Multicomponent C-alkylation reactions of aromatic aldimines with trialkylboranes reagents

Article abstract of DOI:10.1002/ejoc.200901359

The one-pot three-component reaction of an aryl aldehyde, an arylamine, and a trialkylborane in the presence of hydrogen peroxide afforded the alkylated arylamines 1 in good yields via oxidized imine-borane complexes. In addition, the versatility of our procedure has been confirmed by the use of enolizable aldehydes, alkylic amines, and cyclic imines.

Full text of DOI:10.1002/ejoc.200901359

FULL PAPER
DOI: 10.1002/ejoc.200901359
Multicomponent C-Alkylation Reactions of Aromatic Aldimines with
Trialkylboranes Reagents
María Valpuesta,*[a] Carmen Muñoz,[a] Amelia Díaz,*[a] Gregorio Torres,[a] and
Rafael Suau[a]
Dedicated to Professor Luis Castedo
Keywords: Boranes / Alkylation / Amines / Multicomponent reactions / Aldehydes
The one-pot three-component reaction of an aryl aldehyde,
an arylamine, and a trialkylborane in the presence of hydro-
gen peroxide afforded the alkylated arylamines 1 in good
yields via oxidized imine–borane complexes. In addition, the
versatility of our procedure has been confirmed by the use of
enolizable aldehydes, alkylic amines, and cyclic imines.
overcome by using stoichiometric amounts of tributyltin
hydride[4] as a source of tin radicals which are able to ab-
stract the halogen atom efficiently from the alkyl halide. A
novel dimethylzinc/air radical initiation system able to act
as an efficient source of unstable methyl radicals has re-
cently been developed.[5] Two further drawbacks of the radi-
cal addition reaction are the low reactivity and yields at-
tainable with nonactivated imines in comparison with
those reported for other derivatives such as oxime
ethers,[3a,3b,3e,3g] hydrazones,[3b,3d–3f] or tosylimines.[3c,3g,5]
We recently described a new one-pot alkylative amin-
ation reaction involving three components, which are benz-
aldehyde, an aniline, and a dialkylchloroborane as alkylat-
ing agent (Scheme 1). In this reaction, the chloroborane
reagent acts both as a Lewis acid catalyst in the formation
of the imine and as a chain donor to the C=N bond.[6]
Introduction
Alkylic 1,2-addition to the carbon–nitrogen double bond
is a useful tool for preparing a variety of alkylated amines.
However, the low electrophilicity displayed by the imino
group and the formation of reductive coupling products are
severe disadvantages of these addition reactions.[1] In these
reactions, organometallic reagents are typically used to gen-
erate the carbon–carbon bond, but the reactions of organo-
metallics with imines are often accompanied by the enoli-
zation of substrates bearing acidic α protons. Recently, free-
radical reactions have also emerged as a valuable tool for
C=N alkylation. The 1,2-addition to the C=N bond using
radicals as alkylating agents has been studied as both intra-
and intermolecular processes.[2] The limited data available
in the literature on the intermolecular addition reaction
highlights the low reactivity of the C=N bond. Neverthe-
less, the low reactivity of imines can be overcome either by
attaching activating substituents to the nitrogen atom or by
using a Lewis acid as an external activator.
The intermolecular radical alkylation of activated imine
derivatives can be performed by usingthe Et3B/air/RI alkyl-
ating system;[3] the ethyl radical generated from triethylbo-
rane abstracts iodine from the alkyl iodide to produce a
new carbon-centered alkyl radical. However, the scope of
this method is limited to the generation of radicals that are
more stable than the ethyl radical, that is, secondary, terti-
ary, and stabilized alkyl radicals. Such a limitation is usually
Scheme 1. General one-pot alkylation reaction with R2BCl.
As a continuation of this previous investigation, we fo-
cused in this work on the use of trialkylboranes as chain
donors for the nonactivated imine group with the aim of
developing a general one-pot procedure for the alkylative
amination reaction. To the best of our knowledge a similar
one-pot reaction has previously been described only for ac-
tivated oxime ethers in the presence of a strong Lewis acid
catalyst using Et3B or Et3B/RI as the alkylating agent.[7] It
is noteworthy that our methodology is the first example of
a one-pot alkylative amination process for nonactivated im-
ines using a wide variety of trialkylboranes as alkylating
agents. Such a broad choice of trialkylboranes, which allows
[a] Departamento de Química Orgánica, Facultad de Ciencias,
Universidad de Málaga,
Campus de Teatinos s/n, 29071 Málaga, Spain
Fax: +34-952-13-19-41
E-mail: mvalpuesta@uma.es
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200901359.
1934
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Eur. J. Org. Chem. 2010, 1934–1942

Multicomponent C-Alkylation Reactions of Aromatic Aldimines
the addition of different alkyl groups (either primary or sec- increased (entries 3, 6, and 9). This methodology is very
ondary) to the C=N bond in good yield, is perhaps the useful because the use of H2O2 allows us to adjust the
foremost advantage of this reaction.
amount of co-reagent employed to enable the reaction to
proceed more cleanly.
The second observation was that the overall yield was
much higher when 3 equiv. of Et3B and 1 equiv. of H2O2
were used (Table 1, entry 9). Under such conditions the re-
action showed good regioselectivity and only the imine-eth-
ylated product 1a was obtained. In contrast, a mixture of
1a and polyalkylated amines was obtained when oxygen was
used instead of H2O2 (Table 1, entry 8).
A double role, as Lewis acid catalyst for the formation
of the imine and as chain donor to the carbon–nitrogen
double bond, is assumed to be played by Et3B in this reac-
tion. Furthermore the imine activation is thought to pro-
ceed via the formation of an imino–borane complex.
Reported examples are limited to the addition of Et3B to
the activated C=N bond. However, our procedure offers an
alternative method for introducing a primary or secondary
alkyl group. To evaluate the influence of the alkyl group
of R3B on the efficiency of the reaction, p-anisaldehyde, p-
methoxyaniline, and different primary and secondary alkyl-
ating agents were assayed. The results obtained from the
reactions with different R3B (R = nBu, sBu, n-Hex, and
Chx; Chx = cyclohexyl) are summarized in Table 2.
Results and Discussion
We herein report our preliminary results for the one-pot
reaction between R3B, p-methoxyaniline, and aromatic al-
dehydes with different substitution patterns (Scheme 2). To
establish the basics for this reaction, a study was initially
carried out using p-anisaldehyde, p-methoxyaniline, and a
1  solution of commercially available triethylborane (Et3B)
in hexane as the starting compounds. In general, the reac-
tions were performed in dichloromethane at 25 °C using
equimolar amounts of amine and aldehyde. We studied the
reactions under various experimental conditions (Table 1),
including varying the amount of added Et3B (1–3 mmol)
and the influence of co-reagents. The first observation was
that no reaction occurs in the absence of co-reagents. Even
an excess of Et3B had no perceivable beneficial effect; the
imine–borane complex was the only observed reaction
product in this case.
Table 2. Synthesis of the amines 1a–e by the three-component reac-
tions with different R3B.[a]
Scheme 2. General alkylation reaction.
Table 1. Synthesis of amine 1a by the three-component reaction.[a]
Entry
R
Time [h]
Amine
Yield [%][b]
1
2
3
4
5
Et
nBu
n-Hex
Chx
sBu
96
85
85
72
72
1a
1b
1c
1d
1e
95 (90)
85 (80)
85 (79)
95 (89)
95 (91)
Entry
Et3B [equiv.]
co-reagent
Yield [%][b]
1
2
3
4
5
6
7
8
9
1
1
1
2
2
2
3
3
3
–
Ͻ5
10
15
Ͻ5
25
35
Ͻ5
O2
H2O2
[a] Reactions carried out with equimolar amounts of aldehyde and
amine, 3 equiv. of R3B, and 1 equiv. of H2O2. [b] Yields of com-
pounds 1a–e were determined by 1H NMR spectroscopy with an
estimated detection limit of 5%. The yields obtained after purifica-
tion by silica gel chromatography are given in parentheses.
[c]
–
O2
H2O2
[c]
–
O2
H2O2
polyalkylated[d]
90–95
[c]
The desired alkylated amines were obtained in good
yields (Table 2, entries 1–5) even when primary trialkylbor-
[a] Reactions carried out with equimolar amounts of aldehyde and
1
amine for 96 h. [b] Yields of compound 1a were determined by H anes were used (Table 2, entries 1–3). With secondary tri-
NMR spectroscopy with an estimated detection limit of 5% (yields
alkylboranes, a shorter reaction time was required for com-
quoted as Ͻ5% for no detection). [c] 1 Equiv. of H2O2. [d] A mix-
pletion than with primary trialkylboranes (Table 2, entries 4
ture of polyalkylated products plus compound 1a was observed.
and 5). These results show that the limitations of the alk-
A more detailed assessment of the influence of co-rea- ylation associated with the generation of primary alkyl radi-
gents on the alkylation reaction was attained by evaluating cals by the standard tin-free method (triethylborane/iodo-
separately the effects of H2O2 and O2 on the reaction yield alkane)[5] may be circumvented by using this methodology.
(Table 1). It was found that although the alkyl(aryl)amine An additional advantage of the method is that a wide vari-
1a was produced in the presence of both co-reagents, only ety of trialkylboranes can be prepared in situ by the hydro-
H2O2 afforded good yields when the quantity of Et3B was boration of alkenes. In fact, both Hex3B and Chx3B were
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1935

M. Valpuesta, C. Muñoz, A. Díaz, G. Torres, R. Suau
FULL PAPER
prepared and directly used, yielding the corresponding agent. A representative selection of the aldehydes listed in
amines without any detrimental effect (Table 2, entries 3 Table 3 was chosen to study the reaction of p-methoxyan-
and 4).
iline with either nBu3B or sBu3B (Table 4) using the same
To delineate the scope of the present method, a number reaction conditions as established above. As can be seen in
of aryl aldehydes were studied in the reaction of p-meth- Table 4, the two trialkylboranes reacted efficiently to afford
oxyaniline and Et3B, including a set of substituted benzal- good yields of the alkylated amine; sBu3B (entries 2, 4, 6,
dehydes and some representative heterocyclic aldehydes and 8) reacted faster than the primary nBu3B. With regard
(Table 3). In all cases, the alkylated amines 1a,f–q were ob- to the influence of the aldehyde substitution pattern, the
tained in good or very good yields. As expected, the reactiv- results obtained were similar to those observed with Et3B;
ity of the benzaldehydes was found to be significantly influ- reactions involving aryl aldehyde derivatives with electron-
enced by the electronic effect of the substituent. Electron- withdrawing substituents needed longer periods of time to
withdrawing groups led to a significant decrease in the reac- be completed (Table 4, entries 5–8). Also, here o-methoxy-
tion rate and required higher quantities of Et3B for comple- benzaldehyde showed the highest reactivity (Table 4, en-
tion (Table 3, entries 6–10), whereas exactly the opposite ef- tries 1 and 2) with both nBu3B and sBu3B, which is in full
fects were exerted by electron-releasing groups (Table 3, en- agreement with the results described above for Et3B.
tries 2–5). Moreover, the highest alkylating rates were ob-
served for benzaldehydes bearing a methoxy substituent at
Table 4. Synthesis of the amines 1r–y by the three-component reac-
the ortho position (Table 3, entries 4 and 5). The favorable
effect of the o-methoxy group may be associated with the
occurrence of a coordinating state involving the oxygen and
boron atoms; such an interaction would provide higher sta-
bility to the amine–borane complex and faster release of
the ethyl radicals. The reaction was also perfectly applicable
to heterocyclic aromatic aldehydes (Table 3, entries 11–13),
rendering good yields in the desired ethylated amines. The
particularly high reactivities observed with 2-furfural and
2-pyridinecarbaldehyde may be related to the presence of
the heteroatom at the vicinal position with respect to the
amine group, which would allow a coordination interaction
similar to that in o-methoxybenzaldehyde.
tion.
Entry Ar
R
Time [h] Amine
Yield [%][a]
1
2
3
4
5
6
7
8
2-MeOC6H4
nBu
sBu
nBu
sBu
nBu
sBu
nBu
sBu
Ͻ48
28
85
72
120
96
1r
1s
82
91
80
90
70
82
72
83
3-MeOC6H4
4-FC6H4
1t
1u
1v
1w
1x
1y
4-ClC6H4
120
96
Table 3. Synthesis of the amines 1a,f–q by the three-component re-
action.
[a] Isolated yields after silica gel chromatography.
The versatility of this alkylation method was evidenced
by its application to enolizable aldehydes, alkylic amines,
and cyclic imines. Thus, the amines shown in Figure 1 were
synthesized by using the standard procedure with slight
modifications.
Entry Ar
Et3B [equiv.] Time [h] Amine Yield [%][a]
1
2
3
4
5
6
7
8
C6H5
3
3
3
3
3
4
4
4
4
4
3
3
3
126
96
96
48
48
168
168
126
126
126
48
1f
1a
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
70
90
91
93
90
82
81
89
80
82
79
76
70
4-MeOC6H4
3-MeOC6H4
2-MeOC6H4
2,3-(MeO)2C6H3
4-FC6H4
4-ClC6H4
4-MeC6H4
4-NCC6H4
4-NO2C6H4
2-furyl
4-pyridyl
2-pyridyl
9
10
11
12
13
75
72
[a] Yields after purification by silica gel chromatography.
Figure 1. Synthesis of the amines 2–6 by the three-component reac-
tion.
Encouraged by the above results, we turned our attention
The one-pot reaction between p-methoxyaniline, Et3B,
to the combined effect of the aldehyde substitution pattern and the enolizable aldehyde, 2-methylpropanal, afforded the
and the nature of the trialkylborane used as the alkylating expected amine 2 in 35% yield. Further experimentation
1936
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Eur. J. Org. Chem. 2010, 1934–1942

Multicomponent C-Alkylation Reactions of Aromatic Aldimines
revealed that the yield of the amine could be significantly
increased if the alkylation addition was performed with the
previously formed imine. In this way amine 2 was obtained
in 70% yield after 48 h. The extension of this reaction to
other enolizable aldehydes is under investigation.
To test the effect of a heteroatom at the position vicinal
to the amine group in the reaction with enolizable alde-
hydes, we next investigated the one-pot reaction with tetra-
hydro-2-furancarbaldehyde, p-methoxyaniline, and Et3B.
Although reaction times of 2–6 days were used in most of
these experiments, conversion was almost complete after
20 min with an 80% yield of the amine 3. Note that 1,2-
stereoinduction was detected at room temperature with the
formation of an 87:13 mixture of the ethylated amine 3. The
presence of the chelate-forming Lewis acid may explain the
higher reactivity observed in the 1,2-stereoinduction.
Subsequently we examined the reactivity of aliphatic
amines with p-methoxybenzaldehyde and Et3B. The one-
pot reaction using MeNH2 and BuNH2 failed to give the
expected products 4 and 5; the imine–borane complex was
obtained instead. The low reactivity of these aliphatic im-
ines was overcome by Lewis acid activation. Two equiva-
lents of BF3·OEt2 were required for a successful one-pot
addition to give the desired alkylated amines 4 and 5 (38
and 40% yields, respectively). On the other hand, when we
carried out the alkylation addition with the preformed
imine in the presence of 2 equiv. of BF3·OEt2, the yield was
increased significantly so that amines 4 and 5 were obtained
in 80 and 83% yields, respectively.
Scheme 3. Proposed mechanism for the alkylative amination reac-
tion.
Conclusions
A one-pot alkylative amination reaction of aryl aldehyde
derivatives that involves three components with trialkylbor-
ane as the alkylating agent has been developed. The reac-
tion can be applied to differently substituted aldehydes as
well as to hetaryl aldehydes, as well as being used to attach
primary and secondary alkyl chains depending on the radi-
cal stability. The broad applicability of the procedure was
ascertained by extending this reaction to enolizable alde-
hydes and aliphatic amines. Additional studies to ascertain
the detailed mechanism of the reaction and to extend its
synthetic potential to different types of nonactivated imines
are underway in our laboratory.
We next chose the 3,4-dihydro-6,7-dimethoxyisoquinol-
ine as a model substrate to investigate the influence of reac-
tion conditions on the ethyl addition to endocyclic imines.
Again activation with 2 equiv. of BF3·OEt2 was found to be
Experimental Section
General: EI-MS spectra were recorded with an HP-MS 5988A spec-
essential in the reaction with Et3B. Under these conditions trometer operating at 70 eV and HRMS spectra with a VG Au-
tospec spectrometer. Infrared spectra were obtained with an ATR
accessory (MIRacle ATR, PIKE Technologies, USA) coupled to a
FTIR Jasco FT/IR–4100 spectrometer. All spectra were recorded
in the range 4000–600 cm–1 with a resolution of 4 cm–1. NMR spec-
tra were registered with a Bruker AC 200 instrument at 200 MHz
the ethylated amine 6 was obtained in 60% yield.
Our studies on the mechanism of this reaction initially
focused on the standard one-pot reaction between p-meth-
oxyaniline, p-anisaldehyde, and Et3B (3 equiv.). First obser-
vations showed that under a stream of oxygen the reaction
was not reliable and polyalkylated compounds were the
main products. A second feature to note is that the addition
of radical scavengers such as cumene or AIBN inhibited in
part the alkylation reaction. Moreover, when the reaction
1
for H and 50.3 MHz for 13C or a Bruker ARX 400 instrument at
400 MHz for 1H and 100.6 MHz for 13C. Chemical shifts are given
relative to residual CHCl3 (δH = 7.24 ppm) and CDCl3 (δC
=
77.0 ppm). All solvents were dried and distilled prior to use. Reac-
tions were monitored by TLC using silica gel 60 F254 (Merck); ali-
was performed with BF3·Et2O as the catalyst for imine for- quots were removed after 2, 4, 8, 24 h, and 2 d and so forth. Prod-
ucts were purified by column chromatography using 0.040–
0.063 mm silica gel (Merck 9385). All experiments were performed
under an inert atmosphere (Ar) in oven-dried glassware sealed with
a rubber septum and with anhydrous solvents. Triethyl-, tributyl-,
and tri-sec-butylborane were purchased from Aldrich Chemical
Co., whereas trihexyl- and tricyclohexylborane were synthesized as
previously from borane in THF and the corresponding alkene.[9]
Tetrahydrofuran-2-carbaldehyde was obtained from tetra-
hydrofuran-2-methanol according to the previously described pro-
cedure.[10]
mation, the amount of trialkylborane required could be re-
duced to 2 equiv. All these results suggest the mechanism
for the one-pot procedure that is illustrated in Scheme 3.
Accordingly, Et3B must act not only as an alkylating agent,
but also as a Lewis acid catalyst for imine formation and
activation. Thus, the first equivalent of Et3B would be used
for the formation of the imine. The imine formed would
be activated by the second equivalent of Et3B through the
formation of an imine–borane complex, and the third
equivalent of Et3B would act as the radical initiator. In
agreement with previously reported studies,[8] a free-radical
chain mechanism is proposed in which the generated alkyl
radical playing the role of chain carrier is regenerated in the
propagation step.
General Procedure for the One-Pot Reaction of Aldehyde, Amine,
and Trialkylborane: Trialkylborane (3 mmol) was added to a solu-
tion of aldehyde (1 mmol) and amine (1 mmol) in dichloromethane
and the reaction mixture was left to stir for 2 h at room tempera-
ture. An aqueous solution of hydrogen peroxide (0.1 mL, 33%) was
Eur. J. Org. Chem. 2010, 1934–1942
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1937

M. Valpuesta, C. Muñoz, A. Díaz, G. Torres, R. Suau
FULL PAPER
then added and the mixture stirred for 2–7 d. The crude reaction
was concentrated to dryness under reduced vacuum. The 1H NMR
spectrum of the residue exhibited signals corresponding to the al-
most exclusive presence of the expected amines. The residue was
purified by column chromatography (SiO2, 10% ethyl acetate in
hexane) to yield the alkylated amines 1a–1y, 2, and 3 in 70–93%
yields.
(t, J = 6.5 Hz, 3 H, CH2-CH3), 0.87 (d, J = 6.5 Hz, 3 H, CH-
CH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 158.2 (C-4Ј), 151.6
(C-4ЈЈ), 142.1 (C-1ЈЈ), 135.1 (C-1Ј), 127.9 (C-2Ј, C-6Ј), 114.6, 114.2,
113.5 (6ϫCHAr), 61.8 (C-1), 56.6, 55.1 (2ϫOCH3), 41.9 (CH),
26.6 (CH2), 14.5, 12.0 (2ϫCH3) ppm. MS (EI): m/z (%) = 299 (8)
[M]+, 243 (16), 242 (100), 177 (5), 121 (19). HRMS: calcd. for
C19H25NO2 299.1885; found 299.1891.
N-(4-Methoxyphenyl)-N-[1-(4-methoxyphenyl)propyl]amine (1a):[11]
Yield 244 mg, 90%, colorless oil. Rf = 0.66 (silica gel, 30% ethyl
Isomer b: Yield 137 mg, 46%, colorless oil. Rf = 0.68 (silica gel,
30% ethyl acetate in hexane). IR (neat): ν
= 3408, 3018, 2967,
˜
max
2920, 1611, 1509, 1458, 1240 cm–1. 1H NMR (200 MHz, CDCl3):
δ = 7.19 (d, J = 8.9 Hz, 2 H, 2Ј-H, 6Ј-H), 6.78 (d, J = 8.5 Hz, 2 H,
3Ј-H, 5Ј-H), 6.61–6.59 (m, 4 H, CHAr), 4.10 (d, J = 5.7 Hz, 1 H,
1-H), 3.74 (s, 3 H, OCH3), 3.65 (s, 3 H, OCH3), 1.99–1.81 (m, 1
H, CH), 1.62–1.42 (m, 1 H, CH2), 1.20–1.03 (m, 1 H, CH2), 0.89
(t, J = 6.5 Hz, 3 H, CH2-CH3), 0.87 (d, J = 6.5 Hz, 3 H, CH-
CH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 158.1 (C-4Ј), 151.7
(C-4ЈЈ), 141.6 (C-1ЈЈ), 134.0 (C-1Ј), 128.2 (C-2Ј, C-6Ј), 114.5, 114.4,
113.3 (6ϫCHAr), 62.9 (C-1), 55.5, 54.9 (2ϫOCH3), 41.2 (CH),
25.4 (CH2), 15.7, 11.6 (2ϫCH3) ppm. MS (EI): m/z (%) = 299 (8)
[M]+, 243 (16), 242 (100), 177 (5), 121 (19). HRMS: calcd. for
C19H25NO2 299.1885; found 299.1895.
acetate in hexane). IR (neat): ν
= 3400, 3036, 2959, 2932, 1609,
˜
max
1508, 1460, 1440, 1378, 1299, 1231 cm–1. 1H NMR (200 MHz,
CDCl3): δ = 7.21 (d, J = 7.5 Hz, 2 H, 2Ј-H, 6Ј-H), 6.82 (d, J =
7.5 Hz, 2 H, 3Ј-H, 5Ј-H), 6.66 (d, J = 8.8 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H),
6.45 (d, J = 8.8 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.08 (t, J = 6.8 Hz, 1 H, 1-
H), 3.76 (s, 3 H, OCH3), 3.67 (s, 3 H, OCH3), 1.85–1.68 (m, 2 H,
CH2), 0.92 (t, J = 7.0 Hz, 3 H, CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 158.2 (C-4Ј), 152.0 (C-4ЈЈ), 141.9 (C-1ЈЈ), 135.2 (C-1Ј),
127.4 (C-2Ј, C-6Ј), 114.5, 114.3, 113.5 (6ϫCHAr), 60.3 (C-1), 55.4,
54.8 (2ϫOCH3), 30.9 (CH2), 10.4 (CH3) ppm. MS (EI): m/z (%) =
271 (12) [M]+, 242 (34), 149 (92), 121 (100), 91 (38), 77 (39).
HRMS: calcd. for C17H21NO2 271.1572; found 271.1566.
N-(4-Methoxyphenyl)-N-[1-(4-methoxyphenyl)pentyl]amine
Yield 239 mg, 80%, colorless oil. Rf = 0.73 (silica gel, 30% ethyl
acetate in hexane). IR (neat): ν = 3401, 3010, 2954, 2930, 1604,
(1b):
N-(4-Methoxyphenyl)-N-[1-phenylpropyl]amine
169 mg, 70%, colorless oil. Rf = 0.75 (silica gel, 30% ethyl acetate
in hexane). IR (neat): ν = 3400, 3059, 3025, 2961, 2930, 1601,
(1f):[11]
Yield
˜
max
˜
max
1508, 1462, 1440, 1378, 1238 cm–1. 1H NMR (200 MHz, CDCl3):
δ = 7.30 (d, J = 8.8 Hz, 2 H, 2Ј-H, 6Ј-H), 6.90 (d, J = 8.8 Hz, 2 H,
3Ј-H, 5Ј-H), 6.74 (d, J = 9.1 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 6.52 (d, J =
9.1 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.22 (t, J = 6.7 Hz, 1 H, 1-H), 3.83 (s,
3 H, OCH3), 3.74 (s, 3 H, OCH3), 1.86–1.70 (m, 2 H, CH2), 1.46–
1.29 (m, 4 H, 2ϫCH2), 0.92 (t, J = 7.0 Hz, 3 H, CH3) ppm. 13C
NMR (50 MHz, CDCl3): δ = 158.3 (C-4Ј), 151.6 (C-4ЈЈ), 141.8 (C-
1ЈЈ), 136.5 (C-1Ј), 127.3 (C-2Ј, C-6Ј), 114.6, 114.4, 113.7
(6ϫCHAr), 58.4 (C-1), 55.6, 55.1 (2ϫOCH3), 38.7, 28.4, 22.6
(3ϫCH2), 13.9 (CH3) ppm. MS (EI): m/z (%) = 300 (6), 299 (30)
[M]+, 243 (17), 242 (100), 177 (26), 121 (83). HRMS: calcd. for
C19H25NO2 299.1885; found 299.1876.
1582, 1509, 1451, 1379, 1294 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 7.35–7.15 (m, 5 H, CHAr), 6.67 (d, J = 8.6 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-
H), 6.43 (d, J = 8.6 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.14 (t, J = 6.9 Hz, 1
H, 1-H), 3.62 (s, 3 H, OCH3), 1.89–1.72 (m, 2 H, CH2), 0.93 (t, J
= 6.9 Hz, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 151.8
(C-4ЈЈ), 143.9, 141.6 (C-1Ј, C-1ЈЈ), 128.4, 126.8, 126.5, 114.7, 114.5
(9ϫCHAr), 60.6 (C-1), 55.7 (OCH3), 31.6 (CH2), 10.7 (CH3) ppm.
MS (EI): m/z (%) = 242 (3), 241 (20) [M]+, 213 (15), 212 (100).
HRMS: calcd. for C14H17NO2 241.1467; found 241.1461.
N-(4-Methoxyphenyl)-N-[1-(3-methoxyphenyl)propyl]amine
(1g):
Yield 247 mg, 91%, colorless oil. Rf = 0.68 (silica gel, 30% ethyl
acetate in hexane). IR (neat): ν˜max = 3397, 3020, 2959, 2933, 1598,
1509, 1454, 1379, 1294 cm–1. 1H NMR (400 MHz, CDCl3): δ =
7.22 (t, J = 8.1 Hz, 1 H, 5Ј-H), 6.92 (d, J = 8.1 Hz, 1 H, 6Ј-H),
6.88 (d, J = 2.5 Hz, 1 H, 2Ј-H), 6.75 (dd, J = 8.1, J = 2.5 Hz, 1 H,
4Ј-H), 6.67 (d, J = 8.6 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 6.47 (d, J = 8.6 Hz,
2 H, 2ЈЈ-H, 6ЈЈ-H), 4.11 (t, J = 6.5 Hz, 1 H, 1-H), 3.77 (s, 3 H,
OCH3), 3.68 (s, 3 H, OCH3), 1.85–1.73 (m, 2 H, CH2), 0.94 (t, J =
7.2 Hz, 3 H, CH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 159.8
(C-3Ј), 151.8 (C-4ЈЈ), 146.0 (C-1Ј), 141.8 (C-1ЈЈ), 129.4 (C-5Ј), 118.9
(C-6Ј), 114.7, 114.4 (4ϫCHAr), 112.3, 111.8 (C-2Ј, C-4Ј), 60.5 (C-
1), 55.7, 55.0 (2ϫOCH3), 31.6 (CH2), 10.8 (CH3) ppm. MS (EI):
m/z (%) = 272 (4), 271 (23) [M]+, 243 (15), 242 (100), 121 (14).
HRMS: calcd. for C17H21NO2 272.1606; found 272.1607.
N-(4-Methoxyphenyl)-N-[1-(4-methoxyphenyl)heptyl]amine (1c):[6]
Yield 258 mg, 79%, colorless oil. Rf = 0.75 (silica gel, 30% ethyl
acetate in hexane). IR (neat): ν
= 3404, 3005, 2953, 2927, 2833,
˜
max
1585, 1504, 1462, 1440, 1377, 1236 cm–1. The NMR spectral data
have previously been reported by us. MS (EI): m/z (%) = 328 (1),
327 (14) [M]+, 243 (11), 242 (63), 205 (18), 134 (11), 123 (15), 122
(11), 121 (100). HRMS: calcd. for C21H29NO2 327.2198; found
327.2188.
N-[1-Cyclohexyl-1-(4-methoxyphenyl)methyl]-N-(4-methoxyphenyl)-
amine (1d):[6] Yield 289 mg, 89%, colorless liquid. Rf = 0.78 (silica
gel, 30% ethyl acetate in hexane). IR (neat): ν
= 3401, 3040,
˜
max
2923, 2850, 1609, 1547, 1508, 1461, 1450, 1236 cm–1. The NMR
spectral data have previously been reported by us. MS (EI): m/z
(%) = 325 (4) [M]+, 243 (18), 242 (100), 134 (14), 121 (76). HRMS:
calcd. for C21H27NO2 325.2042; found 325.2047.
N-(4-Methoxyphenyl)-N-[1-(2-methoxyphenyl)propyl]amine
Yield 252 mg, 93%, colorless oil. Rf = 0.71 (silica gel, 30% ethyl
acetate in hexane). IR (neat): ν = 3378, 3025, 2963, 2931, 1592,
(1h):
˜
max
N-(4-Methoxyphenyl)-N-[1-(4-methoxyphenyl)-2-methylbutyl]-
amine (1e)
1577, 1509, 1462, 1374, 1231 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 7.24 (d, J = 7.5 Hz, 1 H, 6Ј-H), 7.16 (t, J = 7.5 Hz, 1 H, 4Ј-
H), 6.87–6.84 (m, 2 H, 3Ј-H, 5Ј-H), 6.66 (d, J = 8.9 Hz, 2 H, 3ЈЈ-
H, 5ЈЈ-H), 6.47 (d, J = 8.9 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.55 (t, J =
6.7 Hz, 1 H, 1-H), 3.86 (s, 3 H, OCH3), 3.67 (s, 3 H, OCH3), 1.86–
Isomer a: Yield 137 mg, 46%, colorless oil. Rf = 0.73 (silica gel,
30% ethyl acetate in hexane). IR (neat): ν
= 3413, 3062, 2993,
˜
max
2961, 1608, 1585, 1508, 1458, 1379, 1239 cm–1. 1H NMR
(200 MHz, CDCl3): δ = 7.17 (d, J = 8.5 Hz, 2 H, 2Ј-H, 6Ј-H), 6.81 1.72 (m, 2 H, CH2), 0.93 (t, J = 7.5 Hz, 3 H, CH3) ppm. 13C NMR
(d, J = 8.5 Hz, 2 H, 3Ј-H, 5Ј-H), 6.65 (d, J = 9.1 Hz, 2 H, 3ЈЈ-H, (100 MHz, CDCl3): δ = 157.0 (C-2Ј), 151.7 (C-4ЈЈ), 141.7 (C-1ЈЈ),
5ЈЈ-H), 6.42 (d, J = 9.1 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.14 (d, J = 4.9 Hz, 131.5 (C-1Ј), 127.6, 127.2 (C-4Ј, C-6Ј), 120.6 (C-5Ј), 114.6, 114.5
1 H, 1-H), 3.75 (s, 3 H, OCH3), 3.66 (s, 3 H, OCH3), 1.81–1.65 (m,
(4ϫCHAr), 110.4 (C-3Ј), 55.6, 55.2 (2ϫOCH3), 55.0 (C-1), 29.5
1 H, CH), 1.58–1.27 (m, 1 H, CH2), 1.24–1.06 (m, 1 H, CH2), 0.89 (CH2), 11.0 (CH3) ppm. MS (EI): m/z (%) = 272 (12), 271 (66)
1938
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 1934–1942

Multicomponent C-Alkylation Reactions of Aromatic Aldimines
1
[M]+, 243 (60), 242 (100), 149 (40), 121 (79). HRMS: calcd. for
C17H21NO2 271.1572; found 271.1572.
1461, 1382, 1235 cm–1. H NMR (200 MHz, CDCl3): δ = 7.58 (d,
J = 8.2 Hz, 2 H, 3Ј-H, 5Ј-H), 7.43 (d, J = 8.2 Hz, 2 H, 2Ј-H, 6Ј-
H), 6.66 (d, J = 8.7 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 6.38 (d, J = 8.7 Hz, 2
H, 2ЈЈ-H, 6ЈЈ-H), 4.15 (t, J = 6.4 Hz, 1 H, 1-H), 3.66 (s, 3 H,
OCH3), 1.85–1.67 (m, 2 H, CH2), 0.94 (t, J = 7.6 Hz, 3 H,
CH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 152.1 (C-4ЈЈ), 150.1,
141.0 (C-1Ј, C-1ЈЈ), 132.3, 127.3 (4ϫCHAr), 118.9 (C-4Ј), 114.7,
114.4 (4ϫCHAr), 110.6 (CN), 60.2 (C-1), 55.6 (OCH3), 31.5 (CH2),
10.6 (CH3) ppm. MS (EI): m/z (%) = 267 (4), 266 (21) [M]+, 238
(23), 237 (100), 122 (11). HRMS: calcd. for C17H18N2O 266.1419;
found 266.1411.
N-(4-Methoxyphenyl)-N-[1-(2,3-dimethoxyphenyl)propyl]amine (1i):
Yield 271 mg, 90%, colorless oil. Rf = 0.66 (silica gel, 30% ethyl
acetate in hexane). IR (neat): ν
= 3396, 2961, 2933, 1618, 1585,
˜
max
1509, 1476, 1378, 1229 cm–1. 1H NMR (400 MHz, CDCl3): δ =
6.96 (t, J = 8.1 Hz, 1 H, 5Ј-H), 6.85 (dd, J = 8.1, J = 1.6 Hz, 1 H,
4Ј-H), 6.77 (dd, J = 8.1, J = 1.6 Hz, 1 H, 6Ј-H), 6.67 (d, J = 8.6 Hz,
2 H, 3ЈЈ-H, 5ЈЈ-H), 6.51 (d, J = 8.6 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.57 (t,
J = 6.7 Hz, 1 H, 1-H), 3.90 (s, 3 H, OCH3), 3.84 (s, 3 H, OCH3),
3.67 (s, 3 H, OCH3), 1.80 (m, 2 H, CH2), 0.96 (t, J = 7.5 Hz, 3 H,
CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 152.5, 151.6 (C-4ЈЈ,
C-3Ј), 146.6 (C-2Ј), 141.8 (C-1ЈЈ), 137.4 (C-1Ј), 123.9, 118.9, 114.7,
114.3, 110.6 (7ϫCHAr), 60.6 (C-1), 55.6, 55.5, 54.7 (3ϫOCH3),
30.4 (CH2), 11.1 (CH3) ppm. MS (EI): m/z (%) = 302 (7), 301 (34)
[M]+, 273 (17), 272 (100). HRMS: calcd. for C18H23NO3 301.1678;
found 301.1676.
N-(4-Methoxyphenyl)-N-[1-(4-nitrophenyl)propyl]amine (1n): Yield
234 mg, 82%, colorless oil. Rf = 0.62 (silica gel, 30% ethyl acetate
in hexane). IR (neat): ν
= 3405, 3025, 2964, 2932, 1596, 1508,
˜
max
1
1460, 1380, 1230 cm–1. H NMR (200 MHz, CDCl3): δ = 8.15 (d,
J = 8.9 Hz, 2 H, 3Ј-H, 5Ј-H), 7.49 (d, J = 8.9 Hz, 2 H, 2Ј-H, 6Ј-
H), 6.65 (d, J = 8.8 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 6.39 (d, J = 8.8 Hz, 2
H, 2ЈЈ-H, 6ЈЈ-H), 4.24 (t, J = 6.6 Hz, 1 H, 1-H), 3.66 (s, 3 H,
OCH3), 1.87–1.75 (m, 2 H, CH2), 0.95 (t, J = 7.6 Hz, 3 H,
CH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 152.3, 152.2, 146.9
(3ϫCquat,Ar), 140.9 (C-1ЈЈ), 127.3, 123.8, 114.7, 114.4 (8ϫCHAr),
60.1 (C-1), 55.6 (OCH3), 31.5 (CH2), 10.6 (CH3) ppm. MS (EI):
m/z (%) = 287 (7), 286 (39) [M]+, 258 (16), 257 (100), 122 (17).
HRMS: calcd. for C16H18N2O3 286.1317; found 286.1310.
N-[1-(4-Fluorophenyl)propyl]-N-(4-methoxyphenyl)amine (1j): Yield
212 mg, 82%, colorless oil. Rf = 0.68 (silica gel, 30% ethyl acetate
in hexane). IR (neat): ν
= 3404, 3045, 2963, 2932, 1602, 1506,
˜
max
1461, 1379, 1279, 1235 cm–1. 1H NMR (200 MHz, CDCl3): δ =
7.27 (dd, J = 8.5, JF,H = 5.5 Hz, 2 H, 2Ј-H, 6Ј-H), 6.97 (t, J =
8.5 Hz, 2 H, 3Ј-H, 5Ј-H), 6.66 (d, J = 9.1 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H),
6.42 (d, J = 9.1 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.11 (t, J = 6.7 Hz, 1 H, 1-
H), 3.67 (s, 3 H, OCH3), 1.87–1.64 (m, 2 H, CH2), 0.90 (t, J =
7.6 Hz, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 161.7
N-[1-(2-Furyl)propyl]-N-(4-methoxyphenyl)amine
182 mg, 79%, colorless oil. Rf = 0.66 (silica gel, 30% ethyl acetate
in hexane). IR (neat): ν = 3400, 3030, 2963, 2932, 1617, 1509,
(1o):
Yield
1
(d, JF,C = 243.2 Hz, C-4Ј), 152.0 (C-4ЈЈ), 141.3, 139.6 (C-1Ј, C-
˜
max
3
2
1461, 1441, 1380, 1230 cm–1. 1H NMR (200 MHz, CDCl3): δ =
7.34 (d, J = 1.8 Hz, 1 H, 5Ј-H), 6.76 (d, J = 9.2 Hz, 2 H, 3ЈЈ-H,
5ЈЈ-H), 6.60 (d, J = 9.2 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 6.29 (dd, J = 3.1, J
= 1.8 Hz, 1 H, 4Ј-H), 6.16 (d, J = 3.1 Hz, 1 H, 3Ј-H), 4.32 (t, J =
6.7 Hz, 1 H, 1-H), 3.73 (s, 3 H, OCH3), 1.98–1.46 (m, 2 H, CH2),
0.97 (t, J = 7.4 Hz, 3 H, CH3) ppm. 13C NMR (50 MHz, CDCl3):
δ = 156.3 (C-2Ј), 152.2 (C-4ЈЈ), 141.4, 141.3 (C-5Ј, C-1ЈЈ), 114.9,
114.6 (4ϫCHAr), 109.9 (C-4Ј), 105.9 (C-3Ј), 55.6, 54.4 (C-1Ј,
OCH3), 28.0 (CH2), 10.4 (CH3) ppm. MS (EI): m/z (%) = 232 (11),
231 (65) [M]+, 203 (19), 202 (100), 123 (24), 109 (16), 107 (15).
HRMS: calcd. for C14H17NO2 231.1259; found 231.1256.
1ЈЈ), 127.9 (d, JF,C = 8 Hz, C-2Ј, C-6Ј), 115.2 (d, JF,C = 20.8 Hz,
C-3Ј, C-5Ј), 114.7, 114.6 (4ϫCHAr), 60.1 (C-1), 55.7 (OCH3), 31.6
(CH2), 10.7 (CH3) ppm. MS (EI): m/z (%) = 260 (5), 259 (27)
[M]+, 231 (17), 230 (100), 123 (13), 109 (40). HRMS: calcd. for
C16H18FNO 259.1372; found 259.1372.
N-[1-(4-Chlorophenyl)propyl]-N-(4-methoxyphenyl)amine (1k): Yield
223 mg, 81%, colorless oil. Rf = 0.71 (silica gel, 30% ethyl acetate
in hexane). IR (neat): ν
= 3404, 3020, 2964, 2931, 2874, 1617,
˜
max
1592, 1509, 1488, 1460, 1380, 1230 cm–1. 1H NMR (200 MHz,
CDCl3): δ = 7.24 (s, 4 H, CHAr), 6.65 (d, J = 8.8 Hz, 2 H, 3ЈЈ-H,
5ЈЈ-H), 6.40 (d, J = 8.8 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.08 (t, J = 6.8 Hz,
1 H, 1-H), 3.66 (s, 3 H, OCH3), 1.87–1.64 (m, 2 H, CH2), 0.92 (t,
J = 7.0 Hz, 3 H, CH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 152.0
(C-4ЈЈ), 142.6, 141.4, 132.4 (3ϫCquat,Ar), 128.6, 127.9, 114.7, 114.5
(8ϫCHAr), 60.0 (C-1), 55.7 (OCH3), 31.6 (CH2), 10.6 (CH3) ppm.
MS (EI): m/z (%) = 277 (8), 275 (25) [M]+, 248 (40), 247 (6), 246
(100), 127 (8), 125 (24). HRMS: calcd. for C16H18ClNO 275.1077;
found 275.1080.
N-(4-Methoxyphenyl)-N-[1-(4-pyridyl)propyl]amine (1p): Yield
184 mg, 76%, colorless oil. Rf = 0.20 (silica gel, 30% ethyl acetate
in hexane). IR (neat): ν
= 3400, 3033, 2964, 2931, 1600, 1560,
˜
max
1509, 1460, 1361, 1231 cm–1. 1H NMR (400 MHz, CDCl3): δ =
8.50 (d, J = 6.0 Hz, 2 H, 2Ј-H, 6Ј-H), 7.25 (d, J = 6.0 Hz, 2 H, 3Ј-
H, 5Ј-H), 6.66 (d, J = 8.5 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 6.39 (d, J =
8.5 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.13 (t, J = 6.6 Hz, 1 H, 1-H), 3.65 (s,
3 H, OCH3), 1.98–1.46 (m, 2 H, CH2), 0.94 (t, J = 7.4 Hz, 3 H,
CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.6, 152.1 (C-4Ј,
C-4ЈЈ), 149.7 (C-2Ј, C-6Ј), 140.9 (C-1ЈЈ), 121.8 (C-3Ј, C-5Ј), 114.7,
114.3 (4ϫCHAr), 59.5 (C-1), 55.6 (OCH3), 31.0 (CH2), 10.5
(CH3) ppm. MS (EI): m/z (%) = 243 (3), 242 (21) [M]+, 214 (14),
213 (100). HRMS: calcd. for C15H18NO2 242.1419; found
242.1425.
N-(4-Methoxyphenyl)-N-[1-(4-methylphenyl)propyl]amine
Yield 227 mg, 89%, colorless oil. Rf = 0.75 (silica gel, 30% ethyl
acetate in hexane). IR (neat): ν = 3401, 2960, 2925, 2853, 1606,
(1l):[12]
˜
max
1509, 1460, 1450, 1377, 1240 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 7.19 (d, J = 8.0 Hz, 2 H, 3Ј-H, 5Ј-H), 7.09 (d, J = 8.0 Hz, 2 H,
2Ј-H, 6Ј-H), 6.66 (d, J = 8.5 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 6.46 (d, J =
8.5 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.09 (t, J = 6.8 Hz, 1 H, 1-H), 3.66 (s,
3 H, OCH3), 2.29 (s, 3 H, CH3), 1.85–1.71 (m, 2 H, CH2), 0.91 (t,
J = 7.3 Hz, 3 H, CH2-CH3) ppm. 13C NMR (50 MHz, CDCl3): δ
= 152.6 (C-4ЈЈ), 139.8, 136.6, 136.5 (3ϫCquat,Ar), 129.1, 126.7,
115.7, 114.6 (8ϫCHAr), 61.4 (C-1), 55.6 (OCH3), 30.9 (CH2), 21.0
(CH3), 10.7 (CH2-CH3) ppm. MS (EI): m/z (%) = 256 (6), 255 (31)
[M]+, 227 (23), 226 (100), 123 (15), 105 (40). HRMS: calcd. for
C17H21NO 255.1623; found 255.1621.
N-(4-Methoxyphenyl)-N-[1-(2-pyridyl)propyl]amine (1q): Yield
169 mg, 70%, colorless oil. Rf = 0.42 (silica gel, 30% ethyl acetate
in hexane). IR (neat): ν
= 3272, 3105, 3075, 3035, 3005, 2952,
˜
max
2930, 1615, 1590, 1507, 1459, 1381, 1250 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 8.55 (dd, J = 5.9, J = 1.6 Hz, 1 H, 6Ј-H),
7.59 (dt, J = 7.5, J = 1.6 Hz, 1 H, 4Ј-H), 7.29 (d, J = 7.5 Hz, 1 H,
3Ј-H), 7.13 (dd, J = 7.5, J = 5.9 Hz, 1 H, 5Ј-H), 6.67 (d, J = 9.1 Hz,
2 H, 3ЈЈ-H, 5ЈЈ-H), 6.51 (d, J = 9.1 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.30 (t,
J = 6.6 Hz, 1 H, 1-H), 3.67 (s, 3 H, OCH3), 1.93–1.79 (m, 2 H,
CH2), 0.92 (t, J = 7.2 Hz, 3 H, CH3) ppm. 13C NMR (100 MHz,
4-[1-(Methoxyanilino)propyl]benzonitrile (1m):[13] Yield 213 mg,
80%, colorless oil. Rf = 0.58 (silica gel, 30% ethyl acetate in hex-
ane). IR (neat): ν
= 3402, 3045, 2963, 2929, 2366, 1604, 1509,
˜
max
Eur. J. Org. Chem. 2010, 1934–1942
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1939

M. Valpuesta, C. Muñoz, A. Díaz, G. Torres, R. Suau
FULL PAPER
CDCl3): δ = 163.0 (C-2Ј), 151.9 (C-4ЈЈ), 149.2 (C-6Ј), 141.5 (C-1ЈЈ), 1.24 (m, 4 H, 2ϫCH2), 0.94 (t, J = 7.2 Hz, 3 H, CH3) ppm. 13C
136.5 (C-4Ј), 121.9, 121.3 (C-3Ј, C-5Ј), 114.7, 114.6 (4ϫCHAr), NMR (100 MHz, CDCl3): δ = 159.7 (C-3Ј), 152.1 (C-4ЈЈ), 146.0
61.5 (C-1), 55.6 (OCH3), 29.9 (CH2), 10.5 (CH3) ppm. MS (EI): (C-1Ј), 141.1 (C-1ЈЈ), 129.4 (C-5Ј), 118.9 (C-6Ј), 114.6 (4ϫCHAr),
m/z (%) = 243 (3), 242 (13) [M]+, 214 (14), 213 (100). HRMS: calcd.
for C15H18NO2 242.1419; found 242.1424.
112.2, 111.9 (C-4Ј, C-2Ј), 59.5 (C-1), 55.6, 55.1 (2ϫOCH3), 38.3,
28.5, 22.6 (3ϫCH2), 13.9 (CH3) ppm. MS (EI): m/z (%) = 300 (6),
299 (27) [M]+, 243 (53), 242 (100), 121 (30). HRMS: calcd. for
C19H25NO2 299.1885; found 299.1876.
N-(4-Methoxyphenyl)-N-[1-(2-methoxyphenyl)pentyl]amine
Yield 245 mg, 82%, colorless oil. Rf = 0.77 (silica gel, 30% ethyl
acetate in hexane). IR (neat): ν = 3403, 3020, 2954, 2931, 1617,
(1r):
N-(4-Methoxyphenyl)-N-[1-(3-methoxyphenyl)-2-methylbutyl]-
˜
max
1587, 1509, 1461, 1377, 1284 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 7.26 (d, J = 7.8 Hz, 1 H, 6Ј-H), 7.17 (t, J = 7.8 Hz, 1 H, 4Ј-
H), 6.87–6.85 (m, 2 H, 5Ј-H, 3Ј-H), 6.68 (d, J = 8.1 Hz, 2 H, 3ЈЈ-
H, 5ЈЈ-H), 6.49 (d, J = 8.1 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.63 (t, J =
6.7 Hz, 1 H, 1-H), 3.87 (s, 3 H, OCH3), 3.68 (s, 3 H, OCH3), 1.84–
1.68 (m, 2 H, CH2), 1.38–1.27 (m, 4 H, 2ϫCH2), 0.89 (t, J =
7.0 Hz, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 156.9
(C-2Ј), 151.7 (C-4ЈЈ), 141.7 (C-1ЈЈ), 131.9 (C-1Ј), 127.5, 127.1 (C-
4Ј, C-6Ј), 120.6 (C-5Ј), 114.7, 114.4 (4ϫCHAr), 110.4 (C-3Ј), 55.6,
55.2 (2ϫOCH3), 53.5 (C-1), 36.5, 28.6, 22.5 (3ϫCH2), 13.9
(CH3) ppm. MS (EI): m/z (%) = 300 (8), 299 (35) [M]+, 243 (50),
242 (100), 177 (3), 121 (72). HRMS: calcd. for C19H25NO2
299.1885; found 299.1872.
amine (1u)
Isomer a: Yield 134 mg, 45%, colorless oil. Rf = 0.78 (silica gel,
30% ethyl acetate in hexane). IR (neat): ν
= 3411, 3011, 2959,
˜
max
2931, 1606, 1584, 1509, 1454, 1379, 1221 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 7.19 (t, J = 8.1 Hz, 1 H, 5Ј-H), 6.87 (d, J
= 8.1 Hz, 1 H, 6Ј-H), 6.83 (d, J = 2.5 Hz, 1 H, 2Ј-H), 6.72 (dd, J
= 8.1, J = 2.5 Hz, 1 H, 4Ј-H), 6.65 (d, J = 8.9 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-
H), 6.43 (d, J = 8.9 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.16 (d, J = 4.8 Hz, 1
H, 1-H), 3.76 (s, 3 H, OCH3), 3.66 (s, 3 H, OCH3), 1.79–1.73 (m,
1 H, CH), 1.53–1.43 (m, 1 H, CH2), 1.24–1.12 (m, 1 H, CH2), 0.91
(t, J = 7.1 Hz, 3 H, CH2-CH3), 0.88 (d, J = 7.1 Hz, 3 H, CH-
CH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 159.6 (C-3Ј), 151.7
(C-4ЈЈ), 145.2 (C-1Ј), 142.1 (C-1ЈЈ), 129.1 (C-5Ј), 119.5 (C-6Ј),
114.7, 114.2 (4ϫCHAr), 113.2, 111.5 (C-2Ј, C-4Ј), 62.4 (C-1), 55.7,
55.1 (2ϫOCH3), 41.8 (CH), 26.8 (CH2), 14.5 (CH-CH3), 11.9
(CH2-CH3) ppm. MS (EI): m/z (%) = 300 (2), 299 (11) [M]+, 243
(17), 242 (100), 121 (4). HRMS: calcd. for C19H25NO2 299.1885;
found 299.1885.
N-(4-Methoxyphenyl)-N-[1-(2-methoxyphenyl)-2-methylbutyl]-
amine (1s)
Isomer a: Yield 137 mg, 46%, colorless oil. Rf = 0.85 (silica gel,
30% ethyl acetate in hexane). IR (neat): ν
= 3407, 3060, 3031,
˜
max
3001, 2959, 2932, 1617, 1587, 1509, 1459, 1380, 1284 cm–1. 1H
NMR (400 MHz, CDCl3): δ = 7.19 (d, J = 7.8 Hz, 1 H, 6Ј-H), 7.15
(t, J = 7.8 Hz, 1 H, 4Ј-H), 6.85–6.81 (m, 2 H, 5Ј-H, 3Ј-H), 6.64 (d,
J = 7.5 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 6.44 (br. s, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.58
(br. s, 1 H, 1-H), 3.85 (s, 3 H, OCH3), 3.65 (br. s, 3 H, OCH3),
1.88–1.82 (m, 1 H, CH), 1.47–1.37 (m, 1 H, CH2), 1.27–1.16 (m, 1
H, CH2), 0.90 (t, J = 7.1 Hz, 3 H, CH2-CH3), 0.89 (d, J = 7.1 Hz,
3 H, CH-CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 157.0 (C-
2Ј), 151.8 (C-4ЈЈ), 142.1 (C-1ЈЈ), 131.4 (C-1Ј), 128.4, 127.8 (C-4Ј, C-
6Ј), 120.3 (C-5Ј), 114.5 (4ϫCHAr), 110.3 (C-3Ј), 55.9 (C-1), 55.2
(2ϫOCH3), 39.4 (CH), 26.9 (CH2), 14.9 (CH-CH3), 11.7 (CH2-
CH3) ppm. MS (EI): m/z (%) = 299 (7) [M]+, 243 (27), 242 (100),
121 (13). HRMS: calcd. for C19H25NO2 299.1885; found 299.1882.
Isomer b: Yield 134 mg, 45%, colorless oil. Rf = 0.75 (silica gel,
30% ethyl acetate in hexane). IR (neat): ν
= 3405, 3010, 2960,
˜
max
2932, 1599, 1584, 1509, 1461, 1380, 1232 cm–1. 1H NMR
(200 MHz, CDCl3): δ = 7.18 (t, J = 7.9 Hz, 1 H, 5Ј-H), 6.86 (d, J
= 7.9 Hz, 1 H, 6Ј-H), 6.82 (d, J = 2.4 Hz, 1 H, 2Ј-H), 6.71 (dd, J
= 7.9, J = 2.4 Hz, 1 H, 4Ј-H), 6.65 (d, J = 9.1 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-
H), 6.42 (d, J = 9.1 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.06 (d, J = 6.1 Hz, 1
H, 1-H), 3.75 (s, 3 H, OCH3), 3.66 (s, 3 H, OCH3), 1.79–1.73 (m,
1 H, CH), 1.70–1.43 (m, 1 H, CH2), 1.24–1.12 (m, 1 H, CH2), 0.91
(t, J = 6.7 Hz, 3 H, CH2-CH3), 0.90 (d, J = 6.7 Hz, 3 H, CH-
CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 159.4 (C-3Ј), 151.3
(C-4ЈЈ), 144.4 (C-1Ј), 141.9 (C-1ЈЈ), 129.0 (C-5Ј), 119.8 (C-6Ј),
114.7, 114.3 (4ϫCHAr), 113.3, 111.6 (C-2Ј, C-4Ј), 63.4 (C-1), 55.7,
55.1 (2ϫOCH3), 41.5 (CH), 25.4 (CH2), 16.0 (CH-CH3), 11.7
(CH2-CH3) ppm. MS (EI): m/z (%) = 300 (2), 299 (12) [M]+, 243
(16), 242 (100), 121 (3). HRMS: calcd. for C19H25NO2 299.1885;
found 299.1883.
Isomer b: Yield 137 mg, 46%, colorless oil. Rf = 0.80 (silica gel,
30% ethyl acetate in hexane). IR (neat): ν
= 3397, 3020, 2959,
˜
max
2930, 1598, 1586, 1509, 1461, 1378, 1288 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 7.17 (t, J = 7.8 Hz, 1 H, 4Ј-H), 7.13 (d, J
= 7.8 Hz, 1 H, 6Ј-H), 6.85–6.82 (m, 2 H, 3Ј-H, 5Ј-H), 6.64 (d, J =
8.6 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 6.46 (br. s, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.45 (br.
s, 1 H, 1-H), 3.85 (s, 3 H, OCH3), 3.66 (br. s, 3 H, OCH3), 1.87–
1.79 (m, 1 H, CH), 1.72–1.66 (m, 1 H, CH2), 1.26–1.12 (m, 1 H,
CH2), 0.89 (t, J = 7.2 Hz, 3 H, CH2-CH3), 0.82 (d, J = 7.2 Hz, 3
H, CH-CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 157.3 (C-2Ј),
151.6 (C-4ЈЈ), 142.4 (C-1ЈЈ), 131.4 (C-1Ј), 128.3, 127.5 (C-4Ј, C-6Ј),
120.3 (C-5Ј), 114.6 (4ϫCHAr), 110.4 (C-3Ј), 57.0 (C-1), 55.7, 55.3
(2ϫOCH3), 39.8 (CH), 25.3 (CH2), 16.3 (CH-CH3), 11.7 (CH2-
CH3) ppm. MS (EI): m/z (%) = 299 (13) [M]+, 243 (48), 242 (100),
121 (24). HRMS: calcd. for C19H25NO2 299.1885; found 299.1896.
N-[1-(4-Fluorophenyl)pentyl]-N-(4-methoxyphenyl)amine (1v): Yield
201 mg, 70%, colorless oil. Rf = 0.77 (silica gel, 30% ethyl acetate
in hexane). IR (neat): ν
= 3402, 3033, 2955, 2931, 2858, 1602,
˜
max
1507, 1463, 1379 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.30 (dd,
J = 8.6, JF,H = 5.5 Hz, 2 H, 2Ј-H, 6Ј-H), 6.96 (t, J = 8.6 Hz, 2 H,
3Ј-H, 5Ј-H), 6.66 (d, J = 8.9 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 6.43 (d, J =
8.9 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.17 (t, J = 6.6 Hz, 1 H, 1-H), 3.67 (s,
3 H, OCH3), 1.80–1.63 (m, 2 H, CH2), 1.36–1.22 (m, 4 H, 2ϫCH2),
0.86 (t, J = 7.0 Hz, 3 H, CH3) ppm. 13C NMR (50 MHz, CDCl3):
1
δ = 161.7 (d, JF,C = 243.9 Hz, C-4Ј), 152.2 (C-4ЈЈ), 140.8, 139.7
3
2
(C-1Ј, C-1ЈЈ), 127.9 (d, JF,C = 7.5 Hz, C-2Ј, C-6Ј), 115.2 (d, JF,C
= 21.4 Hz, C-3Ј, C-5Ј), 114.9, 114.7 (4ϫCHAr), 58.9 (C-1), 55.6
(OCH3), 38.5, 28.3, 22.5 (3ϫCH2), 13.9 (CH3) ppm. MS (EI): m/z
(%) = 288 (6), 287 (28) [M]+, 231 (22), 230 (100), 109 (55). HRMS:
calcd. for C18H22FNO 287.1685; found 287.1687.
N-(4-Methoxyphenyl)-N-[1-(3-methoxyphenyl)pentyl]amine
Yield 239 mg, 80%, colorless oil. Rf = 0.73 (silica gel, 30% ethyl
acetate in hexane). IR (neat): ν = 3401, 3020, 2995, 2953, 2931,
(1t):
˜
max
1598, 1509, 1484, 1377, 1233 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 7.21 (t, J = 7.8 Hz, 1 H, 5Ј-H), 6.90 (d, J = 7.8 Hz, 1 H, 6Ј-
H), 6.87 (d, J = 2.4 Hz, 1 H, 2Ј-H), 6.74 (dd, J = 7.8, J = 2.4 Hz,
1 H, 4Ј-H), 6.66 (d, J = 8.9 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 6.47 (d, J =
N-[1-(4-Fluorophenyl)-2-methylbutyl]-N-(4-methoxyphenyl)amine
(1w)
8.9 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.16 (t, J = 6.7 Hz, 1 H, 1-H), 3.77 (s, Isomer a: Yield 118 mg, 41%, colorless oil. Rf = 0.82 (silica gel,
3 H, OCH3), 3.67 (s, 3 H, OCH3), 1.78–1.71 (m, 2 H, CH2), 1.39– 30% ethyl acetate in hexane). IR (neat): ν = 3419, 3010, 2960,
˜
max
1940
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 1934–1942

Multicomponent C-Alkylation Reactions of Aromatic Aldimines
2928, 1602, 1507, 1461, 1380, 1294 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.26–7.20 (m, 4 H, CHAr), 6.65 (d, J = 9.1 Hz, 2 H,
CDCl3): δ = 7.23 (dd, J = 8.5, JF,H = 5.3 Hz, 2 H, 2Ј-H, 6Ј-H),
6.96 (t, J = 8.5 Hz, 2 H, 3Ј-H, 5Ј-H), 6.64 (d, J = 8.8 Hz, 2 H, 3ЈЈ- 5.9 Hz, 1 H, 1-H), 3.67 (s, 3 H, OCH3), 1.78–1.69 (m, 1 H, CH),
H, 5ЈЈ-H), 6.40 (d, J = 8.8 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.17 (d, J = 1.59–1.46 (m, 1 H, CH2), 1.21–1.10 (m, 1 H, CH2), 0.90 (t, J =
3ЈЈ-H, 5ЈЈ-H), 6.40 (d, J = 9.1 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.10 (d, J =
4.5 Hz, 1 H, 1-H), 3.66 (s, 3 H, OCH3), 1.81–1.70 (m, 1 H, CH), 7.0 Hz, 3 H, CH2-CH3), 0.84 (d, J = 7.0 Hz, 3 H, CH-CH3) ppm.
1.58–1.42 (m, 1 H, CH2), 1.23–1.12 (m, 1 H, CH2), 0.90 (t, J = 13C NMR (50 MHz, CDCl3): δ = 151.9 (C-4ЈЈ), 141.6, 141.1, 132.3
7.5 Hz, 3 H, CH2-CH3), 0.88 (d, J = 7.5 Hz, 3 H, CH-CH3) ppm.
(3ϫCquat,Ar), 128.7, 128.3, 114.7, 114.4 (8ϫCHAr), 62.8 (C-1), 55.7
(OCH3), 41.5 (CH), 25.3 (CH2), 15.9 (CH-CH3), 11.7 (CH2-
CH3) ppm. MS (EI): m/z (%) = 305 (4), 303 (17) [M]+, 249 (5), 248
(37), 247 (16), 246 (100). HRMS: calcd. for C18H22NOCl 303.1390;
1
13C NMR (100 MHz, CDCl3): δ = 161.7 (d, JF,C = 215.0 Hz, C-
3
4Ј), 151.7 (C-4ЈЈ), 141.7, 138.5 (C-1Ј, C-1ЈЈ), 128.4 (d, JF,C
=
=
2
7.5 Hz, C-2Ј, C-6Ј), 115.1, 114.9 (4ϫCHAr), 114.8 (d, JF,C
20.2 Hz, C-3Ј, C-5Ј), 61.7 (C-1), 55.7 (OCH3), 41.9 (CH), 26.6 found 303.1396.
(CH2), 14.4 (CH-CH3), 11.9 (CH2-CH3) ppm. MS (EI): m/z (%) =
N-[1-Ethyl-2-methylpropyl]-N-(4-methoxyphenyl)amine (2): Yield
73 mg, 35% (one-pot procedure); 145 mg, 70% (from the pre-
formed imine), colorless oil. Rf = 0.77 (silica gel, 12% methanol in
288 (2), 287 (8) [M]+, 231 (14), 230 (100). HRMS: calcd. for
C18H22NOF 287.1685; found 287.1698.
Isomer b: Yield 118 mg, 41%, colorless oil. Rf = 0.78 (silica gel,
chloroform). IR (neat): νmax = 3399, 3057, 2958, 2931, 2830, 1616,
˜
1579, 1509, 1462, 1380, 1240 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 6.73 (d, J = 8.5 Hz, 2 H, 3Ј-H, 5Ј-H), 6.52 (d, J = 8.5 Hz, 2 H,
2Ј-H, 6Ј-H), 3.71 (s, 3 H, OCH3), 2.99 (dt, J = 8.6, J = 7.5 Hz, 1
H, 1-H), 1.89–1.80 (m, 1 H, 2-H), 1.59–1.51 (m, 1 H, CH2), 1.38–
1.28 (m, 1 H, CH2), 0.90 (d, J = 7.5 Hz, 6 H, 2ϫCH3), 0.88 (t, J
= 6.9 Hz, 3 H, CH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 151.7
(C-4Ј), 136.8 (C-1Ј), 114.8 (4ϫCHAr), 62.0 (C-1), 55.7 (OCH3),
30.1 (C-2), 23.4 (CH2), 18.6 (2ϫCH3), 10.9 (CH3) ppm. MS (EI):
m/z (%) = 207 (7) [M]+, 178 (29), 164 (100), 121 (17). HRMS: calcd.
for C13H21NO 207.1623; found 207.1615.
30% ethyl acetate in hexane). IR (neat): ν
= 3409, 3015, 2960,
˜
max
2931, 1602, 1508, 1461, 1380, 1292 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 7.23 (dd, J = 8.5, JF,H = 5.4 Hz, 2 H, 2Ј-H, 6Ј-H),
6.95 (t, J = 8.5 Hz, 2 H, 3Ј-H, 5Ј-H), 6.65 (d, J = 9.1 Hz, 2 H, 3ЈЈ-
H, 5ЈЈ-H), 6.39 (d, J = 9.1 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.10 (d, J =
5.9 Hz, 1 H, 1-H), 3.66 (s, 3 H, OCH3), 1.78–1.68 (m, 1 H, CH),
1.60–1.47 (m, 1 H, CH2), 1.21–1.14 (m, 1 H, CH2), 0.90 (t, J =
7.0 Hz, 3 H, CH2-CH3), 0.83 (d, J = 7.0 Hz, 3 H, CH-CH3) ppm.
13C NMR (50 MHz, CDCl3): δ = 161.8 (d, 1JF,C = 215.0 Hz, C-4Ј),
3
151.8 (C-4ЈЈ), 141.8, 138.1 (C-1ЈЈ, C-1Ј), 128.7 (d, JF,C = 7.6 Hz,
2
C-2Ј, C-6Ј), 114.9 (d, JF,C = 20.1 Hz, C-3Ј, C-5Ј), 114.7, 114.4
N-(4-Methoxyphenyl)-N-[1-(tetrahydro-2-furanyl)propyl]amine (3)
(4ϫCHAr), 62.7 (C-1), 55.7 (OCH3), 41.6 (CH), 25.4 (CH2), 15.9
(CH-CH3), 11.7 (CH2-CH3) ppm. MS (EI): m/z (%) = 288 (2), 287
(9) [M]+, 231 (15), 230 (100). HRMS: calcd. for C18H22NOF
287.1685; found 287.1689.
Isomer a: Yield 23 mg, 10%, colorless oil. Rf = 0.51 (silica gel, 20%
ethyl acetate in hexane). Spectroscopic data for an enriched mixture
of this isomer: 13C NMR (100 MHz, CDCl3): δ = 151.6 (C-4ЈЈ),
142.6 (C-1ЈЈ), 114.9, 114.3 (4ϫCHAr), 80.3 (C-2Ј), 68.6 (C-5Ј), 58.0
(C-1), 55.7 (OCH3), 28.3, 26.1, 25.6 (3ϫCH2), 10.8 (CH3) ppm.
N-[1-(4-Chlorophenyl)pentyl]-N-(4-methoxyphenyl)amine (1x): Yield
218 mg, 72%, colorless oil. Rf = 0.77 (silica gel, 30% ethyl acetate
in hexane). IR (neat): ν
= 3402, 3025, 2954, 1617, 1592, 1509,
˜
max
1
Isomer b: Yield 164 mg, 70%, colorless oil. Rf = 0.44 (silica gel,
1463, 1378, 1233 cm–1. H NMR (200 MHz, CDCl3): δ = 7.24 (br.
s, 4 H, CHAr), 6.65 (d, J = 8.7 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 6.41 (d, J =
8.7 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 4.15 (t, J = 6.8 Hz, 1 H, 1-H), 3.70 (s,
3 H, OCH3), 1.79–1.63 (m, 2 H, CH2), 1.37–1.19 (m, 4 H, 2ϫCH2),
0.85 (t, J = 6.9 Hz, 3 H, CH3) ppm. 13C NMR (50 MHz, CDCl3):
δ = 151.9 (C-4ЈЈ), 143.1, 141.4 (C-1ЈЈ, C-4Ј), 132.3 (C-1Ј), 128.6,
127.8, 114.7, 114.4 (8ϫCHAr), 58.4 (C-1), 55.7 (OCH3), 38.7, 28.3,
22.5 (3ϫCH2), 13.9 (CH3) ppm. MS (EI): m/z (%) = 305 (8), 303
(23) [M]+, 249 (7), 248 (41), 247 (21), 246 (100), 127 (13), 125 (38).
HRMS: calcd. for C18H22ClNO 303.1390; found 303.1381.
20% ethyl acetate in hexane). IR (neat): ν
= 3408, 3068, 2965,
˜
max
2937, 1605, 1509, 1460, 1380, 1253 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 6.73 (d, J = 8.5 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 6.61 (d, J =
8.5 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 3.87 (dt, J = 7.5, J = 7.0 Hz, 1 H, 5Јa-
H), 3.82 (dt, J = 8.0, J = 7.0 Hz, 1 H, 5Јb-H), 3.70–3.64 (m, 4 H,
2Ј-H, OCH3), 3.24 (dt, J = 7.5, J = 5.0 Hz, 1 H, 1-H), 1.95–1.65
(m, 5 H, 2ϫ3Ј-H, 2ϫ4Ј-H, CH2-CH3), 1.48-1.37 (m, 1 H, CH2-
CH3), 0.94 (t, J = 7.3 Hz, 3 H, CH2-CH3) ppm. 13C NMR
(100 MHz, CDCl3):
δ = 152.1 (C-4ЈЈ), 141.9 (C-1ЈЈ), 114.8
(4ϫCHAr), 81.1 (C-2Ј), 68.2 (C-5Ј), 59.6 (C-1), 55.7 (OCH3), 27.9,
25.9, 24.3 (3ϫCH2), 10.4 (CH3) ppm. MS (EI): m/z (%) = 235 (10)
[M]+, 164 (100), 122 (13). HRMS: calcd. for C14H21NO2 235.1572;
found 235.1579.
N-[1-(4-Chlorophenyl)-2-methylbutyl]-N-(4-methoxyphenyl)amine
(1y)
Isomer a: Yield 127 mg, 42%, colorless oil. Rf = 0.84 (silica gel,
Synthesis of Amines 4 and 5: Boron trifluoride–diethyl ether
(250 µL, 2 mmol) was added to a solution of the corresponding
amine (1 mmol) and p-methoxybenzaldehyde (0.12 mL, 1 mmol) in
dichloromethane. The reaction mixture was stirred at room tem-
perature for 2 h and then a 1  solution of triethylborane in hexane
(3 mL, 3 mmol) was added. Subsequently, an aqueous solution of
hydrogen peroxide (0.1 mL, 33%) was added and the mixture
stirred for 30 min. The crude mixture was concentrated to dryness
under vacuum and purified by column chromatography (SiO2, 10%
ethyl acetate in hexane) to afford the alkylated amines in yields of
38–40%.
30% ethyl acetate in hexane). IR (neat): ν
= 3414, 3025, 2960,
˜
max
2930, 1591, 1577, 1509, 1460, 1381, 1295 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 7.25–7.20 (m, 4 H, CHAr), 6.65 (d, J =
9.1 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 6.40 (d, J = 9.1 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H),
4.17 (d, J = 4.8 Hz, 1 H, 1-H), 3.67 (s, 3 H, OCH3), 1.84–1.69 (m,
1 H, CH), 1.53–1.43 (m, 1 H, CH2), 1.24–1.14 (m, 1 H, CH2), 0.90
(t, J = 7.5 Hz, 3 H, CH2-CH3), 0.87 (d, J = 7.5 Hz, 3 H, CH-
CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 151.9 (C-4ЈЈ), 141.6,
141.5, 132.1 (3ϫCquat,Ar), 128.4, 128.3, 114.7, 114.3 (8ϫCHAr),
61.8 (C-1), 55.6 (OCH3), 41.7 (CH), 26.6 (CH2), 14.5 (CH-CH3),
11.9 (CH2-CH3) ppm. MS (EI): m/z (%) = 305 (5), 303 (16) [M]+,
249 (5), 248 (32), 247 (16), 246 (100). HRMS: calcd. for
C18H22NOCl 303.1390; found 303.1391.
N-Methyl-N-[1-(4-methoxyphenyl)propyl]amine (4): Yield 68 mg,
38% (one-pot procedure); 143 mg, 80% (from the preformed im-
ine), colorless oil. Rf = 0.30 (silica gel, 12% methanol in chloro-
Isomer b: Yield 127 mg, 42%, colorless oil. Rf = 0.80 (silica gel,
30% ethyl acetate in hexane). IR (neat): ν
= 3409, 3025, 2961,
form). IR (neat): ν
= 3291, 3064, 2932, 2873, 1610, 1585, 1509,
˜
˜
max
max
2931, 1592, 1509, 1461, 1381, 1233 cm–1. 1H NMR (400 MHz, 1462, 1421, 1376, 1241 cm–1. 1H NMR (200 MHz, CDCl3): δ =
Eur. J. Org. Chem. 2010, 1934–1942
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1941

M. Valpuesta, C. Muñoz, A. Díaz, G. Torres, R. Suau
FULL PAPER
7.15 (d, J = 8.5 Hz, 2 H, 2Ј-H, 6Ј-H), 6.86 (d, J = 8.5 Hz, 2 H, 3Ј-
H, 5Ј-H), 3.78 (s, 3 H, OCH3), 3.28 (dd, J = 8.2, J = 5.8 Hz, 1 H,
1-H), 2.23 (s, 3 H, NCH3), 1.79–1.49 (m, 2 H, CH2), 0.76 (t, J =
7.4 Hz, 3 H, CH2-CH3) ppm. 13C NMR (50 MHz, CDCl3): δ =
158.5 (C-4Ј), 135.7 (C-1Ј), 128.2 (C-2Ј, C-6Ј), 113.6 (C-3Ј, C-5Ј),
66.4 (C-1), 55.1 (OCH3), 34.4 (NCH3), 30.5 (CH2), 10.7 (CH2-
CH3) ppm. MS (EI): m/z (%) = 151 (8), 150 (100), 121 (5). HRMS:
calcd. for C11H18NO [MH]+ 180.1382; found 180.1386.
Acknowledgments
This work was supported by the Spanish Ministerio de Educación
y Ciencia (MEC) (Grant nos. CTQ2004-0565 and CTQ2007-60190.
[1] For reviews, see: a) D. Enders, U. Reinhol, Tetrahedron: Asym-
metry 1997, 8, 1895–1946; b) R. Bloch, Chem. Rev. 1998, 98,
1407–1438; c) T. Vilaivan, W. Bhanthumnavin, Y. Sritana-An-
ant, Curr. Org. Chem. 2005, 9, 1315–1392; d) G. K. Friestad,
A. K. Mathies, Tetrahedron 2007, 63, 2541–2569; e) K. Yam-
ada, K. Tomioka, Chem. Rev. 2008, 108, 2874–2886.
[2] For reviews of radical addition to C=N bonds, see: a) A. G.
Fallis, I. M. Brinza, Tetrahedron 1997, 53, 17543–17594; b) T.
Naito, Heterocycles 1999, 50, 505–541; c) G. K. Friestad, Tetra-
hedron 2001, 57, 5461–5496; d) H. Miyabe, M. Ueda, T. Naito,
Synlett 2004, 7, 1140–1157.
[3] a) H. Miyabe, R. Shibata, M. Sangawa, C. Ushiro, T. Naito,
Tetrahedron 1998, 54, 11431–11444; b) M. P. Bertrand, L.
Feray, R. Nouguier, P. Perfetti, J. Org. Chem. 1999, 64, 9189–
9193; c) H. Miyabe, M. Ueda, T. Naito, Chem. Commun. 2000,
2059–2060; d) G. K. Friestad, Y. Shen, E. L. Ruggles, Angew.
Chem. Int. Ed. 2003, 42, 5061–5063; e) H. Miyabe, Y. Ya-
maoka, Y. Takemoto, J. Org. Chem. 2005, 70, 3324–3327; f)
G. K. Friestad, Eur. J. Org. Chem. 2005, 3157–3172; g) M.
Ueda, H. Miyabe, O. Miyata, T. Naito, Tetrahedron 2009, 65,
1321–1326.
[4] H. Miyabe, C. Ushiro, M. Ueda, K. Yamakawa, T. Naito, J.
Org. Chem. 2000, 65, 176–185.
[5] K. Yamada, Y. Yamamoto, M. Maekawa, T. Akindele, H.
Umeki, K. Tomioka, Org. Lett. 2006, 8, 87–89.
[6] M. Valpuesta, C. Muñoz, A. Díaz, R. Suau, G. Torres, Eur. J.
Org. Chem. 2007, 4467–4470.
[7] a) H. Miyabe, K. Yamakawa, N. Yoshioka, T. Naito, Tetrahe-
dron 1999, 55, 11209–11218; b) H. Miyabe, M. Ueda, N.
Yoshioka, K. Yamakawa, T. Naito, Tetrahedron 2000, 56,
2413–2420.
N-Butyl-N-[1-(4-methoxyphenyl)propyl]amine (5): Yield 88 mg, 40%
(one-pot procedure); 183 mg, 83% (from the preformed imine), col-
orless oil. Rf = 0.64 (silica gel, 12% methanol in chloroform). IR
(neat): νmax = 3400, 3061, 2956, 2928, 1610, 1585, 1509, 1460, 1376,
˜
1
1244 cm–1. H NMR (200 MHz, CDCl3): δ = 7.16 (d, J = 8.5 Hz,
2 H, 2Ј-H, 6Ј-H), 6.83 (d, J = 8.5 Hz, 2 H, 3Ј-H, 5Ј-H), 3.77 (s, 3
H, OCH3), 3.39 (dd, J = 7.9, J = 5.4 Hz, 1 H, 1-H), 2.39 (dt, J =
6.7, J = 2.4 Hz, 2 H, CH2), 1.78–1.19 (m, 6 H, 3ϫCH2), 0.85 (t, J
= 7.3 Hz, 3 H, CH3), 0.83 (t, J = 7.3 Hz, 3 H, CH3) ppm. 13C
NMR (50 MHz, CDCl3): δ = 158.4 (C-4Ј), 136.3 (C-1Ј), 128.2 (C-
2Ј, C-6Ј), 113.5 (C-3Ј, C-5Ј), 64.5 (C-1), 55.2 (OCH3), 47.4 (HN-
CH2), 32.4, 30.9, 20.5 (3ϫCH2), 13.9, 10.8 (2ϫCH3) ppm. MS
(EI): m/z (%) = 221 (1) [M]+, 193 (11), 192 (100), 164 (1), 149 (13),
136 (15), 121 (15). HRMS: calcd. for C14H23NO 221.1779; found
221.1783.
1-Ethyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6):[14] Boron
trifluoride–diethyl ether (250 µL, 2 mmol) was added to a solution
of 6,7-dimethoxy-3,4-dihydroisoquinoline[15] (191 mg, 1 mmol) in
dichloromethane. The reaction mixture was stirred at room tem-
perature for 10 min and then a 1  solution of triethylborane in
hexane (3 mL, 3 mmol) was added. Subsequently, an aqueous solu-
tion of hydrogen peroxide (0.1 mL, 33%) was added and the mix-
ture stirred for 24 h. The crude mixture was concentrated to dry-
ness under vacuum and purified by column chromatography (SiO2,
10% ethyl acetate in hexane) to afford the alkylated amine 6
(32 mg, 60%) as a colorless oil. Rf = 0.44 (silica gel, 12% methanol
[8] a) A. G. Davies, S. C. W. Hook, B. P. Roberts, J. Organomet.
Chem. 1970, 23, C11–C13; b) M. P. Bertrand, L. Feray, R.
Nouguier, L. Stella, Synlett 1998, 780–782.
in chloroform). IR (neat): ν
= 3423, 3034, 2930, 1609, 1560,
˜
max
1509, 1462, 1374, 1253 cm–1. 1H NMR (200 MHz, CDCl3): δ =
6.59, 6.54 (2 s, 1 H each, 5-H, 8-H), 3.88–3.87 (m, 1 H, 1-H), 3.82
(s, 6 H, 2ϫOCH3), 3.17, (ddd, J = 12.2, J = 4.9, J = 4.9 Hz, 1 H,
3eq-H), 2.90 (ddd, J = 12.2, J = 7.3, J = 4.9 Hz, 1 H, 3ax-H), 2.75–
2.57 (m, 2 H, 4eq-H, 4ax-H), 1.93–1.59 (m, 2 H, CH2-CH3), 0.98 (t,
J = 7.3 Hz, 3 H, CH2-CH3) ppm. 13C NMR (50 MHz, CDCl3): δ
= 147.1, 147.0 (C-6, C-7), 132.2, 127.2 (C-4a, C-8a), 111.7, 109.2
(C-5, C-8), 56.6 (C-1), 55.9, 55.8 (2ϫOCH3), 41.0 (C-3), 29.5, 29.0
(C-4, CH2-CH3), 10.5 (CH2-CH3) ppm. MS (EI): m/z (%) = 221 (2)
[M]+, 193 (63), 192 (100), 177 (43), 176 (72), 148 (31). HRMS:
calcd. for C13H19NO2 221.1416; found 221.1411.
[9] A. Pelter, K. Smith, H. C. Brown, Borane Reagents, Academic
Press, London, 1988, p. 382.
[10] P. Bianchi, G. Roda, S. Riva, B. Danieli, A. Zabelinskaja-
Mackova, H. Griengl, Tetrahedron 2001, 57, 2213–2220.
[11] C. Li, B. Villa-Marcos, J. Xiao, J. Am. Chem. Soc. 2009, 131,
6967–6969.
[12] C. Li, C. Wang, B. Villa-Marcos, J. Xiao, J. Am. Chem. Soc.
2008, 130, 14450–14451.
[13] T. Iwai, T. Ito, T. Mizuno, Y. Ishino, Tetrahedron Lett. 2004,
45, 1083–1086.
[14] C. Li, J. Xiao, J. Am. Chem. Soc. 2008, 130, 13208–13209.
[15] F. Werner, N. Blank, T. Opatz, Eur. J. Org. Chem. 2007, 3911–
3915.
Supporting Information (see also the footnote on the first page of
Received: November 24, 2009
Published Online: February 19, 2010
1
this article): H NMR and 13C NMR spectra for new compounds.
1942
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Eur. J. Org. Chem. 2010, 1934–1942