Palladium-catalyzed highly regioselective and stereoselective arylation of electron-rich allylamines with aryl bromides

Article abstract of DOI:10.1016/j.tet.2012.02.081

A palladium-catalyzed, highly efficient Heck arylation of electron-rich N,N-diprotected allylamine derivatives with a wide range of aryl bromides under ligand-free conditions has been developed. In the presence of Pd(OAc) ₂ and an appropriate a

Full text of DOI:10.1016/j.tet.2012.02.081

Tetrahedron 68 (2012) 4919e4926
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Palladium-catalyzed highly regioselective and stereoselective arylation
of electron-rich allylamines with aryl bromides
,
b
,
b,
*
Zhen Jiang a, Lingjuan Zhang a, Chaonan Dong a, Baode Ma b, Weijun Tang c, Lijin Xu a , Qinghua Fan
,
*
,
Jianliang Xiao c
*
a Department of Chemistry, Renmin University of China, Beijing 100872, China
b Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences,
Beijing 100190, China
c Liverpool Centre for Materials and Catalysis, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 January 2012
Received in revised form 20 February 2012
Accepted 24 February 2012
Available online 29 March 2012
A palladium-catalyzed, highly efficient Heck arylation of electron-rich N,N-diprotected allylamine de-
rivatives with a wide range of aryl bromides under ligand-free conditions has been developed. In the
presence of Pd(OAc)2 and an appropriate additive, the reaction proceeds with excellent regioselectivity
and stereoselectivity, leading exclusively to the g-arylated (E)-allylamine products in good to excellent
yields. It was found that the choice of solvent, olefin, additive and temperature has an important in-
fluence on the reaction. Worthy of note is that good results were observed only when using N,N-di-
protected allylamines containing carbamate moiety, and the steric properties of allylamines also have
important impacts on the regiocontrol. The use of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) or HQ
(hydroquinone) as the additive is also crucial for securing a faster reaction rate. This method provides
Keywords:
Heck reaction
Allylamine
Arylation
a straightforward approach for the efficient synthesis of various
g-arylated, linear (E)-allylamines.
Palladium
Ó 2012 Elsevier Ltd. All rights reserved.
Regioselectivity
1. Introduction
regioselective arylation of electron-rich olefins, such as vinyl
ethers, allylic alcohol derivatives, and enamides.5ꢀ14 In this regard,
the application of Pd-catalyzed Heck arylation of electron-rich
allylamines to prepare arylated allylamines has recently gained
much attention.2d,2f,2i,15e18 However, this kind of transformation is
often complicated by the formation of mixtures of internal and
terminal regioisomers (Scheme 1). The efforts of Hallberg and
Larhed,16a,b Wu16c and Baxter2i have resulted in useful strategies for
Allylamines are widespread structural units in a large number of
natural and biologically active compounds, and the presence of two
highly versatile functional groups renders them valuable substrates
for many types of reactions to afford useful products.1,2 Because of
their importance, it is not surprising that much effort has been
devoted to the efficient construction of these compounds.1,3 Con-
sequently, a variety of methods for the synthesis of various func-
tionalized allylamines can now be found in the literature. However,
despite the progress made in this area, there is still significant room
for improvement of the synthetic efficiency, for example, in terms
of reactivity and selectivity.
The Pd-catalyzed Heck reaction has become one of the most
powerful tools for the construction of CeC bonds in organic syn-
thesis owing to its simplicity and tolerance of various functional
groups.4 Over the past two decades, improved strategies have been
developed to broaden its application, particularly toward highly
highly selective internal
However, the -regioselective arylation of allylamines has not been
well-developed. Ripin17a and Wilson17b reported that Pd-catalyzed
highly regioselective and stereoselective terminal -arylation of
b-arylation of allylamine derivatives.
g
g
allylamine derivatives could be accomplished in alcoholic solvents
under ligand-free conditions to give exclusively linear (E)-allyl-
amine products, but only one aryl iodide substrate was attempted,
and the general utility of this chemistry has not been explored. Very
recently, Sigman,18a Cacchi18b and Correia18c reported that
Pd2(dba)3 could efficiently catalyze the preferential g-arylation of
allylamines with arenediazonium salts in the absence of ligand.
However, the synthetic utility of this chemistry might be restricted
by the intrinsic drawbacks of arenediazonium salt, such as in-
* Corresponding authors. Tel.: þ86 106251 1528; fax: þ86 10 6251 6664 (L.X.);
tel./fax: þ86 10 62554472 (Q.F.); tel.: þ44 1517942937; fax: þ44 1517943589 (J.X.);
e-mail addresses: xulj@chem.ruc.edu.cn (L. Xu), fanqh@iccas.ac.cn (Q. Fan), j.xiao@
liv.ac.uk (J. Xiao).
stability and explosive potential. Considering the importance of g-
arylated allylamines in chemical synthesis and particularly that
leading to biologically active compounds,19 it is of great interest to
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.02.081

4920
Z. Jiang et al. / Tetrahedron 68 (2012) 4919e4926
coupling reaction was carried out in CH3CN at 85 ꢁC with Pd(OAc)2/
P
P
Ar
R
Pd
PPh3 as catalyst and K2CO3 as the base. Only the linear (E)-allyl-
amine product 3aa was observed, while the internal isomer 4aa or
the Z isomer could not be detected after 12 h (Table 1, entry 1). This
result indicates that the reaction follows the neutral route (Scheme
1, path B), and the ionic pathway (Scheme 1, path A) is either
completely suppressed or its involvement in the arylation is in-
significant. Similar experimental observations have been reported
in the regioselective Heck coupling reaction of 2a with aryl iodide
and arenediazonium salts under ligand-free conditions.17a,18 In
view of the significant advantage of ligand-free conditions, we then
decided to examine the reaction of 1a and 2a in the absence of li-
gand. However, employing Ripin’s protocol17a resulted in no re-
action (Table 2, entry 2). The combination of Pd2(dba)3, NaOAc and
NEt3, which was reported to work well for the regioselective linear
arylation of N-allyl-2-methoxyacetamide with aryl iodide,17b gave
similarly poor result (Table 2, entry 3). Delightfully, the reaction in
CH3CN remained active and regioselectivity was unchanged in the
absence of a ligand (Table 2, entry 4). In order to further improve
the efficiency, a number of solvents were screened. The use of
DMSO, dioxane and toluene afforded the desired product 3aa in
higher yields of 77e81% (Table 1, entries 5e7), and the highest yield
of 85% was observed in DMF (Table 1, entry 8). Although ethylene
glycol (EG) has been recently identified as a useful solvent for
highly regioselective internal arylation of electron-rich olefins,9 no
reaction occurred in this case (Table 1, entry 9). The use of Pd(OAc)2
as a source of palladium was essential for this transformation, with
catalysts derived from other Pd precursors being not very efficient
(Table 1, entries 10e12). For comparison, the performance of other
bases, including Cs2CO3, K3PO4, KOAc, KOtBu and tetrabuty-
lammonium acetate (TBAA) (Table 1, entries 13e17), was in-
vestigated, but none of them could work as effectively as K2CO3.
The effect of additive was also studied. When 10 mol % HQ was
introduced, the reaction could go to completion in 6 h, exclusively
giving the desired product 3aa in 82% yield (Table 1, entry 18). The
reaction could proceed more quickly at 100 ꢁC, giving a full con-
version in 3 h with a slightly higher yield (Table 1, entry 19). When
the temperature was increased to 120 ꢁC, the reaction finished in
1.2 h, but the yield diminished due to the formation of side products
(Table 1, entry 20). Interestingly, replacing HQ with TEMPO could
enable the reaction to finish in 1.2 h at 100 ꢁC with 89% yield (Table
1, entry 21). It is clear that TEMPO is a better choice. A further in-
crease to 1 equiv TEMPO had negligible effect on the reactivity
(Table 1, entry 22). HQ or TEMPO may either inhibit the polymer-
ization of the olefin or function as a ligand or both. The accelerating
effect of the free-radical scavenger in Pd-catalyzed cross-coupling
reactions has been recently disclosed in the literature.20 We tried
the effect of tetrabutylammonium bromide and tetrabutylammo-
nium chloride, which have been shown to promote the Heck re-
action,21 but none of them led to an increase in yield. The effect of
reducing agents, such as hydrazine and sodium formate were also
examined, but no acceleration was observed.22
Ar
Ar
R
A
B
P
P
Pd
Ar
X
R
P
P
Ar
R
Pd
X
R
Scheme 1. Formation of regioisomers via two competing pathways in the Heck reaction.
develop practical and highly efficient catalytic synthetic methods to
access these compounds from safe and stable aryl halides. In con-
tinuing our research in regioselective Heck arylation of electron-
rich olefins,7,9,11 herein we report that, in the presence of
Pd(OAc)2 catalyst and appropriate additive, electron-rich N,N-
diprotected allylamines could undergo highly efficient g-arylation
with aryl bromides under ligand-free conditions, affording the
desired (E)-allylamine products in good to excellent yields in
a highly regioselective and stereoselective manner.
2. Results and discussion
We started our investigation with methyl 4-bromobenzoate (1a)
as the model substrate and N,N-(Boc)2-allylamine (2a) as the model
olefin under various reaction conditions (Table 1). Initially, the
Table 1
Screening conditions for Heck arylation of methyl 4-bromobenzoate (1a) with al-
lylamine 2aa
Br
Pd(OAc)2
base, solvent
N(Boc)2
N(Boc)2
Ar
N(Boc)2
+
+
Ar
MeO2C
4aa
3aa
1a
2a
Ar = 4-methyl benzoate
Entry
Solvent
Base
Time (h)
Yield (%)b
3aa/4aac
1d
CH3CN
iPrOH
EtOH
CH3CN
DMSO
dioxane
toluene
DMF
K2CO3
NEt3
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
6
30
nd
nd
30
81
77
80
85
nd
80
82
44
nd
83
55
nd
76
82
86
75
89
89
>99/1
nd
nd
2e
3e
NaOAc
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
K3PO4
KOAc
4
5
6
7
8
9
>99/1
>99/1
>99/1
>99/1
>99/1
nd
>99/1
>99/1
>99/1
nd
>99/1
>99/1
nd
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
EG
10e
11f
12g
13
14
15
16
17
18h
19h,i
20h,j
21i,k
22i,l
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
KOtBu
TBAA
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
3
1.2
1.2
1.2
Having established the optimal reaction conditions, we then
explored the reaction of 2a with a range of aryl bromides. As
summarized in Table 2, all the reactions proceeded rapidly, with
reaction times of as short as less than 2 h observed in some cases
(Table 2, entries 1e5). It is notable that all reactions exhibited ex-
cellent regioselectivivites (terminal/internal>99:1) and no Z iso-
mers could be observed in these transformations. The reaction
DMF
a
Unless otherwise noted, all reactions were carried out with 1a (1.0 mmol), 2a
(1.2 mmol), Pd(OAc)2 (1 mol %), base (2.0 mmol), solvent (3.0 ml), 85 ꢁC.
b
Isolated yield.
Determined by 1H NMR analysis. When no
b-arylated product was detected,
c
a value of >99/1 was assigned.
d
2 mol % PPh3 was added.
e
afforded good to excellent yields of the expected g-arylated linear
Pd2(dba)3 was used to replace Pd(OAc)2.
PdCl2 was used to replace Pd(OAc)2.
Pd(COCF3)2 was used to replace Pd(OAc)2.
f
(E)-allylamines, tolerating electronically different substituents on
the aromatic ring. No significant electronic effect on the isolated
yield of the desired products was observed, but the reaction pro-
ceeded slightly faster in the olefination of electron-deficient aryl
bromides (Table 2, entries 1e10), and slightly longer reaction times
were needed for the electron-rich ones (Table 2, entries 12e15). The
g
h 10 mmol% HQ was added.
i
Reaction temperature 100 ꢁC.
j
Reaction temperature 120 ꢁC.
k 10 mmol% TEMPO was added.
l
1.0 equiv TEMPO was added.

Z. Jiang et al. / Tetrahedron 68 (2012) 4919e4926
Table 2 (continued )
4921
Table 2
Regioselective and stereoselective Heck arylation of 2a with aryl bromidesa
Entry
Substrate
Br
Time (h)
3
Yield (%)b
Br
Pd(OAc)2
K2CO3, DMF,100 o
TEMPO
N(Boc)2
R
N(Boc)2
R
+
19
1r
1s
82
C
N
1
2a
3a
Entry
1
Substrate
Time (h)
1.2
Yield (%)b
89
Br
Br
Br
20
3
79
1a
1b
1c
1d
N
MeO2C
2
3
4
1.5
1.5
1.2
90
83
88
a
Unless otherwise noted, all reactions were carried out with aryl bromide
(1.0 mmol), allylamine 2a (1.2 mmol), Pd(OAc)2 (1 mol %), TEMPO (10 mmol%),
K2CO3 (2.0 mmol), DMF (3.0 ml), 100 ꢁC.
MeOC
Br
b
Isolated yield.
2.4 mmol allylamine 2a was added.
c
OHC
F3C
Br
Br
catalytic system also worked effectively for the olefination of
a polyhaloarene, furnishing mono- or poly-olefinated products in
good yields (Table 2, entries 16e17). Thus, in the presence of
1.2 equiv 2a, compound 1p (1,4-dibromobenzene) was mono-
olefinated to provide the product 3pa1 as the main product, leav-
ing another position for further functionalization (Table 2, entry
16). Indeed, using 2.4 equiv 2a led to the di-olefinated product 3pa2
(Table 2, entry 17). The reaction is not only limited to aryl bromides,
and heteroaryl bromides participated equally well to afford the
corresponding allylamines in good yields (Table 2, entries 18e20).
Noteworthy is that all the substrates underwent clean conversions
without any allylic migration, diarylation or partial deprotection.
With the success in allylamine 2a, we then turned our attention
to the Heck arylation of other allylamine derivatives. However,
under the conditions established for 2a the arylation of N,N-
diprotected allylamines 2b-d proved to be problematic. For exam-
ple, the coupling reaction of 1a with allylamine 2b (2-
allylisoindoline-1,3-dione) provided the desired (E)-allylamine
3ab in only 30% yield along with a number of unknown side
products after 6 h. Gratifyingly, replacing TEMPO with HQ could
result in a clean reaction, furnishing an improved yield of 90%
(Table 3, entry 1). As can be seen from the results shown in Table 3,
the combination of Pd(OAc)2 with HQ could efficiently catalyze the
regioselective and stereoselective coupling reactions of aryl bro-
mides with 2b regardless of the nature of the substituents on the
aryl ring, exclusively delivering the linear (E)-allylamine products
in good to excellent yields. It should be noted, however, that the
reaction of aryl bromide bearing electron-rich group required
a longer reaction time of 10 h (Table 3, entries 6e7). In the arylation
of allylamine 2c (N-Boc-N-Cbz-allylamine), it was found that the
5
6
1e
1f
1.5
3
87
85
NC
CN
Br
Br
7
8
9
1g
1h
1i
2
2
2
81
80
83
O
MeOC
Br
O
Br
O
Br
10
11
12
13
1j
1k
1l
2
3
3
3
85
82
79
81
Br
Br
MeO
MeO
Br
Br
1m
main reaction product was the g-arylated N-Boc-allylamine prod-
uct, most probably as a result of the deprotection of Cbz group
during the reaction. This problem could be easily resolved simply
by decreasing the reaction temperature from 100 ꢁC to 85 ꢁC, which
allowed the smooth olefination of electron-deficient aryl bromides
MeO
MeO
14
1n
3
86
OMe
Br
to exclusively afford
g-arylated (E)-N-Boc-N-Cbz-allylamines in
high yields (Table 3, entries 9e13), albeit with longer reaction
times. Likewise, due to the occurrence of deprotection at 100 ꢁC, the
more electron-rich allylamine 2d (ethyl allyl(naphthalen-1-
ylmethyl)carbamate) was also arylated at a low temperature of
85 ꢁC, which afforded the (E)-allylamine products in high yields
with excellent regioselectivities (Table 3, entries 14e15). However,
the reaction of electron-rich aryl bromides with either 2c or 2d did
not proceed under the present conditions. No reaction was ob-
served in the arylation of N,N-diethyl allylamine (2e) (Table 3, entry
16). It is believed that the strong coordination of the nitrogen atom
of allylamine 2e to Pd could result in catalyst poisoning, thereby
15
16
1o
1p
4
2
78
79
Br
Br
Br
Br
17c
18
1p
1q
4
3
83
75
Br
N

4922
Z. Jiang et al. / Tetrahedron 68 (2012) 4919e4926
inhibiting the arylation. Similar poor performance of N,N-dialkyl
Table 3
allylamine has been reported recently.16b,18b We also tried the
Regioselective and stereoselective Heck arylation of 2bef with aryl bromidesa
arylation of monosubstituted allylamide 2f (N-Boc-allylamine)
NR1R2
Pd(OAc)2
K2CO3, DMF, HQ, 100 o
NR1R2
Ar-Br
+
Ar
NR1R2
+
(Table 3, entry 17), but a mixture of
g- and b-arylated products were
Ar
C
1
2b-f
obtained with a ratio of 43/57. It should be pointed out that no
g/b
3
4
2b: R1, R2 = Pht
product from a potentially competing allylic migration reaction
could be detected in all these reactions.
2c: R1 = Boc, R2 = Cbz
2d: R1 = NaphCH2, R2 = CO2Et
2e: R1 = R2 = Et
The results presented in Tables 2and 3 indicate that high
regioselectivities and stereoselectivities could be obtained only in
the arylation of N,N-diprotected allylamines bearing carbamate
protecting groups. In recent studies by Jiao and co-workers,14a the
high regioselectivities and stereoselectivities observed in the ary-
lation of allyl esters and allylamides was attributed to the chelation
between the carbonyl O atom and the Pd atom. In our current in-
vestigation, this chelation effect, as shown in 5, may contribute
2f:
R
1 = Boc, R2 = H
Entry
Substrate
Olefin
3/4b
Time (h)
6
Yield (%)c
90
Br
1
1a
2b
>99/1
MeO2C
MeOC
Br
similarly to the stereoselectivity, as the
g carbon is ideally posi-
2
3
1b
1c
2b
2b
>99/1
>99/1
6
6
91
88
tioned to accept the migrating aryl group. The necessity for di-
protection may partly stem from the steric effect; with decreased
Br
steric demanding from the amino moiety,
b arylation may become
OHC
easier, leading to regioisomers in the case of 2f.
X
MeOC
Br
O
R'
4
5
1h
1l
2b
2b
>99/1
>99/1
6
89
83
Ar Pd
N
R
Br
10
5
MeO
Br
3. Conclusions
6
7
1o
1r
2b
2b
>99/1
>99/1
10
6
79
80
Br
In summary, we have developed efficient Pd-catalyzed Heck cross-
couplingconditionsthatallowawiderangeofarylbromidestocouple,
highly regioselectively and stereoselectively, with electron-rich allyl-
N
Br
amine derivatives, furnishing g-arylated (E)-allylamines in good to
8
1s
1a
2b
2c
>99/1
6
75
87
excellent yields. The reaction proceeds under ligand-free conditions,
and tolerates a diverse range of functionalities. The catalytic efficacy
was influenced by a number of factors, such as solvent, protection
group, reaction temperature and additives. It is noteworthy that the
choice of allylamine derivatives was found to be essential for securing
high regioselectivity and stereoselectivity. Further investigation fo-
cusing on the arylation of aryl chlorides with allylamines is underway
in our laboratory, and will be reported in due course.
N
Br
Br
9d
98/2
12
MeO2C
MeOC
10d
11d
1b
1e
2c
2c
98/2
97/3
12
12
89
83
Br
4. Experimental section
4.1. General
NC
MeOC
Br
12d
13d
1h
1r
2c
2c
98/2
98/2
12
12
88
81
Unless otherwise noted, all experiments were carried out under an
atmosphere of nitrogen using standard Schlenk techniques. 1H NMR
and 13C NMR spectra were recorded on a Bruker Model Avance DMX
400 Spectrometer (1H 400 MHz and 13C 106.6 MHz, respectively).
Br
N
Br
14d
15d
1k
1b
2d
2d
99/1
99/1
12
12
79
82
Chemical shifts (d) are given in parts per million and are referenced to
residual solvent peaks. All organic solvents were dried using standard,
published methods and were distilled before use. N,N-(Boc)2-allyl-
amine (2a),17a 2-allylisoindoline-1,3-dione (2b),23 N-Boc-N-Cbz-allyl-
amine (2c),2l ethyl allyl(naphthalen-1-ylmethyl)carbamate (2d),18c
N,N-diethyl-allylamine (2e)2n and N-Boc-allylamine (2f)2e were pre-
pared according to the previous reports. All other chemicals were used
as received from Aldrich or Acros without further purification.
Br
Br
MeOC
16
1a
1a
2e
2f
nd
12
12
0
MeO2C
Br
17
43/57
30
4.2. General procedure for the Heck arylation of N,N-(Boc)2-
MeO2C
allylamine (2a)
a
Unless otherwise noted, all reactions were carried out with aryl bromide
(1.0 mmol), allylamine (1.2 mmol), Pd(OAc)2 (3 mol %), HQ (10 mmol%), K2CO3
An oven-dried, two-necked round-bottom flask containing a stir
bar was charged with an aryl bromide 1 (1.0 mmol), Pd(OAc)2
(6.8 mg, 0.03 mmol), K2CO3 (165.9 mg, 1.2 mmol), TEMPO (15.6 mg,
0.1 mmol), N,N-(Boc)2-allylamine (308.8 mg, 1.2 mmol) and DMF
(3.0 ml) under nitrogen at room temperature. Following degassing
(2.0 mmol), DMF (3.0 ml), 100 ꢁC; Pht¼phthalimidoyl.
b
Determined by 1H NMR analysis. When no
b-arylated product was detected,
a value of >99/1 was assigned.
c
Isolated yield after column chromatography.
The reaction temperature was 85 ꢁC.
d

Z. Jiang et al. / Tetrahedron 68 (2012) 4919e4926
4923
three times, the flask was placed in an oil bath, and the mixture was
stirred and heated at 100 ꢁC. After an appropriate reaction time
(Tables 2 and 3), the flask was removed from the oil bath and cooled
to room temperature. Water (20 ml) was added, and the mixture
was extracted with CH2Cl2 (3ꢂ20 ml). The combined organic layer
was washed with brine, dried (Na2SO4), filtered, and concentrated
in vacuo. The linear arylated allylamine was isolated out of the
crude product by flash chromatography on silica gel using a mix-
ture of ethyl acetate and hexane.
128.6, 125.5, 124.1, 123.6, 82.3, 47.9, 36.2, 27.9, 25.5; HRMS (ESI)
calcd for C22H29NNaO5 [MþNa]þ: 410.1938, found: 410.1941.
4.2.8. (E)-N,N-Bis(tert-butoxycarbonyl)-3-(3-acetylphenyl)prop-2-
en-1-amine (3ha). Colorless oil; 1H NMR (400 MHz, CDCl3)
d 7.94 (s,
1H), 7.81 (d, J¼7.72 Hz,1H), 7.56 (d, J¼7.76 Hz,1H), 7.41 (t, J¼7.72 Hz,
1H), 6.57 (d, J¼15.92 Hz, 1H), 6.31 (dt, J¼6.12, 15.88 Hz, 1H), 4.36 (d,
J¼6.12 Hz, 2H), 2.61 (s, 3H), 1.52 (s, 18H); 13C NMR (100.6 MHz,
CDCl3)
d 198.0, 152.4, 137.4, 137.3, 131.2, 130.8, 128.8, 127.5, 126.7,
126.1, 82.5, 48.0, 28.1, 26.7; HRMS (ESI) calcd for C21H29NNaO5
4.2.1. (E)-Methyl 4-(3-(bis(tert-butoxycarbonyl)amino)prop-1-enyl)
[MþNa]þ: 398.1938, found: 398.1943.
benzoate (3aa).18b White solid, mp 82e83 ꢁC; 1H NMR (400 MHz,
CDCl3)
J¼15.92 Hz,1H), 6.32 (dt, J¼15.94, 6.04 Hz,1H), 4.33 (d, J¼6.04 Hz, 2H),
3.86 (s, 3H), 1.49 (s, 18H); 13C NMR (100.6 MHz, CDCl3)
166.6, 152.2,
d
7.95 (d, J¼8.24 Hz, 2H), 7.38 (d, J¼8.28 Hz, 2H), 6.53 (d,
4.2.9. (E)-Di-tert-butyl-3-(8-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)
allyliminodicarbonate (3ia). Yellow oil; 1H NMR (400 MHz, CDCl3)
d
d
7.99 (s, 1H), 7.45 (m, 1H), 7.18 (d, J¼7.92 Hz, 1H), 6.51 (d,
141.2,131.1,129.8,129.0,128.0,126.2, 82.4, 51.8, 47.9, 28.0; HRMS (ESI)
J¼15.88 Hz, 1H), 6.25 (dt, J¼15.88, 6.08 Hz, 1H), 4.32 (d, J¼6.08 Hz,
calcd for C21H29NNaO6 [MþNa]þ: 414.1887, found: 414.1896.
2H), 2.89 (m, 2H), 2.60 (m, 2H), 2.08 (m, 2H), 1.50 (s, 18H); 13C NMR
(100.6 MHz, CDCl3)
d 198.3, 152.3, 143.7, 135.3, 132.6, 131.1, 131.0,
4.2.2. (E)-N,N-Bis(tert-butoxycarbonyl)-3-(4-acetylphenyl)prop-2-
129.1, 125.9, 124.8, 82.4, 48.0, 39.1, 29.4, 28.1, 23.2; HRMS (ESI) calcd
en-1-amine (3ba).18b Colorless liquid; 1H NMR (400 MHz, CDCl3)
for C23H31NNaO5 [MþNa]þ: 424.2094, found: 424.2099.
d
7.79 (d, J¼8.16 Hz, 2H), 7.33 (d, J¼8.08 Hz, 2H), 6,46 (d,
J¼15.88 Hz, 1H), 6.26 (dt, J¼15.88, 5.92 Hz, 1H), 4.26 (d, J¼5.76 Hz,
4.2.10. (E)-N,N-Bis(tert-butoxycarbonyl)-3-(3-(cyclohexanecarbonyl)
2H), 2.45 (s, 3H), 1.41 (s, 18H); 13C NMR (100.6 MHz, CDCl3)
phenyl)prop-2-en-1-amine (3ja). White solid, mp: 76e78 ꢁC; 1H
d
197.6, 152.2, 141.3, 135.9, 130.9, 128.6, 128.2, 126.3, 82.4, 47.6,
NMR (400 MHz, CDCl3)
d
7.87 (s, 1H), 7.75 (d, J¼7.72 Hz, 1H), 7.50 (d,
28.0, 26.4; HRMS (ESI) calcd for C21H29NNaO5 [MþNa]þ:
J¼7.72 Hz, 1H), 7.35 (m, 1H), 6.54 (d, J¼15.92 Hz, 1H), 6.28 (dt,
398.1938, found: 398.1939.
J¼15.92, 6.08 Hz, 1H), 4.32 (d, J¼6.08 Hz, 2H), 3.20 (m, 1H), 1.78 (m,
4H), 1.38 (m, 24H); 13C NMR (100.6 MHz, CDCl3)
d 203.5, 152.3,
4.2.3. (E)-N,N-Bis(tert-butoxycarbonyl)-3-(4-formylphenyl)prop-2-
137.3, 136.6, 131.3, 130.3, 128.7, 127.3, 126.5, 126.1, 82.4, 47.9, 45.6,
29.3, 28.0, 25.9, 25.7; HRMS (ESI) calcd for C26H37NNaO5 [MþNa]þ:
466.2564, found: 466.2568.
en-1-amine (3ca). Yellow oil; 1H NMR (400 MHz, CDCl3)
d 9.97 (s,
1H), 7.82 (d, J¼8.20 Hz, 2H), 7.50 (d, J¼8.20 Hz, 2H), 6.57 (d,
J¼15.92 Hz, 1H), 6.39 (dt, J¼15.92, 6.00 Hz, 1H), 4.37 (d, J¼6.00 Hz,
2H), 1.52 (s, 18H); 13C NMR (100.6 MHz, CDCl3)
d
152.3, 142.8, 135.4,
4.2.11. (E)-N,N-Bis(tert-butoxycarbonyl)-3-phenyl prop-2-en-1-
130.9, 130.1, 129.1, 126.9, 82.7, 47.9, 28.1; HRMS (ESI) calcd for
amine (3ka).18b Yellow oil; 1H NMR (400 MHz, CDCl3)
d 7.36 (m,
C20H27NNaO5 [MþNa]þ: 384.1781, found: 384.1789.
2H), 7.31 (t, J¼7.76, 2H), 7.24 (t, J¼7.16 Hz, 1H), 6.54 (d, J¼15.88 Hz,
1H), 6.23 (dt, J¼15.88, 6.24 Hz, 1H), 4.34 (d, J¼6.08 Hz, 2H), 1.52 (s,
4.2.4. (E)-N,N-Bis(tert-butoxycarbonyl)-3-(3-(trifluoromethyl)phe-
nyl)prop-2-en-1-amine (3da).18b Yellow oil; 1H NMR (400 MHz,
18H); 13C NMR (100.6 MHz, CDCl3)
d 152.4, 136.8, 133.8, 128.5, 127.6,
126.4, 125.1, 82.4, 48.5, 28.1; HRMS (ESI) calcd for C19H27NNaO4
CDCl3)
d
7.58 (s, 1H), 7.51 (d, J¼7.56 Hz, 1H), 7.45 (d, J¼7.68 Hz, 1H),
[MþNa]þ: 356.1832, found: 356.1836.
7.40 (t, J¼7.64 Hz, 1H), 6.54 (d, J¼15.92 Hz, 1H), 6.29 (dt, J¼15.88,
6.08 Hz, 1H), 4.35 (d, J¼6.08 Hz, 2H), 1.51(s, 18H); 13C NMR
4.2.12. (E)-N,N-Bis(tert-butoxycarbonyl)-3-(4-methoxyphenyl)prop-
(100.6 MHz, CDCl3)
d
152.4, 137.6, 130.7, 129.5, 129.0, 127.3, 124.0,
2-en-1-amine (3la).18b,c Colorless oil; 1H NMR (400 MHz, CDCl3)
123.0, 122.9, 116.1, 82.5, 47.9, 28.0; HRMS (ESI) calcd for
d
7.78 (d, J¼8.68 Hz, 2H), 7.30 (d, J¼8.64 Hz, 2H), 6.49 (d, J¼15.84 Hz,
1H), 6.26 (dt, J¼15.84, 6.00 Hz, 1H), 4.26 (d, J¼8.00 Hz, 2H), 2.45 (s,
3H), 1.41 (s, 18H); 13C NMR (100.6 MHz, CDCl3)
159.2, 152.4, 131.9,
C20H26NNaF3O4 [MþNa]þ : 424.1706, found: 424.1708.
d
4.2.5. (E)-N,N-Bis(tert-butoxycarbonyl)-3-(4-cyanophenyl)prop-2-
129.5, 127.5, 122.7, 113.9, 82.2, 55.1, 48.2, 28.1; HRMS (ESI) calcd for
en-1-amine (3ea).18b Yellow solid, mp 79e81 ꢁC; 1H NMR
C20H29NNaO5 [MþNa]þ: 386.1938, found: 386.1941.
(400 MHz, CDCl3)
d
7.59 (d, J¼8.16 Hz, 2H), 7.43 (d, J¼8.24 Hz, 2H),
6.53 (d, J¼15.96 Hz, 1H), 6.35 (dt, J¼15.88, 5.96 Hz, 1H), 4.36 (d,
4.2.13. (E)-N,N-Bis(tert-butoxycarbonyl)-3-(3-methoxyphenyl)prop-
J¼7.72 Hz, 2H), 1.51 (s, 18H); 13C NMR (100.6 MHz, CDCl3)
d
152.3,
2-en-1-amine (3ma). Colorless oil; 1H NMR (400 MHz, CDCl3)
d 7.22
141.3, 132.4, 130.3, 129.4, 126.9, 118.9, 110.8, 82.7, 47.8, 28.1; HRMS
(m, 1H), 6.95 (d, J¼7.68 Hz, 1H), 6.90 (s, 1H), 6.78 (m, 1H), 6.51 (d,
(ESI) calcd for C20H26N2NaO4 [MþNa]þ: 381.1785, found: 381.1789.
J¼15.84 Hz,1H), 6.22 (dt, J¼15.84, 5.90 Hz,1H), 4.34 (m, 2H), 3.79 (s,
3H), 1.51 (s, 18H); 13C NMR (100.6 MHz, CDCl3)
d 159.8, 152.3, 138.2,
4.2.6. (E)-N,N-Bis(tert-butoxycarbonyl)-3-(2-cyanophenyl)prop-2-
132.2, 129.5, 125.4, 119.0, 113.2, 111.7, 82.4, 55.1, 48.1, 28.1; HRMS
en-1-amine (3fa). Colorless liquid; 1H NMR (400 MHz, CDCl3)
(ESI) calcd for C20H29NNaO5 [MþNa]þ: 386.1938, found: 386.1943.
d
7.49 (m, 3H), 7.22 (m, 1H), 6.77 (d, J¼15.88 Hz, 1H), 6.35 (dt,
J¼15.88, 5.94 Hz, 1H), 4.31 (d, J¼6.00 Hz, 2H), 1.44 (s, 18H), 13C
4.2.14. (E)-N,N-Bis(tert-butoxycarbonyl)-3-(3,4,5-trimethoxyphenyl)
NMR (100.6 MHz, CDCl3)
d
152.1, 139.7, 132.8, 132.7, 130.6, 127.7,
prop-2-en-1-amine (3na). Yellow oil; 1H NMR (400 MHz, CDCl3)
127.5, 125.6, 117.6, 110.9, 82.6, 47.8, 28.0; HRMS (ESI) calcd for
d
6.57 (s, 2H), 6.44 (d, J¼15.76 Hz, 1H), 6.12 (dt, J¼15.76, 6.28 Hz,
1H), 4.31(d, J¼6.26 Hz, 2H), 3.85 (s, 6H), 3.82 (s, 3H), 1.50 (s, 18H);
13C NMR (100.6 MHz, CDCl3)
153.3, 152.5, 137.8, 132.5, 132.3, 124.6,
C20H26N2NaO4 [MþNa]þ: 381.1785, found: 381.1792.
d
4.2.7. (E)-Di-tert-butyl 3-(1-oxo-2,3-dihydro-1H-inden-5-yl)allyli-
103.5, 82.4, 60.9, 56.1, 48.1, 28.1; HRMS (ESI) calcd for C22H33NNaO7
minodicarbonate (3ga). Yellow solid, mp 55e57 ꢁC; 1H NMR
[MþNa]þ: 446.2149, found: 446.2157.
(400 MHz, CDCl3)
d
7.48 (d, J¼7.96 Hz, 1H), 7.27 (s, 1H), 7.20 (d,
J¼8.08 Hz, 1H), 6.42 (d, J¼15.92 Hz, 1H), 6.24 (dt, J¼15.92, 5.96 Hz,
4.2.15. (E)-N,N-Bis(tert-butoxycarbonyl)-3-(4-tolyl)prop-2-en-1-
1H), 4.22 (d, J¼5.76 Hz, 2H), 2.93 (m, 2H), 2.47 (m, 2H), 1.37 (s, 18H);
amine (3oa). Yellow oil; 1H NMR (400 MHz, CDCl3)
d
7.27 (d,
13C NMR (100.6 MHz, CDCl3)
d 205.8, 155.6, 152.1, 142.9, 136.1, 131.2,
J¼7.04 Hz, 2H), 7.11 (d, J¼8.0 Hz, 2H), 6.50 (d, J¼15.88 Hz, 1H), 6.16

4924
Z. Jiang et al. / Tetrahedron 68 (2012) 4919e4926
(dt, J¼15.88, 6.12 Hz, 1H), 4.32 (d, J¼6.28 Hz, 2H), 2.33 (s, 3H), 1.51
(s, 18H); 13C NMR (100.6 MHz, CDCl3)
152.3, 133.8, 132.3, 129.2,
J¼8.28 Hz, 2H), 6.71 (d, J¼15.84, 1H), 6.41 (dt, J¼15.84, 6.28 Hz, 1H),
4.51 (d, J¼6.24 Hz, 2H), 3.94 (s, 3H); 13C NMR (100.6 MHz, CDCl3)
d
126.3, 124.0, 116.2, 82.2, 48.5, 28.0; HRMS (ESI) calcd for
d 168.0, 166.8, 140.8, 134.3, 134.2, 132.7, 132.2, 129.9, 126.5, 125.6,
C20H29NNaO4 [MþNa]þ: 370.1989, found: 370.1995.
123.4, 52.1, 39.6; HRMS (ESI) calcd for C19H15NNaO4 [MþNa]þ:
344.0893, found: 344.0899.
4.2.16. (E)-N,N-Bis(tert-butoxycarbonyl)-3-(4-bromophenyl)prop-2-
en-1-amine (3pa1).18b Colorless oil; 1H NMR (400 MHz, CDCl3)
4.3.2. (E)-2-(3-(4-acetylphenyl)allyl)isoindoline-1,3-dione (3bb).
d
7.42 (d, J¼8.45 Hz, 2H), 7.24 (d, J¼8.44 Hz, 2H), 6.46 (d, J¼15.88 Hz,
1H), 6.22 (dt, J¼15.88, 6.12 Hz, 1H), 4.32 (d, J¼6.28 Hz, 2H), 1.51(s,
18H); 13C NMR (100.6 MHz, CDCl3)
152.3, 135.7, 131.6, 131.0, 127.9,
White solid, mp 145e147 ꢁC; 1H NMR (400 MHz, CDCl3)
d 7.89 (m,
4H), 7.74 (d, J¼8.44 Hz, 2H), 7.44 (d, J¼8.28 Hz, 2H), 6.69 (d,
d
J¼15.84 Hz, 1H), 6.39 (dt, J¼15.84, 6.28 Hz, 1H), 4.49 (d, J¼6.28 Hz,
126.0, 121.3, 82.5, 48.0, 28.1; HRMS (ESI) calcd for C19H26BrNNaO4
2H), 2.59 (s, 3H); 13C NMR (100.6 MHz, CDCl3)
d 197.5, 167.9, 140.9,
[MþNa]þ: 434.0937, found: 434.0933.
136.3, 134.1, 132.5, 132.1, 128.7, 126.6, 125.8, 123.4, 39.5, 26.6;
HRMS (ESI) calcd for C19H15NNaO3 [MþNa]þ: 328.0944, found:
328.0946.
4.2.17. (2E,20E)-N,N,N,N-Tetra(tert-butoxycarbonyl)-3,30-
(1,4-phenylene)diprop-2-en-1-amine (3pa2). White solid, mp
119e121 ꢁC; 1H NMR (400 MHz, CDCl3)
d
7.34 (m, 4H), 6.52 (d,
J¼15.86 Hz, 2H), 6.22 (dt, J¼6.24, 15.86 Hz, 2H), 4.34 (d, J¼6.0 Hz,
4H), 1.53 (s, 36H); 13C NMR (100.6 MHz, CDCl3)
152.4, 136.1, 131.9,
4.3.3. (E)-4-(3-(1,3-Dioxoisoindolin-2-yl)prop-1-enyl)benzaldehyde
(3cb). White solid, mp 168e170 ꢁC; 1H NMR (400 MHz, CDCl3)
d
d
9.99 (s, 1H), 7.90 (m, 2H), 7.82 (d, J¼8.2 Hz, 2H), 7.76 (m, 2H), 7.52
126.6, 125.1, 82.4, 48.2, 28.1; HRMS (ESI) calcd for C32H48N2NaO8
(d, J¼8.2 Hz, 2H), 6.71 (d, J¼15.88 Hz,1H), 6.44 (dt, J¼15.88, 6.28 Hz,
[MþNa]þ: 611.3303, found:611.3308.
1H), 4.50 (d, J¼6.25 Hz, 2H); 13C NMR (100.6 MHz, CDCl3)
d 191.7,
167.9, 142.2, 135.6, 134.1, 132.4, 132.1, 130.1, 127.0, 126.6, 123.4, 39.5;
HRMS (ESI) calcd for C18H13NNaO3 [MþNa]þ: 314.0788, found:
314.0794.
4.2.18. (E)-N,N-Bis(tert-butoxycarbonyl)-3-(3-pyridyl)prop-2-en-1-
amine (3qa). Yellow oil; 1H NMR (400 MHz, CDCl3)
d 8.42 (d,
J¼1.6 Hz,1H), 8.29 (m, 1H), 7.52 (d, J¼7.92 Hz,1H), 7.07 (m, 1H), 6.36
(d, J¼16.00 Hz, 1H), 6.16 (dt, J¼16.00, 5.98 Hz, 1H), 4.20 (d,
4.3.4. (E)-2-(3-(3-Acetylphenyl)allyl)isoindoline-1,3-dione (3hb).
J¼5.92 Hz, 2H), 1.36 (s, 18H); 13C NMR (100.6 MHz, CDCl3)
d
152.1,
White solid, mp 153e155 ꢁC; 1H NMR (400 MHz, CDCl3)
d 7.92 (s,
148.3, 148.0, 132.6, 132.2, 128.3, 127.5, 123.2, 82.2, 47.7, 27.8; HRMS
1H), 7.88 (m, 2H), 7.81 (d, J¼7.68 Hz, 1H), 7.74 (m, 2H), 7.55 (d,
J¼7.72 Hz, 1H), 7.39 (t, J¼7.72 Hz, 1H), 6.69 (d, J¼15.84 Hz, 1H),
6.34 (dt, J¼15.84, 6.28 Hz, 1H), 4.48 (d, J¼6.24 Hz, 2H), 2.60 (s,
(ESI) calcd for C18H27N2O4 [MþH]þ : 335.1965, found: 335.1971.
4.2.19. (E)-N,N-Bis(tert-butoxycarbonyl)-3-(quinolin-3-yl)prop-2-
3H); 13C NMR (100.6 MHz, CDCl3)
d 197.9, 167.9, 137.4, 136.7, 134.1,
en-1-amine (3ra). White solid, mp 108e110 ꢁC; 1H NMR (400 MHz,
132.6, 132.1, 130.9, 128.8, 127.7, 126.4, 124.3, 123.4, 39.5, 26.7;
HRMS (ESI) calcd for C19H15NNaO3 [MþNa]þ: 328.0944, found:
328.0949.
CDCl3)
d
8.99 (d, J¼2.04 Hz, 1H), 8.06 (m, 2H), 7.80 (d, J¼8.08 Hz,
1H), 7.67 (m, 1H), 7.54 (m, 1H), 6.70 (d, J¼16.00 Hz, 1H), 6.48 (dt,
J¼16.00, 5.98 Hz 1H), 4.42 (m, 2H), 1.54 (s, 18H); 13C NMR
(100.6 MHz, CDCl3)
d
152.4, 149.3, 147.5, 132.4, 129.7, 128.9, 128.0,
4.3.5. (E)-2-(3-(4-Methoxyphenyl)allyl)isoindoline-1,3-dione
127.8, 126.9, 82.7, 48.1, 28.1; HRMS (ESI) calcd for C22H29N2O4
(3lb).18c White solid, mp 140e142 ꢁC; 1H NMR (400 MHz, CDCl3)
[MþH]þ: 385.2122, found: 385.2125.
d
7.87 (m, 2H), 7.73 (m, 2H), 7.31 (d, J¼8.72 Hz, 2H), 6.83 (d,
J¼8.72 Hz, 2H), 6.63 (d, J¼15.78 Hz, 1H), 6.13 (dt, J¼15.76, 6.56 Hz,
4.2.20. (E)-N,N-Bis(tert-butoxycarbonyl)-3-(isoquinolin-4-yl)prop-
1H), 4.44 (dd, J¼6.62, 1.04 Hz, 2H), 3.81 (s, 3H); 13C NMR
2-en-1-amine (3sa). Yellow solid, mp 90e92 ꢁC; 1H NMR (400 MHz,
(100.6 MHz, CDCl3) d 168.0, 159.4, 134.0, 133.4, 132.2, 129.0, 127.8,
CDCl3)
d
9.17 (s, 1H), 8.59 (s, 1H), 8.05 (d, J¼8.44 Hz, 1H), 7.98 (d,
123.3, 120.5, 113.9, 55.3, 39.8; HRMS (ESI) calcd for C18H15NNaO3
J¼8.08 Hz, 1H), 7.73 (t, J¼7.26 Hz, 1H), 7.62 (t, J¼7.28 Hz, 1H), 7.14 (d,
J¼15.72 Hz,1H), 6.33 (dt, J¼15.76, 5.92 Hz,1H), 4.47 (d, J¼5.88 Hz, 2H),
[MþNa]þ: 316.0944, found: 316.0947.
1.55 (s, 18H); 13C NMR (100.6 MHz, CDCl3)
d
152.4, 151.9, 140.6, 133.7,
4.3.6. (E)-2-(3-p-Tolylallyl)isoindoline-1,3-dione (3ob). White solid,
130.4, 130.2, 128.2, 128.1, 127.3, 127.2, 126.1, 122.9, 82.6, 48.2, 28.1;
mp 164e166 ꢁC; 1H NMR (400 MHz, CDCl3)
d 7.87 (m, 2H), 7.73 (m,
HRMS (ESI) calcd for C22H29N2O4 [MþH]þ: 385.2122, found:385.2129.
2H), 7.27 (d, J¼8.08 Hz, 2H), 7.11 (d, J¼8.08 Hz, 2H), 6.65 (d,
J¼15.84 Hz, 1H), 6.22 (dt, J¼15.84, 6.56 Hz, 1H), 4.45 (d, J¼6.52 Hz,
4.3. General procedure for Heck arylation of allylamines 2bef
2H), 2.33 (s, 3H); 13C NMR (100.6 MHz, CDCl3)
d 168.0, 127.8, 134.0,
133.8, 133.5, 132.2, 129.2, 126.5, 123.3, 121.7, 39.8, 21.2; HRMS (ESI)
An oven-dried, two-necked round-bottom flask containing a stir
bar was charged with an aryl bromide 1 (1.0 mmol), Pd(OAc)2
(6.8 mg, 0.03 mmol), K2CO3 (165.9 mg, 1.2 mmol), HQ (15.6 mg,
0.1 mmol), allylamine (1.2 mmol), and DMF (3.0 ml) under nitrogen
at room temperature. Following degassing three times, the flask
was placed in an oil bath, and the mixture was stirred and heated at
the appropriate temperature. After an appropriate reaction time,
the flask was removed from the oil bath and cooled to room tem-
perature. Water (20 ml) was added, and the mixture was extracted
with CH2Cl2 (3ꢂ20 ml). The combined organic layer was washed
with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The
product was purified by flash column chromatography on silica gel
using ethyl acetate/hexane as an eluent.
calcd for C18H15NNaO2 [MþNa]þ: 300.0995, found: 300.0997.
4.3.7. (E)-2-(3-(Quinolin-3-yl)allyl)isoindoline-1,3-dione (3rb).
White solid, mp 178e180 ꢁC 1H NMR (400 MHz, CDCl3)
d 8.96 (d,
J¼2.12 Hz, 1H), 8.05 (m, 2H), 7.88 (m, 2H), 7.74 (m, 3H), 7.67 (m,
1H), 7.48 (m, 1H), 6.80 (d, J¼16.32 Hz, 1H), 6.50 (dt, J¼16.32,
6.28 Hz, 1H), 4.54 (d, J¼6.28 Hz, 2H); 13C NMR (100.6 MHz, CDCl3)
d
167.9, 149.2, 147.6, 134.1, 132.8, 132.1, 130.4, 129.4, 129.2, 129.1,
127.9, 127.0, 125.3, 123.4, 122.7, 39.6; HRMS (ESI) calcd for
C20H15N2O2 [MþH]þ: 315.1128, found: 315.1135.
4.3.8. (E)-2-(3-(Isoquinolin-4-yl)allyl)isoindoline-1,3-dione (3sb).
White solid, mp 162e164 ꢁC 1H NMR (400 MHz, CDCl3)
d 9.11 (s,
1H), 8.53 (s, 1H), 8.00 (d, J¼8.36 Hz, 1H), 7.91 (d, J¼8.12 Hz, 1H),
7.84 (m, 2H), 7.69 (m, 3H), 7.57 (m, 1H),7.23 (d, J¼15.72 Hz, 1H),
6.31 (dt, J¼15.68, 6.32 Hz, 1H), 4.54 (d, J¼6. 32 Hz, 2H); 13C NMR
4.3.1. (E)-methyl 4-(3-(1,3-dioxoisoindolin-2-yl)prop-1-enyl)benzo-
ate (3ab). White solid, mp 153e155 ꢁC; 1H NMR (400 MHz, CDCl3)
d
7.99 (d, J¼8.24 Hz, 2H), 7.91 (m, 2H), 7.77 (m, 2H), 7.44 (d,
(100.6 MHz, CDCl3) d 167.9, 152.1, 140.6, 134.1, 133.9, 133.5, 132.1,

Z. Jiang et al. / Tetrahedron 68 (2012) 4919e4926
4925
130.6, 128.0, 127.9, 127.8, 127.7, 127.2, 123.4, 122.9, 39.8; HRMS
(dd, J¼6.49, 1.5 Hz, 2H), 4. 02 (m, 2H), 1.34 (t, J¼8.2 Hz, 3H); 13C
(ESI) calcd for C20H15N2O2 [MþH]þ: 315.1128, found: 315.1132.
NMR (100.6 MHz, CDCl3) d 156.6, 136.7, 133.9, 132.9, 132.3, 128.8,
128.6, 128.2, 127.7, 126.8, 126.4, 125.9, 125.4, 125.3, 124.8, 124.0,
123.0, 61.8, 47.6, 47.2, 14.9; HRMS (ESI) calcd for C23H23NNaO2
[MþNa]þ: 368.1621, found: 368.1629.
4.3.9. (E)-Methyl4-(3-(N-carbobenzyloxy-N-tert-butoxycarbonyl
amino)prop-1-enyl)benzoate (3ac). Yellow oil; 1H NMR (400 MHz,
CDCl3)
1H), 6.33 (dt, J¼15.92, 6.08 Hz, 1H), 5.26 (s, 2H), 4.44 (d, J¼5.88 Hz,
2H), 3.91 (s, 3H), 1.50 (s, 9H); 13C NMR (100.6 MHz, CDCl3)
166.8,
d
7.98 (d, J¼8.24 Hz, 2H), 7.36 (m, 7H), 6.53 (d, J¼15.92 Hz,
4.3.16. (E)-Methyl 4-(3-((tert-butoxycarbonyl)amino)prop-1-en-1-
d
yl)benzoate (3af). Yellow oil; 1H NMR (400 MHz, CDCl3)
d 7.99 (d,
153.6, 151.8, 141.1, 135.4, 131.6, 129.9, 129.1, 128.6, 128.4, 128.3, 127.4,
126.3, 83.2, 68.5, 52.1, 48.1, 28.0; HRMS (ESI) calcd for C24H27NNaO6
[MþNa]þ: 448.1731, found: 448.1738.
J¼8.21 Hz, 2H), 7.41 (d, J¼8.24 Hz, 2H), 6.55 (d, J¼15.92 Hz,1H), 6.33
(dt, J¼15.88, 5.72 Hz,1H), 4.81 (bs,1H), 3.95 (s, 2H), 3.92 (s, 3H),1.49
(s, 9H) zHzHz H; 13C NMR (100.6 MHz, CDCl3)
d 166.9, 155.8, 141.2,
130.2, 129.9, 129.4, 128.6, 126.2, 79.6, 52.1, 42.6, 28.4; HRMS (ESI)
4.3.10. (E)-N-Carbobenzyloxy-N-tert-butoxycarbonyl-3-(4-acetylph-
calcd for C16H22NO4 [MþH]þ: 292.1543, found: 292.1548.
enyl)prop-2-en-1-amine (3bc). Yellow oil; 1H NMR (400 MHz,
CDCl3)
1H), 6.36 (dt, J¼15.92, 6.08 Hz, 1H), 5.28 (s, 2H), 4.46 (d, J¼5.88 Hz,
2H), 2.62 (s, 3H), 1.52 (s, 9H); 13C NMR (100.6 MHz, CDCl3)
197.5,
153.6,151.8,141.3,136.2,135.4,131.6,128.7,128.6, 128.4,128.3,127.7,
126.5, 83.2, 68.6, 48.2, 28.0, 26.6; HRMS (ESI) calcd for
C24H27NNaO5 [MþNa]þ: 432.1781, found: 432.1783.
d
7.94 (d, J¼8.24 Hz, 2H), 7.38 (m, 7H), 6.55 (d, J¼15.92 Hz,
Acknowledgements
d
Financial support from the National Natural Science Foundation
of China (21072225, 20910102051, 21172258 and 91127039), the
Fundamental Research Funds for the Central Universities, and the
Research funds of Renmin University of China (11XNL011) and CAS
Key Laboratory of Molecular Recognition and Function is greatly
acknowledged.
4.3.11. (E)-N-Carbobenzyloxy-N-tert-butoxycarbonyl-3-(4-cyanoph-
enyl)prop-2-en-1-amine (3ec). Yellow oil; 1H NMR (400 MHz,
CDCl3)
1H), 6.35 (dt, J¼15.92, 5.96 Hz, 1H), 5.26 (s, 2H), 4.45 (d, J¼5.96 Hz,
2H), 1.50 (s, 9H); 13C NMR (100.6 MHz, CDCl3)
153.6, 151.8, 141.1,
135.4,132.4,130.8,128.8, 128.6, 128.5,128.4,126.9,118.9,110.9, 83.4,
68.6, 48.0, 28.0; HRMS (ESI) calcd for C23H24N2NaO4 [MþNa]þ:
415.1628, found: 415.1635.
d
7.59 (d, J¼8.28 Hz, 2H), 7.38 (m, 7H), 6.50 (d, J¼15.96 Hz,
References and notes
d
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4.3.12. (E)-N-Carbobenzyloxy-N-tert-butoxycarbonyl-3-(3-acetylph-
enyl)prop-2-en-1-amine (3hc). Yellow oil; 1H NMR (400 MHz,
CDCl3)
d
7.90 (s, 1H), 7.82 (d, J¼7.72 Hz, 1H), 7.62 (d, J¼7.76 Hz, 1H),
7.39 (m, 6H), 6.54 (d, J¼15.88 Hz,1H), 6.30 (dt, J¼15.88, 6.16 Hz,1H),
5.25 (s, 2H), 4.43 (d, J¼6.12 Hz, 2H), 2.60 (s, 3H), 1.50 (s, 9H); 13C
NMR (100.6 MHz, CDCl3)
d 198.0, 153.6, 151.9, 137.4, 137.1, 135.4,
131.7, 130.8, 128.8, 128.6, 128.4, 128.3, 127.6, 126.2, 126.1, 83.2, 68.5,
48.1, 28.0, 26.7; HRMS (ESI) calcd for C24H27NNaO5 [MþNa]þ:
432.1781, found: 432.1787.
4.3.13. (E)-N-Carbobenzyloxy-N-tert-butoxycarbonyl-3-(quinolin-3-
yl)prop-2-en-1-amine (3rc). Yellow oil; 1H NMR (400 MHz, CDCl3)
d
8.93 (d, J¼2.12 Hz, 1H), 8.08 (d, J¼8.52 Hz, 1H), 7.97 (s, 1H), 7.78 (d,
J¼7.68 Hz, 1H), 7.67 (m, 1H), 7.53 (m, 1H), 7.42 (m, 2H), 7.35 (m, 3H),
6.64 (d, J¼16.02 Hz, 1H), 6.45 (dt, J¼16.04, 6.08 Hz, 1H), 5.28 (s, 2H),
4.49 (d, J¼6.08 Hz, 2H), 1.52 (s, 9H) H; 13C NMR (100.6 MHz, CDCl3)
d
153.6, 151.9, 149.2, 147.5, 135.4, 132.6, 129.5, 129.4, 129.3, 129.2,
128.6, 128.4, 128.3, 127.9, 127.8, 127.2, 127.0, 83.3, 68.6, 48.2, 28.0;
HRMS (ESI) calcd for C25H27N2O4 [MþH]þ: 419.1965, found:
419.1971.
4.3.14. (E)-Ethyl 3-(4-acetylphenyl)(naphthalen-1-ylmethyl)allylcar-
bamate (3bd). Yellow oil; 1H NMR (400 MHz, CDCl3)
d 8.05 (m, 1H),
7.76 (d, J¼7.36 Hz, 3H), 7.70 (d, J¼8.28 Hz, 1H), 7.39 (m, 4H), 7.19 (d,
J¼8.24 Hz, 2H), 6.16 (m, 2H), 4.97 (d, J¼15.44 Hz, 2H), 4.24 (dd,
J¼7.08, 1.6 Hz, 2H), 3.95 (m, 2H), 2.44 (s, 3H), 1.25 (t, J¼7.92 Hz, 3H);
13C NMR (100.6 MHz, CDCl3)
d 197.2, 156.3, 141.2, 135.9, 133.9, 132.8,
131.8, 131.3, 130.8, 128.6, 128.0, 126.8, 126.3, 125.9, 125.3, 124.9,
123.8, 123.0, 61.7, 48.0, 47.2, 26.4, 14.8; HRMS (ESI) calcd for
C25H25NNaO3 [MþNa]þ: 410.1727, found: 410.1723.
4.3.15. Ethyl cinnamyl(naphthalen-1-ylmethyl)carbamate (3kd).
White solid, mp 48e50 ꢁC; 1H NMR (400 MHz, CDCl3)
d 8.12 (m,
1H), 7.92 (d, J¼7.60 Hz, 1H), 7.85 (d, J¼8.21 Hz, 1H), 7.56 (m, 2H),
7.51 (m, 1H), 7.41 (s, 1H), 7.34 (m, 4H), 7.27 (m, 1H), 6.41 (d,
J¼15.88 Hz, 1H), 6.24 (dt, J¼15.88, 6.48 Hz, 1H), 5.07 (s, 2H), 4.32

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Z. Jiang et al. / Tetrahedron 68 (2012) 4919e4926
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