Photoreduction of imines. An environmentally friendly approach to obtain amines

Article abstract of DOI:10.1016/j.tet.2005.09.047

The photoreduction of different imines to amines in alcoholic solvents is reported. The reduction involves a versatile and chemoselective methodology that is environmentally friendly in that it avoids the use of metal hydrides and other dangerous reducing agents.

Full text of DOI:10.1016/j.tet.2005.09.047

Tetrahedron 61 (2005) 11686–11691
Photoreduction of imines. An environmentally friendly approach
to obtain amines
*
´ ´
Marıa Ortega, Miguel A. Rodrıguez and Pedro J. Campos
´
´
´
Departamento de Quımica, Universidad de La Rioja, Grupo de Sıntesis Quımica de La Rioja, U.A.-C.S.I.C, E-26006 Logron˜o, Spain
Received 1 July 2005; revised 15 September 2005; accepted 15 September 2005
Available online 10 October 2005
Abstract—The photoreduction of different imines to amines in alcoholic solvents is reported. The reduction involves a versatile and
chemoselective methodology that is environmentally friendly in that it avoids the use of metal hydrides and other dangerous reducing agents.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
leads to symmetrical vicinal diamines 2 in good-to-excellent
yields. The reaction involves the formation of triplet
species’ that progress to give radical species’ through
hydrogen abstraction of the isopropyl alcohol.9a Interest-
ingly, we detected the presence of secondary amines 3 as
minor products (%5%) in this process, particularly in cases
where the formation of the imine radical was less effective.
This finding prompted us to modify the experimental
conditions with the goal of obtaining monoamines as the
major products of the photoreaction.
One of the current challenges that faces organic synthesis,
and chemistry in general, is the development of new and
cleaner processes that minimise or eliminate the use of
hazardous substances.1 However, a wide variety of reactions
that are not environmentally friendly are currently used in
the chemical industry. One of these reactions is the
reduction of imines—a useful method for the synthesis of
secondary amines2—which are important precursors of key
compounds in the pharmaceutical and agricultural indus-
tries.3 Furthermore, amines play a significant role as
pharmacophoric groups in biologically active substances.
In this sense, catalytic hydrogenation,4 metal hydrides5 and
dissolving metals6 are usually employed for this
transformation.
In this report, we present the photoreduction of a wide
variety of aldimines and ketimines to amines with the aim of
developing a new methodology that is compatible with the
principles of green chemistry.1 In this process the
combination of light and an alcoholic solvent is used as
the reducing system.
The photochemical behavior of compounds containing a
carbon–nitrogen double bond has been the focus of our
attention for almost a decade7 and, more specifically, we
have been concerned with the photoreduction of imines-a
topic that has not been extensively studied.8
2. Results and discussion
2.1. Photoreduction of aldimines to amines
We initially studied the conditions under which the
secondary amines could be obtained as the major products
in the photoreaction of aldimines. Our experience in this
type of process led us to believe that the control of radical
formation is essential to achieve the objective. In this sense,
we initially tested the effect of different features such as
aldimine concentration, iPrOH/acetone ratio and filter glass
on the reaction of aldimine 1a.
In this context, we have previously reported the sensitized
photoreductive coupling of aldimines 19 (Scheme 1), which
Scheme 1. Sensitized photocoupling of aldimines.
i
When a solution of 1a in a mixture of PrOH and acetone
was irradiated through Pyrex glass (i.e., sensitized con-
ditions) at different imine concentrations or with different
iPrOH/acetone ratios, amine 3a was detected by NMR
Keywords: Photoreduction; Imines; Monoamines; Stereoselectivity.
*
Corresponding author. Tel.:C34 941299650; fax: C34 941299621;
e-mail: pedro.campos@dq.unirioja.es
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.047

M. Ortega et al. / Tetrahedron 61 (2005) 11686–11691
Table 1. Modulation of the photoreduction of aldimine 1a Table 2. Photoreduction of aldimine 1a in the presence of Et3N
11687
Concentration 1aa Ratio 2a/3ab
Entry
Et3N (equiv)a
Ratio 2a/3ab
Yield 3a (%)c
Entry
Conditions
1
2
3
4
5
0
7
10
15
25
R5/95
16/84
10/90
15/85
15/85
32
41
48
62
55
1
2
3
4
5
6
iPrOH/acetone (7/3), Pyrex
iPrOH/acetone (7/3), Pyrex
iPrOH/acetone (9/1), Pyrex
iPrOH, Pyrex
3
R95/5
94/6
93/7
No reaction
55/45
1.5
1.5
1.5
1.5
0.7
iPrOH, Vycor
iPrOH, Vycor
%5/95
a Refer to initial imine 1a.
b Determined by 1H NMR analysis of the crude reaction mixture.
c Isolated yield after purification by column chromatography.
a 10K2 molar concentration.
1
b Determined by H NMR analysis of the crude reaction mixture.
photoreaction was increased. The best result was obtained
on using 15 equiv of Et3N with respect to the initial imine 1a
(see entry 4 in Table 2). Fortunately, under these modified
reaction conditions, the ratio 2a/3a was not significantly
modified. In these reactions it is Et3N, which is a tertiary
amine in excess, that mainly undergoes the photodegrada-
tion and this sacrificial effect leads to an increase in the yield
of the secondary amines 3.
spectroscopy but diamines 2a were the major products of
the reaction (see Table 1, entries 1–3). In any case, amine 3a
could not be isolated from the reaction mixture. Further-
more, the photoreaction through Pyrex glass did not proceed
in the absence of acetone and only the starting imine was
recovered (Table 1, entry 4).
We therefore, decided to analyse the effect of using a
different filter. When a Vycor glass filter was employed, the
presence of acetone as a sensitizer was not necessary since
1a absorbs above 260 nm and, as a result, the irradiation was
carried out successfully using only isopropyl alcohol. The
reaction was monitored under these conditions and a
substantial decrease in the 2a/3a ratio was observed (see
Table 1, entries 5 and 6), particularly when the imine
concentration was quite low. This observation demonstrates
that the reaction is concentration-dependent. In fact, as
shown in entry 6, the irradiation of a 7.5!10K3 M solution
of imine 1a in isopropyl alcohol for 2 h through Vycor glass
gave amine 3a almost exclusively (2a/3a ratio%5/95). The
yield of this reaction was 32% after purification by column
chromatography. However, prolonged reaction times
through Vycor gave large amounts of polymeric material,
which indicates that the amine formed may not be
photostable under the reaction conditions described above.
This photodegradation was also detected in the irradiation of
other aldimines tested in this study. This situation clearly
limits the utility of the photoreduction, because the yields
obtained using this approach were in the range 20–35% in
all cases.
Bearing in mind the effect of Et3N, we aimed at exploring
the scope and synthetic possibilities of monoamine
formation. Thus, we tested the reaction with a representative
set of aldimines with different R1 and R2 groups, imines
1b–1g, and we carried out the photoreduction of these
compounds using the conditions optimized for aldimine 1a
(see Table 3).
Table 3. Photoreduction of different aldimines in the presence of Et3N
Imine
R1
R2
Time (h)
Yield 3 (%)a
1a
1b
1c
1d
1e
1f
3-Py
3-Py
2-Py
4-Py
Ph
2-Naphthyl
2-Quinolyl
Cy
tBu
Cy
Cy
Cy
Cy
Cy
2
2
2
2
2
4
9
62
65
46
55
47b
50
1g
30c
a Isolated yield after purification by column chromatography.
b The aminoalcohol resulting from addition of the isopropyl radical was
isolated (23%).
It is well known that amines are involved in photoreduction
processes of different unsaturated compounds, such as
ketones, due to their lower ionization potential.10 In the
context of our photoreduction process, the degradation of
the desired monoamines 3 can be explained in terms of a
similar process, in which the amine reacts with aldimine 1
but mainly gives polymeric material and, consequently,
decreases the yield of the reaction. It would be expected that
the presence of a more reactive amine in the irradiation,
such as triethylamine (Et3N), would avoid the photo-
decomposition of the resulting secondary monoamines 3.
c The irradiation was carried out through Pyrex glass.
In general, the photoreduction gave the corresponding
amines 3 in moderate-to-good yields. As mentioned above,
the use of Et3N has a marked effect on the yield of the
photoreaction but hardly alters the diamine/monoamine
ratio. However, some points concerning these reactions
should be noted. On the one hand, the irradiation of
benzaldimine 1e yielded both the desired monoamine and
the aminoalcohol resulting from addition of the isopropyl
radical, which is generated by hydrogen abstraction of the
alcoholic solvent. On the other hand, the irradiation of
aldimine 1g warrants particular attention since it was
possible in this case to carry out the irradiation through
Pyrex glass. This finding shows that the UV–vis absorption
In fact, the use of an excess of Et3N in the irradiations led to
a considerable improvement in the yield of the desired
monoamine 3a. As can be seen in Table 2, the yield of
monoamine 3a became higher as the amount of Et3N in the

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M. Ortega et al. / Tetrahedron 61 (2005) 11686–11691
Table 4. Photoreduction of ketimines
Imine
R1
R2
R3
Time (h)
Yield 3 (%)a
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
Ph
2-Naphthyl
CH3
CH3
CH3
Ph
Ph
Ph
Ph
Ph
CO2Et
CO2Et
Cy
Cy
Cy
H
Cy
c-Pr
CH2CN
CH2CO2Et
Cy
3
7
23b
52b
58
80
62
2-Py
Ph
Ph
Ph
Ph
Ph
Ph
Ph
11
9
12
10
6
13
5
5.5
75
70
61
60c
48c
(R)-CH(CH)3Ph
1r
1s
2
15b
14
51
a Isolated yield after purification by column chromatography.
b The irradiation was carried out through Vycor glass in the presence of Et3N.
c The irradiation was carried out through Vycor glass and ethanol was used as the alcoholic solvent.
characteristics of the materials depend on the nature of the
substituents on the imine. It is well known that the active
band in the photoreduction is an n/p* electronic transition
(lz250–285 nm),8b which can experience a bathochromic
shift-particularly when R1 (aryl group) includes a hetero-
atom or is a group that provides conjugation to the system.
Interestingly, it was observed that the photochemical
reduction of different cyclic imines proceeded successfully.
Some of the most significant results are gathered in Table 4.
As can be seen in this table, the irradiation of imines 1r and
1s under general conditions11 gave the expected amines in
moderate yields. Cyclic derivatives of indolenine (such as
1r) have previously been reported as being unreactive
toward hydrogen atom abstraction.12
2.2. Photoreduction of ketimines and cyclic imines to
amines
As far as the chemoselectivity of the photoreaction is
concerned, it should be noted that photoreduction of
bifuncional imines, such as ketimine 1n and imino esters
1o–1q, was carried out in a chemoselective way and gave
only the desired amines. Moreover, in the case of imino
esters 1p–1q, we employed Vycor-filtered light since these
compounds did not absorb above 290 nm. In addition, it was
observed that the resulting amino esters are more stable to
the photodegradation than monoamines and, as a conse-
quence, it was not necessary to use Et3N. Other byproducts,
such as diamines or aminoalcohols, could not be detected.
Moreover, the reaction rate increased markedly when
ethanol was used as the solvent.
The next step in our study involved exploring the generality
and versatility of the photoreduction. In order to achieve this
goal we extended this investigation to other imines. As
detailed in Table 4, a number of representative ketimines
and cyclic imines were irradiated through Pyrex or Vycor
glass, depending on the absorption spectrum of the
compound in question. The desired monoamines 3 were
obtained in moderate-to-good yields.
It is worth noting that the larger substituents in the imine
group made the coupling reaction more difficult. As a result,
formation of the monoamine is favourable and the
photoreduction does not depend on imine concentration-as
it did in the case of aldimines. Moreover, ultraviolet
irradiation through Pyrex glass (which filters out radiation
below 290 nm) of ketimines 1j–1o and 1s also gave the
monoamines in good yields and without decomposition. As
example, irradiation of imine 1k through Vycor glass
mainly gave polymeric material; the corresponding amine
3k was detected but could not be isolated. However,
irradiation through Pyrex led to monoamine 3k in excellent
yield. In this case, lower energy radiation is involved and
clearly the reaction times required are longer. In contrast,
ketimines 1h and 1i did not react when Pyrex-filtered light
was used and these irradiations were carried out as
described previously for aldimines, using Vycor glass and
in the presence of Et3N.
Finally, it is worth noting that the photoreduction of chiral
imino ester 1q (Scheme 2) was carried out with moderate/
high diastereoselectivity [(R,S)/(S,S) ratioZ4:1]. The two
diastereomers 3q could be easily separated by simple
column chromatography. As shown in Scheme 2, the
Scheme 2. Stereoselectivity in the photoreduction of ketimines.

M. Ortega et al. / Tetrahedron 61 (2005) 11686–11691
11689
diastereoselectivity of the reaction depends on the
irradiation temperature and the best diastereomeric excess
(72%) was obtained at K20 8C.
condensation of benzophenone imine with the correspond-
ing primary amine in dry toluene at 80 8C. Imino esters 1p
and 1q were prepared by condensation of ethyl benzoyl-
formate with the corresponding amine (1.1 equiv) in toluene
at 100 8C catalyzed by AlCl3. Cyclic imine 1s was obtained
by an N-cyclopropylimine-1-pyrroline rearrangement.7
Imines 1k, 1n, 1o and 1r are commercially available
The absolute configuration of the amino ester (R,R)-3q was
determined by reduction with LiAlH4 and comparison of the
resulting aminoalcohol with data reported in the literature.13
Interestingly, the amino esters 3q can be transformed into
the corresponding a-amino acids,14 providing an alternative
method to that described in the literature15 to obtain this
type of molecule.
4.3. General procedure for irradiation of imines 1a–s
Argon was bubbled through a solution of the corresponding
imine 1 (0.75 mmol for 1a–g and 1s, and 1.5 mmol for
1h–r) in an alcoholic solvent (100 mL) and the solution was
irradiated through Vycor or Pyrex glass (depending on the
absorption spectra, see Tables 3 and 4) at room temperature
using a medium-pressure mercury lamp (450 W) until
complete consumption of starting material was observed
(monitored by 1H NMR spectroscopy and GC–MS
chromatography). The alcoholic solvent was distilled off
and the residue was purified by ion exchange column
chromatography (Amberlite CG-50 I, NH3/MeOH 0.28 M)-
except amino esters 3p–q, which were purified by silica
column chromatography (hexane/AcOEt 9:1).
3. Conclusions
From the results described above, we conclude that the
photoreduction of different imines bearing a hydrogen atom,
alkyl or aryl groups leads to the corresponding amines
through a new and versatile approach that is compatible
with the environment. Moreover, we have modulated, for
the first time, the photoreduction of aldimines to obtain
secondary amines as reaction products instead of vicinal
diamines. The use of Et3N delays the decomposition of
monoamines and improves the synthetic utility of this
process.
4.4. Irradiation of imines in presence of triethylamine
We have also demonstrated that cyclic imines are reactive
toward hydrogen atom abstraction. Moreover, the
irradiation of a variety of bifunctional imines has
demonstrated that photoreduction of the carbon–nitrogen
double bond is chemoselective in the presence of other
functional groups such as ester and cyano groups. Finally,
the reduction of chiral imino esters led to enantiopure amino
esters that can be easily converted into the corresponding
a-amino acids, thus providing a new method for the
synthesis of this kind of compound. Finally, studies to
elucidate the mechanism and to extend the scope of this
reaction are in progress.
Et3N (1.5 mL, 10 mmol) was added to a solution of the
corresponding imine 1 (0.75 mmol) in isopropyl alcohol
(20 mL). Isopropyl alcohol was added to give a total volume
of 100 mL and argon was bubbled through the solution. The
reaction mixture was irradiated through Vycor at room
temperature using a medium-pressure mercury lamp
(450 W) until 90% conversion of starting material was
observed (monitored by 1H NMR spectroscopy and GC–MS
chromatography). The isopropyl alcohol was distilled off
and the residue was purified by ion exchange column
chromatography (Amberlite CG-50 I, NH3/MeOH 0.28 M).
4.5. Characterization data of isolated monoamines 3
4. Experimental
1
4.5.1. N-[(3-pyridinyl)methyl]cyclohexanamine (3a). H
NMR (CDCl3): d 1.10–1.93 (m, 11H), 2.48 (m, 1H), 3.83 (s,
2H), 7.23–7.27 (m, 1H), 7.67–7.69 (m, 1H), 8.49–8.50 (m,
1H), 8.56 (m, 1H). 13C NMR (CDCl3): d 25.1, 26.2, 33.8,
48.4, 56.4, 123.4, 135.8, 136.4, 148.4, 149.8. GC–MS: 190,
147, 92. MS-ES(C): 191.2 (MC1). Anal. Calcd for
C12H18N2: C, 75.74; H, 9.53; N, 14.72. Found: C, 75.1; H,
9.85; N, 15.05.
4.1. General aspects
1H and 13C NMR spectra were recorded on a Bruker ARX-
300 spectrometer in CDCl3 with TMS as internal standard.
Electrospray mass spectra were obtained on an HP 5989 B
apparatus with an HP 59987A interface, in positive-ion
mode with methanol–water–acetic acid (60/35/5) as the
mobile phase. GC–MS spectra were recorded on an HP
G1800A apparatus. Elemental analyses were obtained using
a CE Instrument Model 1110. Optical rotations were
measured on a Perkin-Elmer 341 polarimeter in 1.0 dm
cells of 1.0 and 0.35 mL capacity. All solvents were purified
by standard procedures and freshly distilled prior to use.
Reagents were of commercial grade (Aldrich).
4.5.2. N-[(3-pyridinyl)methyl]tert-butanamine (3b). 1H
NMR (CDCl3): d 1.19 (s, 9H), 1.53 (br s, 1H), 3.75 (s, 2H),
7.22–7.28 (m, 1H), 7.70–7.73 (m, 1H), 8.48 (m, 1H), 8.5 (m,
1H). 13C NMR (CDCl3): d 29.2, 44.7, 51.1, 123.5, 136.1,
148.4, 149.9. GC–MS: 163, 149, 92. MS-ES(C): 164.2
(MC1). Anal. Calcd for C10H16N2: C, 73.13; H, 9.82; N,
17.06. Found: C, 73.55; H, 9.75; N, 16.70.
4.2. General procedure for synthesis of imines 1a–s
1
4.5.3. N-[(2-pyridinyl)methyl]cyclohexanamine (3c). H
Imines 1a–j were prepared by condensation of different
carboxaldehydes with the corresponding primary amine in
chloroform or toluene under reflux according to literature
procedures.16 Imines 1l and 1m were prepared by
NMR (CDCl3): d 1.10–1.97 (m, 11H), 2.50 (m, 1H), 3.94 (s,
2H), 7.15 (m, 1H), 7.30 (m, 1H), 7.64 (m, 1H), 8.56 (m, 1H).
13C NMR (CDCl3): d 25.2, 26.3, 33.6, 52.5, 56.8, 122.0,
122.5, 136.6, 149.3, 160.2. GC–MS: 190, 147, 92. MS-

11690
M. Ortega et al. / Tetrahedron 61 (2005) 11686–11691
ES(C): 191.2 (MC1). Anal. Calcd for C12H18N2: C, 75.74;
H, 9.53; N, 14.72. Found: C, 75.61; H, 9.50; N, 14.73.
4.5.11. N-benzhydrylcyclohexanamine (3l). 1H NMR
(CDCl3): d 1.06–1.94 (m, 11H), 2.36–2.42 (m, 1H), 5.03
(s, 1H), 7.16–7.39 (m, 10H). 13C NMR (CDCl3): d 25.2,
26.4, 34.1, 54.1, 63.8, 126.9, 127.5, 128.5, 144.9. GC–MS:
265, 188, 167. MS-ES(C): 266.2 (MC1). Anal. Calcd for
C19H23N: C, 85.99; H, 8.74; N, 5.28. Found: C, 84.20; H,
8.70; N, 5.31.
1
4.5.4. N-[(2-pyridinyl)methyl]cyclohexanamine (3d). H
NMR (CDCl3): d 1.02–1.93 (m, 11H), 2.46 (m, 1H), 3.84 (s,
2H), 7.27 (m, 2H), 8.54 (m, 2H). 13C NMR (CDCl3): d 25.1,
26.3, 33.7, 49.9, 56.4, 123.1, 150.0. GC–MS: 190, 147, 92.
MS-ES(C): 191.2 (MC1). Anal. Calcd for C12H18N2: C,
75.74; H, 9.53; N, 14.72. Found: C, 75.64; H, 9.52; N, 14.70.
1
4.5.12. N-benzhydrylcyclopropanamine (3m). H NMR
(CDCl3): d 0.38 (d, JZ5.1 Hz, 4H), 1.98 (br s, 1H), 2.07 (m,
1H), 4.91 (s, 1H), 7.12–7.36 (m, 10 H). 13C NMR (CDCl3):
d 6.8, 29.7, 67.3, 127.0, 127.5, 128.5, 144.3. GC–MS: 223,
222, 167, 152. MS-ES(C): 224.3 (MC1). Anal. Calcd for
C16H17N: C, 86.05; H, 7.67; N, 6.27. Found: C, 85.88; H,
7.72; N, 6.40.
1
4.5.5. N-benzylcyclohexanamine (3e). H NMR (CDCl3):
d 1.15–1.96 (m, 11H), 2.48–2.60 (m, 1H), 3.84 (s, 2H),
7.25–7.37 (m, 5H). 13C NMR (CDCl3): d 25.0, 26.0, 33.0,
50.6, 56.1, 127.1, 128.6, 139.6. GC-MS: 189, 146, 91. MS-
ES(C): 190.4 (MC1). Anal. Calcd for C13H19N: C, 82.48;
H, 10.12; N, 7.40. Found: C, 82.02; H, 10.09; N, 7.36.
1
4.5.13. 2-(Benzhydrylamino)acetonitrile (3n). H NMR
4.5.6. N-[(2-naphthyl)methyl]cyclohexanamine (3f). 1H
NMR (CDCl3): d 0.91–1.98 (m, 11H), 2.49–2.55 (m, 1H),
3.98 (s, 2H), 7.41–7.53 (m, 3H), 7.70–7.82 (m, 4H). 13C
NMR (CDCl3): d 25.2, 26.3, 33.8, 51.3, 56.3, 125.6, 126.1,
126.4, 126.7, 127.7, 127.8, 128.1, 132.7, 133.6, 138.7. GC–
MS: 239, 196, 141, 115, 98. MS-ES(C): 240.3 (MC1).
Anal. Calcd for C17H21N: C, 85.30; H, 8.84; N, 5.85. Found:
C, 84.98; H, 8.81; N, 5.83.
(CDCl3): d 1.95 (br s, 1H), 3.50 (s, 2H), 5.06 (s, 1H), 7.21–
7.44 (m, 10H). 13C NMR (CDCl3): d 35.4, 65.8, 117.7,
127.4, 127.8, 128.9, 141.9. GC–MS: 222, 167, 145, 104, 67.
MS-ES(C): 223.4 (MC1). Anal. Calcd for C15H14N2: C,
81.05; H, 6.35; N, 12.60. Found: C, 81.36; H, 6.52; N, 12.12.
4.5.14. 2-(Benzhydrylamino)acetic acid ethyl ester (3o).
1H NMR (CDCl3): d 1.24 (t, JZ7.2 Hz, 3H), 2.22 (m, 1H),
3.37 (s, 2H), 4.17 (q, JZ7.2 Hz, 2H), 4.88 (s, 1H), 7.18–
7.47 (m, 10H). 13C NMR (CDCl3): d 14.3, 49.2, 60.8, 66.7,
127.3, 127.5, 128.6, 143.4, 172.6. GC–MS: 182, 167, 118,
91. MS-ES(C): 270.2 (MC1). Anal. Calcd for C17H19NO2:
C, 75.81; H. 7.11; N, 5.20; O, 11.88. Found: C, 75.51; H,
7.33; N, 5.02.
4.5.7. N-[(2-quinolinyl)methyl]cyclohexanamine (3g). 1H
NMR (CDCl3): d 1.24–2.02 (m, 11H), 2.61 (m, 1H), 4.17 (s,
2H), 7.44–8.18 (m, 6H). 13C NMR (CDCl3): d 25.1, 26.2,
33.4, 52.8, 57.1, 120.7, 126.2, 127.5, 127.7, 129.1, 129.6,
136.6, 147.8, 160.2. GC–MS: 238, 195, 182, 157, 129, 77,
55. MS-ES(C): 241.3 (MC1). Anal. Calcd for C16H20N2:
C, 79.96; H, 8.39; N, 11.66. Found: C, 80.15; H, 8.39; N,
11.46.
4.5.15. 2-Cyclohexylamino-2-phenyl acetic acid ethyl
ester (3p). 1H NMR (CDCl3): d 1.08–1.84 (m, 13H),
2.03–2.04 (br s, 1H), 2.33–2.37 (m, 1H), 4.08–4.22 (m, 2H),
4.51 (s, 1H), 7.26–7.39 (m, 5H). 13C NMR (CDCl3): d 14.2,
25.0, 26.2, 33.4, 33.6, 54.6, 61.2, 62.5, 127.4, 128.0, 128.8,
138.9, 173.8. GC–MS: 260, 188, 106, 79. MS-ES(C): 262.1
(MC1). Anal. Calcd for C16H23NO2: C, 73.53; H, 8.87; N,
5.36; O, 12.24. Found: C, 73.23; H, 8.69; N, 5.47.
1
4.5.8. N-(1-phenylethyl)cyclohexanamine (3h). H NMR
(CDCl3): d 1.33 (d, JZ7.0 Hz, 3H), 1.01–1.72 (m, 11H),
2.26 (m, 1H), 3.96 (q, JZ7.0 Hz, 1H), 7.16–7.34 (m, 5H).
13C NMR (CDCl3): d 14.2, 25.1, 25.4, 26.3, 33.3, 34.6, 53.8,
54.6, 126.5, 128.5, 146.4. GC–MS: 203, 188, 160, 105, 77,
56. MS-ES(C): 204.3 (MC1). Anal. Calcd for C14H21N: C,
82.70; H, 10.41; N, 6.89. Found: C, 82.34; H, 10.43; N, 6.87.
4.5.16. 2-Phenyl-(10-phenylethylamino)acetic acid ethyl
ester [(S,R)-3q and (R,R)-3q]. The two diastereomers 3q
were separated by simple column chromatography (silica
gel, hexane/AcOEt 9:1). Major product: (S,R)-3q. 1H NMR
(CDCl3): d 1.13 (t, JZ7.2 Hz, 3H), 1.34 (d, JZ6.6 Hz, 3H),
2.30–2.50 (br s, 1H), 3.56 (q, JZ6.6 Hz, 1H), 4.00–4.13 (m,
2H), 4.17 (s, 1H), 7.22–7.38 (m, 10H). 13C NMR (CDCl3): d
14.1, 24.5, 54.8, 61.2, 62.8, 127.1, 127.3, 127.8, 128.1,
128.6, 128.7, 138.6, 144.8, 173.0. [a]2D5 (c 0.50, MeOH)
C130.6. GC–MS: 283, 210, 105, 79. MS-ES(C): 284.3
(MC1). Anal. Calcd for C19H23NO2: C, 76.73; H, 7.80; N,
4.71; O, 10.76. Found: C, 76.13; H, 7.96; N, 4.60. Minor
product: (R,R)-3q. 1H NMR (CDCl3): d 1.22 (t, JZ7.2 Hz,
3H), 1.39 (d, JZ6.6 Hz, 3H), 2.25–2.40 (br s, 1H), 3.56 (q,
JZ6.6 Hz, 1H), 4.11–4.26 (m, 3H), 7.23–7.35 (m, 10H).
13C NMR (CDCl3): d 14.3, 24.9, 56.7, 61.2, 63.1, 127.1,
127.2, 127.3, 128.0, 128.6, 128.7, 128.8, 138.7, 145.0,
173.9. [a]2D5 (c 0.49, MeOH) ZK19.5. GC–MS: 283, 210,
105, 79. MS-ES(C): 284.3 (MC1). Anal. Calcd for
C19H23NO2: C, 76.73; H, 7.80; N, 4.71; O, 10.76. Found:
C, 76.24; H, 8.06; N, 4.52.
1
4.5.9. N-[1-(20-naphthyl)ethyl]cyclohexanamine (3i). H
NMR (CDCl3): d 1.01–1.12 (m, 5H), 1.40 (d, JZ6.6 Hz,
3H), 1.53–1.72 (m, 5H), 2.03 (m, 1H), 2.30 (m, 1H), 4.13 (q,
JZ6.6 Hz, 1H), 7.41–7.47 (m, 3H), 7.71 (s, 1H), 7.74–7.83
(m, 3H). 13C NMR (CDCl3): d 25.2, 26.3, 33.4, 34.8, 53.9,
54.8, 125.0, 125.2, 125.5, 126.0, 127.8, 127.9, 128.3, 132.9,
133.6, 144.0. GC–MS: 254, 238, 155, 98, 56, 41. MS-ES(C
): 254.4 (MC1). Anal. Calcd for C18H23N: C, 85.32; H,
9.15; N, 5.53. Found: C, 84.92; H, 9.11; N, 5.50.
4.5.10. N-[1-(20-pyridinyl)ethyl]cyclohexanamine (3j). 1H
NMR (CDCl3): d 1.02–1.98 (m, 11H), 1.36 (d, JZ6.6 Hz,
3H), 2.23 (m, 1H), 4.03 (q, JZ6.6 Hz, 1H), 7.12–7.16 (m,
1H), 7.27–7.31 (m, 1H), 7.61–7.66 (m, 1H), 8.54–8.57 (m,
1H). 13C NMR (CDCl3): d 23.6, 25.1, 25.3, 26.3, 33.4, 34.5,
54.3, 55.9, 121.3, 121.9, 136.5, 149.4, 165.5. GC–MS: 203,
189, 161, 107, 97. MS-ES(C): 205.3 (MC1). Anal. Calcd
for C13H20N2: C, 76.42; H, 9.87; N, 13.71. Found: C, 76.81;
H, 9.68; N, 13.51.

M. Ortega et al. / Tetrahedron 61 (2005) 11686–11691
11691
4.5.17. 2,3,3-Trimethyl-2,3-dihydro-1H-indole (3r). 1H
NMR (CDCl3): d 1.04 (s, 3H), 1.18 (d, JZ6.6 Hz, 3H), 1.28
(s, 3H), 3.52 (q, JZ6.6 Hz, 1H), 3.76–3.79 (br s, 1H), 6.61–
6.64 (m, 1H), 6.72–6.77 (m, 1H), 6.99–7.04 (m, 1H), 7.26
(s, 1H). 13C NMR (CDCl3): d 15.3, 22.5, 26.3, 43.5, 65.3,
109.5, 119.0, 122.4, 127.3, 139.3, 149.4. GC–MS: 161, 146,
131, 77. MS-ES(C): 162.3 (MC1). Anal. Calcd for
C11H15N: C, 81.94; H, 9.38; N, 8.69. Found: C, 82.32; H,
9.19; N, 8.49.
686. (b) Anastas, P. T.; Warner, J. C. Green Chemistry: Theory
and Practice; Oxford University Press: Oxford, 1998.
2. Marson, C. M.; Hobson, A. D. In Katritzky, A. R., Meth-Cohn,
O., Rees, C. W., Eds.; Comprehensive Organic Functional
Group Transformations; Pergamon: Oxford, 1995; Vol. 2;
Chapter 2.05.
3. Salvatore, R. N.; Yoon, C. H.; Jung, K. W. Tetrahedron 2001,
57, 7785.
´
4. Hudlicky, M. Reductions in Organic Synthesis; In ACS
Monograph; Washington: DC, 1996.
4.5.18. 2,2,3-Triphenylpyrrolidine (3s). 1H NMR
(CDCl3): d 2.18–2.34 (m, 2H), 3.08–3.12 (m, 1H), 3.36–
3.41 (m, 1H), 3.25 (br s, 1H), 4.12–4.17 (m, 1H), 6.90–7.08
(m, 10H), 7.22–7.35 (m, 3H), 7.54–7.57 (m, 2H). 13C NMR
(CDCl3): d 33.2, 44.0, 52.9, 75.3, 126.0, 126.8, 127.2, 127.9,
128.2, 128.4, 129.4, 142.6, 144.5, 147.6. GC–MS: 299, 194,
135, 116, 91, 77. MS-ES(C): 300.4 (MC1). Anal. Calcd for
C22H21N: C, 88.25; H, 7.07; N, 4.68. Found: C, 88.61; H,
6.89; N, 4.50.
5. Abdel-Magid, A. F. Reductions in Organic Synthesis: Recent
Advances and Practical Applications; In ACS Symposium;
Washington: DC, 1996; Chapters 11 and 12.
6. Huffman, J. W. In Trost, B. M., Fleming, I., Eds.;
Comprehensive Organic Synthesis; Pergamon: Oxford, 1991;
Vol. 8; Chapter 1.4.
´
7. (a) Sampedro, D.; Soldevilla, A.; Rodrıguez, M. A.; Campos,
P. J.; Olivucci, M. J. Am. Chem. Soc. 2005, 127, 441. (b)
´
Campos, P. J.; Soldevilla, A.; Sampedro, D.; Rodrıguez, M. A.
Org. Lett. 2001, 3, 4087. (c) Campos, P. J.; Caro, M.;
´
Rodrıguez, M. A. Tetrahedron Lett. 2001, 42, 3575. (d)
4.6. Reduction of amino esters 3q
´ ´
Campos, P. J.; An˜on, E.; Malo, M. C.; Rodrıguez, M. A.
´
Tetrahedron 1999, 55, 14079. (e) Campos, P. J.; An˜on, E.;
A solution of pure amino ester (S,R)-3q or (R,R)-3q (50 mg,
0.18 mmol) in dry THF (5 mL) was added to a solution of
LiAlH4 (40 mg, 1.05 mmoles) in dry THF (10 mL) at 0 8C
under argon. The mixture was stirred at room temperature
until complete formation of the corresponding aminoalcohol
was observed by TLC. The reaction mixture was decom-
posed by the careful dropwise addition of water (2 mL) and
the product extracted with ethyl acetate (3!15 mL). The
combined organic layers were dried (Na2SO4), concentrated
and purified by column chromatography (hexane/AcOEt
1:1) to give the corresponding aminoalcohol in 84% yield
(38 mg, 0.15 mmol).
´
Malo, M. C.; Rodrıguez, M. A. Tetrahedron 1998, 54, 14113.
´ ´
(f) Campos, P. J.; An˜on, E.; Malo, M. C.; Rodrıguez, M. A.
Tetrahedron 1998, 54, 6929. (g) Campos, P. J.; Tan, C.-Q.;
´
´
An˜on, E.; Rodrıguez, M. A. J. Org. Chem. 1996, 61, 7195.
8. (a) Gilbert, A.; Baggott, J. Essentials of Molecular Photo-
chemistry; Blackwell Scientific: Oxford, 1991; Chapter 9.2.
(b) Mariano, P. S. In Padwa, A., Ed.; Organic Photochemistry;
Marcel Dekker: New York, 1987; Vol. 9.
´
9. (a) Ortega, M.; Rodrıguez, M. A.; Campos, P. J. Tetrahedron
´
2004, 60, 6475. (b) Campos, P. J.; Arranz, J.; Rodrıguez, M. A.
Tetrahedron 2000, 56, 7285.
10. (a) Cohen, S. G.; Parola, A.; Parsons, G. H., Jr. Chem. Rev.
1973, 73, 141. (b) See Ref. 8a, p 307.
Acknowledgements
11. For more details see Section 4.
´
We thank the Ministerio de Ciencia y Tecnologıa (project
CTQ2004-3134), the Comunidad Autonoma de La Rioja
(project ACPI2003/08) and the Universidad de La Rioja
12. Ohta, H.; Tokumura, K. Tetrahedron Lett. 1974, 2965.
13. Higashiyama, K.; Inoue, H.; Yamauchi, T.; Takahashi, H.
J. Chem. Soc., Perkin Trans. 1 1995, 111.
´
´
(project API-04/06). M. O. thanks the Comunidad Auto-
noma de La Rioja for her fellowship.
14. Alvaro, G.; Savoia, D.; Valentinetti, M. R. Tetrahedron 1996,
52, 12571.
15. (a) Calmes, M.; Daunis, J. Amino Acids 1999, 16, 215.
´
(b) Cativiela, C.; Dıaz-de-Villegas, M. D. Tetrahedron:
Asymmetry 1998, 9, 3517. (c) Williams, R. M. Synthesis of
Optically Active a-Amino Acids; Pergamon: Oxford, 1989.
16. Hatano, B.; Ogawa, A.; Hirao, T. J. Org. Chem. 1998, 63,
9421.
References and notes
1. (a) Anastas, P. T.; Kirchhoff, M. M. Acc. Chem. Res. 2002, 35,