Coupling and cycloaddition of ynamides: Homo- and Negishi coupling of tosylynamides and intramolecular [4 + 2] cycloaddition of N-(o-ethynyl)phenyl ynamides and arylynamides

Article abstract of DOI:10.1016/j.tet.2005.11.082

N,N′-aryl- and N,N′-alkyl-buta-1,3-diyne-1,4-ditosylamides have been synthesized for the first time, in good to excellent yields, by copper-catalyzed dimerization of the corresponding N-aryl or N-alkyl tosylynamides. Negishi coupling of N-ethynylzinc tosy

Full text of DOI:10.1016/j.tet.2005.11.082

Tetrahedron 62 (2006) 3843–3855
Coupling and cycloaddition of ynamides: homo- and Negishi
coupling of tosylynamides and intramolecular [4D2]
cycloaddition of N-(o-ethynyl)phenyl ynamides and arylynamides
*
´
´ ´ ´ ´
Marıa Fernanda Martınez-Esperon, David Rodrıguez, Luis Castedo and Carlos Saa
´ ´ ´
Departamento de Quımica Organica y Unidad Asociada al CSIC, Facultad de Quımica, Universidad de Santiago de Compostela,
15782 Santiago de Compostela, Spain
Received 14 November 2005; accepted 26 November 2005
Available online 28 February 2006
Abstract—N,N0-aryl- and N,N0-alkyl-buta-1,3-diyne-1,4-ditosylamides have been synthesized for the first time, in good to excellent yields,
by copper-catalyzed dimerization of the corresponding N-aryl or N-alkyl tosylynamides. Negishi coupling of N-ethynylzinc tosylamides
derivatives with (hetero)aryl iodides in the presence of Pd2dba3 and triphenylphosphine affords N-aryl and N-alkyl arylynamides in yields of
up to 90%. Intramolecular [4C2] cycloaddition reactions of N-ethynylphenyl ynamides and arylynamides allow the synthesis of carbazoles
and benzannulated and heteroannulated carbazoles in moderate-to-good yields.
q 2006 Elsevier Ltd. All rights reserved.
1. Introduction
dichloroenamides 2 (Scheme 1, route a) or by direct
alkynylation of amide derivatives 4 (route b). Bru¨ckner’s
elimination protocol,13 based on Viehe’s pioneer work,14 is
really a tandem process, a base-promoted elimination
followed by lithium–halogen exchange.15,16 Direct alkyny-
lation was initially developed by Stang2d0 and Feldman17 to
prepare ‘push–pull’-type ynamines (R ZCO2R, SO2Ar,
etc), and consists in the reaction of metalated amides with
alkynyl(phenyl)iodonium salts 5 (XZIPh).18 Though
extended by Witulski and Rainier to the preparation of
ynamides 1 in which R0ZH, TMS, or phenyl,4,6 this
approach is of limited use for synthesis of alkyl ynamides
(R0Z alkyl), and also gives relatively low yields with some
amide substrates.1a A second direct alkynylation approach,
based on the methods developed by Buchwald and Hartwig
for nitrogen–carbon bond formation,19 involves the
Ynamides 1 have emerged as potentially more useful than
other ynamines for organic synthesis because of their superior
thermal stability.1,2,3 Typically, ynamides withstand aqueous
work-up and chromatographic purification on silica gel, and
are often crystalline solids that are stable in air. These features
have allowed their recent use in an array of procedures such as
Pauson–Khand reactions,4 hydroboration,5 Rh(I)- and Ru(II)-
catalyzed [2C2C2] cycloadditions,6 Ni(0)- and Rh(I)-
catalyzed [4C2] cycloadditions,7 ring-closing metatheses,8
radical cyclizations,9 Pt-catalyzed cycloisomerizations,10
Heck reactions11 and pericyclic reactions.12
Although not all possible ynamides are currently accessible,
many can be obtained by subjecting to elimination reactions
Scheme 1. General approaches to ynamides.
Keywords: Alkynylation; Carbazoles; Coupling; Cycloaddition; Ynamides.
*
Corresponding author. Fax: C34 981 595 012; e-mail: qocsaa@usc.es
0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.11.082

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M. F. Martınez-Esperon et al. / Tetrahedron 62 (2006) 3843–3855
3844
Table 1. Dimerization of N-phenyl tosylynamides 1a and 1b
Cu(I)-catalyzed cross-coupling of amide derivatives 4 with
readily available alkynyl halides 5 (XZBr, I).20 This latter
strategy was first developed by Hsung21 and Danheiser,22 for
acyclic and cyclic carbamates, and cyclic ureas and was
extended to sulfonamides and heteroaromatic substrates by
Hsung23 (using CuSO4 as catalyst) and Sato.24 Another
straightforward protocol for the synthesis of ynamides
involves base-induced isomerization of propargylic amides.25
Entry
Ynamide
Conditionsa
Time
Yield 6a
(%)
1
2
1a
1a
PdCl2(PPh3)2, CuI,
I2, i-Pr2NH, THF, rt
CuCl, TMEDA,
acetone, O2, rt
1 min
3 h
See text
63
3
4
1a
1a
Cu(OAc)2, Py, rt
CuI, TMEDA,
acetone, O2, rt
0.5 h
3 h
See text
91
In the course of our research on the synthesis of heterocyclic
compounds we required several N-aryl ynamides (1; RZ
aryl, R0ZH or protecting group) and arylynamides (1; R,
R0Zaryl).26 To our surprise, only one such compound had
previously been synthesized.23 Here we describe the
preparation of N-aryl and N-alkyl tosylynamides by
Bru¨ckner’s method; their homocoupling reactions; the
preparation of N-aryl and N-alkyl arylynamides by Negishi
coupling between the corresponding N-ethynylzinc tosyla-
mides and appropriate aryl iodides, the preparation of
N-ethynylphenyl ynamides and arylynamides by combi-
nations of Sonogashira reactions27 and Stang’s18 ethynyl-
(phenyl)iodonium salt approach; and the intramolecular
[4C2] cycloaddition reactions of N-ethynylphenyl yna-
mides and arylynamides, which afford carbazoles and
benzannulated and heteroannulated carbazoles.
5
6
1a
1b
CuI, TMEDA,
acetone, O2, rt
CuCl, DMF, 60 8C
1 h
88
88
0.5 h
a Amounts of catalyst: entry 1, 5% PdCl2(PPh3)2, 5% CuI; entries 2 and 4,
10% CuX, 20% TMEDA; entry 3, 250% Cu(OAc)2; entry 5, 50% CuI,
100% TMEDA; entry 6, 100% CuCl.
Classical Hay33 conditions (CuCl, TMEDA, acetone, O2)
afforded dimer 6a in 63% isolated yield as an air-stable
white solid (entry 2). Copper(II) acetate in pyridine
(entry 3) also brought about fast, clean conversion of the
starting material (as shown by TLC monitoring), but the
reaction product could not be isolated due to its
decomposition in the presence of Cu2SO4 (5%) or HCl
(5%) during work-up.34 By contrast, the conditions
35
reported by Pericas for the synthesis of 1,4-dialkoxy-
`
1,3-butadiynes, which use 10% CuI instead of CuCl,
afforded 6a in 91% yield (entry 4). Furthermore,
increasing the amount of catalyst to 50% shortened
the reaction time to 1 h with minimal reduction of yield (entry
5). Trimethylsilyl ynamide 1b was efficiently dimerized in
DMF at 60 8C in the presence of CuCl (entry 6).36
2. Results and discussion
2.1. Preparation and homocoupling of N-aryl and
N-alkyl tosylynamides16a
Our interest in the metal-catalyzed cyclization of diynes28 led
ustosearchthe literaturefor methodsfor homodimerizationof
ynamides.29 Finding none, we decided to evaluate the
performance of common alkyne dimerization methods30
when applied to selected ynamides, starting with aniline
ynamides. Aniline ynamide 1a was prepared as per
Bru¨ckner13a by sequential treatment of the dichlorovinyla-
mide 2a with n-butyllithium and methanol (Scheme 2);
similarly, trimethylsilyl ynamide 1b was obtained in 78%
yield by trapping the lithium acetylide with trimethylsilyl
chloride.
`
We next applied the Pericas conditions to ynamides 1c–f
(Scheme 3), all of which were prepared following
Bru¨ckner’s procedure.13a All these substrates afforded
high yields of the corresponding Glaser adduct 6 (Table 2).
Scheme 3. Homocoupling of N-aryl and N-alkyl tosylynamides 1c–f.
Table 2. Dimerization of N-substituted tosylynamides 1a,c,d,e and fa
Entry
Ynamide, R
Product, yield (%)
1
2
3
4
5
1a, Ph
1c, p-MePh
1d, Pr
1e, Allyl
1f, Bn
6a, 91
6c, 84
6d, 100
6e, 86
6f, 91
Scheme 2. Preparation of N-phenyltosylynamides 1a,b.
a Conditions: CuI (10%), TMEDA (20%), acetone, O2, rt, 3 h.
In our first attempt to dimerize ynamide 1a (Table 1,
entry 1) we used a palladium catalyst that had proved
useful for other alkyne dimerizations in our laboratory.31
However, in the presence of this catalyst 1a gave a
mixture from which the dimer 6a could only be isolated
in 40% yield, and similar results were obtained with
other terminal alkynes.32 We then tried copper catalysts.
All the N,N0-substituted-buta-1,3-diyne-1,4-ditosylamides 6
were isolated as air-stable white solids that withstood
aqueous work-up procedures and chromatographic purifi-
cation on silica gel. They have been stored at rt for weeks
with no appreciable decomposition. Note that dimer 6f,
obtained in 91% yield from benzyl ynamide 1f, can be

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M. F. Martınez-Esperon et al. / Tetrahedron 62 (2006) 3843–3855
3845
considered as masked 1,3-butadiyne-1,4-diamine, the tosyl
and benzyl groups being easily removable under standard
conditions.37
under the reaction conditions, affording only small amounts
of 6g.39
The optimized conditions (5% Pd2dba3, 20% PPh3) were
then employed for the synthesis of the new N-phenyl aryl
and heteroarylynamides 1h–o (Table 4). The 1-naphthyl,
4-methylphenyl and phenyl derivatives 1h–j, were obtained
in quite good yields (entries 2–4). The m-anisole derivative
1k was obtained in the same yield as its para analogue 1g
had been (entries 1 and 5), and the yield of the ortho
analogue 1l was only 25% (entry 6). As expected, however,
coupling partners with an electron-withdrawing group
(entry 7) or with electronegative heteroatoms (entries 8
and 9) afforded higher yields (81–92% after purification).
Finally, the N-propyl arylynamides 1p–r were also
synthesized, in yields very similar to those of their N-phenyl
counterparts 1l, 1m and 1o (Table 4, entries 10–12).
2.2. Synthesis of N-aryl and N-alkyl arylynamides by
Negishi coupling16b
In our first experiments on using the Negishi approach38 to
obtain arylynamides, sequential treatment of N-phenyl
ynamide 1a with n-BuLi and ZnBr2, followed by addition
of PdCl2(PPh3)2 and iodobenzene, led only to a low yield of
dimer 6a. When Pd2dba3 was used as palladium source, the
cross-coupled product was obtained as well as 6a, but the
yield was very poor and the catalyst was contaminated by
the starting ynamide. Finally, however, complete formation
of zinc acetylide 7a was achieved by treating the precursor
of 1a, dichlorovinylamide 2a, with 2 equiv of n-BuLi
followed by ZnBr2 (Scheme 4).
Table 4. Synthesis of arylynamides 1g–r by Negishi cross-coupling
Entry Vinyl-amide I-Ar
Ynamide
Yield
(%)a
1
2
2a
2a
I-benzene
48
63
1g
2-I-naphtha-
lene
1h
1i
3
4
2a
2a
4-I-toluene
4-I-anisole
68
69
Scheme 4. Preparation of N-aryl and N-alkyl arylynamides 1g–r by Negishi
coupling.
1j
With zinc acetylide 7a in hand we explored its palladium-
catalyzed coupling with p-iodoanisole. PdCl2(PPh3)2 and
Pd(PPh3)4 showed no catalytic activity (Table 3, entries 1
and 2) and, when used alone, Pd2dba3 produced only small
amounts of the desired coupled ynamide 1g (entry 3).39
However, when 20 mol% of PPh3 was added the yield
increased to 48% and was accompanied by an 18% yield of
the dimer 6g (entry 4). Using triphenylarsine or P(o-Tol)3
instead of PPh3 gave lower yields of 1g with or without
increased production of dimer 6g (entries 5 and 6), and there
was no reaction when PPh3 was added without palladium
(entry 7). The lithium analogue of 7a slowly decomposed
5
2a
3-I-anisole
2-I-anisole
48
1k
6
7
8
9
2a
2a
2a
2a
25
83
92
81
1l
4-I-nitroben-
zene
1m
2-I-pyridine
1n
1o
2-I-pyrimi-
dine
Table 3. Optimization of Negishi coupling of alkynylzinc 7a and p-
iodoanisolea
Entry
Catalyst (5%)
Additive
(20%)
1g (%)
6g (%)b
10
2b
2-I-anisole
24
1
2
3
4
5
6
7
8c
PdCl2(PPh3)2
Pd (PPh3)4
Pd2dba3
Pd2dba3
Pd2dba3
Pd2dba3
None
None
None
None
PPh3
AsPh3
P(o-Tol)3
PPh3
0
0
ND
ND
ND
18
18
33
1p
1q
!5
48
38
35
0
4-I-nitroben-
zene
11
12
2b
2b
81
85
0
ND
2-I-pyrimi-
dine
Pd2dba3
PPh3
0
a Catalyst amountZ5%, additive amountZ20%; rt, 2 h.
b NDZnot determined.
1r
a Isolated yields of products purified by column chromatography.
c Reaction with the lithium analogue of zinc acetylide 7a.

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3846
2.3. Intramolecular [4D2] cycloadditions of N-aryl
ynamides 8 and N-aryl arylynamides 926
group.6c N-aryl arylynamides 9 were synthesized in good
yields by Sonogashira cross-coupling of aryl iodides with
ynamide 8k27 (RZH, R0ZTIPS) followed by desilylation.
In this section we report our approach to the synthesis of
carbazoles40 and benzannulated carbazoles 10 by means of
intramolecular dehydro Diels–Alder (IDDA) reactions,41
specifically, the intramolecular [4C2] cycloaddition of
N-aryl ynamides 8 and N-aryl arylynamides 9 (Scheme 5).42
Carbazoles constitute an important class of alkaloid
displaying a wide variety of biological activities,43 and
their derivatives are also widely used as building blocks for
new organic materials.44
Heating ynamides 8 in toluene at 150 8C (conditions A)
generally gave poor to moderate yields of the desired
intramolecular [4C2] cycloaddition.41 Not unexpectedly, in
most cases better results were obtained in a mixture of
toluene and Et3N (Table 5, conditions B).41b,d For example,
for ynamide 8a the change of medium raised the yield of
2-methylcarbazole 10a from a poor 16% to an acceptable
40% (Table 5, entry 1). Remarkably, however, access to the
interesting tetrahydro-5H-benzo[b]carbazole nucleus 10b
was achieved in 55% yield using toluene alone (entry 2).46
This nucleus was also obtained using a carbamate instead of
a tosylamide as substrate (10c, entry 3). Thus our metal-free
IDDA approach to carbazoles nicely complements the
intermolecular Rh(I)-catalyzed [2C2C2] cycloaddition of
ynamides with alkynes,6c which is unable to create fused
cyclohexyl rings.
Benzannulated carbazole ring systems are found only rarely in
nature but are of considerable interest because of their
potential antitumoral and other pharmacological properties,40
and as building blocks for organic materials.44 Several
synthetic approaches to benzo[b]carbazoles (2-deazaellipti-
cines) have been developed over the past half century,40
including benzannulation of indoles,47 Fischer indolization of
phenylhydrazones,48 Diels–Alder reactions of pyrano[3,4-
b]indol-3-ones,49 4H-furo[3,4-b]indoles50 and 2,4-dihydro-
pyrrolo[3,4-b]indoles,51 and cycloaromatization of N-[2-(1-
alkynyl)phenyl]keteneimines;52 yields have varied between
22 and 98%. The main failing of these methods is their lack of
flexibility, since they almostexclusively allow the synthesis of
the parent benzo[b]carbazole nucleus but not that of
benz[b]annulated analogues. In this work, the 30% yield of
benzo[b]carbazole 10d that was obtained by heating 8d in
toluene was surprisingly reduced to 12–15% in basic or protic
media (Table 5, entry 4).41 Indeed, when a mixture of toluene
and AcOH was used, hydrolysis of the ynamide group
occurred giving 14d in 68% yield (Fig. 1). However, the
carbamate substrate 8e gave more satisfactory yields of up to
50% (entry 5). Gratifyingly, unlike the methods mentioned
above, the ynamide IDDA approach allowed uneventful
preparation of benz[b]annulated carbazoles with additional
benzenerings:heating ynamides8f–h inconditions B gavethe
known naphtho[1,2-b]carbazole47d 10f in 90% yield (entry 6)
and the hitherto unknown naphtho[2,1-b]carbazole 10g (30%
yield, entry 7) and dibenzo[a,c]carbazole 10h (58% yield,
entry 8).
Scheme 5. Carbazoles by intramolecular [4C2] cycloaddition of N-aryl
ynamides 8 and N-aryl arylynamides 9.
N-Aryl ynamides 8 and N-aryl arylynamides 9 were
prepared in three and five steps, respectively, starting
from commercially available o-iodoaniline (11) (Scheme 6).
Sonogashira reactions between 11 and terminal alkynes 12,
followed by N-tosylation,45 gave alkynes 13 (which were
also obtained by Sonogashira reactions of tosylated 11 with
12), and N-ethynylation of alkynes 13 with (trimethylsily-
l)ethynyliodonium salt 5 then gave the desired N-aryl
ynamides 8 (Table 5), generally, in good overall yields.
Using Cs2CO3 as the base in the last step afforded terminal
acetylenes 8 (RZH), using KHMDS retained the TMS
We then investigated whether benzo[c]carbazoles might be
prepared through rearrangement of the cyclic allene
intermediate that would be formed in the course of the
IDDA reaction of silylynamide 8i.53 Unfortunately, all
attempts at IDDA reaction of 8i led to its decomposition
(entry 9), even when we tried to trap the putative initial
cyclic allene in the presence of MeOH (entry 9). By
contrast, silylynamide 8j, in which the terminal phenyl of 8i
was replaced by a cyclohexenyl ring, smoothly cyclized in
very good yields to the 6-(trimethylsilyl)tetrahydroben-
zo[b]carbazole 10j (entry 10).
Scheme 6. Preparation of N-aryl ynamides 8 and N-aryl arylynamides 9.

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M. F. Martınez-Esperon et al. / Tetrahedron 62 (2006) 3843–3855
3847
Table 5. Results of intramolecular [4C2] cycloaddition of ynamides 8
Entry
Ynamide
Carbazole
Yield (%)
16,a 40b
1
10a
8a
8b
8c
8d
8e
8f
2
3
4
5
6
55a
10b
10c
10d
10e
10f
35,a 43b
30,a 12,b 15c
42,a 50b
21,a 90b
7
10,a 30b
8g
10g
8
27,a 58b
10h
8h
9
decomp.a,c
8i

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3848
Table 5 (continued)
Entry
Ynamide
Carbazole
Yield (%)
72,b 85c
10
10j
8j
8b
11d
8C16
10q
10r
a Experimental conditions. A: 8 (0.01 M), toluene (typically, 6 mL), 150 8C, sealed tube (normal).
b Conditions B: conditions A plus 0.5 mL of Et3N.
i
c Conditions C: conditions A plus 0.5 mL of MeOH or PrOH.
d PhI (1.1 equiv), 5% Pd(PPh3)4, 2% CuI, 2:1 Et3N/toluene, 60 8C.
10d was obtained from 9a than from 8d, 50% (Table 6,
entry 1) as against 12% (Table 5, entry 4). This exemplifies
a trend noted by Danheiser,22b that conjugated enynamides
(in our case, 9a) give better results than ynamides lacking
such conjugation, such as 8d, and in the case of 8d may be
due to the cyclic allene intermediate undergoing ring-
opening reactions.41,57 However, naphthylynamide 9d gave
a lower yield of naphthocarbazole 10f than did 8f, 73%
(Table 6, entry 4) as against 90% (Table 5, entry 7).
Surprisingly, the yields of the IDDA reactions of arylyna-
mides 9 did not seem to be influenced by the electronic
nature of the arylynamide moiety (Table 6, entries 2 and 3).
Ts
N
H
N
Me
Me
X
O
N
Me
X = C, 14d
X = N, 17
Ellipticine
Ts
N
Ts
N
C
N
Y
Unlike ynamides 15 and 16, heteroarylynamides 9e and 9f
responded to IDDA conditions, giving moderate yields
of thienocarbazole 10m and pyridocarbazole 10n (Table 6,
entries 5 and 6).58 Also, the silylated benzo[b]carbazole
10o was obtained in 31% yield from phenylynamide 9g
(Table 6, entry 7), silylynamide 8i had failed to react
(Table 5, entry 9).
X
18
15,Y = N, X = C
16, Y = C, X = N
Figure 1.
We were also unsuccessful in our attempts to prepare
pyrido[4,3-b]benzo[f]indoles, pyrido[3,2-b]carbazoles or
indolo[2,3-b]quinolines, which we sought as isomers of
the skeleton of the interesting antitumoral agent ellipticine
(Fig. 1).40 Heating 1554 or 16 in toluene at 150 8C led to
their decomposition, giving at best traces of the desired
cyclized products; heating 16 in the presence of AcOH
resulted in its 85% conversion into the hydrolysis product
17; and heating cyanamide 1855 had no effect, a result that
contrasts with the exceptionally easy photocyclizations of
the related aryldiimides.56
Finally, we examined the regioselectivity of the dehydro
Diels–Alder reaction by installing a second phenyl ring in the
aryl N-substituent of the starting arylynamide: heating 9h
gave the 2-nitro-11-phenylbenzo[b]carbazole 10p regioselec-
tively,59 (though in rather poor yield), showing that the
cycloaddition occurred selectively on the conjugated areny-
namidemoiety(Table6, entry8). Interestingly,howeverwhen
ynamide 8b was subjected to Sonogashira conditions in
the presence of iodobenzene, two carbazoles were isolated,
11-cyclohexenylbenzo[b]carbazole 10q in 8% yield and
6-phenyltetrahydrobenzo[b]carbazole 10r in 16% yield,
suggesting that after initial phenylation of 8b27 the two
possible cycloadditions had occurred in roughly 1:2 ratio
(Table 5, entry 11).
When we investigated the intramolecular [4C2] cyclo-
addition reactions of arylynamides 9 we found that in
toluene/Et3N a much better yield of the benzo[b]carbazole

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3849
Table 6. Results of intramolecular [4C2] cycloaddition of arylynamides 9
perspectives for the application of ynamides in the field of
poly- and heterocyclic aromatic chemistry.
Entry
Arylynamide
Carbazole
Yield
(%)a
4. Experimental
4.1. General
1
50
50
10d
10k
10l
9a
9b
All reactions were carried out under argon atmosphere with
magnetic stirring. The solvents were purified and dried
using standard procedures. All reagents were purchased and
used without further purification. Melting points were
measured using a Koefler melting point apparatus, and are
2
3
1
uncorrected. H and 13C NMR spectra were obtained on a
Brucker DPX-250 (250 and 63 MHz), AMX-300 (300 and
75 MHz) and Brucker WM-500 (500 and 125 MHz)
spectrometers using CDCl3 as solvent with tetramethylsi-
lane as internal standard. Mass spectra were recorded on
either a Hewlett-Packard HP5988A and Micromass Auto-
spec MS (EI and HRMS) or an Applied ‘API 4000’ (ESI).
Microanalyses were performed on a Thermo Finnigan
Flash 112 at the University of Santiago de Compostela,
Spain. Column chromatography was carried out using
Merck 230–400 mesh ASTM silica gel.
60
73
34
21
9c
9d
9e
4
5
6
10f
4.2. Typical procedure for the homocoupling of
tosylynamides
10m
4.2.1. N,N0-1,3-Butadiyn-1,4-diyl-N,N0-diphenyl ditosyl-
amide 6a. TMEDA (5 mL, 0.033 mmol) was added to a
suspension of CuI (3 mg, 0.017 mmol) in dry acetone
(4 mL) under O2 atmosphere, at rt. After 15 min, a solution
of 1a (45 mg, 0.177 mmol) in acetone (4 mL) was added
and the mixture was vigorously stirred until TLC showed
complete comsuption of the starting material (3 h). After
removal of the solvent, the crude residue was purified by
column chromatography on silica gel using a mixture of
hexanes/EtOAc 1:3 as eluent, yielding 41 mg (91%) of 6a as
10n
10o
9f
7
8
31
16
9g
9h
1
white prisms, mp 157–159 8C (dec). H NMR (250 MHz,
CDCl3) d: 7.62–7.56 (m, 4H, ArH), 7.36–7.26 (m, 10H,
ArH), 7.25–7.17 (m, 4H, ArH), 2.44 (s, 6H, 2!CH3). 13C
NMRCDEPT (62.83 MHz, CDCl3) d: 145.3 (2!C), 138.2
(2!C), 133.1 (2!C), 129.7 (4!CH), 129.2 (4!CH),
128.7 (2!CH), 128.1 (4!CH), 126.4 (4!CH), 75.7 (2!
C), 58.5 (2!C), 21.7 (2!CH3). MS (70 eV) m/z (%): 545
(MCKCH3, 29), 369 (57), 322 (55), 278 (97), 247 (63), 218
(82), 139 (100), 91 (60). Elemental analysis calcd (%) for
C30H24N2O4S2: C 66.65, H 4.47, N 5.18, S 11.86; found: C
66.21, H 4.21, N 5.27, S 11.67.
10p
a Experimental conditions: 9 (0.01 M), toluene (typically, 6 mL) plus
3
0.5 mL of Et N, 150 8C, sealed tube.
3. Conclusions
4.2.2. N,N0-1,3-Butadiyn-1,4-diyl-N,N0-di-4-methyl-
phenyl ditosylamide 6c. Brown powder, mp 125 8C (dec).
1H NMR (CDCl3) d: 7.59 (d, JZ8.2 Hz, 4H, ArH), 7.29 (d,
JZ8.2 Hz, 4H, ArH), 7.12 (d, JZ8.5 Hz, 4H, ArH), 7.05 (d,
JZ8.5 Hz, 4H, ArH), 2.44 (s, 6H, CH3), 2.34 (s, 6H, CH3).
13C NMR/DEPT (CDCl3) d: 145.2 (2!C), 138.8 (2!C),
135.5 (2!C), 133.0 (2!C), 129.8 (4!CH), 128.0
(4!CH), 126.3 (4!CH), 75.8 (2!C), 58.2 (2!C), 21.6
(2!CH3), 21.0 (2!CH3).
The catalytic system CuI/TMEDA promotes dimerization of
N-aryl- and N-alkyl tosylynamides in high yield. The
resulting N,N0-substituted-buta-1,3-diyne-1,4-ditosylamides
are air-stable solids. The use of these diynes in metal-
catalyzed cyclization reactions is currently being explored
in our laboratories.
Negishi coupling allows one-pot synthesis of N-aryl and
N-alkyl arylynamides starting from readily available dichlor-
ovinylamides, and intramolecular [4C2] cycloaddition
reactions of N-ethynylphenyl ynamides and arylynamides
afford carbazoles and benzannulated and heteroannulated
carbazoles in relatively good yields. These results open new
4.2.3. N,N0-1,3-Butadiyn-1,4-diyl-N,N0-dipropyl ditosyl-
amide 6d. White powder, mp 90–92 8C. 1H NMR (CDCl3)
d: 7.79 (d, JZ8.2 Hz, 4H, ArH), 7.37 (d, JZ8.2 Hz, 4H,

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3850
ArH), 3.31 (t, JZ7.2 Hz, 4H, CH2), 2.47 (s, 6H, CH3),
1.71–1.60 (m, 4H, CH2), 0.89 (t, JZ7.4 Hz, 6H, CH3). 13
NMR/DEPT (CDCl3) d: 144.9 (2!C), 134.5 (2!C), 128.8
(4!CH), 127.4 (4!CH), 75.1 (2!C), 59.3 (2!C), 53.2
(2!CH2), 21.5 (2!CH3), 21.1 (2!CH2), 10.6 (2!CH3).
MS (70 eV) m/z (%): 472 (MC, 8), 248 (85), 206 (88), 162
(100).
CH3). 13C NMR/DEPT (CDCl3) d: 159.6 (C), 144.8 (C),
139.1 (C), 133.4 (CH), 133.0 (C), 129.4 (2!CH), 129.0
(2!CH), 128.3 (2!CH), 128.1 (2!CH), 126.2 (2!CH),
114.5 (C), 113.9 (2!CH), 81.5 (C), 70.2 (C), 55.3 (OCH3),
21.7 (CH3). MS (70 eV) m/z (%): 377 (MC, 71), 222 (100),
119 (20).
C
4.3.3. N-(1-Naphthyl)ethynyl-N-phenyl tosylamide 1h.
Clear oil. 1H NMR (CDCl3) d: 7.87–7.83 (m, 1H, ArH), 7.80
(d, JZ7.5 Hz, 1H, ArH), 7.69 (d, JZ8.4 Hz, 2H, ArH), 7.60
(dd, JZ7.2, 1.2 Hz, 1H, ArH), 7.56–7.52 (m, 2H, ArH),
7.43–7.38 (m, 7H, ArH), 7.28 (d, JZ8.4 Hz, 2H, ArH), 2.43
(s, 3H, CH3). 13C NMR/DEPT (CDCl3) d: 145.0 (C), 143.3
(C), 149.0 (C), 133.2 (C), 133.1 (C), 133.0 (C), 129.8 (CH),
129.6 (2!CH), 129.2 (2!CH), 128.9 (CH), 128.4 (CH),
128.3 (2!CH), 128.2 (CH), 126.7 (CH), 126.3 (CH), 126.2
(2!CH), 126.2 (CH), 125.2 (CH), 80.0 (C), 69.0 (C), 21.7
(CH3). MS (70 eV) m/z (%): 397 (MC, 15), 242 (100), 139
(13).
4.2.4. N,N0-1,3-Butadiyn-1,4-diyl-N,N0-di-2-propenyl
ditosylamide 6e. White powder, mp 109–111 8C. 1H
NMR (CDCl3) d: 7.79 (d, JZ8.3 Hz, 4H, ArH), 7.36
(d, JZ8.3 Hz, 4H, ArH), 5.49–5.63 (m, 2H, CH]CH2),
5.24 (t, JZ8.6 Hz, 4H, CH]CH2), 4.00 (d, JZ6.3 Hz, 4H,
CH2), 2.47 (s, 6H, CH3). 13C NMR/DEPT (CDCl3) d: 145.0
(2!C), 134.5 (2!C), 130.3 (2!CH), 129.8 (4!CH),
127.6 (4!CH), 120.4 (2!CH2), 75.2 (2!C), 59.5 (2!C),
54.3 (2!CH2), 21.6 (2!CH3).
4.2.5. N,N0-1,3-Butadiyn-1,4-diyl-N,N0-dibenzyl ditosyl-
amide 6f. White needles, mp 153 8C (dec). 1H NMR
(CDCl3) d: 7.68 (d, JZ8.4 Hz, 4H, ArH), 7.30–7.21 (m,
14H, ArH), 4.52 (s, 4H, CH2), 2.45 (s, 6H, CH3). 13C NMR/
DEPT (CDCl3) d: 144.9 (2!C), 134.6 (2!C), 134.1 (2!
C), 129.8 (4!CH), 128.5 (4!CH), 128.4 (4!CH), 128.3
(2!CH), 127.6 (4!CH), 75.9 (2!C), 60.0 (2!C), 55.8
(2!CH2), 21.7 (2!CH3). MS (70 eV) m/z (%): 568 (MC,
22), 413 (100), 139 (62).
4.3.4. N-(4-Methylphenyl)ethynyl-N-phenyl tosylamide
1i. Pale brown powder, mp 113–115 8C. 1H NMR (CDCl3)
d: 7.61 (d, JZ8.3 Hz, 2H, ArH), 7.32–7.25 (m, 9H, ArH),
7.10 (d, JZ8.0 Hz, 2H, ArH), 2.43 (s, 3H, CH3), 2.33 (s, 3H,
CH3). 13C NMR/DEPT (CDCl3) d: 144.9 (C), 139.0 (C),
138.1 (C), 132.9 (C), 131.5 (2!CH), 129.4 (2!CH), 129.0
(3!CH), 128.2 (2!CH), 128.1 (2!CH), 126.2 (2!CH),
119.4 (C), 82.2 (C), 70.5 (C), 21.7 (CH3), 21.4 (CH3). MS
(70 eV) m/z (%): 361 (MC, 96), 297 (10), 206 (100).
4.3. Typical procedure for the preparation of aryl-
ynamides by Negishi coupling of zinc acetylides
and aromatic iodides
4.3.5. N-Phenyl-N-(phenyl)ethynyl tosylamide 1j. Pale
brown powder, mp 68–70 8C. 1H NMR (CDCl3) d: 7.64 (d,
JZ7.9 Hz, 2H, ArH), 7.43–7.39 (m, 4H, ArH), 7.34–7.29
(m, 8H, ArH), 2.44 (s, 3H, CH3). 13C NMR/DEPT (CDCl3)
d: 144.9 (C), 138.8 (C), 132.8 (C), 131.3 (2!CH), 129.4
(2!CH), 129.0 (2!CH), 128.9 (CH), 128.3 (2!CH),
128.2 (2!CH), 127.9 (CH), 126.2 (2!CH), 122.5 (C), 82.9
(C), 70.4 (C), 21.6 (CH3). MS (70 eV) m/z (%): 347 (MC,
22), 192 (100), 89 (18).
4.3.1. N-Phenyl-N-(pyrimidin-2-yl)ethynyl tosylamide
1o. n-BuLi (0.56 mL, 1.6 M in hexanes) was slowly added
to a solution of 2a (0.15 g, 0.43 mmol) in dry THF (8 mL)
cooled at K78 8C and the mixture was stirred for 5 min. A
solution of ZnBr2 (0.31 mL, 1.5 M in THF) was added via
syringe and, after stirring for 20 additional minutes at rt, the
reaction mixture was transferred via cannula to a solution of
Pd2dba3 (22 mg, 0.02 mmol), PPh3 (22 mg, 0.09 mmol) and
2-iodopyrimidine (0.11 g, 0.51 mmol) in dry THF (4 mL).
After 3 h TLC showed complete consumption of the
intermediate acetylide. The volatiles were removed and
the resulting residue was solved in EtOAc (20 mL) and
washed with brine (2!20 mL). The organic layer was dried
over anhydrous Na2SO4 and evaporated to dryness. The
crude residue was purified by column chromatography on
silica gel using hexane/EtOAc 1:2 as eluent to yield 1o
(0.12 g, 81%) as colorless prisms, mp 107–109 8C. 1H NMR
(250 MHz, CDCl3) d: 8.68–8.63 (m, 2H, ArH), 7.75–7.67
(m, 2H, ArH), 7.38–7.24 (m, 7H, ArH), 7.19–7.12 (m, 1H,
ArH), 2.43 (s, 3H, CH3). 13C NMRCDEPT (62.83 MHz,
CDCl3) d: 157.0 (2!CH), 153.2 (C), 145.3 (C), 137.7 (C),
132.8 (C), 129.6 (2!CH), 129.2 (2!CH), 128.7 (CH),
128.2 (2! CH), 126.5 (2!CH), 119.0 (CH), 82.3 (C), 71.4
(C), 21.6 (CH3). Elemental analysis calcd (%) for
C19H15N3O2S (349.41): C 65.31, H 4.33, N 12.03, S 9.18;
found: C 65.62, H 4.21, N 11.90, S 9.38.
4.3.6. N-(3-Methoxyphenyl)ethynyl-N-phenyl tosylamide
1
1k. Clear oil. H NMR (CDCl3) d: 7.62 (d, JZ8.4 Hz, 2H,
ArH), 7.34–7.27 (m, 7H, ArH), 7.20 (t, JZ7.9 Hz, 1H,
ArH), 6.98 (d, JZ7.6 Hz, 1H, ArH), 6.91 (dd, JZ2.6,
1.1 Hz, 1H, ArH), 6.84 (ddd, JZ8.3, 2.6, 1.0 Hz, 1H, ArH),
3.79 (s, 3H, OCH3), 2.44 (s, 3H, CH3). 13C NMR/DEPT
(CDCl3) d: 159.3 (C), 145.0 (C), 138.9 (C), 133.0 (C), 129.5
(2!CH), 129.3 (CH), 129.5 (2!CH), 128.3 (2!CH),
128.28 (CH), 126.3 (2!CH), 123.9 (CH), 123.6 (C), 116.3
(CH), 114.4 (CH), 82.8 (C), 70.5 (C), 55.3 (OCH3), 21.7
(CH3). MS (70 eV) m/z (%): 377 (MC, 100), 222 (61),
119 (27).
4.3.7. N-(2-Methoxyphenyl)ethynyl-N-phenyl tosylamide
1
1l. Clear oil. H NMR (CDCl3) d: 7.69 (d, JZ8.3 Hz, 2H,
ArH), 7.38–7.23 (m, 9H, ArH), 6.91–6.85 (m, 2H, ArH),
3.87 (s, 3H, OCH3), 2.43 (s, 3H, CH3). 13C NMR/DEPT
(CDCl3) d: 160.0 (C), 144.7 (C), 139.1 (C), 133.1 (CH),
133.0 (C), 129.3 (2!CH), 128.9 (2!CH), 128.4 (2!CH),
128.0 (2!CH), 126.1 (2!CH), 120.4 (CH), 112.0 (C),
110.7 (CH), 86.6 (C), 67.0 (CH3), 21.7 (CH3). MS (70 eV)
m/z (%): 377 (MC, 24), 222 (100), 119 (27).
4.3.2. N-(4-Methoxyphenyl)ethynyl-N-phenyl tosylamide
1g. White powder, mp 106–108 8C. H NMR (CDCl3) d:
1
7.62 (d, JZ8.3 Hz, 2H, ArH), 7.35–7.26 (m, 9H, ArH), 6.83
(d, JZ8.3 Hz, 2H, ArH), 3.80 (s, 3H, OCH3), 2.44 (s, 3H,

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4.3.8. N-(4-Nitrophenyl)ethynyl-N-phenyl tosylamide
1m. Pale brown needles, mp 129–131 8C. 1H NMR
(250 MHz, CDCl3) d: 8.17 (d, JZ8.7 Hz, 2H, ArH), 7.62
(d, JZ8.2 Hz, 2H, ArH), 7.48 (d, JZ8.7 Hz, 2H, ArH),
7.39–7.26 (m, 7H, ArH), 2.45 (s, 3H, CH3). 13C NMR/
DEPT (62.83 MHz, CDCl3) d: 146.3 (C), 145.4 (C), 138.1
(C), 132.7 (C), 131.0 (2!CH), 130.0 (C), 129.7 (2!CH),
129.3 (2!CH), 128.7 (CH), 128.1 (2!CH), 126.3 (2!
CH), 123.5 (2!CH), 89.7 (C), 69.8 (C), 21.7 (CH3). MS
(70 eV) m/z (%): 392 (MC, 14), 237 (74), 91 (100).
123 (51), 91 (100). HRMS (C20H17NO2S): calcd: 335.0980,
found: 335.0979.
4.4.2. N-Ethynyl-N-2-[2-cyclohexen-1-ynyl]phenyl tosyl-
amide 8b. Obtained in 80% yield as a clear oil. H NMR
1
(CDCl3) d: 7.55 (d, JZ8.2 Hz, 2H, ArH), 7.28–7.24 (m, 1H,
ArH), 7.14–7.11 (m, 5H, ArH), 5.92 (br s, 1H, ArH), 2.70 (s,
1H, CCH), 2.27 (s, 3H, CH3), 1.95–1.89 (m, 4H, CH2),
1.46–1.44 (m, 4H, CH2). 13C NMR/DEPT (CDCl3) d: 144.6
(C), 137.8 (C), 135.8 (CH), 134.4 (C), 133.0 (CH), 129.4
(CH), 129.2 (2!CH), 128.9 (CH), 128.3 (CH), 128.2
(2!CH), 123.3 (C), 120.4 (C), 97.3 (C), 82.1 (C), 75.7
(CH), 58.7 (C), 28.5 (CH2), 25.7 (CH2), 22.1 (CH2), 21.5
(CH3), 21.4 (CH2). MS (70 eV) m/z (%): 375 (MC, 17), 180
(74), 123 (100). HRMS (C23H21NO2S): calcd: 375.1293,
found: 375.1290.
4.3.9. N-Phenyl-N-(pyridin-2-yl)ethynyl tosylamide 1n.
Clear oil. H NMR (DMSO) d: 8.55–8.51 (m, 1H, ArH),
1
7.79 (dt, JZ7.9, 1.8 Hz, 1H, ArH), 7.67–7.60 (m, 2H, ArH),
7.52–7.42 (m, 6H, ArH), 7.36 8 (ddd, JZ7.6, 4.8, 1.2 Hz,
1H, ArH), 7.30–7.25 (m, 2H, ArH), 2.42 (s, 3H, CH3). 13
C
NMR/DEPT (DMSO) d: 150.0 (CH), 145.8 (C), 141.9 (C),
137.7 (CH), 136.7 (CH), 132.0 (C), 130.1 (2!CH), 129.7
(2!CH), 129.0 (C), 127.8 (2!CH), 126.5 (CH), 126.0 (2!
CH), 123.0 (CH), 82.2 (C), 70.5 (C), 21.1 (CH3). MS
(70 eV) m/z (%): 348 (MC, 14), 283 (100), 193 (10).
4.4.3. Methyl N-ethynyl-N-2-[2-cyclohexen-1-ynyl]-
phenyl carbamate 8c. Clear oil, 10% yield. 1H NMR
(CDCl3) d: 7.45 (dd, JZ6.5, 2.4 Hz, 1H, ArH), 7.41–7.24
(m, 3H, ArH), 6.22 (br s, 1H, ArH), 3.82 (s, 3H, CH3), 2.82
(s, 1H, C^CH), 2.21–2.18 (m, 4H, CH2), 1.71–1.60 (m, 4H,
CH2). 13C NMR/DEPT (CDCl3) d: 139.5 (C), 136.1 (CH),
132.4 (CH), 128.6 (CH), 128.3 (CH), 126.9 (CH), 122.4 (C),
120.4 (C), 97.3 (C), 81.9 (C), 76.3 (CH), 57.5 (C), 54.4
(CH3), 29.0 (CH2), 25.9 (CH2), 22.3 (CH2), 21.5 (CH2).
4.3.10. N-(4-Nitrophenylethynyl)-N-propyl tosylamide
1
1q. Clear oil. H NMR (250 MHz, CDCl3) d: 8.15 (d, JZ
8.7 Hz, 2H, ArH), 7.83 (d, JZ8.0 Hz, 2H, ArH), 7.40 (d,
JZ8.7 Hz, 2H, ArH), 7.37 (d, JZ8.0 Hz, 2H, ArH), 3.41 (t,
JZ7.2 Hz, 2H, CH2N), 2.46 (s, 3H, CH3), 1.78–1.70 (m,
2H, CH2), 0.96 (t, JZ7.4 Hz, 2H, CH3). 13C NMR/DEPT
(62.83 MHz, CDCl3) d: 146.1 (C), 145.0 (C), 134.3 (C),
130.7 (2!CH), 130.3 (C), 129.9 (2!CH), 127.4 (2!CH),
123.5 (2!CH), 88.4 (C), 70.4 (C), 53.0 (CH2), 21.6 (CH3),
21.3 (CH2), 10.7 (CH3). MS (70 eV) m/z (%): 358 (MC, 7),
150 (37), 91 (100).
4.4.4. N-Ethynyl-N-2-(2-phenylethynyl)phenyl tosyl-
amide 8d. Obtained in 77% yield as a clear oil. H NMR
1
(CDCl3) d: 7.68 (d, JZ7.8 Hz, 2H, ArH), 7.51–7.30 (m, 9H,
ArH), 7.07 (d, JZ7.8 Hz, 2H, ArH), 2.94 (s, 1H, C^CH),
2.15 (s, 3H, CH3). 13C NMR/DEPT (CDCl3) d: 144.9 (C),
138.0 (C), 134.2 (C), 133.1 (CH), 131.4 (2!CH), 129.7
(CH), 129.5 (2!CH), 129.1 (CH), 128.9 (CH), 128.4 (CH),
128.1 (2!CH), 127.9 (2!CH), 122.6 (C), 122.5 (C), 95.3
(C), 84.6 (C), 75.6 (CH), 59.1 (C), 21.3 (CH3). MS (FAB)
m/z: 372 (MCC1, 3), 231 (61), 154 (79), 137 (100). HRMS
FAB (C23H17NO2S): calcd: (MC1) 372.1058, found:
372.1052.
4.4. Typical procedure for the preparation of ynamides 8
To a stirred solution of N-tosylaniline 13 (1 mmol) (or the
corresponding carbamate) in dry DMF (20 mL) at rt was
added Cs2CO3 (1.3 equiv). After 30 min, a solution of 5
(1.3 mmol) in dry CH2Cl2 (8 mL) was added dropwise.
Stirring was continued until starting materials disappeared
(TLC monitoring, typically 5 h). Then, ether was added
(10 mL) and the combined organic layers were extracted
with water and brine, dried over anhydrous Na2SO4 and
concentrated to dryness. Purification of the residue by flash
chromatography on silica gel using a gradient mixture of
EtOAc/hexanes as eluent afforded ynamides 8 in good
yields.
4.4.5. Methyl N-ethynyl-N-2-(2-phenylethynyl)phenyl
carbamate 8e. White solid, 20% yield, mp 111–112 8C.
1H NMR (CDCl3) d: 7.61 (dd, JZ7.6, 1.7 Hz, 1H, ArH),
7.57–7.54 (m, 2H, ArH), 7.44–7.39 (m, 2H, ArH), 7.38–
7.34 (m, 4H, ArH), 3.85 (s, 3H, CH3), 2.88 (s, 1H, C^CH).
13C NMR/DEPT (CDCl3) d: 139.9 (C), 132.7 (CH), 131.7
(2!CH), 129.3 (CH), 128.7 (CH), 128.5 (CH), 128.3 (2!
CH), 127.2 (CH), 122.7 (C), 121.9 (C), 95.3 (C), 84.6 (C),
76.3 (CH), 57.7 (C), 54.5 (CH3).
Ynamides 15 and 16 have been prepared following the same
procedure.
4.4.1. N-Ethynyl-N-2-[(Z)-pent-3-en-1-ynyl]phenyl tosyl-
amide 8a. Obtained in 68% yield as a clear oil. H NMR
4.4.6. N-Ethynyl-N-2-[2-(naphthalen-2-yl)ethynyl]-
phenyl tosylamide 8f. Clear oil, 31% yield. 1H NMR
(CDCl3) d: 7.80–7.71 (m, 6H, ArH), 7.54–7.37 (m, 7H,
ArH), 7.05 (d, JZ8.2 Hz, 2H, ArH), 2.98 (s, 1H, C^CH),
2.01 (s, 3H, CH3). 13C NMR/DEPT (CDCl3) d: 144.9 (C),
138.3 (C), 134.5 (C), 133.3 (CH), 132.9 (C), 132.7 (C),
131.5 (CH), 130.0 (CH), 129.6 (CH), 129.5 (2!CH), 129.2
(CH), 129.0 (CH), 128.3 (2!CH), 128.2 (CH), 127.7 (CH),
127.6 (CH), 126.8 (CH), 126.6 (CH), 122.6 (C), 120.1 (C),
95.8 (C), 85.2 (C), 75.9 (CH), 59.2 (C), 21.3 (CH3). MS
(FAB) m/z (%): 422 (MCC1, 13), 397 (74), 243 (100).
1
(CDCl3) d: 7.71 (d, JZ8.3 Hz, 2H, ArH), 7.47–7.44 (m, 1H,
ArH), 7.35–7.21 (m, 5H, ArH), 6.07–5.94 (m, 1H, C]CH),
5.47 (dd, JZ10.7, 1.6 Hz, 1H, C]CH), 3.83 (s, 1H,
C^CH), 2.41 (s, 3H, CH3), 1.90 (dd, JZ6.9, 1.6 Hz, 3H,
CH3). 13C NMR/DEPT (CDCl3) d: 139.4 (CH), 137.8 (C),
134.2 (C), 133.4 (CH), 129.5 (2!CH), 129.1 (2!CH),
128.7 (CH), 128.3 (2!CH), 123.5 (C), 110.4 (C), 109.7
(CH), 92.2 (C), 89.0 (C), 75.8 (CH), 58.6 (C), 21.6 (CH3),
16.2 (CH3). MS (70 eV) m/z (%): 335 (MC, 2), 156 (31),

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3852
4.4.7. N-Ethynyl-N-2-[2-(naphthalen-1-yl)ethynyl]phe-
nyl tosylamide 8g. Clear oil, 25% yield. 1H NMR
(CDCl3) d: 8.35–8.31 (m, 1H, ArH), 7.84 (d, JZ7.9 Hz,
2H, ArH), 7.69–7.39 (m, 10H, ArH), 6.87 (d, JZ7.9 Hz,
2H, ArH), 3.02 (s, 1H, C^CH), 1.83 (s, 3H, CH3). 13C
NMR/DEPT (CDCl3) d: 144.9 (C), 138.1 (C), 134.3 (C),
133.6 (CH), 132.94 (C), 132.89 (C), 130.7 (CH), 130.1
(CH), 129.4 (2!CH), 129.3 (CH), 129.2 (CH), 129.0 (CH),
128.2 (2!CH), 128.0 (CH), 126.7 (CH),126.6 (CH), 126.4
(CH), 125.0 (CH), 122.9 (C), 120.5 (C), 93.4 (C), 89,4 (C),
76.1 (CH), 59.1 (C), 21.1 (CH3). MS (FAB) m/z (%): 422
(MCC1, 5), 301 (13), 282 (100). HRMS FAB
(C27H19NO2S): calcd (MC1): 422.1214, found: 422.1212.
4.4.11. N-Ethynyl-N-3-(2-phenylethynyl)pyridyl tosyl-
amide 15. Clear oil, 12% yield. H NMR (CDCl3) d: 8.75
1
(s, 1H, ArH), 8.59 (d, JZ5.3 Hz, 1H, ArH), 7.69 (d, JZ
8.1 Hz, 2H, ArH), 7.42–7.27 (m, 6H, ArH), 7.13 (d, JZ
8.1 Hz, 2H, ArH), 2.99 (s, 1H, C^CH), 2.20 (s, 3H, CH3).
13C NMR/DEPT (CDCl3) d: 154.3 (CH), 149.4 (CH), 145.5
(C), 145.2 (C), 133.9 (C), 131.5 (2!CH), 129.8 (2!CH),
129.1 (CH), 128.2 (2!CH), 128.1 (2!CH), 123.5 (CH),
122.1 (C), 118.7 (C), 98.9 (C), 81.7 (C), 74.4 (CH), 60.6 (C),
21.5 (CH3). MS (70 eV) m/z (%): 372 (MC, 2), 308 (59),
217 (100). HRMS (C22H16N2O2S): calcd: 372.0925, found:
372.0932.
4.4.12. N-Ethynyl-N-2-[2-(pyrid-2-yl)ethynyl)]phenyl
tosylamide 16. Clear oil, 50% yield. H NMR (CDCl3) d:
4.4.8. N-Ethynyl-N-2-[2-(phenanthren-10-yl)ethynyl]-
phenyl tosylamide 8h. Clear oil, 69% yield. 1H NMR
(CDCl3) d: 8.71–8.67 (m, 3H, ArH), 8.44 (d, JZ7.5 Hz, 1H,
ArH), 7.87–7.85 (m, 2H, ArH), 7.72–7.63 (m, 6H, ArH),
7.47–7.43 (m, 3H, ArH), 6.86 (d, JZ8.0 Hz, 2H, ArH), 3.05
(s, 1H, C^CH), 1.74 (s, 3H, CH3). 13C NMR/DEPT
(CDCl3) d: 144.9 (C), 138.2 (C), 134.3 (C), 133.6 (CH),
132.2 (CH), 130.9 (C), 130.6 (C), 130.2 (C), 130.0 (CH),
129.7 (C), 129.34 (2!CH), 129.28 (CH), 129.2 (CH), 128.5
(CH), 128.2 (2!CH), 127.6 (CH), 127.3 (CH), 127.0 (CH),
126.9 (2!CH), 122.8 (C), 122.5 (CH), 122.4 (CH), 119.2
(C), 93.6 (C), 89.1 (C), 76.2 (CH), 59.2 (C), 20.9 (CH3).
FAB m/z (%): 472 (MCC1, 13), 293 (100), 137 (67).
HRMS FAB (C31H21NO2S): calcd (MC1): 472.1371,
found: 472.1369.
1
8.58 (d, JZ4.4 Hz, 1H, ArH); 7.70 (d, JZ8.2 Hz, 2H, ArH),
7.64–7.60 (m, 2H, ArH), 7.40–7.39 (m, 3H, ArH), 7.27–
7.22 (m, 1H, ArH), 7.12 (d, JZ8.1 Hz, 2H, ArH), 2.94 (s,
1H, C^CH), 2.22 (s, 3H, CH3). 13C NMR/DEPT (CDCl3)
d: 149.7 (CH), 145.0 (C), 142.9 (C), 138.6 (C), 135.8 (CH),
134.1 (C), 133.8 (CH), 129.7 (CH), 129.6 (2!CHCCH),
129.2 (CH), 128.2 (2!CH), 127.5 (CH), 122.9 (CH), 94.1
(C), 84.4 (C), 75.8 (CH), 59.1 (C), 21.5 (CH3). MS (70 eV)
m/z (%): 372 (MC, 100), 217 (36), 190 (14). HRMS
(C22H16N2O2S): calcd: 372.0932, found: 372.0943.
4.5. Typical procedure for the preparation of aryl
ynamides 9
4.4.9. N-(Trimethylsilyl)ethynyl-N-2-(2-phenylethynyl)-
phenyl tosylamide 8i. To a stirred solution of N-tosyla-
niline 13 (1 mmol) in dry toluene (10 mL) at 0 8C was added
KHMDS dropwise (1.2 equiv). After 15 min a solution of 5
(1.4 mmol) in dry CH2Cl2 (4 mL) was added and stirring
was continued overnight. The reaction mixture was
concentrated, dissolved in ether (10 mL), extracted with
brine, dried over anhydrous Na2SO4 and concentrated to
dryness. Purification of the residue by flash chromatography
on silica gel using a mixture of 10% EtOAc in hexanes as
eluent afforded ynamide 8i as a white powder in 62% yield,
A solution of 1 mmol of ynamide 8k, 1.1 mmol of iodoarene
and 0.05 mmol of Pd(PPh3)4 in 7.5 mL of Et3N and 3.7 mL
of toluene was stirred at rt for 10 min. Then, 0.02 mmol of
CuI was added and the reaction mixture was heated at 60 8C
until starting material disappeared (TLC monitoring, 4–8 h).
The mixture was diluted with EtOAc, filtered through silica,
and concentrated to dryness. Purification of the residue by
flash chromatography on silica gel using a gradient mixture
of EtOAc/hexanes as eluent afforded TIPS-protected
arylynamides 9a–f0 in good yields.
1
mp 124–126 8C. H NMR (CDCl3) d: 7.85 (d, JZ8.2 Hz,
Excess of tetrabutylammonium fluoride (1.0 M solution in
THF) was added to a solution of TIPS-protected arylyna-
mides 9a–f0 (0.1 mmol) in THF (10 mL), and the resulting
mixture was stirred at rt for 10 min. After solvent removal,
the residue was dissolved in EtOAc, washed with brine,
dried over anhydrous Na2SO4 and concentrated to dryness.
The residue was purified by flash chromatography on silica
gel using a gradient mixture of EtOAc/hexanes as eluent
giving arylynamides 9a–f in good yields.
2H, ArH), 7.66–7.61 (m, 9H, ArH), 7.24 (d, JZ8.2 Hz, 2H,
ArH), 2.32 (s, 3H, CH3), 0.24 (s, 9H, Si(CH3)3); 13C NMR/
DEPT (CDCl3) d: 144.8 (C), 138.5 (C), 134.4 (C), 133.2
(CH), 131.6 (2!CH), 129.8 (CH), 129.4 (2!CH), 128.9
(2!CH), 128.8 (CH), 128.5 (2!CH), 127.9 (2!CH),
122.7 (C), 122.5 (C), 95.4 (C), 94.3 (C), 85.0 (C), 73.1 (C),
21.4 (CH3), 0.0 (Si(CH3)3). MS (70 eV) m/z (%): 443 (MC,
6), 304 (32), 288 (100); HRMS (C26H25NO2SSi): calcd:
443.1375, found: 443.1368.
4.5.1. N-2-Ethynylphenyl-N-2-phenylethynyl tosylamide
9a. Clear oil, 60% yield (overall). 1H NMR (CDCl3) d: 7.77
(d, JZ8.3 Hz, 2H, ArH), 7.53 (dd, JZ6.3, 3.3 Hz, 1H,
ArH), 7.41–7.26 (m, 10H, ArH), 3.09 (s, 1H, C^CH), 2.44
(s, 3H, CH3). 13C NMR/DEPT (CDCl3) d: 144.9 (C), 139.7
(C), 134.1 (CHCCH), 133.7 (C), 131.3 (2!CH), 129.5
(2!CH), 128.9 (2!CH), 128.4 (2!CH), 128.1 (2!CH),
127.7 (CH), 122.6 (C), 122.0 (C), 83.1 (C), 82.5 (C), 78.7
(CH), 70.1 (C), 21.5 (CH3). FAB m/z (%): 372 (MCC1) (1),
154 (89), 137 (100). HRMS (C23H18NO2S): calcd:
372.1058, found: 372.1064.
4.4.10. N-(Trimethylsilyl)ethynyl-N-2-[2-cyclohexen-1-
ynyl]phenyl tosylamide 8j. Clear oil, 45% yield. 1H
NMR (CDCl3) d: 7.71 (d, JZ8.4 Hz, 2H, ArH), 7.42–7.40
(m, 1H, ArH), 7.31–727 (m, 5H, ArH), 6.1 (s, 1H, C]CH),
2.43 (s, 3H, CH3), 2.09–2.08 (br s, 2H, CH2), 2.02–2.01 (br
s, 2H, CH2), 1.62–1.58 (m, 4H, CH2), 0.13 (s, 3H,
Si(CH3)3). 13C NMR/DEPT (CDCl3) d: 144.5 (C), 138.2
(C), 135.9 (CH), 134.6 (C), 133.2 (CH), 129.3 (3!CH),
128.9 (CH), 128.7 (2!CH), 128.3 (CH), 123.4 (C), 120.5
(C), 97.4 (C), 94.4 (C), 82.4 (C), 72.8 (C), 28.7 (CH2), 25.7
(CH2), 22.2 (CH2), 21.7 (CH3), 21.5 (CH2), 0.0 (Si(CH3)3).

´ ´
M. F. Martınez-Esperon et al. / Tetrahedron 62 (2006) 3843–3855
3853
4.5.2.
N-2-Ethynylphenyl-N-2-(4-methoxyphenyl)-
4.5.7. N-2-(2-Trimethylsilylethynyl)phenyl-N-2-phenyl-
ethynyl tosylamide 9g. Obtained as a white powder in
80% yield by silylation of 9a. 1H NMR (CDCl3) d: 7.75 (d,
JZ8.3 Hz, 2H, ArH), 7.52–7.50 (m, 1H, ArH), 7.36–7.24
(m, 10H, ArH), 2.45 (s, 3H, CH3), 0.08 (s, 9H, Si(CH3)3).
13C NMR/DEPT (CDCl3) d: 144.7 (C), 139.2 (C), 134.5 (C),
134.1 (CH), 131.0 (2!CH), 129.6 (2!CH), 129.1 (2!
CH), 128.7 (CH), 128.5 (2!CH), 128.1 (2!CH), 127.4
(CH), 123.0 (C), 122.8 (C), 101.3 (C), 98.8 (C), 82.5 (C),
70.6 (C), 21.7 (CH3), K0.4 (Si(CH3)3). MS (ESI-TOF) m/z
(%): 466 (MCCNa, 16). HRMS (C26H25NO2SSiNa): calcd:
466.1267, found: 466.1282.
1
ethynyl tosylamide 9b. Clear oil, 44% yield (overall). H
NMR (CDCl3) d: 7.75 (d, JZ8.4 Hz, 2H, ArH), 7.52 (dd,
JZ6.9, 2.4 Hz, 1H, ArH), 7.39–7.27 (m, 7H, ArH), 6.81 (d,
JZ8.9 Hz, 2H, ArH), 3.79 (s, 3H, OCH3), 3.06 (s, 1H,
C^CH), 2.46 (s, 3H, CH3). 13C NMR/DEPT (CDCl3) d:
159.5 (C), 144.8 (C), 140.1 (C), 134.2 (CH), 134.1 (C),
133.5 (2!CH), 129.5 (CH), 129.5 (2!CH), 129.1 (CH),
128.8 (CH), 128.6 (2!CH), 122.2 (C), 114.7 (C), 113,8
(2!CH), 82.9 (C), 81.2 (C), 79.0 (CH), 69.9 (C), 55.2
(CH3), 27.7 (CH3).
4.5.3. N-2-Ethynylphenyl-N-2-(4-nitrophenyl)ethynyl
tosylamide 9c. Clear oil, 65% yield (overall). H NMR
1
4.5.8. N-2-(2-Phenylethynyl)phenyl-N-2-(4-nitrophenyl)-
ethynyl tosylamide 9h. Clear oil, 46% yield. 1H NMR
(CDCl3) d: 8.10 (d, JZ8.5 Hz, 2H, ArH), 7.73 (d, JZ
8.5 Hz, 2H, ArH), 7.57–7.52 (m, 2H, ArH), 7.46–7.41 (m,
(CDCl3) d: 8.14 (d, JZ8.9 Hz, 2H, ArH), 7.75 (d, JZ
8.3 Hz, 2H, ArH), 7.55 (dd, JZ6.6, 2.7 Hz, 1H, ArH), 7.48–
7.34 (m, 7H, ArH), 3.05 (s, 1H, C^CH), 2.47 (s, 3H, CH3).
13C NMR/DEPT (CDCl3) d: 146.2 (C), 145.4 (C), 138.9 (C),
134.2 (CH), 130.9 (2!CH), 130.2 (C), 129.7 (2!CH),
129.6 (CH), 129.3 (CH), 129.1 (CH), 128.4 (2!CH), 123.4
(2!CH), 121.9 (C), 88.3 (C), 83.3 (CH), 78.4 (C), 70.0 (C),
60.3 (C), 21.6 (CH3).
4H, ArH), 7.28–7.10 (m, 7H, ArH), 2.18 (s, 3H, CH3). 13
C
NMR/DEPT (CDCl3) d: 146.1 (C), 145.3 (C), 138.0 (C),
134.0 (C), 133.4 (CH), 131.3 (2!CH), 130.8 (2!CH),
130.3 (C), 129.9 (CH), 129.7 (2!CH), 129.3 (CH), 129.1
(CH), 128.6 (CH), 128.2 (2!CH), 127.9 (2!CH), 123.5
(2!CH), 122.4 (C), 122.3 (C), 95.6 (C), 88.4 (C), 84.4 (C),
70.6 (C), 21.4 (CH3). MS (70 eV) m/z (%): 492 (MC, 29),
337 (100), 281 (59). HRMS (C29H20N2O4S): calcd:
492.1143, found: 492.1127.
4.5.4.
N-2-(2-Triisopropylsilylethynyl)phenyl-N-2-
(naphthalen-1-yl)ethynyl tosylamide 9d0. Clear oil, 62%
1
yield. H NMR (CDCl3) d: 8.26 (d, JZ8.0 Hz, 1H, ArH),
7.86–7.72 (m, 4H, ArH), 7.63 (t, JZ7.1 Hz, 1H, ArH), 7.52
(d, JZ6.0 Hz, 2H, ArH), 7.44–7.17 (m, 6H, ArH), 6.98 (d,
JZ8.0 Hz, 1H, ArH), 2.45 (s, 3H, CH3), 1.09 (br s, 21H,
Si(CH(CH3)2)3). 13C NMR/DEPT (CDCl3) d: 144.8 (C),
144.7 (C), 139.5 (C), 136.6 (C), 134.7 (C), 134.6 (CH),
133.1 (C), 133.06 (C), 129.7 (2!CH), 129.5 (CH), 129.2
(CH), 129.1 (CH), 129.0 (CH), 128.9 (CH), 128.4 (2!CH),
128.0 (CH), 127.8 (CH), 126.4 (CH), 126.2 (CH), 125.0
(CH), 102.0 (C), 98.1 (C), 87.7 (C), 68.5 (C), 21.6 (CH3),
18.6 (CH3), 11.3 (CH).
Obtained by Negishi coupling of 2 (EWGZTs, RZ2-(2-
phenylethynyl)phenyl) with p-nitroiodobenzene.
4.5.9. N-2-[2-(Pyrid-2-yl)ethynyl)]phenyl tosylacetamide
1
17. Clear oil, 50% yield. H NMR (CDCl3) d: 8.56 (d, JZ
4.5 Hz, 1H, ArH), 8.01 (d, JZ8.2 Hz, 2H, ArH), 7.75–7.71
(m, 1H, ArH), 7.57–7.47 (m, 4H, ArH), 7.25–7.20 (m, 1H,
ArH), 7.14 (d, JZ8.2 Hz, 2H, ArH), 6.97 (d, JZ7.8 Hz, 1H,
ArH), 2.21 (s, 3H, CH3), 1.98 (s, 3H, CH3). MS (70 eV) m/z
(%): 390 (MC, 1), 348 (70), 283 (100).
4.5.5.
N-2-(2-Triisopropylsilylethynyl)phenyl-N-2-
(thien-2-yl)ethynyl tosylamide 9e0. Clear oil, 80% yield.
1H NMR (CDCl3) d: 7.77 (d, JZ8.3 Hz, 2H, ArH), 7.58 (dd,
JZ7.0, 2,0 Hz, 1H, ArH), 7.34–7.22 (m, 5H, ArH), 7.13
(dd, JZ3.6, 1.1 Hz, 1H, ArH), 7.04 (dd, JZ7.5, 1.7 Hz, 1H,
ArH), 6.93 (dd, JZ5.2, 3.6 Hz, 1H, ArH), 2.46 (s, 3H, CH3),
1.16 (br s, 21H, Si(CH(CH3)2)3). 13C NMR/DEPT (CDCl3)
d: 144.7 (C), 139.4 (C), 134.6 (C), 134.4 (CH), 132.8 (CH),
129.6 (2!CH), 129.0 (CH), 128.9 (CH), 128.3 (2!CH),
127.9 (CH), 127.6 (CH), 126.8 (CH), 124.2 (C), 123.0 (C),
102.0 (C), 97.8 (C), 86.3 (C), 63.2 (C), 21.7 (CH3), 18.7
(CH3), 11.3 (CH).
4.5.10. N-2-(2-Phenylethynyl)phenyl tosylcyanamide 18.
White solid, 51% yield. H NMR (CDCl3) d: 7.97 (d, JZ
1
8.1 Hz, 2H, ArH), 7.53–7.34 (m, 4H, ArH), 7.21–7.05 (m,
5H, ArH), 6.70 (d, JZ8.1 Hz, 2H, ArH), 2.09 (s, 3H, CH3).
13C NMR/DEPT (CDCl3) d: 162.0 (C), 145.6 (C), 136.9 (C),
135.1 (C), 132.8 (CH), 131.2 (CH), 131.1 (2!CH), 130.7
(2!CH), 129.7 (CH), 129.3 (CH), 128.9 (2!CH), 128.6
(CH), 127.9 (2!CH), 122.8 (C), 121.5 (C), 95.1 (C), 85.2
(C), 21.4 (CH3).
Acknowledgements
4.5.6. N-2-Ethynylphenyl-N-2-(pyridin-3-yl)ethynyl
tosylamide 9f. Clear oil, 55% yield (overall). H NMR
´
We thank the Ministerio de Ciencia y Tecnologıa (Spain),
1
the European Regional Development Fund and the Xunta de
Galicia (XUGA) for financial support under projects
BQU2002-02135 and PGIDT03PXIC20909PN. M.F. Mar-
tınez-Esperon and D. Rodrıguez also thank XUGA and the
Universidad de Santiago de Compostela for predoctoral and
postdoctoral grants, respectively.
(CDCl3) d: 8.59 (s, 1H, ArH), 8.49 (d, JZ4.8 Hz, 1H, ArH),
7.76 (d, JZ8.4 Hz, 2H, ArH), 7.66 (dt, JZ7.9, 1.7 Hz, 1H,
ArH), 7.55 (dd, JZ6.9, 2.3 Hz, 1H, ArH), 7.44–7.32 (m,
5H, ArH), 7.22 (dd, JZ7.8, 4.8 Hz, 1H, ArH), 3.05 (s, 1H,
C^CH), 2.48 (s, 3H, CH3). 13C NMR/DEPT (CDCl3) d:
152.0 (CH), 148.1 (CH), 145.2 (C), 139.4 (C), 138.2 (CH),
134.3 (2!CH CC), 133.9 (C), 129.6 (2!CHCCH), 129.2
(CH), 129.1 (CH), 128.5 (CH), 122.9 (CH), 122.0 (C), 85.5
(C), 83.2 (CH), 78.6 (C), 67.3 (C), 21.7 (CH3). FAB m/z
(%): 373 (MCC1, 100), 218 (90). HRMS ESI-TOF:
(C22H17N2O2S): calcd: 373.1005, found: 373.1013.
´
´
´
References and notes
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´ ´
M. F. Martınez-Esperon et al. / Tetrahedron 62 (2006) 3843–3855
3854
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¨
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54. Obtained following the same procedure as for 8 (Scheme 6)
but starting with 4-amino-3-bromopyridine.
55. Prepared in 51% yield by treatment of 13d with BrCN in the
presence of KH.
´
56. Schmittel, M.; Rodrıguez, D.; Steffen, J.-P. Angew. Chem., Int.
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45. For carbamates 8c and 8e, treatment with methyl cloroformate
instead tosyl chloride was performed.
57. In fact, careful examination of the IDDA reaction of 8d
showed it to produce both the benzo[b]carbazole 10d and
small amounts of an isomer.
46. For an extraordinarily slow Diels–Alder approach to 5,6-
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J. Chem. Soc., Perkin Trans. 1 1992, 415–419.
58. Although the 2-pyridylynamide (not shown) decomposed
under thermal conditions, as also did the 2-pyridyl analogue
of 8d (not shown).
47. (a) Kano, S.; Sugino, E.; Shibuya, S.; Hibino, S. J. Org. Chem.
1981, 46, 2979–2981. (b) Bergman, J.; Pelcman, B.
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59. Previously misidentified as the other regioisomer in Ref. 26
Table 1, entry 23.