Cobalt-Catalyzed Cycloisomerization of N,N-Diallylanilines

Article abstract of DOI:10.1055/s-0037-1611832

Cobalt catalysts bearing 2-imino-1,10-phenanthroline ligands are quite efficient bench-stable catalysts for the oligomerization of ethylenes. Herein, their further application was developed in the catalytic transformation of N, N -diallylanilines to pyrro

Full text of DOI:10.1055/s-0037-1611832

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–G
paper
A
en
J. Liu et al.
Paper
Synthesis
Cobalt-Catalyzed Cycloisomerization of N,N-Diallylanilines
Jun Liua,b
Zhanhui Yanga
Minfang Zhengb
Hongfei Wub
0
0
0
0-0
0
0
1-
7
0
5
0-8
7
8
0
Co-I (10 mol%),
Et3Al (33 mol%),
PhCl (33 mol%)
N
N
R
R
N
N
Ning Chen*a
Jiaxi Xu*a
0
0
0
0-0
0
0
1-6
6
6
0-4
8
9
2
toluene (0.3 M)
Co
Cl
N
Cl
15 examples
moderate to good yields
a State Key Laboratory of Chemical Resource Engineering,
Department of Organic Chemistry, College of Chemistry,
Beijing University of Chemical Technology, Beijing
100029, P. R. of China
Co-I
chenning@mail.buct.edu.cn
jxxu@mail.buct.edu.cn
b Sinopec Beijing Research Institute of Chemical Industry
Yanshan Branch, Beijing 102500, P. R. of China
Received: 01.03.2019
Accepted after revision: 24.04.2019
Published online: 09.05.2019
clization of 1,6-enynes with catalysts generated from
Co(acac)2 and chiral bisphosphine ligands (Scheme 1c).12c,d
Recently, one of us13 and Sun’s group14 developed iron and
cobalt catalysts bearing the 2-imino-1,10-phenanthroline
ligands as efficient bench-stable catalysts for the oligomeri-
zation of ethylene.
DOI: 10.1055/s-0037-1611832; Art ID: ss-2019-f0137-op
Abstract Cobalt catalysts bearing 2-imino-1,10-phenanthroline li-
gands are quite efficient bench-stable catalysts for the oligomerization
of ethylenes. Herein, their further application was developed in the cat-
alytic transformation of N,N-diallylanilines to pyrrolidines through a cy-
cloisomerization process. In this protocol, chlorobenzene is a vital addi-
tive to promote reaction efficiency.
Previous work:
(i) Cycloisomerization of diallylamines
[M]-H
Key words cycloisomerization, cobalt-catalyzed, pyrrolidine, N,N-dial-
lylaniline, phenanthroline ligand
and/or
RN
RN
RN
(a)
(b)
M: Ru, Rh, Pd, Ir, Ti, Ni...
Pyrrolidines are fundamental chemical feedstocks in
nature and drugs.1 One of the general procedures for the
synthesis of pyrrolidines is designed through the transi-
tion-metal-catalyzed cycloisomerization of diallylamines,
as typical 1,6-diene analogues.2 Generally, precious metals,
like Ru,3 Rh,4 and Pd,5 are highly efficient pre-catalysts in
this transformation, while metal hydrides are active cata-
lysts (Scheme 1a). Moreover, first-row, earth-abundant
metal catalysts, like Ti,6 Ni,7 and Fe,8 also serve as sustain-
able alternatives in recent decade, and have been further
explored in the asymmetric cycloisomerization synthesis.9
However, there is still no example for the cycloisomeriza-
tion of dienes under the catalysis of the earth-abundant co-
balt catalysts.
Due to the fact of low costs and toxicity, economical co-
balt catalyst-mediated transformations have gained contin-
uous attention during the last two decades.10 Chirik and
Thomas observed [2+2] cycloaddition of dienes under
the catalysis of iron or cobalt complexes bearing bis(imino-
pyridine) ligands, respectively (Scheme 1b).11 Moreover, Lu
reported the cobalt-iminopyridine complex-catalyzed hyd-
roboration or hydrosilation/cyclization of 1,6-enynes,12a,b
while Ge reported the cobalt-catalyzed hydroboration/cy-
(ii) Fe or Co-catalyzed [2+2] cycloaddition of dienes
H
[Fe] and [Co]
E
E
E = NR, O, CR2
H
(iii) Co-catalyzed hydroboration/hydrosilation-cyclization of enynes
R
(c)
(d)
R
R
Co-Cat
H
X
E
X
H
or
E
E
HSiR3/NaBHEt3
or HBpin
X = Bpin; SiR3
E = C(CO2R')2, NTs, NR, O
This work:
Co-catalyzed cycloisomerization of diallylanilines
[Co]-H
Ar
N
Ar
N
PhCl, toluene
Scheme 1 Transition-metal-catalyzed transformations of diallylamines
and related analogues
As we know, before ethylene oligomerization/polymer-
ization, metal hydrides (M-Hs) are in-situ generated from
metal halides, triethylaluminum, and imino-1,10-phenan-
throline ligands. The M-Hs and co-catalyst methylalumi-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

B
J. Liu et al.
Paper
Synthesis
noxane (MAO) then promote the ethylene oligomerization
through a stepwise intermolecular 1,2-insertion and end
up with a -hydride elimination. For the further study, we
thus surmise that an intramolecular insertion of dienes
may also be realized under similar conditions. Hence, here-
in we have developed the cycloisomerization of N,N-dial-
lylanilines under the catalysis of bench-stable cobalt-imi-
no-1,10-phenanthroline complexes.
Cobalt and iron catalysts I to VI were easily prepared
from the corresponding 2-imino-1,10-phenanthroline li-
gands with CoCl2 and FeCl2 by following the references.13,14
At the beginning, both heptan-1,6-diene and diallyl ether
were attempted in toluene under the catalysis of catalyst
Co-I and triethylaluminum, but none of the desired cyclized
products was generated (see SI). N,N-Diallylanilines were
next investigated. In order to facilitate the analysis, N,N-di-
allylmesitylamine (1a) was chosen as the substrate to opti-
Table 1 Optimization of the Transformationa
catalyst (10 mol%),
Et3Al, PhCl
N
N
solvent
1a
2a
Entry
Catalyst
Cocatalyst (mol%)
Additive (mol%)
Solvent
Temp (°C)
Yield (%)b
1
2
Co-I
Co-I
Co-I
Co-I
Co-I
Co-II
Fe-III
Fe-IV
Fe-V
Fe-VI
Co-I
Co-I
Co-I
Co-I
Co-I
Co-I
Co-I
Co-I
Co-I
Co-I
Co-I
Et3Al (100)
MAO (100)
AmMgCl (100)
Me3Al (100)
EtAlCl2 (100)
Et3Al (100)
Et3Al (100)
Et3Al (100)
Et3Al (100)
Et3Al (100)
Et3Al (100)
Et3Al (100)
Et3Al (100)
Et3Al (100)
Et3Al (100)
Et3Al (250)
Et3Al (50)
–
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
THF
0–25
0–25
0–25
0–25
0–25
0–25
0–25
0–25
0–25
0–25
0–25
0–25
0–25
0–25
0–25
0–25
0–25
0–25
0–25
0–40
0–60
28
–
0
3
–
0
4
–
0
5
–
0
6
–
messy
messy
messy
messy
messy
17
7
–
8
–
9
–
10
11
12
13
14
15
16
17
18
19
20
21
–
–
–
n-Hexane
DCM
0
–
0
–
PhCl
trace
72
PhCl (40)
PhCl (40)
PhCl (40)
PhCl (40)
PhCl (40)
PhCl (33)
PhCl (33)
toluene
toluene
toluene
toluene
toluene
toluene
toluene
0
70
Et3Al (33)
78
Et3Al (20)
50
Et3Al (33)
52
Et3Al (33)
25
a Reaction conditions: 1a (0.6 mmol), catalyst (0.06 mmol), and cocatalyst in solvent (2 mL) under N2 at 0 °C for 1 h and then at 25 °C for 4 h.
b Yields are determined by 1H NMR analysis with the internal standard of 1,3,5-trimethoxybenzene.
N
N
R
N
N
R
N
N
R
Fe
Cl
Fe
Cl
Co
Cl
N
R
N
R
N
R
Cl
Cl
Cl
(Fe-V) R = Et
(Fe-VI) R = i-Pr
(Co-I) R = Et
(Co-II) R = i-Pr
(Fe-III) R = Et
(Fe-IV) R = i-Pr
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

C
J. Liu et al.
Paper
Synthesis
lysts produced very complicated systems (entries 1 vs 6–
10).
Cat-I (10 mol%),
Et3Al (33 mol%),
PhCl (33 mol%)
R
R
We next screened the solvents, including toluene, n-
hexane, dichloromethane (DCM), tetrahydrofuran (THF),
and chlorobenzene (PhCl) (entries 1 vs 11–14). Most of the
solvents showed no efficiency, but the reactions were car-
ried out smoothly in toluene (28%) and THF (17%). Interest-
ingly, all raw materials were totally converted when the re-
action was performed in chlorobenzene, but only trace of
2a was detected. Inspired by this, we thus explored to use
toluene as the solvent with PhCl as additive to promote the
reaction efficiency. To our great delight, when PhCl (40
mol%) was added as additive, the yield of the isolated prod-
uct 2a was raised directly to 72% in toluene (entry 15). The
loading of Et3Al was then investigated (entries 15–19) and
the best yield was obtained when decreasing the loading to
33 mol% (entry 18). Generally, the reaction was first con-
ducted at 0 °C when Et3Al was added, and then slowly
raised up to 25 °C (room temperature). The yield dropped
dramatically when the reaction temperature was raised up
to 40 and 60 °C (entries 20 and 21).
N
N
toluene, 1) 0 °C, 1 h. 2) 25 °C, 4 h
2
1
N
N
N
2a (75%)
2b (72%)
2c (68%)
N
N
N
2d (72%)
2e (65%)
2f (64%)
N
N
N
2g (38%)
2h (70%)
2i (65%)
We next investigated the scope of the reaction. N,N-Di-
allylaniline (1b) gave the corresponding pyrrolidine 2b in
72% yield under the optimized conditions. A variety of or-
tho-, meta-, and para-alkyl mono- and disubstituted ani-
lines were tested, affording the desired products in good
yields (Scheme 2). First, o-methyl and o-ethyl N,N-dial-
lylanilines 1c and 1d gave the desired pyrrolidines 2c and
2d in good yields. Moreover, m-methyl N,N-diallylaniline
1e, p-ethyl and tert-butyl N,N-diallylanilines 1f and 1g also
provided the desired products 2e–g in 65%, 64%, and 38%
yields, respectively. Notably, the yield of 2g was relatively
low because some unknown by-products with similar po-
larity were accompanied with 2g so that the isolation of 2g
was less effective during the column chromatography. Com-
paring the ortho-substituents with meta- and para-ones,
the above results also demonstrated that the steric hin-
drance on the arene ring did not affect the reaction trans-
formation. Further evidences were obtained by introducing
2,6-dimethyl 1h, diethyl 1i, and especially bulky diisopro-
pyl 1j substituents to N,N-diallylanilines, all of which gave
the corresponding pyrrolidines 2h–j in good yields. More-
over, the current conditions were also well tolerant with
halogens. Fluoro 1k, chloro 1l, and bromo 1m substrates af-
forded the desired products 2k–m in 68%, 68%, and 67%
yields, respectively. It is worthy to mention that both 1-
F
N
Cl
N
N
2l (68%)
2k (68%)
2j (74%)
N
Br
N
N
2o (75%)
2m (67%)
2n (68%)
Scheme 2 Scope of N,N-diallylanilines. Reagents and conditions: 1 (0.6
mmol), Co-I (0.06 mmol), Et3Al (0.2 mmol), and PhCl (0.2 mmol) in tol-
uene (2.0 mL) under N2 at 0 °C for 1 h and then at 25 °C for 4 h.
mize the conditions in toluene owing to its typical singlet
aromatic proton signal in the 1H NMR spectrum (Table 1). A
co-catalyst was indispensable to activate the precatalyst to
afford the active metal hydride. Methylaluminoxane, pen-
tylmagnesium chloride (AmMgCl), trimethylaluminum
(Me3Al), triethylaluminum (Et3Al), and ethyl aluminum di-
chloride (EtAlCl2) were subsequently investigated, while
only Et3Al gave the corresponding cycloisomerization prod-
uct 2a in a moderate yield (entries 1–5). A variety of precat-
alysts Co-II and Fe-III to VI were then explored, but only
Co-I could promote the reaction, and all of the rest of cata-
Cat-I (10 mol%),
Et3Al (33 mol%),
PhCl (33 mol%)
Cl
Ph
Cl
N
N
H
toluene, 1) 0 °C, 1 h. 2) 25 °C, 4 h
3p, 87.5 mg
1p (0.6 mmol)
60%
Scheme 3 Reaction of 4-chloro-N-cinnamylaniline under the optimal conditions
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

D
J. Liu et al.
Paper
Synthesis
naphthyl and 2-naphthyl substrates provided the desired
products 2n and 2o in 68% and 75% yields, respectively.
Other substrates with electron-withdrawing substitu-
ents on the nitrogen atom, such as N,N-diallyl-4-nitroani-
line, ethyl 4-diallylaminobenzoate, and N,N-diallylbenzene-
sulfonamide, were also investigated, but all of them afford-
ed the desired cyclized products in very low yields (<5%)
possibly because the strong electron-withdrawing substitu-
ents inhibited the reactions. For substrate with N-alkyl sub-
stituent, N,N-diallylbenzylamine gave messy products un-
der the optimal conditions. Finally, sterically demanding N-
allyl-4-chloro-N-cinnamylaniline (1p) was also investigat-
ed, affording a deallylation product, 4-chloro-N-cinnamy-
laniline (3p), in 60% yield (Scheme 3).
The reaction mechanism is finally proposed in Scheme
4 by referring similar transition-metal-catalyzed transfor-
mations.3–8 First, under the chlorobenzene promotion, co-
balt hydride complex A is first generated from Co-I catalyst
and triethylaluminum. Both Me3Al and MAO [O–Al(Me)]
are inefficient, supporting the formation of Co-H catalyst
because Co-Et undergoes a -H elimination to generate Co-
H catalyst, but Co-Me cannot. The cobalt hydride A coordi-
nates with diallylanilines 1 followed by an insertion step to
form the intermediates B. The subsequent cycloisomeriza-
tion of B through a 1,2-insertion is realized via a 5-exo-trig
process to generate cyclized C. Finally, the -hydride elimi-
nation of the complexes C affords the desired pyrrolidines 2
and regenerates the catalyst Co-H (A).
fied as an effective catalyst for not only oligomerization of
olefins, but also for the cyclization of N,N-diallylanilines. In
this transformation, chlorobenzene was identified as the vi-
tal additive to promote reaction efficiency. Moreover, vari-
ous alkyl- and halo-substituted N,N-diallylanilines were
tolerated in these transformations. The current cobalt-cata-
lyzed system is only suitable for electron-rich N,N-dial-
lylanilines.
Unless otherwise noted, all materials were purchased from commer-
cial suppliers. All reactions were performed in a Schlenk flask
equipped with a magnetic stir bar under N2 atmosphere. Flash col-
umn chromatography was performed using silica gel (normal phase,
200–300 mesh) from Branch of Qingdao Haiyang Chemical Industry.
Petroleum ether (PE) used for column chromatography is 60−90 °C
fraction, and the removal of residue solvent was accomplished under
rotovap. Reactions were monitored by TLC on silica gel GF254 coated
0.2 mm plates from Institute of Yantai Chemical Industry. The plates
were visualized under UV light. All commercially available reactants
are used directly. Anhydrous toluene was prepared by reflux with Na.
Melting points were obtained on a Yanaco MP-500 melting point ap-
1
paratus and are uncorrected. H NMR and 13C NMR spectra were re-
corded on a Bruker 400 spectrometer in CDCl3 and acetone-d6 with
TMS as an internal standard. IR spectra were recorded directly on a
Nicolet AVATAR 330 FTIR spectrophotometer. HRMS spectra were re-
corded on an Agilent Liquid Chromatography/Mass Spectrometry/Da-
ta and Time-of-Flight (LC/MSD /TOF) mass spectrometer.
Cobalt-Catalyzed Cycloisomerization of N,N-Diallylanilines; Gen-
eral Procedure
Cobalt-I (29.0 mg, 0.067 mmol) was added to a reaction tube (or a
Schlenk tube) and the whole system was replaced with N2 gas three
times. PhCl (22.4 mg, 20 L, 0.2 mmol), Et3Al (1 M in n-hexane, 0.2
mL), and toluene (2 mL) were then introduced into the tube and the
resulting solution was stirred for 10 min at 0 °C to activate the cata-
lyst. The respective N,N-diallylaniline 1 (0.6 mmol) was added and the
reaction mixture was first stirred for 1 h at 0 °C and then warmed up
to 25 °C for 4 h. The reaction was quenched with aq 25% NaOH (1.0
mL) and filtered through Celite (1.0 g) to remove the aluminum com-
plex. DCM (2.0 mL) was added to flush the Celite. The filtrate was sep-
arated and the aqueous phase was extracted with DCM (2 × 1.0 mL).
The combined organic phases were dried (Na2SO4) and concentrated
under vacuum. The residue was finally purified by silica gel column
chromatography with hexanes as eluent.
[Co]
Cl (Co-I)
PhCl
Et3Al
R
N
[Co]
H
R
N
A
1
2
β-elimination
R
N
R
[Co]
N
H
H
B
1-Mesityl-3-methyl-4-methylenepyrrolidine (2a)7c
C
Colorless liquid; yield: 78.0 mg (75%); Rf = 0.40 (hexanes).
IR (film): 2961, 2917, 2868, 1482, 1459, 1372, 1343, 1270, 1194,
1,2-insertion
1156, 1032, 947, 881, 850 cm–1
.
1H NMR (400 MHz, CDCl3):  = 6.84 (s, 2 H), 4.93 (d, J = 2.2 Hz, 1 H),
4.91 (d, J = 2.2 Hz, 1 H), 4.01–3.70 (m, 2 H), 3.38 (dd, J = 7.6, 7.6 Hz, 1
H), 2.95 (dd, J = 7.6, 7.6 Hz, 1 H), 2.91–2.80 (m, 1 H), 2.25 (s, 3 H), 2.23
(s, 6 H), 1.20 (d, J = 6.8 Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 154.9, 141.8, 138.1, 134.8, 129.4,
103.3, 58.6, 55.0, 38.7, 20.8, 18.7, 17.1.
Scheme 4 Proposed reaction mechanism of the cycloisomerization of
diallylanilines
In conclusion, we have developed an efficient way to
prepare pyrrolidines from N,N-diallylanilines through a cy-
cloisomerization process in the presence of earth-abundant
cobalt catalyst. One of the quite inexpensive and bench-sta-
ble cobalt-2-imino-1,10-phenanthroline catalysts was veri-
3-Methyl-4-methylene-1-phenylpyrrolidine (2b)6
Colorless oil; yield: 74.7 mg (72%); Rf = 0.35 (hexanes).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

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1H NMR (400 MHz, acetone-d6):  = 7.18 (dd, J = 7.4, 7.4 Hz, 2 H), 6.64
(t, J = 7.3 Hz, 1 H), 6.59 (d, J = 7.9 Hz, 2 H), 5.06 (d, J = 2.3 Hz, 1 H), 4.98
(d, J = 2.3 Hz, 1 H), 4.05 (d, J = 14.0 Hz, 1 H), 3.84 (dd, J = 14.0, 1.7 Hz, 1
H), 3.66 (t, J = 8.0 Hz, 1 H), 2.98–2.87 (m, 1 H), 2.85 (d, J = 8.4 Hz, 1 H),
1.21 (d, J = 6.6 Hz, 3 H).
1H NMR (400 MHz, CDCl3):  = 7.09 (d, J = 8.3 Hz, 2 H), 6.55 (d, J = 8.3
Hz, 2 H), 5.02 (s, 1 H), 4.95 (s, 1 H), 4.07 (d, J = 13.8 Hz, 1 H), 3.85 (d, J =
13.8 Hz, 1 H), 3.64 (dd, J = 7.6, 7.6 Hz, 1 H), 2.96–2.81 (m, 2 H), 2.56 (q,
J = 7.6 Hz, 2 H), 1.21 (d, J = 6.4 Hz, 3 H), 1.20 (t, J = 7.5 Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 152.0, 146.2, 132.1, 128.5, 112.1,
104.5, 55.6, 53.6, 37.4, 27.9, 16.9, 16.0.
13C NMR (101 MHz, acetone-d6):  = 152.9, 149.0, 129.8, 117.0, 112.9,
105.0, 56.1, 53.9, 38.1, 17.1.
HRMS (APCI): m/z calcd for C12H16N+ [M + H]+: 174.1277; found:
HRMS (APCI): m/z calcd for C14H20N+ [M + H]+: 202.1590; found:
202.1597.
174.1284.
1-[4-(tert-Butyl)phenyl]-3-methyl-4-methylenepyrrolidine (2g)
Colorless oil; yield: 52.0 mg (38%); Rf = 0.45 (hexanes).
3-Methyl-4-methylene-1-(o-tolyl)pyrrolidine (2c)
Colorless liquid; yield: 76.3 mg (68%); Rf = 0.35 (hexanes).
FT-IR (film): 3078, 2961, 2864, 1613, 1520, 1391, 1363, 1233, 918,
FT-IR (film): 3075, 3016, 2978, 2924, 2810, 1642, 1598, 1459, 1417,
813 cm–1
.
1357, 1218, 919, 765, 729 cm–1
.
1H NMR (400 MHz, acetone-d6):  = 7.23 (d, J = 8.7 Hz, 2 H), 6.55 (d, J =
8.7 Hz, 2 H), 5.04 (s, 1 H), 4.97 (s, 1 H), 4.03 (d, J = 14.0 Hz, 1 H), 3.82
(d, J = 14.0 Hz, 1 H), 3.64 (t, J = 8.0 Hz, 1 H), 2.91–2.89 (m, 1 H), 2.84–
2.81 (m, 1 H), 1.26 (s, 9 H), 1.19 (d, J = 6.4 Hz, 3 H).
13C NMR (101 MHz, acetone-d6):  = 153.2, 147.0, 139.4, 126.4, 112.8,
104.9, 56.3, 54.1, 38.2, 34.3, 31.9, 17.2.
1H NMR (400 MHz, CDCl3):  = 7.05 (t, J = 7.0 Hz, 2 H), 6.84–8.80 (m, 2
H), 4.89 (d, J = 0.8 Hz, 1 H), 4.83 (d, J = 1.2 Hz, 1 H), 3.95 (d, J = 13.6 Hz,
1 H), 3.56 (d, J = 13.6 Hz, 1 H), 3.34–3.28 (m, 1 H), 2.78–2.74 (m, 2 H),
2.25 (s, 3 H), 1.14 (d, J = 6.0 Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 153.2, 148.6, 131.5, 129.9, 126.3,
121.3, 116.6, 103.7, 58.8, 56.4, 37.5, 20.0, 17.0.
HRMS (APCI): m/z calcd for C13H18N+ [M + H]+: 188.1443; found:
HRMS (APCI): m/z calcd for C16H24N+ [M + H]+: 230.1903; found:
230.1908.
188.1434.
1-(2,6-Dimethylphenyl)-3-methyl-4-methylenepyrrolidine (2h)
Colorless liquid; yield: 84.3 mg (70%); Rf = 0.40 (hexanes).
1-(2-Ethylphenyl)-3-methyl-4-methylenepyrrolidine (2d)
Colorless liquid; yield: 86.0 mg (72%); Rf = 0.45 (hexanes).
FT-IR (film): 3075, 3017, 2924, 2810, 1642, 1599, 1492, 1450, 1416,
FT-IR (film): 3074, 3010, 2977, 2920, 1640, 1473, 1435, 1415, 1372,
1215, 990, 917, 768 cm–1
.
1357, 1218, 919, 753 cm–1
.
1H NMR (400 MHz, CDCl3):  = 6.95–6.90 (m, 3 H), 4.98–4.93 (m, 2 H),
3.83 (dq, J = 13.5, 1.0 Hz, 1 H), 3.80 (dq, J = 13.5, 2.0 Hz, 1 H), 3.34 (t,
J = 7.6 Hz, 1 H), 2.89 (t, J = 7.6 Hz, 1 H), 2.84–2.79 (m, 1 H), 2.19 (s, 6
H), 1.14 (d, J = 6.8 Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 154.7, 144.5, 138.3, 128.6, 125.3,
103.3, 58.5, 54.9, 38.7, 18.9, 17.0.
1H NMR (400 MHz, acetone-d6):  = 7.18 (d, J = 7.6 Hz, 1 H), 7.11 (t, J =
7.4 Hz, 1 H), 7.01 (d, J = 7.6 Hz, 1 H), 6.94 (t, J = 7.4 Hz, 1 H), 4.97 (d, J =
1.6 Hz, 1 H), 4.92 (d, J = 2.0 Hz, 1 H), 3.90 (d, J = 13.6 Hz, 1 H), 3.63 (dt,
J = 13.6, 2.0 Hz, 1 H), 3.37–3.31 (m, 1 H), 2.84–2.78 (m, 2 H), 2.73–2.65
(m, 2 H), 1.22 (t, J = 7.6 Hz, 3 H), 1.21 (t, J = 6.2 Hz, 3 H).
13C NMR (101 MHz, acetone-d6):  = 154.6, 149.0, 137.8, 130.0, 127.2,
123.2, 118.7, 104.2, 60.5, 58.0, 38.5, 17.7, 14.8.
HRMS (APCI): m/z calcd for C14H20N+ [M + H]+: 202.1590; found:
202.1599.
HRMS (APCI): m/z calcd for C14H20N+ [M + H]+: 202.1590; found:
202.1596.
1-(2,6-Diethylphenyl)-3-methyl-4-methylenepyrrolidine (2i)
Colorless liquid; yield: 89.3 mg (65%); Rf = 0.35 (hexanes).
3-Methyl-4-methylene-1-(m-tolyl)pyrrolidine (2e)
FT-IR (film): 3075, 2965, 2931, 2873, 2813, 1639, 1456, 1415, 1371,
Colorless liquid; yield: 73.0 mg (65%); Rf = 0.35 (hexanes).
990, 917, 765 cm–1
.
FT-IR (film): 3075, 2978, 2924, 2810, 1642, 1599, 1492, 1463, 1385,
1H NMR (400 MHz, CDCl3):  = 7.13–6.98 (m, 3 H), 4.86–4.84 (m, 2 H),
3.83 (d, J = 13.5, 1.0 Hz, 1 H), 3.80 (d, J = 13.5, 1.8 Hz, 1 H), 3.33 (t, J =
7.7 Hz, 1 H), 2.90 (t, J = 7.7 Hz, 1 H), 2.87–2.80 (m, 1 H), 2.56 (q, J = 7.5
Hz, 4 H), 1.13 (t, J = 7.5 Hz, 6 H), 1.12 (d, J = 6.6 Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 154.8, 145.1, 143.7, 126.9, 126.1,
103.4, 60.3, 56.8, 38.8, 24.8, 17.0, 15.7.
1218, 919, 837, 765, 691 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.05 (t, J = 8.1 Hz, 1 H), 6.46 (d, J = 7.4
Hz, 1 H), 6.32 (s, 1 H), 6.31 (d, J = 8.1 Hz, 1 H), 4.94 (s, 1 H), 4.87 (s, 1
H), 3.99 (d, J = 13.8 Hz, 1 H), 3.78 (d, J = 13.8 Hz, 1 H), 3.61–3.46 (m, 1
H), 2.88–2.71 (m, 2 H ), 2.24 (s, 3 H), 1.13 (d, J = 6.4 Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 151.7, 148.0, 138.8, 129.0, 117.2,
112.7, 109.2, 104.5, 55.3, 53.3, 37.3, 21.8, 16.8.
HRMS (APCI): m/z calcd for C16H24N+ [M + H]+: 230.1903; found:
230.1912.
HRMS (APCI): m/z calcd for C13H18N+ [M + H]+: 188.1440; found:
188.1434.
1-(2,6-Diisopropylphenyl)-3-methyl-4-methylenepyrrolidine
(2j)7c
1-(4-Ethylphenyl)-3-methyl-4-methylenepyrrolidine (2f)
Colorless liquid; yield: 77.2 mg (64%); Rf = 0.35 (hexanes).
FT-IR (film): 3078, 3007, 2961, 2925, 1615, 1519, 1384, 1232, 917,
Colorless liquid; yield: 114.0 mg (74%); Rf = 0.45 (hexanes).
1H NMR (400 MHz, acetone-d6):  = 7.18–7.10 (m, 3 H), 4.97–4.95 (m,
2 H), 3.92 (dq, J = 13.4, 0.9 Hz, 1 H), 3.87 (dq, J = 13.4, 1.8 Hz, 1 H), 3.44
(t, J = 7.2 Hz, 1 H), 3.40–3.18 (m, 2 H), 2.99 (t, J = 7.4 Hz, 1 H), 2.98–
2.87 (m, 1 H), 1.22 (d, J = 6.5 Hz, 3 H), 1.19 (d, J = 6.9 Hz, 6 H), 1.18 (d,
J = 6.9 Hz, 6 H).
813 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

F
J. Liu et al.
Paper
Synthesis
13C NMR (101 MHz, acetone-d6):  = 155.3, 150.6, 142.8, 127.6, 124.8,
HRMS (APCI): m/z calcd for C16H18N+ [M + H]+: 224.1434; found:
104.8, 62.0, 58.4, 39.5, 28.8, 24.8, 24.6, 17.3.
224.1441.
HRMS (APCI): m/z calcd for C18H28N+ [M + H]+: 258.2216; found:
258.2221.
3-Methyl-4-methylene-1-(naphthalen-2-yl)pyrrolidine (2o)
Colorless oil; yield: 108.0 mg (75%); Rf = 0.45 (hexanes).
1-(4-Fluorophenyl)-3-methyl-4-methylenepyrrolidine (2k)
Colorless oil; yield: 77.9 mg (68%); Rf = 0.40 (hexanes).
FT-IR (film): 3057, 3008, 2978, 2915, 1628, 1599, 1510, 1392, 1220,
918, 824, 743 cm–1
.
FT-IR (film): 3081, 3007, 2980, 2915, 1642, 1519, 1387, 1229, 1181,
1H NMR (400 MHz, CDCl3):  = 7.63 (d, J = 8.9 Hz, 1 H), 7.61 (d, J = 8.0
Hz, 1 H), 7.57 (d, J = 8.3 Hz, 1 H), 7.28 (ddd, J = 8.2, 6.8, 1.2 Hz, 1 H),
7.11 (ddd, J = 8.0, 6.8, 1.2 Hz, 1 H), 6.93 (dd, J = 8.9, 2.5 Hz, 1 H), 6.71
(d, J = 2.2 Hz, 1 H), 5.00 (q, J = 2.0 Hz, 1 H), 4.92 (q, J = 2.2 Hz, 1 H), 4.13
(d, J = 13.8 Hz, 1 H), 3.92 (dq, J = 13.8, 1.7 Hz, 1 H), 3.75–3.67 (m, 1 H),
2.94 (t, J = 7.9 Hz, 1 H), 2.92–2.85 (m, 1 H), 1.18 (d, J = 6.5 Hz, 3 H).
13C NMR (101 MHz, acetone-d6):  = 154.3, 147.9, 135.9, 129.5, 129.1,
126.8, 126.5, 125.6, 125.1, 123.3, 113.7, 104.5, 61.1, 58.8, 38.5, 17.7.
HRMS (APCI): m/z calcd for C16H18N+ [M + H]+: 224.1434; found:
224.1443.
1227, 920, 813 cm–1
.
1H NMR (400 MHz, CDCl3):  = 6.95 (t, J = 8.8 Hz, 2 H), 6.50 (dd, J = 8.8,
4.3 Hz, 2 H), 5.03 (q, J = 2.2 Hz, 1 H), 4.96 (q, J = 2.2 Hz, 1 H), 4.05 (d, J =
13.6 Hz, 1 H), 3.82 (dq, J = 13.6, 1.6 Hz, 1 H), 3.61 (t, J = 7.9 Hz, 1 H),
2.98–2.87 (m, 1 H), 2.84 (t, J = 8.1 Hz, 1 H), 1.22 (d, J = 6.6 Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 155.3 (d, J = 234.3 Hz), 151.6, 144.7,
115.5 (d, J = 22.1 Hz), 112.6 (d, J = 7.3 Hz), 104.7, 55.9, 53.9, 37.4, 16.8.
19F NMR (377 MHz, acetone-d6):  = –131.3.
HRMS (APCI): m/z calcd for C12H15FN+ [M + H]+: 192.1183; found:
192.1192.
4-Chloro-N-cinnamylaniline (3p)
White powder; yield: 87.5 mg (60%); mp 69–71 °C (Lit.15 mp 77–79
°C); Rf = 0.50 (PE/DCM 1:1, v/v).
1H NMR (400 MHz, CDCl3):  = 7.37–7.28 (m, 4 H), 7.26–7.21 (m, 1 H),
7.11 (d, J = 8.8 Hz, 2 H), 6.60 (d, J = 15.9 Hz, 1 H), 6.57 (d, J = 8.8 Hz, 2
H), 6.28 (td, J = 15.9, 5.7 Hz, 1 H), 3.90 (dd, J = 5.7, 1.5 Hz, 2 H), 3.86 (br
s, 1 H).
1-(4-Chlorophenyl)-3-methyl-4-methylenepyrrolidine (2l)
Colorless oil; yield: 84.5 mg (68%); Rf = 0.30 (hexanes).
FT-IR (film): 3075, 2979, 2920, 1642, 1597, 1499, 1387, 1234, 920,
808 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.15 (d, J = 8.90 Hz, 2 H), 6.46 (d, J = 8.9
Hz, 2 H), 5.02 (q, J = 2.1 Hz, 1 H), 4.95 (q, J = 2.2 Hz, 1 H), 4.02 (d, J =
13.7 Hz, 1 H), 3.81 (dq, J = 13.7, 1.7 Hz, 1 H), 3.59 (t, J = 7.9 Hz, 1 H),
3.15–2.87 (m, 1 H), 2.83 (t, J = 8.2 Hz, 1 H), 1.20 (d, J = 6.5 Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 146.5, 136.7, 131.8, 129.1, 128.6,
127.6, 126.4, 126.3, 122.2, 114.1, 46.2.
13C NMR (101 MHz, CDCl3):  = 151.2, 146.3, 128.9, 121.0, 112.9,
104.8, 77.3, 77.0, 76.7, 55.4, 53.3, 37.3, 16.6.
HRMS (APCI): m/z calcd for C16H24ClN+ [M + H]+: 208.0888; found:
Funding Information
This work was supported partially from the National Natural Science
Foundation of China (No. 21702014 and 21572017) and the Funda-
208.0897.
mental Research Funds for the Central Universities (XK1802-6).
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1-(4-Bromophenyl)-3-methyl-4-methylenepyrrolidine (2m)
Colorless oil; yield: 100.9 mg (67%); Rf = 0.30 (hexanes).
FT-IR (film): 3082, 3007, 2980, 2911, 2865, 1642, 1590, 1497, 1389,
Supporting Information
1233, 1181, 920, 806 cm–1
.
Supporting information for this article is available online at
1H NMR (400 MHz, acetone-d6):  = 7.30 (d, J = 9.0 Hz, 2 H), 6.54 (d, J =
9.0 Hz, 2 H), 5.06 (q, J = 2.2 Hz, 1 H), 4.99 (q, J = 2.3 Hz, 1 H), 4.04 (d, J =
14.0 Hz, 1 H), 3.85 (dq, J = 14.0, 1.9 Hz, 1 H), 3.66 (t, J = 8.1 Hz, 1 H),
2.96–2.88 (m, 1 H), 2.85 (t, J = 8.2 Hz, 1 H), 1.21 (d, J = 6.6 Hz, 3 H).
https://doi.org/10.1055/s-0037-1611832.
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References
13C NMR (101 MHz, acetone-d6):  = 152.5, 148.0, 132.4, 114.7, 108.3,
105.3, 56.0, 53.8, 38.1, 17.0.
HRMS (APCI): m/z calcd for C12H15BrN+ [M + H]+: 252.0382; found:
252.0384.
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Colorless oil; yield: 92.0 mg (68%); Rf = 0.35 (hexanes).
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G