Palladium-catalyzed, highly efficient, regiocontrolled arylation of electron-rich allylamines with aryl halides

Article abstract of DOI:10.1002/adsc.201100835

The highly efficient and regioselective palladium-catalyzed Heck coupling of aryl bromides with electron-rich allylamine derivatives is described. It was found that the choice of solvent, olefin, ligand and additive had a fundamental influence on the regi

Full text of DOI:10.1002/adsc.201100835

FULL PAPERS
DOI: 10.1002/adsc.201100835
Palladium-Catalyzed, Highly Efficient, Regiocontrolled Arylation
of Electron-Rich Allylamines with Aryl Halides
Yuheng Deng,a,* Zhen Jiang,b Min Yao,a Dan Xu,b Lingjuan Zhang,b
Huanrong Li,b Weijun Tang,b and Lijin Xub,*
a
Department of Chemistry, Capital Normal University, Beijing 100048, Peopleꢀs Republic of China
Fax : (+86)-10-6251-6444; e-mail: dyh@mail.cnu.edu.cn
Department of Chemistry, Renmin University of China, Beijing 100872, Peopleꢀs Republic of China
b
E-mail: xulj@chem.ruc.edu.cn
Received: October 26, 2011; Published online: March 13, 2012
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100835.
Abstract: The highly efficient and regioselective pal- bromides to give good to excellent regioselectivities,
ladium-catalyzed Heck coupling of aryl bromides while the catalyst system consisting of PdACHTUNRGTNEUNG(OAc)2, tet-
with electron-rich allylamine derivatives is described. rabutylammonium bromide (TBAB) and 2,2,6,6-tet-
It was found that the choice of solvent, olefin, ligand ramethyl-1-piperidinyloxy (TEMPO) additive allows
and additive had a fundamental influence on the re- for a variety of aryl bromides to react efficiently
gioselectivity and reactivity of the reaction. The com- with N,N-(Boc)2-allylamine (di-tert-butyl allylimino-
bination of palladium acetate [PdACTHNURTGNENG(U OAc)2] and 1,3- dicarbonate) in water to exclusively afford the linear
bis(diphenylphosphino)propane (dppp) in ethylene (E)-allylamine products in high yields.
glycol (EG) constitutes a highly effective catalyst
system for internal arylation of N-Boc-allylamine Keywords: allylamines; arylation; Heck reaction;
(tert-butyl methyl allyliminodicarbonate) with aryl palladium; regioselectivity
Introduction
being neutral which leads to a linear product and the
other ionic which favors branched substitution.[2]
Earlier studies reported that the poor internal re-
The Pd-catalyzed Heck arylation of olefins with aryl
halides has become one of the most powerful tools gioselectivity could be greatly improved under
À
for the construction of C C bonds in organic synthe- Pd-dppp catalysis by employing aryl triflates or by
sis.[1] However, the arylation of electron-rich olefins adding stoichiometric silver or thallium salts when
with aryl halides is often complicated by the forma- aryl halides are chosen.[3] Owing to the lability of the
À
tion of mixtures of regioisomers. It is generally be- Pd OTf (Tf: trifluoromethanesulfonyl) bond, the re-
lieved that this regioselectivity problem arises from gioselective arylation of electron-rich olefins with aryl
two competing reaction pathways (Scheme 1), one triflates in the presence of a chelating bidentate
ligand is channelled into the ionic pathway
(Scheme 1, path A) to give the branched products.
Silver and thallium salts could remove the halogen,
thereby promoting internal arylation. Recent reports
have revealed that a number of electron-rich olefins
could undergo highly regioselective internal arylation
with aryl halides by employing an ionic liquid,[4] aque-
ous DMF (N,N-dimethylformamide),[5] ethylene
gylcol (EG),[6a–e] 2-propanol[6f] or water[7] as the reac-
tion medium or in the presence of a hydrogen-bond
donor ammonium salt additive.[6f,8] It is assumed that
the ionic or polar environment provided by the sol-
vent or the ammonium salt additive facilitates the for-
Scheme 1. The two competing pathways in the Heck reac-
tion.
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Yuheng Deng et al.
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mation of the cationic species, thereby enabling the ence of Pd-dppp catalyst, and that PdACHTNUTGRNEUNG(OAc)2 could
ionic pathway (Scheme 1, path A). The recent kinetic catalyze the coupling reaction of aryl bromides with
studies of Amatore, Jutand and co-workers support electron-rich N-(Boc)2-allylamine 2b in water under
this view.[9] On the other hand, studies on how to im- ligand-free conditions to give the g-arylated products
prove the linear regioselectivity along the neutral way in a highly regioselective and stereoselective manner.
(Scheme 1, path B) in the Pd-catalyzed Heck aryla-
tion of electron-rich olefins has also been report-
ed.[10–12] For example, it has been suggested that using Results and Discussion
monophosphines or no ligand is advantageous for the
linear arylation of allylic alcohol.[10] Highly linear ary- At the outset methyl 4-bromobenzoate 1a was chosen
lations of vinyl ethers have been observed in poly- as the model substrate to couple with 2a under vari-
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
Jiao revealed that aryl halides could couple highly re- bonyl) group. Considering the remarkable perfor-
gioselectively with allyl esters to provide the linear mance of dppp in the Pd-catalyzed Heck arylation of
products with a Pd
(OAc)2 catalyst under ligand-free electron-rich olefins,[3–8] the catalyst was generated in
ACHTUNGTRENNUNG
conditions.[12]
situ from dppp and PdACTHNUTRGNE(NUG OAc)2, and the reaction mix-
Allylamines are versatile building blocks and struc- ture was heated at 908C for 20 h with Et3N (triethyla-
tural units in a large number of natural and synthetic mine) as the base. Regioselectivities were determined
1
products, and much effort has been devoted to the ef- by H NMR spectral analysis of the crude reaction
ficient construction of these useful compounds.[13] Re- mixture. The effect of different solvents was firstly
cently the application of Pd-catalyzed Heck arylations surveyed. As shown in Table 1, using EG resulted in
of allylamines to prepare arylated allylamines has a full conversion and 96/4 regioselectivity favoring b-
gained much attention owing to its simplicity and tol- arylation (Table 1, entry 1), while switching to other
erance of various functional groups.[14–17] However, alcoholic solvents [EtOH (ethanol) and i-PrOH (2-
the regioselectivity remains problematic. Hallber- propanol)] led to lower conversions and regioselectiv-
g,[15a,b] Wu[15c] and Baxter[15d] disclosed that the catalyst ities (Table 1, entries 2 and 3). The better reactivity
generated in situ from the bidentate ligand dppf [1,1’- and b-regioselectivity achieved in EG may be partly
bis(diphosphino)ferrocene] and PdACTHNUGTRENUNG(OAc)2 could work ascribed to its better capability to form hydrogen
well to catalyze the coupling reaction of aryl triflates bonding with the bromide anion, thereby enhancing
with the readily available allylamine derivatives to the concentration of the cationic Pd(II) intermediate
give the b-arylated allylamines with good to excellent of the ionic pathway A (Scheme 1). The efficiencies
regioselectivities and high yields, but a significant were low when the coupling reactions were carried
drawback lies in the fact that triflates are base sensi- out in CH3CN (acetonitrile), DMSO (dimethyl sulfox-
tive, thermally labile, and rarely commercially avail- ide), DMF and dioxane, albeit the b-arylated allyl-
able. The work of Ripin and Wilson revealed that the
ACHTUNGTRENaNUNG mines were the major products (Table 1, entries 4–
Pd-catalyzed highly regioselective and stereoselective 7). No reaction was observed in toluene and water
terminal (g-)arylation of allylamine derivatives could (Table 1, entries 8 and 9). Bearing in mind the signifi-
be accomplished in alcoholic solvents under ligand- cant promoting effect of the hydrogen bond donor
free conditions, but only one aryl iodide substrate was [H2NACHTNUTRGENN(UG i-Pr)2]ACHTUGNTREN[NUGN BF4] (diisopropylammonium tetrafluoro-
attempted, and the general utility of this chemistry borate) on the regioselectivity and reaction rate in
has not been explored.[16] Very recently, Sigman,[17a] the arylation of electron-rich olefins,[6f,8] we then ex-
Cacchi[17b] and Correia[17c] reported that Pd
2ACTHNUTRGNEUNG(dba)3 plored the effect of this ammonium salt additive, but
could efficiently catalyze the preferential g-arylation no obvious accelerating effect and improved regiose-
of allylamines with arenediazonium salts in the ab- lectivity could be detected (Table 1, entry 10). The in-
sence of ligand. However, the synthetic utility of this ability of the ammonium salt may result from its pref-
chemistry might be restricted by the intrinsic draw- erential hydrogen bonding with the solvent EG. Addi-
backs of the arenediazonium salt, such as instability tion of a silver salt did not have an obvious effect on
and explosive potential. Given the importance of g- the rate and regioselectivity (Table 1, entry 11).
and b-arylated allylamines in chemical and particular-
Considering the important impact of ligands on re-
ly biologically active compound synthesis,[18] the de- activity and regioselectivity, we were interested in
velopment of practical and highly efficient catalytic finding out if a ligand other than dppp could display
synthetic methods to access these compounds from better performance in EG. In the presence of dppf,
safe and stable aryl bromides appeared to be highly a ligand which has been proved to be highly efficient
desirable. Herein we report that electron-rich N-Boc- in the regioselective Heck reaction of allylamines
allylamine 2a could undergo highly efficient internal with aryl triflates,[15] the reaction gave a lower regiose-
(b-)arylation with aryl bromides in EG in the pres- lectivity of 80/20 albeit with a full conversion
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Palladium-Catalyzed, Highly Efficient, Regiocontrolled Arylation of Electron-Rich Allylamines
Table 1. Screening conditions for Heck arylation of methyl 4-bromobenzoate 1a with allylamine 2a.[a]
Entry
Solvent
Ligand[b]
Conversion [%][c]
Ratio of 3a/4a[c]
1
2
3
4
5
6
7
8
EG
dppp
dppp
dppp
dppp
dppp
dppp
dppp
dppp
dppp
dppp
dppp
dppf
dppb
dppe
dppm
BINAP
PPh3
100
78
70
42
32
96/4
95/5
93/7
86/14
80/20
86/14
75/25
nd
C2H5OH
i-PrOH
CH3CN
DMSO
DMF
dioxane
toluene
H2O
EG
EG
EG
EG
EG
EG
EG
EG
EG
EG
EG
EG
EG
10
40
nd
nd
100
100
100
100
nd
nd
100
26
9
nd
10[d]
11[e]
12
13
14
15
16
17
18
19
20
21
22[f]
23[g]
96/4
96/4
80/20
60/40
nd
nd
70/30
23/77
20/80
nd
nd
nd
P
N
21
phen
dmphen
bpy
dppp
dppp
nd
nd
nd
100
100
96/4
96/4
EG
[a]
Reaction conditions: 1a (1.0 mmol), 2a (1.2 mmol), Pd
(3.0 mL), 908C, 20 h.
ACHTUNGTREN(UNNG OAc)2 (3 mol%), ligand (6 mol%), NEt3 (2.0 mmol), solvent
[b]
Abbreviations: dppe=1,2-bis(diphenylphosphino)ethane, dppb=1,4-bis(diphenylphosphino)butane, dppm=bis(diphenyl-
phosphino)methane, BINAP=2,2’-bis(diphenylphosphino)-1,1’-binaphthyl, phen=1,10-phenanthroline, 2,9-dmphen=2,9-
dimethyl-1,10-phenanthroline, bpy=2,2’-bipyridine.
[c]
[d]
[e]
[f]
1
Determined by H NMR data.
1.5 equivalents [H2NACHTNUGTRENN(UG i-Pr)2]ACHTUGNTNER[NUGN BF4] were added.
1.1 equivalents AgOTf (silver trifluoromethanesulfonate) were added.
Reaction temperature 1208C, 4 h.
[g]
Reaction temperature 1458C, 2 h.
(Table 1, entry 12). Employing other ligands regard- competing Pd-catalyzed amidation reaction could be
less of being bidentate or monodentate led to either detected.[19]
poor yields or selectivities or both (Table 1, en-
Having established the optimal reaction conditions,
tries 13–21). Obviously, the combination of Pd(OAc)2 we then extended the chemistry to other aryl bro-
AHCTUNGTRENNUNG
and dppp afforded the most active catalyst in terms of mides. The results are shown in Table 2. As can be
both reactivity and regioselectivity. Interestingly, fur- seen, all the reactions proceeded rapidly, and reaction
ther experimental studies demonstrated that increas- times of as little as 2 h were observed in most cases.
ing the reaction temperature could dramatically A range of aryl bromides with electron-rich or elec-
reduce the reaction time without compromising the tron-deficient groups reacted smoothly with 2a to give
regioselectivity. For example, the reaction went to the expected b-arylated allylamines in good to excel-
completion in 4 h at 1208C without compromising the lent yields. The reactions involving electron-deficient
regioselectivity (Table 1, entry 22), and the reaction aryl bromides exhibited excellent regioselectivities re-
time could be further shortened to 2 h at 1458C with gardless of the position of the substituent on the aro-
retained regioselectivity (Table 1, entry 23). It should matic ring (Table 2, entries 1–14), and no or only
be pointed out that no product from a potentially traces of linear products were detected. However,
slightly lower regioselectivities were obtained in the
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Yuheng Deng et al.
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reactions of electron-rich aryl bromides (Table 2, en- CH3CN [Eq. (1)]. The reaction finished in 20 h, af-
tries 16 and 17), and the reason for the slight erosion fording a mixture of g-arylated and b-arylated isomers
is not clear at the moment. The reaction is not only with the ratio of g/b being 85/15. In order to further
limited to aryl bromides, but (also) heteroaryl bro- increase the g-regioselectivity, we envisioned that,
mides participated equally well (Table 2, entries 18–
20).
Next we turned our attention to the regioselective
terminal Heck arylation of allylamines. Based on
Scheme 1 and the previous reports,[10,14,20] the use of
a monophosphine ligand and a quaternary ammonium
salt is expected to promote the arylation to proceed
preferentially via the neutral route (Scheme 1, path
B) to give the linear product. We first examined the
coupling reaction of 1a and 2a with PdACHTUNTGRNEUNG(OAc)2-PPh3 as
the catalyst in the presence of TBAB additive in
Table 2. Regioselective Heck arylation of 2a with aryl bromides.[a]
Entry
Substrate
Time [h]
Selectivity [%][b]
Yield [%][c]
1
2
3
4
5
1a
1b
1c
1d
1e
2
2
2
3
3
96/4
96/4
95/5
95/5
94/6
85
82
81
79
80
6
1f
3
93/7
82
7
1g
1h
1i
2
2
2
3
>99/1
>99/1
>99/1
>99/1
91
93
89
87
8
9
10
1j
11
12
13
1k
1l
2
2
2
95/5
94/6
95/5
80
81
79
1m
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Palladium-Catalyzed, Highly Efficient, Regiocontrolled Arylation of Electron-Rich Allylamines
Table 2. (Continued)
Entry
Substrate
Time [h]
2
Selectivity [%][b]
94/6
Yield [%][c]
81
14
1n
15
16
1o
1p
2
3
91/9
80
71
88/12
17
18
19
1q
1r
1s
3
3
3
86/14
95/5
96/4
70
80
81
20
1t
3
96/4
80
[a]
Reaction conditions: aryl bromide (1.0 mmol), allylamine 2a (1.2 mmol), Pd
(2.0 mmol), ethylene glycol (3.0 mL), 1458C.
Determined by H NMR.
ACHTUGNTERN(NUNG OAc)2 (3 mol%), dppp (6 mol%), NEt3
[b]
[c]
1
Isolated yield.
when a more sterically hindered allylamine is em- rise to b-arylation. Indeed, the arylation of a bulky
ployed, the bulky substituent would inhibit the rota- N,N-(Boc)2-allylamine 2b with 1a resulted in exclu-
tion of the olefin from the initial out-of-plane position sively the g-arylated linear (E)-allylamine product 4b
to the in-plane position and the subsequent migratory with a 85% conversion (Table 3, entry 1), and no b-
À
insertion of the olefin into the Pd Ar bond that gives arylated product 3b was detected. This result indicat-
Table 3. Screening conditions for Heck arylation of 2b with 1a.[a]
Entry
Solvent
Ligand
Time [h]
Conversion [%][b]
Ratio of 4b/3b[b]
1
CH3CN
i-PrOH
EtOH
CH3CN
H2O
EG
H2O
H2O
H2O
PPh3
none
none
none
none
none
none
none
none
20
20
20
20
20
20
4
86
>99/1
nd
nd
>99/1
>99/1
nd
>99/1
>99/1
>99/1
2[c]
3[c,d]
4
nd
nd
86
5
6
85
nd
100
100
100
7[e]
8[f]
9[g]
2
2
[a]
Reaction conditions: 1a (1.0 mmol.), 2b (1.2 mmol), PdACHTNUGRTNEUNG(OAc)2 (3 mol%), ligand (6 mol%), K2CO3 (2.0 mmol), solvent
(3.0 mL), 908C, 20 h.
[b]
[c]
[d]
[e]
[f]
1
Determined by H NMR data. When no b-arylated product was detected, a value of >99/1 was assigned.
Pd
2ACHTUNGTRENNUNG(dba)3 was used to replace PdACHUTNGTREN(NUGN OAc)2.
Molar ratio NaOAc/NEt3 =1/5.1.
10 mol% hydroquinone were added.
10 mol% TEMPO were added.
1.0 equivalent TEMPO was added.
[g]
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Yuheng Deng et al.
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ed that the steric property of the allylamine has a deci- allylamines – were obtained. These results suggested
sive effect. This is in agreement with the reported ex- that the ionic pathway is either completely suppressed
perimental observations of regioselective Heck cou- or its involvement in the arylation is insignificant
pling reaction of 2b with aryl iodides and arenediazo- compared with the neutral pathway. It is noted that
nium salts under ligand-free conditions.[16,17] The bene- heteroaryl substrates were also efficiently transformed
ficial effect of ligand-free conditions led us to exam- to give the corresponding linear products in high
ine the reaction of 1a and 2b without using a ligand. yields (Table 4, entries 11–14). Noteworthy is that all
However, when Ripinꢀs protocol[16a] was employed, no the substrates underwent clean conversions without
reaction took place after 20 h (Table 3, entry 2). The competing formation of amidation products.[19]
catalyst system consisting of Pd2ACTHNUTRGNEUNG(dba)3 [tris(dibenyli-
deneacetone)dipalladium (0)], NaOAc (sodium ace-
tate) and NEt3 with EtOH as solvent, reported to be Conclusions
highly effective for the regioselective linear arylation
of N-allyl-2-methoxyacetamide by aryl iodide,[16b] In summary, we have developed highly efficient, Pd-
proved to be ineffective in our case (Table 3, entry 3). catalyzed Heck cross-coupling conditions that allow
We were pleased to observe that the reaction in a wide range of aryl bromides to highly regioselective-
CH3CN could still maintain its reactivity and regiose- ly couple with electron-rich allylamine derivatives to
lectivity in the absence of a ligand (Table 3, entry 4). give the arylated allylamines in good to excellent
Interestingly, similar reactivity and regioselectivity yields. The catalytic efficacy was influenced by many
were obtained when switching the reaction medium factors, such as solvent, allylamine derivative, ligand,
to water (Table 3, entry 5). However, EG totally in- reaction temperature and additive. It is noteworthy
hibited the reaction (Table 3, entry 6). Considering that the choice of solvent and allylamine derivative
a number of attractive advantages in the case of using was found to be essential for securing high regioselec-
water as a solvent for organic reactions,[21] we there- tivity. Both of these factors are expected to facilitate
fore chose water as the reaction medium for subse- the formation of the corresponding palladium inter-
quent study. Appropriate additives proved to be very mediate (ionic or neutral), enabling the reaction to
useful. The addition of the free-radical scavenger hy- regioselectively afford the desired products. The pres-
droquinone (10 mol%) to the reaction mixture could ent catalysis is more general, and greener than the
significantly accelerate the reaction in water, and the methods reported so far for arylation of allylamines.
arylation of 2b was finished in 4 h to exclusively form
the linear product without the branched products
being detected (Table 3, entry 7). Replacing hydroqui- Experimental Section
none with TEMPO could reduce the reaction time to
3 h with similar results (Table 3, entry 8). Further General Methods
study indicated that increasing the amount of
TEMPO additive had no significant effect on the re-
under an atmosphere of nitrogen using standard Schlenk
Unless otherwise noted, all experiments were carried out
techniques. 1H NMR and 13C NMR spectra were recorded
on a Bruker Model Avance DMX 400 Spectrometer (1H
400 MHz and 13C 106 MHz, respectively). Chemical shifts
(d) are given in ppm and are referenced to residual solvent
peaks. All organic solvents were dried using standard, pub-
lished methods and were distilled before use. All other
chemicals were commercially available and used as received
without further purification.
action (Table 3, entry 9). The addition of a free-radi-
cal scavenger to accelerate the Pd-catalyzed cross-
coupling reactions has been recently reported in the
literature.[22] We also tried the effect of reducing
agents, such as hydrazine and sodium formate, but
none of them showed any effect of acceleration.[23]
Based on the optimized reaction conditions,
a series of aryl bromides with different substituents
wase employed to survey the substrate scope of the
reaction. The results are summarized in Table 4. As
can be seen, all these coupling reactions went to com-
pletion within 4 h, and the catalyst system was found
to work well to result in good to excellent yields of
the desired products, tolerating activated, unactivated,
para-, meta- as well as ortho-substituted aryl bro-
mides. However, longer reaction times were required
in the olefination of ortho-substituted bromobezenes
presumably due to the steric effects (Table 4, entries 5
and 17). Moreover, the regioselectivities and stereose-
lectivities were well-controlled in these transforma-
General Procedure for the Heck Arylation of N-Boc-
allylamine
An oven-dried, two-necked, round-bottom flask containing
a stir bar was charged with an aryl bromide (1.0 mmol),
PdACTHUNTRGENNG(U OAc)2 (6.8 mg, 0.03 mmol), dppp (24.8 mg, 0.06 mmol),
N-Boc-allylamine (188.7 mg, 1.2 mmol) and EG (3.0 mL)
under nitrogen at room temperature. Following degassing
three times, NEt3 (202.4 mg, 2.0 mmol) were injected. The
flask was placed in an oil bath, and the mixture was stirred
and heated at 1458C. After an appropriate reaction time,
the flask was removed from the oil bath and cooled to room
tions, and only the linear arylation products – the (E)- temperature. Water (20 mL) was added, and the mixture
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Palladium-Catalyzed, Highly Efficient, Regiocontrolled Arylation of Electron-Rich Allylamines
Table 4. Regioselective Heck arylation of 2b with aryl bromides.[a]
Entry
1
Substrate
Time [h]
2
Yield [%][b]
90
1a
2
3
4
1c
1g
1h
3
3
3
84
81
85
5
6
1j
4
3
81
80
1k
7
8
1l
3
3
81
79
1m
9
1o
1p
1r
3
3
3
80
81
78
10
11
12
13
1s
1t
3
3
81
80
14
15
1u
1v
3
3
76
83
16
17
1w
1x
3
4
84
86
18
1y
2
91
[a]
Reaction conditions: aryl bromide (1.0 mmol), allylamine 2b (1.2 mmol), Pd
TEMPO (10 mol%), K2CO3 (2.0 mmol), water (3.0 mL), 908C.
Isolated yield.
ACHTUNGERTN(NUNG OAc)2 (3 mol%), TBAB (1.0 mmol),
[b]
was extracted with CH2Cl2 (3ꢂ20 mL). The combined or-
ganic layer was washed with brine, dried (Na2SO4), filtered,
and concentrated under vacuum. The arylated allylamine
was isolated out of the crude product by flash chromatogra-
phy on silica gel using a mixture of ethyl acetate and hexane
(1/99 to 10/90) as eluant.
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Lett. 2001, 3, 295–297.
General Procedure for the Heck Arylation of N,N-
(Boc)2-allylamine
An oven-dried, two-necked, round-bottom flask containing
a stir bar was charged with an aryl bromide (1.0 mmol),
PdACHTUNGTRENNUNG(OAc)2 (6.8 mg, 0.03 mmol), K2CO3 (165.9 mg, 1.2 mmol),
TBAB (322.4 mg, 1.0 mmol), TEMPO (15.6 mg, 0.1 mmol),
N,N-(Boc)2-allylamine (308.8 mg, 1.2 mmol) and water
(3.0 mL) under nitrogen at room temperature. Following de-
gassing three times, the flask was placed in an oil bath, and
the mixture was stirred and heated at 908C. After an appro-
priate reaction time, 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 (3ꢂ
20 mL). The combined organic layer was washed with brine,
dried (Na2SO4), filtered, and concentrated under vacuum.
The linear arylated (E)-allylamine was isolated out of the
crude product by flash chromatography on silica gel using
a mixture of ethyl acetate and hexane (5/95 to 20/80).
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Acknowledgements
Financial support from the National Natural Science Founda-
tion of China (20873179, 21072225, 20971091 and 21172258),
the Fundamental Research Funds for the Central Universities,
and the Research funds of Renmin University of China
(11XNL011) are gratefully acknowledged.
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