Copper(I)-catalyzed nucleophilic addition of ynamides to acyl chlorides and activated N-heterocycles

Article abstract of DOI:10.1021/jo500365h

The addition of ynamides to acyl chlorides and N-heterocycles activated in situ with ethyl chloroformate has been accomplished at room temperature using copper iodide as catalyst. This economical and practical carbon-carbon bond formation provides convenient access to a variety of 3-aminoynones from aliphatic and aromatic acyl chlorides in up to 99% yield. The addition to pyridines and quinolines occurs under almost identical conditions and proceeds with good to high regioselectivity, producing the corresponding 1,2-dihydro-N-heterocycles in up to 95% yield.

Full text of DOI:10.1021/jo500365h

Note
pubs.acs.org/joc
Copper(I)-Catalyzed Nucleophilic Addition of Ynamides to Acyl
Chlorides and Activated N‑Heterocycles
Peng Zhang, Andrea M. Cook, Yang Liu, and Christian Wolf*
Department of Chemistry, Georgetown University, Washington, DC 20057, United States
S
* Supporting Information
ABSTRACT: The addition of ynamides to acyl chlorides and N-heterocycles activated in situ with ethyl chloroformate has been
accomplished at room temperature using copper iodide as catalyst. This economical and practical carbon−carbon bond
formation provides convenient access to a variety of 3-aminoynones from aliphatic and aromatic acyl chlorides in up to 99%
yield. The addition to pyridines and quinolines occurs under almost identical conditions and proceeds with good to high
regioselectivity, producing the corresponding 1,2-dihydro-N-heterocycles in up to 95% yield.
he unique chemistry of ynamines has received
continuous attention due to the huge synthetic potential
absence of a catalytic procedure that allows mild carbon−
carbon bond formation with acyl chlorides and N-heterocycles
is in stark contrast to the wealth of reports on this reaction
with terminal alkynes. Encouraged by our previous finding
that indole-derived ynamines undergo zinc-catalyzed additions
with aldehydes toward N-substituted propargylic alcohols, we
decided to search for a catalytic variant that is applicable to
other electrophiles.13 We now wish to report the copper-
catalyzed nucleophilic addition of a readily available terminal
ynesulfonamide to acyl chlorides and activated pyridines and
quinolines furnishing 3-aminoynones and the corresponding
1,2-dihydro-2-(3-aminoethynyl) N-heterocycles.
Propargylic ketones are key intermediates for the
preparation of natural products and heterocyclic compounds
and most conveniently prepared through catalytic alkynylation
of acyl chlorides14 or via carbonylative Sonogashira coupling.15
Many procedures require heating and long reaction times and
are not applicable to ynamides, which lack the thermal
stability of alkynes.16 We therefore investigated the possibility
of carbon−carbon bond formation with the readily available
N-ethynyl-N-phenyl-4-tolylsulfonamide, 1, under mild reaction
conditions. Following a literature procedure, we synthesized
gram amounts of 1 from N-tosyl aniline, Scheme 1.3 Initial
analysis of the reaction between ynesulfonamide 1 and
benzoyl chloride showed that copper(I) salts were superior
over both zinc and palladium complexes commonly used in
alkynylation reactions. Using 10 mol % of cuprous iodide and
2 equiv of diisopropylethylamine in THF, we obtained the
desired N-(3-phenyl-3-oxoprop-1-ynyl)-N-phenyl-4-tolylsulfo-
T
of these remarkably versatile building blocks. In particular, C-
substituted ynamines exhibiting an internal triple bond have
found widespread use in a variety of reactions and in the total
synthesis of natural compounds.1 The reaction scope of
ynamines and derivatives thereof differs considerably from
that of enamines and alkynes as the reactivity of the electron-
rich triple bond is dominated by the adjacent, strongly
polarizing amine moiety. Because ynamines are very reactive
and therefore of limited practical use, ynamides that can be
isolated and stored have become more popular in recent
years. The increasing availability of terminal ynamides,
ynesulfonamides, and ynecarbamates based on practical
procedures developed by Witulski,2 Bruckner,3 Saa,4 and
others has further extended the general utility of ynamine
chemistry, Figure 1.5 Among the most noteworthy reactions
Figure 1. Structures of terminal ynamines and less reactive ynamide
and ynesulfonamide analogues.
are cycloadditions,6 cycloisomerizations,7 homo- and cross-
couplings,8 ring-closing metathesis,9 radical additions,10 and
titanium-mediated carbon−carbon bond formations.11
Surprisingly, few examples of nucleophilic additions of
terminal ynamides, ynesulfonamides, and ynecarbamates to
aldehydes, ketones, and other electrophiles, all requiring
strongly basic conditions, can be found in the literature.12 The
Received: February 14, 2014
Published: April 11, 2014
© 2014 American Chemical Society
4167
dx.doi.org/10.1021/jo500365h | J. Org. Chem. 2014, 79, 4167−4173

The Journal of Organic Chemistry
Note
examples with aliphatic electrophiles typically producing
ynones in only moderate yields have been reported.14a,e
This can probably be attributed to fast ketene formation and
subsequent side reactions when acyl chlorides exhibiting α-
hydrogens are used in the presence of base. While the
reaction with pivaloyl chloride gave the corresponding
propargylic ketone 8 in high yield as expected, we were
very pleased to find that the ynone formation with 2-
methylpropanoyl chloride proceeds smoothly at 15 °C
providing 9 in 70% yield, entries 7 and 8.
Scheme 1. Synthesis of Ynesulfonamide 1 (Top) and
Targeted Catalytic 1,2-Additions (Bottom)
As discussed above, the properties and reactivity of
ynamines and ynamides are influenced by the amine moiety,
which strongly polarizes the triple bond. We therefore decided
to investigate if the sulfonamide unit has a similar effect on
the ynone unit. A single crystal of 2 was obtained by slow
evaporation of a solution in CDCl3. Crystallographic analysis
of this compound and a survey of representative C-substituted
propargylic ketones from the Cambridge Structural Database
showed that the bond lengths of the carbonyl group, the
adjacent C(sp2)−C(sp) bond, and the triple bond in the α,β-
unsaturated ketone functionalities are almost identical, Figure
2. Similarly, IR analysis of 2 shows the alkyne and the
namide, 2, in 50% yield after 20 h. The screening of various
copper(I) salts, organic solvents, base, and temperature
revealed that 2 can be isolated in 90% yield when the
reaction is performed in the presence of 10 mol % of copper
iodide in chloroform at 30 °C; see entry 1 in Table 1. To the
Table 1. Copper(I)-Catalyzed Addition to Acyl Chlorides
Figure 2. Crystal structure of 2. Selected crystallographic separations
[Å]: N1···C3, 1.345; C3···C2, 1.197; C2···C1, 1.448; C1···O1, 1.224.
carbonyl stretchings at 2202 and 1637 cm−1, respectively,
which suggests that push−pull conjugation plays a minor role
in this 3-aminoynone.17
In contrast to the results obtained with acyl chlorides, we
did not observe any reaction when we applied methyl or ethyl
chloroformate in our copper-catalyzed ynamide addition
procedure. This led us to investigate the possibility of a
catalytic ynamide addition to pyridines by a one-pot
procedure in which the heterocycle is activated toward a
nucleophilic attack through formation of an N-acylpyridinium
intermediate. Substituted 1,2-dihydropyridines and the corre-
sponding 1,2-dihydroquinolines are important N-heterocycles
that serve as key intermediates in organic synthesis and are
ubiquitous units in many biologically active compounds. The
direct incorporation of versatile functionalities into readily
available, inexpensive pyridine and quinoline compounds has
therefore received increasing attention in recent years. While
several reports on regioselective 1,2-additions of organo-
metallic species to pyridine and its analogues exist, the
nucleophilic attachment of an ynamide moiety has not been
accomplished to date.18
a
b
c
Isolated yields. 20 °C. 15 °C.
best of our knowledge, this is the first catalytic addition of an
ynamide to an acyl chloride. It is noteworthy that the order of
addition of the reagents is important for this reaction. The
best yields were obtained when the catalyst, base, and the
ynamide were stirred for 30 min prior to addition of the acyl
chloride. The reaction also proceeds with high yields when
other aromatic substrates are employed, and we obtained
ynones 3−7 in 79−99% yield, entries 2−6. In contrast to the
impressive number of high-yielding catalytic cross-couplings of
aromatic acyl chlorides with terminal alkynes, very few
4168
dx.doi.org/10.1021/jo500365h | J. Org. Chem. 2014, 79, 4167−4173

The Journal of Organic Chemistry
Note
With the mild protocol for the ynamide addition to acyl
chlorides in hand, the optimization of the reaction between 1
and pyridine toward N-ethoxycarbonyl-1,2-dihydro-2-(N-phe-
nyl-N-tosylaminoethynyl)pyridine, 10, was straightforward.
We systematically changed solvents, temperature, and base,
screened zinc and copper catalysts, and tested different
chloroformates at varying amounts to activate the pyridine
ring for a nucleophilic ynamide attack. We found that
quantitative conversion can be achieved for the reaction
between pyridine and ynesulfonamide 1 using copper(I)
iodide as catalyst and 2 equiv of diisopropylethylamine in
dichloromethane at room temperature. The heterocycle
activation requires the presence of 2 equiv of ethyl
chloroformate; the overall reaction is significantly faster
when 5 equiv is used, but this has no effect on the isolated
yields. Replacement of ethyl chloroformate with the methyl or
benzyl derivative proved detrimental to the conversion. Using
our optimized procedure with ethyl chloroformate and 2
equiv of base, we were able to isolate 10 in 71% yield after
2.5 h at room temperature; see entry 1 in Table 2.
Table 2. Copper(I)-Catalyzed Ynamide Addition to
Activated Pyridines and Quinolones
We then applied our catalytic procedure to several pyridine
analogues and obtained the corresponding 1,2-dihydropyr-
idines 11−14 in 72−96% yield, entries 2−5. The copper-
catalyzed ynamide addition to activated pyridines and
quinolines typically shows quantitative conversion, but the
yield of the desired 1,2-dihydro-2-(2-aminoethynyl)-
heterocycles is in some cases compromised by concomitant
formation of noticeable amounts of the 1,4-regioisomer. With
pyridine substrates we observed that the ratio of the 1,2-
versus the 1,4-addition product varied between 3:1 and 7:1
unless the para-position was blocked, while solvents
(acetonitrile, N-methylpyrrolidinone, acetone, nitromethane,
tetrahydrofuran, chloroform, and dichloromethane) and
temperature changes (−78 to 25 °C) had literally no impact
on the regioselectivity but affected the conversion of this
reaction.19 The 1,2-dihydropyridine generated from 4-
methoxypyridine rapidly hydrolyses upon acidic workup and
careful chromatographic purification on basic alumina gave
ketone 15 in 78% yield, entry 6. It is noteworthy that the
synthesis of functionalized piperidinones such as 15 has
become increasingly important due to the use of these
versatile intermediates in medicinal chemistry.18a We were
pleased to find that our method can also be applied to
quinolines. The ynamide addition to quinoline gave N-
ethoxyarbonyl-1,2-dihydro-2-(N-phenyl-N-tosylaminoethynyl)-
quinoline, 16, in 91% yield, entry 7 in Table 2. In contrast to
pyridines, the reaction with quinolines apparently occurs with
high 1,2-regioselectivity and no sign of the 1,4-addition
product was observed. Finally, 4,7-dichloro- and 4-chloro-6-
methoxyquinoline were converted to 17 and 18 with 82−88%
yield and 19 was obtained in 95% yield from phenanthridine,
entries 8−10.
a
Isolated yield.
without the catalyst. NMR monitoring of the catalytic
ynamide addition to the activated quinoline ring showed
quantitative conversion to 1,2-dihydro-2-aminoethynylquino-
line, 16, within 20 min, whereas no product was isolated
when the reaction was carried out in the absence of CuI for
2.5 h.
In conclusion, we have developed the first catalytic addition
of a readily available ynesulfonamide to aliphatic and aromatic
acyl chlorides. A slightly modified procedure has been
successfully used for regioselective 1,2-addition of ynamides
to pyridines and quinolines. Both reactions occur under mild
conditions and provide unprecedented access to a variety of 3-
aminoynones and 1,2-dihydro-N-heterocycles in good to high
In analogy to metal-catalyzed nucleophilic additions with
alkynes, we believe that side-on coordination of the ynamide
to copper(I) increases the acidity of the terminal CH bond.
Deprotonation by the tertiary amine base then produces a
copper complex that reacts with the electrophilic acyl chloride
or activated N-heterocycle and regenerates the catalyst, Figure
3. The ynamide additions are sluggish in the absence of CuI.
We found that the synthesis of aminoynone, 2, from 1 and
benzoyl chloride is almost complete after 10 h, but less than
50% ynamide consumption and formation of unidentified
byproducts were observed when the reaction was performed
4169
dx.doi.org/10.1021/jo500365h | J. Org. Chem. 2014, 79, 4167−4173

The Journal of Organic Chemistry
Note
Figure 3. (Left) Proposed mechanism of the CuI-catalyzed formation of aminoynone, 2, and 1,2-dihydro-2-aminoethynylquinoline, 16, and
(right) conversion of the ynamide to 2 and 16 vs time.
purified by column chromatography (5:2 dichloromethane/hexanes)
to give 45 mg (0.11 mmol, 92%) of a white solid. H NMR (400
yields. The convenient access to these synthetically versatile
ynamide derivatives is expected to prove invaluable to
medicinal chemistry and natural product synthesis.
1
MHz): δ 8.06 (d, J = 7.6 Hz, 1H), 7.60 (d, J = 8.3 Hz, 2H), 7.45 (d,
J = 3.6 Hz, 2H), 7.45−7.31 (m, 4H), 7.31−7.21 (m, 4H), 2.43 (s,
3H). 13C NMR (100 MHz): δ 175.3, 145.9, 137.1, 135.4, 133.1,
133.0, 132.9, 132.4, 131.4, 129.9, 129.4, 129.2, 128.2, 126.8, 126.5,
91.0, 76.3, 21.7. Anal. Calcd For C22H16ClNO3S: C, 64.47; H, 3.93;
N, 3.42. Found: C, 64.65; H, 4.07; N, 3.41. Mp >105 °C (decomp)
N-(3-(4-Chlorophenyl)-3-oxoprop-1-ynyl)-N-phenyl-4-tolyl-
sulfonamide, 4. The reaction with 4-chlorobenzoyl chloride (31.4
mg, 0.18 mmol) and the ynamide (32.5 mg, 0.12 mmol) was
performed at 30 °C for 20 h. The concentrated crude residue was
purified by column chromatography (2:1 dichloromethane/hexanes)
EXPERIMENTAL SECTION
■
Commercially available reagents and solvents were used without
further purification. Anhydrous solvents were used as purchased and
not dried any further. NMR spectra were obtained at 400 MHz (1H
NMR) and 100 MHz (13C NMR) in deuterated chloroform.
Chemical shifts are reported in ppm relative to TMS.
General Procedure for the Copper-Catalyzed Ynamide
Addition to Acyl Chlorides. Copper iodide (2.3 mg, 12 μmol),
N-ethynyl-N-phenyl-4-tolylsulfonamide (32.5 mg, 0.12 mmol), and
N,N-diisopropylethylamine (31.0 mg, 0.24 mmol) were dissolved in
chloroform (0.15 mL) under nitrogen. After 30 min an acyl chloride
(0.18 mmol) was added, and the mixture was stirred until
completion as determined by TLC. Solvents were evaporated
under a stream of nitrogen, and the crude residue was purified by
flash chromatography on silica gel (particle size 40−63 μm) as
described below.
General Procedure for the Copper-Catalyzed Ynamide
Addition to Pyridines and Quinolines. The ynamide (54.2 mg,
0.20 mmol), CuI (3.8 mg, 0.02 mmol), and N,N-diisopropylethyl-
amine (70 μL, 0.40 mmol) were dissolved in 1 mL of anhydrous
dichloromethane. Then, a solution of the N-heterocycle (0.24 mmol)
and ethyl chloroformate (38 μL, 0.40 mmol) in 1 mL of anhydrous
dichloromethane was added. The mixture was stirred under nitrogen
until the reaction was completed based on NMR and TLC analysis.
Solvents were then removed, and the crude residue was directly
loaded onto a silica gel column (particle size 32−63 μm) and
purified by flash chromatography as described below unless stated
otherwise.
1
to give 47 mg (0.115 mmol, 96%) of a white solid. H NMR (400
MHz): δ 8.09 (d, J = 8.6 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H), 7.45 (d,
J = 8.5 Hz, 2H), 7.39−7.28 (m, 3H), 7.28−7.18 (m, 4H), 2.39 (s,
3H). 13C NMR (100 MHz): δ 175.4, 146.0, 140.2, 137.0, 135.4,
132.9, 130.5, 129.9, 129.5, 129.3, 128.9, 128.1, 126.4, 90.7, 74.7, 21.6.
Anal. Calcd For C22H16ClNO3S: C, 64.47; H, 3.93; N, 3.42. Found:
C, 64.38; H, 4.05; N, 3.46. Mp 105−107 °C.
N-(3-(4-Cyanophenyl)-3-oxoprop-1-ynyl)-N-phenyl-4-tolyl-
sulfonamide, 5. The reaction with 4-cyanobenzoyl chloride (30.0
mg, 0.18 mmol) and the ynamide (32.7 mg, 0.12 mmol) was
performed at 30 °C for 18 h. The concentrated crude residue was
purified by column chromatography (3:1 dichloromethane/hexanes)
1
to give 46.5 mg (0.116 mmol, 97%) of a white solid. H NMR (400
MHz): δ 8.29 (d, J = 8.3 Hz, 2H), 7.82 (d, J = 8.1 Hz, 2H), 7.60 (d,
J = 8.3 Hz, 2H), 7.47−7.34 (m, 3H), 7.29 (d, J = 8.1 Hz, 2H),
7.27−7.23 (m, 2H), 2.43 (s, 3H). 13C NMR (100 MHz): δ 174.8,
146.2, 139.8, 136.8, 136.7, 132.8, 132.4, 130.0, 129.6, 129.4, 128.1,
126.4, 117.9, 116.8, 92.3, 75.1, 21.7. Anal. Calcd For C23H16N2O3S:
C, 68.98; H, 4.03; N, 7.00. Found: C, 68.67; H, 4.14; N, 6.92. Mp
>155 °C (decomp)
N-(3-(2-Naphthyl)-3-oxoprop-1-ynyl)-N-phenyl-4-tolylsulfo-
namide, 6. The reaction with 2-naphthoyl chloride (35.0 mg, 0.18
mmol and the ynamide (32.9 mg, 0.121 mmol) was performed at 30
°C for 12 h. The concentrated crude residue was purified by column
chromatography (1:1 dichloromethane/hexanes) to give 51.5 mg
N-(3-Phenyl-3-oxoprop-1-ynyl)-N-phenyl-4-tolylsulfona-
mide, 2. The reaction with benzoyl chloride (25.1 mg, 0.18 mmol)
and the ynamide (32.5 mg, 0.12 mmol) was performed at 30 °C for
22 h. The concentrated crude residue was purified by column
chromatography (2:1 dichloromethane/hexanes) to give 40.5 mg
1
1
(0.12 mmol, 99%) of a white solid. H NMR (400 MHz): δ 8.88 (s,
(0.108 mmol, 90%) of a white solid. H NMR (400 MHz): δ 8.19
1H), 8.19 (dd, J = 8.6, 1.7 Hz, 1H), 8.06 (d, J = 8.1 Hz, 1H), 7.94
(d, J = 8.7 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 8.2 Hz,
2H), 7.65−7.54 (m, 2H), 7.44−7.34 (m, 3H), 7.35−7.27 (m, 2H),
7.28−7.22 (m, 2H), 2.41 (s, 3H). 13C NMR (100 MHz): δ 176.8,
145.9, 137.1, 135.9, 134.5, 132.9, 132.6, 132.5, 130.0, 129.9, 129.5,
129.2, 128.8, 128.4, 128.1, 127.8, 126.8, 126.6, 123.6, 90.2, 75.0, 21.7.
Anal. Calcd For C26H19NO3S: C, 73.39; H, 4.50; N, 3.29. Found: C,
73.32; H, 4.77; N, 3.32.
(d, J = 6.9 Hz, 2H), 7.67−7.57 (m, 3H), 7.52 (dd, J = 8.4 Hz, 6.9
Hz, 2H), 7.41−7.34 (m, 3H), 7.30−7.22 (m, 4H), 2.42 (s, 3H). 13C
NMR (100 MHz): δ 176.8, 145.9, 137.2, 136.9, 133.6, 132.9, 129.9,
129.5, 129.17, 129.15, 128.6, 128.1, 126.5, 90.1, 74.9, 21.6. Anal.
Calcd For C22H17NO3S: C, 70.38; H, 4.56; N, 3.73. Found: C,
70.51; H, 4.73; N, 3.86. Mp 139−140 °C.
N-(3-(2-Chlorophenyl)-3-oxoprop-1-ynyl)-N-phenyl-4-tolyl-
sulfonamide, 3. The reaction with 2-chlorobenzoyl chloride (32.6
mg, 0.186 mmol) and the ynamide (32.5 mg, 0.12 mmol) was
performed at 30 °C for 18 h. The concentrated crude residue was
N-(3-(1-Naphthyl)-3-oxoprop-1-ynyl)-N-phenyl-4-tolylsulfo-
namide, 7. The reaction with 1-naphthoyl chloride (55.0 mg, 0.28
4170
dx.doi.org/10.1021/jo500365h | J. Org. Chem. 2014, 79, 4167−4173

The Journal of Organic Chemistry
Note
mmol) and the ynamide (54.5 mg, 0.20 mmol) was performed at 20
°C for 38 h. The concentrated crude residue was purified by column
chromatography (1:1 dichloromethane/hexanes) to give 67 mg (0.16
NMR (400 MHz): δ 7.44−7.59 (m, 2H), 7.22−7.33 (m, 5H), 7.14−
7.21 (m, 2H), 6.77 (m, 1H), 6.10 (d, J = 6.2 Hz, 1H), 5.69 (m, 1H),
5.33 (m, 1H), 4.19−4.35 (m, 2H), 2.43 (s, 3H), 1.31 (m, 3H). 13C
NMR (100 MHz): δ 144.9, 138.5, 132.7, 129.4, 128.9, 128.3, 128.1,
126.0, 123.8, 123.3, 120.7, 120.4, 104.4, 104.1, 78.3, 66.9, 63.0, 50.0,
49.4, 34.1, 21.6, 14.3. Anal. Calcd for C23H21ClN2O4S: C, 60.46; H,
4.63; N, 6.13. Found: C, 60.64; H, 4.46; N, 5.96.
1
mmol, 79%) of a colorless oil. H NMR (400 MHz): δ δ 9.21 (d, J =
8.5 Hz, 1H), 8.56 (d, J = 7.1 Hz, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.89
(d, J = 8.1 Hz, 1H), 7.68−7.57 (m, 4H), 7.54 (dd, J = 7.6, 7.4 Hz,
1H), 7.41- 7.33 (m, 3H), 7.32−7.26 (m, 2H), 7.23 (d, J = 8.1 Hz,
2H), 2.38 (s, 3H). 13C NMR (100 MHz): δ 178.7, 145.9, 137.2,
134.6, 134.0, 133.9, 132.8, 132.7, 130.7, 129.9, 129.5, 129.2, 128.7,
128.5, 128.2, 126.6, 126.5, 125.9, 124.7, 88.7, 76.0, 21.7. Anal. Calcd
For C26H19NO3S: C, 73.39; H, 4.50; N, 3.29. Found: C, 73.30; H,
4.89; N, 3.30.
N-Ethoxycarbonyl-1,2-dihydro-2-(N-phenyl-N-tosylamino-
ethynyl)-4-bromopyridine, 13. The ynamide (54.2 mg, 0.20
mmol), CuI (3.8 mg, 0.02 mmol) and N,N-diisopropylethylamine
(70 μL, 0.40 mmol) were dissolved in 1 mL of anhydrous
acetonitrile. Then, a solution of 4-bromopyridine hydrochloride
(46.7 mg, 0.24 mmol), N,N-diisopropylethylamine (70 μL, 0.40
mmol), and ethyl chloroformate (38 μL, 0.40 mmol) in 2 mL of
anhydrous acetonitrile was added. The reaction was completed after
20 h. Chromatographic purification (1:4 EtOAc/hexanes) gave 72.4
N-(4,4-Dimethyl-3-oxopent-1-ynyl)-N-phenyl-4-tolylsulfona-
mide, 8. The reaction with pivaloyl chloride (21.6 mg, 0.179 mmol)
and the ynamide (33.5 mg, 0.124 mmol) was performed at 30 °C for
18 h. The concentrated crude residue was purified by column
chromatography (2:1 dichloromethane/hexanes) to give 39.5 mg
1
mg (0.14 mmol, 72%) of a slightly yellow oil. H NMR (400 MHz):
1
(0.111 mmol, 90%) of a white solid. H NMR (400 MHz): δ 7.56
δ 7.47−7.61 (m, 2H), 7.23−7.36 (m, 5H), 7.14−7.22 (m, 2H), 6.82
(m, 1H), 5.71 (m, 1H), 5.57 (d, J = 6.8 Hz, 1H), 5.31 (dd, J = 8.0,
2.1 Hz, 1H), 4.20−4.34 (m, 2H), 2.44 (s, 3H), 1.30 (s, 3H). 13C
NMR (100 MHz): δ 144.9, 138.4, 132.5, 129.4, 129.0, 128.4, 128.2,
127.1, 126.6, 126.0, 113.8, 113.3, 106.6, 78.4, 68.2, 63.0, 45.5, 45.1,
21.7, 14.3. Anal. Calcd for C23H21BrN2O4S: C, 55.10; H, 4.22; N,
5.59. Found: C, 54.73; H, 4.63; N, 5.28.
(d, J = 7.9 Hz, 2H), 7.36−7.28 (m, 3H), 7.26 (d, J = 8.1 Hz, 2H),
7.21−7.13 (m, 2H), 2.40 (s, 3H), 1.19 (d, J = 1.3 Hz, 9H). 13C
NMR (100 MHz): δ 193.0, 145.8, 137.4, 133.1, 129.8, 129.3, 129.0,
128.1, 126.4, 89.2, 73.6, 44.6, 26.2, 21.6. Anal. Calcd For
C20H21NO3S: C, 67.58; H, 5.95; N, 3.94. Found: C, 67.68; H,
6.29; N, 3.86. Mp 98−101 °C.
N-(4-Methyl-3-oxopent-1-ynyl)-N-phenyl-4-tolylsulfona-
mide, 9. The reaction with isobutyryl chloride (30.4 mg, 0.28
mmol) and the ynamide (54.0 mg, 0.20 mmol) was performed at 15
°C for 52 h. The concentrated crude residue was purified by column
chromatography (2:1 dichloromethane/hexanes) to give 47.3 mg
(0.14 mmol, 70%) of a colorless oil.1H NMR (400 MHz): δ 7.58 (d,
J = 7.9 Hz, 2H), 7.40−7.26 (m, 5H), 7.23−7.14 (m, 2H), 2.63 (hept,
J = 7.1 Hz, 1H), 2.42 (s, 3H), 1.20 (d, J = 7.1 Hz, 6H). 13C NMR
(100 MHz): δ 190.9, 145.9, 137.3, 132.9, 129.9, 129.4, 129.1, 128.1,
126.5, 89.1, 74.3, 42.7, 21.7, 18.1. Anal. Calcd For C19H19NO3S: C,
66.84; H, 5.61; N, 4.10. Found: C, 66.59; H, 5.86; N, 4.00.
N-Ethoxycarbonyl-1,2-dihydro-2-(N-phenyl-N-tosylamino-
ethynyl)pyridine, 10. The reaction between the ynamide (54.2 mg,
0.20 mmol) and pyridine (20 μL, 0.24 mmol) was completed after
2.5 h. Chromatographic purification (1:7 Et2O/hexanes) gave 60.3
N-Ethoxycarbonyl-1,2-dihydro-2-(N-phenyl-N-tosylamino-
ethynyl)-4-phenylpyridine, 14. The reaction between the
ynamide (54.2 mg, 0.20 mmol) and 4-phenylpyridine (37.2 mg,
0.24 mmol) was completed after 2.5 h. Chromatographic purification
(1:4 EtOAc/hexanes) gave 95.5 mg (0.19 mmol, 96%) of a slightly
1
yellow oil. H NMR (400 MHz): δ 7.46−7.58 (m, 2H), 7.23−7.46
(m, 8H), 7.16−7.23 (m, 2H), 7.02−7.16 (m, 2H), 6.92 (m, 1H),
5.69−5.91 (m, 3H), 4.22−4.37 (m, 2H), 2.36 (s, 3H), 1.27−1.40 (m,
3H). 13C NMR (100 MHz): δ 153.6, 152.8, 144.8, 144.7, 138.6,
138.3, 134.6, 134.3, 132.6, 129.3, 128.9, 128.6, 128.4, 128.2, 128.1,
128.0, 126.0, 125.8, 125.5, 113.9, 113.4, 106.2, 77.7, 69.1, 62.7, 44.5,
44.0, 21.6, 14.5. Anal. Calcd for C29H26N2O4S: C, 69.86; H, 5.26; N,
5.62. Found: C, 69.76; H, 5.47; N, 5.56.
N-Ethoxycarbonyl-2-(N-phenyl-N-tosylaminoethynyl)-2,3-di-
hydro-4-pyridone, 15. The reaction between the ynamide (54.2
mg, 0.20 mmol) and 4-methoxypyridine (25 μL, 0.24 mmol) was
completed after 2.5 h. Acidic workup (1 M aqueous HCl) followed
by chromatographic purification (1:1 EtOAc/hexanes, Al2O3) gave
1
mg (0.14 mmol, 71%) of a slightly yellow oil. H NMR (400 MHz):
δ 7.42−7.72 (m, 2H), 7.21−7.33 (m, 5H), 7.14−7.21 (m, 2H), 6.76
(m, 1H), 5.99 (dd, J = 9.3, 5.6 Hz, 1H), 5.43−5.82 (m, 2H), 5.35
(d, J = 7.3 Hz, 1H), 4.18−4.34 (m, 2H), 2.43 (s, 3H), 1.24−1.36
(m, 3H). 13C NMR (100 MHz): δ 153.8, 153.0, 145.0, 144.8, 138.7,
132.6, 129.4, 128.9, 128.5, 128.2, 128.1, 126.0, 125.1, 124.7, 122.5,
122.2, 118.4, 117.9, 105.2, 69.1, 62.6, 44.1, 43.5, 21.7, 14.5. Anal.
Calcd for C23H22N2O4S: C, 65.38; H, 5.25; N, 6.63. Found: C,
65.17; H, 5.36; N, 6.51.
1
68.2 mg (0.16 mmol, 78%) of a slightly yellow oil. H NMR (400
MHz): δ 7.75 (d, J = 8.4 Hz, 1H), 7.47 (d, J = 8.3 Hz, 2H), 7.22−
7.34 (m, 5H), 7.08−7.18 (m, 2H), 5.51 (d, J = 6.3 Hz, 1H), 5.43
(dd, J = 8.4, 1.3 Hz, 1H), 4.27−4.41 (m, 2H), 2.88 (dd, J = 16.3, 6.5
Hz, 1H), 2.59 (ddd, J = 16.3, 1.6, 1.6 Hz, 1H), 2.44 (s, 3H), 1.35 (t,
J = 7.1 Hz, 3H). 13C NMR (100 MHz): δ 191.3, 152.1, 145.2, 141.3,
138.2, 132.5, 129.6, 129.1, 128.3, 128.2, 126.0, 107.5, 77.9, 66.9, 63.9,
45.5, 41.6, 21.7, 14.3. Anal. Calcd for C23H22N2O5S: C, 63.00; H,
5.06; N, 6.39. Found: C, 62.74; H, 4.99; N, 6.09.
N-Ethoxycarbonyl-1,2-dihydro-2-(N-phenyl-N-tosylamino-
ethynyl)-4-chloropyridine, 11. The ynamide (54.2 mg, 0.20
mmol), CuI (3.8 mg, 0.02 mmol), and N,N-diisopropylethylamine
(70 μL, 0.40 mmol) were dissolved in 1 mL of anhydrous
dichloromethane. Then, a solution of 4-bromopyridine hydrochloride
(46.7 mg, 0.24 mmol), N,N-diisopropylethylamine (70 μL, 0.40
mmol), and ethyl chloroformate (38 μL, 0.40 mmol) in 1 mL of
anhydrous dichloromethane was added. The reaction was completed
after 2.5 h. Chromatographic purification (3:8 Et2O/hexanes) gave
N-Ethoxycarbonyl-1,2-dihydro-2-(N-phenyl-N-tosylamino-
ethynyl)quinoline, 16. The reaction between the ynamide (54.2
mg, 0.20 mmol) and quinoline (29 μL, 0.24 mmol) was completed
after 2.5 h. Chromatographic purification (3:8 Et2O/hexanes) gave
1
86.0 mg (0.18 mmol, 91%) of a slightly yellow oil. H NMR (400
MHz): δ 7.59 (d, J = 8.3 Hz, 1H), 7.11−7.30 (m, 8H), 7.06−7.11
(m, 2H), 6.93−7.00 (m, 2H), 6.55 (d, J = 9.1 Hz, 1H), 6.06 (dd, J =
9.2, 6.2 Hz, 1H), 5.98 (d, J = 6.1 Hz, 1H), 4.19−4.41 (m, 2H), 2.41
(s, 3H), 1.33 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz): δ 153.6,
144.6, 138.5, 134.5, 132.5, 129.2, 128.9, 128.1, 128.0, 127.7, 126.8,
126.6, 125.9, 125.9, 125.2, 124.4, 124.2, 78.0, 67.8, 62.5, 44.3, 21.7,
14.5. Anal. Calcd for C27H24N2O4S: C, 68.62; H, 5.12; N, 5.93.
Found: C, 68.82; H, 5.36; N, 5.66.
1
83.0 mg (0.18 mmol, 91%) of a slightly yellow oil. H NMR (400
MHz): δ 7.54 (d, J = 8.0 Hz, 2H), 7.22−7.35 (m, 5H), 7.11−7.21
(m, 2H), 6.82 (m, 1H), 5.71 (s, 1H), 5.56 (m, 1H), 5.31 (dd, J =
8.0, 2.1 Hz, 1H), 4.19−4.34 (m, 2H), 2.44 (s, 3H), 1.27−1.34 (m,
3H). 13C NMR (100 MHz): δ 144.9, 138.5, 132.7, 129.4, 129.0,
128.4, 128.1, 126.6, 126.0, 113.6, 106.6, 78.5, 68.2, 63.0, 45.3, 21.6,
14.3. Anal. Calcd for C23H21ClN2O4S: C, 60.46; H, 4.63; N, 6.13.
Found: C, 60.28; H, 4.90; N, 6.13.
N-Ethoxycarbonyl-1,2-dihydro-2-(N-phenyl-N-tosylamino-
ethynyl)-4,7-dichloroquinoline, 17. The reaction between the
ynamide (54.2 mg, 0.20 mmol) and 4,7-dichloroquinoline (47.5 mg,
0.24 mmol) was completed after 20 h. Chromatographic purification
(1:6 Et2O/hexanes) gave 95.0 mg (0.18 mmol, 88%) of a slightly
N-Ethoxycarbonyl-1,2-dihydro-2-(N-phenyl-N-tosylamino-
ethynyl)-5-chloropyridine, 12. The reaction between the ynamide
(54.2 mg, 0.20 mmol) and 3-chloropyridine (23 μL, 0.24 mmol) was
completed after 2.5 h. Chromatographic purification (1:7 Et2O/
1
1
hexanes) gave 67.1 mg (0.15 mmol, 73%) of a slightly yellow oil. H
yellow oil. H NMR (400 MHz): δ 7.63 (s, 1H), 7.58 (d, J = 8.4 Hz,
4171
dx.doi.org/10.1021/jo500365h | J. Org. Chem. 2014, 79, 4167−4173

The Journal of Organic Chemistry
Note
1H), 7.20−7.30 (m, 6H), 7.15−7.20 (m, 2H), 6.92−6.97 (m, 2H),
6.20 (d, J = 6.9 Hz, 1H), 6.00 (d, J = 6.8 Hz, 1H), 4.19−4.46 (m,
2H), 2.45 (s, 3H), 1.35 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz) δ
152.7, 144.9, 138.3, 135.8, 134.7, 132.5, 129.3, 128.9, 128.2, 128.1,
125.9, 125.8, 124.6, 124.2, 123.8, 122.4, 79.3, 66.4, 63.1, 45.3, 21.7,
14.4. Anal. Calcd for C27H22Cl2N2O4S: C, 59.89; H, 4.10; N, 5.17.
Found: C, 60.08; H, 4.49; N, 5.28.
Hsung, R. P. Org. Lett. 2008, 10, 661−663. Nucleophilic alkylations
with lithiated ynamides: (f) Frederick, M. O.; Mulder, J. A.; Tracey,
M. R.; Hsung, R. P.; Huang, J.; Kurtz, K. C. M.; Shen, L.; Douglas,
C. J. J. Am. Chem. Soc. 2003, 125, 2368−2369. Homologation with
aldehydes or ketones: (g) You, L.; Al-Rashid, Z. F.; Figueroa, R.;
Ghosh, S. K.; Ti, G.; Lu, T.; Hsung, R. P. Synlett 2007, 1656−1662.
(6) [3 + 2] Cycloadditions: (a) IJsselstijn, M.; Cintrat, J.-C.
Tetrahedron 2006, 62, 3837−3842. (b) Li, H.; You, L.; Zhang, X.;
Johnson, W. L.; Figueroa, R.; Hsung, R. P. Heterocycles 2007, 74,
553−568. (c) Li, H.; Hsung, R. P. Org. Lett. 2009, 11, 4462−4465.
(d) Zhang, X.; Li, H.; You, L.; Tang, Y.; Hsung, R. P. Adv. Synth.
Catal. 2006, 348, 2437−2442. (e) Zhang, X.; Hsung, R. P.; Li, H.
Chem. Commun. 2007, 2420−2422. (f) Kim, J. Y.; Kim, S. H.;
Chang, S. Tetrahedron Lett. 2008, 49, 1745−1749. (g) Zhang, X.;
Hsung, R. P.; Li, H.; Zhang, Y.; Johnson, W. L.; Figueroa, R. Org.
Lett. 2008, 10, 3477−3479. [4 + 2] Cycloadditions: (h) Martinez-
Esperon, M. F.; Rodriguez, D.; Castedo, L.; Saa, C. Org. Lett. 2005,
7, 2213−2216. [2 + 2+1] Cycloadditions: (i) Witulski, B.;
Goessmann, M. Synlett 2000, 1793−1797. [2 + 2+2] Cyclo-
additions: (j) Witulski, B.; Stengel, T. Angew. Chem., Int. Ed. 1999,
38, 2426−2430. (k) Witulski, B.; Stengel, T.; Fernandez-Hernandez,
J. Chem. Commun. 2000, 1965−1966. (l) Witulski, B.; Alayrac, C.
Angew. Chem., Int. Ed. 2002, 41, 3281−3284. (m) Dateer, R. B.;
Shaibu, B. S.; Liu, R.-S. Angew. Chem., Int. Ed. 2012, 51, 113−117.
(7) (a) Marion, F.; Coulomb, J.; Courillon, C.; Fensterbank, L.;
Malacria, M. Org. Lett. 2004, 6, 1509−1511. (b) Marion, F.;
Coulomb, J.; Servais, A.; Courillon, C.; Fensterbank, L.; Malacria, M.
Tetrahedron 2006, 62, 3856−3871. (c) Hashmi, A. S.; Rudolph, M.;
Bats, J.; Frey, W.; Rominger, F.; Oeser, T. Chem.Eur. J. 2008, 14,
6672−6678. (d) Couty, S.; Meyer, C.; Cossy, J. Tetrahedron 2009,
65, 1809−1832.
N-Ethoxycarbonyl-1,2-dihydro-2-(N-phenyl-N-tosylamino-
ethynyl)-4-chloro-6-methoxyquinoline, 18. The reaction be-
tween the ynamide (54.2 mg, 0.20 mmol) and 4-chloro-6-
methoxyquinoline (46.5 mg, 0.24 mmol) was completed after 2.5
h. Chromatographic purification (1:4 Et2O/hexanes) gave 88.1 mg
1
(0.16 mmol, 82%) of a slightly yellow oil. H NMR (400 MHz): δ
7.47 (s, 1H), 7.13−7.32 (m, 8H), 6.92−7.00 (m, 2H), 6.90 (dd, J =
8.9, 3.0 Hz, 1H), 6.21 (d, J = 6.8 Hz, 1H), 6.01 (d, J = 7.0 Hz, 1H),
4.18−4.36 (m, 2H), 3.87 (s, 3H), 2.43 (s, 3H), 1.32 (t, J = 7.1 Hz,
3H). 13C NMR (100 MHz): δ 156.6, 144.7, 138.5, 132.7, 130.0,
129.3, 128.9, 128.2, 128.1, 126.5, 125.9, 114.9, 109.7, 78.7, 66.7, 62.7,
55.7, 45.2, 21.7, 14.5. Anal. Calcd for C28H25ClN2O5S: C, 62.62; H,
4.69; N, 5.22. Found: C, 62.69; H, 5.02; N, 5.28.
N-Ethoxycarbonyl-5,6-dihydro-6-(N-phenyl-N-tosylamino-
ethynyl)phenanthridine, 19. The reaction between the ynamide
(54.2 mg, 0.20 mmol) and phenanthridine (43.0 mg, 0.24 mmol)
was completed after 3 h. Chromatographic purification (1:3 Et2O/
pentanes) gave 99.5 mg (0.19 mmol, 95%) of a colorless oil. 1H
NMR (400 MHz): δ 7.76 (dd, J = 7.0 Hz, 7.0 Hz, 2H), 7.58 (m,
1H), 7.42 (m, 1H), 7.24−7.37 (m, 4H), 7.00−7.21 (m, 7H), 6.71 (d,
J = 7.7 Hz, 2H), 6.48 (s, 1H), 4.16−4.37 (m, 2H), 2.41 (s, 3H), 1.32
(t, J = 7.1 Hz, 3H). 13C NMR (100 MHz): δ 153.1, 144.4, 138.5,
135.0, 132.2, 130.7, 129.2, 128.8, 128.7, 128.1, 128.0, 127.8, 125.7,
125.6, 125.1, 123.9, 78.9, 68.5, 62.5, 48.1, 21.7, 14.5. Anal. Calcd for
C31H26N2O4S: C, 71.24; H, 5.01; N, 5.36. Found: C, 70.89; H, 5.26;
N, 5.57.
(8) Homocoupling reactions: (a) Rodriguez, D.; Castedo, L.; Saa,
C. Synlett 2004, 377−379. Negishi cross-couplings: (b) Rodriguez,
D.; Castedo, L.; Saa, C. Synlett 2004, 783−786. (c) Martinez-
Esperon, M. F.; Rodriguez, D.; Castedo, L.; Saa, C. Tetrahedron
2006, 62, 3843−3855. Sonogashira couplings: (d) Tracey, M. R.;
Zhang, Y.; Frederick, M. O.; Mulder, J. A.; Hsung, R. P. Org. Lett.
2004, 6, 2209−2212. (e) Dooleweerdt, K.; Ruhland, T.; Skrydstrup,
T. Org. Lett. 2009, 11, 221−224. Heck reactions: (f) Couty, S.;
Liegault, B.; Meyer, C.; Cossy, J. Org. Lett. 2004, 6, 2511−2514.
(g) Couty, S.; Liegault, B.; Meyer, C.; Cossy, J. Tetrahedron 2006,
62, 3882−3895.
ASSOCIATED CONTENT
* Supporting Information
NMR spectra and crystallographic details. This material is
available free of charge via the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
*E-mail: cw27@georgetown.edu.
■
(9) Saito, N.; Sato, Y.; Mori, M. Org. Lett. 2002, 4, 803−805.
(10) Banerjee, B.; Litvinov, D. N.; Kang, J.; Bettale, J. D.; Castle, S.
L. Org. Lett. 2010, 12, 2650−2652.
Notes
The authors declare no competing financial interest.
(11) (a) Tanaka, R.; Hirano, S.; Urabe, H.; Sato, F. Org. Lett. 2003,
5, 67−70. (b) Tanaka, R.; Yuza, A.; Watai, Y.; Suzuki, D.; Takayama,
Y.; Sato, F.; Urabe, M. J. Am. Chem. Soc. 2005, 127, 7774−7780.
(c) Tanaka, D.; Sato, Y.; Mori, M. J. Am. Chem. Soc. 2007, 129,
7730−7731.
ACKNOWLEDGMENTS
We gratefully acknowledge financial support from the
National Institutes of Health (GM106260).
■
(12) (a) Joshi, R. V.; Xu, Z.-Q.; Ksebati, M. B.; Kessel, D.; Corbett,
T. H.; Drach, J. C.; Zemlicka, J. J. Chem. Soc., Perkin Trans. 1 1994,
10, 1089−1098. (b) Rodriguez, D.; Castedo, L.; Saa, C. Synlett 2007,
1963−1965. (c) Egi, M.; Yamaguchi, Y.; Fujiwara, N.; Akai, S. Org.
Lett. 2008, 10, 1867−1870. (d) Wang, X.-N.; Winston-McPherson,
G. N.; Walton, M. C.; Zhang, Y.; Hsung, R. P.; DeKorver, K. A. J.
Org. Chem. 2013, 78, 6233−6244.
REFERENCES
■
(1) For excellent reviews, see: (a) Zificsak, C. A.; Mulder, J. A.;
Hsung, R. P.; Rameshkumar, C.; Wei, L.-L. Tetrahedron 2001, 57,
7575−7606. (b) Evano, G.; Coste, A.; Jouvin, K. Angew. Chem., Int.
Ed. 2010, 49, 2840−2859. (c) DeKorver, K. A.; Li, H.; Lohse, A. G.;
Hayashi, R.; Lu, Z.; Zhang, Y.; Hsung, R. P. Chem. Rev. 2010, 110,
5064−5106.
(2) Witulski, B.; Goessmann, M. Chem. Commun. 1999, 1879−
1880.
(3) (a) Bruckner, D. Synlett 2000, 1402−1404. (b) Bruckner, D.
Tetrahedron 2006, 62, 3809−3814.
(4) Rodriguez, D.; Castedo, L.; Saa, C. Synlett 2007, 1963−1965.
(5) Selected examples. Hydroboration: (a) Witulski, B.;
Buschmann, N.; Bergstraesser, U. Tetrahedron 2000, 56, 8473−
8480. Oxoarylations and cyclizations: (b) Bhunia, S.; Chang, C.-J.;
Liu, R.-S. Org. Lett. 2012, 14, 5522−5525. (c) Yang, L.-Q.; Wang, K.-
B.; Li, C.-Y. Eur. J. Org. Chem. 2013, 2775−2779. (d) Couty, S.;
Meyer, C.; Cossy, J. Synlett 2007, 2819−282. (e) Al-Rashid, Z. F.;
(13) (a) Cook, A. M.; Wolf, C. Chem. Commun. 2014, 50, 3151−
3154.
For the synthesis of indole-derived ynamines, see:
(b) Hamada, T.; Ye, X.; Stahl, S. S. J. Am. Chem. Soc. 2008, 130,
833−835.
(14) Selected examples: (a) Tohda, Y.; Sonogashira, K.; Hagihara,
N. Synthesis 1977, 777−778. (b) Chowdhury, C.; Kundu, N. G.
Tetrahedron 1999, 55, 7011−7016. (c) Guo, M.; Li, D.; Zhang, Z. J.
Org. Chem. 2003, 68, 10172−10174. (d) Chen, L.; Li, C.-J. Org. Lett.
2004, 6, 3151−3153. (e) Likhar, P. R.; Subhas, M. S.; Roy, M.; Roy,
S.; Kantam, M. L. Helv. Chim. Acta 2008, 91, 259−264. (f) Yuan, H.;
Jin, H.; Li, B.; Shen, Y.; Yue, R.; Shan, L.; Sun, Q.; Zhang, W. Can. J.
Chem. 2013, 91, 333−337.
4172
dx.doi.org/10.1021/jo500365h | J. Org. Chem. 2014, 79, 4167−4173

The Journal of Organic Chemistry
Note
(15) Selected examples: (a) Kang, S.-K.; Lim, K.-H.; Ho, P.-S.; Kim,
W.-Y. Synthesis 1999, 874−876. (b) Liang, B.; Huang, M.; You, Z.;
Xiong, Z.; Lu, K.; Fathi, R.; Chen, J.; Yang, Z. J. Org. Chem. 2005,
70, 6097−6100. (c) Fusano, A.; Fukuyama, T.; Nishitani, S.; Inouye,
T.; Ryu, I. Org. Lett. 2010, 12, 2410−2413. (d) Wu, X.-F.; Neumann,
H.; Beller, M. Chem.Eur. J. 2010, 16, 12104−12107.
(16) We observed that the ynesulfonamide used in this study
undergoes thermal decomposition at 60 °C.
(17) For comparison we prepared 1,3-diphenylprop-2-yn-1-one
from phenylacetylene and benzoyl chloride. This C-substituted ynone
has the alkyne and the carbonyl stretchings at 2199 and 1640 cm−1,
respectively.
(18) Selected examples: (a) Fernandez-Ibanez, M.; Macia, B.;
Pizzuti, M. G.; Minnaard, A. J.; Feringa, B. L. Angew. Chem. 2009,
48, 9339−9341. (b) Sun, Z.; Yu, S.; Ding, Z.; Ma, D. J. Am. Chem.
Soc. 2007, 129, 9300−9301. (c) Black, D. A.; Beveridge, R. E.;
Arndtsen, B. A. J. Org. Chem. 2008, 736, 1906−1910. (d) Chen, Q.;
du Jourdin, X. M.; Knochel, P. J. Am. Chem. Soc. 2013, 135, 4958−
4961. (e) Chau, S. T.; Lutz, P.; Wu, K.; Doyle, A. G. Angew. Chem.
2013, 51, 9153−9156. For recent reviews, see: (f) Bull, J. A.;
Mousseau, J. J.; Pelletier, G.; Charette, A. B. Chem. Rev. 2012, 112,
2642−2713. (g) Silva, E. M. P.; Varandas, P. A. M. M.; Silva, A. M.
S. Synthesis 2013, 45, 3053−3089. (h) Larionov, O. V.; Stephens, D.;
Mfuh, A.; Chavez, G. Org. Lett. 2014, 16, 864−867.
(19) We observed exclusive 1,2-addition of the ynesulfonamide to
quinoline, but slow conversion was observed when acridine and
isoquinolines were applied in this procedure. It is noteworthy that
this protocol is not limited to ynesulfonamide 1, and we found that
ynecarbamates or indole-derived ynamines react smoothly with
pyridine under the same conditions.
4173
dx.doi.org/10.1021/jo500365h | J. Org. Chem. 2014, 79, 4167−4173