Palladium-catalyzed highly selective intramolecular bromoamination of alkenes: Efficient synthesis of substituted pyrrolidines

Article abstract of DOI:10.1002/aoc.3631

A new method has been developed for the preparation of substituted pyrrolidines by the palladium-catalyzed intramolecular bromoamination of substituted aminoalkenes. The catalytic system and reaction conditions used for this transformation have been fully optimized. Notably, this reaction exhibits excellent selectivity, affording the pyrrolidine products as single 5-exo-bromoalkylpyrrolidines in excellent yields. Furthermore, this reaction occurs at room temperature under mild conditions, reaching completion within 1?h.

Full text of DOI:10.1002/aoc.3631

Received: 7 May 2016
DOI 10.1002/aoc.3631
Revised: 26 July 2016
Accepted: 21 August 2016
F U L L PA P E R
Palladium‐catalyzed highly selective intramolecular
bromoamination of alkenes: Efficient synthesis of substituted
pyrrolidines
†
†
*
Jingfang Zhang | Xie Wang | Yulong Liu | Xiaoyun Wang | Wei He
Department of Chemistry, School of Pharmacy,
A new method has been developed for the preparation of substituted pyrrolidines by
the palladium‐catalyzed intramolecular bromoamination of substituted
aminoalkenes. The catalytic system and reaction conditions used for this transforma-
tion have been fully optimized. Notably, this reaction exhibits excellent selectivity,
affording the pyrrolidine products as single 5‐exo‐bromoalkylpyrrolidines in excel-
lent yields. Furthermore, this reaction occurs at room temperature under mild con-
ditions, reaching completion within 1 h.
Fourth Military Medical University, Xi'an 710032,
People's Republic of China
Correspondence
Wei He, Department of Chemistry, School of
Pharmacy, Fourth Military Medical University,
Xi'an 710032, People's Republic of China.
Email: weihechem@fmmu.edu.cn
KEYWORDS
bromoamination, palladium catalysis, substituted pyrrolidines
1
|
INTRODUCTION
intramolecular haloamination reactions using Fe,[6] Cu,[7]
Ag[8] and Pd catalysts.[9]
The aminohalogenation of alkenes is a direct method for
obtaining compounds containing both halogen and amino
functional groups.[1] In particular, vicinal amines have drawn
substantial attention due to their promising application as
chemotherapy agents in antitumor therapy.[2] The halogen
atom in an aminohalogenation product has a high reactivity,
which can be replaced by other functional groups to generate
many other drug intermediates and participate in a variety of
other types of reactions.[3] Several studies have been reported
during the past two decades concerning the intermolecular
haloamination of alkenes.[4] However, reports concerning
the intramolecular haloamination of aminoalkenes, which is
a powerful tool for the construction of nitrogen‐containing
heterocycles carrying a halogen atom vicinal to the nitrogen,
are relatively scarce.[5] The substrates required for intramo-
lecular haloamination reactions usually need to be designed
and synthesized to obtain useful azacycles. Metal catalysis
can potentially provide excellent regioselectivity, as well as
providing a platform for the development of asymmetric
transformations. For these reasons, there has been consider-
able interest in the development of metal‐catalyzed
Among the various methods reported for the intramolec-
ular haloamination of aminoalkenes, palladium‐catalyzed
haloamination has attracted particular attention. In 2004,
Chemler and co‐workers[9a] reported the first intramolecular
aminohalogenation reaction of sulfonamidoalkenes using a
Pd(TFA)2 catalyst in the presence of a copper halide additive,
which served as a stoichiometric oxidant and a source of
halide, and gave the desired products in high yields but only
moderate regioselectivity. In the same year, Lu and co‐
workers[9b] reported that alkenes bearing
a pendant
acylsulfonamide moiety could be cyclized in the presence
of a Pd(OAc)2 catalyst with the same halogen source as used
by Chemler and co‐workers. In 2008, Michael et al.[9c]
reported the development of an exo‐selective intramolecular
reaction for the aminochlorination of unsaturated amides
and carbamates using [PdCl2(CH3CN)2] as a catalyst in the
presence of N‐chlorosuccinimide as oxidant and halogen
source. In 2009, Liu and co‐workers[9d] reported the endo‐
selective
Pd‐catalyzed
intramolecular
cyclization/
aminofluorination of γ‐pentenylsulfonamides for the synthe-
sis of piperidines in the presence of PhI(OPiv)2 and AgF.
Liu and co‐workers[9e] subsequently reported an endo‐selec-
tive Pd‐catalyzed aminofluorination for the synthesis of
fluoro‐substituted pyrrolidines from β‐alkenylstyrenes.
†These authors contributed equally to this article
Appl Organometal Chem 2016; 1–8
wileyonlinelibrary.com/journal/aoc
Copyright © 2016 John Wiley & Sons, Ltd.
1

2
ZHANG ET AL.
However, this reaction exhibited poor substrate scope, as well
as poor levels of cis/trans diastereoselectivity. Despite these
efforts in this area, the development of highly regio‐ and
(entries 5–7). Organic bases such as pyridine, 2,2′‐bipyridine
and pyrrolidine also gave lower yields(entries 8–10).
The effects of various Pd sources and solvents on the
bromoamination reaction were further investigated. As evi-
dent from Table 2, Pd(OAc)2 and Pd(TFA)2 both performed
well as catalysts for this reaction and provided high yields
of the corresponding N‐heterocyclic compound 1d (Table 2,
entries 1 and 2). In contrast, [PdCl2(MeCN)2] and PdCl2 gave
only moderate yields of the desired product (Table 2, entries
3 and 4). Pleasingly, Pd(PPh3)2Cl2 gave a much higher yield
stereoselective
methods
for
the
intramolecular
aminohalogenation of aminoalkenes still represents a consid-
erable challenge in organic chemistry.
2
| RESULTS AND DISCUSSION
Bromoamination has attracted considerable interest following
the discovery of bromine‐containing compounds in the bio-
synthesis of halogenated marine natural products[10] and
medicinal plants.[11] We conducted a series of preliminary
experiments involving the bromoamination of 4‐methyl‐N‐
(2‐phenylpent‐4‐en‐1‐yl)benzenesulfonamide (1c) with Pd
(OAc)2 and N‐bromosuccinimide (NBS) in the presence of
bases (Table 1).
Initially, the reaction was conducted without palladium
and any additive. It was found that the bromoamination of
1c could occur but with low conversion (Table 1, entry 1).
Then 2 eq. of K2CO3 was added into the reaction, and the
yield was improved obviously (entry 2). However, when the
substrate was replaced by another olefin, 4‐methyl‐N‐(5‐
methyl‐2‐phenylhex‐4‐en‐1‐yl)benzenesulfonamide, which
has two methyl substituent groups on terminal double bond,
a mixture of products was observed and the bromoamination
yield was only 15% (entry 3). Then, Pd(OAc)2 was intro-
duced into this reaction, and full conversion was observed
within 1 h and the isolated yield was improved to 93% (entry
4). Then other bases were investigated. The addition of KOH
and KF gave similar results, but NaOH gave lower yields
than
any
other
catalyst,
giving
the
5‐exo‐
bromoalkylpyrrolidine as the sole product with an isolated
yield of 98% (Table 2, entry 5). We also investigated the addi-
tion of a Pd(0) complex (Table 2, entry 6) to the reaction mix-
ture, under the assumption that it would be oxidized to a Pd
(II) species under the reaction conditions using oxygen as
an oxidant. However, this reaction gave a poor yield of the
desired product. PdBF4(MeCN)4 failed to catalyze the
bromoamination of 1c (Table 2, entry 7). Several solvents
were also screened for this reaction, including xylene, ether,
acetonitrile, CHCl3 and tetrahydrofuran (THF) (Table 2,
entries 8–12), but all of these solvents gave inferior results
compared with CH2Cl2. Based on these results, the optimum
conditions were determined to be 10% Pd(PPh3)2Cl2, K2CO3
(2 eq.), NBS (1.5 eq.) and CH2Cl2.
With the optimum conditions in hand, we then synthe-
sized a series of substituted aminoalkene substrates, which
included eight unknown compounds (4c, 5c, 6c, 7c, 8c,
10c, 11c, 12c), and their structures were confirmed using
infrared (IR), 1H NMR, 13C NMR and high‐resolution
(HR)‐MS spectra. These substrates, with varying nature of
TABLE 2 Bromoamination of protected alkenesa
TABLE 1 Effect of bases on yielda
Entry
Pd source
Solvent
T (°C)
Yield (%)b
1
Pd(OAc)2
Pd(TFA)2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
Et2O
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
93
90
71
86
98
15
NRc
91
82
81
79
82
Entry
Pd (%)
Base
Time (h)
Yield (%)b
2
1
None
none
K2CO3
12
2
10
3
PdCl2(MeCN)2
PdCl2
2
3c
None
50
4
None
K2CO3
2
15 (mixed products)
5
Pd(PPh3)2Cl2
Pd2(dba)3
4
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
K2CO3
1
93
90
90
80
86
80
75
6
5
KOH
1
7
PdBF4(MeCN)4
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
6
KF
1
8
7
NaOH
1
9
8
Pyridine
2,2′‐Bipyridine
Pyrrolidine
1
10
11
12
THF
9
1
MeCN
Xylene
10
1
aReaction conditions: alkene (0.05 mmol), 10 mol% catalyst, NBS (1.5 eq.) and
base (2 eq.) in 1.5 ml of CH2Cl2.
bIsolated yield after chromatographic separation.
cWith a different substrate bearing two methyl substituent groups on terminal dou-
ble bond.
aReaction conditions: alkene (0.05 mmol), 10 mol% catalyst, NBS (1.5 eq.) and
K2CO3 (2 eq.) in 1.5 ml of CH2Cl2.
bIsolated yield after chromatographic separation.
cNo reaction.

ZHANG ET AL.
3
TABLE 3 Scope of bromoamination reactions of alkenesa
Entry
Substrate
1c
R
PG
Yield (%)b
1
R1 = Ph
Ts
98
R
R
2 = H
3 = H
2
2c
3c
R
1 = p‐ClPh
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Boc
94
97
95
86
80
80
93
96
92
90
NRc
R2 = H
3 = H
R
3
R
1 = Bn
R2 = H
3 = H
R
4
4c
R1 = BnCH2
2 = H
R
R3 = H
FIGURE 1 ORTEP drawing of compound 1d
5
5c
R1 = BnCH2
R2 = H
R3 = Ph
regioselectivities, this result therefore provides a good sup-
plement for the literature of Pd‐catalyzed intramolecular
chloroamination of unactivated alkenes.[9c]
6
6c
R
1 = Bn
2 = H
3 = CH3
R
R
In order to confirm the relative configuration of the prod-
ucts, which were observed in high diastereoselectivity and
regioselectivity using our catalyst system, X‐ray crystallogra-
phy of a single crystal of compound 1d was conducted. As
shown in the ORTEP drawing of compound 1d (Figure 1),
the five‐membered nitrogen heterocyclic product has enve-
lope conformation, C3‐phenyl ring and C5‐bromomethyl
group is in cis‐position, which are away from the aromatic
ring of p‐toluenesulfonyl. This configuration may reduce
the steric interaction. Crystallographic data have been depos-
ited with the Cambridge Crystallographic Data Centre
(CCDC 1443994).
7
7c
R1 = BnCH2
R2 = H
R
3 = CH3
8
8c
R1 = 2‐thienyl
R2 = H
R
3 = H
1 = Ph
2 = allyl
9
9c
R
R
R3 = H
10
11
12
10c
11c
12c
R
1 = 2‐thienyl
R
2 = allyl
R3 = H
1 = Bn
2 = 2‐butenyl
3 = CH3
R
R
R
R1 = Ph
R2 = allyl
3
| CONCLUSIONS
R3 = H
aReaction conditions: alkene (0.5 mmol), 10 mol% Pd(PPh3)2Cl2, NBS (1.5 eq.)
and K2CO3 (2 eq.) in 10.0 ml of CH2Cl2. The relative configurations of the prod-
ucts were determined by X‐ray and NOE experiments.
bIsolated yield after chromatographic separation.
cNo reaction.
In summary, an efficient and highly selective palladium‐cata-
lyzed intramolecular bromoamination reaction was success-
fully developed for the synthesis of substituted pyrrolidines
from acyclic aminoalkenes under mild conditions. This
reaction occurred with excellent regioselectivity to give the
5‐exo‐bromoalkylpyrrolidines as single products, which
provides another good example for the high selectivity of
palladium catalysis. Moreover, the palladium‐catalyzed pro-
cess also could provide a platform for the development of
an enantioselective version of this reaction, and further work
including developing asymmetric catalysis and a study of the
mechanism is currently underway in our laboratory.
substituents at the R1, R2 and R3 positions, as well as the
protecting group on the nitrogen atom, were evaluated under
the optimized bromoamination conditions (Table 3). The
results revealed that the majority of the tested substrates gave
the desired products in excellent yields, also tolerating the
unactivated alkenes bearing thiophene ring (Table 3, entries
1–11). Notably, all the desired products were formed as sin-
gle 5‐exo‐diastereomers under the optimized conditions,
which shows the excellent regioselectivities of the palladium
catalysis. However, we also found that this methodology only
worked well for substrates bearing an N‐Ts substituent, while
the corresponding N‐Boc‐containing substrates failed to give
the desired cyclization products (Table 3, entry 12). With the
mild conditions, fast reaction speed, high yields and high
4
| EXPERIMENTAL
4.1 | General remarks
All available reagents and solvents were used as supplied
commercially and all were purchased from Aldrich, Alfa

4
ZHANG ET AL.
Aesar and Acros. Analytical TLC was performed on 0.2 mm
coated science silica gel (GF‐254) plates purchased from
Yantai, China. Visualization was accomplished with UV light
(254 nm). MS were recorded with a Dionex UltiMate3000
liquid chromatograph–Bruker microTOF‐QII mass spectrom-
C24H3), 2.12–2.07 (m, 1 H, C7H), 1.60–1.57 (m, 3 H,
C9H, C10H2). 13C NMR (100 MHz, CDCl3, δ, ppm):
150.1 (C5), 143.4 (C13), 141.9 (C21), 139.7 (C18), 136.8
(C20), 135.6 (C22), 129.7 (C1), 128.3 (C3), 128.2 (C4),
127.1 (C6), 125.8 (C19), 117.2 (C23), 111.5 (C2), 45.8
(C14), 37.2 (C11), 35.9 (C10), 32.9 (C7), 32.7 (C8), 27.3
(C9), 21.5 (C21). HR‐MS (ESI) calcd for C20H25NO2S
[M − H]+ 342.1524, found 342.1528. Anal. Calcd (%):
C, 69.94; H, 7.34; N, 4.08. Found (%): C, 69.87; H,
7.38; N, 4.04.
1
eter. H NMR and 13C NMR spectra were recorded with
Varian Mercury 300 MHz or Varian Unity 400 MHz spec-
trometers, and CDCl3 was purchased from Aldrich. Flash col-
umn chromatography was performed on silica gel 60 (particle
size 200–300 mesh ASTM, purchased from Yantai, China)
with hexanes–ethyl acetate. The chemical shifts (δ) are
reported in ppm from tetramethylsilame (TMS) with the sol-
vent resonance as the internal standard (CDCl3,
δ = 7.26 ppm). 13C NMR chemical shifts are reported in
ppm from TMS with the solvent resonance as internal stan-
dard (CDCl3, δ = 77.0 ppm).
4.3.2
| 4‐Methyl‐N‐(2‐phenethyl‐5‐phenylpent‐4‐en‐1‐yl)
benzenesulfonamide (5c)
White solid; m.p. 107–108°C. IR (KBr, cm−1): ν 3282,
3024, 2954, 2923, 2854, 1600, 1461, 1377, 1157, 1091,
1
813, 744, 694, 551. H NMR (400 MHz, CDCl3, δ, ppm):
7.72 (d, J = 8.0 Hz, 2 H, C25H, C29H), 7.31–7.17 (m, 10 H,
C
11‐15H5, C16‐20H5), 7.12 (d, J = 7.6 Hz, 2 H, C26H, C28H),
4.2 | Preparation of starting materials
6.34 (d, J = 16.0 Hz, 1 H, C6H), 6.06–5.98 (m, 1 H, C5H),
4.66 (br.s, 1 H, NH), 2.92 (t, J = 5.8 Hz, 2 H, C8H2), 2.59
(t, J = 7.6 Hz, 2 H, C1H2), 2.37 (s, 3 H, C30H3), 2.30–2.17
(m, 2 H, C3H2), 1.71–1.60 (m, 3 H, C2H, C8H2). 13C NMR
(100 MHz, CDCl3, δ, ppm): 143.4 (C10), 141.8 (C27), 137.3
(C23), 136.7 (C22), 132.3 (C6), 129.7 (C28), 128.5 (C26),
128.4 (C25), 128.3 (C29), 127.2 (C20), 127.1 (C16), 126.0
(C19), 125.9 (C17), 45.8 (C11), 37.7 (C12), 34.9 (C14), 33.0
(C15), 32.9 (C18), 31.9 (C3), 29.7 (C5), 29.4 (C3), 24.5 (C8),
22.7 (C1), 21.5 (C2), 19.8 (C4), 14.2 (C30). HR‐MS (ESI)
calcd for C26H29NO2S [M + Na]+ 442.1814, found
442.1819. Anal. Calcd (%): C, 74.43; H, 6.97; N, 3.34. Found
(%): C, 74.47; H, 7.04; N, 3.19.
All starting materials were synthesized using reported
methods.[12] Twelve kinds of compounds were obtained
through these methods, including eight unknown compounds
(4c, 5c, 6c, 7c, 8c, 10c, 11c, 12c), which were confirmed
using IR, 1H NMR, 13C NMR, HR‐MS and elemental analy-
sis. The steps are summarized in Scheme 1.
4.3 | Spectra data for new starting materials
4.3.1
| 4‐Methyl‐N‐(2‐phenethylpent‐4‐enyl)
benzenesulfonamide (4c)
Yellow solid; m.p. 33–34°C. IR (KBr, cm−1): ν 3286,
3052, 3024, 2927, 2858, 1639, 1600, 1496, 1454, 1300,
1161, 1095, 914, 813, 698, 663, 551. 1H NMR
(400 MHz, CDCl3, δ, ppm): 7.72 (d, J = 8.0 Hz, 2 H,
C19H, C23H), 7.29 (d, J = 8.0 Hz, 3 H, C2H, C20H,
C23H), 7.24 (br.s, 1 H, C1H), 7.18 (t, J = 7.4 Hz, 1
H, C3H), 7.11 (d, J = 7.2 Hz, 2 H, C4H, C6H), 5.72–
5.62 (m, 1 H, C13H), 5.12–4.99 (m, 2 H, C14H2), 4.46
(t, J = 6.2 Hz, 1 H, NH), 4.13 (dd, J = 14.0,
J = 6.8 Hz, 1 H, C7H), 2.91 (t, J = 5.8 Hz, 2 H,
C11H2), 2.55 (t, J = 7.4 Hz, 2 H, C8H2), 2.42 (s, 3 H,
4.3.3
| N‐(2‐Benzylhex‐4‐en‐1‐yl)‐4‐
methylbenzenesulfonamide(6c)
White solid; m.p. 47–48°C. IR (KBr, cm−1): ν 3282,
3058, 3028, 2958, 2923, 2854, 1600, 1496, 1323, 1261,
1157, 1091, 1029, 802, 744, 659, 551. 1H NMR
(400 MHz, CDCl3, δ, ppm): 7.67 (d, J = 8.0 Hz, 2 H,
C19H, C23H), 7.26 (dd, J = 18.0, J = 8.0 Hz, 4 H,
C2H, C3H, C5H, C6H), 7.20 (d, J = 7.2 Hz, 1 H,
C1H), 7.05 (d, J = 7.2 Hz, 2 H, C20H, C22H), 5.44–5.36 (m,
SCHEME 1 Substrate synthesis

ZHANG ET AL.
5
1H, C11H), 5.31–5.21(m, 1H, C12H), 4.37–4.34(m, 1H, NH),
2.89–2.78 (m, 2 H, C9H2), 2.58–2.47 (m, 2 H, C7H2), 2.43 (s, 3
H, C24H3), 2.01–1.88 (m, 2 H, C10H2), 1.85–1.76 (m, 1 H,
C8H), 1.62 (d, J = 6.0 Hz, 3 H, C14H3). 13C NMR (100 MHz,
CDCl3, δ, ppm): 143.3 (C4), 139.7 (C24), 136.8 (C18), 129.6
(C20), 129.0 (C22), 128.3 (C11), 127.9 (C3), 127.8 (C5), 127.4
(C19), 127.1 (C23), 126.1 (C2), 46.2 (C6), 45.7 (C1), 40.5
(C12), 40.0 (C9), 38.0 (C7), 34.5 (C8), 28.9 (C10), 21.5 (C24),
17.9 (C14). HR‐MS (ESI) calcd for C20H25NO2S [M − H]+
342.1524, found: 342.1528. Anal. Calcd (%): C, 69.94; H,
7.34; N, 4.08. Found (%): C, 70.03; H, 7.10; N, 4.12.
4.3.6
| N‐(2‐Allyl‐2‐(thiophen‐2‐yl)pent‐4‐en‐1‐yl)‐4‐
methylbenzenesulfonamide (10c)
White solid; m.p. 104–105°C. IR (KBr, cm−1): ν 3290,
3074, 2954, 2923, 2873, 1635, 1596, 1323, 1161, 1080,
1002, 918, 813, 702, 667, 551. 1H NMR (400 MHz,
CDCl3, δ, ppm): 7.65 (d, J = 8.4 Hz, 2 H, C17H, C21H),
7.30 (d, J = 8.0 Hz, 2 H, C18H, C20H), 7.21 (d,
J = 6.0 Hz, 2 H, C2H, C3H), 6.95–6.93 (m, 1 H, C4H),
6.79 (d, J = 4.4 Hz, 1 H, C7H), 5.67–5.57 (m, 2 H, C9H,
C12H), 5.08 (d, J = 4.0 Hz, 2 H, C10H, C15H), 5.05 (br.s,
2 H, C10H, C15H), 4.13 (t, J = 6.6 Hz, 1 H, NH), 3.04
(d, J = 6.8 Hz, 2 H, C11H2), 2.53–2.48 (m, 1 H, C7H),
2.44 (s, 3 H, C24H3), 2.41 (t, J = 7.0 Hz, 2 H, C8H2).
13C NMR (100 MHz, CDCl3, δ, ppm): 148.4 (C1), 143.4
(C16), 136.3 (C12,C9), 132.5 (C20), 129.7 (C18), 127.0
(C21), 126.8 (C17), 124.6 (C2), 124.4 (C3), 119.1 (C4),
50.9 (C15, C10), 43.9 (C7), 40.7 (C8, C11), 29.7 (C6), 21.5
(C24). HR‐MS (ESI) calcd for C19H23NO2S2 [M + Na]+
384.1063, found 384.1068. Anal. Calcd (%): C, 63.13; H,
6.41; N, 3.87. Found (%): C, 63.17; H, 6.37; N, 3.91.
4.3.4
| 4‐Methyl‐N‐(2‐phenethylhex‐4‐en‐1‐yl)
benzenesulfonamide (7c)
White solid; m.p. 49–50°C. IR (KBr, cm−1): ν 3282, 3052,
3024, 2923, 2854, 1598, 1454, 1323, 1161, 1091, 968, 813,
1
740, 663, 551. H NMR (400 MHz, CDCl3, δ, ppm): 7.72
(d, J = 8.0 Hz, 2 H, C20H, C24H), 7.29 (d, J = 8.0 Hz, 3
H, C21H, C23H, C1H), 7.24 (s, 1 H, C2H), 7.17 (t,
J = 7.4 Hz, 1 H, C6H), 7.10 (d, J = 7.6 Hz, 2 H, C3H,
C4H), 5.44–5.35 (m, 1 H, C11H), 5.29–5.21 (m, 1 H,
C12H), 4.42 (t, J = 6.4 Hz, 1 H, NH), 2.91–2.87 (m, 2 H,
C13H2), 2.54 (t, J = 7.0 Hz, 2 H, C7H2), 2.42 (s, 3 H,
C25H3), 2.02–1.93 (m, 1 H, C9H), 1.61 (d, J = 6.4 Hz, 3
H, C15H3), 1.58–1.53 (m, 4 H, C8H2, C10H2). 13C NMR
(100 MHz, CDCl3, δ, ppm): 143.3 (C5), 142.0 (C23),
136.8 (C19), 129.6 (C11), 128.3 (C21), 128.2 (C23), 127.8
(C24), 127.6 (C20), 127.0 (C1), 125.8 (C3), 46.2 (C4), 45.8
(C6), 37.7 (C2), 37.4 (C12), 34.5 (C13), 32.9 (C7), 32.8
(C8), 28.9 (C10), 21.5 (C9), 17.9 (C25), 12.9 (C15). HR‐
MS (ESI) calcd for C21H27NO2S [M − H]+ 356.1678,
found 356.1684. Anal. Calcd (%): C, 70.55; H, 7.61; N,
3.92. Found (%): C, 70.51; H, 7.65; N, 4.01.
4.3.7
| N‐(2‐Benzyl‐2‐(2‐buten‐1‐yl)hex‐4‐en‐1‐yl)‐4‐
methylbenzenesulfonamide (11c)
Pale yellow solid; m.p. 142–143°C. IR (KBr, cm−1): ν
3286, 3028, 2923, 2854, 1600, 1496, 1454, 1415, 1326,
1164, 1080, 972, 910, 813, 732, 702, 667, 551. H NMR
1
(400 MHz, CDCl3, δ, ppm): 7.68 (d, J = 8.0 Hz, 2 H,
C27H, C23H), 7.30 (d, J = 8.4 Hz, 2 H, C24H, C26H),
7.22–7.19 (m, 3 H, C15H, C16H, C17H), 7.11–7.07 (m, 2
H, C14H, C18H), 5.50–5.34 (m, 4 H, C8H, C5H, C3H,
C7H), 4.40 (t, J = 7.6 Hz, 1 H, NH), 2.64 (d,
J = 6.8 Hz, 2 H, C6H2), 2.56 (d, J = 12.8 Hz, 2 H,
C12H2), 2.43 (s, 3 H, C28H3), 1.89 (d, J = 6.0 Hz, 3 H,
C11H3), 1.64 (d, J = 5.2 Hz, 4 H, C4H2, C2H2), 1.55 (d,
J = 6.4 Hz, 3 H, C10H3). 13C NMR (100 MHz, CDCl3, δ,
ppm): 143.3 (C25), 137.5 (C13), 137.4 (C22), 136.4 (C24),
130.4 (C26), 129.6 (C23), 129.0 (C27), 128.1 (C3), 127.1
(C5), 126.9 (C15), 126.3 (C17), 125.9 (C14), 125.1 (C18),
48.7 (C16), 48.6 (C7), 41.2 (C8), 41.1 (C6), 40.7 (C12),
40.5 (C2), 38.0 (C4), 31.9 (C1), 21.5 (C28), 18.1 (C10),
13.2 (C11). HR‐MS (ESI) calcd for C24H31NO2S [M + H]
4.3.5
| 4‐Methyl‐N‐(2‐(thiophen‐2‐yl)pent‐4‐en‐1‐yl)
benzenesulfonamide(8c)
Yellow solid; m.p. 40–41°C. IR (KBr, cm−1): ν 3282, 3024,
2954, 2923, 2854, 1600, 1461, 1377, 1157, 1091, 813, 744,
1
694, 551. H NMR (400 MHz, CDCl3, δ, ppm): 7.67 (d,
J = 8.0 Hz, 2 H, C16H, C20H), 7.30 (d, J = 8.0 Hz, 2 H,
C17H, C19H), 7.18 (d, J = 5.2 Hz, 2 H, C2H, C3H), 6.93
(t, J = 4.2 Hz, 1 H, C4H), 6.76 (d, J = 2.8 Hz, 1 H,
C6H), 5.70–5.60 (m, 1 H, C9H), 5.04–4.99 (m, 2 H,
C10H2), 4.34 (br.s, 1 H, NH), 3.14–3.07 (m, 1 H, C7H),
2.99–2.93 (m, 1 H, C7H), 2.44 (s, 3 H, C21H3), 2.37 (t,
J = 7.0 Hz, 2 H, C8H2). 13C NMR (100 MHz, CDCl3, δ,
ppm): 144.5 (C1), 143.4 (C18), 136.8 (C15), 134.8 (C9),
129.7 (C17), 127.0 (C19), 126.9 (C20), 125.1 (C16), 124.2
(C2), 117.5 (C3), 48.4 (C4), 40.9 (C11), 38.8 (C7), 30.6
(C6), 29.7 (C8), 21.5 (C21). HR‐MS (ESI) calcd for
C16H19NO2S2 [M + Na]+ 344.0746, found 344.0755. Anal.
Calcd (%): C, 59.78; H, 5.96; N, 4.36. Found (%): C, 60.01;
H, 5.98; N, 4.35.
+
398.2154, found 398.2125. Anal. Calcd (%): C, 72.51;
H, 7.86; N, 3.52. Found (%): C, 72.60; H, 8.01; N, 3.53.
4.3.8
(12c)
| Tert‐butyl‐(2‐allyl‐2‐phenylpent‐4‐en‐1‐yl)carbamate
Colorless solid; m.p. 105–106°C. IR (KBr, cm−1): ν 3448,
2977, 2927, 2360, 2333, 1745, 1701, 1508, 1454, 1365,
1238, 1168, 914, 702. 1H NMR (400 MHz, CDCl3, δ,
ppm): 7.37–7.35 (m, 4 H, C2H, C3H, C5H, C6H), 7.23 (t,
J = 6.6 Hz, 1 H, C1H), 5.69–5.59 (m, 2 H, C11H, C9H),
5.08 (s, 1 H, C14H), 5.05–5.03 (m, 3 H, C14H, C13H2),
4.29 (br.s, 1 H, NH), 3.46 (d, J = 5.6 Hz, 2 H, C12H2),
2.51–2.41 (m, 4 H, C18H2, C10H2), 1.39 (s, 9 H, C5H3,

6
ZHANG ET AL.
C6H3, C7H3). 13C NMR (100 MHz, CDCl3, δ, ppm): 155.7
(C1), 145.7 (C4), 143.5 (C11, C9), 133.9 (C2), 128.4 (C6),
126.7 (C1), 126.3 (C3), 118.2 (C5), 79.1 (C13, C14), 60.4
(C4), 47.0 (C12), 44.5 (C8, C10), 40.2 (C7), 28.3 (C5, C6,
C7). HR‐MS (ESI) calcd for C19H27NO2 [M + Na]+
324.1939, found: 324.1918. Anal. Calcd (%): C, 75.71; H,
9.03; N, 4.65. Found (%): C, 75.67; H, 8.96; N, 4.63.
J2 = 8.4 Hz, 2 H, C19H, C23H), 7.26 (q, J1 = 16.4,
J2 = 8.4 Hz, 2 H, C20H, C22H), 7.21–7.17 (m, 2 H, C4H,
C6H), 7.13 (t, J = 7.2 Hz, 1 H, C2H), 6.95 (q, J1 = 14.8,
J2 = 7.2 Hz, 2 H, C1H, C3H), 3.78–3.70 (m, 2 H, C14H2),
3.48–3.43 (m, 2 H, C12H2), 2.97 (t, J = 11.0 Hz, 1 H,
C10H), 2.55–2.42 (m, 2 H, C7H2), 2,38 (s, 3 H, C24H3),
2.14–2.07 (m, 1 H, C8H), 1.71 (s, 1H, C9H), 1.40 (s, 1H,
C9H). 13C NMR (400 MHz, CDCl3, δ, ppm): 142.8 (C18),
138.4 (C5), 133.6 (C21), 128.8 (C20), 127.5 (C22), 127.3
(C1), 126.6 (C3), 126.4 (C19), 125.4 (C23), 59.5 (C4), 54.0
(C6), 38.9 (C2), 37.4 (C10), 37.3 (C12), 37.1 (C7), 37.0
(C14), 36.5 (C8), 28.7 (C9), 20.6 (C24). HR‐MS (ESI) calcd
for C19H22BrNO2S [M + Na]+ 430.0432, found 430.0452.
Anal. Calcd (%): C, 55.88; H, 5.43; N, 3.43. Found (%): C,
56.01; H, 5.38; N, 3.28.
4.4 | General procedure for bromoamination
Bis(triphenylphosphine)palladium(II) dichloride (17.96 mg,
0.08 mmol), c (0.8 mmol) and K2CO3 (2 eq.) were dissolved
in CH2Cl2 (15 ml) and allowed to stir for 5 min. NBS
(266.97 mg, 1.5 mmol) was then added at room temperature.
The reactions were stirred for 1 h. Then the reaction mixture
was extracted with water (10 ml), and the combined organic
phases dried over Mg2SO4, filtered and concentrated in
vacuo. The residue was purified by column chromatography
on silica gel (hexane–EtOAc, 160:1) to afford the desired
product d (Scheme 2). Notably, all the products are unknown
compounds except 1d, and their structures were confirmed
using IR, 1H NMR, 13C NMR, HR‐MS and elemental
analysis.
1
4d. Pale yellow oil; yield 95%. H NMR (400 MHz,
CDCl3, δ, ppm): 7.63 (q, J1 = 16.4, J2 = 8.4 Hz, 2 H,
C20H, C24H), 7.19 (q, J1 = 17.6, J2 = 8.4 Hz, 4 H, C21H,
C23H, C12H, C16H), 7.12 (d, J = 6.8 Hz, 1 H, C14H), 6.99
(d, J = 7.2 Hz, 2 H, C13H, C15H), 3.78–3.68 (m, 2 H,
C8H2), 3.55 (q, J1 = 11.6, J2 = 6.0 Hz, 1 H, C3H), 3.42 (t,
J = 9.0 Hz, 1 H, C5H), 2.90 (t, J = 10.6 Hz, 1 H, C5H),
2.47–2.40 (m, 2 H, C6H2), 2.36(s, 3 H, C25H3), 2.15 (t,
J = 6.4 Hz, 1 H, C1H), 1.57–1.49 (m, 2 H, C6H), 1.43–
1.37 (m, 2 H, C7H). 13C NMR (400 MHz, CDCl3, δ, ppm):
143.8 (C19), 141.2 (C11), 134.6 (C22), 129.9 (C21), 128.4
(C23), 128.2 (C20), 127.4 (C24), 126.1 (C13), 60.5 (C15),
55.2 (C12), 38.4 (C16), 37.6 (C14), 37.5 (C3), 36.2 (C5),
36.0 (C7), 35.9 (C6), 34.2 (C8), 33.7 (C1), 29.7 (C2), 21.6
(C25). HR‐MS (ESI) calcd for C20H24BrNO2S [M + Na]+
444.0597, found: 444.0609. Anal. Calcd (%): C, 56.87; H,
5.73; N, 3.32. Found (%): C, 56.76; H, 6.03; N, 3.61.
4.5 | Spectral data for bromoamination products
2d. White solid; yield 94%; m.p. 114–115°C. 1H NMR
(400 MHz, CDCl3, δ, ppm): 7.79 (d, J = 8.0 Hz, 2 H,
C19H, C23H), 7.37 (d, J = 8.0 Hz, 2 H, C20H, C22H), 7.27–
7.25 (m, 2 H, C2H, C6H), 7.04 (d, J = 4.4 Hz, 2 H, C3H,
C5H), 4.05–3.98 (m, 1 H, C9H), 3.88–3.83 (m, 2 H,
C12H2), 3.63–3.58 (m, 1 H, C11H), 3.34 (t, J = 11.2 Hz, 1
H, C11H), 2.73–2.62 (m, 1 H, C7H), 2.51–2.45 (m, 1 H,
C8H), 2.46 (s, 3 H, C24H3), 2.02–1.94 (m, 1 H, C8H). 13C
NMR (100 MHz, CDCl3, δ, ppm): 144.1 (C18), 137.3 (C21),
134.8 (C4), 133.0 (C1), 130.0 (C3), 128.8 (C5), 128.4 (C20),
127.6 (C22), 127.5 (C2), 60.3 (C6), 55.5 (C19), 42.5 (C23),
40.7 (C9), 39.0 (C11), 37.4 (C12), 36.3 (C7), 35.6 (C8), 21.6
(C24). HR‐MS (ESI) calcd for C18H19BrClNO2S [M + Na]+
451.9850, found: 449.9906. Anal. Calcd (%): C, 50.42; H,
4.47; N, 3.27. Found (%): C, 50.64; H, 4.61; N, 3.03.
5d. Colorless oil; yield 86%. IR (KBr, cm−1): ν 3028,
2923, 2858, 1596, 1496, 1454, 1338, 1157, 1091, 813, 729.
1H NMR (400 MHz, CDCl3, δ, ppm): 7.35–7.33 (m, 2 H,
C26H, C30H), 7.29–7.26 (m, 2 H, C27H, C29H), 7.22–7.17
(m, 5 H, C18H, C19H, C20H, C21H, C22H), 7.16–7.13 (m, 3
H, C14H, C15H, C16H), 7.09–7.07 (m, 2 H, C13H, C17H),
4.58–4.56 (m, 1 H, C8H), 4.41–4.36 (m, 2 H, C5H2), 3.97
(dd, J = 12.8 Hz, J = 17.2 Hz, 1 H, C3H), 2.99–2.94 (m, 1
H, C7H), 2.66–2.57 (m, 2 H, C5H2), 2.46–2.40 (m, 1 H,
C7H), 2.33 (s, 3 H, C31H3), 1.92–1.89 (s, 1 H, C1H), 1.77–
1.72 (m, 4H, C6H2, C2H2). 13C NMR (100 MHz, CDCl3, δ,
ppm): 142.9 (C25), 141.4 (C12), 137.6 (C11), 136.3 (C28),
129.0 (C27), 128.6 (C29), 128.3 (C30), 128.2 (C26), 127.9
(C14), 127.9 (C16), 127.8 (C19), 127.3 (C21), 125.9 (C13),
67.0 (C17), 51.5 (C18), 49.3 (C22), 38.9 (C15), 35.4 (C20),
35.1 (C3), 34.7 (C5), 34 (C8), 32.8 (C7), 31.5 (C6), 29.6
(C1), 22.6 (C2), 21.4 (C31). HR‐MS (ESI) calcd for
C26H28BrNO2S [M + K]+ 536.1689, found 536.0661. Anal.
Calcd (%): C, 62.65; H, 5.66; N, 2.81. Found (%): C,
63.01; H, 5.96; N, 2.6%.
1
3d. White solid; yield 97%; m.p. 104–105°C. H NMR
(400 MHz, CDCl3, δ, ppm): 7.62 (q, J1 = 23.6,
1
6d. White solid; yield 80%; m.p. 79–80°C. H NMR
(400 MHz, CDCl3, δ, ppm): 7.74 (d, J = 8.0 Hz, 1 H,
SCHEME 2 Procedure for bromoamination
C20H), 7.68 (s, 1 H, C24H), 7.66 (s, 1 H, C21H), 7.33

ZHANG ET AL.
7
(d, J = 4.0 Hz, 1 H, C23H), 7.29 (d, J = 8.8 Hz, 3 H,
C13H, C14H, C15H), 7.24 (s, 1 H, C12H), 7.02 (d,
J = 6.8 Hz, 1 H, C16H), 4.80–4.74 (m, 1 H, C7H),
3.70–3.65 (m, 1 H, C3H), 3.56–3.51 (m, 1 H, C5H),
2.98 (t, J = 11.2 Hz, 1 H, C5H), 2.58 (t, J = 7.4 Hz,
2 H, C6H2), 2.44 (s, 5 H, C35H3, C6H2), 1.99–1.93 (m,
1 H, C10H), 1.85–1.78 (m, 1 H, C10H), 1.74–1.70 (m,
1 H, C10H), 1.66 (d, J = 7.2 Hz, 1 H, C1H). 13C
NMR (400 MHz, CDCl3, δ, ppm): 143.6 (C19), 139.6
(C11), 135.8 (C22), 129.8 (C21), 128.5 (C23), 128.3
(C20), 127.7 (C24), 127.3 (C13), 126.4 (C15), 65.0 (C12),
56.2 (C16), 54.5 (C14), 53.9 (C3), 40.2 (C5), 39.1 (C7),
38.9 (C6), 37.9 (C1), 33.7 (C2), 22.7 (C10), 21.6 (C25).
HR‐MS (ESI) calcd for C20H24BrNO2S [M + Na]+
446.0564, found 446.0588. Anal. Calcd (%): C, 56.87;
H, 5.73; N, 3.32. Found (%): C, 57.26; H, 5.96; N, 3.16.
4.91–4.85 (m, 2 H, C9H2), 4.02 (q, J1 = 10.0, J2 = 3.2 Hz,
1 H, C4H), 3.71 (d, J = 10.0 Hz, 2 H, C10H2), 3.52–3.42
(m, 2 H, C6H2), 2.43 (t, J = 7.60 Hz, 1 H, C7H), 2.35 (t,
J = 6.8 Hz, 2 H, C3H2), 2.29 (s, 3 H, C26H3), 2.17 (q,
J1 = 13.6, J2 = 6.0 Hz, 1 H, C7H). 13C NMR (400 MHz,
CDCl3, δ, ppm): 142.6 (C1), 142.4 (C20), 132.3 (C8), 132.1
(C23), 128.8 (C22), 128.6 (C24), 127.4 (C21), 126.4 (C25),
125.3 (C14), 125.1 (C16), 117.6 (C15), 59.1 (C13), 58.9
(C17), 47.1 (C9), 44.6 (C4), 42.7 (C6), 40.0 (C7), 39.3 (C3),
35.8 (C5), 28.7 (C10), 20.5 (C26). HR‐MS (ESI) calcd for
C21H24BrNO2S [M + Na]+ 458.0577, found 458.0588. Anal.
Calcd (%): C, 58.06; H, 5.57; N, 3.22. Found (%): C, 58.67;
H, 5.97; N, 3.09.
10d. Colorless oil; yield 92%. 1H NMR (400 MHz,
CDCl3, δ, ppm): 7.78 (d, J = 8.0 Hz, 2 H, C20H, C24H),
7.36 (d, J = 8.2 Hz, 2 H, C21H, C23H), 7.19 (d, J = 5.2 Hz,
1 H, C4H), 6.93–6.91 (m, 1 H, C2H), 6.80 (d, J = 3.6 Hz, 1
H, C3H), 5.42–5.32 (m, 1 H, C12H), 4.94 (d, J = 10.0 Hz,
1 H, C13H), 4.79 (d, J = 16.8 Hz, 1 H, C13H), 4.03–3.99
(m, 1 H, C8H), 3.79 (dd, J = 9.6, J = 2.8 Hz, 1 H, C14H),
3.70 (d, J = 10.4 Hz, 1 H, C14H), 3.51–3.48 (m, 1 H,
C10H), 3.30 (t, J = 5.6 Hz, 1 H, C10H), 2.49 (s, 3H,
C25H3), 2.46–2.21(m, 2H, C11H2), 2.17–1.98 (m, 2H,
C7H2). 13C NMR (100 MHz, CDCl3, δ, ppm): 147.6 (C1),
144.0 (C26), 134.7 (C12), 132.9 (C22), 129.8 (C21), 127.5
(C23), 126.7 (C20), 124.0 (C24), 123.9 (C2), 118.7 (C3), 59.7
(C4), 59.5 (C13), 46.7 (C8), 44.3 (C10), 42.6 (C11), 36.4
(C7), 30.5 (C5), 29.7 (C14), 21.6 (C25). HR‐MS (ESI) calcd
for C19H22BrNO2S2 [M + Na]+ 462.0167, found: 462.0173.
Anal. Calcd (%): C, 51.82; H, 5.03; N, 3.18. Found (%): C,
51.67; H, 4.93; N, 3.09.
1
7d. White solid; yield 80%; m.p. 81–82°C. H NMR
(400 MHz, CDCl3, δ, ppm): 7.74 (d, J = 8.4 Hz, 1 H,
C21H), 7.67 (d, J = 8.4 Hz, 1 H, C25H), 7.31 (q,
J1 = 15.6, J2 = 8.0 Hz, 3 H, C21H, C25H, C15H), 7.24–
7.18 (m, 2 H, C13H, C17H), 7.0 (t, J = 9.0 Hz, 2 H,
C14H, C16H), 4.80–4.61 (m, 1 H, C8H), 3.80–3.65 (m, 1
H, C3H), 3.56–3.41 (m, 1 H, C5H), 3.01–2.91 (m, 1 H,
C5H), 2.58 (t, J = 7.6 Hz, 2 H, C7H2), 2.44 (s, 5 H,
C26H3, C7H2), 2.00–1.93 (m, 1 H, C11H), 1.81–1.70 (m, 2
H, C11H2), 1.66 (d, J = 6.8 Hz, 1 H, C1H), 1.60–1.56 (m,
2 H, C2H2). 13C NMR (400 MHz, CDCl3, δ, ppm): 143.6
(C20), 139.7 (C12), 135.8 (C23), 129.8 (C24), 128.6 (C22),
128.5 (C21), 128.3 (C25), 127.7 (C14), 127.3 (C16), 126.4
(C13), 64.9 (C17), 56.2 (C15), 54.5 (C3), 40.2 (C5), 39.1
(C8), 38.9 (C7), 33.6 (C6), 29.7 (C1), 23.2 (C2), 22.7
(C11), 21.6 (C26). HR‐MS (ESI) calcd for C21H26BrNO2S
[M + Na]+ 460.0758, found: 460.0745. Anal. Calcd (%):
C, 57.80; H, 6.01; N, 3.21. Found (%): C, 58.11; H, 6.41;
N, 2.99.
11d. Colorless oil; yield 90%. 1H NMR (400 MHz,
CDCl3, δ, ppm): 7.82 (d, J = 8.4 Hz, 1 H, C24H), 7.73 (d,
J = 8.0 Hz, 1 H, C28H), 7.35–7.20 (m, 5 H, C25H, C27H,
C17H, C18H, C19H), 7.12–7.07 (m, 2 H, C16H, C20H),
5.57–5.42 (m, 1 H, C8H), 5.34–5.26 (m, 1 H, C9H), 4.96–
4.84 (m, 1 H, C10H), 4.03–3.71 (m, 1 H, C4H), 3.32–3.19
(m, 2 H, C6H2), 2.66–2.58 (m, 1 H, C1H), 2.40 (s, 3 H,
C29H3), 2.32–2.22 (m, 1 H, C1H), 2.11–2.04 (m, 1 H,
C7H), 1.99–1.91 (m, 1 H, C7H), 1.87–1.77 (m, 2 H, C3H2),
1.71–1.67 (m, 3 H, C13H3), 1.54 (d, J = 6.8 Hz, 3 H,
C14H3). 13C NMR (400 MHz, CDCl3, δ, ppm): 143.4 (C23),
137.8 (C26), 137.1 (C15), 130.6 (C8), 130.0 (C25), 129.7
(C27), 128.2 (C24), 127.2 (C28), 126.5 (C17), 126.0 (C19),
63.6 (C16), 57.7 (C20), 55.8 (C18), 45.4 (C20), 41.7 (C4),
40.5 (C6), 38.5 (C1), 37.3 (C7), 36.7 (C10), 36.1 (C2), 29.7
(C3), 22.3 (C13), 21.6 (C29), 18.2 (C14). HR‐MS (ESI) calcd
for C24H30BrNO2S [M + Na]+ 500.1039, found: 500.1058.
Anal. Calcd (%): C, 60.50; H, 6.35; N, 2.94. Found (%): C,
60.43; H, 6.19; N, 2.69.
1
8d. White solid; yield 93%; m.p. 71–72°C. H NMR
(400 MHz, CDCl3, δ, ppm): 7.79–7.77 (m, 2 H, C17H,
C21H), 7.36 (d, J = 7.2 Hz, 2 H, C20H, C18H), 7.16–7.15
(m, 1 H, C4H), 6.93–6.89 (m, 1 H, C2H), 6.77–6.73 (m, 1
H, C3H), 4.00–3.92 (m, 1H, C8H), 3.92–3.81 (m, 2 H,
C11H2), 3.58–3.44 ( m, 1 H, C10H), 3.43–3.38 (m, 1 H,
C10H), 2.96–2.92 (m, 1 H, C6H), 2.57–2.51 (m, 1 H,
C7H), 2.45 (s, 3 H, C22H3), 2.06–1.97 (m, 1 H, C7H). 13C
NMR (100 MHz, CDCl3, δ, ppm): 144.1 (C1), 142.2
(C16), 134.7 (C19), 129.9 (C20), 130.0 (C18), 127.4 (C21),
126.9 (C17), 124.1 (C3), 123.9 (C2), 123.8 (C4), 60.3 (C8),
56.0 (C10), 40.1 (C11), 38.7 (C7), 37.1 (C6), 21.6 (C22).
HR‐MS (ESI) calcd for: C16H18BrNO2S2 [M + H]+
400.0012, found: 400.0041. Anal. Calcd (%): C, 48.00; H,
4.53; N, 3.50. Found (%): C, 48.59; H, 4.91; N, 3.05.
1
9d. White solid; yield 96%; m.p. 90–91°C. H NMR
(400 MHz, CDCl3, δ, ppm): 7.46 (d, J = 8.4 Hz, 2 H,
C21H, C25H), 7.30–7.17 (m, 2 H, C22H, C24H), 7.10 (d,
J = 3.6 Hz, 1 H, C15H), 7.08 (s, 2 H, C13H, C17H), 6.91–
6.89 (m, 2 H, C14H, C16H), 5.50–5.19 (m, 1 H, C8H),
ACKNOWLEDGMENTS
The financial support of the National Natural Science
Foundation of China (no. 21072228) and the Young Scholar

8
ZHANG ET AL.
Ding, L. Zhang, T. T. Li, L. Li, L. L. Duan, Y. M. Li, Adv. Synth. Catal.
2014, 356, 2303.
Foundation of the Fourth Military Medical University is
gratefully acknowledged. We also express our great thanks
to Professor Wei‐ping Chen for valuable discussions and
language revision.
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Additional Supporting Information may be found online in
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How to cite this article: Zhang, J., Wang, X., Liu, Y.,
Wang, X., and He, W. (2016), Palladium‐catalyzed
highly selective intramolecular bromoamination of
alkenes: Efficient synthesis of substituted pyrrolidines,
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