Nickel-palladium-catalyzed hydroamination/cyclization of sulfur-substituted 1,6-diynes with secondary amines

Article abstract of DOI:10.1016/j.tet.2013.12.049

Hydroamination/cyclizations of sulfur-substituted 1,6-diynes catalyzed by nickel or nickel-palladium in DMSO were examined. Pyrroles 2a-l and furans 5a-i bearing various secondary amines were obtained in high yields. The organosulfanylmethyl group on pyrr

Full text of DOI:10.1016/j.tet.2013.12.049

Tetrahedron 70 (2014) 1306e1316
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Nickelepalladium-catalyzed hydroamination/cyclization of
sulfur-substituted 1,6-diynes with secondary amines
*
Hayami Nagata, Yuko Sugimoto, Yukiteru Ito, Miki Tanaka, Mitsuhiro Yoshimatsu
Department of Chemistry, Faculty of Education, Gifu University, Yanagido 1-1, Gifu 501-1193, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Hydroamination/cyclizations of sulfur-substituted 1,6-diynes catalyzed by nickel or nickelepalladium in
DMSO were examined. Pyrroles 2ael and furans 5aei bearing various secondary amines were obtained
in high yields. The organosulfanylmethyl group on pyrroles was easily oxidized with ceric ammonium
nitrate to produce the pyrrolecarboxaldehyde and corresponding acetal.
Received 18 November 2013
Received in revised form 14 December 2013
Accepted 18 December 2013
Available online 22 December 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Hydroamination
1,6-Diynes
Cyclization
Pyrrole
Organosulfur
1. Introduction
anti-cancer tanshinone derivatives.17 Furthermore, the organo-
sulfur functional group on the 1,6-diynes could be coordinated with
Hydroamination (HA) of alkynes, defined as a simple and atom-
economical process leading to enamines and imines, has been
usually applied to the intramolecular cyclizations for the syntheses
of a wide variety of nitrogen containing heterocycles such as pyr-
rolidines, pyrazoles, indoles, isoindoles, and imidazoles scaffolds.1
Recently, considerable attention has been paid to HA-triggered
cyclizations of alkynes for the synthesis of heterocyclic skeletons
of greater structural complexity in a variety of biologically active
natural products.2 General and convenient methods for HA/cycli-
zation processes consist of two common important strategies: i,
activation of alkynes using transition metals3e13 as well as
lanthanides;14e16 ii, nucleophilic attack of the intramolecular ni-
trogen atom, where, the possibility of successful construction of
heterocycles is attributed to the nucleophilicity of nitrogen. Re-
cently we investigated metal-free and metal-catalyzed cyclizations
of sulfanyl 1,6-diynes triggered by some useful functionalization.
Our concept is one of the useful approaches for the synthesis of
heterocycles from 1,6-diynes bearing organosulfur substituents,
which could activate their alkynes by their strong electron-
donating effect. We previously reported that the alkoxylation-
and aryloxylation-triggered cyclizations of oxygen-tethered
1,6-diynes afforded alkoxymethyl- and aryloxymethyl-furans and
some transition metals.18 Therefore, the transition metal-catalyzed
functionalization-cyclizations of the sulfanyl 1,6-diynes are ex-
pected to proceed with high regioselectivities. During the course of
our study on the functionalization-cyclizations, we explored the
HA-triggered cyclizations of 1,6-diynes, as shown in Fig. 1. To date,
the only example of amine functionalization-cyclizations of 1,6-
diynes is cobalt-mediated reactions using carboxamides,19 which
have very low nucleophilicities. However, the development the
clinical drugs requires the preparation of heterocycles bearing
a wide variety of highly nucleophilic amines, rather than amides
(Fig. 2). A metal-free or metal-catalyzed amine functionalization-
cyclization of 1,6-diynes leading to the amine-functionalized het-
erocycles will be an important tool in drug-discovery processes.
Here we report the first catalytic HA/cyclization of 1,6-diynes
leading to functionalized heterocycles as shown in Eq. 1. Further-
more, we demonstrate that the organosulfanylmethyl group on the
* Corresponding author. E-mail address: yoshimae@gifu-u.ac.jp (M. Yoshimatsu).
Fig. 1. Intermolecular hydroaminations/cyclizations.
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.12.049

H. Nagata et al. / Tetrahedron 70 (2014) 1306e1316
1307
Table 1
Screening for HA of 1,6-diyne 1 with pyrrolidine
Entry Condition: catalyst (mol %), amine (equiv), solv, time
Yielda (%)
Fig. 2. Representative aminomethylpyrrole, TAK-438.
2a
3
1
2
3
4
5
6
7
8
CuOTf (10), DBU (1.5), DMF, rt, 0.5 h
CuI (3), DBU (1), DMF/H2O, 0 ꢀC, 1 h
CuBr SMe2, DBU (1.5), DMSO, rt, 0.5 h
NiCl2(PPh3)2 (10), DMSO, rt, 3 h
PdCl2(PPh3)2 (10), DMSO, rt, 4 h
PdCl2(PPh3)2 (10), DBU (1), DMSO, rt, 4 h
NiCl2 (10), DMSO, rt, 2.5 h
32
19
36
70
55
59
64
57
64
39
59
62
52
88f
15f
78
18f
72
60
89f
0
0
0
16
16
5
15
10
16
19
13
15
23
0
heterocycles is successively transformed to the formyl group, which
is potentially useful for further transformations.
Ni(OTf)2 (10), DMSO, rt, 2 h
9
NiCl2(dppe) (10), DMSO, rt, 1.5 hb
NiCl2(dppe) (10), DMSO/H2O, TBA,c rt, 4 h
NiCl2(dppe) (10), MS,d DMSO, rt, 3.5 h
Ni(dedt) (10), DMSO, rt, 2 he
10
11
12
13
14
15
16
17
18
19
20
21
22
Nickelocene (10), DMSO, rt, 2 h
NiCl2(PPh3)2 (10), DMSO, DBU (1), rt, 1 h
NiCl2(PPh3)2 (10), THF, rt, 4 h
2. Results and discussion
8
9
11
13
19
Ni(hfa)2 (10), DMSO, rt, 3.5 hg
First, we screened the suitable reaction condition for HA/cycli-
zation of a simple N-tosyl 1,6-diyne 1, which were simply prepared
by Mitsunobu reaction from N-tosylpropyne and phenyl-
sulfanylpropargyl alcohol, using pyrrolidine. We attempted the
metal-free amination/cyclization of 1; however, the reaction did
not proceed. According to our alkynylation condition of 1,6-diynes,
we examined the Cu(I)-catalyzed reactions and obtained the
4-pyrrolidinylmethylpyrrole 2a in low yields (entry 1). Next, we
performed the copper-catalyzed amination/cyclizations under the
similar conditions. The results were not satisfied (entries 2 and 3),
however, we continued to perform the HA/cyclizations catalyzed by
transition metals such as palladium, nickel, and other lanthanides.
Lanthanide metals were not effective. Nickel and palladium dra-
matically improved the yields of 2a (entries 4 and 5), however,
ynone 3 was obtained as a side product.
Ni(hfa)2 (10),g MeNO2, rt, 3 h
Ni(hfa)2 (10), DMSO, rt, 1.2 h
Ni(hfa)2 (10), DMF, rt, 2.5 h
Ni(hfa)2 (10),g DBU (1), DMSO, rt, 4 h
Ni(hfa)2 (10),g PdCl2(PPh3)2 (10), DBU (1), DMSO, rt, 4 h Quant.
0
Ni(hfa)2 (10),g PPh3 (10), DBU (1), DMSO, rt, 4 h
91f
a
Yield of isolated product.
dppe: diphenylphosphinoethane.
Tetrabutylammonium hydrogensulfate (0.2 equiv) was added.
MS: molecular sieves.
dedt: diethyl dithiocarbamate. Ni(dedt) were used as mono hydrate.
The diyne 1 was recovered in 8% (entry 14), 70% (entry 16), 70% (entry 17), 4%
b
c
d
e
f
(entry 20) and 3% (entry 22) yields.
g
hfa: hexafluoroacetylacetone. Ni(hfa)2 was used as mono hydrate.
We attempted the palladium-catalyzed HA/cyclizations in the
presence of some ligands and bases, however, the yields of the
products did not dramatically change (entries 5 and 6). Then, we
next performed the nickel-catalyzed amination/cyclizations as
shown in entries 7e22. The inert ligands like chloride, triflate and
diphenylphophinoethane (dppe), diethyl dithiocarbamate (dedt)
were not effective (entries 7e9, 12). The reaction of 1 in DMSO/H2O
gave rise to increasing the yield of 3 (entry 10). The molecular
sieves (MS) were not effective for the formation of 2a (entry 11).
The reaction using Ni(0), nickelocene, of which reactions would
usually provide the nickellacycle intermediates, also afforded the
pyrrolidinylmethyl 2a in moderate yield (entry 13). DBU also ac-
celerated the HA/cyclization reaction at room temperature (entry
14). Bis(hexafluoroacetylacetonato)nickel mono hydrate in DMSO
was found to give superior results by comparing the examinations
of both the solvent effects and the additives (entries 15e20). When
the nickel-catalyzed HA/cyclizations were examined, the diyne 1
was not disappeared in the reaction mixture (entries 20 and 22).
Since the reaction under the nickelepalladium mixed catalyst
condition was complete without the formations of any side prod-
ucts (entry 21), we selected the suitable reaction condition (method
B): Ni(hfa)2 (0.1 equiv)/Pd(PPh3)2Cl2 (0.1 equiv), DBU (1 equiv) in
DMSO. We next performed amination/cyclizations using various
amines. The results are shown in Table 2.
2b (entry 2) (method B). A similar tendency was observed in the
reactions with morpholine and N-methylpiperadine (entries
3e6). As shown in the entries 7 and 8, piperadine bearing further
functionalized amines provided the aminomethylated product
2e; however, the reaction with thiazolidine gave a ring-opening
product 2f in low yield (entry 9). Next we performed amina-
tions using the linear amines and obtained diethylaminomethyl-,
hydroxyethylmethylaminomethyl-, and 2-(N,N-dimethylamino)
ethylmethylaminomethylpyrrole presented as 2g, 2h, and 2i,
respectively (entries 10e14). N-containing heterocycles also
afforded the hetarylmethylpyrroles 2je2l in moderate-to-good
yields (entries 15e20).
We also examined the HA/cyclizations of 3-aryl-4-oxahepta-1,6-
diynes 4, which were easily prepared by our usual method20 from
sulfur-substituted propargyl alcohol and prop-2-yn-1-ol, using the
similar cyclic amines. The results are shown in Table 3. The cycli-
zations
of
4-oxahepta-1,6-diynes
provided
2-aryl-4-
aminomethylfurans 5aei in good yields. Piperidinylmethyl-,
4-methylpiperadinylmethyl, benzimidazolylmethyl, and 3-oxo-1,4-
benzthiazin-4-ylmethyl 2-arylfuran presented as 5aed, re-
spectively, are shown in entries 1e4. 2-p-Bromophenyl- and
p-chlorophenyl, and 1-naphthyl-1,6-diynes also afforded furans
4eei (entries 5e9).
Although the details of the mechanism of this HA/cyclization
reaction are not completely understood, a speculative pathway is
shown in Scheme 1. According to our previous reports,17a,b the
sulfanyl 1,6-diynes isomerized to the alkyneeallene 8 or allene-
eallene intermediates 9 via a carbanion 7. The nickel catalyst binds
to give the sulfur-coordinated intermediate 10, which would acti-
vate the alkyne toward intermolecular attack by the amine, and
For a series of cyclic amines, two kinds of experiments were
performed to investigate HA/cyclizations of 1,6-diynes 1. The
reaction with piperidine using Ni-catalyst at room temperature
gave
4-(1-piperidinylmethyl)-3-(phenylsulfanylmethyl)-1-(4-
methylphenylsulfonyl)pyrrole 2b in 79% yield (entry 1)
(method A). The Ni/Pd-catalyzed reaction quantitatively afforded

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H. Nagata et al. / Tetrahedron 70 (2014) 1306e1316
Table 2
Table 3
HA/cyclization of 1,6-diyne 1
HA/cyclization of aryl-1,6-diyne 4
NR1R2
Method A or B,a,b reaction time (h)
A, 4 h
Yield of 2c (%)
2b (79)
Entry Ar
R1R2N
Method A or B,b,c Time (h) Yielda of 5 (%)
Entry
1
1
p-MeOC6H4
A, 6 h
5a (63)
2
3
p-MeOC6H4
p-MeOC6H4
A, 8 h
B, 8 h
5b (71)
5c (71)
2
B, 8 h
A, 6 h
B, 8 h
A, 8 h
B, 8 h
A, 8 h
B, 8 h
B, 8 h
A, 8 h
B, 8 h
A, 8 h
B, 72 h
B, 72 h
A, 4 h
B, 4 h
A, 7 h
B, 1 h
A, 4 h
B, 2 h
2b (quant.)
2c (77)
2c (88)
2d (75)
2d (quant.)
2e (50)
2e (76)
2f (43)
3
4
p-MeOC6H4
B, 8 h
5d (70)
4
5
6
4-BrC6H4
4-BrC6H4
B, 8 h
5e (61)
5f (39)d
5
B, 72 h
6
7
4-ClC6H4
B, 72 h
5g (61)
7
8
9
4-ClC6H4
A, 4 h
B, 1 h
5h (65)
5i (69)
1-Naphthyl
8
a
Yield of isolated product.
Method A: Ni(hfa)2 hydrate (10 mol %), amine (2e5 equiv), and DBU (1 equiv)
b
9
were added to the substrate in DMSO at rt.
c
Method B: Ni(hfa)2 hydrate (10 mol %), bis(triphenylphosphinie)palladium
dichloride (10 mol %), DBU (1 equiv), and amine (2e5 equiv) were added to the
10
11
12
13
14
15
16
17
18
19
Et2N
2g (49)
2g (82)
2h (71)
2h (84)
2i (66)
substrate in DMSO at rt.
d
Another isomer was obtained, however, it could not be isolated.
molecules attack the sulfur-substituted alkynyl carbon to yield
a side product 17 via path b. Because the reaction of 4-methyl-N-[3-
phenyl-2-propyn-1-yl]-N-2-propyn-1-ylbenzenesulfonamide
(which bears no-sulfanyl group) with pyrrolidine yielded a com-
plex mixture rather than a product such as 16, it appears that the
organosulfanyl group is highly effective for the selective formation
and reaction of the key intermediate 10.
As we found a process that proved to be the most powerful tool
for the direct synthesis of aminomethylpyrroles and amino-
methylfurans through nickel or nickelepalladiumecatalyzed
HAecyclizations of 1,6-diynes, which can be used to access com-
pounds like TAK-438, we attempted the unique transformation of
2j (70)
2j (43)
the 3-organosulfanylmethyl-4-aminomethylpyrroles
2 to other
2k (74)
2k (92)
2l (48)
useful compounds (Scheme 2). Then we found the excellent trans-
formation of the organosulfanylmethyl functional group of pyrrole 2
easily changed to the formyl and/or acetal moiety 18a,b,k and 19k by
oxidations of the representative pyrroles with ceric ammonium ni-
trate (CAN). These results show that the organosulfanyl group would
activate 1,6-diynes in the HA/cyclization. Then, the organo-
sulfanylmethyl group of the product, pyrroles and furans, could
easily be converted to the formyl group, which could explore further
transformations. The reaction of 2k with NaOH/MeOH underwent
desulfonylation of pyrrole to give 1H-pyrrole 20k, exclusively.22
20
2l (53)
a
Method A: Ni(hfa)2 hydrate (10 mol %), amine (2e5 equiv), and DBU (1 equiv)
were added to the substrate in DMSO at rt.
b
Method B: Ni(hfa)2 hydrate (10 mol %), bis(triphenylphosphinie)palladium
dichloride (0.1 equiv), DBU (1 equiv), and amine (2e5 equiv) were added to the
substrate in DMSO at rt.
c
Yield of isolated product.
3. Conclusion
generating dienamino metal intermediate 13 through the 5-exo-
cyclization of 11 and the subsequent isomerization of 12 (path a).21
Then, the second intramolecular cyclization of 13 would proceed to
produce a metalacycles 15 after the b-elimination of cationic in-
termediate 14. Protonolysis and isomerization of 15 afford product
16 along with metal(II). When the amines are less nucleophilic, H2O
In summary, we have discovered a powerful tool for synthe-
sizing 3- or 4-aminomethylpyrroles and aminomethylfurans
through nickel- or nickelepalladium-catalyzed HA/cyclizations of
nitrogen- or oxygen-tethered 1,6-diynes bearing a sulfur sub-
stituent. The methodology is considered to be useful for drug-
discovery processes because a wide variety of secondary amines

H. Nagata et al. / Tetrahedron 70 (2014) 1306e1316
1309
13C NMR spectra were determined with JEOL ECA600 (600 MHz)
spectrometer at Gifu University. Chemical shifts are expressed in
parts per million (ppm) with respect to tetramethylsilane as an in-
ternal standard. Splitting patterns are designated as follows: s, sin-
glet; d, doublet; t, triplet; q, quartet. IR spectra were determined on
a JASCO FT-IR 460-Plus infrared spectrometer and are expressed in
reciprocal centimeters. EI mass spectra (MS) were obtained using
JEOL MS-700 spectrometer with direct-insertion probe at 70 eV. All
high-resolution mass determinations were obtained on the JMSD300
JMS 2000 on line system. O-Tetrahydropyranyl propargyl alcohol,23
phenylsulfanyl chloride,24 and the phenylsulfanyl 4-oxahepta-1,6-
diynes 3aej were prepared according to the previous report.20
N-Propargyl p-toluenesulfonamide was prepared according to the
almost same method for the previous report.25
4.2. Preparation of 3-(phenylsulfanyl)prop-2-yn-1-ol
To a THF (100 mL) solution of O-tetrahydropyranylpropargyl
alcohol23 (20.0 g, 0.14 mol) was added n-butyllithium (2.6 M,
53.8 mL, 0.14 mol) at 0 ꢀC under an Ar atmosphere. After stirring for
10 min, phenylsulfanyl chloride24 (20.2 g, 0.14 mol) in THF (30.0 mL)
was added dropwise to the mixture. The whole was stirred for 0.5 h
and poured into water (500 mL). The organic layer was separated
and the aqueous layer was extracted with ether (100 mLꢁ2). The
combined organic layer was dried over MgSO4. The solvent was
removed under reduced pressure. The residue was used for the
deprotection of tetrahydropyranyl group without further purifica-
tion. To a mixed solution of both isopropyl alcohol (140 mL) and
diethyl ether (35 mL) of the residue was added p-toluenesulfonic
acid (1.30 g, 7.00 mol) at room temperature. The reaction mixture
was stirred for 12 h. A small amount of triethylamine (0.8 ml) was
added to the mixture. The solvent was removed under reduced
pressure. The residue was poured into water (300 mL). The organic
layer was separated and the aqueous layer was extracted with
ether. The combined organic layer was dried over MgSO4. The sol-
vent was removed under reduced pressure. The residue was puri-
fied by column chromatography on silica gel eluting with AcOEt/
n-hexane (1:10 to 1:5) to give the title compound26 (15.2 g, 66%) as
Scheme 1. Speculative mechanism for HA/cyclization of 6.
a pale yellow oil. 1H NMR (600 MHz, CDCl3)
d 2.61 (1H, br s, OH),
4.47 (2H, s, CH2), 7.20e7.22 (1H, m, ArH), 7.31e7.33 (2H, m, ArH),
7.42 (2H, d, J¼8.3 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 51.7 (t), 72.8
(s), 97.3 (s), 126.3 (dꢁ2), 126.6 (d), 129.2 (dꢁ2), 132.2 (s).
4.3. Preparation of 4-methyl-N-[3-(phenylthio)-2-propyn-1-
yl]-N-2-propyn-1-ylbenzenesulfonamide (1)
Scheme 2. Transformation of aminomethylpyrroles 2.
are applicable to this HA/cyclization process. While currently lim-
ited to sulfur-substituted 1,6-diynes, it would be solved by eluci-
dating oxidation with CAN to produce pyrrolecarboxaldehydes,
which could be utilized for further transformations.
Diethyl azodicarboxylate (2.80 ml, 6.09 mmol) was added drop-
wise to
a THF (8.0 mL) solution of 4-methyl-N-2-propyn-1-
ylbenzensulfonamide (1.2 g, 6.09 mmol), 3-(phenylthio)prop-2-yn-
1-ol (1.0 g, 6.09 mmol) and triphenyl phosphine (1.6 g, 6.09 mmol)
under an Ar atmosphere. The reaction mixture was stirred for 45 min
at room temperature. The solvent was removed under reduced
pressure. The residue was purified by column chromatography
on silica gel eluting with AcOEt/n-hexane (1:40 then 1:20) to
4. Experimental section
4.1. General
Melting points were determined on a J-Science Lab. Micro melt-
ing point apparatus and uncorrected. Elemental analyses were per-
formed at the Center of Instrumentation of Gifu University. 1H and
give
4-methyl-N-[3-(phenylthio)-2-propyn-1-yl]-N-2-propyn-1-
ylbenzenesulfonamide (1) (1.82 g, 85%) as white powders.

1310
H. Nagata et al. / Tetrahedron 70 (2014) 1306e1316
Mp 38e42 ꢀC; IR (KBr, cmꢂ1) 3437, 3291, 3061, 2923, 2189, 1598,
1583, 1479,1442, 1352,1165,1094, 893, 815, 743, 666, 580, 558, 541;
1H NMR (600 MHz, CDCl3)
analysis calcd (%) for C23H26N2O2S2: C, 64.76; H, 6.14; N, 6.57.
Found: C, 64.71; H, 6.38; N, 6.28.
d
2.20 (1H, t, J¼2.1 Hz, acetylenic H), 2.35
(3H, s, Me), 4.16e4.17 (2H, d, J¼2.7 Hz, CH2), 4.43 (2H, s, CH2),
4.5.1. 3-[N-(Prop-2-ynyl)-N-(4-methylphenylsulfonyl)amino]-1-
(phenylsulfanyl)propan-2-one (3).
7.23e7.33 (7H, m, ArH), 7.70e7.71 (2H, d, J¼9.0 Hz, ArH); 13C NMR
(150 MHz, CDCl3)
d 21.5 (q), 36.5 (t), 37.7 (t), 73.0 (s), 74.2 (s), 76.2
(d), 91.2 (s), 126.2 (dꢁ2), 126.7 (d), 127.8 (dꢁ2), 129.2 (dꢁ2), 129.6
(dꢁ2), 131.9 (s), 134.9 (s), 144.1 (s); MS (70 eV): m/z: 355 (Mþ), 200
(MþꢂTos); elemental analysis calcd (%) for C19H17NO2S2: C, 64.20;
H, 4.82; N, 3.94. Found: C, 64.50; H, 4.89; N, 3.90.
4.4. Synthesis of 4-(1-pyrrolidinylmethyl)-3-(phenyl-
sulfanylmethyl)-1-(4-methylphenylsulfonyl)pyrrole (2a),
typical Procedure for NiePd-catalyzed amination/cyclizations
(method B)
Yield 9%, a yellow oil; IR (KBr, cmꢂ1) 3282, 2923, 2121, 1729, 1598,
1482,1440,1403,1349,1261,1162,1092,1060, 912, 815, 743, 691, 663,
580, 547; 1H NMR (600 MHz, CDCl3):
d 1.59 (1H, br s, acetylenic H),
2.42 (3H, s, Me), 3.81 (2H, s, CH2), 4.14 (2H, d, J¼2.1 Hz, CH2), 4.21
(2H, s, CH2), 7.23e7.32 (5H, m, ArH), 7.37 (2H, d, J¼6.9 Hz, ArH), 7.66
(2H, d, J¼8.2 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 21.6 (q), 38.1 (t),
41.2 (t), 53.3 (t), 74.5 (d), 76.2 (s), 127.3 (d), 127.7 (dꢁ2), 129.2 (dꢁ2),
129.7 (dꢁ2), 130.1 (dꢁ2), 133.9 (s), 135.1 (s), 144.1 (s), 200.0 (s); MS
(70 eV): m/z: 373 (Mþ), 264 (MþꢂSPh). High-resolution mass calcd
for C19H19NO3S2: 373.0806, found m/z 373.0837.
4.6. 4-(1-Piperidinylmethyl)-3-(phenylsulfanylmethyl)-1-
(4-methylphenylsulfonyl)pyrrole (2b) (Table 2, entries 1 and 2)
Bis(hexafluoroacetylacetonato)nickel(II) hydrate (66.5 mg,
0.14 mmol), bis(triphenylphosphine)palladium(II) dichloride
(98.7 mg, 0.14 mmol), and DBU (0.21 g, 1.40 mmol) were added to
a DMSO (5.0 ml) solution of 4-methyl-N-[3-(phenylthio)-2-propyn-
1-yl]-N-2-propyn-1-ylbenzenesulfonamide (1) (0.50 g, 1.41 mmol),
pyrrolidine (0.50 g, 7.03 mmol) at room temperature. The mixture
was stirred for 1 h and then poured into water (50 ml). The organic
layer was separated and the aqueous layer was extracted with
AcOEt. The combined organic layer was washed with water and
dried over MgSO4. The solvent was removed under reduced pres-
sure. The residue was purified by preparative TLC on silica gel
eluting with CHCl3/MeOH (10:1) to give 4-(1-pyrrolidinylmethyl)-
3-(phenylsulfanylmethyl)-1-(4-methylphenylsulfonyl)pyrrole (2a)
(0.60 g, quant.) as a yellow oil.
Yield quant, a yellow oil; IR (KBr, cmꢂ1) 3135, 3058, 2929, 2856,
2796, 2761, 1596, 1519, 1481, 1440, 1371, 1300, 1255, 1188, 1173,
1093, 1065, 1039, 993, 966, 861, 813; 1H NMR (600 MHz, CDCl3)
d
1.39 (2H, br s, CH2), 1.50e1.52 (4H, m, CH2), 2.28 (4H, br s, CH2),
2.39 (3H, s, Me), 3.28 (2H, s, NCH2), 4.01 (2H, s, SCH2), 6.90 (1H, br s,
4.5. Synthesis of 4-(1-pyrrolidinylmethyl)-3-(phenyl-
sulfanylmethyl)-1-(4-methylphenylsulfonyl)pyrrole, typical
procedure for Ni-catalyzed HA/cyclizations (method A, Table 1,
entry 20)
ArH), 6.93 (1H, br s, ArH), 7.13e7.25 (7H, m, ArH), 7.59e7.60 (2H, d,
J¼8.2 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 21.6 (q), 24.4 (t), 26.0
(tꢁ2), 29.4 (t), 54.3 (t), 54.4 (tꢁ2),119.7 (d),119.8 (d),124.9 (s),125.5
(s), 126.1 (d), 126.6 (dꢁ2), 128.6 (dꢁ2), 129.7 (dꢁ2), 129.8 (dꢁ2),
136.0 (s), 136.2 (s), 144.6 (s); MS (70 eV): m/z: 440 (Mþ), 355
(MþꢂC5H10N), 285 (MþꢂTos); elemental analysis calcd (%) for
Bis(hexafluoroacetylacetonato)nickel(II) hydrate (6.7 mg,
0.0141 mmol) was added to a DMSO (0.50 mL) solution of 4-methyl-
N-[3-(phenylthio)-2-propyn-1-yl]-N-2-propyn-1-ylbenzene-sulfon-
amide (1) (50 mg, 0.14 mmol), pyrrolidine (50 mg, 0.70 mmol), and
DBU (21 mg, 0.14 mmol) at room temperature. The mixture was
stirred for 4 h and poured into water (50 mL). The organic layer was
separated and the aqueous layer was extracted with AcOEt. The
combined organic layer was dried over MgSO4. The solvent was re-
moved under reduced pressure. The residue was purified by pre-
parative TLC on silica gel eluting with AcOEt/n-hexane (1:2) to give
4-(1-pyrrolidinylmethyl)-3-(phenylsulfanylmethyl)-1-(4-
C24H28N2O2S2: C, 65.42; H, 6.41; N, 6.36. Found: C, 65.23; H, 6.39; N,
6.18.
4.7. 4-(4-Morpholinylmethyl)-3-(phenylsulfanylmethyl)-1-
(4-methylphenylsulfonyl)pyrrole (2c) (entries 3 and 4)
methylphenylsulfonyl)pyrrole (2a) (53 mg, 89%) as a yellow oil.
IR (KBr, cmꢂ1) 3428, 3133, 3059, 2959, 2926, 2795, 1661, 1542,
1371, 1298, 1255, 1191, 1173, 1146, 1092, 1067, 969, 946, 877, 792,
742, 674, 662, 586, 540; 1H NMR (600 MHz, CDCl3)
d
1.74 (4H, br s,
Yield 88%, a yellow oil; IR (KBr, cmꢂ1) 2925, 2853, 2809, 1596,
1518, 1481, 1453, 1371, 1303, 1171, 1118, 1092, 1062, 1005, 865, 809,
CH2ꢁ2), 2.40 (3H, s, Me), 2.45 (4H, br s, CH2ꢁ2), 3.47 (2H, s, NCH2),
3.96 (2H, s, SCH2), 6.89 (1H, br s, ArH), 6.98 (1H, br s, ArH), 7.14e7.19
(3H, m, ArH), 7.22e7.26 (4H, m, ArH), 7.59e7.61 (2H, d, J¼8.3 Hz,
747, 670, 585, 540, 428; 1H NMR (600 MHz, CDCl3)
d 2.34 (4H, br s,
CH2), 2.40 (3H, s, Me), 3.33 (2H, s, NCH2), 3.63e3.64 (4H, m, CH2),
4.00 (2H, s, SCH2), 6.90 (1H, br s, ArH), 6.95 (1H, br s, ArH),
7.14e7.20 (2H, m, ArH), 7.21e7.26 (5H, m, ArH), 7.60e7.61 (2H, d,
ArH); 13C NMR (150 MHz, CDCl3)
d
21.6 (q), 23.5 (tꢁ2), 29.4 (t), 50.9
(t), 54.2 (tꢁ2),119.2 (d), 119.6 (d), 124.3 (s), 126.2 (d), 126.3 (s), 126.7
(dꢁ2), 128.7 (dꢁ2), 129.8 (dꢁ2), 130.1 (dꢁ2), 136.0 (s), 144.6 (s); MS
(70 eV): m/z: 426 (Mþ), 355 (MþꢂC4H8N), 271 (MþꢂTos); elemental
J¼9.0 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 21.6 (q), 29.6 (t), 53.5
(tꢁ2), 54.0 (t), 67.0 (tꢁ2), 119.9 (dꢁ2), 124.4 (s), 124.6(s), 126.3 (d),

H. Nagata et al. / Tetrahedron 70 (2014) 1306e1316
1311
126.7 (dꢁ2), 128.7 (dꢁ2), 129.8 (dꢁ2), 130.0 (dꢁ2), 135.9 (s), 136.1
(s), 144.7 (s); MS (70 eV): m/z: 442 (Mþ), 355 (MþꢂC4H8ON), 333
(MþꢂSPh), 287 (MþꢂTos); elemental analysis calcd (%) for
1063, 967, 890, 812; 1H NMR (600 MHz, CDCl3)
d
1.51 (1H, br s, SH),
2.41 (3H, s, Me), 2.45 (2H, t, J¼6.8 Hz, CH2), 2.76e2.78 (2H, t,
J¼6.2 Hz, CH2), 3.57 (2H, s, NCH2), 3.99 (2H, s, SCH2), 6.91 (1H, br s,
ArH), 6.98 (1H, d, J¼2.1 Hz, ArH), 7.16e7.26 (7H, m, ArH), 7.61e7.62
C
23H26N2O3S2: C, 62.42; H, 5.92; N, 6.33. Found: C, 62.16; H, 5.91;
N, 6.21.
(2H, d, J¼8.3 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 21.6 (q), 26.1 (t),
29.5 (t), 35.3 (t), 40.7 (t),119.6 (d),120.4 (d),123.8 (s),124.1 (s),126.5
(d), 126.7 (dꢁ2), 128.8 (dꢁ2), 129.9(dꢁ2), 130.4 (dꢁ2), 135.6 (s),
135.8 (s), 144.9 (s) (s); MS (70 eV): m/z: 432 (Mþ), 356
(MþꢂC2H6NS), 323 (MþꢂTos); elemental analysis calcd (%) for
4.8. 4-[(4-Methyl-1-piperazinyl)methyl]-3-(phenyl-
sulfanylmethyl)-1-(4-methylphenylsulfonyl)pyrrole (2d)
(entries 5 and 6)
C21H24N2O2S3: C, 58.30; H, 5.59; N, 6.48. Found: C, 58.00; H, 5.61; N,
6.30.
4.11. 4-(Diethylaminomethyl)-3-(phenylsulfanylmethyl)-1-
(4-methylphenylsulfonyl)pyrrole (2g) (entry 9)
Yield quant, a yellow oil; IR (KBr, cmꢂ1) 3131, 3058, 2933, 2796,
1737, 1596, 1519, 1480, 1456, 1370, 1301, 1172, 1092, 1065, 1011, 967,
925, 881, 813, 741, 703, 673, 588, 540; 1H NMR (600 MHz, CDCl3)
d
2.25 (3H, s, Me), 2.37 (8H, br s, NCH2), 2.40 (3H, s, NMe), 3.33 (2H,
s, NCH2), 4.00 (2H, s, SCH2), 6.90 (1H, d, J¼2.8 Hz, ArH), 6.94 (1H, d,
J¼2.8 Hz, ArH), 7.14e7.19 (3H, m, ArH), 7.21e7.27 (4H, m, ArH),
7.59e7.61 (2H, d, J¼8.3 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 21.5
(q), 29.5 (t), 45.9 (q), 52.9 (tꢁ2), 53.5 (t), 55.1 (tꢁ2), 119.8 (dꢁ2),
124.7 (s), 125.0 (s), 126.1 (d), 126.6 (dꢁ2), 128.6 (dꢁ2), 129.8 (dꢁ2),
129.9 (dꢁ2), 135.9 (s), 136.1 (s), 144.6 (s); MS (70 eV): m/z: 455
(Mþ), 355 (MþꢂC5H11N2), 300 (MþꢂTos); elemental analysis calcd
(%) for C24H29N3O2S2: C, 63.27; H, 6.42; N, 9.22. Found: C, 62.98; H,
6.45; N, 8.99.
Yield 82%, a yellow oil; IR (KBr, cmꢂ1) 3135, 3055, 2972, 2928,
2871, 2797, 1915,1731, 1596, 1519, 1480, 1439, 1376, 1304, 1189, 1091,
967, 909, 810, 741, 703, 692, 589, 540, 487, 476, 408; 1H NMR
(600 MHz, CDCl3)
d
0.96 (6H, t, J¼7.3 Hz, Meꢁ2), 2.39 (3H, s, CH3),
2.43 (4H, q, J¼7.5 Hz, NCH2ꢁ2), 3.38 (2H, s, NCH2), 4.00 (2H, s,
SCH2), 6.89 (1H, d, J¼2.1 Hz, ArH), 6.95 (1H, d, J¼2.1 Hz, ArH),
7.15e7.23 (7H, m, ArH), 7.58e7.60 (2H, d, J¼8.3 Hz, ArH); 13C NMR
4.9. 4-[4-(N,N-Dimethylaminoethyl)-1-piperadinyl]methyl-3-
(phenylsulfanylmethyl)-1-(4-methylphenylsulfonyl)pyrrole
(2e) (entry 7)
(150 MHz, CDCl3)
d
11.7 (qꢁ2), 21.6 (q), 29.3 (t), 46.6 (tꢁ2), 48.6 (t),
119.8 (d), 119.9 (d), 124.9 (s), 126.1 (d), 126.6 (s, dꢁ2), 128.6 (dꢁ2),
129.8 (dꢁ2), 129.9 (dꢁ2), 136.1 (sꢁ2), 144.6 (s); MS (70 eV): m/z:
428 (Mþ), 355 (MþꢂC4H10N), 273 (MþꢂTos); elemental analysis
calcd (%) for C23H28N2O2S2: C, 64.45; H, 6.58; N, 6.54. Found: C,
64.36; H, 6.57; N, 6.52.
4.12. N-[3-(Phenylsulfanylmethyl)-1-(4-
methylphenylsulfonyl)pyrrol-4-ylmethyl]-N-methyl-
aminoethanol (2h) (entry 10)
Yield 76%, a yellow oil; IR (KBr, cmꢂ1) 2949, 2935, 2811, 1597,
1519, 1458, 1371, 1303, 1188, 1173, 1133, 1093, 1065, 1010, 968, 813;
1H NMR (600 MHz, CDCl3)
d
2.24 (6H, s, Meꢁ2), 2.41 (3H, s, Me),
2.42e2.45 (12H, m, CH2), 3.33 (2H, s, NCH2), 4.00 (2H, s, SCH2), 6.90
(1H, br s, ArH), 6.94 (1H, br s, ArH), 7.14e7.24 (7H, m, ArH),
7.60e7.61 (2H, d, J¼8.2 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 21.6
(q), 29.5 (t), 45.8 (qꢁ2), 52.9 (tꢁ2), 53.6 (t), 53.7 (tꢁ2), 56.6 (t), 56.9
(t), 119.8 (dꢁ2), 124.7 (s), 125.0 (s), 126.2 (d), 126.7 (dꢁ2), 128.6
(dꢁ2), 129.8 (dꢁ2), 130.0 (dꢁ2), 136.0 (s), 136.1 (s), 144.7 (s); MS
(70 eV): m/z: 512 (Mþ), 403 (MþꢂSPh); elemental analysis calcd (%)
for C27H36N4O2S2: C, 63.25; H, 7.08; N, 10.93. Found: C, 63.20; H,
7.09; N, 10.77.
Yield 84%, a yellow oil; IR (KBr, cmꢂ1) 3132, 3060, 2950, 2925,
2876, 2848, 2794, 1596, 1584, 1519, 1480, 1456, 1439, 1369, 1302,
1172, 1121, 1092, 1067, 1025, 968, 876, 813; 1H NMR (600 MHz,
4.10. 4-(2-Mercaptoethylaminomethyl)-3-(phenyl-
sulfanylmethyl)-1-(4-methylphenylsulfonyl)pyrrole (2f) (entry 8)
CDCl3)
d 2.15 (3H, s, Me), 2.47 (3H, s, Me), 2.51e2.53 (2H, t,
J¼5.5 Hz, CH2), 3.39 (2H, s, NCH2), 3.58e3.60 (2H, t, J¼5.5 Hz,
CH2), 3.92 (2H, s, SCH2), 6.89 (1H, d, J¼2.1 Hz, ArH), 6.97e6.98
(1H, d, J¼2.0 Hz, ArH), 7.16e7.26 (7H, m, ArH), 7.61e7.63 (2H, d,
J¼8.2 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 21.6 (q), 29.8 (t), 41.5
(q), 53.2 (t), 58.7 (t), 58.8 (t), 120.0 (d), 120.1 (d), 124.2 (s), 125.2
(s), 126.6 (d), 126.7 (dꢁ2), 128.8 (dꢁ2), 129.9 (dꢁ2), 130.4 (dꢁ2),
135.7 (s), 135.9 (s), 144.8 (s); MS (70 eV): m/z: 430 (Mþ), 356
(MþꢂC3H8ON), 275 (MþꢂTos); elemental analysis calcd (%) for
A yellow oil; IR (KBr, cmꢂ1) 3365, 3131, 3058, 2922, 1711, 1661,
1595, 1583, 1517, 1480, 1439, 1369, 1369, 1306, 1237, 1170, 1092,
C22H26N2O3S2: C, 61.37; H, 6.09; N, 6.51. Found: C, 61.08; H, 6.07;
N, 6.35.

1312
H. Nagata et al. / Tetrahedron 70 (2014) 1306e1316
4.13. 4-[2-(N,N-Dimethylaminoethyl)-N-methylamino]
methyl-4-(phenylsulfanylmethyl)-1-(4-methylphenylsulfonyl)
pyrrole (2i) (entry 11)
7.14e7.20 (4H, m, ArH), 7.48e7.50 (2H, d, J¼8.2 Hz, ArH), 7.70e7.72
(1H, d, J¼7.8 Hz, ArH), 7.75 (1H, s, ArH); 13C NMR (150 MHz, CDCl3)
d
21.6 (q), 29.7 (t), 40.6 (t), 109.9 (d), 120.1 (d), 120.3 (d), 120.8 (d),
122.3 (d, s), 122.7 (s), 123.0 (d), 126.7 (dꢁ2), 126.9 (d), 128.8 (dꢁ2),
130.0 (dꢁ2), 130.8 (dꢁ2), 133.6 (s), 134.6 (s), 135.4 (s), 142.8 (d),
143.7 (s), 145.2 (s); MS (70 eV): m/z: 473 (Mþ); elemental analysis
calcd (%) for C26H23N3O2S2: C, 65.94; H, 4.89; N, 8.87. Found: C,
65.75; H, 4.84; N, 8.86.
4.16. 1-[4-(Phenylsulfanylmethyl)-1-
(4-methylphenylsulfonyl)-pyrrol-3-ylmethyl]pyrazole (2l)
(entry 14)
Yield 66%, a yellow oil; IR (KBr, cmꢂ1) 3132, 3059, 2943, 2815,
2770, 2360, 2342, 1713, 1596, 1584, 1519, 1480, 1457, 1440, 1370,
1300,1219,1188, 1171, 1121,1093,1064,1026, 967, 879, 812; 1H NMR
(600 MHz, CDCl3)
d
2.13 (3H, s, NMe), 2.16 (6H, s, NCH3ꢁ2),
2.36e2.43 (4H, m, NCH2ꢁ2), 2.40 (3H, s, Me), 3.33 (2H, s, NCH2),
3.99 (2H, s, SCH2), 6.89 (1H, br s, ArH), 6.96 (1H, d, J¼2.1 Hz, ArH),
7.14e7.27 (7H, m, ArH), 7.59e7.61 (2H, d, J¼8.9 Hz, ArH); 13C NMR
(150 MHz, CDCl3)
d
21.6 (q), 29.3 (t), 42.4 (q), 45.6 (qꢁ2), 53.4 (t),
Yield 53%, a yellow oil; IR (KBr, cmꢂ1) 3132, 3060, 2924, 2854,
1711, 1596, 1584, 1514, 1481, 1439, 1371, 1300, 1172, 1092, 1068, 968,
55.4 (t), 57.4 (t), 119.8 (dꢁ2), 124.6 (s), 125.8 (s), 126.2 (d), 126.6
(dꢁ2), 128.6 (dꢁ2), 129.8 (dꢁ2), 130.0 (dꢁ2), 136.0 (sꢁ2), 144.6 (s);
MS (70 eV): m/z: 457 (Mþ), 356 (MþꢂC5H13N2), 302 (MþꢂTos);
elemental analysis calcd (%) for C24H31N3O2S2: C, 62.99; H, 6.83; N,
9.18. Found: C, 62.78; H, 6.84; N, 9.03.
918, 881, 814; 1H NMR (600 MHz, CDCl3)
d 2.35 (3H, s, Me), 3.63 (2H,
s, NCH2), 5.12 (2H, s, SCH2), 6.16 (1H, d, J¼2.0 Hz, ArH), 6.82 (1H, d,
J¼2.8 Hz, ArH), 6.94 (1H, d, J¼2.7 Hz, ArH), 7.10 (5H, br s, ArH),
7.18e7.20 (2H, m, ArH), 7.24 (1H, d, J¼2.8 Hz, ArH), 7.43 (1H, d,
J¼1.4 Hz, ArH), 7.54 (2H, d, J¼8.3 Hz, ArH); 13C NMR (150 MHz,
4.14. 1-[3-(Phenylsulfanylmethyl)-1-
(4-methylphenylsulfonylpyrrol-4-yl)methyl]imidazole (2j)
(entry 12)
CDCl3) d 21.6 (q), 29.4 (t), 47.2 (t),105.8 (d),120.1 (d),120.3 (d),123.2
(s), 123.3 (s), 126.7 (d), 126.8 (dꢁ2), 128.8 (dꢁ2), 128.9 (d), 130.0
(dꢁ2), 130.6 (dꢁ2), 135.2 (s), 135.7 (s), 139.4 (d), 145.1 (s); MS
(70 eV): m/z: 423 (Mþ), 355 (MþꢂC3H3N2), 314 (MþꢂSPh), 268
(MþꢂTos); elemental analysis calcd (%) for C22H21N3O2S2: C, 62.39;
H, 5.00; N, 9.92. Found: C, 62.19; H, 5.03; N, 9.71.
4.17. 1-[2-(p-Methoxyphenyl)-3-(phenylsulfanylmethyl)-4-
(furanylmethyl)]piperidine (5a) (entry 1)
Yield 43%, a yellow oil; IR (KBr, cmꢂ1) 3130, 2927, 1710, 1671,
1596,1506,1481,1440,1372,1301,1225,1189,1171,1092,1065, 1027,
969, 815; 1H NMR (600 MHz, CDCl3)
d 2.36 (3H, s, Me), 3.56 (2H, s,
NCH2), 4.91 (2H, s, SCH2), 6.76 (1H, br s, NArH), 6.83 (1H, br s,
NArH), 6.89 (1H, br s, ArH), 6.97 (1H, br s, ArH), 7.11 (5H, br s, ArH),
7.21 (2H, d, J¼7.8 Hz, ArH), 7.37 (1H, br s, NArH), 7.55 (2H, d,
J¼8.2 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 21.6 (q), 29.7 (t), 42.2
Yield 63%, a yellow oil; IR (KBr, cmꢂ1) 3432, 2934, 1713, 1607,
1577, 1506, 1440, 1362, 1301, 1253, 1179, 1145, 1107, 1065, 1032, 992,
951, 908, 861, 835, 795, 741, 691, 599, 533, 410; 1H NMR (600 MHz,
(t), 119.0 (d), 119.9 (d), 120.6 (d), 122.6 (s), 123.0 (s), 126.8 (dꢁ2),
127.0 (d), 128.9 (dꢁ2), 129.5 (d), 130.1 (dꢁ2), 130.8 (dꢁ2), 134.8 (s),
135.5 (s), 137.1 (d), 145.3 (s); MS (70 eV): m/z: 355 (MþꢂC3H3N2);
elemental analysis calcd (%) for C22H21N3O2S2: C, 62.39; H, 5.00; N,
9.92. Found: C, 62.17; H, 5.01; N, 9.72.
CDCl3)
d 1.41 (2H, br s, CH2), 1.51e1.55 (4H, m, CH2), 2.36 (4H, br s,
CH2), 3.34 (2H, s, CH2), 3.82 (3H, s, Me), 4.30 (2H, s, CH2), 6.92e6.94
(2H, d, J¼8.9 Hz, ArH), 7.18e7.20 (1H, m, ArH), 7.25e7.28 (3H, m,
ArH), 7.38 (2H, d, J¼7.6 Hz, ArH), 7.56 (2H, d, J¼9.0 Hz, ArH); 13C
4.15. 1-[4-(Phenylsulfanylmethyl)-1-(4-
methylphenylsulfonyl)-pyrrol-3-ylmethyl]benzimidazole (2k)
(entry 13)
NMR (150 MHz, CDCl3)
d
24.5 (t), 26.1 (tꢁ2), 29.1 (t), 52.8 (t), 54.5
(tꢁ2), 55.3 (q), 114.0 (dꢁ2), 115.0 (s), 123.8 (s), 126.2 (d), 127.5
(dꢁ2), 128.8 (dꢁ2), 129.9 (dꢁ2), 137.0 (s), 139.3 (d), 144.8 (s), 151.4
(s), 159.0 (s); MS (70 eV): m/z: 393 (Mþ), 284 (MþꢂSPh); elemental
analysis calcd (%) for C24H27NO2S: C, 73.25; H, 6.92; N, 3.56. Found:
C, 73.11; H, 6.89; N, 3.35.
4.18. 1-[2-(p-Methoxyphenyl)-3-(phenylsulfanylmethyl)-4-
(furanylmethyl)]-4-methylpiperazine (5b) (entry 2)
Yield 92%, white prisms, mp 143e150 ꢀC; IR (KBr, cmꢂ1) 3132,
3059, 2923, 2568, 1711, 1669, 1615, 1596, 1520, 1496, 1458, 1439,
1371, 1301, 1254, 1170, 1144, 1092, 1065, 1025, 968, 812; 1H NMR
(600 MHz, CDCl3)
d 2.34 (3H, s, Me), 3.54 (2H, s, NCH2), 5.12 (2H, s,
SCH2), 6.81 (1H, s, ArH), 6.87 (1H, s, ArH), 7.05e7.12 (6H, m, ArH),

H. Nagata et al. / Tetrahedron 70 (2014) 1306e1316
1313
Yield 71%, a yellow oil; IR (KBr, cmꢂ1) 3435, 2934, 2836, 2795,
4.21. 1-[2-(p-Bromophenyl)-3-(phenylsulfanylmethyl)-4-
(furanylmethyl)]pyrrolidine (5e) (entry 5)
1606, 1581, 1506, 1480, 1456, 1440, 1350, 1294, 1253, 1178, 1147,
1112, 1089, 1065, 1032, 1011, 952, 925, 834; 1H NMR (600 MHz,
CDCl3)
d 2.26 (3H, s, Me), 2.41 (8H, br s, NCH2), 3.39 (2H, s, NCH2),
3.81 (3H, s, OMe), 4.29 (2H, s, SCH2), 6.91e6.93 (2H, d, J¼8.7 Hz,
ArH), 7.17e7.20 (1H, t, J¼7.3 Hz, ArH), 7.24e7.28 (3H, m, ArH), 7.37
(2H, d, J¼7.4 Hz, ArH), 7.55 (2H, d, J¼8.7 Hz, ArH); 13C NMR
(150 MHz, CDCl3)
d
29.1 (t), 46.0 (q), 52.0 (t), 53.0 (tꢁ2), 55.2 (tꢁ2,
q), 114.0 (dꢁ2), 114.9 (s), 123.3 (s), 123.6 (s), 126.2 (d), 127.5 (dꢁ2),
128.8 (dꢁ2), 129.9 (dꢁ2), 136.9 (s), 139.4 (d), 151.5 (s), 159.1 (s); MS
(70 eV): m/z: 408 (Mþ), 299 (MþꢂSPh); elemental analysis calcd (%)
for C24H28N2O2S: C, 70.56; H, 6.91; N, 6.86. Found: C, 70.36; H, 6.89;
N, 6.73.
Yield 61%, a yellow oil; IR (KBr, cmꢂ1) 3058, 2959, 2926, 2873,
2790, 2360, 1714, 1654, 1483, 1584, 1559, 1542, 1507, 1483, 1458,
1439, 1395, 1376, 1349, 1322, 1293, 1221, 1025, 1009, 944, 877, 829,
691; 1H NMR (600 MHz, CDCl3)
d 1.77 (4H, br s, CH2), 2.51 (4H, br s,
CH2), 3.50 (2H, s, CH2), 4.23 (2H, s, CH2), 7.20e7.22 (1H, m, ArH),
7.25e7.28 (2H, m, ArH), 7.35e7.37 (3H, m, ArH), 7.46e7.50 (4H, m,
4.19. 1-[2-(p-Methoxyphenyl)-3-(phenylsulfanylmethyl)fu-
ran-4-methyl]-1H-benzimidazole (5c) (entry 3)
ArH); 13C NMR (150 MHz, CDCl3)
d
23.5 (tꢁ2), 29.1 (t), 49.4 (t), 54.3
(tꢁ2), 116.5 (s), 124.1 (s), 125.0 (s), 126.6 (d), 127.4 (dꢁ2), 128.9
(dꢁ2), 129.7 (s), 130.3 (dꢁ2), 131.7 (dꢁ2), 136.2 (s), 139.7 (d), 150.0
(s); MS (70 eV): m/z: 427 (Mþ), 356 (MþꢂC4H9N); elemental
analysis calcd (%) for C22H22BrNOS: C, 61.68; H, 5.18; N, 3.27. Found:
C, 61.45; H, 5.13; N, 3.16.
4.22. 1-[2-(p-Bromophenyl)-3-(phenylsulfanylmethyl)-4-
furanylmethyl]-1H-benzotriazole (5f) (entry 6)
Yield 71%, a yellow oil; IR (KBr, cmꢂ1) 3434, 3058, 2925, 2853,
2361, 1615, 1506, 1459, 1440, 1287, 1253, 1179, 1065, 1027, 950,
836, 745, 691; 1H NMR (600 MHz, CDCl3)
d 3.82 (3H, s, Me), 3.90
(2H, s, CH2), 5.24 (2H, s, CH2), 6.91 (2H, d, J¼9.1 Hz, CH2),
7.25e7.26 (8H, m, ArH), 7.40e7.42 (1H, m, ArH), 7.46 (2H, d,
J¼8.9ꢂHz, ArH), 7.81 (1H, dd, J¼1.8 and 6.9 Hz, ArH), 7.93 (1H, s,
ArH); 13C NMR (150 MHz, CDCl3)
d 29.2 (t), 39.5 (t), 55.4 (q), 102.2
Yield 39%, white prisms, 85e88 ꢀC; IR (KBr, cmꢂ1) 3438, 3059,
(s), 110.1(d), 113.3 (s), 114.3 (dꢁ2), 120.5 (d), 121.3 (s), 121.7 (s),
122.4 (d), 122.9 (s), 123.2 (d), 127.1 (dꢁ2), 128.1 (dꢁ2), 129.1
(dꢁ2), 130.6 (dꢁ2), 135.4 (s), 140.0 (d), 153.0 (s), 159.7 (s); MS
(70 eV): m/z: 426 (Mþ), 317 (MþꢂSPh); elemental analysis calcd
(%) for C26H22N2O2S2: C, 68.10; H, 4.84; N, 6.11. Found: C, 68.26;
H, 4.83; N, 6.10.
2927, 1567, 1483, 1439, 1394, 1324, 1275, 1146, 1075, 1009, 948, 851,
829, 747, 690; 1H NMR (600 MHz, CDCl3)
d 4.18 (2H, s, CH2), 5.80
(2H, s, CH2), 7.23e7.28 (4H, m, ArH), 7.34e7.40 (7H, m, ArH), 7.48
(1H, dd, J¼2.1 and 6.9 Hz, ArH), 7.63 (1H, s, ArH), 7.83 (1H, dd, J¼2.1
and 6.9 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 28.9 (t), 49.9 (t),116.0
(s), 118.1 (dꢁ2), 121.1 (s), 122.1 (s), 126.4 (s), 126.5 (dꢁ2), 127.1 (d),
127.8 (dꢁ2), 129.0 (dꢁ2), 129.1 (s), 131.1 (dꢁ2), 131.8 (dꢁ2), 135.1
(s), 141.5 (d), 144.5 (s), 151.2 (s); MS (70 eV): m/z: 477 (Mþ), 369
(MþꢂSPh); elemental analysis calcd (%) for C24H18BrN3OS: C, 60.51;
H, 3.81; N, 8.82. Found: C, 60.33; H, 3.78; N, 8.75.
4.20. 1-[2-(p-Methoxyphenyl)-3-(phenylsulfanylmethyl)-4-
furanylmethyl]-2H-1,4-benzothiazin-3(4H)one (5d) (entry 4)
4.23. 1-[2-(p-Chlorophenyl)-3-(phenylsulfanylmethyl)-4-
(furanylmethyl)]pyrrolidine (5g) (entry 7)
Yield 70%, a yellow oil; IR (KBr, cmꢂ1) 3446, 2926, 2854, 1759,
1711, 1672, 1608, 1584, 1506, 1479, 1447, 1376, 1308, 1285, 1253,
1179, 1151, 1091, 1067, 1029, 962, 897, 836, 755, 690, 529; 1H NMR
Yield 61%, a yellow oil; IR (KBr, cmꢂ1) 2962, 2926, 2789, 2364,
1714, 1653, 1559, 1542, 1488, 1458, 1438, 1362, 1221, 1120, 1093,
1062, 1026, 1012, 944, 909, 876, 832, 741, 690, 531, 511, 444, 412; 1H
(600 MHz, CDCl3)
d 3.45 (2H, s, CH2), 3.82 (3H, s, CH3), 4.14 (2H, s,
CH2), 5.11 (2H, s, COCH2), 6.91 (2H, d, J¼8.9 Hz, ArH), 6.97e7.02
(1H, m, ArH), 7.12 (1H, s, ArH), 7.17e7.23 (3H, m, ArH), 7.25e7.28
(2H, m, ArH), 7.35e7.37 (3H, dd, J¼1.1 and 9.6 Hz, ArH), 7.48 (2H, d,
NMR (600 MHz, CDCl3)
d 1.77e1.78 (4H, m, CH2), 2.52 (4H, br s,
CH2), 3.50 (2H, s, CH2), 4.23 (2H, s, CH2), 7.20e7.22 (1H, m, ArH),
7.25e7.28 (2H, m, ArH), 7.33e7.37 (5H, m, ArH), 7.53e7.54 (2H, d,
J¼8.9 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 29.2 (t), 31.6 (t), 39.8
(t), 55.3 (q), 113.0 (s), 114.1 (dꢁ2), 118.3 (d), 122.8 (s), 123.2 (s),
123.7 (d), 123.8 (s), 126.6 (d), 127.3 (d), 127.8 (dꢁ2), 128.3 (d), 128.9
(dꢁ2), 130.1 (dꢁ2), 135.9 (s), 138.6 (d), 139.3 (s), 152.1 (s), 159.3 (s),
165.1 (s); MS (70 eV): m/z: 473 (Mþ), 364 (MþꢂSPh); high-
J¼8.9 Hz, ArH); 13C NMR (150 MHz, CDCl3)
23.6 (tꢁ2), 29.1 (t), 49.4
d
(t), 54.3 (tꢁ2),116.5 (s),124.9 (s),126.6 (d),127.2 (dꢁ2),128.8 (dꢁ2),
128.9 (dꢁ2), 129.3 (s), 130.4 (dꢁ2), 133.3 (s), 136.3 (s), 139.7 (d),
150.1 (s); MS (70 eV): m/z: 383 (Mþ), 311 (MþꢂC4H9N); high-
resolution mass calcd for
473.1092.
C
27H23NO3S2: 473.1119, found m/z
resolution mass calcd for
383.1104.
C22H22ClONS: 383.1110, found m/z

1314
H. Nagata et al. / Tetrahedron 70 (2014) 1306e1316
4.24. 1-[2-(p-Chlorophenyl)-3-(phenylsulfanylmethyl)-4-
furanylmethyl]-1H-benzimidazole (5h) (entry 8)
White plates, mp 147e149 ꢀC; IR (KBr, cmꢂ1) 3124, 2924, 2853,
1735, 1681, 1596, 1512, 1496, 1459, 1381, 1310, 1287, 1191, 1175, 1901,
1066, 968, 887, 817, 754, 703, 674, 887, 817, 754, 703, 674, 590, 539;
Yield 65%, a yellow oil; IR (KBr, cmꢂ1) 3057, 2925, 2855, 2359,
1710, 1615, 1583, 1489, 1458, 1439, 1364, 1331, 1286, 1268, 1202,
1150, 1093, 1062, 1011, 949, 833, 742, 691, 618, 507, 473, 426; 1H
1H NMR (600 MHz, CDCl3)
d 2.42 (3H, s, Me), 5.46 (2H, s, CH2), 6.81
(1H, s, ArH), 7.23e7.28 (3H, m, ArH), 7.31 (2H, d, J¼7.6 Hz, ArH), 7.70
(2H, d, J¼8.2 Hz, ArH), 7.76 (1H, d, J¼2.7 Hz, ArH), 7.81 (1H, d,
J¼8.2 Hz, ArH), 8.01 (1H, s, ArH), 9.85 (1H, s, CHO); 13C NMR
NMR (600 MHz, CDCl3)
d 3.89 (2H, s, CH2), 5.24 (2H, s, CH2),
7.24e7.32 (10H, m, ArH), 7.34 (1H, d, J¼9.0 Hz, ArH), 7.44 (2H, d,
J¼8.2 Hz, ArH), 7.82 (1H, d, J¼6.9 Hz, ArH), 7.93 (1H, s, ArH); 13C
(150 MHz, CDCl3)
d 21.8 (q), 40.8 (t), 109.8 (d), 120.6 (d), 120.8 (d),
122.3 (d), 123.1 (d), 126.6 (s), 127.4 (dꢁ2), 130.6 (dꢁ2), 130.8 (d),
133.6 (s), 134.3 (s), 143.4 (d), 143.4 (s), 146.6 (s), 185.6 (d); MS
(70 eV): m/z: 379 (small Mþ); elemental analysis calcd (%) for
NMR (150 MHz, CDCl3)
d 29.1 (t), 39.1 (t), 109.9 (d), 115.1 (s), 120.5
(d), 122.0 (s), 122.4 (d), 123.1 (d), 127.3 (d), 127.6 (dꢁ2), 128.4 (s),
128.9 (dꢁ2), 129.1 (dꢁ2), 131.0 (dꢁ2), 133.7 (s), 134.2 (s), 134.7 (s),
140.3 (d), 142.8 (d), 143.9 (s), 151.7 (s); MS (70 eV): m/z: 430 (Mþ),
321 (MþꢂSPh); elemental analysis calcd (%) for C25H19Cl N2OS: C,
69.68; H, 4.44; N, 6.50. Found: C, 69.34; H, 4.42; N, 6.25.
C20H17N3O3S: C, 63.31; H, 4.52; N, 11.07. Found: C, 63.25; H, 4.46; N,
11.02.
4.25. 1-[2-(Naphthyl)-3-(phenylsulfanylmethyl)-4-
(furanylmethyl)]pyrrolidine (5i) (entry 9)
A pale yellow oil; IR (KBr, cmꢂ1) 2931, 1615, 1596, 1496, 1459,
1373, 1331, 1287, 1266, 1190, 1173, 1093, 1066, 983, 814, 746, 703,
676; 1H NMR (600 MHz, CDCl3)
2.41 (3H, s, Me), 3.21 (6H, s,
OMeꢁ2), 5.06 (1H, s, CH), 5.18 (2H, s, CH2), 6.97 (1H, br s, ArH), 7.18
(1H, br s, ArH), 7.20e7.28 (5H, m, ArH), 7.68 (2H, d, J¼8.3 Hz, ArH),
7.79 (1H, d, J¼8.2 Hz, ArH), 7.89 (1H, br s, ArH); MS 308
(Mþꢂimidazole).
d
Yield 69%, a yellow oil; IR (KBr, cmꢂ1) 3450, 3055, 2963, 2926,
2873, 2790, 1584, 1558, 1507, 1480, 1460, 1438, 1412, 1389, 1376,
1347, 1322, 1292, 1251, 1199, 1123, 1104, 1068, 1024, 935, 877, 864,
802, 777, 740, 691, 568; 1H NMR (600 MHz, CDCl3)
d 1.81 (4H, br s,
CH2), 2.60 (4H, br s, CH2), 3.68 (2H, s, CH2), 4.09 (2H, s, CH2),
7.04e7.05 (3H, m, ArH), 7.16e7.17 (2H, m, ArH), 7.41e7.47 (4H, m,
ArH), 7.49 (1H, s, ArH), 7.83e7.86 (3H, m, ArH); 13C NMR (150 MHz,
4.27. Oxidation of 1-[4-(phenylsulfanylmethyl)-1-
(4-methylphenylsulfonyl)pyrrol-4-ylmethyl]pyrrolidine (2a)
with ceric ammonium nitrate (CAN) (Scheme 2)
CDCl3)
d
23.6 (tꢁ2), 29.0 (t), 49.9 (t), 54.4 (tꢁ2), 118.2 (s), 124.2 (s),
125.1 (s), 125.9 (d), 126.0 (d), 126.1 (d), 126.4 (d), 127.8 (s), 128.1 (d),
128.1 (d), 128.6 (dꢁ2), 129.2 (d), 130.0 (dꢁ2), 132.1 (s), 133.7 (s),
136.3 (s), 140.1 (d), 151.2 (s); MS (70 eV): m/z: 399 (Mþ), 328
(MþꢂC4H9N); elemental analysis calcd (%) for C26H25NOS: C, 78.16;
H, 6.31; N, 3.51. Found: C, 77.93; H, 6.30; N, 3.46.
4.26. Oxidation of 1-[4-(phenylsulfanylmethyl)-1-
(4-methylphenylsulfonyl)pyrrol-4-ylmethyl]benzimidazole
(2k) with ceric ammonium nitrate (CAN) (Scheme 2)
CAN (0.17 g, 0.31 mmol) was added to a MeOH (1.0 mL) solution of
2k (50 mg, 0.10 mmol) at room temperature. The reaction mixture
was stirred for 1 h and poured into water (50 mL). The organic layer
was separated and the aqueous layer was extracted with CHCl3.
The combined organic layer was dried over MgSO4. The solvent was
removed under reduced pressure. The residue was purified by pre-
parativeTLConsilicagelelutingwithCHCl3/MeOH (40:1)to give 4-(1-
benzimidazolylmethyl)-N-(4-methylphenylsulfonyl)-1H-pyrrole-3-
carboxaldehyde (18k) (36 mg, 89%) and 4-(1-benzimidazolylmethyl)-
N-(4-methylphenylsulfonyl)-1H-pyrrole-3-carboxaldehyde dimethyl
acetal (19k) (2.0 mg, 5%).
A yellow oil; IR (KBr, cmꢂ1) 2957, 2925, 2854, 1684, 1596, 1507,
1458, 1380, 1312, 1261, 1191, 1174, 1092, 1064, 814, 758, 703, 673,
d 1.76e1.78 (4H, m, CH2), 2.43 (3H,
s, Me), 2.55 (4H, br s, CH2), 3.75 (2H, s, CH2), 7.13 (1H, br s, ArH), 7.34
592; 1H NMR (600 MHz, CDCl3)
(2H, d, J¼8.2 Hz, ArH), 7.71 (1H, d, J¼2.7 Hz, ArH), 7.80 (2H, d,
J¼8.2 Hz, ArH), 9.89 (1H, s, CHO); 13C NMR (150 MHz, CDCl3)
d 21.7
(q), 23.5 (tꢁ2), 51.0 (t), 54.2 (tꢁ2), 120.3 (d), 126.5 (s), 127.3 (dꢁ2),
127.5 (s), 128.8 (d), 130.3 (dꢁ2), 134.9 (s), 146.0 (s), 186.1 (d); MS
(70 eV): m/z: 332 (Mþ). High-resolution mass calcd for
C17H20N2O3S: 332.1194, found m/z 332.1176.

H. Nagata et al. / Tetrahedron 70 (2014) 1306e1316
1315
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K. C.; Yus, M.; Foubelo, F.; Tada, M. Chem. Rev. 2008, 108, 3795e3892; (m)
Chemler, S. R. Org. Biomol. Chem. 2009, 7, 3009e3019; (n) Andrea, T.; Eisen, M. S.
Chem. Soc. Rev. 2008, 37, 550e567.
4.28. Oxidation of 1-[4-(phenylsulfanylmethyl)-1-
(4-methylphenylsulfonyl)pyrrol-4-ylmethyl]piperidine (2b)
with ceric ammonium nitrate (CAN) (Scheme 2)
€
2. (a) Trost, B. M.; Tang, W. J. Am. Chem. Soc. 2002, 124, 14542e14543; (b) Nagle,
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lenbeck, T.; Tuntland, T.; Isbell, J.; Chuan, T.; Alper, P. B.; Fischli, C.; Brun, R.;
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Zhang, S.; Lou, Z.; Su, X.; Wen, L.; Li, M. Org. Lett. 2013, 15, 4794e4797; (g)
Bhonde, V. R.; Looper, R. E. J. Am. Chem. Soc. 2011, 133, 20172e20174; (h) Nolan,
S. P. PCT Int. Appl. WO 2011107736 A1 20110909, 2011; (i) Perl, N. R.; Ide, N. D.;
Prajapati, S.; Perfect, H. H.; Duron, S. G.; Gin, D. Y. J. Am. Chem. Soc. 2010, 132,
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9272e9274; (b) Xu, M.; Samala, S.; Krishna, D. G. V.; Kundu, B. Synthesis 2013,
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2012, 14, 326e329; (d) Demir, A. S.; Emrullahoglu, M.; Buran, K. Chem. Commun.
2010, 8032e8034; (e) Hirano, K.; Inaba, Y.; Watanabe, T.; Oishi, S.; Fujii, N.;
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D.; Li, J.; Jiang, H.; Liu, H. J. Org. Chem. 2009, 74, 7344e7348; (g) Kang, J.-E.; Kim,
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Dovey, M. C.; Gravestock, D. Eur. J. Org. Chem. 2005, 505e511.
Colorless prisms, mp 128e129 ꢀC; IR (KBr, cmꢂ1) 3129, 2934,
2348, 1685, 1596, 1508, 1455, 1380, 1313, 1175, 1091, 1063, 968, 815,
756, 673, 592, 539; 1H NMR (600 MHz, CDCl3)
d 1.41 (2H, br s, CH2),
1.53e1.55 (4H, m, CH2), 2.39 (4H, br s, CH2), 2.43 (3H, s, Me), 3.57
(2H, s, CH2), 7.09 (1H, br s, ArH), 7.34 (2H, d, J¼8.2 Hz, ArH), 7.71
(1H, d, J¼2.8 Hz, ArH), 7.79 (2H, d, J¼8.2 Hz, ArH), 9.92 (1H, s, CHO);
13C NMR (150 MHz, CDCl3)
d
21.7 (q), 24.2 (t), 25.9 (tꢁ2), 53.9 (t),
54.5 (tꢁ2), 120.4 (d), 125.7 (s), 127.3 (dꢁ2), 128.9 (s), 128.3 (d), 130.3
(dꢁ2), 135.0 (s), 146.0 (s), 186.4 (d); MS (70 eV): m/z: 346 (Mþ);
elemental analysis calcd (%) for C18H22N2O3S: C, 62.40; H, 6.40; N,
8.09. Found: C, 62.19; H, 6.38; N, 7.88.
4. Ti: (a) Shen, H.; Xie, Z. J. Am. Chem. Soc. 2010, 132, 11473e11480; (b) Facotti, D.;
Abbiati, G.; d’Avolio, L.; Ackermann, L.; Rossi, E. Synlett 2009, 2273e2276; (c)
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Kaspar, L. T.; Gschrei, C. J. Chem. Commun. 2004, 2824e2825; (g) Ramanathan,
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Bytschkov, I.; Doye, S. Tetrahedron Lett. 2002, 43, 3715e3718.
4.29. Desulfonylation of N-tosylpyrrole 4k22
5. Zn: (a) Biyikal, M.; Loehnwitz, K.; Meyer, N.; Dochnahl, M.; Roesky, P. W.;
Blechert, S. Eur. J. Inorg. Chem. 2010, 1070e1081; (b) Yin, Y.; Chai, Z.; Ma, W.-Y.;
Zhao, G. Synthesis 2008, 4036e4040.
6. Pt: (a) Patil, N. T.; Kavthe, R. D.; Shinde, V. S.; Sridhar, B. J. Org. Chem. 2010, 75,
3371e3380; (b) Krogstad, D. A.; Cho, J.; DeBoer, A. J.; Klitzke, J. A.; Sanow, W. R.;
Williams, H. A.; Halfen, J. A. Inorg. Chim. Acta 2006, 359, 136e148.
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B. A. Organometallics 2012, 31, 7500e7510.
8. Rh: (a) Hua, C.; Vuong, K. Q.; Bhadbhade, M.; Messerle, B. A. Organometallics
2012, 31, 1790e1800; (b) Clentsmith, G. K. B.; Field, L. D.; Messerle, B. A.; Bar-
bara, A.; Shasha, A.; Turner, P. Tetrahedron Lett. 2009, 50, 1469e1471; (c)
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2058e2069.
The 5 M NaOH solution (1.0 mL) was added to 2k (30 mg,
0.06 mmol) in isopropanol (1.0 mL). The mixture was refluxed for
8 h. The cooled mixture was poured into water (50 mL). The organic
layer was separated and the aqueous layer was extracted with
AcOEt. The combined organic layer was dried over MgSO4. The
solvent was removed under reduced pressure. The residue was
purified by preparative TLC on silica gel eluting with AcOEt/n-
hexane (1:2) to give 20k (16 mg, 80%).
9. Ca: Datta, S.; Roesky, P. W.; Blechert, S. Organometallics 2007, 26, 4392e4394;
Fe: Majumdar, K. C.; De, N.; Roy, B. Synthesis 2010, 4207e4212.
Colorless needles, mp 156e157 ꢀC; IR (KBr, cmꢂ1) 3419, 2924,
1853, 1716, 1615, 1583, 1496, 1480, 1459, 1439, 1381, 1332, 1287,
1267, 1197, 1121, 1072, 1025, 744, 692; 1H NMR (600 MHz, CDCl3)
10. (a) Patil, N.; Lutete, L. M.; Wu, H.; Pahadi, N. K.; Gridnev, I. D.; Yamamoto, Y. J.
€
Org. Chem. 2006, 71, 4270e4279; (b) Muller, T. E.; Berger, M.; Grosche, M.;
Herdtweck, E.; Schmidtchen, F. P. Organometallics 2001, 20, 4384e4393; (c)
€
Muller, T. E.; Grosche, M.; Herdtweck, E.; Pleier, A.-K.; Walter, E.; Yan, Y.-K.
Organometallics 2000, 19, 170e183; (d) Kadota, I.; Shibuya, A.; Lutete, L. M.;
Yamamoto, Y. J. Org. Chem. 1999, 64, 4570e4571.
d
3.86 (2H, s, CH2), 5.35 (2H, s, CH2), 6.65 (1H, br s, ArH), 6.76 (1H, br
s, ArH), 7.14e7.28 (7H, m, ArH), 7.51 (1H, brd, J¼8.2 Hz, ArH),
11. Ru: (a) Ackermann, L.; Althammer, A. Synlett 2006, 3125e3129; (b) Kuninobu,
Y.; Nishina, Y.; Takai, K. Org. Lett. 2006, 8, 2891e2893; (c) Yi, C. S.; Yun, S. Y. J.
Am. Chem. Soc. 2005, 127, 17000e17006; (d) Yi, C. S.; Yun, S. Y.; Guzei, I. A. J. Am.
Chem. Soc. 2005, 127, 5782e5783.
7.62e7.68 (1H, m, ArH), 7.96 ppm (1H, s, ArH); 13C NMR (150 MHz,
CDCl3) d 29.1 (t), 40.3 (t), 109.9 (d), 114.9 (s), 115.8 (s), 117.9 (d), 118.1
(d), 118.3 (d), 121.6 (d), 122.2 (d), 125.4 (d), 127.9 (dꢁ2), 129.0 (dꢁ2),
133.2 (s), 136.0 (s), 142.3 (sꢁ2); MS (70 eV): m/z: 319 (Mþ); ele-
mental analysis calcd (%) for C19H17N3S: C, 71.44; H, 5.36; N, 13.15.
Found: C, 71.25; H, 5.35; N, 12.93.
12. Y: Gribkov, D. V.; Hultzsch, K. C.; Hampel, F. Chem.dEur. J. 2003, 9, 4796e4810.
13. In: Chanda, T.; Verma, R. K.; Singh, M. S. Chem. Asian J. 2012, 7, 778e787.
14. Lanthanides: (a) Seo, S.-Y.; Marks, T. J. Chem.dEur. J. 2010, 16, 5148e5162; (b)
Yuen, H.; Marks, T. J. Organometallics 2009, 28, 2423e2440; (c) Seo, S.-Y.; Yu, X.;
Marks, T. J. J. Am. Chem. Soc. 2009, 131, 263e276; (d) Motta, A.; Fragala, I.; Marks,
T. J. Organometallics 2006, 25, 5533e5539; (e) Rastaetter, M.; Zulys, A.; Roesky,
P. W. Chem. Commun. 2006, 874e876; (f) Kim, H.; Livinghouse, T.; Shim, J.-H.;
Lee, S. G.; Lee, P. H. Adv. Synth. Catal. 2006, 348, 701e704; (g) Panda, T. K.; Zulys,
A.; Gamer, M. T.; Roesky, P. W. J. Organomet. Chem. 2005, 690, 5078e5089; (h)
Zulys, A.; Panda, T. K.; Gamer, M. T.; Roesky, P. W. Chem. Commun. 2004,
2584e2585; (i) Ryu, J.-S.; Li, G. Y.; Marks, T. J. J. Am. Chem. Soc. 2003, 125,
12584e12605; (j) Burgstein, M. R.; Berberich, H.; Roesky, P. W. Chem.dEur. J.
2001, 7, 3078e3085; (k) Ki, Y.; Marks, T. J. J. Am. Chem. Soc. 1996, 118,
9295e9306; (l) Li, Y.; Fu, P.-F.; Marks, T. J. Organometallics 1994, 13, 439e440.
15. Actinides: (a) Stubbert, B. D.; Marks, T. J. J. Am. Chem. Soc. 2007, 129,
4253e4271; (b) Stubbert, B. D.; Stern, C. L.; Marks, T. J. Organometallics 2003,
22, 4836e4838.
References and notes
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en-
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Holscher, B. Angew. Chem., Int. Ed. 2001, 40, 3983e3985; (e) Beller, M.; Breindl,
C.; Eichberger, M.; Hartung, C. G.; Seayad, J.; Thiel, O. R.; Tillack, A.; Trauthwein,
H. Synlett 2002, 1579e1594; (f) Bytschkov, I.; Doye, S. Eur. J. Org. Chem. 2003,
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Widenhoefer, R. A.; Han, X. Eur. J. Org. Chem. 2006, 4555e4563; (j) Severin, R.;

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