Cross dehydrogenative coupling strategy for allylation of benzylanilines promoted by DDQ

Article abstract of DOI:10.1016/j.tet.2019.130798

A cross dehydrogenative coupling strategy for allylation of benzylanilines promoted by DDQ is reported, which uses nonmetallic quinone DDQ as an oxidant in the allylation of N-benzylanilines under mild conditions. C–C bond with high selectivity and activity was constructed in this reaction and homoallylic amines were obtained with yields of up to 99%.

Full text of DOI:10.1016/j.tet.2019.130798

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Cross dehydrogenative coupling strategy for allylation of benzylanilines promoted by
DDQ
Ruimei Xiong, Muhammad Ijaz Hussain, Qing Liu, Wen Xia, Yan Xiong
PII:
S0040-4020(19)31200-1
https://doi.org/10.1016/j.tet.2019.130798
TET 130798
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 3 September 2019
Revised Date: 9 November 2019
Accepted Date: 12 November 2019
Please cite this article as: Xiong R, Hussain MI, Liu Q, Xia W, Xiong Y, Cross dehydrogenative
coupling strategy for allylation of benzylanilines promoted by DDQ, Tetrahedron (2019), doi: https://
doi.org/10.1016/j.tet.2019.130798.
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Cross Dehydrogenative Coupling Strategy for Allylation of N-Benzylanilines
Promoted by DDQ
Ruimei Xionga, Muhammad Ijaz Hussainb, Qing Liua, Wen Xiaa, Yan Xionga,
nBu3Sn
DDQ
No products (with NMR evidence)
H
N
R2
H
R1
N
R2
DDQ
nBu3Sn
R1
R2 = aryl, styryl
yields: up to 99%

1
Tetrahedron
journal homepage: www.elsevier.com
Cross Dehydrogenative Coupling Strategy for Allylation of Benzylanilines Promoted
by DDQ
Ruimei Xionga, Muhammad Ijaz Hussainb, Qing Liua, Wen Xiaa, Yan Xionga,
a School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 401331, China
a Department of Chemistry, Ghazi University, Dera Gazi Khan, Punjab 32200, Pakistan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A cross dehydrogenative coupling strategy for allylation of benzylanilines promoted by DDQ is
reported, which uses nonmetallic quinone DDQ as an oxidant in the allylation of N-benzylanilines
under mild conditions. C-C bond with high selectivity and activity was constructed in this reaction and
homoallylic amines were obtained with yields of up to 99% .
Available online
2019 Elsevier Ltd. All rights reserved.
Keywords:
Allylation
Benzyl aniline
DDQ
Dehydrogenative coupling
Homoallylic amines
1
.
Introduction
oxidized by DDQ, and hereby report DDQ promoted green and
efficient direct cross dehydrogenative coupling strategy for
allylation reactions of amines.
Homoallylic amines with extensive biological profile,
especially in terms of antifungal effects, are key motifs in natural
products and drug molecules[1-5]. Moreover, homoallylic amines
are also important organic synthesis intermediates, which are
often used to synthesize nitrogen-containing heterocyclic
compounds[6-8]
.
Several
previously
reported
synthetic
methodologies to excess homoallylic amine-based compounds
can be divided into the following three categories: 1) C–H bond
oxidation of α-position of the amino group to generate iminium
cation in situ, which is available to accept the nucleophilic
attack[9-13]; 2) cooking reaction of three components of aldehydes,
amines and allyl reagents[14-16]; 3) addition reaction of imine with
allylic metal reagents [17-18]. Among these methods, for the
reported α-C–H bond oxidation, transition metals such as silver
and iron were indispensable. Therefore, the metal free synthetic
way was highly expected to pursue.
Scheme 1. Phosphonation, cyanidation and allylation oxidized by DDQ.
2. Results and discussion
Preliminary endeavors were focused on product yield
optimization. Considering further development of the reaction
system and the excellent chemical selectivity of allyltin reagent[21]
we first attempted to investigate the efficiency of allyltributyltin
as allyl reagent and successfully obtained the corresponding allyl
products. Initial screening with N-benzyl aniline and
allyltributytin in THF afforded homoallylic amine 2a in a 27%
yield in 2 hours. Encouraged by the preliminary results, we then
investigated the effects of the types of oxidants and their amounts
on the reaction yields, which are summarized in Table 1.
,
Recently our approaches to access phosphonation and
cyanidation reactions of N-alkyl anilines through α-C–H
oxidaiton by DDQ, as depicted in Scheme 1, have been
successfully achieved[19]
.
Following our interests in the
development of oxidation coupling reaction in a transition-metal
free system[20], our group attempted to prepare homoallylic amine
derivatives through direct allylation reactions of amine
compounds. In view of the unique oxidability of DDQ, we
continued to conduct an extended study on the coupling reaction
Table 1. Screening of different oxidants and amounts.a
———between
system
benzylaniline substrates and nucleophile
* Corresponding author. School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 401331, China.
E-mail address: xiong@cqu.edu.cn (Y. Xiong)

2
Tetrahedron
time. A direct relation between allyl reagent uploading and yield
of homoallylic amine have been observed. When the amount of
allyl tributyltin reagent was reduced, the yield of the target
product showed a decreasing trend (entries 13-14). When the
dosage of allyltributyltin was increased, the yield of the target
product showed a trend of first increasing and then decreasing. 1.5
Equivalents of allyltributyltin reagent were the best dosage, and
the corresponding yield rate was 92% (entries 15-17). Finally,
when examining the effect of reaction time on yield, it was found
that 2 hours was the best reaction time at room temperature, and
shortening and prolonging the reaction time both led to a
decreased yield of the target product (entries 18-22). Therefore,
the optimal conditions for the allylation were: N-benzyl aniline
substrate (0.5 mmol), allyltributyltin (0.75 mmol, 1.5 equiv),
oxidant DDQ (0.6 mmol, 1.2 equiv), solvent ether (2 mL)and
room temperature for 2 hours.
Entry
Quinones
(x equiv)a
Yield (%)b
1
2
3
4
5
6
7
8
9
Q1
Q2
Q3
Q4
Q1
Q1
Q1
Q1
Q1
1.5
1.5
1.5
1.5
1.2
27
0
0
Table 2. Optimization of the reaction condition a
.
0
54
37
24
5
1.0
0.8
0.6 (+O2 baloon)
0.2 (+O2 baloon)
trace
a
Reaction conditions: N-benzyl aniline (0.5 mmol), allyl tributyltin (0.6
mmol, 1.2 equiv) and quinone reagent (specified) in 2 mL tetrahydrofuran
solvent at room temperature for 2 hours.
b NMR yield.
Allyltributyltin
(x equiv)
Entry
Solvent
CH3CN
MTBE
Bu2O
t (h)
Yield (%)b
74
66
44
82
From Table 1, 1.5 equivalents of DDQ (Q1) made the reaction
take place smoothly, and produced the corresponding
homoallyllic amine product in 27% yield (entry 1). When other
quinone based oxidants instead of DDQ , such as benzoquinone
(Q2), 2,5-di-hydroxy-3,6-dichlorobenzoquinone(Q3), 3,3',5,5'-
tetra-butyl-4,4' biphenyl quinone(Q4) were subjected to reaction
conditions, no target products were generated (entries 2-4). After
that the amount of DDQ was studied, we found that when DDQ
was reduced to 1.2 equivalents, a significant increase in yield was
up to 54% (entry 5). However, when the DDQ continued to
decrease, the yield decreases accordingly (entries 6 and 7). In
addition, the effect of green and environment friendly oxidant
utilizing molecular oxygen by decreasing equivalency of DDQ
resulted in a huge fall in yield of only 5% for the target product
(entry 8). The reaction did not occur when only 0.2 equivalent of
DDQ was added in an oxygen atmosphere (entry 9). Therefore,
we speculate that this process is not a cycle of DDQ catalytic
oxidation.
1
1.2
1.2
2
2
2
2
2
3
1.2
Et2O
4
5
1.2
1,4-
Dioxane
1.2
2
27
Toluene
DCM
DCE
6
7
8
9
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.0
0.8
1.5
1.8
2.0
1.5
1.5
1.5
1.5
2
2
2
2
2
2
2
2
2
2
2
2
1
3
4
5
65
39
53
39
45
28
40
DMSO
DMF
10
11
12
13
14
15
16
17
18
19
20
21
EtOH
After determining the type and dosage of oxidants, the reaction
conditions were further optimized, and the experimental results
are shown in Table 2. First, the solvent effect was investigated.
When the solvent was replaced by acetonitrile from
tetrahydrofuran, the yield was significantly amplified up to 74%
(entry 1). Both cyclic and acyclic ethereal solvents, when
subjected to this coupling strategy, demonstrated a dramatic
change in the yield. This study of ethereal medium revealed that
among tert-butyl ether, dibutyl ether and diethyl ether later one
provides a better medium for reaction system, while 1,4-dioxane
as solvent was not conducive to the reaction (entries 2-5). Besides,
some common laboratory solvents were investigated one by one,
such as toluene, dichloromethane, dichloroethane, dimethyl
sulfoxide, N,N-dimethyl formamide, and ethanol. Although
reactions proceeded in these solvents, the yield of the target
product is far lower than that of ethyl ether as a solvent (entries 6-
11). The reaction system was also capable to produce the product
without solvent, but the yield was only 40% (entry 12). After
determining ether as the best solvent for this reaction, we
investigated the effects of equivalent of allyl reagent and reaction
[c]
-
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
58
49
92
89
81
89
90
88
84

3
Table 3. Investigation of substrate scope.a
22
Et2O
1.5
6
78
a Reaction conditions: N-benzylaniline (0.5 mmol), allyltributyltin (specified),
DDQ (0.6 mmol, 1.2 equiv) in solvent (2 mL) at room temperature for
reaction time (specified). MTBE = methyl tert-butyl ether.
b NMR yield.
c No solvent.
Under the optimal reaction conditions, we examined the scope
of the reaction with the objective of identifying the structural and
electronic parameters of the substrates that resulted in good
yields and selectivities. We first investigated the compatibility of
the substrates when the benzene rings of aniline and benzyl
substrates were replaced by different functional groups, and the
experimental results are shown in Table 3. When the para-
position of benzyl was replaced by fluorine atom, the
corresponding substrate shows excellent reactivity with a yield of
99% (2b). The substrates of the substitution on the phenyl
moieties also showed excellent reactivity, when para-position of
the benzene ring is substituted by halogen atoms, and the
corresponding products were obtained with a yield of 99% (2c to
2e). Both the meta-substituted benzyl substrates and meta-
substituted phenyl substrates showed good reactivity, the reaction
efficiency of the corresponding substrates was slightly lower than
para-substituted substrates with yields of 81% and 89% (2f and
2g), respectively. When the para-position of benzyl was replaced
by bromine atom, the corresponding substrate showed excellent
reactivity with a yield of 95% (2h). While the ortho-position of
benzyl was replaced by halogen atoms, the reaction hardly
occurred. We speculate that steric hindrance is the main factor
leading to the non-reaction (2i and 2j). In order to enrich the
diversity of substrates, the substituted diphenyl ring of substrates
were also investigated. 4-Bromo-n-(4-chloro-phenyl) aniline
2a, 92%b (90%)c
2d, 99% (99%)
2b, 99% (99%)
2e, 92% (89%)
2c, 99% (96%)
HN
Br
2f, 81% (69%)
2g, 89% (85%)
2h, 95% (91%)
2i, 0%
2j, trace
2k, 84% (81%)
2l, 86% (79%)
2o, 55% (42%)
showed excellent reactivity with
a yield of 84% (2k).
Subsequently, when the benzene ring of benzyl part was replaced
in substrates with different substituents, it was found that the
methyl and methoxy substrates with electron-giving effects could
proceeded well, and the corresponding homoallyllic amine
products (2l and 2m) were obtained in 86% and 93% yields,
respectively. When aniline counterpoint is replaced by electron-
donating group methyl, the corresponding substrate showed low
reactivity and selectivity under standard reaction conditions. TLC
point plate analysis results showed that the reaction was very
complex and nearly half of the raw materials did not react (2n).
Similarly, the aniline counterpoint was replaced by electron-rich
group methoxy, it was incompatible with the optimal conditions.
When the benzene-ring counterpoint was replaced by strongly
electron-withdrawing trifluoro methyl and cyano groups, the
corresponding substrates showed only moderate reactivity, with
yields of 55% and 46% (2o and 2p), respectively. In addition, the
para-position of phenyl and benzyl moieties were replaced by
nitro group showed good reactivity with yields of 71% and 76%
(2q and 2r), respectively. Heterocyclic secondary amines such as
N-(thiophene-2-methyl) aniline led to better yield (2s). Cinnamyl
aniline also occurred successfully, but the yield is low, only in
32% (2t). However, N-(pyridine-3-methyl) aniline showed poor
reactivity, and TLC analysis showed that only a trace amount of
product was generated, while a large number of raw materials did
not react (2u). When the ortho-position of the phenyl moieties
was replaced by fluorine atom, the reaction also hardly occurs
(2v). We speculate that it is caused by steric hindrance.
Unfortunately, aliphatic substrates such as N-tert-butyl
2m, 93% (89%)
2n, <10%b
N
H
O2N
2p, 46% (46%)
2s, 66% (58%)
2q, 71% (70%)
2t, 32% (28%)
2r, 76% (73%)
2u, trace
Ph
HN
2v, 0%
2y, 0%
2w, 0%
2z, 0%
2x, 0%
benzylamine,
N-(cyclohexylmethyl)aniline,
N-
a Reaction conditions: secondary amine substrate (0.5 mmol), allyl tributyltin
(0.75 mmol, 1.5 equiv) and oxidant DDQ (0.6 mmol, 1.2 equiv) in solvent
ether (2 mL) at room temperature for 2 hours.
(cyclopropylmethyl)aniline and N-octyl aniline did not react (2w
to 2z). We speculate that it is caused by the poor stability of the
imine intermediate after oxidative dehydrogenation.
b NMR yield.

4
Tetrahedron
c Isolated yield by silica-gel column.
O
O
O
Cl
CN
CN
Cl
Cl
CN
CN
Et2O
rt
nBu3Sn
+
Cl
To explore the potential value of this reaction in industrial
application, we conducted an appropriately scaled-up study on it,
and the experimental results are shown in Scheme 2 Taking 10
25%
OSnnBu3
.
- e
+ e
mmol of N-benzyl aniline and 15 mmol of allyl tributyltin as raw
materials in 10 mL of ethyl ether as a solvent, and 12 mmol of
DDQ was subjected slowly under constant agitation at room
temperature. After two hours of reaction, 1.965g of allylated
product was obtained, with a yield of 88%. In this experiment, the
yield of homoallylic amines decreased slightly, which indicated
that the preparation of homoallylic amines by this method has
certain practicability.
O
O
nBu
3 Sn
+
Cl
CN
CN
+
Cl
Scheme 4. Reaction of DDQ with allyltributyltin.
Scheme 2. Gram-scale experiment of allylation.
To testify this conjecture and acquire forthright proof,
chemical quenching of radicals was investigated by adding 3
equivalents of TEMPO (2,2,6,6-tetramethylpiperidine oxide,
Scheme 3), a well-known radical-trapping reagent, to the standard
reaction. The surveillance was persistent with conjecture that the
reaction may have radical process.
Fig. 1. Comparison of allyltributyltin and allylated phenol intermediate.
In addition, the reaction effect of N-benzyl aniline with DDQ
was investigated. To the mixture of N-benzyl aniline and
excessive DDQ was added CDCl3, and the resulting solution was
transferred into NMR tube for nuclear magnetic characterization
at room temperature. The experimental results are shown in Fig.
2 below. The chemical displacement of N-H in N-benzyl aniline
is 4.03 ppm before the reaction with DDQ. After the reaction
with DDQ, the signal peak of N-H is almost disappeared, and a
new peak appears at 8.46 ppm. It can be seen that in the reaction
process, DDQ firstly oxidized N-benzyl aniline into imine
intermediate. In another case of N-(2-bromobenzyl) aniline (2j)
which was inactive in this allylation, the N-H signal likewise
demonstrated the imine formation. So the reason of inactivity
might exist in the later nucleophilic addition stage.
Scheme 3. Radical trapping experiment.
The sequence of adding starting materials was found crucial
for this transformation as well. When adding the allyltributyltin
before DDQ, the reaction failed to generate the allylation product
with N-benzyl aniline recovered in above 99%. Therefore,
nuclear magnetic hydrogen spectrum analysis of allyltributyltin
reagent was used as a reference standard in interpreting our
hypotheses and exploring the formation of intermediate in the
reaction process. 1H NMR shows that methylene in
allyltributyltin has double peaks, and its chemical displacement is
1.77 ppm. One hydrogen on the inner side of the olefinic double
bond has multiple peaks, and its chemical displacement is 5.98-
5.89 ppm. The chemical displacements for terminal sp2
hybridized hydrogens appeared at 4.78 ppm and 4.64 ppm,
respectively. When mixing 0.75 mmol of allyltributyltin reagent
and DDQ (1.2 eq.) at room temperature for half an hour, allylated
phenol intermediate was formed in 25% NMR yield (Scheme 4).
1H NMR spectrum showed that the allyltributyltin reagent was
oxidized directly and the peak of methylene downshifted to 4.66
ppm (Fig. 1). Consequently, we speculated that DDQ did oxidize
allyltributyltin reagent into allylic radical by single electron
transfer and DDQ was converted into radical anion after
acquiring one electron, both of which resulted in generation of
the coupling product. Even when mixing N-benzylamine,
allyltributyltin and DDQ in CDCl3, the oxidation of
allyltributyltin was observed from mixture NMR spectrum,
which indicates that oxidative process of allyltributyltin was
unable to be neglected, especially in changing of addition
sequence.
Fig. 2. The reaction of DDQ with N-benzyl aniline
Based on the above experimental results, we proposed the
possible mechanism of allylation reaction, as shown in Fig. 3.
Firstly the single electron transfer process takes place, and DDQ
oxidizes N-benzyl aniline to imine intermediate, and then allyl tin
reagent attacks it via nucleophilic addition, and allyl C-C bond
formation occurs when tributyltin groups are removed, and
corresponding homoallylic amine products are generated. When

5
ortho-halogen substitution is on the benzene ring, no products (2i,
2j and 2v) were obtained in spite of the observed imine formation
in NMR tests. The inactivity probably resulted from steric
repulsion between allyl and halogen.
residue was purified by column chromatography on silica gel
column using EtOAc−petroleum ether solution as eluent to afford
secondary amine.
4.3 General procedure for synthesizing the homoallylic amines
(2a-z)
Secondary amine (0.5 mmol), ether (2 mL), DDQ (0.6 mmol,
1.2 equiv), allyl tributyltin (0.75 mmol, 1.5 equiv) were added
successively to the 10 mL test tube at room temperature for 2
hours. The reaction was monitored by TLC point plate. After the
reaction, saturated sodium thiosulfate solution (10 mL) was
added to quench the reaction, and organic phase was extracted by
dichloroform, dried by anhydrous magnesium sulfate, filtered
and vapored to get the oil residue, which was separated by
column chromatography to afford pure allylated products.
4.3.1 N-(1-phenylbut-3-en-1-yl)aniline (2a) [12]
1
Fig. 3. Possible mechanism of allylation.
Light yellow viscous liquid; 90% yield, 100 mg; H NMR
(500 MHz, CDCl3) δ 7.30-7.28 (m, 2H), 7.26-7.23 (t, J = 7.5 Hz,
2H), 7.17-7.14 (m, 1H), 7.02-6.98 (t, J = 7.5 Hz, 2H), 6.58-6.55
(t, J = 7.0 Hz, 1H), 6.43-6.41 (d, J = 7.5 Hz, 2H), 5.73-5.64 (m,
1H), 5.13-5.06 (m, 2H), 4.32- 4.29 (m, 1H), 4.10 (s, 1H), 2.56-
2.51 (m, 1H), 2.45-2.39 (m, 1H). 13C NMR (125 MHz, CDCl3) δ
147.5, 143.7, 134.8, 129.2, 128.8, 127.2, 126.5, 118.5, 117.6,
113.7, 57.3, 43.5.
3. Conclusion
In summary, based on the previous work of phosphonation
and cyanidation, we continued to develop the application of
DDQ-promoted oxidation coupling system in C-C construction,
and effectively prepared
a series of homoallylic amine
compounds. The reaction conditions were mild and free of
transition metals, and the operation was simple, which provided a
convenient and feasible way for the preparation of homoallylic
amine compounds. In the mechanism study experiment, the
specific oxidation effect of DDQ in this process was
demonstrated through the comparison experiment and imine
intermediate capture, and the single electron transfer process
mediated by DDQ was proposed. The gram scale experiment is
progressing smoothly, provides the potential industrial
application value.
4.3.2 N-(1-(4-fluorophenyl)but-3-en-1-yl)aniline (2b)[12]
1
Light yellow viscous liquid; 99% yield, 119 mg; H NMR
(500 MHz, CDCl3) δ 7.31-7.29 (m, 2H), 7.08-7.05 (t, J = 8.5 Hz,
2H), 6.70-6.96 (t, J = 8.5 Hz, 2H), 6.65-6.63 (t, J = 7.0 Hz, 1H),
6.47-6.45 (d, J = 8.5 Hz, 2H), 5.77-5.68 (m, 1H), 5.18-5.12 (m,
2H), 4.36-4.34 (t, J = 7.0 Hz, 1H), 4.12 (s, 1H), 2.58-2.53 (m,
1H), 2.48-2.42 (m,1H). 13C NMR (125 MHz, CDCl3) δ 162.0 (d,
J = 243.75 Hz), 147.3, 139.3 (d, J = 2.5 Hz), 134.5, 129.2, 127.9
(d, J = 7.5 Hz), 118.7, 117.7, 115.5 (d, J = 20.0 Hz), 113.6, 56.7,
43.5.
4. Experimental section
4.3.3 4-fluoro-N-(1-phenylbut-3-en-1-yl)aniline (2c) [12]
4.1 General Information
The 1H and 13C NMR spectra were recorded in CDCl3 solution
1
Light yellow viscous liquid; 96% yield, 116 mg; H NMR
o
1
on a Bruker Avance 500/125 MHz spectrometer at 20-25 C. H
NMR chemical shifts were reported in ppm using
tetramethylsilane (TMS, δ = 0.00 ppm) as the internal standard.
(500 MHz, CDCl3) δ 7.34-7.29 (m, 4H), 7.23-7.21 (m, 1H), 6.78-
6.74 (t, J = 9.0 Hz, 2H), 6.41-6.39 (m, 2H), 5,79-5,71 (m, 1H),
5.18-5.13 (m, 2H), 4.31-4.29 (m, 1H), 4.04 (s, 1H), 2.61-2,56 (m,
1H), 2.49-2.43 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 155.9 (d,
J = 233.75 Hz), 143.9, 143.5, 134.8, 128.8, 127.3, 126.4, 118.5,
115.6 (d, J = 22.5 Hz), 114.4 (d, J = 7.5 Hz), 57.9, 43.5.
1
The data of H NMR was reported as follows: chemical shift,
multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m =
multiplet), coupling constant (J value) in Hz and integration. 13C
NMR spectra were reported in parts per million using solvent
CDCl3 (δ = 77.2 ppm) as an internal standard. All the reagents
used were of analytical grade, purchased locally and used without
any purification unless otherwise specified. Solvents purchased
from chemical supplier were firstly dried over 4Å molecular
sieve for one week. Column chromatographys were performed
using silica gel, and analytical thin-layer chromatography (TLC)
was used to monitor the reactions, performed on silica gel plates.
4.3.4 4-chloro-N-(1-phenylbut-3-en-1-yl)aniline (2d)[12]
1
Light yellow viscous liquid; 99% yield, 127 mg; H NMR
(500 MHz, CDCl3) δ 7.31-7.29 (m, 4H), 7.24-7.21 (m, 1H), 7.0-
6.98 (d, J = 8.5 Hz, 2H), 6.40-6.34 (d, J = 9.0 Hz, 2H), 5.78-5.69
(m, 1H), 5.18-5.13 (m, 2H), 4.33 (s, 1H), 4.16 (s, 1H), 2.62-2.57
(m, 1H), 2.50-2.44 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 146.0,
143.1, 134.5, 129.0, 128.8, 127.3, 126.4, 122.1, 118.7, 114.7,
57.3, 43.3.
4.2 General procedure for synthesis of substrates(1a-u)
4.3.5 4-bromo-N-(1-phenylbut-3-en-1-yl)aniline (2e) [12]
To a 100 mL round flask that was equipped with a stirring
bar, corresponding aniline (10.0 mmol), corresponding aldehyde
(11.0 mmol), NaOEt (1.36 g, 20.0 mmol) and methanol (20 mL)
were added successively. The resulting mixture was stirred at 80
oC in atmosphere and monitored by TLC. When aniline was
converted completely, the mixture was cooled to room
temperature, and NaBH4 (0.416 g, 11.0 mmol) was added to the
reaction mixture in portions. The continuous stirring was kept for
additional 1-4 hours at 80 oC. TLC monitored the completion of
the reaction. The solvent was evaporated and the resulting
1
Light yellow viscous liquid; 89% yield, 135 mg; H NMR
(500 MHz, CDCl3) δ 7.24-7.23 (m, 4H), 7.17-7.15 (m, 1H), 7.07-
7.05 (d, J = 8.5 Hz, 2H), 6.29-6.27 (d, J = 8.5 Hz, 2H), 5.70-5.62
(m, 1H), 5.12-5.06 (m, 2H), 4.27-4.24 (m, 1H), 4.15 (s, 1H),
2.55-2.51 (m, 1H), 2.44-2.38 (m, 1H). 13C NMR (125 MHz,
CDCl3) δ 146.3, 143.0, 134.5, 131.9, 128.9, 127.4, 126.4, 118.7,
115.3, 109.3, 57.3, 43.3.
4.3.6 3-bromo-N-(1-phenylbut-3-en-1-yl)aniline (2f) [12]

6
Tetrahedron
1
Light yellow viscous liquid; 79% yield, 120 mg; H NMR
White solid; 46% yield, 57 mg; 1H NMR (500 MHz, CDCl3) δ
7.61-7.60 (d, J = 8.0 Hz, 2H), 7.49-7.47 (d, J = 8.0 Hz, 2H),
7.09-7.06 (t, J = 8.5 Hz, 2H), 6.69-6.66 (t, J = 7.5 Hz, 1H), 6.43-
6.41 (d, J = 7.5 Hz, 2H), 5.76-5.68 (m, 1H), 5.21-5.17 (m, 2H),
4.43-4.40 (m, 1H), 4.17 (s, 1H), 2.62-2.57 (m, 1H), 2.50-2.44 (m,
1H). 13C NMR (125 MHz, CDCl3) δ 149.5, 146.8, 133.7, 132.7,
129.3, 127.3, 119.4, 119.0, 118.2, 113.6, 111.1, 57.1, 43.1.
(500 MHz, CDCl3) δ 7.26-7.25 (m, 3H), 7.19-7.17 (m, 2H), 6.85-
6.82 (t, J = 8.0 Hz, 1H), 6.69-6.68 (d, J = 7.5 Hz, 1H), 6.60 (s,
1H), 6.33-6.31 (d, J = 6.5 Hz, 1H), 5.70-5.62 (m, 1H), 5.13-5.07
(m, 2H), 4.30-4.16 (m, 2H), 2.56-2.54 (m, 1H), 2.44-2.40 (m,
1H). 13C NMR (125 MHz, CDCl3) δ 146.3, 143.0, 134.5, 131.9,
128.9, 127.4, 126.4, 118.7, 115.3, 109.3, 57.3, 43.3.
4.3.7 N-(1-(3-bromophenyl)but-3-en-1-yl)aniline(2g) [12]
4.3.14 4-nitro-N-(1-phenylbut-3-en-1-yl)aniline (2q)[22]
1
1
Light yellow viscous liquid; 85% yield, 129 mg; H NMR
Light yellow viscous liquid; 70% yield, 94 mg; H NMR (500
(500 MHz, CDCl3) δ 7.32-7.31 (d, J = 5.0 Hz, 4H), 7.25-7.23 (m,
2H), 6.91-6.87 (t, J = 10.0 Hz, 1H), 6.74-6.73 (d, J = 5.0 Hz, 1H),
6.65 (s, 1H), 6.37-6.36 (d, J = 5.0 Hz, 1H), 5.77-5.69 (m, 1H),
5.19-5.13 (m, 2H), 4.35 (s, 1H), 4.21 (s, 1H), 2.62-2.57 (m, 1H),
2.50-2.44 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 148.7, 143.0,
134.5, 130.5, 128.9, 127.4, 126.4, 123.2, 118.7, 112.1, 57.1, 43.3.
MHz, CDCl3) δ 8.19-8.17 (d, J = 10.0 Hz, 2H), 7.55-7.53 (d, J =
10.0 Hz, 2H), 7.10-7.06 (t, J = 10.0 Hz, 2H), 6.69-6.66 (t, J = 7.5
Hz, 1H), 6.44-6.42 (d, J = 10.0 Hz, 2H), 5.77-5.69 (m, 1H), 5.22-
5.19 (m, 2H), 4.48-4.47 (m, 1H), 4.21 (s, 1H), 2.65-2.60 (m, 1H),
2.52-2.46 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 151.7, 147.3,
146.7.5, 133.6, 129.4, 127.4, 124.2, 119.5, 118.3, 113.7, 57.0,
43.1.
4.3.8 N-(1-(4-bromophenyl)but-3-en-1-yl)aniline(2h) [12]
4.3.15 N-(1-(4-nitrophenyl)but-3-en-1-yl)aniline(2r)[22]
Light yellow viscous liquid; 91% yield, 138 mg; 1H NMR (500
MHz, CDCl3) δ 7.44-7.42 (d, J = 10.0 Hz, 2H), 7.24-7.23 (d, J =
5.0 Hz, 2H), 7.09-7.06 (t, J = 7.5 Hz, 2H), 6.67-6.64 (t, J = 7.5
Hz, 1H), 6.46-6.44 (d, J = 10.0 Hz, 2H), 5.75-5.70 (m,1H), 5.19-
5.14 (m, 2H), 4.33 (s, 1H), 4.12 (s, 1H) 2.58-2.54 (m, 1H), 2.48-
2.43 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 147.2, 142.9, 134.3,
131.9, 129.3, 128.3, 120.8, 118.9, 117.9, 113.7,77.5, 56.8, 43.3.
1
Light yellow viscous liquid; 73% yield, 98 mg; H NMR (500
MHz, CDCl3) δ 8.24 (s, 1H), 8.10-8.08 (d, J = 10.0 Hz 1H), 7.72-
7.70 (d, J = 10.0 Hz, 1H), 7.50-7.47 (t, J = 7.5 Hz, 2H), 6.69-6.66
(t, J = 7.5 Hz 1H), 6.46-6.45 (d, J = 5.0 Hz, 2H), 5.76-5.71 (m,
1H), 5.22-5.18 (m, 2H), 4.48 (s, 1H), 4.22 (s, 1H), 2.65-2.60 (m,
1H), 2.53-2.47 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 148.9,
146.8, 133.7, 132.8, 129.8, 129.4, 122.4, 121.5, 118.2, 113.7,
59.9, 43.2.
4.3.9 4-bromo-N-(1-(4-chlorophenyl)but-3-en-1-yl)aniline(2k) [12]
1
Light yellow viscous liquid; 81% yield, 136 mg; H NMR
4.3.16 N-(1-(thiophen-2-yl)but-3-en-1-yl)aniline (2s) [12]
(500 MHz, CDCl3) δ 7.37-7.35 (d, J = 8.5 Hz, 2H), 7.13-7.11 (d,
J = 8.5 Hz, 2H), 6.94-6.92 (d, J = 9.0 Hz, 2H), 6.30-6.28 (d, J =
9.0 Hz, 2H), 5.67-5.59 (m, 1H), 5.12-5.07 (m, 2H), 4.22-4.20 (m,
1H), 4.11 (s, 1H), 2.51-2.46 (m, 1H), 2.40-2.34 (m, 1H). 13C
NMR (125 MHz, CDCl3) δ 145.7, 142.3, 134.1, 132.0, 129.1,
128.2, 122.5, 121.0, 119.1, 114.8, 56.9, 43.2.
Yellow viscous liquid; 68% yield, 78 mg; 1H NMR (500
MHz, CDCl3) δ 7.16-7.10 (m, 3H), 6.97-6.96 (m, 1H), 6.94-6.92
(m, 1H), 6.71-6.68 (t, J = 7.5 Hz, 1H), 6.60-6.59 (d, J = 8.0 Hz,
2H), 5.84-5.76 (m, 1H), 5.21-5.14 (m, 2H), 4.70 (s, 1H), 4.12 (s,
1H), 2.69-2.62 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 148.9,
147.2, 134.2, 129.3, 127.0, 123.9, 123.6, 118.9, 118.1, 113.8,
53.6, 43.3.
4.3.10 N-(1-(p-tolyl)but-3-en-1-yl)aniline (2l) [12]
1
Light yellow viscous liquid; 79% yield, 94 mg; H NMR (500
4.3.17 N-(1-phenylhexa-1,5-dien-3-yl)aniline (2t)
MHz, CDCl3) δ 7.25-7.23 (d, J = 7.5 Hz, 2H), 7.13-7.11 (d, J =
7.5 Hz, 2H), 7.08-7.05 (t, J = 8.0 Hz, 2H), 6.64-6.61 (t, J = 7.5
Hz, 1H), 6.50-6.48 (d, J = 8.0 Hz, 2H), 5.78-5.71 (m, 1H), 5.19-
5.12 (m, 2H), 4.36-4.33 (t, J = 7.0 Hz, 1H), 4.13 (s, 1H), 2.60-
2.56 (m, 1H), 2.50-2.46 (m, 1H), 2.32 (s, 3H). 13C NMR (125
MHz, CDCl3) δ 147.6, 140.7, 136.7, 135.0, 129.4, 129.2, 126.4,
118.4, 117.4, 113.6, 57.0, 43.5, 21.2.
1
Light yellow viscous liquid; 28% yield, 31mg; H NMR (500
MHz, CDCl3) δ 7.35-7.34 (m, 2H), 7.30-7.27 (t, J = 7.5 Hz, 2H),
7.22-7.19 (m, 1H), 7.16-7.13 (t, J = 8.5 Hz, 2H), 6.70-6.67 (t, J =
7.0 Hz, 1H), 6.65-6.63 (d, J = 7.5 Hz, 2H), 6.61-6.58 (m, 1H),
6.21-6.17 (m, 1H), 5.89-5.81 (m, 1H), 5.20-5.14 (m, 2H), 4.06-
4.05 (m, 1H), 3.83 (s, 1H), 2.52-2.42 (m, 2H). 13C NMR (125
MHz, CDCl3) δ 147.7, 137.1, 134.6, 131.7, 130.5, 129.3, 128.7,
127.6, 126.5, 118.5,117.5,113.7, 54.9, 40.7.
4.3.11 N-(1-(4-methoxyphenyl)but-3-en-1-yl)aniline (2m)[12]
1
Light yellow viscous liquid; 89% yield, 113 mg; H NMR
Notes
(500 MHz, CDCl3) δ 7.27-7.26 (d, J = 8.5 Hz, 2H), 7.09-7.05 (t,
J = 7.5 Hz, 2H), 6.86-6.84 (d, J = 8.5 Hz, 2H), 6.65-6.62 (t, J =
7.0 Hz, 1H), 6.50-6.48 (d, J = 8.0 Hz, 2H), 5.79-5.71 (m, 1H),
5.18-5.12 (m, 2H), 4.34-4.32 (t, J = 7.0 Hz, 1H), 4.12 (s, 1H),
3.77 (s, 3H), 2.59-2.54 (m, 1H), 2.49-2.44 (m, 1H). 13C NMR
(125 MHz, CDCl3) δ 158.7, 147.6, 135.7, 134.9, 129.2, 127.5,
118.4, 117.5, 114.1, 113.7, 56.7, 55.4, 43.6.
The authors declare no competing financial interest.
Acknowledgments
We gratefully acknowledge funding from the National Natural
Science Foundation of China (No. 21372265) and the Natural
Science Foundation Project of CQ CSTC (cstc2018jcyjAX0155)
for financial support.
Supplementary Material
4.3.12 N-(1-(4-(trifluoromethyl)phenyl)but-3-en-1-yl)aniline (2o)
[12]
Supplementary data associated with this article can be found,
in the online version, at
1
Light yellow viscous liquid; 42% yield, 61 mg; H NMR (500
References
MHz, CDCl3) δ 7.59-7.57 (d, J = 8.5 Hz, 2H), 7.49-7.48 (d, J =
8.5 Hz, 2H), 7.10-7.07 (t, J = 8.5 Hz, 2H), 6.68-6.66 (t, J = 7.0
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Highlights
In this work, we have developed DDQ-promoted allyl reaction approach towards
various N-benzyl anilines from N-benzyl aniline as raw material, allyltributyltin as
allyl reagent and DDQ as oxidant. Detailed optimization of various parameters
including screening of solvents, concentration effect of allyl tributyltin and solvent,
temperature and reaction time was performed and a series of N-benzyl anilines
carrying variety of functional groups such as halides, alkyl groups and cyanogroups
were also scoped with yields of up to 99%. This protocol works smoothly on
preparative scale synthesis and also presents an alternative access to the concise
synthesis of homoallylic amines. Moreover, in the last part of our research, we
explored the mechanism of the reaction.

Declaration of Interest Statement
All the authors declare no competing financial interest.