Stereoselective syntheses of allylic amines through reduction of 1-azadiene intermediates

Article abstract of DOI:10.1016/S0040-4020(00)00736-5

The stereoselective synthesis of primary and secondary E-allylic amines by reduction of 1-azadiene intermediates is described. β-Enamino phosphonium salts are suitable starting materials to prepare secondary allylic amines. Two methods are reported for th

Full text of DOI:10.1016/S0040-4020(00)00736-5

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 8179±8187
Stereoselective Syntheses of Allylic Amines Through Reduction of
1-Azadiene Intermediates
²
³
*
Â
Enrique Aguilar, Jesus Joglar, Isabel Merino, Bernardo Olano, Francisco Palacios and
Santos Fustero§
     Â
Departamento de Quõmica Organica e Inorganica, Facultad de Quõmica, Avda. Julian Claverõa s/n,
Universidad de Oviedo, 33006 Oviedo, Spain
Â
Dedicated to Professor Jose Barluenga on the occasion of his 60th birthday
Received 26 May 2000; revised 2 August 2000; accepted 17 August 2000
AbstractÐThe stereoselective synthesis of primary and secondary E-allylic amines by reduction of 1-azadiene intermediates is described.
b-Enamino phosphonium salts are suitable starting materials to prepare secondary allylic amines. Two methods are reported for the obtention
of primary allylic amines from 4-amino-1-aza-1,3-dienes. Method A leads to the desired compounds by straight reduction with AlH3 or
DIBALH; method B is a stepwise procedure that allows for better yields when sterically hindered 4-amino-1-aza-1,3-dienes are employed.
q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
their oxygenated analogs, for whose preparation numerous
methods have been developed, the number of procedures to
synthesize allylic amines is more scarce. Thus, they can be
accessed from allylic compounds,11 ole®ns,12 azidirines,13
epoxides,14 phosphorylated compounds,15 alkynes16 and by
Diels±Alder cyclization of aminodienes.17 A direct route to
these structural units is the functionalization of the parent
allylamine or the homologation of other allylic amines.18
Allylic amines have become interesting targets for synthetic
organic chemistry, due to the presence of this functionality
in several naturally occurring compounds, such as gaba-
culine or oximicine1 as well as in vinylogous polypeptides
or peptide isosteres2 and to their huge potential as synthetic
intermediates for the preparation of biologically active
products, such as the Streptogramin antibiotics,3 alkaloids4
and antifungal chemotherapeutic agents.5 Other facts that
have contributed to the spurring of research in this ®eld
include the ability of allylic amines to inhibit several
enzymatic complexes6 and the wide range of physiological
properties they show7 as well as their applications as insec-
ticides, bactericides or herbicides.8 The usefulness of allylic
amines in organic synthesis is well documented9 and, for
example, they have been widely employed as precursors for
b-nitrogen functionalized organometallic intermediates.10
Reduction processes have also been employed to prepare
allylic amines. Thus a,b-unsaturated oximes lead to
primary allylic amines by treatment with Zn in acetic or
formic acid19 or complex metal hydrides,20 but in some
cases azidirines are obtained as reaction products. More
recently, Kocovsky has showed that the protection of the
oxime hydroxyl moiety facilitates the reduction with
complex metal hydrides, with the mesyl being the activating
group that allows for better yields.21 N-Allyl hydroxyl-
amines are suitable precursors of allylic amines by reduction
with either complex metal hydrides, microorganisms or Zn/
HCl.22 Other substrates that yield allylic amines by
reduction are allylic azides (which can be obtained by
Pd-catalyzed amination of allyl esters),23 propargyl
amines,24 or N-allylalkylidene ammonium salts.25
In spite of all these facts, and in contrast to allylic alcohols,
Keywords: allylic amines; azadienes; phosphonium salts; reduction.
* Corresponding author. Fax: 134-98-510-3446;
e-mail: eah@sauron.quimica.uniovi.es
Â
Current address: Departamento de Quõmica Organica Biologica, Instituto
de Investigaciones Quõmicas y Ambientales de Barcelona (C.S.I.C.), 08034
²
Â
Â
In this context, and having in mind that a good synthesis of
allylic amines should be able to control both the position
and the geometry of the double bond, a,b-unsaturated
imines have become appropriate substrates to synthesize
allylic amines by treatment with sodium borohydride or
lithium diethylaminoborohydride.26 In this paper we
would like to report our results in the stereoselective
Â
Barcelona, Spain.
Current address: Departamento de Quõmica Organica, Facultad de Farm-
³
Â
acia, Universidad del Paõs Vasco/E.H.U., Apartado 450, 01080 Vitoria,
Â
Â
Spain.
§
Â
Current address: Departamento de Quõmica Organica, Facultad de Farm-
acia, Avda. Vicente Andres Estelles s/n, Universidad de Valencia, 46100
Â
Â
Â
Burjassot, Valencia, Spain.
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00736-5

8180
E. Aguilar et al. / Tetrahedron 56 (2000) 8179±8187
after hydrolysis, to secondary allylic amines 4 (Scheme 1,
Table 1).
Both iminic compounds 3 and allylic amines 4 were fully
characterized by their spectroscopical data (IR, MS, 1H and
13C NMR), which indicated that ketimines 3 coexist in solu-
tion as a mixture of E/Z isomers of the carbon±nitrogen
1
double bond.29 Thus for example, the H NMR spectrum
for compound 3a showed two signals at d 2.48 and
2.05 ppm corresponding to the methyl group for both
isomers in a 1:2 ratio. This fact was corroborated by the
13C NMR spectrum which presented two signals at d
165.1 and 163.6 ppm for the imino group and d 22.5 and
14.9 ppm for the methyl group of the two isomers. Also, the
value of the coupling constants for the vinylic protons
(Jˆ16.5 Hz) indicated an E con®guration for the double
bond.
Scheme 1. Reagents and conditions: (i) n-BuLi, THF, 2788C, 2 h; (ii) H2O
(R2ˆH) [or D2O (R2ˆD)]; (iii) NaBH4/MeOH; (iv) H2O.
preparation of E-allylic amines by 1,2-reduction of
1-azadiene intermediates.27
For allylic amines 4 the con®guration of the double bond
was established to be E on the basis of the coupling constant
values that were found to be between 15.7 and 17.2 Hz. This
fact also indicates that the smooth conditions employed to
reduce the CvN bond did not affect the stereochemistry of
the double bond in 1-azadienes 3.
Results and Discussion
Synthesis of secondary allylic amines from b-enamino
phosphonium salts
b-Enamino phosphonium salts 1 are simply, smoothly and
readily accessible compounds that have found application in
organic synthesis as intermediates for the preparation of
tetrahydropyridines and penta-1,4-dien-3-ones.28 Those
reactions proceeded through the formation of N-substituted
ylide intermediate 2 (Scheme 1) and we have envisioned
that a sequential hydrolysis of 2 followed by a chemo-
selective reduction of the resulting 1-azadiene 3 could result
in an expedient procedure for the formation of secondary
allylic amines.
Synthesis of primary allylic amines from 4-amino-1-aza-
1,3-dienes 5
The chemistry of 4-amino-1-aza-1,3-dienes 530 has been
extensively developed in our group as they have proved to
be versatile intermediates for the synthesis of functionalized
acyclic and heterocyclic compounds.31 We thought that they
could be suitable starting materials for the preparation
of primary allylic amines if we were able to control the
reduction conditions. In this regard we now present two
different methods (A and B) that allowed us to achieve our
goal.
Thus, deprotonation of b-enamino phosphonium salts 1 by
treatment with n-BuLi at 2788C for 2 h and subsequent
hydrolysis yielded 2-alkyl-1-azadienes 3 in good yields
(Scheme 1, Table 1). Compounds 3 and triphenylphosphine
oxide (Ph3PO) generated in the reaction were separated by
column chromatography and 1-azadienes 3a±c were further
puri®ed by recrystallization in hexane. When the hydrolysis
was performed with D2O instead of H2O, the deuterated
azadiene 3b was isolated. 1-Azadienes 3d (R1ˆH) and 3e
(R1ˆEt) were unstable to chromatography and were used in
the following step without further puri®cation. The subse-
quent treatment of N-substituted 2-alkyl-1-azadienes 3 with
an excess of NaBH4 in EtOH at 08C for several hours led,
Method A. Treatment of azadienes 5 with an excess of in situ
generated alane (3LiAlH41AlCl3)32 (AlH3/5$5/1) in
diethyl ether at room temperature for several hours yielded
primary allylic amines 7, after hydrolysis. Carbonyl (or
iminic) compounds 633 were obtained as by-products in
variable amounts depending on the nature of the starting
azadiene 5 (Scheme 2, Table 2). Slightly worse selectivity
was achieved when the reaction was performed using excess
DIBALH (DIBALH/5$3/1) as reducing agent instead of
alane (entries 2, 14, method A, Table 2).
The reaction chemical yield was, in general, very high,
specially when R2ˆMe (entries 1±7, Table 2). Work-up
and further puri®cation of the products could be easily
achieved by an acid±base extraction to separate carbonyl
(or iminic) compounds 6 from the mixture of primary allylic
amines 7 and saturated amines (R1NH2), the latter ones
being removed by high vacuum distillation or by ¯ash
chromatography.
Table 1. 2-Alkyl-1-aza-1,3-butadienes 3 and secondary allylic amines 4
prepared from b-enamino phosphonium salts 1
Entry
R1
R2
3
Yield (%)a
4
Yield (%)b
1
2
3
4
5
Ph
Ph
2-Furyl
H
H
D
H
H
H
a
b
c
d
e
85
82
80
a
b
c
d
e
95
90
93
c
±
75a
78a
c
Et
±
The preparation of primary allylic amines 7 can be
explained by a three-step mechanism. In an initial stage
an N±Al bond is formed, with concomitant evolution of
H2, followed by 1,4-addition of hydride to give intermediate
8. The evolution of 8 by elimination of primary amine
a Isolated yield from 1.
b Isolated yield from 3.
c These compounds were used without puri®cation in the subsequent
reduction step.

E. Aguilar et al. / Tetrahedron 56 (2000) 8179±8187
8181
Scheme 2. Reagents and conditions. Method A: AlH3/Et2O/rt or DIBALH/Toluene/rt.
(R1NH2) leads to N-metallated 1-azadiene intermediate 9,
which should exist as an equilibrium mixture of two con-
formers s-cis 9a and s-trans 9b. These species may suffer
another 1,4- or 1,2-reduction to give respectively carbonyl
(or iminic) compounds 6 and primary allylic amines 7
(Scheme 2).
fact, when the size of R2 in starting azadienes 5 (where
ArˆR3ˆPh) increases, a remarkable decrease in the ratio
of allylic amines 7 to carbonyl compounds 6 is observed
(entries 1, 2, 9, 12 and 14, method A, Table 2). These results
seem to indicate that, for azadienes bearing bulky sub-
stituents, the equilibrium between s-cis 9a and s-trans 9b
species should be displaced towards 9a, due to steric
hindrance between R2 and N±AlZ2 (ZˆH, i-Bu), so
1,4-reduction should be favored leading to carbonyl
compounds 6. On the other hand, for those azadienes having
One of the major drawbacks of method A is that, in some
cases, it leads to mixtures of compounds 6 and primary
allylic amines 7, although they can be easily separated. In
Table 2. Primary allylic amines 7 prepared from 4-amino-1-aza-1,3-dienes 5
Method A
Method B
Ratio 7/6b
Yield (%)c
Entry
7a
R2
R3
R1
AlH3
DIBALH
AlH3
DIBALH
7/6b
5/NaBH4
Yield (%)c
97
1
2
3
4
5
6
7
8
a
a
b
b
c
d
e
f
g
g
g
h
h
i
Me
Me
Me
Me
Me
Me
Me
Et
Et
Et
Et
Allyl
Allyl
Bn
Bn
H
Ph
Ph
p-Tol
p-Tol
Ph
p-Cl±C6H4
Cy
Cy
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
pTol
Ph
p-Tol
Cyd
Ph
p-Tol
Ph
p-Tol
Ph
Ph
p-Tol
Ph
Ph
Ph
Ph
Ph
p-Tol
Ph
p-Tol
Ph
.99/±
.99/±
.99/±
96 (82)
97 (80)
98 (88)
94/6
96
98
.99/±
1/2
.99/±
.99/±
.99/±
.99/±
68/32
98 (85)
97 (82)
93 (77)
95 (52)
94 (50)
9
58/42
70/26e
64/15e
1/2
1/5
89 (50)
98
10
11
12
13
14
15
16
17
18
19
20
26/74
0/57e
93
93
15/85
±/.99
41/30e
90
99
66/31e
60/15e
74/26
39/61
1/2
1/10
1/5
92 (50)
95
94 (61)
85
i
j
j
1/1
H
H
59/16e
91 (50)
95 (68)
k
l
Et
Ph
Ph
88/5e
f
f
Propargyl
Me
88/8e
1/2
99 (70)
mg
.99/1
99 (88)
a ArˆPh, in all cases except for 7c (Arˆp-Cl±C6H4±).
1
b Ratio 7/6 determined from the crude reaction mixture by GC/MS and/or H NMR (300 MHz).
c Combined yield of crude product (617) determined by GC/MS or H NMR; in brackets yield of isolated product 7.
1
d Cyˆc-C6H11.
e Variable amounts (3±43%) of other compounds, mainly saturated amines, were detected by GC/MS.
f A mixture of several products was obtained, among which the compounds resulting from partial (7h) and complete reduction of the triple bond.
g 1,3-Dideuterated allylic amine that was obtained when performing the reaction with AlD3.

8182
E. Aguilar et al. / Tetrahedron 56 (2000) 8179±8187
Thus, in situ treatment of 1-azadiene intermediate 10 with
excess NaBH4 in MeOH at room temperature for several
hours led, after hydrolysis, to primary allylic amines 7 in
the yields and ratios reported in Table 2 (Scheme 3). The
best results were achieved when a ratio NaBH4/5:2/1 was
employed (see Table 2, method B, entries 9, 12 vs 10, 13)
and it should be noted that a great increase in the regios-
electivity and chemoselectivity was afforded when using
method B instead of method A (see Table 2, method B vs
method A, entries 9, 12, 14, 19). Also, by using method B it
is possible to prepare allylic amines 7i and 7l that could not
be accessed by method A (Table 2, entries 14 and 19).
The reaction was highly stereoselective as only one dia-
stereomer was detected in the crude reaction mixture.
Thus, for allylic amines 7j and 7k the E stereochemistry
was easily assigned by straightforward analysis of the
coupling constants of the protons in the double bond (15.8
and 15.9 Hz for 7j and 7k, respectively, which are in the
typical range for trans coupling constants). For other allylic
amines, the product conformation was determined by NOE
experiments, and were also found to be the E diastereomers.
Thus, for example, for compound 7a a positive NOE was
observed between the ole®n hydrogen and the methine
group allowing to establish the proposed E stereochemistry;
moreover, the absence of NOE between the methyl group
and the ole®n hydrogen corroborates a trans disposition for
both of these substituents (Fig. 1).
Scheme 3. Reagents and conditions. Method B: (i) DIBALH (2 equiv.)/
Toluene/rt; (ii) MeOH; (iii) NaBH4/MeOH/rt; (iv) Hydrolysis.
Figure 1.
Some additional experimental results that support the
proposed mechanism are described below. One comes
from the fact that 1-azadiene 10 could be identi®ed by
a small steric effect, the ®nal step should proceed mainly by
1,2-hydride addition34 thus generating allylic amines 7
(Scheme 2).
1
GC/MS and H NMR, in the crude reaction mixture, when
the reaction was performed using a DIBALH/5:2/1 ratio
(method B) (Fig. 1). A second one is the formation of dideut-
erated allylic amine 7m (entry 20, Table 2, Fig. 1) when the
reaction was performed using deuterated alane (AlD3,
prepared in situ from powdered LiAlD4 and AlCl3)32 as
reducing agent. This result is not only evidence for the
proposed mechanism, but it also represents a procedure
for the synthesis of deuterated allylic amines.
Method B. An alternative procedure was developed in order
to avoid the dif®culty of preparing primary allylic amines 7
bearing a bulky R2 substituent. In this new procedure two
equivalents of reducing agent (ratio DIBALH/5:2/1) in
toluene at room temperature were employed. Solvolysis
with anhydrous methanol after several hours led to the
formation of intermediate 10 (Scheme 3). 1-Azadiene 10
presents a N±H bond instead of the N±Al bond that bore
intermediate 9 (Method A, Scheme 2). The repulsive inter-
action between R2 and N±Y (YˆAlZ2 vs H) should there-
fore be greatly diminished, so possible that, even when the
size of R2 was higher than a methyl group, the major con-
former in solution should be s-trans 10b and 1,2-reduction
processes could take place leading to the isolation of
primary allylic amines 7 as major products.
Primary allylic amines 7h and 7l bear several functionalities
that make them interesting compounds and useful synthetic
intermediates. For this reason we decided to look for the
best conditions for their preparation; we were also interested
in determining whether it was possible to achieve the synth-
esis of allylic amine 7h in good yields from propargyl
substituted azadienes 5 (R2ˆpropargyl) instead of allyl
Scheme 4.

E. Aguilar et al. / Tetrahedron 56 (2000) 8179±8187
8183
substituted azadienes 5 (R2ˆallyl). Several essays were
performed varying the DIBALH/5 ratio; thus when an
excess of DIBALH (4.5 equiv.) was employed a mixture
of several compounds was detected, with allylic amine 7h
(40%) the major component and only a 12% of 7l observed;
considerable amounts of carbonyl compounds 6 and satu-
rated amines were also detected (Scheme 4).
dry argon, and the glassware was oven dried (1208C), evac-
uated, and purged with argon. Temperatures are reported as
bath temperatures. Analytical thin layer chromatograms
(TLC) were carried out with Kiesel gel 60 F254 on aluminum
support; compounds were visualized by UV light (254 nm)
and/or iodine. Flash chromatography was performed with
silica gel. Melting points are reported uncorrected and were
measured on a Buchi±Tottoli apparatus using open capillary
tubes. Mass spectral data were measured by electron impact
at 70 eV in a Hewlett±Packard 5987A spectrometer. Infra-
red spectra (cm21) were obtained in a Perkin±Elmer 298 or
Philips PU 9716 FT-IR spectrometers. Oils were analyzed
as pure samples while solids were recorded as Nujol mulls
or KBr pellets. Elemental analyses were carried out with a
Perkin±Elmer 240 B microanalyzer. NMR spectra were
recorded with a Bruker AC-200 or a Bruker AC-300 instru-
ments, with tetramethylsilane as the internal standard for 1H
NMR measurements, deuterated chloroform for 13C NMR
measurements and H3PO4 85% for 31P NMR measurements.
1H NMR: splitting pattern abbreviations are: s, singlet; bs,
broad singlet; d, doublet; t, triplet; q, quartet; m, multiplet.
13C NMR: multiplicities were determined by DEPT experi-
ments, that were performed employing standard pulse
sequences. In the cases where a mixture of diastereomers
was observed, the abbreviation `min' refers to the signals
assigned to the minor diastereomer and the abbreviation
`maj' to the signals belonging to the major one; in the
cases where nothing is speci®ed, either it has not been
possible to assign the signal to any of the diastereomers or
it belongs to both of them.
When the excess of DIBALH was reduced to three equiva-
lents, and CD3OD was used in the solvolysis step, the GC/
MS analysis of the crude reaction residue, after reduction
with NaBH4, showed an increase in the amount of 7l as well
as a decrease in deuterated-7h. Also, the reaction of
DIBALH with the triple bond takes place by regioselective
addition of aluminum to the terminal carbon, as no addition
to the internal carbon was observed. Finally, the best con-
ditions found to prepare 7l (88%) were the employment of
just 2 equiv. of DIBALH; in this case 7h was not detected
(Scheme 4).
In conclusion, 1-aza-dienes are valuable synthetic inter-
mediates for the preparation of both primary and secondary
allylic amines. In the case of secondary allylic amines, the
required N-substitued 1-aza-dienes are easily obtained from
b-enamino phosphonium salts 1, and can be regio- and
chemoselectively reduced by treatment with NaBH4. On
the other hand, 4-amino-1-aza-1,3-dienes 5 are suitable
starting materials to prepare N-unsubstituted 1-azadienes
that will lead to the synthetically important primary allylic
amines. Two ef®cient, simple, complementary and stereo-
selective one-pot methods have been developed to that end:
in method A only one reducing agent is used, either alane or
DIBALH, and due to its simplicity, it should be the method
of choice for the reduction of 4-amino-1-aza-1,3-dienes 5
bearing a small R2 substituent (R2ˆH, Me), while method B
requires the sequential employment of two reducing agents
(DIBALH, only two equivalents, to avoid further reduction
at the N-unsubstituted 1-azadiene stage, and NaBH4) and
should be the method of choice for the reduction of
compounds 5 bearing a bulky R2 substituent. Moreover,
this methodology allows the preparation of primary allylic
amines, such as 7h and 7l, dif®cult to obtain by other pro-
cedures, that can be highly versatile synthons in organic
synthesis.
General procedure for the synthesis of 2-alkyl-1-aza-1,3-
dienes 3a±c
n-BuLi (2.5 mmol, 1 mL, 2.5 M in hexanes) was slowly
added to a solution of b-enamino phosphonium salt 1
(2.5 mmol) in dry THF (50 mL) at 2788C under inert
atmosphere. After 2 h, the reaction was hydrolyzed at low
temperature (2508C), the stirring was maintained for 12 h at
room temperature and the organic layer was extracted with
diethyl ether (3£50 mL), dried over Na2SO4, and ®ltered.
Solvents were evaporated under vacuum and the oily
residue was puri®ed by column chromatography on silica
gel using hexane/AcOEt (20/1 to 1/1) as sequential eluents
to give 1-azadienes 3 in the yields reported in Table 1. The
solid compounds thus obtained could be recrystallized in
Experimental
1
hexane. H and 13C NMR spectra of compounds 3 show
several sets of paired signals due to the presence of syn/
anti isomers. Compounds 3d and 3e were unstable to
chromatographic puri®cation and therefore, they were
reduced to amines 4 without isolation.
General
THF and diethyl ether were distilled under argon from
sodium/benzophenone ketyl as drying agent. Diisopropyl-
amine, used to generate LDA, was re¯uxed over KOH,
Ê
1-Aza-2-methyl-1,4-diphenyl-1,3-butadiene 3a. Yellow
distilled, and stored under argon in the presence of 4 A
1
solid; mp 95±978C; IR (nmax, cm21) 1620, 1600, 1590; H
molecular sieves at 48C. Solvents used in extractions,
recrystallizations and in chromatographic columns were
distilled prior to use. b-Enamino phosphonium salts 1
were prepared following previously described procedures.28
AlCl3 was purchased from Merck, sublimed prior to use,
stored under argon and manipulated using inert atmosphere
techniques. All other reagents were commercially available
and were used without further puri®cation. All reactions
which required an inert atmosphere, were conducted under
NMR (CDCl3, TMS) d 7.58±6.78 (m, 11H), 6.75 (d, 1H,
Jˆ16.5 Hz), 2.48 (s, 3H, min), 2.05 (s, 3H, maj); 13C NMR
(CDCl3) d 165.1 (CvN, maj), 163.6 (CvN, min), 150.1,
149.4, 137.6, 136.3, 130.6, 128.0, 127.8, 127.7, 126.3,
122.5, 119.4, 118.6, 22.5 (CH3, min), 14.9 (CH3, maj);
MS (EI) (m/z,%): 221 (M1), 220 (78), 182 (13), 77 (100);
Anal. calcd for C16H15N: C 86.84, H 6.83, N 6.33; found: C
87.01, H 6.73, N 6.24.

8184
E. Aguilar et al. / Tetrahedron 56 (2000) 8179±8187
1-Aza-2-dideuteromethyl-1,4-diphenyl-1,3-butadiene 3b.
Yellow solid; mp 97±988C; H NMR (CDCl3, TMS) d
7.0 Hz); 13C NMR (CDCl3) d 152.5, 147.1, 141.5, 131.5,
129.0, 117.6, 117.2, 113.2, 111.1, 107.3, 50.3 (CH±N), 21.8
(CH3); MS (EI) (m/z,%): 213 (M1, 34), 131 (M12NHPh,
100), 77 (46); Anal. calcd for C14H16NO: C 78.84, H 7.56, N
6.57; found: C 78.70, H 7.69, N 6.69.
1
7.60±6.78 (m, 11H), 6.75 (d, 1H, Jˆ16.5 Hz), 2.36 (m,
1H, CHD2, min), 1.95 (m, 1H, CHD2, maj); 13C NMR
(CDCl3) d 166.0 (CvN, maj), 164.5 (CvN, min), 150.9,
150.3, 138.4, 137.1, 135.6, 135.5, 131.8, 131.4, 130.3,
129.1, 129.0, 128.9, 128.6, 128.5, 127.3, 127.1, 120.2,
119.5, 22.0 (m, CHD2, min), 15.2 (CHD2, maj); MS (EI)
(m/z,%): 223 (M1, 20), 222 (20), 146 (M12Ph, 13), 77
(100); Anal. calcd for C16H13D2N: C 86.07, H/D 7.66, N
6.27; found: C 86.21, H/D 7.53, N 6.15.
General procedure for the synthesis of secondary allylic
amines 4d±e
LDA (2.5 mmol, prepared in situ from diisopropylamine
and n-BuLi) was slowly added to a solution of b-enamino
phosphonium salt 1d or 1e (2.5 mmol) in dry THF (40 mL)
under inert atmosphere at 2788C. After stirring for 2 h the
reaction was hydrolyzed at low temperature (2508C),
extracted with diethyl ether (3£50 mL) and the combined
organic layer was dried over Na2SO4. Solvents were evapo-
rated under reduced pressure to give an oil that was
dissolved in EtOH (25 mL), treated with an excess of
NaBH4 (25 mmol) at 08C and stirred for 15 h. The reaction
mixture was hydrolyzed with ice-water, concentrated in
vacuum and extracted with CH2Cl2 (3£50 mL). The
combined organic layer was washed with brine, dried over
anhydrous Na2SO4, ®ltered and evaporated under reduced
pressure. The crude oily residue was puri®ed by column
chromatography (hexane/AcOEt 7/3 as eluent) to give the
corresponding secondary allylic amines in the yields
reported in Table 1.
1-Aza-4-(2-furyl)-2-methyl-1-phenyl-1,3-butadiene 3c.
Yellow solid; mp 84±858C; H NMR (CDCl3, TMS) d
1
7.46±6.39 (m, 10H), 2.39 (s, 3H, min), 2.00 (s, 3H, maj);
13C NMR (CDCl3) d 165.6 (CvN, maj), 164.3 (CvN,
min), 151.9, 151.6, 143.9, 143.6, 128.7, 125.5, 124.3,
123.4, 123.3, 119.5, 119.1, 111.9, 111.5, 23.0 (CH3, min),
15.8 (CH3, maj); MS (EI) (m/z,%): 211 (M1, 5), 196
(M12Me, 4), 136 (58), 146 (M12NPh, 100), 92 (51);
Anal. calcd for C14H13NO: C 79.59, H 6.20, N 6.63;
found: C 79.77, H 6.11, N 6.71.
General procedure for the synthesis of secondary allylic
amines 4a±c
Excess NaBH4 (25 mmol) was added in portions to a
solution of the corresponding a,b-unsaturated imine 3
(2.5 mmol) in EtOH (20 mL). After 15 h the reaction was
quenched with ice/water, concentrated in vacuum to remove
EtOH and extracted with diethyl ether (3£50 mL). The
combined organic layer was washed with brine, dried over
anhydrous Na2SO4, ®ltered and evaporated under reduced
pressure. The crude oily residue was puri®ed by column
chromatography (hexane/AcOEt 7/3 as eluent) to give the
corresponding secondary allylic amine in the yields reported
in Table 1.
N-Phenyl-3-buten-2-amine 4d. Yellow oil; Rfˆ0.71
1
(hexane/AcOEt 7/3); H NMR (CDCl3, TMS) d 7.60±6.52
(m, 5H), 5.81 (ddd, 1H, Jˆ5.6, 10.3, 17.2 Hz), 5.20 (dt, 1H,
Jˆ1.3, 17.2 Hz), 5.06 (dt, 1H, Jˆ1.3, 10.3 Hz), 3.97 (m,
1H), 3.40 (bs, 1H, NH), 1.15 (d, 3H, Jˆ6.9 Hz); 13C NMR
(CDCl3) d 147.4, 133.1, 129.1, 129.0, 116.8, 113.1, 48.5
(CH±N), 21.5 (CH3); Anal. calcd for C10H13N: C 81.59, H
8.90, N 9.51; found: C 81.43, H 9.00, N 9.65.
(E)-N-Phenyl-3-hexen-2-amine 4e. Yellow oil; Rfˆ0.60
(hexane/AcOEt 7/3); IR (nmax, cm21) 3380, 2900, 1650;
1H NMR (CDCl3, TMS) d 7.60±6.58 (m, 5H), 5.62 (dt,
1H, Jˆ5.9, 15.6 Hz), 5.40 (dd, 1H, Jˆ6.1, 15.6 Hz), 3.92
(m, 1H), 3.62 (bs, 1H, NH), 2.00 (m, 2H), 1.26 (d, 3H,
Jˆ6.9 Hz), 0.95 (t, 3H, Jˆ7.2 Hz); 13C NMR (CDCl3) d
147.4, 131.8, 129.1, 128.8, 116.8, 113.2, 50.2 (CH±N),
25.0 (CH2), 21.8 (CH3), 13.4 (CH3); Anal. calcd for
C12H17N: C 82.23, H 9.78, N 7.99; found: C 82.41, H
9.65, N 7.92.
(E)-N,4-Diphenyl-3-buten-2-amine 4a. Yellow oil; Rfˆ
0.40 (hexane/AcOEt 8/1); IR (nmax, cm21) 3400, 2950,
1590; 1H NMR (CDCl3, TMS) d 7.32±6.51 (m, 10H),
6.50 (d, 1H, Jˆ16.0 Hz), 6.30 (dd, 1H, Jˆ5.9, 16.0 Hz),
4.22 (m, 1H), 3.65 (bs, 1H, NH), 1.38 (d, 3H, Jˆ7.0 Hz);
13C NMR (CDCl3) d147.2, 136.8, 133.0, 129.0, 128.3,
127.1, 126.1, 117.1, 113.2, 50.6 (CH±N), 21.8 (CH3); MS
(EI) (m/z,%): 223 (M1, 32), 131 (M12NHPh, 100), 91 (37);
Anal. calcd for C16H17N: C 86.06, H 7.67, N 6.27; found: C
86.30, H 7.54, N 6.15.
Synthesis of primary allylic amines 7
(E)-1,1-Dideutero-N,4-diphenyl-3-buten-2-amine
4b.
)
Yellow oil; Rfˆ0.40 (hexane/AcOEt 8/1); IR (nmax, cm21
Method A. Synthesis by direct reduction of 4-amino-1-aza-
1,3-butadienes 5 with excess of alane (AlH3)ÐGeneral
procedure. A solution of the corresponding 4-amino-1-
aza-1,3-diene 5 (10 mmol) in anhydrous diethyl ether
(20 mL) was slowly added to a suspension of AlH3
(50 mmol, prepared in situ by reaction of 3LiAlH41
AlCl3)32 in ether (20 mL) with stirring at 08C. Once the
addition was complete, the reaction mixture was stirred
for several hours (10±14 h.) at room temperature. The
resulting white suspension was dropwise solvolyzed with
anhydrous methanol (15 mL) at 08C; water (20 mL) was
added and the reaction was extracted with diethyl ether
(3£25 mL). The combined organic layer was dried over
3410, 2970, 1595; 1H NMR (CDCl3, TMS) d 7.46±6.65 (m,
10H), 6.58 (d, 1H, Jˆ16.0 Hz), 6.22 (dd, 1H, Jˆ5.8,
16.0 Hz), 4.18 (m, 1H), 3.60 (bs, 1H, NH), 1.29 (m, 1H);
13C NMR (CDCl3) d 147.2, 136.8, 133.0, 129.0, 128.3,
127.1, 126.1, 117.1, 113.2, 50.5 (CH±N), 21.5 (m,
CHD2); Anal. calcd for C16H15D2N: C 85.30, H/D 8.48, N
6.22; found: C 85.18, H/D 8.54, N 6.37.
(E)-4-(2-Furyl)-N-phenyl-3-buten-2-amine 4c. Yellow
oil; Rfˆ0.38 (hexane/AcOEt 8/1); IR (nmax, cm21) 3395,
3050, 1595; 1H NMR (CDCl3, TMS) d 7.35±6.18 (m,
10H), 4.11 (m, 1H), 3.51 (bs, 1H, NH), 1.38 (d, 3H, Jˆ

E. Aguilar et al. / Tetrahedron 56 (2000) 8179±8187
8185
Na2SO4, ®ltered and solvents were evaporated under vacuum.
The resulting crude residue was analyzed by GC/MS or H
NMR (300 MHz) to determine its composition.
C16H16ClN: C 74.56, H 6.26, N 5.43; found: C 74.64, H
6.18, N 5.36.
1
(E)-1-Cyclohexyl-2-methyl-3-phenyl-2-propen-1-amine
7e. Yellow oil; puri®ed by high vacuum distillation; bp
When ketones (or imines) 6 were detected, they were
separated from the mixture of amines by acid±base extrac-
tion and identi®ed. Primary allylic amines 7 were further
puri®ed by high vacuum distillation of by ¯ash chroma-
1
88±918C (1023 mmHg); H NMR (CDCl3, TMS) d 7.41±
6.57 (m, 5H), 6.31 (s, 1H), 3.05 (d, 1H, Jˆ8.0 Hz), 1.73 (s,
3H), 2.17±0.67 (m, 11H12H); 13C NMR (CDCl3) d 140.6
(C), 137.5 (C), 128.4 (CH), 127.4 (CH), 125.6 (CH), 125.5
(CH), 65.0 (CH), 40.7 (CH), 30.1 (CH2), 28.9 (CH2), 26.0
(CH2), 25.8 (CH2), 25.7 (CH2), 12.7 (CH3); MS (EI)
(m/z,%): 229 (M1, ,5), 146 (M1283); Anal. calcd for
C16H23N: C 83.78, H 10.11, N 6.11; found: C 83.91, H
10.07, N 6.05.
1
tography (n-hexane/ether 7/3). When GC/MS or H NMR
analysis indicated the absence of compounds 6, the crude
residue was directly puri®ed by high-vacuum distillation or
by ¯ash chromatography.
General procedure for the synthesis by direct reduction
of 4-amino-1-aza-1,3-butadienes 5 with excess of
DIBALH
(E)-1-Cyclohexyl-2-ethyl-3-phenyl-2-propen-1-amine 7f.
Yellow oil; puri®ed by ¯ash chromatography; H NMR
1
(CDCl3, TMS) d 7.38±7.06 (m, 5H), 6.29 (s, 1H), 3.06 (d,
1H, Jˆ7.3 Hz), 2.17±0.67 (m, 13H12H), 1.00 (t, 1H, Jˆ
6.9 Hz); 13C NMR (CDCl3) d 147.3 (C), 138.0 (C), 128.4
(CH), 128.0 (CH), 126.0 (CH), 125.2 (CH), 62.9 (CH), 42.0
(CH), 30.9 (CH2), 28.5 (CH2), 26.4 (CH2), 26.2 (CH2), 22.2
(CH2), 13.8 (CH3); MS (EI) (m/z,%): 243 (M1, ,5), 214
(M12Et, ,5), 160 (M12c-C6H11, 100), 129 (23); Anal.
calcd for C17H25N: C 83.89, H 10.36, N 5.75; found: C
83.94, H 10.33, N 5.62.
DIBALH (50 mmol, 1 M in toluene) was slowly added to a
solution of the corresponding 4-amino-1-aza-1,3-diene 5
(10 mmol) at 08C in an inert atmosphere. Once the addition
was complete, the yellow solution was stirred for 10±14 h at
room temperature and solvolyzed with anhydrous methanol
(15 mL). The reaction mixture was worked up and puri®ed
as described above for the reduction with alane.
(E)-2-Methyl-1,3-diphenyl-2-propen-1-amine 7a. Yellow
oil; puri®ed by high vacuum distillation; bp 91±948C (1023
mmHg); H NMR (CDCl3, TMS) d 7.38±7.02 (m, 10H),
1
(E)-1,3-Diphenyl-2-propen-1-amine 7j. Yellow oil; puri-
®ed by ¯ash chromatography; H NMR (CDCl3, TMS) d
1
6.71 (s, 1H), 4.56 (s, 1H), 1.66 (s, 3H), 1.65 (bs, 2H,
NH2); 13C NMR (CDCl3) d 145.2 (C), 142.8 (C), 139.2
(CH), 130.2 (CH), 129.4 (CH), 129.2 (CH), 128.1 (CH),
127.3 (CH), 126.0 (CH), 64.3 (CH), 15.9 (CH3); MS (EI)
(m/z,%): 223 (M1, 48), 208 (M12Me, 100), 106 (83), 91
(16), 77 (18); Anal. calcd for C16H17N: C 86.06, H 7.67, N
6.27; found: C 86.31, H 7.51, N 6.22.
7.38±7.09 (m, 10H), 6.48 (d, 1H, Jˆ15.8 Hz), 6.25 (dd, 1H,
Jˆ6.5, 15.8 Hz), 4.57 (d, 1H, Jˆ6.5 Hz), 1.75 (bs, 2H,
NH2); 13C NMR (CDCl3) d 143.6 (C), 136.0 (C), 133.0
(CH), 127.8 (CH), 127.5 (CH), 126.4 (CH), 126.1 (CH),
125.7 (CH), 125.4 (CH), 56.8 (CH); MS (EI) (m/z,%): 209
(M1, 52), 208 (M121, 100), 106 (M12103, 28); Anal.
calcd for C15H55N: C 86.08, H 7.22, N 6.69; found: C
86.10, H 7.17, N 6.61.
(E)-2-Methyl-3-phenyl-1-p-tolyl-2-propen-1-amine 7b.
Yellow oil; puri®ed by high vacuum distillation; bp 102±
1058C (1023 mmHg); 1H NMR (CDCl3, TMS) d 7.45±7.10
(m, 9H), 6.73 (s, 1H), 4.56 (s, 1H), 2.32 (s1bs, 3H12H,
NH2), 1.70 (s, 3H); 13C NMR (CDCl3) d 142.5 (C), 141.7
(C), 138.6 (C), 136.2 (C), 129.5 (CH), 128.5 (CH), 127.2
(CH), 126.2 (CH), 124.9 (CH), 62.9 (CH), 21.0 (CH3), 14.8
(CH3); MS (EI) (m/z,%): 237 (M1, 31), 222 (M12Me), 120,
91, 77; Anal. calcd for C17H19N: C 86.03, H 8.07, N 5.90;
found: C 85.89, H 8.00, N 6.01.
(E)-1-Phenyl-1-penten-3-amine 7k. Yellow oil; puri®ed
by high vacuum distillation; bp 50±538C (1023 mmHg);
1H NMR (CDCl3, TMS) d 7.36±7.15 (m, 5H), 6.43 (d,
1H, Jˆ15.9 Hz), 6.10 (dd, 1H, Jˆ7.2, 15.9 Hz), 3.32 (m,
1H), 1.59 (bs, 2H, NH2), 1.52 (m, 2H), 0.91 (t, 3H, Jˆ
7.4 Hz); 13C NMR (CDCl3) d 136.8 (C), 134.4 (CH),
128.7 (CH), 128.2 (CH), 126.9 (CH), 125.9 (CH), 55.2
(CH), 30.3 (CH2), 10.2 (CH3); MS (EI) (m/z,%): 161 (M1,
13), 132 (M12Et, 100), 115 (M1246, 32), 91 (7), 77 (7);
Anal. calcd for C11H15N: C 81.94, H 9.38, N 8.68; found: C
81.82, H 9.35, N 8.66.
(E)-1-p-Chlorophenyl-2-methyl-3-phenyl-2-propen-1-
amine 7c. Yellow oil; puri®ed by ¯ash chromatography; 1H
NMR (CDCl3, TMS) d 7.52±6.71 (m, 9H), 6.56 (s, 1H),
4.45 (s, 1H), 1.66 (bs, 2H, NH2), 1.50 (s, 3H); 13C NMR
(CDCl3) d 144.5 (C), 143.2 (C), 137.2 (C), 132.4 (C), 131.8
(CH), 129.6 (CH), 128.9 (CH), 126.9 (CH), 124.2 (CH),
63.7 (CH), 15.6 (CH3); Anal. calcd for C16H16ClN: C
74.56, H 6.26, N 5.43; found: C 74.72, H 6.23, N 5.40.
Reduction with excess AlD3
Formation of (E)-1,3-dideutero-2-methyl-1,3-diphenyl-
2-propen-1-amine 7m. A solution of 1-aza-3-methyl-2,4-
diphenyl-4-phenylamino-but-1,3-diene (5, ArˆR1ˆR3ˆPh,
R2ˆMe) (10 mmol) in anhydrous diethyl ether (20 mL) was
slowly added to a suspension of AlD3 (50 mmol, prepared in
situ by reaction of 3LiAlD41AlCl3)32 in ether (20 mL) with
stirring at 08C. The following operations were identical to
those described above for the reduction with alane. Primary
allylic amine 7m was thus obtained and it was characterized
by NMR and MS. Yellow oil; puri®ed by ¯ash chroma-
(E)-3-p-Chlorophenyl-2-methyl-1-phenyl-2-propen-1-
amine 7d. Yellow oil; puri®ed by ¯ash chromatography; 1H
NMR (CDCl3, TMS) d 7.76±6.98 (m, 9H), 6.69 (s, 1H),
4.56 (s, 1H), 1.71 (bs, 2H, NH2), 1.65 (s, 3H); 13C NMR
(CDCl3) d 143.3 (C), 141.0 (C), 138.6 (C), 133.9 (C), 129.8
(CH), 129.0 (CH), 128.9 (CH), 127.2 (CH), 127.1 (CH),
126.0 (CH), 63.2 (CH), 15.2 (CH3); Anal. calcd for
1
tography; H NMR (CDCl3, TMS) d 7.38±7.12 (m, 10H),

8186
E. Aguilar et al. / Tetrahedron 56 (2000) 8179±8187
1.66 (s, 3H), 1.65 (bs, 2H, NH2); 13C NMR (CDCl3) d 143.5,
140.9, 137.7, 130.8, 128.8, 128.2, 127.9, 126.8, 126.7,
126.1, 124.4 (t, JC-Dˆ23.1 Hz), 62.4 (t, JC±Dˆ23.1 Hz),
14.8 (CH3); MS (EI) (m/z,%): 225 (M1, 30), 210
(M12Me, 79), 107 (100), 91 (8), 77 (23); Anal. calcd for
C16H15D2N: C 85.30, H/D 8.48, N 6.22; found: C 85.15, H/D
8.58, N 6.36.
3.22 (bs, 2H, NH2), 3.15 (m, 1H), 2.72 (m, 1H), 2.02 (s,
1H); 13C NMR (CDCl3) d 143.4 (C), 138.2 (C), 135.6 (C),
128.7 (CH), 128.6 (CH), 128.5 (CH), 125.9 (CH), 125.6
(CH), 124.9 (CH), 123.5 (CH), 81.5 (C) 68.0 (CH), 59.6
(CH), 18.5 (CH2); MS (EI) (m/z,%): 247 (M1, 15), 208
(M12Propargyl, 70), 170 (M12Ph, 35), 106 (100); Anal.
calcd for C18H17N: C 87.41, H 6.93, N 5.66; found: C 87.32,
H 6.84, N 5.69.
Method B. Synthesis by sequential reduction of 4-amino-
1-aza-1,3-butadienes 5 with DIBALH and NaBH4/
MeOHÐGeneral procedure. DIBALH (21 mmol, 1 M
in toluene) was dropwise added to a solution of the corre-
Acknowledgements
sponding 4-amino-1-aza-1,3-diene
5
(10 mmol) in
We are grateful to the DGICYT and to the Ministerio de
Â
anhydrous toluene (20 mL) at 08C. After the addition was
concluded, the resulting yellow solution was stirred at room
temperature for 10±14 h, then solvolyzed with anhydrous
methanol (25 mL) and stirred at room temperature for a
further 4 h. The resulting solution, almost colorless, was
hydrolyzed with water (25 mL), evaporated under vacuum
to remove MeOH and extracted with diethyl ether
(3£25 mL). The following operations were identical to
those described for the reduction with alane (vide supra).
Educacion y Ciencia (Spain) for predoctoral fellowships to
I. M. and E. A., respectively. We also thank Dr Pablo
Bernard for GC/MS measurements and helpful discussions.
References
1. For an excellent review on the synthesis of allylic amines see:
Cheikh, R. B.; Chaabouni, R.; Laurent, A.; Mison, P.; Nafti, A.
Synthesis 1983, 685±700.
(E)-2-Ethyl-1,3-diphenyl-2-propen-1-amine 7g. Pale
yellow oil; puri®ed by ¯ash chromatography; 1H NMR
(CDCl3, TMS) d 7.44±6.87 (m, 10H), 6.73 (s, 1H), 4.62
(s, 1H), 2.41±1.93 (m, 3H, 1H1NH2), 1.80 (m, 1H), 0.80
(t, 3H, Jˆ7.0 Hz); 13C NMR (CDCl3) d 146.7 (C), 143.9
(C), 137.9 (CH), 128.5 (CH), 128.2 (CH), 128.1 (CH),
127.91 (CH), 127.87 (CH), 127.84 (CH), 127.81 (CH),
127.1 (CH), 126.8 (CH), 126.0 (CH), 124.8 (CH), 60.5
(CH), 22.0 (CH2), 13.7 (CH3); MS (EI) (m/z,%): 237 (M1,
14), 208 (M12Et, 100), 106 (94); Anal. calcd for C17H19N:
C 86.03, H 8.07, N 5.90; found: C 86.25, H 8.00, N 5.95.
2. (a) Hagihara, M.; Anthony, N. J.; Stout, T. J.; Clardy, J.;
Schreiber, S. L. J. Am. Chem. Soc. 1992, 114, 6568±6570. (b)
Devadder, S.; Verheyden, P.; Jaspers, H. C. M.; Van Binst, G.;
Â
Tourue, D. Tetrahedron Lett. 1996, 37, 703±706.
3. (a) Schlessinger, R. H.; Li, Y.-J. J. Am. Chem. Soc. 1996, 118,
3301±3302. (b) Tavares, F.; Lawson, J. P.; Meyers, A. I. J. Am.
Chem. Soc. 1996, 118, 3303±3304. (c) Entwistle, D. A.; Jordan,
S. I.; Montgomery, J.; Pattenden, G. J. Chem. Soc., Perkin Trans. 1
1996, 1315±1317.
4. (a) Overman, L. E.; Petty, C. B.; Doedens, R. J. J. Org. Chem.
È
1979, 44, 4183±4185. (b) Backvall, J.-E.; Nordberg, R. E.;
Nystrom, J.-E.; Hogberg, T.; Ulff, B. J. Org. Chem. 1981, 46,
(E)-2-Allyl-1,3-diphenyl-2-propen-1-amine 7h. Pale
yellow oil; puri®ed by ¯ash chromatography; 1H NMR
(CDCl3, TMS) d 7.30±6.92 (m, 10H), 6.84 (s, 1H), 5.72
(m, 1H), 4.96 (m, 2H), 4.60 (s, 1H), 3.00 (dd, 1H, Jˆ7.2,
17.9 Hz), 2.52 (dd, 1H, Jˆ9.0, 17.9 Hz), 1.56 (bs, 2H, NH2);
13C NMR (CDCl3) d 144.1 (C), 142.9 (C), 137.7 (C), 136.4
(CH), 128.7 (CH), 128.5 (CH), 128.3 (CH), 128.2 (CH),
127.4 (CH), 127.2 (CH), 126.6 (CH), 126.1 (CH), 116.1
(CH2), 60.4 (CH), 33.8 (CH2); MS (EI) (m/z,%): 249 (M1,
5), 208 (M12Allyl, 97), 106 (100); Anal. calcd for
C18H19N: C 86.70, H 7.68, N 5.62; found: C 86.67, H
7.65, N 5.69.
È
È
3479±3483 (and references cited therein).
5. StuÈtz, A. Angew. Chem., Int. Ed. Engl. 1987, 26, 320±328.
6. (a) Petranyi, G.; Ryder, N. S.; StuÈtz, A. Science 1984, 224,
1239±1241. (b) McDonald, I. A.; Lacoste, J. M.; Bey, P.;
Palfreyman, M. G.; Zreika, M. J. Med. Chem. 1985, 28, 186±
193. (c) Padgette, S. R.; Wimalasena, K.; Herman, H. H.;
Sirimanne, S. R.; May, S. W. Biochemistry 1985, 24, 5826±
5839. (d) Ohba, T.; Ikeda, E.; Wakayama, J.; Takei, H. Bioorg.
Med. Chem. Lett. 1996, 6, 219±224.
7. (a) Bartmann, W.; Kaiser, J. Ger. Offen. 2,103,119, 1972;
Chem. Abstr. 1972, 77, 140141m. (b) Kato, H. Ger. Offen.
2,350,125, 1974; Chem. Abstr. 1974, 81, 37401e.
(E)-2-Benzyl-1,3-diphenyl-2-propen-1-amine 7i. Pale
yellow oil; puri®ed by ¯ash chromatography; 1H NMR
(CDCl3, TMS) d 7.35±7.10 (m, 16H), 4.49 (s, 1H), 3.86
(d, 1H, Jˆ15.5 Hz), 3.14 (d, 1H, Jˆ15.5 Hz), 2.22 (bs,
2H, NH2); 13C NMR (CDCl3) d 143.7 (C), 142.5 (C),
139.1 (C), 137.1 (C), 128.0 (CH), 127.9 (CH), 127.8
(CH), 126.8 (CH), 126.6 (CH), 126.0 (CH), 125.7 (CH),
125.5 (CH), 59.0 (CH), 34.7 (CH2); MS (EI) (m/z,%): 299
(M1, 4), 282 (M12NH3, 10), 208 (M12Bn, 100), 106 (90);
Anal. calcd for C22H21N: C 88.25, H 7.07, N 4.68; found: C
88.18, H 7.00, N 4.61.
8. (a) Kawazoe, A. Japan Kokai, 73 58,146, 1973; Chem. Abstr.
1974, 80, 815w. (b) Morris, L. R. US Patent, US 3,539,632, 1970;
Chem. Abstr. 1971, 74, 42123a.
9. For selected references see: (a) Sibi, M. P.; Li, B. Tetrahedron
Lett. 1992, 33, 4115±4118. (b) Huwe, C. M.; Blechert, S.
Tetrahedron Lett. 1994, 35, 9537±9540. (c) Lemaire-Audoire,
Ã
S.; Savignac, M.; Genet, J. P. Synlett 1996, 75±78. (d) Weisen-
burger, G. A.; Beak, P. J. Am. Chem. Soc. 1996, 118, 12218±
12219. (e) Kitagawa, O.; Suzuki, T.; Taguchi, T. Tetrahedron
Lett. 1997, 38, 8371±8374. (f) Paquette, L.; Leit, S. M. J. Am.
Chem. Soc. 1999, 121, 8126±8127 (and references cited therein).
Â
10. (a) Barluenga, J.; Canteli, R. M.; Florez, J. J. Org. Chem.
(E)-1,3-Diphenyl-2-propargyl-2-propen-1-amine 7l. Yellow
oil; puri®ed by ¯ash chromatography; H NMR (CDCl3,
TMS) d 7.41±7.15 (m, 10H), 6.83 (s, 1H), 4.87 (s, 1H),
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