Convenient route to primary (Z)-allyl amines and homologs

Article abstract of DOI:10.1080/00397910802369596

A convenient two-step procedure for the synthesis of primary (Z)-allyl amines, (Z)-homoallyl amines [(Z)-but-3-enylamines], and (Z)-pent-4-enylamines using the Wittig reaction was achieved. The use of nonstabilized ylides from triphenylphosphonium salt, potassium salt, and apolar solvent produced (Z/E)-geometric isomer ratios generally greater than 1.6. The amine moiety was masked using a phtalimide group that was removed successfully in the last step of the process in two different conditions, NH2NH2/EtOH/rt or CH3NH2/EtOH/rt. However, in some cases, reduction of the C = C double bond in the deprotection with hydrazine was concomitantly observed. Copyright Taylor & Francis Group, LLC.

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Convenient Route to Primary
(Z)-Allyl Amines and Homologs
Alejandra Gerpe a , Mariela Bollini b , Mercedes
González a & Hugo Cerecetto a
a Laboratorio de Química Orgánica, Facultad de
Química/Facultad de Ciencias, Universidad de la
República, Montevideo, Uruguay
b Cátedra de Química Orgánica, Facultad de
Farmacia y Bioquímica, Universidad de Buenos Aires,
Buenos Aires, Argentina
Published online: 15 Feb 2011.
To cite this article: Alejandra Gerpe , Mariela Bollini , Mercedes Gonzlez & Hugo
Cerecetto (2008) Convenient Route to Primary (Z)-Allyl Amines and Homologs,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 39:1, 29-47, DOI: 10.1080/00397910802369596
To link to this article: http://dx.doi.org/10.1080/00397910802369596
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Synthetic Communications1, 39: 29–47, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802369596
Convenient Route to Primary (Z)-Allyl Amines
and Homologs
1
Alejandra Gerpe, Mariela Bollini, Mercedes Gonzalez,
2
1
ꢀ
and Hugo Cerecetto1
1
ꢀ
´
´
Laboratorio de Quımica Organica, Facultad de Quımica=Facultad de
Ciencias, Universidad de la Repu´blica, Montevideo, Uruguay
2
ꢀ
Catedra de Quımica Organica, Facultad de Farmacia y Bioquımica,
ꢀ
´
Universidad de Buenos Aires, Buenos Aires, Argentina
´
Abstract: A convenient two-step procedure for the synthesis of primary (Z)-allyl
amines, (Z)-homoallyl amines [(Z)-but-3-enylamines], and (Z)-pent-4-enylamines
using the Wittig reaction was achieved. The use of nonstabilized ylides from
triphenylphosphonium salt, potassium salt, and apolar solvent produced (Z=E)-
geometric isomer ratios generally greater than 1.6. The amine moiety was masked
using a phtalimide group that was removed successfully in the last step of the
process in two different conditions, NH2NH2=EtOH=rt or CH3NH2=EtOH=rt.
However, in some cases, reduction of the C ¼ C double bond in the deprotection
with hydrazine was concomitantly observed.
Keywords: (Z)-Allyl amine, (Z)-homoallyl amine, (Z)-pent-4-enylamine
INTRODUCTION
The preparation of primary allyl amines and homologs has been an area
of considerable interest primarily because of their key position as
synthetic intermediates as well as their presence in various bioactive
compounds.[1,2] The synthon allyl amine has been used in different
Received April 27, 2008.
Address correspondence to Mercedes Gonzalez and Hugo Cerecetto
ꢀ
´
ꢀ
´
Laboratorio de Quımica Organica, Facultad de Quımica=Facultad de Ciencias,
ꢀ
Universidad de la Repu´blica, Igua 4225, 11400, Montevideo, Uruguay.
E-mail: megonzal@fq.edu.uy; hcerecet@fq.edu.uy
29

30
A. Gerpe et al.
synthetic procedures as the main structural block for specific transforma-
tions (i.e., heterocycle synthesis via ring-closing metathesis, synthesis of
b-hydroxy-a-amino acids, or synthesis of oxa-bridged tricycle).[3] Our
efforts in the search for new drugs with antichagasic activity[4] have led
us to develop compounds containing these kinds of moieties, specifically
phenylallylamino (3-phenylprop-2-enylamino), phenylhomoallylamino
(4-phenylbut-3-enylamino), and 5-phenylpent-4-enylamino (Fig. 1).[5]
For this reason, we required a facile and an effective synthetic route to
prepare both geometric isomers of primary allyl amines and its homologs.
There are different methods for the preparation of allyl amines N,N-
disubstituted.[6] Diverse synthetic procedures for the preparation of pri-
mary (E)-allyl amines have been described,[7] where one of the most
widely applicable procedures is the formation of the C ¼ C bond by
Wittig-type reactions.[8] Moreover, Meyers et al.[9] described the synthesis
of primary (E)-allyl amines by Schweizer-type reaction, through the reac-
tion between trialkyl vinylphosphonium salt, sodium phthalimide, and
aldehydes. They used the phthalimide moiety as a protector group of
the final primary amine; the deprotection reaction was achieved either
with hydrazine or sodium sulfide treatment. Additionally, De Castro
Dartas et al.[8c] and Olsen et al.[10] described the synthesis of alkenyla-
mines using the Wittig reaction, in which the amine function is located
at different distances from the insaturation, in this way generating homo-
allyl amines. Also, using a Mitsunobu reaction between some allyl alco-
hols and a nucleophiles, like azide or phtalimide, in the presence of the
diethyl azodicarboxylate=triphenylphospine has been described.[11]
Methodologies that yield C ¼ C (E)-geometric isomers as main pro-
ducts were the majority of the reported procedures, so we looked for a
simple methodology that allowed us to prepare the counterpart (Z)-iso-
mers. In this work, we describe an easy synthetic procedure to obtain
mainly (Z)-allyl amines and homologs, applying a combination of the
Wittig reaction and the Gabriel synthesis to yield the desired products
Figure 1. Designed phenylalkenylamino containing anti-chagasic compounds. R1
or R2 ¼ heterocycles with anti-chagasic properties (5-nitrofurane, 5-nitroindazole,
quinoxaline dioxide, benzimidazole dioxide, furoxane); n ¼ 1, 2, and 3; R3 ¼
variable substitution.

Route to Primary (Z)-Allyl Amines
31
Figure 2. General synthetic procedure used to prepare (Z)-allyl amines and
homologs.
in moderate to good yields (Fig 2). We studied the use of different
deprotecting reagents, finding that methylamine allowed us to easily
generate the desired amines in adequate yield, without changes in the
stereochemistry and without secondary reactions. However, the
previously described hydrazine hydrate[9] in our hands yielded significant
amount of the double-bond reduced product.
RESULTS AND DISCUSSION
According to results of Meyers et al.,[9] we first planned the preparation
of triphenylphosphonium salts containing phthalimide with an adequate
linker between nitrogen and phosphorus atoms, bridges of two, three, or
four carbon atoms. This kind of phosphonium salt gave preferentiality
the (Z)-geometric isomer. Consequently, the syntheses of triphenylphos-
phonium salts were assayed via nucleophilic substitution between
haloalkylphthalimides, 1a–d, and triphenylphosphine (Scheme 1).
Derivatives 1a–b were synthesized as shown in Scheme 1 using as
starting material N-(2-hydroxyethyl)phthalimide.[12] We studied the
direct preparation of phosphonium acetate in a one-pot procedure from
N-(2-hydroxyethyl)phthalimide,[13] but this methodology was only ade-
quate for benzylic alcohol substituted by an electron-donor group that
Scheme 1. Synthesis of the phosphonium salt intermediates.

32
A. Gerpe et al.
stabilizes the attack of triphenylphosphine on the electrophile benzylic
carbon. Therefore, the preparation of the halides 1a and 1b was neces-
sary. Chloride 1a and iodide 1b[14] were obtained in good yield, whereas
the reaction with HBr, performed to obtain the corresponding bromine
analog, led to partial deprotection of the amine group. Bromides 1c–d
(Scheme 1) are commercially available, and they were used directly from
commercial sources. The salts 2b and c were obtained in good yield;
nevertheless, nucleophilic substitution of derivative 1a did not produce
the desired salt in any of the assayed conditions.
Second, we planned the C ¼ C formation in (Z)-stereoselective condi-
tions. Accordingly, the olefination reaction was performed with substi-
tuted benzaldehydes applying Boden’s[15] modification of the Wittig
reaction (potassium base and 18-crown-6 as the ylide-forming reagents)
as shown in Scheme 2.
In these conditions, no stabilized ylides were generated. No stabilized
ylides reacted with aldehydes, under classical Wittig conditions, ‘‘salt-
free’’ medium, or nonlithium bases, to afford (Z)-geometric isomer with
high stereoselectivity,[16] whereas the use of lithium salts increases the E
selectivity[9] and the stereoselectivity of the reaction is independent of
the solvent polarity.[8c] Alternatively, for Boden’s conditions, some
reports have indicated that the solvent polarity affects the stereochemis-
try when no stabilized ylides were used.[17] High (Z)-selectivity was
accomplished by using nonpolar solvents, whereas the (E)-geometric iso-
mer was predominant in polar solvents. To confirm these previous
results, we studied the effect of solvent polarity and boiling temperature
in the stereochemistry and yield of the olefination to obtain derivative 3h.
The results showed that in polar solvent[18] (CH2Cl2, Table 1), some little
predominance of (E)-geometric isomer was observed with concomitant
very low yield. Nevertheless, when we used less polar solvents, like
THF or toluene, the (Z)-geometric isomer was predominant, obtaining
the best yield in reflux of toluene. When we used these reaction condi-
tions, in all the cases the prevalence of the (Z)-geometric isomers
was observed (Table 2). In the cases of benzaldehyde and p-nitrobenz-
aldehyde as carbonyl reactants, the best Z=E ratios were observed for
homoallyl amine-precursors synthesis, 3b and 3d, respectively, finding
Scheme 2. Syntheses of the primary (Z)-allyl amines and homologs.

Route to Primary (Z)-Allyl Amines
33
Table 1. Solvent properties and effects on derivative 3h preparation
Solvent
Bp (ꢀC)a
ENTb
Yield (%)c,d,e
Ratio Z=E f
CH2Cl2
THF
Toluene
40.0
66.0
110.6
41.1
37.4
33.9
24
36
70
0.8
6.7
6.7
aBp: boiling point at 760 mm Hg.
bENT: empirical parameter of solvent polarity (kcal molꢁ1).[18]
cThe yield was determined at the same reaction time, 12 h at reflux.
dIsolated products by chromatographic column.
eYield of the geometric isomers mixture.
1
fDetermined by H NMR.
poor stereoselectivity in the cases of homo allyl amine-precursors pre-
parations. Stereochemistry of derivatives 3 around C ¼ C was confirmed
using NMR spectroscopy (1H NMR, correlation spectroscopy–scalar J
coupling [COSY], 13C NMR, heteronuclear multiple quantum correla-
tion [HMQC], and heteronuclear multiple bond correlation [HMBC]).
Conversely, when we studied the olefination processes using semista-
bilized ylides, the opposite ratio of (Z=E)-stereoisomers were obtained,
proving the relevance of the ylide in the stereocourse of the reactions.
In this sense, when syntheses of derivatives 3a, 3d (Table 2), and 3i
(Scheme 3), using benzylidene ylides, were assayed, the contrary geo-
metric isomer ratio were evidenced. The desired allyl amine-precursors
were generated predominantly or exclusively as (E)-geometric isomers
(3a, Z:E ratio ¼ 34:66; 3d, Z:E ratio ¼ 39:61; 3i, Z:E ¼ 0:100). Figure 3
shows the spectroscopic findings, NOE-diff experiments, in the geometric
distribution study for derivative 3i. In these cases, the semistabilized
ylides (benzylidene ylides) and the experimental conditions (Boden’s
conditions in a nonpolar solvent) explain the preferential isomer distri-
butions.[17] No optimization of the yields was studied in this case.
Finally, for the cleavage of the allylic amide, we studied different
deprotecting reagents, HBr, NH2NH2H2O, and CH3NH2. The use of
HBr (48%) at reflux implied drastic reaction conditions that did not war-
rant the double bond integrity, and complete decomposition of the start-
ing material was observed in this situation. However, the treatment of

34
A. Gerpe et al.
Table 2. Synthesis of phthalimido derivatives 3 using no stabilized ylides
Ref.
-R
n
Reaction time (h) Yield (%)a,b Ratio Z=Ec
3a
3b
3c
3d
3e
3f
-Ph
-Ph
-Ph
1
2
3
1
2
3
2
2
16
10
15
14
11
14
8
69
87
57
76
98
99
95
70
1.8
9.0
3.0
1.6
6.7
4.9
9.0
6.7
-pNO2Ph
-pNO2Ph
-pNO2Ph
-pClPh
3g
3h
-benzo[d]1,3-dioxol-5-yl
12
aIsolated products by chromatographic column.
bYield of the geometric isomers mixture.
1
cDetermined by H NMR.
phthalimides 3 (as isomeric mixtures) with hydrazine (method A)[9,10] or
methylamine (method B)[19] at room temperature yielded the desired pri-
mary amines 4a–c, 4e, 4g, and 4h in good to excellent yields (Table 3).
On the other hand, both processes modify differentially the (Z=E)-iso-
meric ratio of the phthalimide starting materials (compare compound
stereochemistry ratios in Tables 2 and 3). Except for compound 4e, methyl-
amine deprotection did not modify the (Z=E) ratios while hydrazine, as
deprotecting reagent, reached high ratio modification levels (compare 3b
isomeric ratio, Table 2, to 4b (method A) isomeric ratio, Table 3). This could
Scheme 3. Syntheses of derivatives 3a, 3d, and 3i using semistabilized ylides.

Route to Primary (Z)-Allyl Amines
35
Figure 3. a) 1H NMR spectra of derivative 3i; b) NOE-diff. experiments for
derivative 3i.
be the result of a differential (Z)-isomers C ¼ C reduction promoted by
hydrazine[20] and could be proven by observing the general low yield of
the desired alkenes in this condition and the presence of reduced products.
Chromatographic separation of reduced product was very difficult, how-
ever, in the synthesis of 4b via method A, the corresponding secondary pro-
duct was isolated and characterized adequately. When hydrazinolysis was
performed at reflux of ethanol (2–5 h) to accelerate the deprotection proce-
dures, the reduction of the double bond was evidenced as the main process.
In the case of 4-nitrophenyl derivative 4e, important modifications in the
(Z=E)-ratios were observed in both conditions (methods A and B). This
could be explain in terms of the Michael-type reactivity of the alkene 3e,
which reacts with the nucleophiles, hydrazine or methylamine, producing
the most stable final alkene (Fig. 4). Stereochemistry of derivatives 4
around C ¼ C was confirmed using NMR spectroscopy (1H NMR, COSY,
13C NMR, HMQC, and HMBC).
Deprotection processes, of allylic amides 3d and 3f methods A and B,
did not give the desired products 4d and 4f, respectively, in any of the
cases. A number of additional experiments were carried out modifying
method A and B experimental conditions, temperature, and amount of
deprotective agents, with absence of the formation of desired products
in all conditions. In general, complex chromatographic inseparable mix-
tures of products were generated. While attempting to obtain compound
4f using hydrazinolysis (method A and modifications) from the allylic
phtalimide 3f, the pyrrolidine 5 (Fig. 5) was generated as the main pro-
duct of the reactions. Once more, like the results with 3e deprotection
reactions (Fig. 4), this pyrrolidine could be explained in terms of the
Michael-type reactivity of alkene 3f, which, in this case after amino group

36
A. Gerpe et al.
Table 3. Synthesis of amino derivatives 4
Deprotecting
reactive, reaction
time (h)
Yield
(%)a,b
Ratio
Z=Ec
Ref.
4a
4b
4c
-R
n
1
2
3
2
2
2
-Ph
NH2NH2, 10d
CH3NH2, 48f
NH2NH2, 10
CH3NH2, 48
NH2NH2, 12
CH3NH2, 12
NH2NH2, 12
CH3NH2, 48
NH2NH2, 12
CH3NH2, 48
NH2NH2, 12
50
77
50
86
99
98
84
67
83
56
33
1.9e
1.8
1.9g
9.0
-Ph
-Ph
3.0
2.9
4e
-pNO2Ph
3.3e
1.2
4g
4h
-pClPh
4.3e
9.0
-benzo[d]1,3-dioxol-5-yl
3.5e
aIsolated products by chromatographic column.
bYield of the geometric isomers mixture.
1
cDetermined by H NMR.
dMethod A.
eLess than 2% of the double bond reduction product was isolated and charac-
1
terized by H NMR.
fMethod B.
gNear to 13% of the double bond reduction product was isolated and charac-
1
terized by H NMR.
deprotection, reacts intramolecularly to produce the cyclic product. The
chemical structure of compound 5 was confirmed in terms of NMR spec-
troscopy (1H NMR and COSY).
EXPERIMENTAL
N-(2-Hydroxyethyl)phthalimide was prepared according to literature.[12]
1H and 13C NMR spectra and COSY, HMQC, and HMBC experiments
were recorded with a Bruker DPX-400 spectrometer using the indicated
solvent. Standard concentration of the samples was 20 mg=mL. Chemical

Route to Primary (Z)-Allyl Amines
37
Figure 4. Speculative isomerization process of 3e in the deprotection conditions.
shifts are reported in ppm (d) relative to TMS as an internal standard.
Elemental analyses were obtained from vacuum-dried samples (over
phosphorous pentoxide at 3–4 mm Hg, 24 h at room temperature),
performed on a Fisons EA 1108 CHNS-O analyzer, and were within
ꢂ 0.4% of theoretical values. Thin-layer chromatographic (TLC) analyses
were carried out on aluminum sheets of silica gel 60 F254. Column chro-
matography was performed on silica gel 60 (Merck, 60–230 mesh) with
typically 30–50 g of stationary phase per gram substance.
2-(N-Phthaloyl)Acetaldehyde
A mixture of N-(2-hydroxyethyl)phthalimide (0.57 g, 3.0 mmol) and PCC
(3.00 g) in CH2Cl2 (50.0 mL) was stirred at room temperature for 72 h.
The solution was filtrated through silica, and the filtrate was evaporated
to dryness. The product was obtained as a white solid (0.23 g, 41%); mp
(ꢀC) 86.2–88.0. 1H NMR (CDCl3) d: 4.58 (s, 2 H), 7.77 (m, 2 H), 7.86 (m,
2 H), 9.68 (s, 1 H).
a-Phthaloylacetophenone
A mixture of phthalimide (1.00 g, 6.8 mmol), a-bromoacetophenone
(1.53 g, 6.8 mmol), and K2CO3 (0.72 g, 6.8 mmol) in absolute EtOH
Figure 5. Main product in derivative 3f hydrazinolysis.

38
A. Gerpe et al.
(30.0 mL) was stirred at room temperature for 4 days. The formed solid
was collected and washed with water, yielding the desired product as a
white solid (1.53 g, 85%); mp (ꢀC) 164.5–166.0 (lit. 165–167[21]).
1H NMR (CDCl3) d: 5.16 (2H, s), 7.55 (2H, t, J ¼ 7.4 Hz), 7.66 (2H, t,
J ¼ 7.4 Hz), 7.78 (2H, m), 7.93 (2H, m), 8.04 (2H, t, J ¼ 7.4 Hz).
13C NMR (CDCl3) d: 44.60, 123.96, 128.55, 129.30, 132.70, 134.41,
134.51, 134.90, 168.29, 191.35.
N-(2-Chloroethyl)phthalimide (1a)
A mixture of N-(2-hydroxyethyl)phthalimide (0.50 g, 2.6 mmol) and
SOCl2 (10.0 mL) was heated at reflux for 5 h. The solution was cooled
and neutralized with aqueous solution of NaHCO3 (10%) and then
extracted with ethyl acetate (3 ꢃ 30.0 mL). The organic layer was dried
(Na2SO4) and concentrated to produce a yellow solid (0.54 g, 99%); mp
(ꢀC) 121.1–123.8. 1H NMR (DMSO-d6) d: 3.93 (t, J ¼ 7.2 Hz, 2 H),
4.02 (t, J ¼ 7.2 Hz, 2 H), 7.88 (m, 2 H), 7.92 (m, 2 H). 13C NMR
(DMSO-d6) d: 41.2, 42.4, 124.1, 132.3, 135.5, 168.4.
N-(2-Iodoethyl)phthalimide (1b)
Triphenylphosphine (0.82 g, 3.1 mmol) and imidazole (0.21 g, 3.1 mmol)
were dissolved in dry dichloromethane (30.0 mL) with stirring under
nitrogen. Iodine (0.80 g, 3.1 mmol) was supplemented slowly and, after
5 min, N-(2-hydroxyethyl)phthalimide (0.50 g, 2.6 mmol) was also added.
The stirring was continued for 4 h at room temperature. After that an
aqueous solution of Na2S2O3 (10%) (30.0 mL) was added and extracted
with CH2Cl2 (3 ꢃ 30.0 mL). The combined organic layers were dried
(Na2SO4) and evaporated to dryness, the mixture was purified by
chromatographic column (silica, hexane), yielding the product as a white
solid (0.55 g, 70%); mp (ꢀC) 92.4–93.0. 1H NMR (DMSO-d6) d: 3.46
(t, J ¼ 7.0 Hz, 2 H), 3.96 (t, J ¼ 7.0 Hz, 2 H), 7.88 (m, 2 H), 7.92 (m, 2
H). 13C NMR (DMSO-d6) d: 41.0 (two carbons), 124.1, 132.3, 135.5, 168.2.
General Method for the Preparation of Phosphonium Salts 2b–d
A mixture of phthalimide derivatives 1b–d (2.0 mmol) and triphenyl-
phosphine (2.0 mmol) in toluene (50.0 mL) was heated at reflux under
nitrogen for 14–16 h. The precipitate was filtered, washed with hexane,
and dried under reduced pressure.

Route to Primary (Z)-Allyl Amines
39
(2-Phthaloylethyl)triphenylphosphonium Iodide (2b)
Yellow solid (0.87 g, 77%); mp (ꢀC) 240.9–243.0. 1H NMR (DMSO-d6) d:
4.01 (m, 4 H), 7.78 (m, 15 H), 7.87 (m, 4 H).
(3-Phthaloylpropyl)triphenylphosphonium Bromide (2c)
1
White solid (1.05 g, 99%); mp (ꢀC) 218.6–221.0. H NMR (DMSO-d6) d:
1.95 (m, 2 H), 3.71 (m, 2 H), 3.77 (t, J ¼ 6.8 Hz, 2 H), 7.77 (m, 15 H), 7.85
(m, 4 H). 13C NMR (DMSO-d6) d: 19.3 (d, J ¼ 51.6 Hz), 21.9, 38.4, 118.1
(d, J ¼ 85.6 Hz), 123.9, 131.2, 132.8, 134.5, 135.2, 135.9, 168.9.
(4-Phthaloylbutyl)triphenylphosphonium Bromide (2d)
1
White solid (0.92 g, 85%); mp (ꢀC) 230.7–232.8. H NMR (DMSO-d6) d:
1.58, (m, 2 H), 1.80 (m, 2 H), 3.61 (m, 4 H), 7.82 (m, 19 H). 13C NMR
(DMSO-d6) d: 20.3, 20.9 (d, J ¼ 50.3 Hz), 29.5, 37.4, 119.2 (d,
J ¼ 85.3 Hz), 123.9, 131.1, 132.4, 134.4, 135.3, 135.8, 168.8.
General Method for the Preparation of Phthalimides 3a–h
A mixture of the corresponding phosphonium salts (2b–d, 2.0 mmol), the
corresponding aldehydes (2.0 mmol), K2CO3 (0.28 g, 2.0 mmol), and 18-
crown-6 (catalytic amounts) in toluene (50.0 mL) was heated at reflux
under nitrogen for 8–16 h. The solvent was evaporated to dryness, and
water (30.0 mL) was added. The aqueous solution was extracted with
ethyl acetate (3 ꢃ 30.0 mL). The combined organic layers was dried
(Na2SO4) and evaporated to dryness; the residue was purified by
chromatographic column (SiO2, hexane–ethyl acetate, 8:2). The com-
pounds were isolated as mixture of geometric isomers.
(E=Z)-N-(3-Phenyl-2-propenyl)phthalimide (3a)
White solid (0.36 g, 69%). Z isomer: 1H NMR (CDCl3) d: 4.62 (dd,
J ¼ 2.0, 6.4 Hz, 2 H), 5.69 (m, 1 H), 6.65 (dd, J ¼ 2.0, 11.6 Hz, 1 H),
7.41 (m, 5 H), 7.74 (m, 2 H), 7.87 (m, 2 H). 13C NMR (CDCl3) d: 36.9,
123.7, 126.2, 126.9, 128.8, 129.2, 132.4, 132.6, 134.3, 137.0, 169.0. E iso-
1
mer: H NMR (CDCl3) d: 4.47 (dd, J ¼ 1.2, 6.4 Hz, 2 H), 6.28 (m, 1 H),
6.69 (dd, J ¼ 1.2, 16.8 Hz, 1 H), 7.41 (m, 5 H), 7.74 (m, 2 H), 7.87 (m, 2
H). 13C NMR (CDCl3) d: 40.1, 123.2, 123.7, 126.9, 128.8, 129.2, 132.6,
134.3, 134.3, 137.0, 169.0.

40
A. Gerpe et al.
(E=Z)-N-(4-Phenyl-3-butenyl)Phthalimide (3b)
1
White solid (0.48 g, 87%). Z isomer: H NMR (CDCl3) d: 2.76 (m, 2 H),
3.84 (t, J ¼ 7.2 Hz, 2 H), 5.70 (m, 1 H), 6.54 (d, J ¼ 11.8 Hz, 1 H), 7.27 (m,
5 H), 7.72 (m, 2 H), 7.84 (m, 2 H). 13C NMR (CDCl3) d: 28.2, 38.0, 123.6,
126.5, 127.6, 128.1, 128.6, 132.1, 133.0, 134.3, 137.3, 168.7. E isomer:
1H NMR (CDCl3) d: 2.64 (m, 2 H), 3.84 (t, J ¼ 7.2 Hz, 2 H), 6.20 (m,
1 H), 6.46 (d, J ¼ 15.8 Hz, 1 H), 7.27 (m, 5 H), 7.72 (m, 2 H), 7.84 (m,
2 H). 13C NMR (CDCl3) d: 32.6, 38.0, 123.6, 123.6, 126.5, 128.1, 128.6,
132.5, 133.0, 134.3, 137.3, 168.7.
(E=Z)-N-(5-Phenyl-4-pentenyl)Phthalimide (3c)
White solid (0.33 g, 57%). Z isomer: 1H NMR (CDCl3) d: 1.87 (m, 2 H), 2.42
(m, 2 H), 3.79 (t, J ¼ 7.2 Hz, 2 H), 5.69 (m, 1 H), 6.46 (d, J ¼ 11.6 Hz, 1 H),
7.26 (m, 5 H), 7.72 (m, 2 H), 7.85 (m, 2 H). 13C NMR (CDCl3) d: 26.4, 29.1,
38.1, 123.6, 127.0, 128.5, 129.1, 130.3, 131.6, 132.6, 134.3, 138.0, 168.8. E
isomer: 1H NMR (CDCl3) d: 1.87 (m, 2 H), 1.93 (m, 2 H), 3.78 (t, J ¼ 7.2 Hz,
Hz, 2 H), 6.22 (m, 1 H), 6.40 (d, J ¼ 15.6 Hz, 1 H), 7.26 (m, 5 H), 7.72 (m, 2
H), 7.85 (m, 2 H). 13C NMR (CDCl3) d: 29.1, 31.0, 38.1, 123.6, 127.0, 128.5,
129.1, 130.3, 132.0, 132.6, 134.3, 138.0, 168.8.
(E=Z)-N-[3-(p-Nitrophenyl)-2-Propenyl]Phthalimide (3d)
1
Yellow solid (0.47 g, 76%). Z isomer: H NMR (CDCl3) d: 4.55 (dd,
J ¼ 2.0, 6.4 Hz, 2 H), 5.88 (m, 1 H), 6.69 (dd, J ¼ 2.0, 11.6 Hz, 1 H),
7.59 (d, J ¼ 8.6 Hz, 2 H), 7.76 (m, 2 H), 7.90 (m, 2 H), 8.26 (d, J ¼ 8.6 Hz,
Hz, 2 H). 13C NMR (CDCl3) d: 36.6, 123.8, 124.0, 129.4, 130.0, 130.6,
1
132.4, 134.6, 143.1, 147.6, 168.2. E isomer: H NMR (CDCl3) d: 4.51
(dd, J ¼ 1.2, 6.0 Hz, 2 H), 6.45 (m, 1 H), 6.72 (dd, J ¼ 1.2, 15.6 Hz, 1
H), 7.50 (d, J ¼ 8.8 Hz, 2 H), 7.76 (m, 2 H), 7.90 (m, 2 H), 8.18 (d,
J ¼ 8.8 Hz, 2 H). 13C NMR (CDCl3) d: 39.8, 123.8, 124.3, 127.5, 128.2,
131.8, 132.4, 134.6, 143.1, 147.6, 168.2.
(E=Z)-N-[4-(p-Nitrophenyl)-3-Butenyl]Phthalimide (3e)
Yellow solid (0.63 g, 98%). Z isomer: 1H NMR (CDCl3) d: 2.75 (m, 2 H),
3.85 (t, J ¼ 7.2 Hz, 2 H), 5.92 (m, 1 H), 6.58 (d, J ¼ 12.0 Hz, 1 H), 7.37 (d,
J ¼ 8.4 Hz, 2 H), 7.74 (m, 2 H), 7.83 (m, 2 H), 8.14 (d, J ¼ 8.4 Hz, 2 H).
13C NMR (CDCl3) d: 28.2, 37.6, 123.7, 123.7, 129.7, 130.4, 131.9, 132.4,
1
134.4, 143.9, 146.9, 168.6. E isomer: H NMR (CDCl3) d: 2.69 (m, 2 H),

Route to Primary (Z)-Allyl Amines
41
3.91 (t, J ¼ 7.2 Hz, 2 H), 6.43 (m, 1 H), 6.52 (d, J ¼ 15.8 Hz, 1 H), 7.43 (d,
J ¼ 8.4 Hz, 2 H), 7.74 (m, 2 H), 7.83 (m, 2 H), 8.14 (d, J ¼ 8.4 Hz, 2 H).
13C NMR (CDCl3) d: 33.0, 37.6, 123.7 (two carbons), 127.0, 129.7, 132.0,
132.4, 134.4, 143.9, 146.9, 168.6.
(E=Z)-[N-(5-(p-Nitrophenyl)-4-Pentenyl]phthalimide (3f)
Yellow solid (0.67 g, 99%). Z isomer: 1H NMR (CDCl3) d: 1.92 (m, 2 H),
2.40 (m, 2 H), 3.73 (t, J ¼ 7.2 Hz, 2 H), 5.90 (m, 1 H), 6.50 (d, J ¼ 11.6 Hz,
1 H), 7.37 (d, J ¼ 8.8 Hz, 2 H), 7.74 (m, 2 H), 7.84 (m, 2 H), 8.14 (d,
J ¼ 8.8 Hz, 2 H). 13C NMR (CDCl3) d: 26.4, 28.8, 37.8, 123.6, 123.9,
128.5, 129.7, 132.4, 134.4, 135.4, 144.4, 147.0, 168.7. E isomer:
1H NMR (CDCl3) d: 1.92 (m, 2 H), 2.40 (m, 2 H), 3.79 (t, J ¼ 7.2 Hz,
2 H), 6.40 (m, 1 H), 6.44 (d, J ¼ 15.2 Hz, 1 H), 7.37 (d, J ¼ 8.8 Hz, 2
H), 7.74 (m, 2 H), 7.84 (m, 2 H), 8.14 (d, J ¼ 8.8 Hz, 2 H). 13C NMR
(CDCl3) d: 28.0, 30.8, 37.8, 123.6, 123.9, 126.8, 129.7, 132.4, 134.4,
134.9, 144.4, 147.0, 168.7.
(E=Z)-N-[4-(p-Chlorophenyl)-3-Butenyl]Phthalimide (3g)
1
White solid (0.59 g, 95%). Z isomer: H NMR (CDCl3) d: 2.67 (m, 2 H),
3.83 (t, J ¼ 7.1 Hz, 2 H), 5.72 (m, 1 H), 6.47 (d, J ¼ 11.6 Hz, 1 H), 7.15 (d,
J ¼ 8.5 Hz, 2 H), 7.25 (d, J ¼ 8.5 Hz, 2 H), 7.73 (m, 2 H), 7.84 (m, 2
H).13C NMR (CDCl3) d: 28.1, 37.9, 123.6, 128.8, 129.0, 130.3 (two car-
1
bons), 131.0, 132.5, 134.3, 135.7, 168.7. E isomer: H NMR (CDCl3) d:
2.62 (m, 2 H), 3.87 (t, J ¼ 7.1 Hz, 2 H), 6.17 (m, 1 H), 6.38 (d, J ¼ 15.2 Hz,
Hz, 1 H), 7.15 (d, J ¼ 8.5 Hz, 2 H), 7.25 (d, J ¼ 8.5 Hz, 2 H), 7.73 (m, 2
H), 7.84 (m, 2 H). 13C NMR (CDCl3) d: 37.0, 37.9, 123.6, 127.0, 128.8,
130.3 (two carbons), 133.0, 132.5, 134.3, 135.7, 168.7.
(E=Z)-N-[4-(Benzo[d]1,3-Dioxol-5-yl)-3-Butenyl]Phthalimide (3h)
1
White solid (0.45 g, 70%). Z isomer: H NMR (CDCl3) d: 2.74 (m, 2
H), 3.83 (t, J ¼ 7.2 Hz, 2 H), 5.60 (m, 1 H), 5.95 (s, 2 H), 6.43 (d,
J ¼ 11.6 Hz, 1 H), 6.73 (m, 3 H), 7.72 (m, 2 H), 7.85 (m, 2 H). 13C
NMR (CDCl3) d: 28.2, 38.0, 101.4, 108.5, 109.3, 122.9, 123.6, 127.0,
131.5, 131.7, 132.5, 134.3, 146.0 (two carbons), 168.7. E isomer: 1H
NMR (CDCl3) d: 2.60 (m, 2 H), 3.83 (t, J ¼ 7.2 Hz, 2 H), 5.95 (s, 2
H), 6.05 (m, 1 H), 6.35 (d, J ¼ 15.6 Hz, 1 H), 6.73 (m, 3 H), 7.72
(m, 2 H), 7.85 (m, 2 H). 13C NMR (CDCl3) d: 33.3, 38.0, 101.4,

42
A. Gerpe et al.
108.5, 109.3, 122.9, 123.6, 128.3, 131.5 (two carbons), 132.5, 134.3,
146.0 (two carbons), 168.7.
General Method for the Preparation of Phthalimides 3a, 3d, and 3i Using
Semistabilized Ylides
A mixture of the corresponding phosphonium salts (benzyltriphenylpho-
sphonium chloride or p-nitrobenzyltriphenylphosphonium bromide,[22]
2.0 mmol), the corresponding carbonyl derivative (2-(N-phthaloyl)-
acetaldehyde or a-pththaloylacetophenone, 2.0 mmol), t-BuOK (0.22 g,
2.0 mmol), and 18-crown-6 (catalytic amounts) in toluene (50.0 mL)
was heated at reflux under nitrogen for 2–10 h. The solvent was evapo-
rated to dryness, and water (30.0 mL) was added. The aqueous solution
was extracted with ethyl acetate (3 ꢃ 30.0 mL). The combined organic
layers was dried (Na2SO4) and evaporated to dryness; the residue was
purified by chromatographic column (SiO2, hexane–ethyl acetate, 8:2).
The products 3a and 3d were isolated as mixture of geometric isomers
(see Scheme 3), and product 3i was isolated as E-isomer.
(E)-N-(2,3-Diphenyl-2-Propenyl)Phthalimide (3i)
1
Yellow solid (0.33 g, 49%). H NMR (CDCl3) d: 4.70 (s, 2 H), 6.60 (s, 1
H), 6.97 (m, 2H), 7.08 (m, 3H), 7.28 (m, 5H), 7.72 (m, 2 H), 7.84 (m, 2 H).
13C NMR (CDCl3) d: 45.61, 123.72, 128.03, 128.24 (two carbons), 128.41,
129.04 (two carbons), 129.32, 129.68, 132.40, 134.34, 136.61, 138.55,
168.32.
General Method for the Preparation of Primary Amines 4a–c, 4e, and 4g–h
Method A
A mixture of the corresponding phthalimide derivatives (3a–c, 3e, 3g, and
3h, 2.0 mmol) and hydrazine hydrate (98%) (4.0 mmol, 0.12 mL) in abso-
lute ethanol (30.0 mL) was stirred at room temperature for 10–12 h. The
forming precipitate was filtered and washed with ethyl acetate. The
organic layer was evaporated to dryness, and the residue was suspended
in acetone to extract the excess of hydrazine. The forming precipitate was
filtered; the organic layer was dried (Na2SO4) and evaporated to dryness.
The desired products, chromatographically isolated (silica, methylene
chloride–methanol, 99.5:0.5), were obtained as oils after evaporation.

Route to Primary (Z)-Allyl Amines
43
Method B
A mixture of the corresponding phthalimide derivatives (3a–c, 3e, 3g,
and 3h, 2.0 mmol) and methylamine monohydrate (40%) (10.0 mmol,
0.12 mL) in absolute ethanol (30.0 mL) was stirred at room temperature
for 12–48 h. The mixture was evaporated to dryness, and the residue
was suspended in aqueous HCl (10%) (30.0 mL) and stirred for 2 h
at room temperature. The aqueous solution was extracted with ethyl
acetate (3 ꢃ 30.0 mL). The aqueous layer was alkalinized by addition of
aqueous solution of Na2CO3 (10%) and extracted with ethyl acetate
(3 ꢃ 30.0 mL). The organic layer was dried (Na2SO4) and evaporated to
dryness. The desired products, chromatographically isolated (silica,
methylene chloride–methanol, 99.5:0.5), were obtained as oils after
evaporation.
(E=Z)-3-Phenyl-2-propenylamine (4a)
1
Method A, 0.13 g, 50%; method B, 0.20 g, 77%. Z isomer: H NMR
(CDCl3) d: 1.53 (brs, 2 H), 3.55 (d, J ¼ 6.8 Hz, 2 H), 5.72 (m, 1 H),
6.45 (d, J ¼ 11.6 Hz, 1 H), 7.26 (m, 5 H). 13C NMR (CDCl3) d: 40.5,
1
128.6, 129.0, 129.2, 129.7, 134.3, 137.5. E isomer: H NMR (CDCl3) d:
1.53 (brs, 2 H), 3.42 (d, J ¼ 5.6 Hz, 2 H), 6.28 (m, 1 H), 6.48 (d,
J ¼ 14.0 Hz, 1 H), 7.26 (m, 5 H). 13C NMR (CDCl3) d: 44.6, 128.6,
129.0, 129.2, 129.8, 131.7, 137.5.
(E=Z)-4-Phenyl-3-butenylamine (4b)
1
Method A, 0.13 g, 50%; method B, 0.25 g, 86%. Z isomer: H NMR
(CDCl3) d: 1.53 (brs, 2 H), 2.63 (m, 2 H), 3.55 (d, J ¼ 6.8 Hz, 2 H),
5.72 (m, 1 H), 6.45 (d, J ¼ 11.6 Hz, 1 H), 7.26 (m, 5 H). 13C NMR
(CDCl3) d: 29.3, 40.5, 128.6, 129.0, 129.2, 129.7, 134.3, 137.5. E
1
isomer: H NMR (CDCl3) d: 1.53 (brs, 2 H), 2.63 (m, 2 H), 3.42 (d,
J ¼ 5.6 Hz, 2 H), 6.28 (m, 1 H), 6.48 (d, J ¼ 14.0 Hz, 1 H), 7.26 (m,
5 H). 13C NMR (CDCl3) d: 29.3, 44.6, 128.6, 129.0, 129.2, 129.8,
131.7, 137.5.
(E=Z)-5-Phenyl-4-pentenylamine (4c)
1
Method A, 0.32 g, 99%; method B, 0.32 g, 98%. Z isomer: H NMR
(CDCl3) d: 1.65 (m, 2 H), 2.39 (m, 2 H), 2.61 (t, J ¼ 7.6 Hz, 2 H), 2.67

44
A. Gerpe et al.
(brs, 2 H), 5.65 (m, 1 H), 6.45 (d, J ¼ 12.0 Hz, 1 H), 7.30 (m, 5 H).
13C NMR (CDCl3) d: 26.9, 33.8, 36.3, 127.0, 128.6, 128.9, 129.8, 132.5,
1
138.0. E isomer: H NMR (CDCl3) d: 1.65 (m, 2 H), 2.30 (m, 2 H),
2.67 (brs, 2 H), 2.76 (t, J ¼ 7.6 Hz, 2 H), 6.21 (m, 1 H), 6.40 (d,
J ¼ 15.6 Hz, 1 H), 7.30 (m, 5 H). 13C NMR (CDCl3) d: 30.7, 31.6, 41.9,
127.0, 128.6, 128.9, 130.5, 130.7, 138.0.
(E=Z)-4-(p-Nitrophenyl)-3-butenylamine (4e)
1
Method A, 0.32 g, 84%; method B, 0.26 g, 67%. Z isomer: H NMR
(CDCl3) d: 1.87 (brs, 2H), 2.52 (m, 2 H), 2.92 (t, J ¼ 7.6 Hz, 2 H), 5.89
(m, 1 H), 6.60 (d, J ¼ 11.8 Hz, 1 H), 7.46 (d, J ¼ 8.7 Hz, 2 H), 8.21 (d,
J ¼ 8.7 Hz, 2 H). 13C NMR (CDCl3) d 32.7, 42.1, 123.9, 129.6, 129.8,
1
133.9, 144.4, 147.0. E isomer: H NMR (CDCl3) d: 1.87 (brs, 2H), 2.47
(m, 2 H), 2.76 (t, J ¼ 7.6 Hz, 2 H), 6.44 (m, 1 H), 6.54 (d, J ¼ 15.2 Hz,
1 H), 7.46 (d, J ¼ 8.7 Hz, 2 H), 8.21 (d, J ¼ 8.7 Hz, 2 H). 13C NMR
(CDCl3) d 35.9, 36.9, 123.9, 129.8, 130.8, 132.0, 144.4, 147.0.
(E=Z)-4-(p-Chlorophenyl)-3-butenylamine (4g)
1
Method A, 0.30 g, 83%; method B, 0.20 g, 56%. Z isomer: H NMR
(CDCl3) d 2.58 (m, 2 H), 2.90 (t, J ¼ 6.8 Hz, 2 H), 5.22 (brs, 2 H),
5.65 (m, 1 H), 6.47 (d, J ¼ 11.6 Hz, 1 H), 7.18 (d, J ¼ 8.4 Hz, 2 H),
7.27 (d, J ¼ 8.4 Hz, 2 H). 13C NMR (CDCl3) d 29.8, 41.0, 128.8,
129.1, 130.3, 130.4, 130.6, 135.7. E isomer: 1H NMR (CDCl3) d:
2.50 (m, 2 H), 2.90 (t, J ¼ 6.8 Hz, 2 H), 5.22 (brs, 2 H), 6.13 (m,
1 H), 6.46 (d, J ¼ 15.6 Hz, 1 H), 7.18 (d, J ¼ 8.4 Hz, 2 H), 7.27 (d,
J ¼ 8.4 Hz, 2 H). 13C NMR (CDCl3) d: 33.4, 40.8, 126.7, 128.8,
130.3, 130.4, 132.2, 135.7.
(E=Z)-4-(Benzo[d]1,3-dioxol-5-yl)-3-butenylamine (4h)
1
Method A, 0.13 g, 33%. Z isomer: H NMR (CDCl3) d: 1.65 (brs, 2H),
2.46 (m, 2 H), 2.80 (t, J ¼ 6.8 Hz, 2 H), 5.56 (m, 1 H), 5.93 (s, 2 H),
6.42 (d, J ¼ 11.6 Hz, 1 H), 6.76 (m, 3 H). 13C NMR (CDCl3) d: 33.0,
42.5, 101.3, 108.54, 109.3, 122.9, 129.1, 130.8, 132.4, 146.7, 147.9.
1
E isomer: H NMR (CDCl3) d: 1.65 (brs, 2H), 2.32 (m, 2 H), 2.80 (t,
J ¼ 6.8 Hz, 2 H), 5.93 (s, 2 H), 5.99 (m, 1 H), 6.35 (d, J ¼ 15.6 Hz, 1 H),
6.76 (m, 3 H). 13C NMR (CDCl3) d: 37.3, 42.5, 101.3, 108.54, 109.3,
122.9, 126.4, 130.8, 132.4, 146.7, 147.9.

Route to Primary (Z)-Allyl Amines
45
2-(4-Nitrophenyl)metilpyrrolidine (5)
Red oil (0.26 g, 63%, method A). 1H NMR (CDCl3) d: 1.50 (m, 1 H), 1.92
(m, 3 H), 2.29 (brs, 1H), 2.96 (m, 3 H), 3.11 (s, 1 H), 3.40 (m, 1 H), 7.40
(d, J ¼ 8.4 Hz, 2 H), 8.16 (d, J ¼ 8.4 Hz, 2 H).
ACKNOWLEDGMENT
ꢀ
Financial support came from Fondo Clemente Estable and Comision
ꢀ
Sectorial de Investigacion Cientifica-Universidad de la Repu´blica
ꢀ
(Uruguay). A. G. thanks Programa de Desarrollo de Ciencias Basicas-
QUIMCIA for a doctoral fellowship. M. B. thanks Network for
´
Research and Training in Parasitic Diseases at the Southern Cone of
Latin America-Swedish Agency for Research Cooperation with Devel-
oping Countries (RTPD-SAREC) for a scholarship.
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