Head-to-tail homo- and heterodimerization of vinylamides by hidden proton catalysis

Article abstract of DOI:10.1016/j.tet.2013.12.041

Chemoselective dimerization of vinylamides is reported. A number of vinylacylamides were shown to undergo stereoselective cationic intermolecular head-to-tail homodimerization. Correspondingly, chemoselective heterodimerization reactions readily afforded hydroalkenylation of vinylacylamide with vinylsulfonamide. Different mild methods for hidden proton catalysis were studied. The in situ generation of, e.g., HSbF₆ from the [Au]SbF₆-PhCCH] catalytic systems was applied. Successful vinylacylamide head-to-tail dimerizations seem to be dependant on the ability of N-C-O acylamide electron delocalization, affording stabilized intermediates. In general, the reactions demonstrate the ability of vinylacylamides to effectively undergo hydroalkenylation to afford 1,3-N,N-functionalized (E)-but-1-ene products.

Full text of DOI:10.1016/j.tet.2013.12.041

Tetrahedron 70 (2014) 1317e1325
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Head-to-tail homo- and heterodimerization of vinylamides by
hidden proton catalysis
*
Naseem Iqbal, Guro Blakstad, Anne Fiksdahl
Department of Chemistry, Høgskoleringen, Norwegian University of Science and Technology, NTNU, NO-7491 Trondheim, Norway
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 June 2013
Received in revised form 3 December 2013
Accepted 16 December 2013
Available online 21 December 2013
Chemoselective dimerization of vinylamides is reported. A number of vinylacylamides were shown to
undergo stereoselective cationic intermolecular head-to-tail homodimerization. Correspondingly, che-
moselective heterodimerization reactions readily afforded hydroalkenylation of vinylacylamide with
vinylsulfonamide. Different mild methods for hidden proton catalysis were studied. The in situ gener-
ation of, e.g., HSbF6 from the [Au]SbF6ePhC^CH] catalytic systems was applied. Successful vinyl-
acylamide head-to-tail dimerizations seem to be dependant on the ability of NeCeO acylamide electron
delocalization, affording stabilized intermediates. In general, the reactions demonstrate the ability of
vinylacylamides to effectively undergo hydroalkenylation to afford 1,3-N,N-functionalized (E)-but-1-ene
products.
Keywords:
Vinylacylamides
Homodimerization
Heterodimerization
Hidden proton catalysis
Gold(I) catalyst
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
Studies of styrene (ii) homodimerization catalyzed by acid ze-
olites2 or with liquid acids (H2SO4)3 have shown that such reactions
Alkenes may undergo different chemoselective dimerization
processes (Scheme 1; (i)e(iii)). Aliphatic coupling products II may
be obtained through metallacycle intermediates by some
transition-metal catalyzed (i) reductive tail-to-tail dimerization of
alkenes I and I0.1 Homodimerization of alkenes I may take place by
tail-to-tail or head-to-head couplings. In contrast, the (ii) head-to-
tail homodimerization would afford the respective branched vi-
nylic dimers III (R^R0). Correspondingly, (iii) heterodimers III
(R¼R0) may chemoselectively be provided by mixed dimerization
of two different vinyl moieties I and I0 in a hydroalkenylation
manner.
suffer from low selectivity since the (cyclo)dimers are formed to-
gether with variable amounts of trimers and oligomers with nearly
lack of Z/E stereoselectivity. A variety of catalytic conditions, based
on e.g., Pd,4aec Co4d and Ni4e complexes are known to promote
selective (ii) head-to-tail homodimerization. Lewis acids, such as
Fe(III) complexes4f or In(OTf)3,4g catalyze regio- and stereoselective
head-to-tail homo- and heterodimerization of vinylarenes. Such
reactions are suggested to take place through
mechanism.
a cationic
We have recently studied the chemoselective cyclopropanation
and [2þ3] cycloaddition reaction pathways taking place by gold(I)
catalyzed reactions of propargyl derivatives with vinylic com-
pounds directly connected to a heteroatom, such as vinylic acetates,
ethers and amides (Scheme 2).5 In some cases, the expected
cyclopropanation or [2þ3] cycloaddition pathways to give products
3 or 30 were not favoured. However, in a reaction of vinyl-
pyrrolidone (2a) and phenylpropargyl pivaloate (1) in the presence
of the gold catalyst Au[P(t-Bu)2(o-biphenyl)CH3CN]SbF6, an in-
termolecular vinyl homodimerization mainly took place by
hydroalkenylation of the vinylamide and, thus, the head-to-tail E-
homodimer 4a was isolated in 85% yield. The unpredicted outcome
of the reaction was limited to the vinylacylamides, such as the
vinylpyrrolidinone 2a. A possible reaction pathway includes the
vinylamide, acting both as a nucleophile and an electrophile, which
is surprising due to their relatively poor nucleophilicity compared
Scheme 1. Dimerization processes.
* Corresponding author. E-mail address: anne.fiksdahl@chem.ntnu.no (A.
Fiksdahl).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.12.041

1318
N. Iqbal et al. / Tetrahedron 70 (2014) 1317e1325
Table 1
Studies on catalysts to promote vinylamide dimerization
Entry
1
Conditionsa
Dimer 4a; isolated
yield (2a conversion)
Au[P(t-Bu)2(o-biphenyl)CH3CN]SbF6
Propargyl ester 1
Au[P(t-Bu)2(o-biphenyl)CH3CN]SbF6
Au[P(t-Bu)2(o-biphenyl)ClþAgSbF6
Au[P(t-Bu)2(o-biphenyl)CH3CN]SbF6
Phenylacetylene
85% (99%)
2
3
4
ndb
ndb
Scheme 2. Gold(I) catalyzed cycloaddition and dimerization processes.
84% (99%)
5
Au[P(t-Bu)2(o-biphenyl)ClþAgSbF6
73% (99%)
Phenylacetylene
6
7
8
AgSbF6, Phenylacetylene
Phenylacetylene
Au[P(t-Bu)2(o-biphenyl)CH3CN]SbF6
1-Phenyl-1-propyne
AgSbF6
Au[P(t-Bu)2(o-biphenyl)Cl
ndb
ndb
ndb
with, e.g., electron-rich enamines used for nucleophile activation in
organocatalysis.
Despite the variety of protocols developed for vinylarene di-
merization, to the best of our knowledge, only a few homo- or
heterodimerization reactions of vinylamides have been reported.
Ruthenium catalyzed codimerization of N-vinylacylamides with
alkenes afforded moderate yields of heterodimers (III, Scheme 1)
with >88% E-selectivity.4h Only N-vinylacylamides did undergo
successful heterodimerization, whereas no codimerization took
place with N-methyl-N-vinyltoluenesulfonamide (see our NMeTs-
vinylamide 2g below), explained by the lack of Ru-chelation
ability of the tosylamide (S]O in contrast to acylamide C]O).
9
10
ndb
ndb
c
11
12
13
14
HSbF6
60% (99%)
35% (40%)
43% (80%)
51% (99%)
TFAc
HOTfc
c
H2SO4
15
16
17
AgSbF6, DCEd
72%
74%
77%
AgOTf, DCEd
AgOTf, DCEþt-BuCld
A
mechanistic study of cationic polymerization of N-vinyl-
a
Catalyst (5 mol %), DCM (10 mL/mmol substrate), reflux, 1.5 h.
No dimer formation.
Bronsted acid (2.5e5 mol %).
Silver salt (5 mol %)þDCE (10 mL/mmol substrate) (þt-BuCl; 0.1 equiv).
acylamides4i has been carried out, due the fact that N-vinyl-
acylamides, being important monomers for industrial free-radical
polymerization, are less frequently applied in cationic induced
polymerizations.4jem Different outcomes of the reactions of two
secondary and two tertiary vinylacylamides were observed as,
respectively, cationic polymerization and head-to-tail homo-
dimerization took place. No optimization studies were carried
out.
b
c
d
procedure, even if some lower yields of dimer 4a were obtained
(73%, entry 5). No dimerization took place in the absence of the
gold(I)SbF6 catalyst (entries 6 and 7) and non-terminal alkynes
did not afford dimerization (entry 8). Simpler Ag(I) or Au(I) cat-
alytic systems also failed to catalyze the reaction (entries 9 and
10).
The fact that the presence of a terminal alkyne was crucial for
the vinyl dimerization to take place, would indicate that a gold(I)-
acetylide complex was formed by PhCCH deprotonation and
a subsequent MeCNeacetylide ligand exchange. The rapid aceto-
nitrile ligand exchange was demonstrated by NMR studies of a 1:1
mixture of propargyl ester 1 and the applied [Au(I)NCMe]SbF6
complex, shown by the instant disappearance of the liganded
acetonitrile 1H NMR singlet (1.50 ppm) and the new recorded ‘free’
acetonitrile new singlet (2.32 ppm).5b
We wanted to explore the potential and limitations of head-to-
tail intramolecular homo-coupling of tertiary N-vinylacylamides
and -sulfonamides, as well as the ability of such substrates to un-
dergo more challenging heterodimerization. In order to identify the
active catalyst and investigate the effect of different catalytic sys-
tems, a further study and optimization of the catalytic system was
essential. We herein report our investigations on catalyzed vinyl-
amide dimerization reactions.
2. Results and discussion
2.1. Studies on the catalytic system
Dual gold catalysis including geminal digold complexes as well
With the aim of revealing the true nature of the active cata-
lyst, promoting the vinylamide dimerization, we investigated the
effect of modified catalytic systems based on the originally ap-
plied reaction conditions (Scheme 2) with vinylpyrrolidone (2a)
and phenylpropargyl pivaloate (1) in the presence of the gold
catalyst Au[P(t-Bu)2(o-biphenyl)CH3CN]SbF6 (Table 1), affording
the head-to-tail homodimer 4a as the major product. However,
we observed that the propargylic ester 1 was not involved in the
reaction, as the propargyl compound was fully recovered (entry
1). On the other hand, the gold-catalyzed dimerization of the
vinylic substrate 2a was unsuccessful in the absence of propargyl
compound 1 (entries 2 and 3), demonstrating its essential effect
on the reaction. Further studies showed that effective di-
merization was also obtained by replacing the propargylic com-
pound 1 by other terminal alkynes, such as phenylacetylene (84%
yield 4a, entry 4). The outcome of the reaction was unaffected by
applying the normal AuðIÞCl=SbF6 counter-ion exchange
as dinuclear gold(I)
s,p-acetylide complexes, is currently given
considerable attention.6 Actually, gold-catalyzed reactions in-
volving terminal alkynes have been reported to involve formation
of gold(I) s,p
-acetylide digold species.6e,f Due to the generation of
a strong Brønsted acid during the reaction, it has been remarked
that the potential involvement of proton catalysis should be con-
sidered in gold-catalyzed transformations involving terminal al-
kynes. Studies of [2þ2] phenylacetyleneealkene cycloaddition in
the presence of ½AuðLÞNCMeꢀþSbFꢁ6 catalysts showed the genera-
tion of the HSbF6 bronsted super-acid by the formation of digold
½ðAuLÞ2CCPhꢀþSbFꢁ6 complexes:6g
h
i
h
i
ꢀ
PhC^CH þ 2 ½AuðLÞNCMeꢀþSbF6ꢁ
þ 2MeCN þ HSbF6
/
ðAuLÞ2C^CPhꢀþSbF6ꢁ
(1)

N. Iqbal et al. / Tetrahedron 70 (2014) 1317e1325
1319
Table 2
Control experiments indicated that HSbF6 directly promoted
Vinylamide homodimerization catalyzed by Au(I)SbF6ealkyne
the formation of mixtures of
products.
a-methylstyrene (cyclo)dimer
There is a recent focus on reactions catalyzed by in situ gen-
erated Bronsted acids from Lewis acid or metal triflate pre-
catalysts. The use of the so-called ‘Hidden Brønsted acid catalysis’
was lately studied and successfully applied in hydroalkoxylation
reactions by generation of HOTf from AgOTf and 1,2-
dichloroethane (DCE) or t-BuCl by chloride abstraction.7 The
AgCl precipitate was either initially filtered off or left in the
resulting suspension to allow in situ proton generation and a one-
pot reaction protocol.
We wanted to study whether the present vinylamide di-
merization would take place by the alternative hidden proton-
catalyzed pathway from the [AuSbF6ePhC^CH] catalytic system.
Thus, by replacing the gold(I)SbF6/terminal alkyne system with the
direct addition of HSbF6 super-acid or other acids (entries 11e14), it
would become clear whether the vinylamide 2a dimerization ac-
tually was catalyzed by HSbF6, generated in situ. In fact, the di-
merization took place in the presence of approximately
2.5e5 mol % HSbF6 (entry 11), affording full conversion of vinyl-
amide 2a, but only moderate yield of dimer 4a (60%). Other acids,
such as TFA, HOTf and sulfuric acid also afforded dimerization, but
lower conversion of 2a and poorer yields of dimer 4a (35e51%,
entries 12e14) were obtained.
Such control experiments were shown to be less reliable, due
to problems arising from the handling of small amounts of strong
acids.7 The hidden proton catalysis methods allow milder condi-
tions by controlled generation of the acid catalyst. Therefore, an
alternative experiment with in situ generation of HSbF6 super-
acid from AgSbF6 in DCE, based on an established protocol,7 was
tested. The dimer 4a was isolated in high yields (72%, entry 15)
from vinylamide 2a (entry 15). Correspondingly, the previously
established method,7 generating HOTf from AgOTf and DCE or t-
BuCl, afforded similar yields of product 4a (74e77%, entries
16 and 17).
Thus, the protocols for hidden Bronsted acid catalysis, generat-
ing HSbF6 or HOTf from the [AuSbF6ePhC^H] (entries 4 and 5)
catalytic system or from the respective silver salts (AgSbF6/AgOTf
and DCE/t-BuCl; entries 15e17), afforded higher yield (more than
72%) of dimer 4a from vinylamide 2a than corresponding control
experiments with direct acid catalysis with HSbF6 or HOTf (60 and
43%, entries 11 and 13).
Entry
1
Monomer
Reaction timea
1.5 h
Dimer (yield)
4a (84%)
2
3
24 h
24 h
4b (79%)
4c (89%)
4
5
6
7
8
20 h
4d (72%)
4e (64%)
4f (69%)d
ndc
2 h
30 min
30 minb
24 h
nde
9
24 h
nde
a
Reaction time needed to give full conversion (GLC).
Reaction at 0 ꢂC.
No dimer, complex product mixture.
49% obtained by in situ HSbF6 generation from AgSbF6/DCE.
No dimer, no conversion.
b
c
d
e
methyl N-acetamides 2e and 2f readily gave homodimers 4e (64%,
entry 5) and 4f (69% (49% obtained with AgSbF6/DCE), entry 6).
Some degree of isomerization of the main N-acetamide product 4f
took place, as shown by the presence of minor amounts of amide
rotamers of 4f (approx. 25% in total by 1H NMR), as also reported by
others.4i A corresponding isomerization of the N-phenyl product 4e
was not observed. In contrast to the rapid reactions of 2a and 2f
(1.5 h and 30 min, entries 1 and 6), the corresponding dimerization
of the heterocyclic vinylacylamides 2bed was slower (more than
20 h, entries 2e4).
The NMeTs-vinylsulfonamide 2g was, however, far too reactive
and gave instantly complex product mixtures, also at 0 ꢂC (entry 7).
Our previous studies5a on gold(I) catalyzed cyclizations of prop-
argyl esters have shown that NMeTs-vinylamide 2g follows a dif-
ferent reaction pathway than other vinylic reactants tested,
showing the deviating reactivity of this vinylic compound. The N-
vinylphthalimide 2h and vinylimidazole 2i compounds were not
reactive and no conversion could be observed, even after 24 h
(entries 8 and 9).
Most of these one-pot methods (entries 5 and 15e17) cause
precipitation of AgCl. The resulting suspensions seem to reduce
the dimer yields (72e77%) relative to the catalysis with proton
generation from the [AuSbF6ealkyne] systems (84e85%, entries
1 and 4), not including chloride counter-ion exchange and AgCl
precipitation. A similar observation was made for the homo-
dimerization of N-methyl N-acetamide 2f (AgSbF6/DCE; 49% vs
AuSbF6/alkyne; 69% yield of dimer 4f; Table 2, entry 6 below).
Hence, the most effective and convenient one-pot reaction was
obtained by the hidden Bronsted acid catalysis protocol by in
situ generation of HSbF6 from the catalytic [Au[P(t-Bu)2(o-bi-
phenyl)CH3CN]SbF6ePhC^CH] system in refluxing dichloro-
methane (Table 1, entry 4), which was used in the subsequent
study.
2.2. Homodimerization
A number of vinylacylamide compounds were shown to un-
dergo homodimerization to afford 1,3-N,N-functionalized (E)-but-
1-ene products (Table 2). Heterocyclic vinylacylamides (vinyl-pyr-
rolidinone, -piperidinone, -azepanone, -oxazolidinone, 2aed)
afforded the respective dimers 4aed in high yields (72e89%; en-
tries 1e4). Likewise, the open-chained vinyl N-phenyl- and N-
2.3. Heterodimerization
By tuning the reactivity of two different vinylamide reactants,
heterodimerization reactions could take place by vinylamide
hydroalkenylation in a mixed dimerization manner. In order to
study possible chemoselective formation of heterodimers, the

1320
N. Iqbal et al. / Tetrahedron 70 (2014) 1317e1325
Table 4 (continued)
electronic or steric nature of different vinylamide substrates was
varied. The results from reactions based on this strategy in the
presence of the [AuSbF6ealkyne] system, are shown in Tables 3
and 4. Since the NMeTs-vinylsulfonamide 2g was too reactive
Entry
5c
Monomer
Monomer
Reaction
time
Heterodimer
(yield, %)
Homodimer
(yield, %)
1 h
ndd
4a (49)
4f (Traces)
Table 3
Optimization of mixed dimerization in the presence of Au(I)SbF6ephenylalkyne
a
The reactions were performed with phenylacetylene (1.0 equiv), vinylamide I
(2g, 2f) (2.0 equiv) and vinylacylamide II (2a, 2b, 2c, 2f) (1.0 equiv) in DCM (10 mL/
mmol) and gold catalyst (0.05 equiv) dissolved in DCM (10 mL/mmol).
b
Product 6 was formed in minor amounts.
Product 7 was formed in minor amounts.
Not detected.
c
d
to allow controlled homodimerization, this compound was cho-
sen for heterodimerization with less reactive vinylacylamide
reactants.
Full conversion of NMeTs-vinylamide 2g with vinyl-
pyrrolidinone 2a (1:1) was obtained in 3 h at room temperature
in DCM (Table 3, entry 1). The E-heterodimer 5a was formed by
hydroalkenylation of vinylacylamide 2a with vinylsulfonamide
2g. The alternative heterodimer 6a, formed by the opposite
hydroalkenylation of vinylsulfonamide 2g with vinylacylamide
Entry 2g
(equiv)
2a (equiv) PhCCH Temp, solvent Conv. 5a Yield,a 4a Yielda
(equiv)
(%)
% (ratio, %) (ratio, %)
1
2
3
4
1
1
1
2
1
1
1
1
1
rt, DCM
ꢂC, DCM
rt, DCM
rt, DCM
99
50
99
99
43 (58)
(74)
(39)
32 (42)
(26)
(61)
1
1
2
0
53 (75)
21 (25)
5
6
7
8
9
2
2
2
2
2
1
1
1
1
1
1
1
1
1
1
rt, THF
78
85
36
39
ndc
50b
23b
10b
12b
d
28b
62b
26b
27b
d
rt, CH3NO2
rt, CH3CN
rt, toluene
rt, MeOH
2a was not observed.
A distinction between the possible
structures 5a and 6a of the isolated dimer could not be con-
cluded based on NOESY NMR experiments, due to the highly
flexible nature of the product. The identity of the isolated het-
erodimer was, however, particularly based on 2D HMBC NMR
data, as shown by the explicit C/H correlations between the
pyrrolidinone CH2eNeCO structure moiety and the neighbour-
ing CHeCH3 group. Also, a general comparison of NMR data of
all heterodimer products discussed below (5a, b, c, f, Table 4)
with the corresponding homodimers 4a, b, c, f supported the
identity of the formed heterodimer. The formation of hetero-
dimer 5a is in accordance with the proposed favoured reaction
pathway discussed below (Scheme 3). The structure of the di-
meric product was finally verified by a deuteration experiment
with 1,1,2-d3-vinylsulfonamide d3-2g and vinylacylamide 2a.
Product d-5a was formed with selective and complete deute-
rium incorporation in positions 1 and 2 as well as partial
deuteration of the methyl group (approx. 50% D), as indicated
by asterisk labelling in Table 3 (see discussion on mechanism
and formation of deuterated d-4a in Part 2.4 and Scheme 3
below).
10d
2
1
1
AgOTf in DCE7 99
AgSbF6 in DCE 99
50
52
19
20
a
Isolated yield.
Yield by GLC.
b
c
No dimer, complex product mixture.
d
(i) HOTf7/HSbF6 generated from AgOTf7/AgSbF6 (5 mol %) in DCE (10 mL/mmol
substrate), reflux, 2 h; (ii) dimerization of 2g (2 equiv)þ2a (1 equiv), rt, 3 h.
Table 4
Au(I)SbF6ePhC^CH catalyzed heterodimerization reactionsa
Product 5a was isolated in 43% yield from a 58:42 mixture of
hetero- and homodimers 5a and 4a. Higher hetero-/homo-che-
moselectivity (74:26), but only 50% conversion, was obtained at
0 ꢂC (Table 3, entry 2). As expected, a 2:1 ratio of vinylacylamide 2a
and vinylsulfonamide 2g favoured the formation of homodimer 4a
(entry 3).
However, a 1:2 ratio of substrates 2a and 2g would compensate
for the high reactivity of NMeTs-vinylamide 2g and afforded full
conversion of monomer 2a and 53% yield of heterodimer 5a, iso-
lated from a 75:25 mixture of hetero- and homodimers (Table 3,
entry 4). By varying the solvent, lower conversion and lower yields
were obtained, as the reactions in both THF and nitromethane did
not afford complete conversion (Table 3, entries 5 and 6; 78e85%)
and, hence, lower yield of heterodimer 5a was obtained (23e50% by
GLC). The effectivity of the reaction was dramatically reduced in
acetonitrile and toluene (Table 3, entries 7 and 8), in contrast to
high yields in toluene being used by others.4i No dimerization took
place in methanol, since conversion into other products was seen
(Table 3, entry 9).
Entry
1b
Monomer
Monomer
Reaction
time
Heterodimer
(yield, %)
Homodimer
(yield, %)
2 h
5a (53)
4a (21)
2b
3b
4b
24 h
24 h
1 h
5b (46)
5c (48)
5f (43)
4b (19)
4c (25)
4f (15)

N. Iqbal et al. / Tetrahedron 70 (2014) 1317e1325
1321
Scheme 3. Proposed mechanism for acid catalyzed vinylamide head-to-tail homo- and heterodimerization.
Similar results as for the [AuSbF6ealkyne] system (Table 3, entry
4) were obtained by hidden proton catalysis performed with the
AgSbF6/DCE or AgOTf/DCE7 methods (Table 3, entry 10) However,
the silver salt protocols require an additional reflux period (2 h) for
the in situ generation of the Bronsted acids before the dimerization
reaction at room temperature (3 h).
vinylsulfonamide 2g. This hydroalkynylation of vinylamides sup-
ports the assumption that an acetylide nucleophile would be gen-
erated by PhCCH deprotonation to give a gold(I)-acetylide complex,
as discussed above. The present observation may also be relevant for
the mechanistic understanding of similar previously reported
gold(I)8 and silver(I)9 catalyzed hydroalkynylation reactions.
These optimization studies indicated that the most convenient
and effective reactions were obtained a 2:1 ratio of vinylamides 2a
and 2g at room temperature in dichloromethane by in situ gener-
ation of HSbF6 from [AuSbF6ePhCCH] (Table 3, entry 4), which was
used in the subsequent study (Table 4, entry 1).
2.4. Rationalization of the dimerization process
Our results discussed above demonstrate the ability of vinyl-
amides to act both as nucleophiles and electrophiles to undergo
dimerization. In fact, vinylamides and vinylsulfonamides, similar to
the vinyl pyrrolidine-2-one 2a (as well as 2b,d) and the vinyl N(Me)
NMeTs-vinylamide 2g did also undergo heterodimerization with
other heterocyclic vinylacylamides, such as vinylpiperidin-2-one 2b
and vinylazepan-2-one 2c (46 and 48%, Table 4, entries 2 and 3). In
contrast to the rapid reactions of 2g with substrate 2a (2 h, Table 4,
entry 1), the corresponding heterodimerization with the heterocy-
clic vinylacylamides 2b,c were slower (24 h, entries 2 and 3). This is
in accordance with observations for homodimerizations (Table 3).
Rapid heterodimerization of 2g did also take place with the non-
cyclic N-methyl N-acetamide 2f and afforded 43% of heterodimer
5f in 1 h (Table 4, entry 4). Heterodimerization of vinyl N-methyl-N-
acetamide 2f with vinylpyrrolidinone 2a was unsuccessful, as only
homodimer 4a was formed as a major product (49%, Table 4, entry 5).
Minor amounts (<5%) of acetylide coupling product 6 were iso-
lated from the reaction with NMeTs-vinylamide 2g (entry 4). The
analogous formation of a corresponding alkyne product 7 (5%) from
N-methyl-N-acetamide 2f was indicated by 1H NMR (entry 5). These
observations demonstrate that the present phenylalkyne compound
reacted to give hydroalkynylation of vinylacetamide 2f and
Ts 2g structure moieties, have been used as p
-nucleophiles.10 These
deactivated vinylamides had the capacity to undergo intra-
molecular alkyne addition as a part of tandem cyclizations, due to
Pt(II), Ag(I) or gold(I) catalysis. Nevertheless, in some instances
both the latent nucleophilic and electrophilic nature of vinyl-
sulfonamides (NTs) were observed.10b
In our acid catalyzed vinyl dimerization reactions, the acyla-
mide functionality attached to at least one of the vinylic substrate
appears to be
reactions.
a crucial prerequisite for vinyl dimerization
(i) Homodimerization (Scheme 3i). Although the electron density
and the nucleophilic character of the vinylic moiety in heterocyclic
vinylacylamides I are moderate, the protonation of vinylamide
monomer I may afford a carbocationic intermediate I0, activated for
subsequent nucleophilic attack by a second monomer of vinyl-
amide I. The driving force in successful vinylamide

1322
N. Iqbal et al. / Tetrahedron 70 (2014) 1317e1325
homodimerization reactions seems to be caused by essential amide
NeCeO electron delocalization. Hence, the CeC bond formation is
favoured, since the second carbocationic intermediate allows sta-
bilization through a six-membered cyclic species III0, formed by an
internal C]O/carbocation coordination. This reaction mechanism
is in accordance with previous studies.4i It was shown that the
secondary N-vinylformamide and N-vinylacetamide monomers
readily afford oligomers by polymerization with various cationic
initiators, while the tertiary substituted N-vinylacylamides, N-
methyl-N-vinylformamide and N-vinylpyrrolidinone (compound
2a above), unexpectedly gave the homodimeric head-to-tail E-
products, corresponding to products III. Neither dimeric nor olig-
omeric products could be obtained from N-methyl-N-vinyl-
acetamide (compound 2f above). The reactions were carried out in
toluene at room temperature and different cationic initiators were
applied (HOTf, TMST, iodine, bromine), but no optimization studies
were carried out. The different outcome of the reactions of sec-
ondary and tertiary vinylacylamides was explained by the impor-
tant role of the acidic NH in secondary amides, allowing
imineeenamide tautomerization and proton transfer of the amide-
bonded hydrogen to a second monomer to provide polymerization.
In tertiary vinylacylamides, the amide hydrogen has been
substituted by an alkyl group, preventing analogous polymeriza-
tions. Thus, the reaction was suggested to follow the alternative
homodimerization pathway, favoured and rationalized by the sta-
I above. Thus, NMeTs-vinylamide II instantly gave complex product
mixtures and no homodimers IV (Scheme 3i) were formed.
The N-vinylphthalimide 2h and vinylimidazole 2i compounds
did not afford the respective dimerization products, probably due
to their lower or missing ability to stabilize intermediates by amide
NeCeO electron delocalization.
(ii) Heterodimerization (Scheme 3ii). In contrast to the un-
controlled reactions of NMeTs-vinylamide II and the homodime-
rization of vinylacylamides I, a competing reaction pathway was
taking place in the presence of both vinylamides I and II. The car-
bocationic intermediate I0, formed by protonation of vinyl-
acylamide I, may readily be trapped in a heterodimerization
manner (Table 4) by NMeTs-vinylamide II to give heterodimers V.
The total outcome of the reaction is a hydroalkenylation of vinyl-
acylamide I. In analogy to the homodimerization reactions above
(Scheme 3i), the driving force would be the favoured formation of
a similar stabilized six-ring oxygen bridged intermediate V0,
allowing the selective formation of head-to-tail heterodimerization
E-products V by a final proton elimination.
The fact that the opposite heterodimer VI was not formed by
hydroalkenylation of vinylsulfonamide II, is in line with the re-
action mechanism, emphasizing the importance of NeCeO elec-
tron delocalization for controlled chemoselective dimerizations to
take place, and explains why the acylamide group is a crucial pre-
requisite for vinylamide dimerization reactions.
The high reactivity of vinyl-NMeTs 2g, observed by the un-
successful controlled homodimerization, may explain why heter-
odimerization and vinylacylamide homodimerization reactions
were taking place at room temperature and at reflux, respectively.
As discussed above for homodimerization, the conversion of N-
methyl-N-acetamide 2f and vinylpyrrolidinone 2a (1e2 h, Table 4,
entries 4 and 1) took place faster than the vinyl heterocyclic amides
2b and c (24 h, entries 2 and 4).
bilized intermediate III0.4i Furthermore, we think that the final
b
-H
elimination from the carbocationic precursor III0 to afford the
homodimeric product III would be assisted by internal H-bonding,
due to NeCeO electron delocalization of the second amide moiety.
Thus, the mechanism would explain why head-to-tail homo-
dimerization of the heterocyclic vinylacylamide I is preferred and
why further polymerization does not take place. The locked con-
figuration of the stabilized bicyclic intermediate III0 would also
rationalize the preferred and exclusive stereoselective formation of
E-products III.
3. Conclusions
The faster conversion of vinylpyrrolidinone 2a (1.5 h, entry 1,
Table 2) than the other vinyl heterocyclic amides 2b,c (20e24 h,
entries 2 and 3), may be caused by more efficient stabilization of
intermediate I0 since the five-membered pyrrolidinone-ring allows
a nearly planar sp2-nitrogen. The delocalization capacity of the
vinylic cyclic carbamate 2d (20 h, entry 4) would also be lower than
the corresponding vinylacylamide 2a.
A catalytic system based on deuterium-phenylalkyne [Au[P(t-
Bu)2(o-biphenyl)CH3CN]SbF6ePhC^D] would afford in situ gener-
ation of Dþ (see Eq. 1) and, hence, enable a deuterium labelling
experiment. The results obtained from vinylpyrrolidinone (2a) and
We have presented an acid catalyzed chemoselective head-to-
tail dimerization method to readily afford intermolecular homo-
dimerization of a series of vinylacylamides as well as hetero-
dimerization of different vinylacylamides with a vinylsulfonamide
reactant. The results demonstrate the ability of vinylacylamides to
effectively undergo hydroalkenylation to afford 1,3-N,N-function-
alized (E)-but-1-ene products. The success of the dimerization of
the vinylacylamides seems to be determined by the ability of
NeCeO acylamide electron delocalization, affording intermediate
stabilization.
1
equiv d-phenylalkyne confirmed the proposed mechanism
The hidden acid catalysis by in situ generation of HSbF6 from the
catalytic [Au[P(t-Bu)2(o-biphenyl)CH3CN]SbF6ePhCCH] system
allowed milder and more convenient reaction conditions and
afforded higher yield than the direct HSbF6 super-acid catalyzed
reactions, and also compared to other hidden acid catalysis
methods based on silver salts. The [AuSbF6ealkyne] protocol pro-
vides a straightforward and efficient method for the stereoselective
synthesis of 1,3-N,N-functionalized (E)-but-1-enes by homo- and
heterodimerization of vinylamides.
(Scheme 3i). Substrate 2a would undergo partly proto-
a
nedeuterium exchange to give approximately 50% incorporation of
deuterium in the terminal vinylic positions (d-2a), since the re-
action would take place in an approximately 50:50% Dþ/Hþ mix-
ture, due to the release of a proton in the final product forming step
(III0 to III; d-4a0 to d-4a). This is in accordance with the observed
50% deuterium incorporation (NMR) in the 2- and 4-positions of
the isolated 1,3-N,N-functionalized (E)-but-1-ene dimer product d-
4a.
The corresponding open-chained N-methyl- and N-phenyl-N-
acetamide substrates 2f and 2e were highly reactive. However,
controlled homodimerization was obtained in 30 min to 2 h (en-
tries 5 and 6), in contrast to the unsuccessful dimerization pre-
viously reported4i for vinyl-NMePh 2f. The high reactivity of this
flexible substrate may be a result of the excellent delocalization and
stabilization of cation intermediates I0 and III0, since a planar sp2-
nitrogen centre readily may be formed. The vinylsulfonylamide II
(Table 2, 2g, entry 7) may not enable intermediate stabilization by
sulfonamide electron delocalization (IV0), similar to the acylamides
4. Experimental
4.1. General
All reactions were performed under an argon atmosphere.
Commercial grade reagents were used as received. Dry solvents
were collected from an MB SPS-800 solvent purification system.
All reactions were monitored by GC and thin-layer chromatog-
raphy (TLC) using E. Merck silica gel 60 F254 (0.25 mm thickness).
Flash chromatography was carried out using Merck silica gel 60

N. Iqbal et al. / Tetrahedron 70 (2014) 1317e1325
1323
(0.040e0.063 mm). High Througput Flash Purification (HPFP)
phenylacetylene (55.0 mg, 0.54 mmol) and gold(I) catalyst
(20.8 mg, 0.027 mmol) in DCM. The reaction mixture was stirred at
reflux for 1.5 h. Flash chromatography (DCM/MeOH 50:1) yielded
dimer 4a (50.4 mg, 84%) as a light yellow oil; Rf 0.35 (DCM/MeOH
50:1); nmax (neat, cmꢁ1) 3194, 3111, 2979, 2359, 1676, 1270,
(SUPELCOÒ)
was performed
on prepacked
cartridges
(VersaPakÔ). 1H and 13C NMR spectra were recorded using
a Bruker Avance DPX 300 or 400 MHz spectrometer, respectively.
Chemical shifts are reported in parts per million
(d, ppm)
downfield from tetramethylsilane (TMS) as internal standard.
Coupling constants (J) are reported in hertz (Hz). The attributions
of the chemical shifts were determined by means of COSY, HMQC,
HMBC and NOESY experiments. Melting points (mp) were de-
termined using a Stuart apparatus. High resolution mass spectra
(HRMS) were determined with an Agilent 6520 QTOF MS in-
strument equipped with a MAT 95XL (TermoQuest Finnigan) MS
instrument. IR spectra were obtained with a Nicolet 20SXC FT-IR
spectrometer by using a Smart Endurance reflexion cell. (Aceto-
957 cmꢁ1
; dH (400 MHz, CDCl3) 7.00 (d, J 14.0 Hz, 1H, NCH]),
4.85e4.96 (m, 2H, CH], CH), 3.49 (t, J 7.2 Hz, 2H, CH2), 3.24e3.34
(m, 2H, CH2), 2.49 (t, J 7.6 Hz, 2H, CH2), 2.39 (t, J 8.0 Hz, 2H, CH2),
2.07e2.15 (m, 2H, CH2), 1.96e2.03 (m, 2H, CH2), 1.29 (d, J 6.8 Hz, 3H,
CH3); dC (100 MHz, CDCl3) 174.2 (C]O), 173.2 (C]O), 125.1 (NCH]
CH), 110.7 (NCH]CH), 46.0 (]CHCH), 45.2 (NCH2), 42.3 (NCH2),
31.4 (COCH2), 31.1 (COCH2), 17.9 (CH2), 17.4 (CH2), 17.0 (CH3), HRMS
(EI) calcd for C12H18N2O2 [M]þ 222.1363, obsd 222.1361.
nitrile)[(2-biphenyl)di-tert-butyl-phosphine]gold(I)
hexa-
4.3.2. (E)-1,10-(But-1-ene-1,3-diyl)bis(piperidin-2-one) (4b). The ti-
tle compound was synthesized according to General procedure (i)
from 1-vinylpiperidin-2-one 2b (54.6 mg, 0.436 mmol), phenyl-
acetylene (44.4 mg, 0.436 mmol) and gold(I) catalyst (16.8 mg,
fluoroantimonate and vinyl amides 2a, 2c, 2f, 2h, 2i were
purchased from Aldrich and were used as received. Vinyl amides
2b, 2d, 2e and 2g were prepared as described elsewhere.10
21.8 mmol) in DCM. The reaction mixture was stirred at reflux for
4.2. General [AuSbF6ePhCCH] procedure for (i) homo- and (ii)
heterodimerization
24 h. Flash chromatography (DCM/MeOH 40:1) yielded dimer 4b
(86.3 mg, 79%) as a white solid; mp 119e121 ꢂC; Rf 0.24 (DCM/
MeOH 20:1); nmax (thin film) 3293, 3064, 2973, 2359, 1656, 1260,
(i) Homodimerization: To
a
Schlenk flask, the gold catalyst
957 cmꢁ1
; dH (400 MHz, CDCl3) 7.48, 7.52 (dd, J 14.9, 1.4 Hz, 1H,
(0.05 equiv) was added and dissolved in DCM. Phenylacetylene
(1.0 equiv) and vinylacylamide (1.0 equiv) in DCM (10 mL/
mmol) were added simultaneously to the gold catalyst. The
reaction mixture was stirred at reflux for 0.5e24 h.
NCH]), 5.39e5.42 (m, 1H, CH), 4.99e5.05 (dd, J 5.6, 14.9 Hz, 1H,
CH]), 3.36e3.39 (t, 2H, NCH2), 3.12e3.14 (m, 2H, OCH2), 2.46e2.50
(t, J 8.0 Hz, 2H, NCH2), 2.38e2.41 (m, 2H, COCH2), 1.78e1.92 (m, 2H,
CH2), 1.69e1.74 (m, 6H, CH2), 1.27e1.29 (d, J 7.2 Hz, 3H, CH3); dC
(100 MHz, CDCl3) 169.3 (C]O), 168.5 (C]O), 128.3 (NCH]CH),
110.1 (NCH]CH), 48.1 (]CHCH), 45.2 (NCH2), 41.7 (COCH2), 32.9
(NCH2), 32.5 (COCH2), 23.2 (CH2), 22.6 (CH2), 21.0 (CH2), 20.5 (CH2),
16.3 (CH3); HRMS (EI) calcd for C14H22N2O2 [M]þ 250.1676, obsd
250.1676.
(ii) Heterodimerization: To a Schlenk flask, the gold catalyst
(0.05 equiv) was added and dissolved in DCM (10 mL/mmol). A
solution of phenylacetylene (1.0 equiv), vinylamide I (2g, 2f)
(2.0 equiv) and vinylacylamide II (2a, 2b, 2c, 2f) (1.0 equiv) in
DCM (10 mL/mmol) was added simultaneously to the gold
catalyst. The reaction mixture was stirred at rt for 1e24 h.
4.3.3. (E)-1,10-(But-1-ene-1,3-diyl)bis(azepan-2-one) (4c). The title
compound was synthesized according to General procedure (i)
from 1-vinylazepan-2-one 2c (40.0 mg, 0.28 mmol), phenyl-
acetylene (28.8 mg, 0.28 mmol) and gold(I) catalyst (10.8 mg,
0.014 mmol) in DCM. The reaction mixture was stirred at reflux
for 24 h. Flash chromatography (DCM/MeOH 50:1) yielded dimer
4c (36 mg, 89.0%) as a light yellow solid; Rf 0.41 (DCM/MeOH
50:1); mp 135e141 ꢂC; nmax (thin film) 3198, 3053, 2989, 2299,
Upon completion, in both cases the reaction mixture was
quenched with NEt3, filtered through CeliteÔ and rinsed with DCM.
The solvent was removed in vacuo to obtain the crude product,
which was purified with silica gel Versa Flash, using an appropriate
MeOH/DCM eluent system to afford the dimer product, pure by
NMR.
4.3. General [[AgSbF6/AgOTf]ealkylchloride] procedure for (i)
1673, 1245, 958 cmꢁ1
; dH (400 MHz, CDCl3) 7.25 (dd, J 14.8, 1.2 Hz,
homo- and (ii) heterodimerization
1H, NCH]), 5.38e5.44 (m, 1H, CH), 5.00 (dd, J 14.8, 4.8 Hz, 1H,
CH]), 3.53 (t, J 4.8 Hz, 2H, CH2), 3.17 (t, J 4.0 Hz, 2H, CH2), 2.62 (t,
J 6.0 Hz, 2H, CH2), 2.53 (t, J 5.2 Hz, 2H, CH2), 1.54e1.74 (m, 12H,
CH2), 1.24 (d, J 7.2 Hz, 3H, CH3); dC (100 MHz, CDCl3) 175.2 (C]O),
174.1 (C]O), 128.0 (NCH]CH), 110.3 (NCH]CH), 48.3 (]CHCH),
45.2 (NCH2), 43.1 (NCH2), 37.6 (COCH2), 37.1 (COCH2), 29.9 (CH2),
29.6 (CH2), 29.3 (CH2), 27.2 (CH2), 23.4 (CH2), 23.3 (CH2), 16.7
(CH3); HRMS (EI) calcd for C16H26N2O2 [M]þ 278.1989, obsd
278.1983.
(i) Homodimerization: To
a Schlenk flask, the AgSbF6/AgOTf
(0.05 equiv) was added and dissolved in DCE (10 mL/mmol). An
alternative procedure included the addition of t-BuCl
(0.1 equiv), as well. The vinylacylamide (1.0 equiv) in DCE
(10 mL/mmol) was added. The reaction mixture was stirred at
reflux for 1.5 h.
(ii) Heterodimerization: To
a
Schlenk flask, AgSbF6/AgOTf
(0.05 equiv) was added and dissolved in DCE (10 mL/mmol).
The solution was stirred at reflux for 2 h and vinylsulfonamide
(2g) (2.0 equiv) and vinylacylamide (2a) (1.0 equiv) in DCE
(10 mL/mmol) were added simultaneously. The reaction mix-
ture was stirred at rt for 3 h.
4.3.4. (E)-3,30-(But-1-ene-1,3-diyl)bis(oxazolidin-2-one) (4d). The
title compound was synthesized according to General procedure
(i) from 3-vinyloxazolidin-2-one 2d (113.4 mg, 1.00 mmol), phe-
nylacetylene (102.0 mg, 1.0 mmol) and gold(I) catalyst (38.6 mg,
0.05 mmol) in DCM. The reaction mixture was stirred at reflux for
20 h. Flash chromatography (DCM/MeOH 30:1) yielded dimer 4d
(81.6 mg, 72.0%) as a light yellow solid; Rf 0.65 (DCM/MeOH
20:1); nmax (neat, cmꢁ1): 3293, 2923, 1731, 1480, 1230, 697; dH
(400 MHz, CDCl3) 6.82 (d, J 14.8 Hz, 1H, NCH]), 4.87 (dd, J 5.9,
8.6 Hz, 1H, CH), 4.54e4.61 (q, J 6.6 Hz, 1H, CH]), 4.46 (t, J 7.8 Hz,
2H, OCH2), 4.31 (t, J 7.9 Hz, 2H, OCH2), 3.70 (t, J 8.2 Hz, 2H, NCH2),
3.41e3.52 (m, 2H, NCH2), 1.35 (d, J 7.0 Hz, 3H, CH3); dC (100 MHz,
CDCl3) 157.7 (C]O), 157.3 (C]O), 126.2 (NCH]CH), 108.9 (NCH]
CH), 62.3 (OCH2), 62.0 (OCH2), 48.2 (]CHCH), 43.2 (NCH2), 40.3
Upon completion, in both cases the reaction mixture was fil-
tered through CeliteÔ and rinsed with DCE. The solvent was re-
moved in vacuo to obtain the crude product, which was purified
with silica gel Versa Flash, using an appropriate MeOH/DCM eluent
system to afford the dimer product, pure by NMR.
4.3.1. (E)-1,10-(But-1-ene-1,3-diyl)bis(pyrrolidin-2-one)
(4a). The
title compound was synthesized according to General procedure (i)
from vinyl pyrrolidin-2-one 2a (60.0 mg, 0.54 mmol),

1324
N. Iqbal et al. / Tetrahedron 70 (2014) 1317e1325
(NCH2), 17.0 (CH3); HRMS (EI) calcd for C10H14N2O4 [M]þ
226.0948, obsd 226.0949.
stirred for 24 h at room temperature. Flash chromatography (DCM/
MeOH 50:1) yielded heterodimer 5b (43.0 mg, 46%) as a yellow oil;
Rf 0.41 (DCM/MeOH 50:1) and homodimer 4b (13.3 mg, 19%) as
a light yellow oil; Rf 0.29 (DCM/MeOH 50:1). 5b: nmax (thin film)
4.3.5. (E)-N,N0-(But-1-ene-1,3-diyl)bis(N-phenylacetamide)
(4e). The title compound was synthesized according to General
procedure (i) from N-phenyl-N-vinylacetamide 2e (77.1 mg,
0.48 mmol), phenylacetylene (48.9 mg, 0.48 mmol) and gold(I)
3205, 3095, 2919, 2310, 1646, 1229, 939 cmꢁ1
; dH (400 MHz, CDCl3)
7.61 (d, J 8.4 Hz, 2H, Harom), 7.30 (d, J 8.4 Hz, 2H, Harom), 6.85 (dd, J
14.4, 1.6 Hz, 1H, NCH¼), 5.35e5.42 (m, 1H, CH), 4.68 (dd, J 14.4,
5.6 Hz, 1H, CH]), 3.04e3.08 (m, 2H, CH2), 2.83 (s, 3H, NCH3), 2.42
(s, 3H, ArCH3), 2.38e2.41 (m, 2H, CH2), 1.66e1.78 (m, 4H, CH2), 1.23
(d, J 7.2 Hz, 3H, CH3); dC (100 MHz, CDCl3) 169.1 (C]O), 143.8
(Carom), 134.3 (Carom), 129.7 (2C, CHarom), 129.7 (NCH]CH), 126.9
(2C, CHarom), 110.0 (NCH]CH), 47.2 (]CHCH), 41.3 (NCH2), 32.4
(NCH3), 32.1 (COCH2), 23.1 (CH2), 21.4 (ArCH3), 21.0 (CH2), 16.4
(1CH3); HRMS (EI) calcd for C16H21N2O3S [MꢁCH3]þ 321.1267, obsd
321.1267.
catalyst (18.5 mg, 24.0 mmol) in DCM. The reaction mixture was
stirred at reflux for 2 h. Flash chromatography (DCM/MeOH 30:1)
yielded compound 4e (49.3 mg, 64%) as a yellow oil; Rf 0.13 (DCM/
MeOH 20:1); nmax (thin film, cmꢁ1) 3293, 3064, 2973, 2359, 1656,
1260, 957; dH (400 MHz, CDCl3) 7.45e7.54 (m, 4Harom), 7.28e7.35
(m, 4Harom), 7.04 (d, J 5.8 Hz, 2Harom), 6.90 (br, 1H, NCH]),
5.47e5.52 (q, J 6.8 Hz, 1H, NCH), 4.25e4.30 (dd, J 6.8, 14.5 Hz, 1H,
CH]), 1.82 (s, 3H, COCH3), 1.69 (s, 3H, COCH3), 1.16e1.18 (d, J 6.8 Hz,
3H, CH3); dC (100 MHz, CDCl3) 169.65 (C]O), 168.68 (C]O), 139.34
(Carom), 130.15 (Carom), 129.99 (CHarom), 129.01 (2C, CHarom), 128.91
(2C, CHarom), 128.73 (2C, CHarom), 128.13 (2C, CHarom), 124.06
(CHarom),119.81 (NCH]CH),114.31 (1C, NCH]CH), 49.80 (]CHCH),
24.54 (COCH3), 23.30 (COCH3), 18.25 (CH3); HRMS (EI) calcd for
4.3.9. (E)-N,4-Dimethyl-N-(4-(2-oxoazepan-1-yl)but-3-en-2-yl)ben-
zenesulfonamide (5c). The title compound was synthesized
according to General procedure (ii) from 1-vinylazepan-2-one 2c
(40.0 mg, 0.28 mmol), N-methyl-N-tosylacetamide 2g (118.0 mg,
0.54 mmol), phenylacetylene (28.5 mg, 0.28 mmol) and gold(I)
catalyst (10.8 mg, 0.014 mmol) in DCM. The reaction mixture was
stirred for 24 h at room temperature. Flash chromatography
(DCM/MeOH 50:1) yielded heterodimer 5c (48.0 mg, 48%) as
yellow oil; Rf 0.43 (DCM/MeOH 50:1) and homodimer 4c
(20.0 mg, 25%) as a light yellow solid; Rf 0.32 (DCM/MeOH 50:1).
Compound 5c: vmax (thin film) 3196, 3105, 2939, 2289, 1673,
C
20H22N2O2 [M]þ 322.1763, obsd 322.1762.
4.3.6. (E)-N,N0-(But-1-ene-1,3-diyl)bis(N-methylacetamide) (4f). The
title compound was synthesized according to General procedure (i)
from N-methyl-N-vinylacetamide 2f (53.4 mg, 0.54 mmol), phenyl-
acetylene (55.0 mg, 0.54 mmol) and gold(I) catalyst (20.8 mg,
0.027 mmol) in DCM. The reaction mixture was stirred at reflux for
0.5 h. Flash chromatography (DCM/MeOH 50:2) yielded compound
4f (37.0 mg, 69%) as a colourless oil; Rf 0.33 (DCM/MeOH 50:1); nmax
(thin film, cmꢁ1) 3323, 3123, 2975, 2410, 1655, 1198, 963; dH
(400 MHz, CDCl3) 6.80 (d, J 14.0 Hz, 1H, NCH]), 5.30e5.43 (m, 1H,
CH), 4.90e4.97 (m, 1H, CH]), 3.05 (s, 3H, NCH3), 2.84 (s, 3H, NCH3),
2.21 (s, 3H, COCH3), 2.09 (s, 3H, COCH3), 1.24 (d, J 6.8 Hz, 3H, CH3); dC
(100 MHz, CDCl3) 170.1 (1C, C]O),169.2 (1C, C]O),131.0 (1C, NCH]
CH), 109.9 (1C, NCH]CH), 47.8 (1C, ]CHCH), 29.8 (1C, NCH3), 29.2
(1C, NCH3), 22.3 (1C, COCH3), 21.8 (1C, COCH3) 17.6 (1C, CH3); HRMS
(EI) calcd for C10H18N2O2 [M]þ 198.1363, obsd 198.1361.
1224, 945 cmꢁ1
; dH (400 MHz, CDCl3) 7.61 (d, J 8.4 Hz, 2H, Harom),
7.30 (d, J 8.0 Hz, 2H, Harom), 6.84 (dd, J 14.4, 1.6 Hz, 1H, NCH]),
5.32e5.39 (m, 1H, CH), 4.67 (dd, J 14.4, 5.2 Hz, 1H, CH]),
3.09e3.13 (m, 2H, CH2), 2.82 (s, 3H, NCH3), 2.50e2.52 (m, 2H,
CH2), 2.42 (s, 3H, ArCH3), 1.64e1.67 (m, 6H, CH2), 1.20 (d, J 6.8 Hz,
3H, CH3); dC (100 MHz, CDCl3) 175.2 (1C, C]O), 143.8 (1C, Carom),
134.3 (1C, Carom), 129.7 (2C, CHarom), 129.6 (1C, NCH]CH), 126.9
(2C, CHarom), 110.9 (1C, NCH]CH), 47.8 (1C, ]CHCH), 42.9 (1C,
NCH2), 37.5 (1C, NCH3), 32.1 (1C, COCH2), 29.9 (1C, CH2), 29.5 (1C,
CH2), 23.3 (1C, CH2), 21.4 (1C, ArCH3), 17.0 (1C, CH3); HRMS (EI)
calcd for C17H24N2O3S [MꢁCH3]þ 336.1457, obsd 336.1460.
4.3.7. (E)-N,4-Dimethyl-N-(4-(2-oxopyrrolidin-1-yl)but-3-en-2-yl)
benzenesulfonamide (5a). The title compound was synthesized
according to General procedure (ii) from 1-vinyl pyrrolidin-2-one
2a (15.5 mg, 0.14 mmol), N-methyl-N-tosylacetamide 2g
(59.0 mg, 0.28 mmol), phenylacetylene (14.2 mg, 0.14 mmol) and
gold(I) catalyst (5.4 mg, 0.007 mmol) in DCM. The reaction mix-
ture was stirred for 2 h at room temperature. Flash chromatog-
raphy (DCM/MeOH 50:1) yielded heterodimer 5a (20.4 mg, 53%)
as yellow oil; Rf 0.40 (DCM/MeOH 50:1) and homodimer 4a
(6.3 mg, 21%) as a light yellow oil; Rf 0.35 (DCM/MeOH 50:1).
Compound 5a: nmax (thin film) 3200, 3113, 2929, 2289, 1663, 1195,
4.3.10. (Z)-N-(3-(N,4-Dimethylphenylsulfonamido)but-1-en-1-yl)-N-
methylacetamide (5f) and N,4-dimethyl-N-(4-phenylbut-3-yn-2-yl)
benzenesulfonamide (6). The title compounds were synthesized
according to General procedure (ii) from N-methyl-N-vinylacetamide
2f (53.4 mg, 0.54 mmol), N-methyl-N-tosylacetamide 2g (236.0 mg,
1.08 mmol), phenylacetylene (55.0 mg, 0.54 mmol) and gold(I) cat-
alyst (20.8 mg, 0.027 mmol) in DCM. The reaction mixture was
stirred for 1 h at room temperature. Flash chromatography (DCM/
MeOH 50:1) yielded heterodimer 5f (71.9 mg, 43%) as a yellow oil; Rf
0.56 (DCM/MeOH 50:1), homodimer 4f (16.2 mg, 15%) as a light
yellow solid; Rf 0.43 (DCM/MeOH 50:1) and compound 6 (17.5 mg,
5%) as a yellow oil Rf 0.76 (DCM/MeOH 50:1). Compound 5f: nmax
957 cmꢁ1
; dH (400 MHz, CDCl3) 7.61 (d, J 8.0 Hz, 2H, Harom), 7.31 (d,
J 8.0 Hz, 2H, Harom), 6.88 (dd, J 14.4, 1.2 Hz, 1H, NCH]), 4.80e4.86
(m, 1H, CH), 4.67 (dd, J 14.4, J 6.0 Hz, 1H, CH]), 3.16e3.31 (m, 2H,
CH2), 2.83 (s, 3H, NCH3), 2.42 (s, 3H, ArCH3), 2.35e2.39 (m, 2H,
CH2), 1.94e2.01 (m, 2H, CH2), 1.25 (d, J 7.2 Hz, 3H, CH3); dC
(100 MHz, CDCl3) 174.0 (C]O), 143.8 (Carom), 134.3 (Carom), 129.7
(2C, CHarom), 129.6 (NCH]CH), 126.9 (2C, CHarom), 109.5 (NCH]
CH), 45.9 (]CHCH), 42.1 (NCH2), 32.0 (NCH3), 31.4 (COCH2), 21.4
(ArCH3), 17.8 (CH2), 17.4 (CH3); HRMS (EI) calcd for C15H19N2O3S
[MꢁCH3]þ 307.1111, obsd 307.1114.
(thin film) 3199, 3095, 2925, 2309, 1686, 1254, 924 cmꢁ1
(400 MHz, CDCl3) 7.61 (d, J 8.0 Hz, 2H, Harom), 7.30 (d, J 8.0 Hz, 2H,
arom), 6.84 (dd, J 14.4, 1.6 Hz, 1H, NCH]), 5.33e5.40 (m, 1H, CH),
; dH
H
4.65 (dd, J 14.0, 5.2 Hz, 1H, CH]), 2.83 (s, 3H, NCH3), 2.73 (s, 3H,
NCH3), 2.42 (s, 3H, ArCH3), 2.07 (s, 3H, COCH3), 1.20 (d, J 6.8 Hz, 3H,
CH3); dC (100 MHz, CDCl3) 170.1 (C]O), 143.8 (Carom), 134.3 (Carom),
129.7 (2C, CHarom), 129.6 (NCH]CH), 126.8 (2C, CHarom), 110.2
(NCH]CH), 47.2 (]CHCH), 32.0 (NCH3), 29.8 (NCH3), 22.2 (COCH3),
21.4 (ArCH3), 16.6 (CH3); HRMS (EI) calcd for C14H20N2O3S [MꢁCH3]þ
296.1247, obsd 296.1250. Compound 6: dH (400 MHz, CDCl3) 7.77 (d, J
8.4 Hz, 2H, Harom), 7.21e7.29 (m, 5H, Harom), 7.30 (d, J 6.4 Hz, 2H,
4.3.8. (E)-N,4-Dimethyl-N-(4-(2-oxopiperidin-1-yl)but-3-en-2-yl)ben-
zenesulfonamide (5b). The title compound was synthesized
according to General procedure (ii) from 1-vinylpiperidin-2-one 2b
(28.5 mg, 0.28 mmol), N-methyl-N-tosylacetamide 2g (10.8 mg,
0.014 mmol), phenylacetylene (58.8 mg, 0.54 mmol) and gold(I)
catalyst (20.8 mg, 0.027 mmol) in DCM. The reaction mixture was
Harom), 5.11 (q, J 6.4 Hz, 1H, CH), 2.84 (s, 3H, NCH3), 2.35 (s, 3H,
ArCH3), 1.50 (d, J 6.8 Hz, 3H, CH3); dC (100 MHz, CDCl3) 143.3 (Carom),
134.6 (Carom), 131.3 (2C, CHAr), 129.3 (2C, CHarom), 128.2 (CHarom),
128.0 (2C, CHarom), 127.8 (2C, CHarom), 122.1 (Carom), 85.4 (Calkyne),

N. Iqbal et al. / Tetrahedron 70 (2014) 1317e1325
1325
85.1 (Calkyne), 46.0 (CH3CH), 29.3 (NCH3), 21.3 (ArCH3), 20.8 (CH3);
HRMS (EI) calcd for C18H19NO2S [MþH]þ 314.1215, obsd 314.1216.
1189, 955 cmꢁ1
;
dH (400 MHz, CDCl3) 7.71 (d, J 8.2 Hz, 2H, Harom), 7.33
(d, J 8.2 Hz, 2H, Harom), 4.84e4.86 (m, 1H, CH), 3.24e3.36 (m, 2H,
CH2), 2.76 (s, 3H, NCH3), 2.44 (s, 3H, ArCH3), 2.33e2.42 (m, 2H, CH2),
1.95e2.10 (m, 2H, CH2), 1.23 (d, J 7.0 Hz, 2.5H, CH3/CH2D); dC
(100 MHz, CDCl3) 174.9 (C]O), 143.5 (Carom),133.9 (Carom),129.7 (2C,
CHarom), 128.7 (t, J 23.5 Hz NCD]CD), 127.0 (2C, CHarom), 108.2 (t, J
21.8 Hz NCD]CD), 43.8 (]CDCH), 42.1 (NCH2), 31.7 (NCH3), 31.2
(COCH2), 21.5 (ArCH3), 18.3 (CH2), 17.2e17.4 (m, CH3/CH2D); HRMS
(ESI) calcd for C16H20D3N2O3S [MþH]þ 326.1618, obsd 326.1613.
4.3.11. N-Methyl-N-(4-phenylbut-3-yn-2-yl)acetamide (7). The title
compound was synthesized according to General procedure (ii) from
N-methyl-N-vinylacetamide 2f (53.4 mg, 0.54 mmol), vinyl pyrro-
lidin-2-one 2a (31.0 mg, 0.28 mmol), phenylacetylene (28.5 mg,
0.28 mmol) and gold(I) catalyst (10.8 mg, 0.014 mmol) in DCM. The
reaction mixture was stirred for 1 h at room temperature. Flash
chromatography (DCM/MeOH 50:1) yielded homodimer 4a (15 mg,
49%, see above) and compound 7 (5.4 mg, 5%) as a yellow oil Rf 0.68
(DCM/MeOH 50:1). Compound 7: dH (400 MHz, CDCl3) 7.42 (d, J
7.2 Hz, 2H, Harom), 7.32 (m, 3H, Harom), 5.85 (q, 6.9 Hz, 3H, CH3), 3.08
(s, 3H, NCH3), 2.13 (s, 3H, COCH3), 1.42 (d, J 6.9 Hz, 3H, CH3).
Acknowledgements
We thank the Research Council of Norway for financial support.
References and notes
4.3.12. 2,4-d2-(E)-1,10-(But-1-ene-1,3-diyl)bis(pyrrolidin-2-one) (d-
4a). The title compound was synthesized according to General
procedure (i) from vinyl pyrrolidin-2-one 2a (60.0 mg, 0.54 mmol),
d1-phenylacetylene (55.6 mg, 0.54 mmol) and gold(I) catalyst
(20.8 mg, 0.027 mmol) in DCM. The reaction mixture was stirred at
reflux for 1.5 h. Flash chromatography (DCM/MeOH 50:1) yielded
dimer d-4a (50.9 mg, 84%) as a light yellow oil; Rf 0.36 (DCM/MeOH
50:1); nmax (neat, cmꢁ1) 3199, 3109, 2963, 2367, 1655, 1211,
1. Jeganmohan, M.; Cheng, C. H. Chem.dEur. J. 2008, 14, 10876.
2. Benito, A.; Corma, A.; Garcia, H.; Primo, J. Appl. Catal., A 1994, 116, 127.
3. Taylor, A. R.; Keen, G. W.; Eisenbraun, E. J. J. Org. Chem. 1977, 42, 3477.
4. (a) Tsuchimoto, T.; Kamiyama, S.; Negoro, R.; Shirakawa, E.; Kawakami, Y.
Chem. Commun. 2003, 852; (b) Ma, H.; Sun, Q.; Li, W.; Wang, J.; Zhang, Z.;
Yang, Y.; Lei, Z. Tetrahedron Lett. 2011, 52, 1569; (c) Kabalka, G. W.; Dong, G.;
Venkataiah, B. Tetrahedron Lett. 2004, 45, 2775; (d) Wang, C.-C.; Lin, P.-S.;
Cheng, C.-H. Tetrahedron Lett. 2004, 45, 6203; (e) Yi, C.; Hua, R.; Zeng, H.
Catal. Commun. 2008, 9, 85; (f) Cabrero-Antonino, J. R.; Leyva-Perez, A.;
Corma, A. Adv. Synth. Catal. 2010, 352, 1571; (g) Dai, J.; Wu, J.-L.; Zhao, G. L.;
Dai, W. M. Chem.dEur. J. 2011, 17, 8290; (h) Tjujita, H.; Ura, Y.; Matsuki, S.;
Wada, K.; Mitsudo, T.-a.; Kondo, T. Angew. Chem., Int. Ed. 2007, 46, 5160; (i)
Madl, A.; Spange, S. Macromolecules 2000, 33, 5325; (j) Inventors: Brei-
tenbach, J.; Schade, C.; Sigwart, C.; Mueller, U.; Hesse, M.; Negele, A.; Rue-
benacker, M.; Eller, K. DE 19642490 A1, 1998; [Chem. Abstr. 1998, 128, 270985
]; (k) Inventors: Carroll, W. E.; Pinschmidt, R. U., Jr. US Patent 5,280,077,
1994; [ Chem. Abstr. 1994, 120, 299557 ]; (l) Inventors: Kobayashi, S.; Uyama,
H.; Sawayama, S.; Satoh, K. DE 44 03519, 1994; [ Chem. Abstr. 1995, 122,
56829 ]; (m) Inventors: Pinschmidt, R. U., Jr.; Carroll, W. E. U.S. Patent
5,373,076, 1994; [ Chem. Abstr. 1995, 122, 315375 ].
5. (a) Sperger, C. A.; Tungen, J. E.; Fiksdahl, A. Eur. J. Org. Chem. 2011, 3719; (b)
Iqbal, N.; Sperger, C. A.; Fiksdahl, A. Eur. J. Org. Chem. 2013, 5, 907.
6. (a) Seidel, G.; Lehmann, C. W.; Fuerstner, A. Angew. Chem., Int. Ed. 2010, 49,
8466; (b) Gomez-Suarez, A.; Dupuy, S.; Slawin, A. M. Z.; Nolan, S. P. Angew.
Chem., Int. Ed. 2013, 52, 938; (c) Weber, D.; Jones, T. D.; Adduci, L. L.; Gagne,
M. R. Angew. Chem., Int. Ed. 2012, 51, 2452; (d) Hashmi, A. S. K.; Lauterbach,
T.; Noesel, P.; Vilhelmsen, M. H.; Rudolph, M.; Rominger, F. Chem.dEur. J.
2013, 19, 1058; (e) Brown, T. J.; Widenhoefer, R. A. Organometallics 2011, 30,
6003; (f) Simonneau, A.; Jaroschik, F.; Lesage, D.; Karanik, M.; Guillot, R.;
Malacria, M.; Tabet, J.-C.; Goddard, J.-P.; Fensterbank, L.; Gandon, V. Chem.
Sci. 2011, 2, 2417; (g) Grirrane, A.; Garcia, H.; Corma, A.; Alvarez, E. ACS Catal.
2011, 1, 1647.
7. Dang, T. T.; Boeck, F.; Hintermann, L. J. Org. Chem. 2011, 76, 9353.
8. Liu, X. Y.; Ding, P.; Huang, J.-S.; Che, C. M. Org. Lett. 2007, 9, 2645.
9. Luo, Y.; Li, Z.; Li, C. J. Org. Lett. 2005, 7, 2675.
947 cmꢁ1
; dH (400 MHz, CDCl3) 7.00 (d and s, J 14.0 Hz, 1H, NCH]
CH/D), 4.85e4.96 (m, 1.5H, ]CH/D, CH), 3.49 (t, J 7.2 Hz, 2H, CH2),
3.24e3.34 (m, 2H, CH2), 2.49 (t, J 7.6 Hz, 2H, CH2), 2.39 (t, J 8.0 Hz,
2H, CH2), 2.07e2.15 (m, 2H, CH2), 1.96e2.03 (m, 2H, CH2), 1.29 (d, J
6.8 Hz, 2.5H, CH3/CH2D); dC (100 MHz, CDCl3) 174.2 (C]O), 173.2
(C]O), 125.1/125.0 (NCH]CH/NCH]CD), 110.7 (s)/110.4 (t,
J
23.5 Hz) (CH]CHCH/CH]CDCH), 45.9e46.0 (m, ]CHCH/]CDCH),
45.1 (NCH2), 42.3 (NCH2), 31.4 (COCH2), 31.1 (COCH2), 17.9 (CH2),
17.4 (CH2), 16.5e17.0 (m, CH3/CH2D); HRMS (EI) calcd for
C
12H17DN2O2 [M]þ 223.1426, obsd 223.1425.
4.3.13. 1,3,4-d3-(E)-N,4-Dimethyl-N-(4-(2-oxopyrrolidin-1-yl)but-3-
en-2-yl)benzenesulfonamide (d-5a). The title compound was syn-
thesized according to General procedure (ii) from 1-vinyl pyrrolidin-
2-one 2a (15.5 mg, 0.14 mmol), 1,2,2-d3-N-methyl-N-tosylvinyla-
mide, d3-2g (60.0 mg, 0.28 mmol), phenylacetylene (14.2 mg,
0.14 mmol) and gold(I) catalyst (5.4 mg, 0.007 mmol) in DCM. The
reaction mixture was stirred for 2 h at room temperature. Flash
chromatography (DCM/MeOH 50:1) yielded heterodimer d-5a
(18.7 mg, 48%) as yellow oil; Rf 0.38 (DCM/MeOH 50:1) and homo-
dimer 4a (7.2 mg, 25%) as a light yellow oil; Rf 0.32 (DCM/MeOH
50:1). Compound d-5a: nmax (thin film) 3216, 3109, 2903, 2271, 1712,
ꢀ
10. (a) Harrison, T. J.; Patrick, B. O.; Dake, G. R. Org. Lett. 2007, 9, 367; (b) Kozak, J. A.;
Todd, J. M.; Harrison, T. J.; Jardine, K. J.; Patrick, B. O.; Dake, G. R. J. Org. Chem. 2009,
74, 6929; (c) Kozak, J. A.; Patrick, B. O.; Dake, G. R. J. Org. Chem. 2010, 75, 8585.