br s, 1 H), 3.51 (dd, J = 10.7, 7.2 Hz, 1
H), 3.54 (dd, J = 8.3, 5.1 Hz, 1 H), 3.74 (dd, J = 10.7, 4.6 Hz, 1 H),
3.82 (dd, J = 7.0, 4.6 Hz, 1 H), 7.17–7.30 (m, 10 H).
13C NMR (62.5 MHz, CDCl3): d = 10.4, 29.4, 61.2, 61.6, 65.5,
127.1, 127.2, 127.4, 128.4, 128.5, 141.3, 143.9.
1H NMR (250 MHz, CDCl3): d = 0.93 (t, J = 7.4 Hz, 3 H), 1.79 (m,
2 H), 2.14 (s, 3 H), 4.18 (t, J = 6.6 Hz, 1 H), 4.24 (br s, 1 H), 6.50
(d, J = 8.1 Hz, 2 H), 6.63 (t, J = 7.3 Hz, 1 H), 7.07 (t, J = 7.8 Hz, 2
H), 7.27 (d, J = 8.2 Hz, 2 H), 7.33 (br s, 1 H), 7.43 (d, J = 8.4 Hz, 2
H).
13C NMR (62.5 MHz, CDCl3): d = 10.7, 24.5, 31.4, 59.4, 113.4,
120.0, 127.0, 129.0, 133.5, 136.5, 139.6, 172.2.
Phenyl(1-phenylpentyl)amine (2f)17a,b
Yellow oil; yield: 75%.
1H NMR (250 MHz, CDCl3): d = 0.89 (t, J = 8.1 Hz, 3 H), 1.26–1.40
(m, 4 H), 1.79 (m, 2 H), 3.82 (br s, 1 H), 4.20 (t, J = 6.5 Hz, 1 H),
6.51 (dd, J = 8.2, 1.0 Hz, 2 H), 6.51 (td, J = 7.3, 1.0 Hz, 1 H), 7.06
(dd, J = 8.2, 7.3 Hz, 2 H), 7.05–7.33 (m, 5 H).
HRMS-ESI: m/z [M + H]+ calcd for C17H21N2O: 269.1654; found:
269.1660.
4-(1-Phenylaminopropyl)benzonitrile (3d)8b
Pale-green oil; yield: 88%.
1H NMR (250 MHz, CDCl3): d = 0.97 (t, J = 7.4 Hz, 3 H), 1.81 (m,
2 H), 4.10 (d, J = 4.5 Hz, 1 H), 4.27 (dd, J = 11.6, 6.4 Hz, 1 H), 6.44
(d, J = 7.8 Hz, 2 H), 6.66 (t, J = 7.3 Hz, 1 H), 7.08 (t, J = 7.9 Hz, 2
H), 7.46 (d, J = 8.2 Hz, 2 H), 7.60 (d, J = 8.2 Hz, 2 H).
13C NMR (62.5 MHz, CDCl3): d = 13.9, 22.6, 28.5, 38.7, 58.2,
113.2, 117.1, 126.4, 126.8, 128.5, 129.1, 144.4, 147.5.
4-Methoxyphenyl(1-phenylpentyl)amine (2g)
Yellow oil; yield: 71%.
IR (film): 3406, 2950, 2853, 1506, 1235 cm–1.
13C NMR (62.5 MHz, CDCl3): d = 10.6, 31.5, 59.4, 113.1, 117.7,
118.9, 127.2, 129.1, 132.4, 132.8, 146.7, 149.8.
2-Methoxy-4-(1-phenylaminopropyl)phenol (3e)
Red oil; yield: 89%.
IR (film): 3505, 3407, 2964, 1603, 750 cm–1.
1H NMR (250 MHz, CDCl3): d = 0.93 (t, J = 7.4 Hz, 3 H), 1.80 (m,
2 H), 3.85 (s, 3 H), 3.95 (m, 1 H), 4.12 (t, J = 6.7 Hz, 1 H), 5.53 (br
s, 1 H), 6.50 (d, J = 7.6 Hz, 2 H), 6.63 (t, J = 7.3 Hz, 1 H), 6.84 (m,
3 H), 7.08 (t, J = 7.3 Hz, 2 H).
13C NMR (62.5 MHz, CDCl3): d = 11.2, 32.1, 56.3, 60.2, 109.1,
113.7, 114.6, 117.5, 119.7, 129.4, 135.1, 144.8, 148.7.
1H NMR (250 MHz, CDCl3): d = 0.88 (t, J = 6.9 Hz, 3 H), 1.24–1.37
(m, 4 H), 1.76 (m, 2 H), 3.68 (s, 3 H), 4.21 (t, J = 6.6 Hz, 1 H), 4.28
(br s, 1 H), 6.46 (d, J = 8.7 Hz, 2 H), 6.67 (d, J = 8.7 Hz, 2 H), 7.15–
7.32 (m, 5 H).
13C NMR (62.5 MHz, CDCl3): d = 14.0, 22.6, 28.5, 38.7, 55.7, 59.0,
114.4, 114.7, 126.4, 126.7, 128.4, 141.8, 144.5, 151.7.
HRMS-ESI: m/z [M + H]+ calcd for C18H24NO: 270.1858; found:
270.1861.
Pentan-3-yl(phenyl)amine (2h)18
Pale yellow oil; yield: 32%.
1H NMR (250 MHz, CDCl3): d = 0.90 (t, J = 6.9 Hz, 6 H), 1.30–1.80
(m, 4 H), 3.05–3.50 (m, 2 H), 6.50–6.80 (m, 3 H), 7.0–7.30 (m, 2 H).
HRMS-ESI: m/z [M + H]+ calcd for C16H20NO2: 258.1494; found:
258.1493.
Phenyl[1-(2-pyridyl)propyl]amine (3f)8b
Pale green oil; yield: 95%.
[1-(2-Bromophenyl)propyl]phenylamine (3a)
Yellow oil; yield: 89%.
IR (film): 3410, 1567, 1495, 759, 693 cm–1.
1H NMR (250 MHz, CDCl3): d = 0.95 (t, J = 7.4 Hz, 3 H), 1.83 (m,
2 H), 4.14 (d, J = 5.1 Hz, 1 H), 4.22 (dd, J = 6.4, 12.5 Hz, 1 H), 6.46
(d, J = 8.5 Hz, 2 H), 6.63 (t, J = 7.3 Hz, 1 H), 7.09 (t, J = 7.9 Hz, 2
H), 7.23 (d, J = 8.2 Hz, 1 H), 7.37 (m, 2 H), 7.55 (d, J = 7.9 Hz, 1 H).
1H NMR (250 MHz, CDCl3): d = 0.95 (t, J = 7.5 Hz, 3 H), 1.85–1.96
(m, 2 H), 4.43 (t, J = 7.5 Hz, 1 H), 4.24 (br s, 1 H), 6.57 (d, J = 8.0
Hz, 2 H), 6.64 (t, J = 2.0 Hz, 1 H), 7.11 (m, 3 H), 7.30 (d, J = 8.0
Hz, 1 H), 7.59 (t, J = 2 Hz, 1 H), 8.58 (d, J = 2 Hz, 1 H).
13C NMR (62.5 MHz, CDCl3): d = 10.6, 25.2, 55.9, 108.6, 112.7,
116.5, 117.2, 124.4, 131.8, 142.7, 144.6, 158.1.
Phenyl[1-(3-pyridyl)propyl]amine (3g)
Pale green oil; yield: 95%.
IR (film): 3251, 3109, 2930, 2875, 1603 cm–1.
13C NMR (62.5 MHz, CDCl3): d = 10.2, 27.2, 68.0, 124.6, 129.4,
129.9, 130.7, 131.2, 132.5, 134.7, 140.3, 145.1.
HRMS-ESI: m/z [M + H]+ calcd for C15H17NBr: 290.0544; found:
290.0546.
1H NMR (250 MHz, CDCl3): d = 0.97 (t, J = 7.4 Hz, 3 H), 1.83 (m,
2 H), 4.09 (d, J = 4.6 Hz, 1 H), 4.28 (dd, J = 6.5, 12.1 Hz, 1 H), 6.49
(d, J = 8.3 Hz, 2 H), 6.65 (t, J = 7.3 Hz, 1 H), 7.09 (t, J = 7.9 Hz, 2
H), 7.23 (dd, J = 5.2, 8.2 Hz, 1 H), 7.65 (d, J = 7.9 Hz, 1 H), 8.48
(dd, J = 4.7, 1.4 Hz, 1 H), 8.61 (d, J = 2.0 Hz, 1 H).
13C NMR (62.5 MHz, CDCl3): d = 10.6, 31.52, 57.4, 113.2, 117.5,
123.5, 129.1, 133.8, 139.1, 146.8, 148.4, 148.7.
2-Iodophenyl(1-phenylpropyl)amine (3b)
Pale-yellow oil; yield: 88%.
IR (film): 3397, 2961, 1589, 1505, 742 cm–1.
1H NMR (250 MHz, CDCl3): d = 1.00 (t, J = 7.3 Hz, 3 H), 1.85 (m,
2 H), 4.26 (q, J = 6.0 Hz, 1 H), 4.64 (br, 1 H), 6.29 (d, J = 8.2 Hz, 1
H), 6.37 (t, J = 7.6 Hz, 1 H), 7.00 (t, J = 7.9 Hz, 1 H), 7.30 (m, 5 H),
7.64 (d, J = 6.3 Hz, 1 H).
HRMS-ESI: m/z [M + H]+ calcd for C14H17N2: 213.1392; found:
213.1395.
13C NMR (62.5 MHz, CDCl3): d = 10.8, 31.85, 60.0, 81.1, 111.7,
118.4, 124.8, 126.2, 126.9, 128.5, 129.1, 138.7, 143.2, 147.3.
Synthesis 2005, No. 12, 2075–2079 © Thieme Stuttgart · New York

SPECIAL TOPIC
Acknowledgment
Addition of Trialkylalanes to Imines under Zirconium Catalysis
2079
(7) (a) Kondakov, D. Y.; Negishi, E. J. Am. Chem. Soc. 1995,
117, 10771. (b) Kondakov, D. Y.; Negishi, E. J. Am. Chem.
Soc. 1996, 118, 1577. (c) Negishi E.; Chem.–Eur. J.; 1999,
5: 411.
We thank the CNRS and the Ministère de l’Education Nationale for
their financial support.
(8) (a) Alberola, A.; Cermeño, F. A.; Anton, A. An. Quim. 1977,
73, 886. Lanthanide-catalyzed addition of Et3Al to aromatic
Schiff bases has recently been reported, see:
(b) Tsvelikhovsky, D.; Gelman, D.; Molander, G. A.; Blum,
J. Org. Lett. 2004, 6, 1995.
(9) These reactions mainly involve the addition of
organolithium and organozinc reagents to imines under
Lewis base, acid, or transition-metal catalysis, for reviews,
see: (a) Denmark, S. E.; Nicaise, O. J.-C. In Comprehensive
Asymmetric Catalysis; Jacobsen, E. N.; Pfaltz, A.;
Yamamoto, H., Eds.; Springer: Berlin, 1999, 923.
(b) Kobayashi, S.; Ishitani, H. Chem. Rev. 1999, 99, 1069.
(10) Ketimines proved to be inert toward Et3Al in these
conditions.
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Synthesis 2005, No. 12, 2075–2079 © Thieme Stuttgart · New York