Reductive Cyclization of 1,6- and 1,7-Enynes Catalyzed by Iron Complexes

Article abstract of DOI:10.1055/s-0035-1561957

Iron-catalyzed reductive cyclization of 1,6- and 1,7-enynes was demonstrated by using an oxazoline iminopyridine ligand. Alcohol, ketone, ester, ether, halide, amine, amide, imine, nitrile, silyl, and alkyne groups are tolerated under the mild reaction co

Full text of DOI:10.1055/s-0035-1561957

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–H
A
special topic
T. Xi et al.
Special Topic
Synthesis
Reductive Cyclization of 1,6- and 1,7-Enynes Catalyzed by Iron
Complexes
Tuo Xi
O
Xu Chen
N
iPr
Heyi Zhang
Zhan Lu*
N
N
Fe
Bn
R
Cl
iPr
Cl
R
Department of Chemistry, Zhejiang University,
Hangzhou 310027, P. R. of China
luzhan@zju.edu.cn
iron catalyst (5 mol%)
X
Et2Zn (2.5 equiv), argon, r.t., 1.5 h
X
syn-selectivity
28 examples
41–92% yield
X = O, NZ, C(CO2Et)2, CH2O
R = H, alkyl, aryl, heteroaryl
Alcohol, ketone, ester, ether, halide, amine, amide,
imine, nitrile, silyl and alkyne groups are tolerated!
Received: 31.12.2015
Accepted after revision: 26.02.2016
Published online: 12.04.2016
standard conditions. Recently, Huang’s group7 and our
group8 independently, using different synthetic strategies,
developed novel oxazoline iminopyridine ligands whose
iron or cobalt complexes efficiently catalyzed asymmetric
reactions. By using our synthetic strategy, bench-stable ox-
azoline iminopyridine ligands can be obtained from the
simple starting material 2,6-dibromopyridine in three steps
without chromatographic purification. Furthermore, the
iron(II) chloride complexes of these ligands are bench-sta-
ble. Here, we report on operationally simple process for the
iron-catalyzed reductive cyclization of 1,6- and 1,7-enynes
with a broad tolerance of functional groups.
DOI: 10.1055/s-0035-1561957; Art ID: ss-2015-c0749-st
Abstract Iron-catalyzed reductive cyclization of 1,6- and 1,7-enynes
was demonstrated by using an oxazoline iminopyridine ligand. Alcohol,
ketone, ester, ether, halide, amine, amide, imine, nitrile, silyl, and
alkyne groups are tolerated under the mild reaction conditions. A
speculative mechanism is proposed on the basis of deuteration studies.
A primary enantioselective transformation was also conducted.
Key words iron, catalysis, enynes, cyclizations, asymmetric synthesis
Earth-abundant transition metals are not only environ-
mentally friendly and resource-conserving, but also show
high reactivities and selectivities in many reactions. Al-
though noble-metal catalysts play an important role in or-
ganic synthesis, their scarcity, high cost, and toxicity make
the development of efficient synthetic processes using
more abundant transition-metal catalysts highly desirable.
Iron is an ideal sustainable metal.1
Transition-metal-catalyzed cyclization of nonactivated
1,6-enynes is a powerful method for constructing carbocy-
clic and heterocyclic molecules.2 Although there are many
examples of catalysis by noble metals,3 there have been few
reports of iron-catalyzed cyclizations of nonactivated 1,6-
enynes. Fürstner et al. showed that a low-valent iron(0)
complex efficiently catalyzes the cycloisomerization and
cycloaddition of 1,6-enynes.4 Chirik and co-workers de-
scribed a bis(imino)pyridine iron bis(dinitrogen) complex-
catalyzed reductive cyclization of 1,6-enynes under four at-
mospheres of hydrogen.5 Yang and co-workers reported a
reductive cyclization of 1,6-enynes in the presence of 20
mol% of FeCl2 and 2-iminopyridine with an additional one
equivalent of MgBr2·Et2O.6 However, active functional
groups such as hydroxy, ketone, imino, and nitrile groups
were either not tolerated or were not examined under their
The easily prepared 1,6-enyne 1a was chosen as a model
substrate, and iron complex I was used as a precatalyst for
the iron-catalyzed reductive cyclization of the enyne (Table
1). The initial reaction of 1a with 2.5 equivalents of Et2Zn as
a reductant in the presence of 5 mol% of I and 15 mol% of
NaBHEt3 in toluene at room temperature for 1.5 hours, fol-
lowed by hydrolysis, gave the desired reductive cyclization
product 2a in 44% yield (Table 1, entry 1). No improvement
in the result was achieved by using 1,4-dioxane, CH2Cl2,
Et2O, or THF as the solvent (entries 2–5). A control reaction
without NaBHEt3 gave 2a in 80% yield, showing that Et2Zn is
not only a good hydrogen source, but that it can also acti-
vate the iron precatalyst (entry 6). In the absence of an ad-
ditional solvent, the yield of 2a increased to 87% (entry 7).
No product was obtained in the absence of the reductant or
the iron catalyst (entries 8 and 9). The reaction did not oc-
cur efficiently when EtMgBr, i-PrMgBr, or t-BuMgCl was
used as a reductant instead of Et2Zn (entries 10–12). The re-
action is operationally simple and practicable with a com-
bination of the iron precatalyst, Et2Zn, and the enyne. Addi-
tionally, iron complexes II9 and III,10 which have been re-
ported to act as precatalysts for reductive cyclization of
1,6-enynes, did not catalyze the reaction under the simple
conditions (entries 13 and 14). The PyBOX iron complex IV
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

B
T. Xi et al.
Special Topic
Synthesis
did catalyze the cyclization reaction, but less efficiently, af-
fording 2a in 46% yield (entry 15). These control experi-
ments with various iron complexes showed that our devel-
oped iron complex I has a unique reactivity for this trans-
formation.
2f in 84% yield, showing that the interaction of the lone pair
of the methoxy group with the iron species had been over-
come.12 A variety of electron-donating and electron-with-
drawing functional groups, such as hydroxy, ketone, ester,
nitrile, trifluoromethyl, halo, amino, amido, imino, silyl,
and alkynyl were tolerated under the mild conditions. Cya-
no, acetyl, or imino groups slowed down the reaction, pos-
sibly through weak coordination to the iron catalyst. Naph-
thyl or hetaryl 1,6-enynes gave pyrrolidines 2s and 2t in
49% and 79% yield, respectively. Alkynes with a terminal
phenylethynyl, pentyl, cyclopropyl, or trimethylsilyl group
or a hydrogen atom readily gave the corresponding reduc-
tive cyclization products 2u–y. A high diastereoselectivity
was observed in the reaction of enyne 1z with a phenyl
substituent at the 3-position. 1,7-Enynes were also suitable
for this transformation, giving tetrahydropyrans 2aa–ac in
slightly lower yields. The presence of a terminal double
bond is necessary for this transformation.
Table 1 Optimization Studies for Reductive Cyclization of 1,6-Enynes
Ph
Ph
iron catalyst (5 mol%)
O
O
Et2Zn (2.5 equiv)
r.t., argon, 1.5 h
2a
1a
O
iPr
N
iPr
iPr
N
N
N
N
N
Fe
Fe
Bn
Cl
iPr
Cl
iPr
Cl
Cl
iPr
II
I
iPr
O
O
N
Ph
Ph
Ph
Ph
N
N
OMe
Fe
N
N
Fe
EtO2C
EtO2C
Cl
iPr
Cl
Bn
MeN
Bn
BnN
TsN
Cl
TsN
Cl
III
IV
2e: 63%a
2b: 92%
2c 73%
2d: 76%
2f: 84%
Entry
Iron catalyst Solvent
Reductant
Yielda of 2a (%)
Y
2g: Y = 3-OMe, 74% 2m: Y = 4-CN, 47%a
2h: Y = 4-OMe, 69% 2n: Y = 4-CO2Et, 74%
1
2
Ib
Ib
Ib
Ib
Ib
I
toluene
Et2Zn
Et2Zn
Et2Zn
Et2Zn
Et2Zn
Et2Zn
Et2Zn
–
44
2i: Y = 4-Me, 79%
2j: Y = 4-Cl, 78%
2k: Y = 4-Br, 71%
2l: Y = 4-CF3, 75%
2o: Y = 4-COMe, 41%
2p: Y = 4-CH2OH, 56%
2q: Y = 3,5-Me2, 73%
1,4-dioxane
28
3
CH2Cl2
14
TsN
4
Et2O
32
Ar
N
5
THF
20
Ph
6
toluene
80
S
C5H11
7
I
–
–
–
–
–
–
–
–
–
87(72)c
TsN
8
I
0
0
TsN
TsN
TsN
9
–
I
Et2Zn
EtMgBr
i-PrMgBr
t-BuMgCl
Et2Zn
Et2Zn
Et2Zn
TsN
10
11
12
13
14
15
5
2v: 75%
Ar = 2,6-iPr2C6H3
2r: 48%a
2s: 49%
2t: 79%
2u: 41%
I
4
Y
I
9
II
III
IV
6
Ph
TMS
TsN
6
O
TsN
O
TsN
46
2aa: Y = H, 49%a
2ab: Y = OMe, 51%a
2ac: Y = Cl, 44%a
a Determined by 1H NMR analysis using PhTMS as an internal standard.
Ph
2z: 65%, dr > 20:1
b With 15 mol% NaBHEt3.
c Isolated yield.
2w: 60%
2x: 90%
2y: 54%
Figure 1 Products of the iron-catalyzed reductive cyclization reactions
of 1,6- and 1,7-enynes. Reagents and conditions: iron complex I (0.025
mmol), enyne (0.5 mmol), Et2Zn (1.25 mmol), r.t., under argon, 1.5 h
(a 24 h).
Having identified the optimal conditions, we studied
the scope of this process, as shown in Figure 1. A high syn-
selectivity was observed in all cases. Oxygen-, nitrogen-,
and carbon11-tethered 1,6-enynes were suitable for this
process, giving tetrahydrofurans 2a and 2z, pyrrolidines
2b–d and 2f–y, and cyclopentane 2e, respectively. The 1,6-
enyne 1f with a methoxy group in the ortho-position of the
phenyl ring participated in the reaction to give pyrrolidine
When quenched with D2O or MeOD, the mixture from
the reaction of 1b gave the corresponding cyclization prod-
uct with >99% deuteration at the methyl position and 69%
deuteration at the vinyl position. A proposed catalytic cycle
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

C
T. Xi et al.
Special Topic
Synthesis
is shown in Scheme 1. The iron complex I is reduced by
Et2Zn and then reacts with enyne 1b to afford an iron–cy-
clopentene species A with high syn-stereoselectivity. This
putative intermediate A might undergo transmetalation
with Et2Zn to form the iron–zinc organobimetallic interme-
diate B, which then either undergoes secondary transmeta-
lation with Et2Zn to form the organodizinc species C or it
undergoes elimination of a β-hydrogen and reductive elimi-
nation to give the organozinc species E. Intermediates C and
E are quenched by saturated aqueous NH4Cl or ethanol to
afford the reductive cyclization products. Both the possible
pathways would result in regeneration of active iron spe-
cies that might react efficiently with the 1,6-enyne to re-
form the iron–cyclopentene species A. Although the nature
of the oxazoline iminopyridine ligand is unknown, we spec-
ulated that this unique ligand might stabilize the active iron
species and promote the catalytic cycle.
Ph
Ph
iron complex V (5 mol%)
BnN
BnN
*
Et2Zn (2.5 equiv), Ar, r.t., 1.5 h
(_)-2b
66% yield
39% ee
1b
O
N
N
N
Fe
tBu
Cl Cl
V
Scheme 2 Asymmetric reductive cyclization of a 1,6-enyne
In summary, we have developed an efficient and opera-
tionally simple iron-catalyzed reductive cyclization of 1,6-
and 1,7-enynes in the presence of an oxazoline iminopyri-
dine ligand to give tetrahydrofurans, pyrrolidines, cyclo-
pentanes, or tetrahydropyrans. Hydroxy, ketone, ester,
ether, halo, amino, amido, imino, nitrile, silyl, and alkyne
groups are tolerated under the simple reaction conditions.
A speculative mechanism is proposed on the basis of deu-
teration studies. A primary asymmetric reductive cycliza-
tion of an enyne was realized with moderate enantioselec-
tivity. Current studies in our laboratory are underway to
elucidate the mechanistic intricacies of this process and to
improve the asymmetric transformation.
Ph
1) iron complex I (5 mol%),
Et2Zn (2.5 equiv), argon, r.t., 1.5 h
Ph
D (69% D)
BnN
BnN
2) D2O or MeOD, –78 °C
D (>99% D)
D2O 2b: 89% yield
MeOD 2b: 85% yield
1b
L[Fe]
Et2Zn
1b
Ph
H
BnN
Ph
Fe
1b
E
EtZn
BnN
L
Diethyl ether, tetrahydrofuran, dioxane and toluene were distilled
from sodium benzophenone ketyl prior to use. Dichloromethane was
distilled from calcium hydride. Diethylzinc (1.0 mol/L in toluene) was
purchased from Energy Chemical. The other commercially available
chemicals were used as received. NMR spectra were recorded on a
Bruker-400 instrument. 1H NMR chemical shifts were referenced to
tetramethylsilane (0 ppm), and 13C NMR chemical shifts were refer-
enced to the solvent resonance (77.00 ppm, CDCl3). The following ab-
breviations (or combinations thereof) were used to explain multiplic-
ities: s = singlet, d = doublet, t = triplet, m = multiplet, br = broad, q =
quadruplet. IR spectra were recorded on a Perkin-Elmer Spectrum
One FTIR spectrometer with a diamond ATR accessory. High-resolu-
tion mass spectra (HRMS) were recorded on EI-TOF (electrospray ion-
ization–time of flight). Enynes and iron complexes have been synthe-
sized according to the reported methods, see the Supporting Informa-
tion.
A
1b
Ph
Et2Zn
L
Fe
BnN
H
EtZn
D
Ph
L
Et2Zn
H
Fe
Ph
BnN
ZnEt
C2H4
BnN
ZnEt
B
ZnEt
C
Scheme 1 Deuteration study and a plausible mechanism for the re-
ductive cyclization
Reductive Cyclization; General Procedure A
A 25 mL Schlenk flask was flame dried, cooled under Ar, and charged
with iron complex I (0.025 mmol) and a 1.0 M soln of Et2Zn in toluene
(1.25 mL). The mixture was stirred for 5 min, then enyne 1 (0.5 mmol)
was added and the resulting mixture was stirred at r.t. for 1.5 h. The
reaction was quenched with sat. aq NH4Cl (5 mL) at –78 °C, and then
the mixture was gradually warmed to r.t. and stirred for 2 h. The mix-
ture was extracted with Et2O (3 × 10 mL), and the organic phases
were combined, dried (Na2SO4), and concentrated in vacuo. The resi-
due was purified by column chromatography [silica gel, EtOAc–PE
(1:10)].
The primary enantioselective reaction of 1,6-enyne 1b
with Et2Zn in the presence of 5 mol% of chiral iron complex
V gave the chiral cyclization product 2b in 66% yield and
39% ee (Scheme 2). To the best of our knowledge, this is the
first example of an iron-catalyzed asymmetric reductive cy-
clization of a 1,6-enyne.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

D
T. Xi et al.
Special Topic
Synthesis
Reductive Cyclization; General Procedure B
1H NMR (400 MHz, CDCl3): δ = 7.72 (d, J = 8.2 Hz, 2 H), 7.40–7.28 (m, 4
H), 7.26–7.20 (m, 1 H), 7.14 (d, J = 7.5 Hz, 2 H), 6.22 (d, J = 2.0 Hz, 1 H),
4.29–4.20 (m, 1 H), 4.09–4.01 (m, 1 H), 3.60–3.51 (m, 1 H), 2.93–2.81
(m, 1 H), 2.73 (t, J = 8.7 Hz, 1 H), 2.41 (s, 3 H), 1.17 (d, J = 6.7 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.6, 141.8, 136.5, 132.9, 129.7,
128.5, 128.0, 127.7, 126.9, 122.0, 53.8, 50.8, 39.1, 21.5, 16.9.
A 25 mL Schlenk flask was flame dried, cooled under Ar, and charged
with iron complex I (0.025 mmol) and a 1.0 M soln of Et2Zn in toluene
(1.25 mL). The mixture was stirred for 5 min, then enyne 1 (0.5 mmol)
was added and the resulting mixture was stirred at r.t. for 1.5 h. The
reaction was quenched with EtOH (5 mL) at r.t., and the mixture was
filtered through a plug of silica gel that was washed with Et2O. The
filtrate was concentrated in vacuo, and the residue was purified by
column chromatography [silica gel, EtOAc–PE (1:10)].
Diethyl (3E)-3-Benzylidene-4-methylcyclopentane-1,1-dicarbox-
ylate (2e)3d
Prepared by General Procedure A from iron complex I (0.0161 g, 0.028
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and diethyl 2-allyl-2-(3-
phenylprop-2-yn-1-yl)malonate (1e; 0.1642 g, 0.5 mmol) to give a
colorless oil; yield: 0.1059 g (63%, E/Z > 20:1).
1H NMR (400 MHz, CDCl3): δ = 7.36–7.27 (m, 4 H), 7.23–7.13 (m, 1 H),
6.22 (d, J = 2.2 Hz, 1 H), 4.26–4.10 (m, 4 H), 3.42–3.32 (m, 1 H), 3.25–
3.16 (m, 1 H), 2.85–2.70 (m, 1 H), 2.65–2.54 (m, 1 H), 1.76 (t, J = 12.4
Hz, 1 H), 1.32–1.15 (m, 9 H).
(3Z)-3-Benzylidene-4-methyltetrahydrofuran (2a)3j
Prepared by General Procedure A from iron complex I (0.0158 g, 0.028
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and [3-(allyloxy)prop-1-yn-
1-yl]benzene (1a; 87 μL, 0.5 mmol) to give a colorless oil; yield:
0.0625 g (72%, Z/E > 20:1).
1H NMR (400 MHz, CDCl3): δ = 7.38–7.30 (m, 2 H), 7.24–7.18 (m, 1 H),
7.18–7.08 (m, 2 H), 6.30 (d, J = 2.2 Hz, 1 H), 4.80–4.54 (m, 2 H), 4.08 (t,
J = 7.9 Hz, 1 H), 3.39 (t, J = 8.1 Hz, 1 H), 2.98–2.84 (m, 1 H), 1.22 (d,
J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.8, 171.7, 146.3, 137.9, 128.23,
128.18, 126.1, 121.4, 61.5, 59.1, 41.3, 39.0, 38.8, 18.3, 14.0, 13.9.
13C NMR (100 MHz, CDCl3): δ = 146.5, 137.4, 128.5, 127.9, 126.5,
119.9, 74.3, 70.3, 39.8, 16.4.
(3Z)-3-(2-Methoxybenzylidene)-4-methyl-1-tosylpyrrolidine
(2f)12
(3Z)-1-Benzyl-3-benzylidene-4-methylpyrrolidine (2b)
Prepared by General Procedure B from iron complex I (0.0156 g, 0.028
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-N-[3-(2-meth-
Prepared by General Procedure B from iron complex I (0.0149 g, 0.026
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-benzyl-N-(3-phenyl-
prop-2-yn-1-yl)prop-2-en-1-amine (1b; 125 μL, 0.5 mmol) to give a
colorless oil; yield: 0.1216 g (92%, Z/E > 20:1).
oxyphenyl)prop-2-yn-1-yl]-4-methylbenzenesulfonamide
(1f;
0.1808 g, 0.5 mmol) to give a white solid; yield: 0.1522 g (84%, Z/E >
20:1); mp 125–127 °C.
IR (neat): 3059, 2961, 1688, 1599, 1493, 1450 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.69 (d, J = 8.2 Hz, 2 H), 7.29 (d, J = 8.1
Hz, 2 H), 7.26–7.20 (m, 1 H), 7.06 (d, J = 7.5 Hz, 1 H), 6.95 (t, J = 7.4 Hz,
1 H), 6.86 (d, J = 8.2 Hz, 1 H), 6.48 (d, J = 2.1 Hz, 1 H), 4.20–4.12 (m, 1
H), 4.04–3.95 (m, 1 H), 3.80 (s, 3 H), 3.59–3.51 (m, 1 H), 2.94–2.81 (m,
1 H), 2.75 (t, J = 8.2 Hz, 1 H), 2.41 (s, 3 H), 1.17 (d, J = 6.7 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.45–7.21 (m, 7 H), 7.21–7.12 (m, 3 H),
6.22 (d, J = 2.1 Hz, 1 H), 3.84–3.75 (m, 1 H), 3.69 (s, 2 H), 3.39–3.29 (m,
1 H), 3.00 (t, J = 7.9 Hz, 1 H), 2.95–2.83 (m, 1 H), 2.11 (t, J = 8.2 Hz, 1
H), 1.20 (d, J = 6.5 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 156.5, 143.5, 141.7, 133.1, 129.6,
128.6, 128.4, 127.7, 125.5, 120.4, 116.7, 110.5, 55.4, 54.0, 50.6, 39.0,
21.5, 17.0.
13C NMR (100 MHz, CDCl3): δ = 147.4, 138.9, 138.1, 128.7, 128.28,
128.26, 127.8, 126.9, 126.0, 120.3, 61.2, 60.6, 58.5, 39.2, 18.0.
HRMS (EI): m/z calcd for [C19H21N]+: 263.1674; found: 263.1671.
(3Z)-3-(3-Methoxybenzylidene)-4-methyl-1-tosylpyrrolidine
(3Z)-3-Benzylidene-1,4-dimethylpyrrolidine (2c)
(2g)12
Prepared by General Procedure B from complex I (0.0146 g, 0.025
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-methyl-N-(3-phenyl-
prop-2-yn-1-yl)prop-2-en-1-amine (1c; 98 μL, 0.5 mmol) to give a
colorless oil; yield: 0.0686 g (73%, Z/E > 20:1).
Prepared by General Procedure B from iron complex I (0.0140 g, 0.025
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-N-[3-(3-meth-
oxyphenyl)prop-2-yn-1-yl]-4-methylbenzenesulfonamide
0.1779 g, 0.5 mmol) to give a white solid; yield: 0.1318 g (74%, Z/E >
20:1); mp 128–129 °C.
(1g;
IR (neat): 2960, 2932, 2770, 1691, 1660, 1494, 1448 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.36–7.28 (m, 2 H), 7.24–7.14 (m, 3 H),
6.21 (d, J = 2.2 Hz, 1 H), 3.75 (dd, J = 1.1, 14.6 Hz, 1 H), 3.34–3.26 (m, 1
H), 3.04–2.84 (m, 2 H), 2.42 (s, 3 H), 2.11 (t, J = 8.0 Hz, 1 H), 1.22 (d,
J = 6.7 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 8.2 Hz, 2 H), 7.35–7.23 (m, 3
H), 6.79 (dd, J = 8.3, 2.3 Hz, 1 H), 6.73 (d, J = 7.7 Hz, 1 H), 6.66 (s, 1 H),
6.19 (d, J = 2.2 Hz, 1 H), 4.52–4.18 (m, 1 H), 4.09–3.99 (m, 1 H), 3.81 (s,
3 H), 3.59–3.51 (m, 1 H), 2.92–2.80 (m, 1 H), 2.72 (t, J = 8.8 Hz, 1 H),
2.41 (s, 3 H), 1.16 (d, J = 6.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 147.7, 138.1, 128.3, 127.9, 126.1,
13C NMR (100 MHz, CDCl3): δ = 159.6, 143.6, 142.2, 137.9, 132.9,
129.7, 129.5, 127.7, 122.0, 120.4, 114.0, 112.3, 55.2, 53.8, 50.8, 39.0,
21.5, 16.9.
120.2, 63.6, 60.5, 42.6, 39.8, 18.0.
HRMS (EI): m/z calcd for [C13H17N]+: 187.1361; found: 187.1363.
(3Z)-3-Benzylidene-4-methyl-1-tosylpyrrolidine (2d)3j
(3Z)-3-(4-Methoxybenzylidene)-4-methyl-1-tosylpyrrolidine
Prepared by General Procedure B from iron complex I (0.0151 g, 0.027
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-4-methyl-N-(3-
phenylprop-2-yn-1-yl)benzenesulfonamide (1d; 0.1643 g, 0.5 mmol)
to give a white solid; yield: 0.1251 g (76%, Z/E > 20:1); mp 94–95 °C.
(2h)12
Prepared by General Procedure B from iron complex I (0.0147 g, 0.025
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-N-[3-(4-meth-
oxyphenyl)prop-2-yn-1-yl]-4-methylbenzenesulfonamide
(1h;
0.1802 g, 0.5 mmol) to give a white solid; yield: 0.1248 g (69%, Z/E >
20:1); mp 131–133 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

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Special Topic
Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.72 (d, J = 8.2 Hz, 2 H), 7.31 (d, J = 8.1
Hz, 2 H), 7.08 (d, J = 8.7 Hz, 2 H), 6.88 (d, J = 8.8 Hz, 2 H), 6.15 (d,
J = 2.1 Hz, 1 H), 4.26–4.17 (m, 1 H), 4.07–3.97 (m, 1 H), 3.82 (s, 3 H),
3.57–3.49 (m, 1 H), 2.91–2.78 (m, 1 H), 2.71 (t, J = 8.8 Hz, 1 H), 2.41 (s,
3 H), 1.15 (d, J = 6.7 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.72 (d, J = 8.2 Hz, 2 H), 7.59 (d, J = 8.1
Hz, 2 H), 7.32 (d, J = 8.0 Hz, 2 H), 7.23 (d, J = 8.0 Hz, 2 H), 6.30–6.22 (m,
1 H), 4.28–4.18 (m, 1 H), 4.07–3.95 (m, 1 H), 3.62–3.52 (m, 1 H), 2.96–
2.84 (m, 1 H), 2.75 (t, J = 9.0 Hz, 1 H), 2.42 (s, 3 H), 1.18 (d, J = 6.7 Hz, 3
H).
13C NMR (100 MHz, CDCl3): δ = 158.5, 143.5, 139.5, 133.0, 129.7,
129.32, 129.30, 127.7, 121.4, 114.0, 55.3, 53.9, 50.8, 39.0, 21.5, 16.9.
13C NMR (100 MHz, CDCl3): δ = 144.7, 143.8, 140.0, 132.8, 129.8,
128.8, 128.2, 127.7, 125.5 (q, J = 3.8 Hz), 122.7, 120.9, 53.7, 50.7, 39.2,
21.5, 16.8.
(4Z)-3-Methyl-4-(4-methylbenzylidene)-1-tosylpyrrolidine (2i)
4-[(Z)-(4-Methyl-1-tosylpyrrolidin-3-ylidene)methyl]benzonitrile
(2m)
Prepared by General Procedure B from iron complex I (0.0152 g, 0.027
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-4-methyl-N-[3-
(4-tolyl)prop-2-yn-1-yl]benzenesulfonamide (1i; 0.1706 g, 0.5 mmol)
to give a colorless oil; yield: 0.1353 g (79%, Z/E > 20:1).
Prepared by General Procedure B from iron complex I (0.0141 g, 0.025
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-N-[3-(4-cyano-
phenyl)prop-2-yn-1-yl]-4-methylbenzenesulfonamide (1m; 0.1782
g, 0.5 mmol) to give a colorless oil; yield: 0.0845 g (47%, Z/E > 20:1)
[recovered 1m: 0.0478 g (27%)].
IR (neat): 2968, 2924, 1596, 1512, 1449, 1376, 1335 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.72 (d, J = 8.2 Hz, 2 H), 7.30 (d, J = 8.2
Hz, 2 H), 7.15 (d, J = 8.0 Hz, 2 H), 7.03 (d, J = 8.0 Hz, 2 H), 6.18 (d,
J = 2.0 Hz, 1 H), 4.27–4.19 (m, 1 H), 4.08–4.00 (m, 1 H), 3.58–3.50 (m,
1 H), 2.92–2.77 (m, 1 H), 2.71 (t, J = 8.3 Hz, 1 H), 2.41 (s, 3 H), 2.34 (s, 3
H), 1.15 (d, J = 6.7 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.5, 140.7, 136.8, 133.7, 133.0,
129.7, 129.2, 128.0, 127.7, 121.9, 53.8, 50.8, 39.0, 21.5, 21.1, 16.9.
IR (neat): 2967, 2871, 2226, 1662, 1602, 1344 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.72 (d, J = 8.1 Hz, 2 H), 7.63 (d, J = 8.1
Hz, 2 H), 7.33 (d, J = 8.1 Hz, 2 H), 7.22 (d, J = 8.1 Hz, 2 H), 6.24 (d,
J = 2.0 Hz, 1 H), 4.26–4.19 (m, 1 H), 4.06–3.97 (m, 1 H), 3.62–3.54 (m,
1 H), 2.99–2.85 (m, 1 H), 2.75 (t, J = 8.5 Hz, 1 H), 2.43 (s, 3 H), 1.19 (d,
J = 6.7 Hz, 3 H).
HRMS (EI): m/z calcd for [C20H23NO2S]+: 341.1450; found: 341.1451.
13C NMR (100 MHz, CDCl3): δ = 146.2, 143.9, 140.9, 132.7, 132.3,
129.8, 128.5, 127.7, 120.8, 118.7, 110.3, 53.6, 50.8, 39.4, 21.5, 16.8.
HRMS (EI): m/z calcd for [C20H20N2O2S]+: 352.1245; found: 352.1243.
(3Z)-3-(4-Chlorobenzylidene)-4-methyl-1-tosylpyrrolidine (2j)3m
Prepared by General Procedure B from iron complex I (0.0144 g, 0.026
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-N-[3-(4-chloro-
phenyl)prop-2-yn-1-yl]-4-methylbenzenesulfonamide (1j; 0.1686 g,
0.5 mmol) to give a white solid; yield: 0.1294 g (78%, Z/E > 20:1); mp
167–168 °C.
1H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 8.2 Hz, 2 H), 7.36–7.27 (m, 4
H), 7.06 (d, J = 8.3 Hz, 2 H), 6.17 (d, J = 2.0 Hz, 1 H), 4.24–4.15 (m, 1 H),
4.04–3.94 (m, 1 H), 3.60–3.51 (m, 1 H), 2.92–2.80 (m, 1 H), 2.72 (t,
J = 8.9 Hz, 1 H), 2.42 (s, 3 H), 1.16 (d, J = 6.7 Hz, 3 H).
Ethyl 4-[(Z)-(4-Methyl-1-tosylpyrrolidin-3-ylidene)methyl]benzo-
ate (2n)12
Prepared by General Procedure B from iron complex I (0.0161 g, 0.028
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and ethyl 4-[3-(N-allyl-4-
methylphenylsulfonamido)prop-1-yn-1-yl]benzoate (1n; 0.2001 g,
0.5 mmol) to give a white solid; yield: 0.1481 g (74%, Z/E > 20:1); mp
144–146 °C.
1H NMR (400 MHz, CDCl3): δ = 8.01 (d, J = 8.2 Hz, 2 H), 7.72 (d, J = 8.0
Hz, 2 H), 7.32 (d, J = 8.2 Hz, 2 H), 7.19 (d, J = 8.2 Hz, 2 H), 6.26 (d,
J = 1.8 Hz, 1 H), 4.38 (q, J = 7.2 Hz, 2 H), 4.30–4.20 (m, 1 H), 4.08–3.99
(m, 1 H), 3.62–3.53 (m, 1 H), 2.96–2.84 (m, 1 H), 2.74 (t, J = 8.9 Hz, 1
H), 2.42 (s, 3 H), 1.41 (t, J = 7.1 Hz, 3 H), 1.18 (d, J = 6.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 166.2, 144.6, 143.7, 140.8, 132.8,
129.79, 129.75, 128.8, 127.9, 127.7, 121.4, 61.0, 53.7, 50.8, 39.3, 21.5,
16.8, 14.3.
13C NMR (100 MHz, CDCl3): δ = 143.7, 142.6, 135.0, 132.8, 132.7,
129.7, 129.2, 128.7, 127.7, 120.9, 53.7, 50.7, 39.1, 21.5, 16.8.
(3Z)-3-(4-Bromobenzylidene)-4-methyl-1-tosylpyrrolidine (2k)
Prepared by General Procedure B from iron complex I (0.0142 g, 0.025
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-N-[3-(4-chloro-
phenyl)prop-2-yn-1-yl]-4-methylbenzenesulfonamide (1k; 0.2074 g,
0.5 mmol) to give a colorless oil; yield: 0.1484 g (71%, Z/E > 20:1).
IR (neat): 3062, 2965, 2929, 1597, 1488, 1453, 1344 cm–1
.
1-{4-[(Z)-(4-Methyl-1-tosylpyrrolidin-3-ylidene)methyl]phe-
nyl}ethanone (2o)
1H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 8.0 Hz, 2 H), 7.46 (d, J = 8.4
Hz, 2 H), 7.31 (d, J = 8.0 Hz, 2 H), 6.99 (d, J = 8.4 Hz, 2 H), 6.15 (d,
J = 1.7 Hz, 1 H), 4.19 (d, J = 14.8 Hz, 1 H), 3.98 (d, J = 14.8 Hz, 1 H),
3.59–3.51 (m, 1 H), 2.91–2.80 (m, 1 H), 2.72 (t, J = 8.5 Hz, 1 H), 2.41 (s,
3 H), 1.16 (d, J = 6.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.7, 142.8, 135.4, 132.9, 131.6,
129.7, 129.5, 127.7, 121.0, 120.8, 53.7, 50.7, 39.1, 21.5, 16.8.
Prepared by General Procedure B from iron complex I (0.0141 g, 0.025
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-N-[3-(4-formyl-
phenyl)prop-2-yn-1-yl]-4-methylbenzenesulfonamide (1o; 0.1915 g,
0.5 mmol) to give a colorless oil; yield: 0.0787 g (41%, Z/E > 20:1).
IR (neat): 2966, 2929, 1679, 1601, 1344, 1268 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.94 (d, J = 8.2 Hz, 2 H), 7.72 (d, J = 8.2
Hz, 2 H), 7.32 (d, J = 8.1 Hz, 2 H), 7.22 (d, J = 8.1 Hz, 2 H), 6.27 (d,
J = 1.9 Hz, 1 H), 4.30–4.20 (m, 1 H), 4.10–4.00 (m, 1 H), 3.62–3.58 (m,
1 H), 2.98–2.84 (m, 1 H), 2.74 (t, J = 8.5 Hz, 1 H), 2.61 (s, 3 H), 2.42 (s, 3
H), 1.19 (d, J = 6.7 Hz, 3 H).
HRMS (EI): m/z calcd for [C19H20BrNO2S]+: 405.0398; found: 405.0393.
(4Z)-3-Methyl-1-tosyl-4-[4-(trifluoromethyl)benzylidene]pyrroli-
dine (2l)6
Prepared by General Procedure B from iron complex I (0.0148 g, 0.026
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-4-methyl-N-[3-
(4-(trifluoromethyl)phenyl]prop-2-yn-1-yl)benzenesulfonamide (1l;
0.1983 g, 0.5 mmol) to give a white solid; yield: 0.1502 g (75%, Z/E >
20:1); mp 159–161 °C.
13C NMR (100 MHz, CDCl3): δ = 197.4, 144.9, 143.7, 141.1, 135.3,
132.7, 129.7, 128.6, 128.1, 127.7, 121.3, 53.7, 50.9, 39.3, 26.5, 21.5,
16.8.
HRMS (EI): m/z calcd for [C21H23NO3S]+: 369.1399; found: 369.1400.
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Special Topic
Synthesis
1-{4-[(Z)-(4-Methyl-1-tosylpyrrolidin-3-ylidene)methyl]phe-
nyl}methanol (2p)
1H NMR (400 MHz, CDCl3): δ = 7.89–7.81 (m, 2 H), 7.77 (d, J = 8.2 Hz, 1
H), 7.62 (d, J = 8.2 Hz, 2 H), 7.53–7.40 (m, 3 H), 7.27–7.17 (m, 3 H),
6.78 (d, J = 1.6 Hz, 1 H), 4.16–4.06 (m, 1 H), 3.92–3.81 (m, 1 H), 3.69–
3.60 (m, 1 H), 3.01–2.89 (m, 1 H), 2.79 (t, J = 8.6 Hz, 1 H), 2.37 (s, 3 H),
1.28 (d, J = 6.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 144.0, 143.5, 133.6, 133.5, 133.1,
131.3, 129.6, 128.5, 127.8, 127.6, 126.0, 125.9, 125.7, 125.4, 124.1,
119.5, 54.3, 50.5, 38.5, 21.5, 16.8.
Prepared by General Procedure B from iron complex I (0.0155 g, 0.027
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-N-{3-[4-(hy-
droxymethyl)phenyl]prop-2-yn-1-yl}-4-methylbenzenesulfonamide
(1p; 0.1791 g, 0.5 mmol) to give a colorless oil; yield: 0.1017 g (56%,
Z/E > 20:1).
IR (neat): 3522, 2965, 2927, 1598, 1453, 1340 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 8.3 Hz, 2 H), 7.38–7.28 (m, 4
H), 7.13 (d, J = 8.0 Hz, 2 H), 6.21 (d, J = 2.2 Hz, 1 H), 4.69 (d, J = 4.0 Hz,
2 H), 4.28–4.19 (m, 1 H), 4.08–3.98 (m, 1 H), 3.60–3.51 (m, 1 H), 2.94–
2.81 (m, 1 H), 2.72 (t, J = 8.5 Hz, 1 H), 2.41 (s, 3 H), 1.95–1.85 (m, 1 H),
1.16 (d, J = 6.7 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.6, 141.8, 139.6, 135.9, 132.9,
129.7, 128.2, 127.7, 127.1, 121.7, 64.9, 53.8, 50.8, 39.1, 21.5, 16.8.
(4Z)-3-Methyl-4-(2-thienylmethylene)-1-tosylpyrrolidine (2t)6
Prepared by General Procedure B from iron complex I (0.0141 g, 0.025
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-4-methyl-N-[3-
(2-thienyl)prop-2-yn-1-yl]benzenesulfonamide (1t; 0.1786 g, 0.5
mmol) to give a white solid; yield: 0.1408 g (79%, Z/E > 20:1); mp 97–
98 °C.
1H NMR (400 MHz, CDCl3): δ = 7.74 (d, J = 8.2 Hz, 2 H), 7.36–7.27 (m, 3
H), 7.05–7.00 (m, 1 H), 6.90–6.85 (m, 1 H), 6.40 (d, J = 1.8 Hz, 1 H),
4.24–4.14 (m, 1 H), 4.04–3.96 (m, 1 H), 3.62–3.54 (m, 1 H), 2.95–2.83
(m, 1 H), 2.72 (t, J = 8.8 Hz, 1 H), 2.42 (s, 3 H), 1.15 (d, J = 6.8 Hz, 3 H).
HRMS (EI): m/z calcd for [C20H23NO3S]+: 357.1399; found: 357.1400.
(3Z)-3-(3,5-Dimethylbenzylidene)-4-methyl-1-tosylpyrrolidine
(2q)
13C NMR (100 MHz, CDCl3): δ = 143.7, 140.3, 132.5, 129.7, 127.8,
127.4, 126.2, 125.5, 115.0, 54.5, 51.3, 38.7, 21.5, 16.7.
Prepared by General Procedure A from iron complex I (0.0142 g, 0.025
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-N-[3-(3,5-di-
methylphenyl)prop-2-yn-1-yl]-4-methylbenzenesulfonamide
0.1768 g, 0.5 mmol) to give a white solid; yield: 0.1310 g (73%, Z/E >
20:1); mp 104–105 °C.
(1q;
(4Z)-3-Methyl-4-(3-phenylprop-2-yn-1-ylidene)-1-tosylpyrroli-
dine (2u)
Prepared by General Procedure B from iron complex I (0.0049 g,
0.0075 mmol), Et2Zn (0.38 mL, 1.0 M in toluene), and N-allyl-4-meth-
yl-N-(5-phenylpenta-2,4-diyn-1-yl)benzenesulfonamide (1u; 0.0524
g, 0.15 mmol) to give a colorless oil; yield: 0.0215 g (41%, Z/E > 20:1).
1H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 8.2 Hz, 2 H), 7.30 (d, J = 8.2
Hz, 2 H), 6.88 (s, 1 H), 6.75 (s, 2 H), 6.15 (d, J = 1.7 Hz, 1 H), 4.24 (d,
J = 15.2 Hz, 1 H), 4.05 (d, J = 15.2 Hz, 1 H), 3.58–3.50 (m, 1 H), 2.88–
2.76 (m, 1 H), 2.71 (t, J = 8.5 Hz, 1 H), 2.41 (s, 3 H), 2.31 (s, 6 H), 1.14
(d, J = 6.6 Hz, 3 H).
IR (neat): 3060, 2965, 2928, 1597, 1490, 1451, 1399 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.74 (d, J = 7.8 Hz, 2 H), 7.45–7.39 (m, 2
H), 7.38–7.30 (m, 5 H), 5.52 (s, 1 H), 4.18 (d, J = 16.2 Hz, 1 H), 4.00 (d,
J = 16.2 Hz, 1 H), 3.62 (t, J = 8.0 Hz, 1 H), 2.88–2.69 (m, 2 H), 2.44 (s, 3
H), 1.10 (d, J = 6.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.5, 141.2, 138.0, 136.5, 133.1,
129.7, 128.7, 127.7, 125.9, 122.2, 53.8, 50.6, 39.0, 21.5, 21.3, 16.9.
2,6-Diisopropyl-N-((1E)-1-{4-[(Z)-(4-methyl-1-tosylpyrrolidin-3-
ylidene)methyl]phenyl}ethylidene)aniline (2r)
13C NMR (100 MHz, CDCl3): δ = 155.1, 143.7, 132.7, 131.4, 129.8,
128.4, 127.8, 123.0, 101.9, 95.0, 85.3, 55.1, 52.0, 37.9, 21.5, 16.3.
HRMS (EI): m/z calcd for [C21H21NO2S]+: 351.1293; found: 351.1295.
Prepared by General Procedure B from iron complex I (0.0096 g,
0.0162 mmol), Et2Zn (0.81 mL, 1.0 M in toluene), and (E)-N-allyl-N-
[3-(4-{1-[(2,6-diisopropylphenyl)imino]ethyl}phenyl)prop-2-yn-1-yl]-
4-methylbenzenesulfonamide (1r; 0.1716 g, 0.326 mmol) to give a
colorless oil; yield: 0.0825 g (48%, Z/E > 20:1) [recovered 1r: 0.0532 g
(31%)].
(3Z)-3-Hexylidene-4-methyl-1-tosylpyrrolidine (2v)12
Prepared by General Procedure B from iron complex I (0.0141 g, 0.025
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-4-methyl-N-
(oct-2-yn-1-yl)benzenesulfonamide (1v; 0.1615 g, 0.5 mmol) to give
a colorless oil; yield: 0.1217 g (75%, Z/E > 20:1).
1H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 8.1 Hz, 2 H), 7.33 (d, J = 8.1
Hz, 2 H), 5.20–5.10 (m, 1 H), 3.92–3.82 (m, 1 H), 3.75–3.66 (m, 1 H),
3.56–3.46 (m, 1 H), 2.70–2.58 (m, 2 H), 2.43 (s, 3 H), 1.91–1.82 (m, 2
H), 1.36–1.15 (m, 6 H), 1.01 (d, J = 6.1 Hz, 3 H), 0.87 (t, J = 7.0 Hz, 3 H).
IR (neat): 2963, 2872, 1635, 1597, 1451, 1345 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.02 (d, J = 8.2 Hz, 2 H), 7.74 (d, J = 8.2
Hz, 2 H), 7.32 (d, J = 7.9 Hz, 2 H), 7.27–7.21 (m, 2 H), 7.15 (d, J = 7.2 Hz,
2 H), 7.11–7.04 (m, 1 H), 6.29 (d, J = 1.6 Hz, 1 H), 4.29 (d, J = 14.9 Hz, 1
H), 4.09 (d, J = 14.9 Hz, 1 H), 3.58 (dd, J = 7.5, 8.6 Hz, 1 H), 2.97–2.85
(m, 1 H), 2.80–2.70 (m, 3 H), 2.42 (s, 3 H), 2.09 (s, 3 H), 1.23–1.10 (m,
15 H).
13C NMR (100 MHz, CDCl3): δ = 164.2, 146.7, 143.6, 143.4, 138.6,
137.5, 136.0, 132.9, 129.7, 128.0, 127.7, 127.3, 123.3, 122.9, 121.6,
53.8, 50.9, 39.2, 28.2, 23.2, 22.9, 21.5, 18.0, 16.9.
13C NMR (100 MHz, CDCl3): δ = 143.4, 139.4, 132.8, 129.6, 127.7,
121.9, 55.0, 49.6, 37.1, 31.3, 29.1, 28.8, 22.4, 21.5, 16.6, 13.9.
(3Z)-3-(Cyclopropylmethylene)-4-methyl-1-tosylpyrrolidine (2w)
HRMS (EI): m/z calcd for [C33H40N2O2S]+: 528.2811; found: 528.2811.
Prepared by General Procedure A from iron complex I (0.0150 g, 0.027
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-N-(3-cyclopro-
pylprop-2-yn-1-yl)-4-methylbenzenesulfonamide (1w; 0.1490 g, 0.5
mmol) to give a colorless oil; yield: 0.0900 g (60%, Z/E > 20:1).
(4Z)-3-Methyl-4-(1-naphthylmethylene)-1-tosylpyrrolidine (2s)3n
Prepared by General Procedure B from iron complex I (0.0138 g, 0.026
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-4-methyl-N-[3-
(1-naphthyl)prop-2-yn-1-yl]benzenesulfonamide (1s; 0.1998 g, 0.5
mmol) to give a white solid; yield: 0.0987 g (49%, Z/E > 20:1); mp
132–133 °C.
IR (neat): 2965, 2870, 1597, 1453, 1343 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

G
T. Xi et al.
Special Topic
Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.72 (d, J = 8.2 Hz, 2 H), 7.33 (d, J = 8.0
Hz, 2 H), 4.63–4.52 (m, 1 H), 4.06–3.96 (m, 1 H), 3.90–3.81 (m, 1 H),
3.57–3.47 (m, 1 H), 2.70–2.57 (m, 2 H), 2.44 (s, 3 H), 1.20–1.09 (m, 1
H), 0.98 (d, J = 6.1 Hz, 3 H), 0.77–0.67 (m, 2 H), 0.35–0.25 (m, 2 H).
1H NMR (400 MHz, CDCl3): δ = 7.36–7.28 (m, 2 H), 7.24–7.15 (m, 3 H),
6.31 (s, 1 H), 3.91–3.84 (m, 1 H), 3.81–3.74 (m, 1 H), 3.59–3.49 (m, 1
H), 3.36–3.26 (m, 1 H), 2.76–2.66 (m, 1 H), 2.54–2.43 (m, 1 H), 2.39–
2.30 (m, 1 H), 1.14 (d, J = 6.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.4, 138.1, 132.9, 129.6, 127.8,
13C NMR (100 MHz, CDCl3): δ = 142.2, 137.8, 129.0, 128.1, 126.2,
125.4, 55.0, 49.9, 37.2, 21.5, 16.5, 11.0, 6.8, 6.7.
121.6, 75.1, 69.1, 38.7, 29.5, 14.8.
HRMS (EI): m/z calcd for [C16H21NO2S]+: 291.1293; found: 291.1290.
HRMS (EI): m/z calcd for [C13H16O]+: 188.1201; found: 188.1203.
(4Z)-3-Methyl-1-tosyl-4-[(trimethylsilyl)methylene]pyrrolidine
(4E)-4-(4-Methoxybenzylidene)-3-methyltetrahydro-2H-pyran
(2ab)
(2x)5a
Prepared by General Procedure A from iron complex I (0.0156 g, 0.028
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-4-methyl-N-[3-
(trimethylsilyl)prop-2-yn-1-yl]benzenesulfonamide (1x; 0.1669 g,
0.5 mmol) to give a colorless oil; yield: 0.1509 g (90%, Z/E > 20:1).
Prepared by General Procedure A from iron complex I (0.0149 g, 0.026
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and 1-[4-(allyloxy)but-1-
yn-1-yl]-4-methoxybenzene (1ab; 0.1100 g, 0.5 mmol) to give a col-
orless oil; yield: 0.0565 g (51%, E/Z > 20:1).
IR (neat): 2956, 1637, 1598, 1494, 1454 cm–1
.
IR (neat): 2958, 2839, 1608, 1511, 1463 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.69 (d, J = 8.0 Hz, 2 H), 7.32 (d, J = 8.0
Hz, 2 H), 5.30 (d, J = 1.6 Hz, 1 H), 3.93 (dd, J = 14.7, 2.0 Hz, 1 H), 3.71
(d, J = 14.7 Hz, 1 H), 3.59–3.54 (m, 1 H), 2.68–2.56 (m, 2 H), 2.42 (s, 3
H), 1.00 (d, J = 6.0 Hz, 3 H), 0.04 (s, 9 H).
1H NMR (400 MHz, CDCl3): δ = 7.11 (d, J = 8.7 Hz, 2 H), 6.86 (d, J = 8.4
Hz, 2 H), 6.25 (s, 1 H), 3.90–3.72 (m, 5 H), 3.58–3.49 (m, 1 H), 3.35–
2.56 (m, 1 H), 2.75–2.65 (m, 1 H), 2.52–2.41 (m, 1 H), 2.39–2.28 (m, 1
H), 1.13 (d, J = 6.7 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 157.1, 143.5, 132.6, 129.6, 127.7,
13C NMR (100 MHz, CDCl3): δ = 158.0, 140.9, 130.2, 130.0, 121.0,
119.5, 54.3, 51.5, 39.9, 21.4, 16.1, –0.7.
113.6, 75.1, 69.0, 55.2, 38.7, 29.4, 14.9.
HRMS (EI): m/z calcd for [C16H25NO2SSi]+: 323.1375; found: 323.1379.
HRMS (EI): m/z calcd for [C14H18O2]+: 218.1307; found: 218.1306.
3-Methyl-4-methylene-1-tosylpyrrolidine (2y)13
(4E)-4-(4-Chlorobenzylidene)-3-methyltetrahydro-2H-pyran (2ac)
Prepared by General Procedure B from iron complex I (0.0148 g, 0.026
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and N-allyl-4-methyl-N-
(prop-2-yn-1-yl)benzenesulfonamide (1y; 0.1263 g, 0.5 mmol) to
give a colorless oil; yield: 0.0754 g (60%, Z/E > 20:1).
Prepared by General Procedure A from iron complex I (0.0152 g, 0.027
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and 1-[4-(allyloxy)but-1-
yn-1-yl]-4-chlorobenzene (1ac; 0.1040 g, 0.5 mmol) to give a color-
less oil; yield: 0.0461 g (44%, E/Z > 20:1).
1H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 8.1 Hz, 2 H), 7.33 (d, J = 8.1
Hz, 2 H), 4.90 (d, J = 1.9 Hz, 1 H), 4.85 (d, J = 1.9 Hz, 1 H), 3.99–3.90 (m,
1 H), 3.79–3.69 (m, 1 H), 3.63–3.57 (m, 1 H), 2.75–2.60 (m, 2 H), 2.43
(s, 3 H), 1.04 (d, J = 6.2 Hz, 3 H).
IR (neat): 2960, 2843, 1651, 1592, 1490, 1463, 1382 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.28 (d, J = 8.3 Hz, 2 H), 7.11 (d, J = 8.3
Hz, 2 H), 6.25 (s, 1 H), 3.91–3.84 (m, 1 H), 3.82–3.74 (m, 1 H), 3.67–
3.48 (m, 1 H), 3.34–3.26 (m, 1 H), 2.70–2.61 (m, 1 H), 2.53–2.42 (m, 1
H), 2.37–2.27 (m, 1 H), 1.13 (d, J = 6.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 149.3, 143.6, 132.9, 129.6, 127.8,
106.0, 55.1, 52.1, 37.4, 21.5, 16.0.
13C NMR (100 MHz, CDCl3): δ = 143.0, 136.1, 131.9, 130.2, 128.3,
120.4, 75.0, 68.9, 38.7, 29.4, 14.7.
HRMS (EI): m/z calcd for [C13H15ClO]+: 222.0811; found: 222.0809.
(4Z)-4-Benzylidene-3-methyl-2-phenyltetrahydrofuran (2z)
Prepared by General Procedure A from iron complex I (0.0147 g, 0.026
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and {3-[(1-phenylal-
lyl)oxy]prop-1-yn-1-yl}benzene (1z; 0.1229 g, 0.5 mmol) to give a
colorless oil; yield: 0.0807 g (65%, Z/E > 20:1, dr > 20:1).
(3Z)-1-Benzyl-3-benzylidene-4-methylpyrrolidine (2b); Enantio-
selective Preparation
A 25 mL Schlenk flask was flame dried, cooled under Ar, and charged
with iron complex V (0.0117 g, 0.025 mmol) and a 1.0 M soln of Et2Zn
in toluene (1.25 mL). The mixture was stirred for 5 min then enyne 1
(0.5 mmol) was added, and the resulting mixture was stirred at 25 °C
for 1.5 h. The reaction was quenched with EtOH (5 mL) at –78 °C. The
mixture was then warmed gradually to r.t., stirred for 2 h, and then
filtered through a plug of silica gel that was washed with Et2O. The
filtrate was concentrated in vacuo, and the residue was purified by
column chromatography [silica gel, EtOAc–PE (1:10)] to give a color-
less oil; yield: 0.0884g (66%; Z/E > 20:1); [α]D20 –11.5 (c 0.98, CHCl3).
IR (neat): 3029, 2963, 2867, 1600, 1493, 1452 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.45–7.29 (m, 7 H), 7.25–7.14 (m, 3 H),
6.27 (d, J = 2.4 Hz, 1 H), 5.02–4.98 (m, 1 H), 4.78–4.70 (m, 1 H), 4.30
(d, J = 9.5 Hz, 1 H), 2.78–2.66 (m, 1 H), 1.20 (d, J = 6.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 146.2, 140.4, 137.2, 128.5, 128.4,
128.01, 127.97, 126.59, 126.56, 119.9, 87.2, 70.3, 47.8, 14.2.
HRMS (EI): m/z calcd for [C18H18O]+: 250.1358; found: 250.1357.
(4E)-4-Benzylidene-3-methyltetrahydro-2H-pyran (2aa)14
HPLC: Chiralcel OD-H [hexane–i-PrOH (90:10), 1.0 mL/min], λ = 254
nm; Tr = 4.4 (major), 6.0 (minor); 39% ee.
Prepared by General Procedure A from iron complex I (0.0138 g, 0.024
mmol), Et2Zn (1.25 mL, 1.0 M in toluene), and [4-(allyloxy)but-1-yn-
1-yl]benzene (1aa; 0.0931 g, 0.5 mmol) to give a colorless oil; yield:
0.0460 g (49%, E/Z > 20:1).
Acknowledgment
IR (neat): 2959, 2845, 1651, 1599, 1491, 1462, 1447 cm–1
.
We are grateful for the financial support provided by the National
Natural and Science Foundation of China (NSFC, 21472162) and the
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

H
T. Xi et al.
Special Topic
Synthesis
Fundamental Research Funds for the Central Universities
(2013QNA3022).
Chung, Y. K. Chem. Eur. J. 2011, 17, 10852. For selected examples
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Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561957.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H