Efficient ZnBr2-catalyzed reactions of allylic alcohols with indoles, sulfamides and anilines under high-speed vibration milling conditions

Article abstract of DOI:10.1039/c3gc40262b

Solvent-free reactions of allylic alcohols with various nucleophiles including indoles, sulfamides and anilines were efficiently achieved in the presence of 20% ZnBr₂ under high-speed vibration milling conditions, and the products were obtained in good to excellent yields with the formation of water as the only byproduct.

Full text of DOI:10.1039/c3gc40262b

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Efficient ZnBr2-catalyzed reactions of allylic alcohols
with indoles, sulfamides and anilines under high-speed
vibration milling conditions†
Cite this: DOI: 10.1039/c3gc40262b
Guang-Peng Fan,a Zi Liua and Guan-Wu Wang*a,b
Received 4th February 2013,
Accepted 4th April 2013
Solvent-free reactions of allylic alcohols with various nucleophiles including indoles, sulfamides and
anilines were efficiently achieved in the presence of 20% ZnBr2 under high-speed vibration milling
conditions, and the products were obtained in good to excellent yields with the formation of water as
the only byproduct.
DOI: 10.1039/c3gc40262b
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the impressive progress, these reaction systems have some
drawbacks: the need for expensive and toxic catalysts, high
Introduction
The Tsuji–Trost reaction using a π-allyl palladium intermediate temperatures and poisonous solvents, such as toluene and
has served as an important reaction in the synthesis of natural dioxane.
products, pharmaceuticals, functional materials and agro-
On the other hand, solvent-free reactions have drawn atten-
chemicals.1,2 The reaction usually employs Pd(0) complexes, tion over the past few decades because it can supply environ-
bases and activated allyl alcohol derivatives. Because of the mentally benign protocols and provide clean, efficient, and
poor leaving ability of the hydroxyl group, alcohols generally high-yielding organic processes in modern synthetic chemi-
require preactivation by transformation into the corresponding stry. The mechanical milling technique is a powerful tool to
halides, carboxylates, esters, phosphonates, sulfonates or promote solvent-free reactions.18–21 With our continuous inter-
related compounds with good leaving groups. A disadvantage est in organic reactions under ball milling conditions, we set
is that large quantities of unwanted byproducts are generated.3 out to explore the catalytic nucleophilic substitution of allylic
The direct reaction between alcohols and nucleophiles alcohols with various carbon and nitrogen nucleophiles invol-
would be an ideal process for C–C and C–N bond formation ving C–C and C–N bond formation in a ball mill.
because the preparation of reactive alcohol derivatives would
not be required and only H2O would be generated as a by-
product. Recently, more and more attention has been paid to
Results and discussion
the direct nucleophilic substitution of alcohols for Tsuji–Trost-
type reactions. Several attempts have been carried out to
perform this transformation in the presence of palladium
and ruthenium catalysts.2,4 Various Lewis acids including
For the reaction of free (N–H) indoles with alcohols, the selec-
tive formation of the N-alkylated products or the C3-alkylated
products is usually a challenging task.22 In order to explore
this process, the direct substitution between (E)-1,3-diphenyl-
prop-2-en-1-ol (1a) and indole (2a) was chosen as the model
reaction and a brief screening of the reaction conditions was
undertaken. It was satisfactory that the C3-alkylated product
3a was obtained exclusively in 89% yield (Table 1, entry 1) in
the presence of 20% ZnBr2 for 1 h. The reaction time was
screened, and it was found that 1.5 h was enough to complete
this reaction with a yield of 97% (Table 1, entries 2 and 3).
With the amount of ZnBr2 decreased to 10%, the yield
dropped to 88% (Table 1, entry 4) and could not be improved
even after prolonging the reaction time to 3 h (Table 1, entry
5). ZnCl2 catalyzed this reaction in 82% yield (Table 1, entry 6),
while Zn(OAc)2·2H2O afforded only a trace amount of 3a
(Table 1, entry 7). Lewis acids FeCl3, AlCl3 and CuCl2·2H2O
InCl3,5 FeCl3,6 Bi(OTf)3,7 Yb(OTf)3,8 Cu(BF4)2,9 AuCl3 and
10
MoO2(acac)2,11 as well as Brønsted acids such as p-toluenesul-
fonic,12 phosphomolybdic acid,13 proton-exchanged mont-
morillonite,14 dodecylbenzenesulfonic acid15 and heteropoly
acids,16 have been used to catalyze this process. Fluorinated
alcohols17 can also work as promoters in this reaction. Despite
aCAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for
Physical Sciences at Microscale, and Department of Chemistry, University of Science
and Technology of China, Hefei, Anhui 230026, P. R. China.
E-mail: gwang@ustc.edu.cn; Fax: (+86)551 3607864; Tel: (+86) 551 3607864
bState Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou,
Gansu 730000, P. R. China
†Electronic supplementary information (ESI) available: NMR spectra of all com-
pounds. See DOI: 10.1039/c3gc40262b
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Table 1 Optimization for the reaction of (E)-1,3-diphenylprop-2-en-1-ol with
indole under high-speed vibration milling conditionsa
Table 2 ZnBr2-catalyzed reactions of allylic alcohols with carbon nucleophiles
under high-speed vibration milling conditionsa
Entry
Catalyst (20%)
Time (h)
Yieldb (%)
1
2
ZnBr2
ZnBr2
ZnBr2
ZnBr2
ZnBr2
ZnCl2
Zn(OAc)2·2H2O
FeCl3
AlCl3
CuCl2·2H2O
CaCl2
Mn(OAc)3·2H2O
PWA
p-Toluenesulfonic acid
PdCl2
1
1.5
2
1.5
3
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
89
97
97
88
87
82
Trace
84
84
3
4c
5c
6
7
8
9
10
11
12
13
14
15
90
n.r.
Trace
75
77
91
a Unless otherwise specified, the reaction mixture of 1a (1 equiv.), 2a (1
equiv.) and catalyst (20 mol%) was milled for a given time. b Isolated
yields obtained by chromatography on silica gel. c 10 mol% catalyst
was used.
affected the reaction efficiency to give 84–90% yields (Table 1,
entries 8–10). In contrast, both CaCl2 and Mn(OAc)3·2H2O
were not effective for this reaction (Table 1, entries 11 and 12).
Product 3a was obtained in 75% yield when 12-tungstophos-
phoric acid (PWA) was employed as the catalyst (Table 1,
entry 13). p-Toluenesulfonic acid, a common Brønsted acid,
catalyzed this reaction in 77% yield (Table 1, entry 14). It is
noteworthy that the use of PdCl2 gave 3a in 91% yield,
which is inferior to that catalyzed by ZnBr2 (Table 1, entry 15
vs. entry 3).
With the optimized reaction conditions in hand, the sub-
strate scope was then investigated. The reactions of various
substituted indoles with several alcohols were explored, and
the results are summarized in Table 2. In general, indoles with
electron-donating or electron-withdrawing groups all furnished
the desired products 3a–3g in good to excellent yields. It is of
interest to observe that the C2-substituted indole with an elec-
tron-withdrawing group could also generate the desired
product, albeit in lower yield. The reaction of 1a with 2-ethoxy-
carbonylindole gave product 3g in 65% yield. The ZnBr2-
mediated reaction also worked well for N-methylindoles and
afforded 3h and 3i in higher yields than those catalyzed by
other Lewis acids.5 However, 1-acetylindole did not provide
any desired products, probably because the N-acetyl group
decreased the nucleophilicity of the C3-position of the indole.
Furthermore, other representative allylic alcohols including
(E)-1,3-bis(4-methoxyphenyl)prop-2-en-1-ol (1b) and (E)-1,3-
bis(4-chlorophenyl)prop-2-en-1-ol (1c) gave 3j, 3k and 3l
in 86–96% yields under our typical reaction conditions.
The thiophene-substituted allylic alcohol (1d) could also be
a Unless otherwise specified, the reaction mixture of 1 (1 equiv.), 2 (1
equiv.) and catalyst (20 mol%) was milled for 1.5 h. The isolated yields
were obtained by chromatography on silica gel.
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allylated to produce 3m and 3n in excellent yields (92–97%) by scrutinized under the present conditions. The reaction con-
the present method. Thiophene derivatives are widely used as ditions and results for the solvent-free reactions of 1a with
medicines, such as the antibiotic sufentanil and cephalospor- nitrogen nucleophiles under high-speed vibration milling con-
ins. Indole derivatives also occur in nature and possess a ditions are collected in Table 3. As revealed in Table 3, sulfa-
variety of biological activities. Therefore, 3m and 3n may have mides with either electron-donating or electron-withdrawing
promising applications in pharmaceutical sciences. It should groups were successfully reacted with 1a to afford the corres-
be pointed out that the sterically hindered 2-substituted ponding products 5a–5d in moderate to good yields. Methane
indoles behaved well and provided the allylation products 3b, sulfonamide, an aliphatic sulfamide, could also be used and
3f, 3g, 3i, 3l and 3n in comparable yields to those of the afforded product 5e, albeit in a lower yield. To our delight, 1a
2-unsubstituted counterparts.
reacted with 4-nitroaniline and 2-nitroaniline to afford pro-
The regiochemistry of the reaction was then studied. The ducts 5f and 5g in 91% and 89% yields, respectively. Product
dissymmetrical allylic alcohol (E)-3-(4-chlorophenyl)-1-phenyl- 5h was formed exclusively with a high yield of 90% when
prop-2-en-1-ol (1e) could be allylated to produce 3o and 3p in a 1-(4-aminophenyl)ethanone was employed as the nucleophile.
total yield of 87%, similar to the previously reported result.11 It is noteworthy that although poorly nucleophilic amines
We also explored the chemoselectivity of the reaction. 1,3- such as sulfonamides or deactivated anilines could undergo
Diphenylpropan-1-ol and (E)-hept-4-en-3-ol were not effective the allylation reaction, activated amines did not react with
for this reaction. When one of two phenyl groups in 1a was allylic alcohols because electron-rich amines may facilely co-
replaced by a H atom, i.e., (E)-3-phenylprop-2-en-1-ol, the reac- ordinate to the metal center, and thus inhibited the allylation
tion did not give the desired product. In contrast, when one of reaction. The same phenomenon has been reported in the
two phenyl groups in 1a was changed to a methyl group, (E)-4- literature.10,11
phenylbut-3-en-2-ol selectively afforded product 3q in 29%
Although mechanochemical nucleophilic reactions under
yield. The above experimental results demonstrated that the neutral and basic conditions have been described, there is no
hydroxy group located at both the allylic and benzylic positions report on Lewis acid-catalyzed nucleophilic substitution reac-
was very important for the successful allylation.
tions to construct C–C and C–N bonds under mechanochem-
To further demonstrate the versatility of our present ical conditions.18f
methodology, the direct substitutions of allylic alcohols with
nitrogen nucleophiles including sulfamides and anilines were
Conclusions
Table 3 ZnBr2-catalyzed reactions of allylic alcohols with nitrogen nucleophiles
under high-speed vibration milling conditionsa
In summary, we have developed an efficient and environmen-
tally friendly methodology for the direct substitution of allylic
alcohols with indoles, sulfamides and anilines catalyzed
by ZnBr2 under high-speed vibration milling conditions,
affording the corresponding allylated products in yields up to
97%, with the formation of water as the only byproduct. The
milder reaction conditions, higher yields, better selectivity and
no use of solvents make this protocol attractive to the
chemistry community.
Experimental section
General procedure for the reactions of allylic alcohols with
carbon nucleophiles
A
mixture of 1 (0.1 mmol), 2 (0.1 mmol) and ZnBr2
(0.02 mmol) was vigorously shaken by high-speed vibration
milling (HSVM) at a frequency of 3500 cycles per min for 1.5 h.
Details of the high-speed vibration mill had been described in
the literature.18a,19c The combined reaction mixture from two
runs was collected and dissolved in ethyl acetate. The solution
was filtrated to remove the residue and then evaporated to
dryness under high vacuum. Finally, the resulting products
3a–3q were purified by column chromatography on silica gel
using ethyl acetate–petroleum ether (60–90 °C) as the eluent.
(E)-3-(1,3-Diphenylallyl)-1H-indole (3a).23 Yellow oil. 1H
NMR (400 MHz, CDCl3): δ 7.91 (brs, 1H), 7.42 (d, J = 8.0 Hz,
a Unless otherwise specified, the reaction mixture of 1 (1 equiv.), 4
(1 equiv.) and catalyst (20 mol%) was milled for 1.5 h. The isolated
yields were obtained by chromatography on silica gel.
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1H), 7.35–7.12 (m, 12H), 7.00 (t, J = 7.5 Hz, 1H), 6.82 (d, J = CDCl3): δ 143.9, 138.6, 137.6, 137.5, 132.5, 131.9, 130.9, 130.6,
1.9 Hz, 1H), 6.71 (dd, J = 15.8, 7.4 Hz, 1H), 6.42 (d, J = 15.8 Hz, 128.4, 128.3, 128.2, 128.1, 127.0, 126.5, 126.3, 125.9, 121.6,
1H), 5.10 (d, J = 7.4 Hz, 1H).
120.8, 119.3, 114.1, 109.4, 45.6, 30.9; HR-MS (+APCI) calcd for
(E)-3-(1,3-Diphenylallyl)-2-methyl-1H-indole (3b).23 Yellow C30H26N: 400.2065 [M + 1]+, found 400.2061.
oil. 1H NMR (400 MHz, CDCl3): δ 7.74 (brs, 1H), 7.36–7.32
(E)-3-(1,3-Bis(4-methoxyphenyl)allyl)-1H-indole (3j). Yellow
(m, 5H), 7.28–7.23 (m, 5H), 7.20–7.15 (m, 2H), 7.07 (td, J = 7.6, oil. IR (KBr) cm−1 3350, 2955, 2929, 2836, 1697, 1603, 1510,
1.1 Hz, 1H), 6.96 (td, J = 7.5, 1.0 Hz, 1H), 6.82 (dd, J = 15.8, 1460, 1303, 1251, 1172, 1110, 1030, 832, 749, 606; 1H NMR
7.2 Hz, 1H), 6.41 (dd, J = 15.8, 1.0 Hz, 1H), 5.13 (d, J = 7.2 Hz, (400 MHz, CDCl3): δ 7.98 (brs, 1H), 7.42 (d, J = 8.0 Hz, 1H),
1H), 2.34 (s, 3H).
7.33 (d, J = 8.2 Hz, 1H), 7.28 (d, J = 8.8 Hz, 2H), 7.23 (d, J =
(E)-3-(1,3-Diphenylallyl)-5-methoxy-1H-indole (3c).23 Yellow 8.8 Hz, 2H), 7.15 (td, J = 7.6, 1.0 Hz, 1H), 7.01 (td, J = 7.5,
1
oil. H NMR (400 MHz, CDCl3): δ 7.87 (brs, 1H), 7.37–7.33 (m, 0.9 Hz, 1H), 6.88 (dd, J = 2.3, 0.8 Hz, 1H), 6.84 (d, J = 8.8 Hz,
4H), 7.32–7.27 (m, 4H), 7.25–7.16 (m, 3H), 6.86–6.80 (m, 3H), 2H), 6.81 (d, J = 8.8 Hz, 2H), 6.56 (dd, J = 15.8, 7.3 Hz, 1H),
6.70 (dd, J = 15.8, 7.3 Hz, 1H), 6.44 (d, J = 15.8 Hz, 1H), 5.06 (d, 6.35 (d, J = 15.8 Hz, 1H), 5.04 (d, J = 7.3 Hz, 1H), 3.78 (s, 6H);
J = 7.3 Hz, 1H), 3.70 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 158.9, 158.1, 136.7, 135.8, 130.8,
(E)-3-(1,3-Diphenylallyl)-7-methyl-1H-indole (3d).23 Yellow 130.4, 129.7, 129.4, 127.4, 126.8, 122.5, 122.0, 120.0, 119.4,
1
oil. H NMR (400 MHz, CDCl3): δ 7.92 (brs, 1H), 7.37–7.16 (m, 119.2, 113.9, 113.8, 111.1, 55.3, 55.2, 45.3; HR-MS (+APCI)
11H), 6.98–6.92 (m, 2H), 6.90 (dd, J = 2.4, 0.7 Hz, 1H), 6.72 (dd, calcd for C25H24NO2: 370.1801 [M + 1]+, found: 370.1798.
J = 15.8, 7.3 Hz, 1H), 6.43 (d, J = 15.8 Hz, 1H), 5.11 (d, J =
7.3 Hz, 1H), 2.47 (s, 3H).
(E)-3-(1,3-Diphenylallyl)-6-fluoro-1H-indole
(E)-3-(1,3-Bis(4-chlorophenyl)allyl)-1H-indole (3k).25 Color-
1
less oil. H NMR (400 MHz, CDCl3): δ 8.00 (brs, 1H), 7.37 (d,
(3e).24 Yellow J = 8.0, 1H), 7.36 (d, J = 8.2, 1H), 7.28–7.22 (m, 8H), 7.18 (td, J =
oil. 1H NMR (400 MHz, CDCl3): δ 7.96 (brs, 1H), 7.36 (d, J = 7.6, 0.7 Hz, 1H), 7.03 (td, J = 7.5, 0.7 Hz, 1H), 6.89 (d, J =
7.2 Hz, 2H), 7.32–7.17 (m, 10H), 7.02 (dd, J = 9.6, 2.3 Hz, 1H), 1.8 Hz, 1H), 6.64 (dd, J = 15.8, 7.2 Hz, 1H), 6.35 (dd, J = 15.8,
6.87 (dd, J = 2.3, 1.0 Hz, 1H), 6.77 (ddd, J = 9.6, 8.8, 2.3 Hz, 0.8 Hz, 1H), 5.08 (d, J = 7.2 Hz, 1H).
1H), 6.69 (dd, J = 15.8, 7.4 Hz, 1H), 6.42 (d, J = 15.8 Hz, 1H),
5.07 (d, J = 7.4 Hz, 1H).
(E)-3-(1,3-Bis(4-chlorophenyl)allyl)-2-methyl-1H-indole (3l).
Colorless oil. IR (KBr) cm−1 3388, 2969, 2922, 1693, 1613,
(E)-3-(1,3-Diphenylallyl)-2-phenyl-1H-indole
(3f).23 Yellow 1590, 1487, 1458, 1402, 1321, 1300, 1243, 1164, 1090, 1012,
1
solid. H NMR (400 MHz, CDCl3): δ 8.05 (brs, 1H), 7.52 (d, J = 969, 821, 747; 1H NMR (400 MHz, CDCl3): δ 7.83 (brs, 1 H),
6.9 Hz, 2H), 7.44–7.41 (m, 3H), 7.39–7.31 (m, 6H), 7.27–7.22 7.31–7.22 (m, 10H), 7.09 (td, J = 7.6, 1.1 Hz, 1H), 6.97 (td, J =
(m, 4H), 7.20–7.13 (m, 3H), 6.99 (td, J = 7.6, 0.9 Hz, 1H), 6.88 7.5, 1.0 Hz, 1H), 6.74 (dd, J = 15.8, 7.2 Hz, 1H), 6.34 (dd, J =
(dd, J = 15.9, 7.3 Hz, 1H), 6.40 (dd, J = 15.9, 0.9 Hz, 1H), 5.28 15.8, 1.3 Hz, 1H), 5.07 (dd, J = 7.2, 1.3 Hz, 1H), 2.36 (s, 3H);
(d, J = 7.3 Hz, 1H).
13C NMR (100 MHz, CDCl3): δ 141.7, 135.8, 135.4, 132.9, 132.3,
(E)-Ethyl 3-(1,3-diphenylallyl)-1H-indole-2-carboxylate (3g). 132.0, 131.7, 129.8, 129.6, 128.7, 128.4, 127.7, 127.5, 121.2,
Colorless oil. IR (KBr) cm−1 3411, 3338, 3058, 3026, 2980, 119.5, 119.2, 112.2, 110.4, 44.5, 12.4; HR-MS (+APCI) calcd for
2931, 1696, 1573, 1537, 1492, 1447, 1376, 1317, 1241, 1176, C24H1835Cl2N: 390.0811 [M − 1]+, found: 390.0806.
1152, 1130, 1095, 1024, 967, 744, 697, 495, 433; 1H NMR
(E)-3-(1,3-Di(thiophen-2-yl)allyl)-1H-indole (3m). Yellow oil.
(400 MHz, CDCl3): δ 8.95 (s, 1H), 7.52 (d, J = 8.0 Hz, 1H), IR (KBr) cm−1 3409, 3102, 3061, 2923, 2853, 1654, 1613, 1516,
7.37–7.35 (m, 5H), 7.28–7.26 (m, 5H), 7.20–7.16 (m, 2H), 6.99 1487, 1453, 1415, 1335, 1222, 1155, 1125, 1094, 1039, 1012,
(td, J = 7.6, 0.8 Hz, 1 H), 6.89 (dd, J = 15.8, 7.5 Hz, 1H), 6.50 (d, 955, 849, 822, 743, 697; 1H NMR (400 MHz, CDCl3): δ 7.98 (brs,
J = 15.8 Hz, 1H), 6.14 (d, J = 7.5 Hz, 1H), 4.41 (qd, J = 7.1, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.2 Hz, 1H), 7.20–7.16
1.6 Hz, 2H), 1.40 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, (m, 3H), 7.10 (d, J = 5.1 Hz, 1H), 7.06 (td, J = 7.5, 0.9 Hz, 1H),
CDCl3): δ 162.3, 143.2, 137.5, 136.3, 131.6, 131.5, 128.5, 128.3, 7.00 (d, J = 2.2 Hz, 1H), 6.94 (dd, J = 5.1, 3.5 Hz, 1H), 6.93–6.90
128.2, 127.3, 126.9, 126.4, 126.2, 125.4, 125.0, 123.5, 123.0, (m, 2H), 6.88 (dd, J = 3.4, 1.1 Hz, 1H), 6.61 (d, J = 15.5 Hz, 1H),
120.3, 112.0, 61.0, 44.6, 14.5; HR-MS (+APCI) calcd for 6.55 (d, J = 15.5 Hz, 1H), 5.32 (d, J = 5.0 Hz, 1H); 13C NMR
C26H24NO2: 322.1807 [M + 1]+, found 322.1802.
(100 MHz, CDCl3): δ 147.4, 142.3, 136.5, 131.6, 127.3, 126.7,
(E)-3-(1,3-Diphenylallyl)-1-methyl-1H-indole (3h).5 Colorless 126.4, 125.4, 124.9, 124.0, 123.9, 122.4, 122.2, 119.7, 119.6,
oil. 1H NMR (400 MHz, CDCl3): δ 7.42 (d, J = 8.0 Hz, 1H), 118.1, 111.2, 41.0; HR-MS (+APCI) calcd for
7.37–7.19 (m, 12H), 7.01 (td, J = 7.5, 1.0 Hz, 1H), 6.74 (s, 1H), 322.0719 [M + 1]+, found: 322.0715.
C19H16NS2:
6.71 (dd, J = 15.8, 7.4 Hz, 1H), 6.43 (d, J = 15.8 Hz, 1H), 5.11
(d, J = 7.4 Hz, 1H), 3.72 (s, 3H).
(E)-3-(1,3-Di(thiophen-2-yl)allyl)-2-methyl-1H-indole (3n).
Yellow oil. IR (KBr) cm−1 3397, 2920, 2852, 1666, 1614, 1457,
1
(E)-3-(1,3-Diphenylallyl)-1-methyl-2-phenyl-1H-indole (3i). 1415, 1231, 955, 744, 698; H NMR (400 MHz, CDCl3): δ 7.77
Yellow solid. IR (KBr) cm−1 3000, 1598, 1466, 1445, 1429, 1335, (brs, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.26 (d, J = 8.0 Hz, 1H), 7.15
1
1268, 1176, 1128, 1026, 989, 835, 745, 700, 496, 487; H NMR (dd, J = 5.1, 1.1 Hz, 1H), 7.11–7.07 (m, 2H), 7.00 (td, J = 7.5,
(400 MHz, CDCl3): δ 7.49–7.32 (m, 8H), 7.31–7.27 (m, 4H), 0.9 Hz, 1H), 6.93–6.90 (m, 2H), 6.89–6.87 (m, 2H), 6.66 (dd, J =
7.25–7.21 (m, 4H), 7.20–7.13 (m, 2H), 7.01 (td, J = 7.5, 0.9 Hz, 15.8, 6.1 Hz, 1H), 6.60 (d, J = 15.8 Hz, 1H), 5.27 (d, J = 6.1 Hz,
1H), 6.81 (dd, J = 15.8, 7.5 Hz, 1H), 6.32 (dd, J = 15.8, 0.9 Hz, 1H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.0, 142.4,
1H), 4.99 (d, J = 7.5 Hz, 1H), 3.60 (s, 3H); 13C NMR (100 MHz, 135.3, 131.6, 131.1, 127.5, 127.3, 126.6, 125.3, 124.6, 124.0,
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123.83, 123.82, 121.1, 119.4, 119.3, 112.7, 110.3, 40.6, 12.3;
(E)-N-(1,3-Diphenylallyl)-4-nitroaniline (5f).11 Yellow solid.
HR-MS (+APCI) calcd for C20H18NS2: 356.0881 [M + 1]+, found: 1H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 9.2 Hz, 2H), 7.40–7.23
356.0876.
(m, 10H), 6.60 (dd, J = 15.8, 0.9 Hz, 1H), 6.58 (d, J = 9.2 Hz,
(E)-3-(3-(4-Chlorophenyl)-1-phenylallyl)-1H-indole (3o) and 2H), 6.37 (dd, J = 15.8, 6.1 Hz, 1H), 5.20 (td, J = 5.8, 0.9 Hz,
(E)-3-(1-(4-chlorophenyl)-3-phenylallyl)-1H-indole (3p).26 The 1H), 4.90 (d, J = 5.4 Hz, 1H).
mixture of the two regioisomers could not be separated. yellow
(E)-N-(1,3-Diphenylallyl)-2-nitroaniline (5g).11 Yellow solid.
oil. 1H NMR (400 MHz, CDCl3): δ 7.97 (s, 1H), 7.42–714 1H NMR (400 MHz, CDCl3): δ 8.51 (d, J = 5.6 Hz, 1H), 8.20 (dd,
(m, 12H), 7.04–7.00 (m, 1H), 6.88–6.85 (m, 1H), 6.77–6.64 J = 8.6, 1.6 Hz, 1H), 7.44–7.22 (m, 11H), 6.83 (d, J = 8.3 Hz,
(m, 1H), 6.42–6.35 (m, 1H), 5.11–5.07 (m, 1H).
1H), 6.66 (td, J = 7.8, 1.2 Hz, 1H), 6.61 (d, J = 16.1 Hz, 1H), 6.41
(E)-3-(4-Phenylbut-3-en-2-yl)-1H-indole (3q).17 White solid. (dd, J = 16.1, 6.1 Hz, 1H), 5.32 (t, J = 5.9 Hz, 1H).
1H NMR (400 MHz, CDCl3): δ 7.93 (s, 1H), 7.67 (d, J = 7.9 Hz,
(E)-1-(4-((1,3-Diphenylallyl)amino)phenyl)ethanone (5h).
1H), 7.36–7.34 (m, 3H), 7.27 (t, J = 7.6 Hz, 2H), 7.20–7.16 (m, White solid. IR (KBr) cm−1 3341, 3027, 2920, 2847, 1650, 1593,
2H), 7.08 (td, J = 7.5, 0.9 Hz, 1H), 7.01 (dd, J = 2.2, 0.4 Hz, 1H), 1526, 1489, 1448, 1423, 1281, 1183, 1028, 966, 951, 832, 812,
6.51 (d, J = 15.9 Hz, 1H), 6.45 (dd, J = 15.9, 5.8 Hz, 1H), 3.93 747, 716, 698, 590, 551, 486; 1H NMR (400 MHz, CDCl3): δ 7.78
(p, J = 6.6 Hz, 1H), 1.56 (d, J = 7.0 Hz, 3H).
(d, J = 8.7 Hz, 2H), 7.41–7.21 (m, 10H), 6.60 (d, J = 8.7 Hz, 2H),
6.59 (d, J = 15.6 Hz, 1H), 6.37 (dd, J = 15.6, 6.1 Hz, 1H), 5.18
(t, J = 5.5 Hz, 1H), 4.67 (d, J = 5.2 Hz, 1H), 2.46 (s, 1H); 13C
NMR (100 MHz, CDCl3): δ 196.3, 151.0, 141.0, 136.3, 131.8,
130.7, 129.4, 129.0, 128.6, 127.94, 127.89, 127.20, 127.16,
General procedure for the reactions of allylic alcohols with
nitrogen nucleophiles
A
mixture of 1 (0.1 mmol), 4 (0.1 mmol) and ZnBr2 126.6, 112.4, 59.9, 26.0; HR-MS (+APCI) calcd for C23H22NO:
(0.02 mmol) was vigorously shaken by HSVM for 1.5 h. The 328.1701 [M + 1]+, found: 328.1699.
combined reaction mixture from two runs was collected and
dissolved in ethyl acetate. The solution was filtrated to remove
the residue and then evaporated to dryness under high
vacuum. Finally, the resulting products 5a–5h were purified
Acknowledgements
by column chromatography on silica gel using ethyl acetate– We are grateful for financial support from the Knowledge
petroleum ether (60–90 °C) as the eluent.
Innovation Project of the Chinese Academy of Sciences
(E)-N-(1,3-Diphenylallyl)benzenesulfonamide (5a).24 White (KJCX2.YW.H16) and the Key Project of Science and Technol-
solid. 1H NMR (400 MHz, CDCl3): δ 7.78–7.75 (m, 2H), 7.45 (tt, ogy of the Department of Education, Anhui Province, China
J = 7.4, 1.2 Hz, 1H), 7.35 (t, J = 7.6 Hz, 2H), 7.28–7.16 (m, 10H), (KJ2010ZD05).
6.38 (d, J = 15.8 Hz, 1H), 6.11 (dd, J = 15.8, 6.3 Hz, 1H),
5.17–5.11 (m, 2H).
(E)-N-(1,3-Diphenylallyl)-4-methylbenzenesulfonamide (5b).24
White solid. H NMR (400 MHz, CDCl3): δ 7.65 (d, J = 8.2 Hz,
Notes and references
1
2H), 7.27–7.15 (m, 10H), 7.12 (d, J = 8.2 Hz, 2H), 6.33 (d, J =
15.8 Hz, 1H), 6.07 (dd, J = 15.8, 6.7 Hz, 1H), 5.18 (d, J = 7.3 Hz,
1H), 5.10 (t, J = 6.8 Hz, 1H), 2.30 (s, 3H).
1 For reviews, see: (a) B. M. Trost and D. L. V. Vranken,
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(E)-N-(1,3-Diphenylallyl)-4-methoxybenzenesulfonamide (5c).27
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White solid. H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.9 Hz,
2H), 7.27–7.16 (m, 10H), 6.78 (d, J = 8.9 Hz, 2H), 6.35 (d, J =
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1H), 5.09 (t, J = 6.9 Hz, 1H), 3.74 (s, 3H).
(E)-4-Chloro-N-(1,3-diphenylallyl)benzenesulfonamide (5d).
White solid. IR (KBr) cm−1 3261, 3031, 2923, 2852, 1580, 1494,
1474, 1431, 1395, 1324, 1278, 1163, 1089, 1041, 1018, 966, 919,
1
866, 821, 749, 697, 632, 549, 480; H NMR (400 MHz, CDCl3):
δ 7.65 (d, J = 8.6 Hz, 2H), 7.29–7.16 (m, 12H), 6.38 (d, J =
15.8 Hz, 1H), 6.09 (dd, J = 15.8, 6.5 Hz, 1H), 5.18–5.13 (m, 2H);
13C NMR (100 MHz, CDCl3): δ 139.4, 139.2, 138.9, 135.8, 132.5,
129.0, 128.8, 128.7, 128.6, 128.13, 128.06, 127.9, 127.1, 126.5,
60.0; HR-MS (+APCI) calcd for C21H1935ClNO2S: 384.0820
[M + 1]+, found: 384.0810.
(E)-N-(1,3-Diphenylallyl)methanesulfonamide (5e).27 Yellow
solid. 1H NMR (400 MHz, CDCl3): δ 7.40–7.23 (m, 10H), 6.62
(d, J = 15.8 Hz, 1H), 6.33 (dd, J = 15.8, 6.8 Hz, 1H), 5.28 (t, J =
6.9 Hz, 1H), 5.00 (t, J = 7.0 Hz, 1H), 2.77 (s, 3H).
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