Substrate Control in the Gold(I)-Catalyzed Cyclization of β-Propargylamino Acrylic Esters and Further Transformations of the Resultant Dihydropyridines

Article abstract of DOI:10.1002/adsc.201600412

N-Protected β-propargylamino acrylic esters with a push-pull olefinic bond afforded good to high yields of dihydropyridines upon treatment with 5% tris(2-furyl)phosphine-gold(I) chloride/silver(I) tetrafluoroborate [(TFP)AuCl/AgBF₄] in anhydrous benzene. Carbamate and sulfonyl groups were employed for nitrogen protection. On a model enyne, the p-methoxybenzenesulfonyl (MBS) group was found to be a better protective group than tosyl in terms of cyclization yield, and also the yield of elimination to the corresponding 2,3,4-trisubstituted pyridines. Boc-protected dihydropyridines underwent partial deprotection/oxidation under the cyclization conditions, which enabled a more straightforward, one-pot preparation of the corresponding pyridines. In another application, an appropriately substituted derivative protected as a stable methoxycarbamate was subjected to catalytic hydrogenation affording the known precursor of paroxetine. The chemoselectivity of enyne cyclization (dihydropyridine vs. pyrrole) is governed, among other factors, by C-3 substitution. Dihydropyridines were obtained as sole products regardless of the catalyst/conditions when C-3 was unsubstituted. (Figure presented.).

Full text of DOI:10.1002/adsc.201600412

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DOI: 10.1002/adsc.201600412
Substrate Control in the Gold(I)-Catalyzed Cyclization of
b-Propargylamino Acrylic Esters and Further Transformations
of the Resultant Dihydropyridines
a
b
a
ˇ
ˇ
ˇ a
ˇ
ˇ
ˇ
ˇ
ˇ a
Jirꢀ Mikusek, Petr Matous, Eliska Matousovꢁ, Martin Janousek, Jirꢀ Kunes,
and Milan Poura,*
a
Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy, Heyrovskꢂho 1203,
Hradec Krꢁlovꢂ 500 05, Czech Republic
E-mail: milan.pour@faf.cuni.cz
Department of Organic Chemistry, Charles University in Prague, Faculty of Science, Hlavova 8, Prague 128 43, Czech
b
Republic
Received: April 18, 2016; Revised: June 28, 2016; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201600412.
Abstract: N-Protected b-propargylamino acrylic one-pot preparation of the corresponding pyridines.
esters with a push-pull olefinic bond afforded good In another application, an appropriately substituted
to high yields of dihydropyridines upon treatment derivative protected as a stable methoxycarbamate
with 5% tris(2-furyl)phosphine-gold(I) chloride/sil- was subjected to catalytic hydrogenation affording
ver(I) tetrafluoroborate [(TFP)AuCl/AgBF4] in an- the known precursor of paroxetine. The chemoselec-
hydrous benzene. Carbamate and sulfonyl groups tivity of enyne cyclization (dihydropyridine vs. pyr-
were employed for nitrogen protection. On a model role) is governed, among other factors, by C-3 substi-
enyne, the p-methoxybenzenesulfonyl (MBS) group tution. Dihydropyridines were obtained as sole prod-
was found to be a better protective group than tosyl ucts regardless of the catalyst/conditions when C-3
in terms of cyclization yield, and also the yield of was unsubstituted.
elimination to the corresponding 2,3,4-trisubstituted
pyridines. Boc-protected dihydropyridines underwent
partial deprotection/oxidation under the cyclization Keywords: dihydropyridines; enynes; gold(I); homo-
conditions, which enabled a more straightforward, genous catalysis; pyridines
Introduction
strates indicated preferential formation of multisubsti-
tuted pyrroles.[6] Therein, N-heterocyclic carbene-
Gold-catalyzed enyne cyclizations have become Au(I)-catalyzed cyclization of the closely related N-
a powerful tool in the assembly of novel heterocyclic propargyl enaminones 3 was described leading to
structures.[1] Depending on the structure of the start- multisubstituted pyrroles 4 via an Au-catalyzed Clais-
ing enynes and/or catalyst used, a variety of oxygen en rearrangement to allene followed by a 5-exo-dig
and nitrogen heterocycles possessing specific substitu- cyclization (Scheme 2). Dihydropyridines arising
tion patterns has been produced.[2,3] A few years ago, through a 6-endo-trig pathway were observed only as
we employed tris(2-furyl)phosphine (TFP) as a ligand by-products in low yields using various other catalysts
to Au(I) in the cyclizations of propargyl vinyl including (PPh3)AuCl/AgBF4. In two cases (R1 =H or
ethers.[4] The cationic gold catalyst generated from CO2Et), however, 6-membered rings were obtained as
(TFP)AuCl effected cyclization of b-propargyloxy
acrylic esters with a push-pull double bond to afford
multisubstituted dihydropyrans in excellent yields
(Scheme 1).
Extension of the protocol to the cycloisomerization
of the analogous b-propargylamino derivatives to di-
hydropyridines[5] was the next logical move, especially
since previous results of Hanzawa with similar sub- Scheme 1. Cyclization of propargyl vinyl ethers 1.
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species[4] generated from (TFP)AuCl/AgBF4. In this
paper, we report that the cyclization led exclusively to
the formation of six-membered rings, and that this be-
havior can be ascribed to the substitution of the start-
ing material. Further synthetic modifications of the
dihydropyridines have been explored, including the
conversion to 2,3,4-trisubstituted pyridines, and syn-
thesis of the known precursor of the antidepressant
paroxetine via catalytic hydrogenation of the dihydro-
pyridine ring.
Results and Discussion
In order to obtain a clue about the course of cycliza-
tion, model compounds 12a and 12b with two differ-
ent sulfonamide protective groups, Ts and MBS (p-
methoxybenzenesulfonamide)
were
prepared
(Scheme 3, see Table S1 in the Supporting Informa-
tion for details) and cyclized (Table 1). The less usual
MBS group was selected in order to explore the feasi-
bility of subsequent elimination. Assuming that elimi-
native removal of the sulfonyl group may proceed via
pyrolytic syn-elimination rather than the E1/E2 path-
way, we reasoned that an electron-donating moiety
Scheme 2. Comparison of this work with previously pub-
lished results.
major products. Recently, catalyst-controlled forma-
tion of dihydropyridines as major products was ob-
served by Menon and co-workers[7] in the cyclizations
of N-propargyl-N-vinyl sulfonamides 5 (Scheme 2).
Somewhat surprisingly, the use of cationic gold spe-
cies generated from (PPh3)AuCl/AgSbF6 gave rise to
dihydropyridines 7, while Echavarrenꢄs[8] [John-
Scheme 3. Synthesis of the starting enynes.
Table 1. Screening of the reaction conditions.
ACHTUNGTRENNUNGPhosAu(MeCN)]SbF6 induced the formation of pyr-
roles 6. Even though the authors ascribed the ob-
served chemoselectivity to catalyst control, enynes 5
furnished dihydropyridines 7 only in those cases when
R2 =H. In both 3 and 5, the double bond acts as a nu-
cleophile attacking the Au(I)-activated triple bond.
While the trisubstituted double bond in 3 possesses
a push-pull character, the other one is a 1,1-disubsti-
tuted olefin of the enamine type. Taken together,
these observations strongly indicate that the chemose-
lectivity of the cycloisomerization observed by both
Hanzawa and Menon is very likely controlled by the
substrate structure as well as the catalyst and/or the
reaction conditions. For the above reasons, we were
tempted to elucidate the possibility of reversing the
chemoselectivity of the cyclization of enynes with po-
larized push-pull double bonds in favor of dihydropyr-
idines.
Entry Z
Catalyst
Solvent Yield
[%]
1
2
Ts
(TFP)AuCl/AgBF4
C6H6
C6H6
88
99
MBS (TFP)AuCl/AgBF4
3
4
5
Ts
MBS (TFP)AuCl/AgBF4
Ts (TFP)AuCl/AgBF4
(TFP)AuCl/AgBF4
toluene 2
toluene 55
CH2Cl2
0
6
7
8
9
MBS (TFP)AuCl/AgBF4
MBS (TFP)AuCl/AgBF4
MBS (TFP)AuCl/AgBF4
MBS (PPh3)AuCl/AgBF4
CH2Cl2 86
THF
DMF
C6H6
85
10
70
80
87
Thus, we set out to prepare a large series of N-pro-
tected b-propargylamino acrylic esters analogous to
propargylic ethers 1 (and Hanzawaꢄs sulfonamides 3),
and study their cyclizations using the cationic Au(I)
10
11
MBS [JohnPhosAu(MeCN)]SbF6 C6H6
MBS [(IPr)Au(MeCN)]BF4 C6H6
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would supply electron density to the sulfonyl oxygen gel/CHCl3, alumina/CHCl3, DBU/THF, DBU/dioxane,
and hence improve its ability to abstract the neighbor- DBU/DMF) afforded the best yields upon heating di-
ing hydrogen. In addition, model enyne 12b with the hydropyridines 14a and 14b with DBU in DMF. As
MBS group was obtained in a higher overall yield expected, MBS-protected 14b furnished a significantly
than its tosyl analog 12a (45% vs. 58%, see Table S1 higher yield (60%) of pyridine 15a compared to its
in the Supporting Information).
Ts-analog 14a (33%). In summary, the screening re-
The exposure of 12a and 12b to various catalytic sults indicated that both MBS protection and
systems is summarized in Table 1. The best results (TFP)AuCl/AgBF4 as the catalyst were reasonable
were obtained when 5% (TFP)AuCl/AgBF4 in ben- choices.
zene was used (entry 2). This combination of catalysts
With the optimized reaction conditions in hand, we
previously reported by us[4] for tetrahydropyrans fur- set out to prepare two series of the starting enynes 12
nished a high isolated yield of dihydropyridine 14a (Z=sulfonyl) and 13 (Z=carbamate) via Michael ad-
(88%), and a quantitative yield of 14b.
dition/Sonogashira cross-coupling (see Table S1 in the
Conversion of dihydropyridines 14 to pyridines was Supporting Information). The carbamate-protected
also briefly evaluated on the model substrates series was prepared with a view to having another
(Scheme 4). Eliminations carried out under various protective group which can be removed in an alterna-
conditions (heating in dioxane/H2O or THF/H2O, tive (and easier) manner, but only compounds with
Cs2CO3/MeOH, K2CO3/THF, Dowex/MeOH, silica R1 =H were accessible for Z=carbamate. The pres-
ence of MBS, on the other hand, allowed the prepara-
tion of derivatives with a substituent at the R1 posi-
tion.
MBS-protected enynes 12 were subjected to cycli-
zation conditions first (Table 2). Similar to the model
compounds, excellent yields of dihydropyridines 14
were obtained. Only moderate yields were recorded
Scheme 4. Outline of the pilot elimination experiments.
Table 2. Cyclization and deprotection of sulfonamide-protected enynes.
Compound
R1
R3
Z
Dihydropyridine
Yield of 14 [%]
Pyridine
Overall yield[a] [%]
12a
12b
12c
12d
12e
12f
12g
12h
12i
12j
12k
12l
12m
12n
12o
12p
12q
H
H
H
H
H
H
H
H
Ph
Ph
Ts
14a
14b
14c
14d
14e
14f
14g
14h
14i
14j
14k
14l
14m
14n
14o
14p
14q
88
99
77
92
24[b]
N
70
71
22[c]
61
52[d]
73
47
27
89
N
15a
15a
15c
15d
15e
–
15g
15h
15i
15j
15k
15l
15m
15n
15o
–
29
59
29
18
15
–
27
28
33
31
49
51
26
3
MBS
MBS
MBS
MBS
MBS
MBS
MBS
MBS
MBS
MBS
MBS
MBS
MBS
MBS
MBS
MBS
p-MeC6H4
p-BrC6H4
p-NO2C6H4
o-NO2C6H4
2-thienyl
p-ClC6H4
1-naphthyl
p-MeOC6H4
m-MeOC6H4
Ph
H
H
H
COOMe
Me
Pr
Ph
H
Ph
Ph
Ph
16
–
–
p-NH2C6H4
pyridin-3-yl
H
N
–
[a]
Based on 12.
[b]
[c]
[d]
NMR yield of 14e, product inseparable from the reaction mixture.
NMR yield of 14i, isolated as a mixture with 15i.
NMR yield of 14k, isolated as a mixture with 15k; N=no reaction.
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for enynes with R1 =alkyl (12m, 12n), while the pres-
ence of phenyl in the same position (12o) did not
have any negative influence.
Table 3. Cyclization and deprotection of carbamate-protect-
ed enynes.
Although the yields of trisubstituted dihydropyri-
dines 14m and 14n were just moderate, no trace of
1
pyrrole formation was detected in the crude H NMR
spectra. p-Nitrophenyl-substituted enyne 12e afforded
an inseparable mixture of products which contained
14e only in a low NMR yield. No product was ob-
tained in the reaction of o-nitrophenyl derivative 12f.
4-Aminophenyl and pyridine-3-yl substituted enynes
12p and 12q afforded no cyclization products, either,
probably due to complexation of the cationic catalyst
by nitrogen.
Thus, in contrast to the results described by Hanza-
wa with the structurally related enynes 3, cyclization
of compounds 12 yielded exclusively dihydropyri-
dines. Elimination to substituted pyridines was at-
tempted under the optimized conditions found for the
model substrate 14a (DBU, DMF, 1408C). Pyridines
15 were obtained in moderate to good overall isolated
yields from the starting enynes 12. The results in
Table 2 show that electron-withdrawing groups (14d,
Compound R3
Z
Product Yield [%]
13a
13b
13c
13d
13e
13f
13g
13h
13i
Ph
Ph
Boc
CO2Me 16b
15a
51
81[a]
48
51
N
p-MeC6H4
p-BrC6H4
p-NO2C6H4
o-NO2C6H4
2-thienyl
p-ClC6H4
1-naphthyl
p-MeOC6H4
m-MeOC6H4
Boc
Boc
Boc
Boc
Boc
Boc
Boc
Boc
Boc
15c
15d
–
–
N
15g
15h
15i
15j
15k
15t
15u
29
30
43
38
32
51
44
85[a]
N
13j
13k
13t
biphenyl-4-yl Boc
13u
p-FC6H4
p-FC6H4
Boc
CO2Me 16v
Boc
14e) as well as substitution in the R1 position (14n, 13v
14o) gave rise to significantly decreased overall yields
of pyridines 15.
Carbamate-protected enynes 13 were studied next.
Carbamates 13a–13k correspond to sulfonamides 12a–
12k, and the series was further expanded by a few
other compounds (13t–13x).
13w
13x
thiazole-2-yl
oct-1-ene-1-yl Boc
–
–
N
[a]
Isolated yield of stable dihydropyridine derivatives 16;
N=no reaction.
Initial experiments with the Boc-protected com-
pound 13a showed that the cyclization resulted in an
inseparable mixture of dihydropyridine 16a and pyri-
dine 15a, as the Boc group was partially deprotected
under the reaction conditions, and the ensuing dihy-
dropyridines 16 were oxidized by atmospheric O2.
The deprotection/elimination step was therefore
driven to completion by replacing the solvent with
toluene and addition of iodine[9] (Table 3). Nitrophen-
yl (13e, 13f), thiazolyl (13w) and octenyl-substituted
(13x) derivatives were resistant to cyclization. It is ap-
parent from overall yields in Table 3 that, in several
Figure 1. Derivatives 12r, 12s and 5a with propargylic substi-
tution.
Finally, having in mind possible applications to the
cases, notable improvement was achieved compared formal synthesis of paroxetine (which would mean re-
to MBS-protected compounds (cf. overall yields in duction of the double bonds in the dihydropyridine
Table 2 and Table 3 for 15c, 15d, 15i, 15j).
ring), enyne 13b with a methoxycarbonyl group was
Since the starting enynes 12 and 13 lack substitu- prepared. Since cyclization of 13b furnished a high
tion in the propargylic position, derivatives 12r and yield of stable dihydropyridine 16b, the p-fluorophen-
12s (Figure 1) were also synthesized from easily avail- yl derivative 16v was synthesized, and converted to
able starting compounds (see the Supporting Informa- the known[10] paroxetine precursor 17 via catalytic hy-
tion). Unfortunately, all attempts to cyclize these drogenation (Scheme 5).
enynes have been unsuccessful, and only the starting
To summarize this part, cyclization of enynes 12
material was observed in the reaction mixture. In ad- and 13 to dihydropyridines in high yields can be en-
dition, Menon observed[7] that the cyclization of sub- forced using (TFP)AuCl/AgBF4, and the dihydropyri-
strate 5a (Figure 1) under various conditions led ex- dines obtained can serve as versatile synthetic inter-
clusively to pyrrole. The presence of propargylic sub- mediates.
stituent(s) is thus clearly an obstacle to dihydropyri-
dine formation.
The last issue to be addressed was applicability of
Hanzawaꢄs pyrrole-selective protocol[6] to substrates
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Scheme 7. Cyclizations of enyne 3a under various condi-
tions.
under four different sets of conditions (Scheme 7): A:
(TFP)AuCl/AgBF4, benzene (reported herein); B:
[(IPr)Au(MeCN)]BF4, CH2Cl2/HFIP 3:1 (Hanzawa);[6]
C: (TFP)AuCl/AgBF4, CH2Cl2/HFIP 3:1; D:
Scheme 5. Synthesis of paroxetine precursor 17.
used throughout this work. Hence, model enyne 12b [(IPr)Au(MeCN)]BF4, benzene.
was subjected to treatment with [(IPr)Au(MeCN)]BF4
In accordance with the previous results, an N-heter-
in CH2Cl2/hexafluoroisopropyl alcohol (HFIP) 3:1. ocyclic carbene-Au(I) catalyst induced pyrrole forma-
Unexpectedly, dihydropyridine 14b was obtained as tion (compound 19), while our cationic gold catalyst
a sole product in high yield. An attempt to enforce gave a moderate yield of dihydropyridine 18. Second-
the cyclization to pyrrole was therefore made using ly, the use of cationic gold species together with HFIP
[8]
Echavarrenꢄs
[JohnPhosAu(MeCN)]SbF6
in led to decomposition. Finally, since conditions D com-
CH2Cl2[7] but only the starting material was recovered. bining [(IPr)Au(MeCN)]BF4 with benzene gave rise
Cyclization with (TFP)AuCl/AgBF4 (see Table 2) is to a 32% isolated yield of dihydropyridine (following
included for comparison (Scheme 6).
extensive purification), we can conclude that the pres-
ence of HFIP is crucial for pyrrole formation.
Overall, the results demonstrate that there are at
least two factors governing the chemoselectivity of
the cyclization of b-propargylamino acrylic esters.
Apart from the solvent, it is the substitution pattern
of the starting enyne. b-Propargylamino acrylic esters
without C-3 substitution gave rise to high yields of di-
hydropyridines as the sole products regardless of the
catalyst and solvent(s) used. Furthermore, in contrast
to enynes of type 5 used by Menon,[7] the activity of
[JohnPhosAu(MeCN)]SbF6 was not sufficient to
effect pyrrole formation.
Scheme 6. Application of pyrrole selective protocols from
refs.[6,7] to 12b.
As regards the mechanism, azacarbenium inter-
mediate A can be considered as the hypothetical key
intermediate[11] (Scheme 8). While pyrroles are likely
Thus, despite the sheer analogy between enynes 12 to arise via Grob-type fragmentation (C), isomeriza-
and 13 on one hand, and compounds 3 (Scheme 2) on tion to allenic amine D and 5-exo-dig cyclization,[6]
the other, model enyne 12b failed to furnish the cor- Menon has proposed[7] that a 1,3-hydrogen shift to
responding pyrrole. As stated above, Hanzawa and yield dienic imine E followed by 6p electrocyclization
co-workers noted[6] two exceptions to the pyrrole for- leads to dihydropyridines.
mation resulting in dihydropyridine, namely in the
Even though the results obtained within this work
cases when C-3 was either unsubstituted or occupied are not in discrepancy with this scheme, it is difficult
with an ester group. In addition, we recorded lower to explain why C-3 substitution (R1 =methyl, phenyl)
yields of dihydropyridines when C-3 was substituted and especially the presence of HFIP support a reac-
with an alkyl (see 12m and 12n, Table 2). Altogether, tion cascade terminated with pyrrole formation (A
these data hinted at the C-3 substitution being the through pyrrole). As Hanzawa and co-workers[6] ob-
governing factor of the cycloizomerization course. In served deuterium incorporation when HFIP-d1 was
order to prove this assumption, enyne 3a used by used, we can only speculate that HFIP (pKa 9.3) ac-
Hanzawa was prepared, and subjected to cyclization celerates isomerization of ketimine C to enamine D
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Scheme 8. Overview of mechanistic considerations.
(Scheme 9). However, since not even traces of pyr- incorporation was observed, which is supportive of in-
roles were detected when R1 =H, the formation of di- termolecular deuterium transfer. While this result is
hydropyridines via several intermediates which can in accord with the proposed pathway, an alternative
also be transformed to pyrroles appears at least ques- route to dihydropyridine via 1,5-shift of intermediate
tionable. We assume that, in such cases, fragmentation D (see Scheme 8) cannot be excluded, either.
of A into the less stable (as opposed to ketimine) N-
sulfonylaldimine C may be slowed down. Loss of an
acidic proton from intermediate A followed by proto- Conclusions
deauration of the ensuing complex B might then
become a viable alternative route towards the six- Contrary to the previous reports, we have shown that
membered rings.
the cyclization of b-propargylamino acrylic acid esters
When Hanzawaꢄs conditions using HFIP-d1 (see with a push-pull olefinic bond to dihydropyridines can
also Scheme 6) were applied to 12b, 73% deuterium be enforced with (TFP)AuCl/AgBF4 in moderate to
Scheme 9. Incorporation of deuterium in 14b.
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a silica gel column eluting with the mobile phases given
below.
high isolated yields, depending on the substitution.
The chemoselectivity of the process (dihydropyridine
vs. pyrrole) is governed by the C-3 substitution, since
esters unsubstituted in this position afforded dihydro-
pyridines as the sole products regardless of the cata-
lyst and/or the reaction conditions. In case of alkyl/
aryl substitution at C-3, formation of pyrrole can be
effected using HFIP as a component of the solvent
mixture. In addition, two different types of N-protec-
tive groups (sulfonamide and carbamate) were evalu-
ated from the viewpoint of further synthetic transfor-
mations of the dihydropyridines. On a model sub-
strate, MBS protection gave a higher yield of the cor-
responding dihydropyridine than Ts (see Table 2), and
resulted in stable products. On the other hand, Boc-
protected dihydropyridines underwent spontaneous
partial deprotection under the cyclization conditions,
and thus allowed a more facile elimination furnishing
the corresponding pyridines. Finally, the preparation
of the known paroxetine precursor was achieved via
hydrogenation of the appropriately substituted dihy-
dropyridine protected as methoxycarbamate.
Methyl 1-(4-methylphenylsulfonyl)-4-phenyl-1,6-dihydro-
pyridine-3-carboxylate (14a): Elution with hexane/EtOAc
8:2; white solid; yield: 250 mg (88%); mp 97.48C (hexane);
1H NMR (300 MHz, CDCl3): d=7.93 (s, 1H), 7.78–7.74 (m,
2H), 7.41–7.36 (m, 2H), 7.30–7.24 (m. 3H), 7.12–7.06 (m,
2H), 5.36 (t, J=4.6 Hz, 1H), 4.18 (d, J=4.6 Hz, 2H), 3.57
(s, 3H), 2.46 (s, 3H); 13C NMR (75 MHz, CDCl3): d=165.4,
145.2, 139.4, 137.8, 136.3, 133.7, 130.3, 127.9, 127.6, 127.4,
126.9, 115.3, 111.8, 51.4, 44.2, 21.7; IR (ATR): n=2952,
2924, 2853, 1720,1629, 1596, 1571, 1435, 1390, 1364, 1296,
1270, 1247, 1186, 1169, 1100 cmÀ1; MS (APCI): m/z (%)=
370.3 [M+H]+ (100), 338.3 (12), 311.2 (3), 246.3 (3), 216.8
(7), 198.0 (2).
Methyl
1-(4-methoxyphenylsulfonyl)-4-phenyl-1,6-dihy-
dropyridine-3-carboxylate (14b): Elution wtih hexane/
EtOAc 8:2; yellow amorphous solid; yield: 381 mg (91%);
1H NMR (300 MHz, CDCl3): d=7.92 (s, 1H), 7.80 (d, J=
9.0 Hz, 2H), 7.55–6.95 (m, 7H), 5.35 (t, J=4.6 Hz, 1H), 4.16
(d, J=4.6 Hz, 2H), 3.88 (s, 3H), 3.56 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=165.4, 163.9, 139.4, 137.9, 136.2, 129.8,
128.0, 127.8, 127.3, 126.8, 115.1, 114.7, 111.4, 55.8, 51.4, 44.0;
IR (ATR): n=2953, 1736, 1638, 1596, 1579, 1546, 1498,
1471, 1439, 1413, 1303, 1259, 1158, 1121, 1024, 1002 cmÀ1
;
MS (APCI): m/z (%)=260.1 (29), 228.0 (93), 216.0 (5),
214.1 [M+HÀMBS]+ (100), 184.1 (51), 182.1 (37), 156.1
(80), 154.1 (37), 129.1 (28), 115.1 (13).
Experimental Section
Methyl 1-(4-methoxyphenylsulfonyl)-4-(4-methyl-phenyl)-
1,6-dihydropyridine-3-carboxylate (14c): Elution with
hexane/EtOAc 9:1; yellow amorphous solid; yield: 339 mg
General Information
All reagents were purchased from Sigma–Aldrich and used
without further purification. (TFP)AuCl was prepared ac-
cording to the published procedure.[4] Solvents were distilled
prior to use. The reactions performed under an argon atmos-
phere were done in oven-dried glassware using Schlenk line
techniques with magnetic stirring and dried solvents. TLC
analyses were performed using Merck TLC Silica gel 60 F254
TLC plates and visualized by UV in combination with stain-
ing. Column chromatography was carried out on Merck
Silica gel 60 (0.040–0.063 mm). 1H and 13C NMR spectra
were recorded with Varian Mercury VxBB 300 or VNMR
S500 instruments. The chemical shifts were reported relative
to TMS and referenced to the residual solvent peaks. IR
spectra were recorded on a Nicolet 6700 FT-IR equipped
with an ATR device. MS data were measured on an Agilent
Tech 500 Iontrap spectrometer. HR-MS data were recorded
on a QTOF mass spectrometer using the electrospray ioni-
zation mode. Melting points are uncorrected.
1
(77%); H NMR (500 MHz, CDCl3): d=7.90 (s, 1H), 7.83–
7.75 (m, 2H), 7.126.93 (m, 6H), 5.33 (t, J=4.6 Hz, 1H), 4.15
(d, J=4.6 Hz, 2H), 3.89 (s, 3H), 3.58 (s, 3H), 2.32 (s, 3H);
13C NMR (125 MHz, CDCl3): d=165.4, 163.9, 137.7, 137.0,
136.4, 136.1, 129.7, 128.5, 128,1, 126.7, 114.8, 114.6, 111.6,
55.7, 51.4, 44.0, 21.2; IR (ATR): n=3081, 2926, 2855, 2283,
2067, 1908, 1721, 1636, 1594, 1578, 1509, 1496, 1458, 1417,
1386, 1360, 1317, 1298, 1261, 1242, 1187, 1161, 1096, 1030,
951, 850, 823, 766, 667 cmÀ1; MS (APCI): m/z (%)=400.0
[M+H]+ (100), 388.0 (5), 387.0 (26), 368.0 (5), 229.0 (5),
228.1 (30), 196.1 (3), 170.9 (4), 123.1 (3).
Methyl 1-(4-methoxyphenylsulfonyl)-4-(4-bromophenyl)-
1,6-dihydropyridine-3-carboxylate (14d): Elution with
hexane/EtOAc 9:1, white amorphous solid; yield: 485 mg
1
(92%); H NMR (500 MHz, CDCl3): d=7.94 (s, 1H), 7.83–
7.76 (m, 2H), 7.41–7.34 (m, 2H), 7.06–6.99 (m, 2H), 6.97–
6.92 (m, 2H), 5.32 (t, J=4.6 Hz, 1H), 4.13 (d, J=4.6 Hz,
2H), 3.89 (s, 3H), 3.59 (s, 3H); 13C NMR (125 MHz,
CDCl3): d=165.1, 164.0, 138.4, 135.3, 132.3, 130.9, 129.8,
128.6, 127.9, 121.3, 115.5, 114.8, 110.6, 55.8, 51.4, 44.0; IR
(ATR): n=2926, 2853, 1702, 1625, 1595, 1577, 1496, 1463,
1437, 1404, 1375, 1364, 1311, 1260, 1242, 1183, 1164, 1117,
1091, 1073, 1023 946, 829, 804, 714, 666 cmÀ1; MS (APCI):
m/z (%)=466.0 [M+H]+ (100), 464.1 (90), 293.9 (28), 292.0
(32), 170.9 (11); HR-MS (TOF-ESI+): m/z=464.0146, calcd.
for C20H18BrNO5S: 464.0162.
Methyl 1-(4-methoxyphenylsulfonyl)-4-(thiophene-2-yl)-
1,6-dihydropyridine-3-carboxylate (14g): Elution with
hexane/EtOAc 8:2; brown oil; yield: 320 mg (70%);
1H NMR (500 MHz, CDCl3): d=7.88 (s, 1H), 7.79 (d, J=
9.0 Hz, 2H), 7.17 (dd, J=5.0, 1.1 Hz, 1H), 7.03 (d, J=
General Method for Cyclization of Sulfonamides 12
to Dihydropyridines 14
An oven-dried flask was flushed with argon and loaded with
enyne 12 (1.0 mmol). AgBF4 (0.1 mmol) was weighed direct-
ly into the flask under an argon atmosphere and the mixture
was dissolved in dry benzene (10 mL). (TFP)AuCl
(0.05 mmol) was added into the flask and the reaction mix-
ture was stirred at room temperature until the consumption
of starting material (monitored by H NMR). The reaction
mixture was then filtered through celite and remaining sol-
vents were evaporated. The residue was separated on
1
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9.0 Hz, 2H), 6.93 (dd, J=5.0, 3.6 Hz, 1H), 6.79 (dd, J=3.6,
1.1 Hz, 1H), 5.52 (t, J=4.7 Hz, 1H), 4.13 (d, J=4.7 Hz,
2H), 3.89 (s, 3H), 3.64 (s, 3H); 13C NMR (126 MHz,
CDCl3): d=165.1, 163.9, 140.5, 137.7, 129.7, 129.6, 128.0,
126.7, 125.2, 124.4, 116.0, 114.8, 111.3, 55.8, 51.5, 43.8; IR
(ATR): n=2927, 2854, 1732, 1619, 1497, 1436, 1311, 1262,
1243, 1184, 1118, 1092, 1020, 835, 703, 667 cmÀ1; MS
(APCI): m/z (%)=392.1 [M+H]+ (49), 360.0 (100), 220.0
(30), 171.0 (19), 123.0 (15).
(APCI): m/z (%)=414.2 [M+H]+ (100), 412.2 (69), 384.2
(58), 356.3 (13), 242.1 (25), 197.1 (39), 186.1 (14), 107.0 (12);
HR-MS (TOF-ESI+): m/z=414.1370, calcd. for C22H23NO5S:
414.1370.
Methyl 1-(4-methoxyphenylsulfonyl)-2-propyl-4-phenyl-
1,6-dihydropyridine-3-carboxylate (14n): Elution with
hexane/EtOAc 9:1; yellow oil; yielkd: 162 mg (27%); could
not be separated from impurities; 1H NMR (500 MHz,
CDCl3): d=7.71–7.57 (m, 2H), 7.21–7.07 (m, 3H), 6.88–6.57
(m, 4H), 5.44 (t, J=4.7 Hz, 1H), 4.37 (d, J=4.7 Hz, 2H),
3.67 (s, 3H), 3.34 (s, 3H), 2.96 (t, J=7.3 Hz, 2H), 1.77–1.53
(m, 2H), 0.93 (t, J=7.4 Hz, 3H); 13C NMR (126 MHz,
CDCl3): d=167.6, 163.0, 146.7, 1378.0, 137.0, 130.9, 129.3,
127.8, 127.3, 126.2, 118.3, 113.8, 55.4, 51.5, 46.1, 34.4, 22.9,
13.6; IR (ATR): n=2967, 2873, 1709, 1595, 1497, 1343, 1310,
1262, 1156, 1091, 1024, 834, 805, 757, 678 cmÀ1; MS (APCI):
m/z (%)=428.2 [M+H]+ (100), 396.2 (84), 352.1 (31), 256.1
(64), 226.1 (15), 155.1 (8); HR-MS (TOF-ESI+): m/z=
428.1530, calcd. for C23H25NO5S: 428.1526.
Methyl 1-(4-methoxyphenylsulfonyl)-4-(4-chlorophenyl)-
1,6-dihydropyridine-3-carboxylate (14h): Elution with
hexane/EtOAc 8:2; yellow amorphous solid; yield: 157 mg
1
(71%); H NMR (500 MHz, CDCl3): d=7.94 (s, 1H), 7.83–
7.75 (m, 2H), 7.25–7.20 (m, 2H), 7.08–6.95 (m, 4H), 5.32 (t,
J=4.6 Hz, 1H), 4.16 (d, J=4.6 Hz, 2H), 3.89 (s, 3H), 3.59
(s, 3H); 13C NMR (126 MHz, CDCl3): d=165.1, 164.0, 138.3,
137.9, 135.3, 133.1, 129.8, 128.2, 128.0, 127.9, 115.5, 114.8,
110.7, 55.8, 51.4, 44.0; IR (ATR): n=2953, 2926, 2853, 2576,
2066, 1910, 1731, 1595, 1498, 1465, 1439, 1303, 1263, 1162,
1092, 1026, 834, 805, 762, 728, 685 cmÀ1; MS (APCI): m/z
(%)=420.1 [M+H]+ (100), 390.1 (44), 388.1 (93), 360.0
(22), 250.1 (31), 248.1 (84), 216.0 (33), 171.1 (36), 123.1 (29);
Methyl 1-(4-methoxyphenylsulfonyl)-2,4-diphenyl-1,6-di-
hydropyridine-3-carboxylate (14o): Elution with hexane/
EtOAc 9:1; light yellow amorphous solid; yield: 447 mg
1
(TOF-ESI+):
m/z=420.0667,
calcd.
for
(89%); H NMR (500 MHz, CDCl3): d=7.64–7.53 (m, 4H),
HR-MS
C20H18ClNO5S: 420.0667.
7.42–7.33 (m, 3H), 7.25–7.14 (m, 3H), 6.92–6.81 (m, 4H),
5.49 (t, J=4.7 Hz, 1H), 4.66 (d, J=4.6 Hz, 2H), 3.81 (s,
3H), 3.22 (s, 3H); 13C NMR (126 MHz, CDCl3): d=167.1,
163.2, 141.8, 137.6, 137.6, 135.7, 131.3, 130.2, 129.6, 129.6,
127.8, 127.8, 127.7, 127.6, 127.6, 125.7, 119.0, 114.2, 113.9,
55.6, 51.8, 46.6; IR (ATR): n=2928, 2851, 1728, 1595, 1497,
1444, 1344, 1300, 1261, 1160, 1095, 1023, 834, 805, 761,
699 cmÀ1; MS (APCI): m/z (%)=462.2 [M+H]+ (34), 292.1
(15), 290.2 (100), 258.1 (6), 232.2 (11); HR-MS (TOF-ESI+):
m/z=462.1375, calcd. for C26H23NO5S: 462.1370.
Methyl 1-(4-methoxyphenylsulfonyl)-4-(4-methoxyphen-
yl)-1,6-dihydropyridine-3-carboxylate (14j): Elution with
hexane/EtOAc 8:2; yellowish oil; yield: 284 mg (61%);
1H NMR (500 MHz, CDCl3): d=7.90 (s, 1H), 7.82–7.75 (m,
2H), 7.05–6.99 (m, 4H), 6.83–6.76 (m, 2H), 5.31 (t, J=
4.6 Hz, 1H), 4.14 (d, J=4.6 Hz, 2H), 3.88 (s, 3H), 3.78 (s,
3H), 3.59 (s, 3H); 13C NMR (126 MHz, CDCl3): d=165.5,
163.9, 158.9, 137.8, 135.7, 131.7, 129.7, 128.1, 127.9, 114.8,
114.2, 113.2, 111.6, 55.7, 55.2, 51.4, 44.0; IR (ATR): n=2927,
2853, 1718, 1595, 1577, 1512, 1498, 1464, 1360, 1301, 1247,
1162, 1094, 1027, 956, 835, 751, 668 cmÀ1; MS (APCI): m/z
(%)=416.1 [M+H]+ (24), 414.1 (39), 384.1 (100), 244.1
(76), 229.1 (17), 212.0 (18), 171.1 (24); HR-MS (TOF-ESI+):
m/z=416.1162, calcd. for C21H21NO6S: 416.1162.
Dimethyl 1-(4-methoxyphenylsulfonyl)-4-phenyl-1,6-dihy-
dropyridine-2,3-dicarboxylate (14l): Elution with hexane/
EtOAc 8:2; white amorphous solid; yield: 124 mg (73%);
1H NMR (500 MHz, CDCl3): d=7.85–7.79 (m, 2H), 7.29–
7.17 (m, 3H), 7.01–6.93 (m, 2H), 6.80–6.73 (m, 2H), 5.40 (t,
J=4.4 Hz, 1H), 4.47 (d, J=4.4 Hz, 2H), 3.91 (s, 3H), 3.85
(s, 3H), 3.55 (s, 3H); 13C NMR (126 MHz, CDCl3): d=
165.7, 164.1, 163.7, 136.5, 135.6, 131.6, 130.4, 130.3, 129.8,
127.9, 127.8, 127.7, 123.9, 114.3, 55.7, 53.0, 52.3, 45.3; IR
(ATR): n=2926, 2853, 2360, 2341, 1736, 1621, 1596, 1579,
1551, 1494, 1438, 1354, 1346, 1300, 1288, 1260, 1202, 1157,
1101, 1094 cmÀ1; MS (APCI): m/z (%)=444.1 [M+H]+
(59), 272.2 [M+HÀMBS]+ (100), 240.2 (26).
Preparation of Pyridines 15
Method A – Elimination of dihydropyridines 14: Dihydro-
pyridine 14 (0.5 mmol) was dissolved in DMF (15 mL).
DBU (2.5 mmol) was added into the mixture and the reac-
tion mixture was stirred at 1408C under a reflux condenser
until consumption of the starting material (monitored by
TLC). The mixture was then cooled down to room tempera-
ture and washed with 50 mL of brine. The organic phase
was extracted with EtOAc (3ꢅ50 mL) and dried with
Na2SO4. Inorganic residues were filtered off, the mixture
was evaporated to dryness and the residue was separated on
a silica gel column eluting with the mobile phases given
below.
Method B – One-pot cyclization and elimination of tert-
butyl carbamate protected enynes 13: An oven-dried flask
was flushed with argon and loaded with enyne 13
(1.0 mmol). AgBF4 (0.1 mmol) was weighed directly into the
flask under an argon atmosphere and the mixture was dis-
solved in dry benzene (10 mL). (TFP)AuCl (0.05 mmol) was
added into the flask and the reaction mixture was stirred at
room temperature until consumption of the starting material
Ethyl 1-(4-methoxyphenylsulfonyl)-2-methyl-4-phenyl-1,6-
dihydropyridine-3-carboxylate (14m): Elution with hexane/
EtOAc 7:3; yellowish oil; yield: 231 mg (47%); 1H NMR
(500 MHz, CDCl3): d=7.72–7.62 (m, 2H), 7.20–7.09 (m,
3H), 6.81–6.74 (m, 4H), 5.44 (t, J=4.8 Hz, 1H), 4.40 (d, J=
4.8 Hz, 2H), 3.82 (q, J=7.1 Hz, 2H), 3.70 (s, 3H), 2.50 (s,
3H), 0.70 (t, J=7.1 Hz, 3H); 13C NMR (126 MHz, CDCl3):
d=166.8, 163.1, 143.6, 138.7, 137.4, 131.1, 129.2, 127.9, 127.3,
126.3, 124.6, 117.5, 114.0, 60.6, 55.4, 45.8, 20.4, 13.3; IR
(ATR): n=2980, 1719, 1595, 1498, 1444, 1347, 1301, 1260,
1159, 1088, 1024, 835, 805, 763, 721, 703, 670 cmÀ1; MS
1
(monitored by H crude NMR). The reaction mixture was
then filtered through a thin layer of silica gel, washed with
EtOAc and the remaining solvents were evaporated. The
residue was dissolved in toluene (20 mL) and iodine
(4.15 mmol) was added into the flask. The temperature was
raised gradually up to 1208C until consumption of the start-
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ing material (monitored by TLC analysis). The solution was
cooled down to room temperature and quenched with
50 mL of saturated Na2S2O3 solution. The organic layer was
washed with saturated Na2CO3 solution (50 mL) and the
combined water phases were re-extracted with EtOAc (2ꢅ
50 mL). The organic layer was dried with Na2SO4, inorganic
residues were filtered off, the mixture was evaporated to
dryness and the residue was separated on a silica gel column
eluting with the mobile phases given below.
Methyl 4-phenylnicotinate (15a): Elution with hexane/
EtOAc 7:3; Method A from 14a: yield: 70 mg (33%);
Method A from 14b: yield: 127 mg (60%); Method B: yield:
132 mg (51%); yellowish amorphous solid; 1H NMR
(500 MHz, CDCl3): d=9.02 (s, 1H), 8.71 (d, J=5.1 Hz, 1H),
7.47–7.36 (m, 3H), 7.34–7.26 (m, 3H), 3.69 (s, 3H);
13C NMR (125 MHz, CDCl3): d=166.6, 151.5, 150.3, 149.5,
137.9, 131.5, 128.9, 128.4, 128.0, 125.5, 52.4; IR (ATR): n=
3057, 3030, 2951, 2850, 1954, 1731, 1588, 1544, 1477, 1435,
1405, 1310, 1289, 1265, 1216, 1179, 1115, 1077, 1053, 1044,
1017 cmÀ1; MS (APCI): m/z (%)=214.1 [M+H]+ (100),
182.2 (7), 175.1 (3), 167.1 (2), 156.0 (3), 139.9 (2), 123.1 (1),
113.0 (1), 89.0 (6), 72.9 (4), 54.1 (4); HR-MS (TOF-ESI+):
m/z=214.0871, calcd. for C13H11NO2: 214.0868.
Methyl 4-(4-methylphenyl)nicotinate (15c): Elution with
hexane/EtOAc 7:3; Method A: yield: 73 mg (38%); Method
B: yield: 110 mg (48%); yellowish amorphous solid;
1H NMR (500 MHz, CDCl3): d=9.01 (bs, 1H), 8.71 (bs,
1H), 7.33–7.18 (m, 5H), 3.74 (s, 3H), 2.42 (s, 3H); 13C NMR
(125 MHz, CDCl3): d=167.3, 151.8, 150.7, 150.1, 138.5,
135.3, 129.1, 127.9, 126.4, 124.9, 52.2, 21.2; IR (ATR): n=
3456, 3101, 2977, 2933, 1731, 1635, 1596, 1578, 1539, 1498
1470, 1438, 1369, 1339, 1300, 1261, 1161, 1138, 1113, 1089,
1025, 819, 786 cmÀ1; MS (APCI): m/z (%)=228.0 [M+H]+
(100), 167.1 (1); HR-MS (TOF-ESI+): m/z=228.1027, calcd.
for C14H13NO2: 228.1025.
Methyl 4-(thiophene-2-yl)nicotinate (15g): Elution with
hexane/EtOAc 7:3; Method A: yield: 70 mg (39%); Method
B: yield: 64 mg (29%); brown oil; 1H NMR (500 MHz,
CDCl3): d=8.89 (s, 1H), 8.66 (d, J=5.2 Hz, 1H), 7.45 (dd,
J=5.1, 1.2 Hz, 1H), 7.39 (d, J=5.2 Hz, 1H), 7.21 (dd, J=
3.6, 1.2 Hz, 1H), 7.10 (dd, J=5.1, 3.6 Hz, 1H), 3.81 (s, 3H);
13C NMR (126 MHz, CDCl3): d=167.3, 151.7, 150.4, 141.6,
138.6, 128.0, 127.9, 127.7, 126.4, 124.5, 52.5; IR (ATR): n=
3108, 2951, 1731, 1586, 1546, 1435, 1404, 1309, 1277, 1254,
1118, 1052, 958, 853, 828, 786, 714 cmÀ1; MS (APCI): m/z
(%)=220.0 [M+H]+ (100), 209.1 (2), 186.9 (2), 136.0 (2),
98.9 (1), 73.0 (8); HR-MS (TOF-ESI+): m/z=220.0433,
calcd. for C11H9NO2S: 220.0432.
Methyl 4-(4-chlorophenyl)nicotinate (15h): Elution with
hexane/EtOAc 7:3; Method A: yield: 37 mg (40%); Method
B: yield: 65 mg (30%); yellow oil; 1H NMR (500 MHz,
CDCl3): d=9.07 (s, 1H), 8.74 (d, J=5.1 Hz, 1H), 7.46–7.39
(m, 2H), 7.30–7.24 (m, 3H), 3.75 (s, 3H); 13C NMR
(126 MHz, CDCl3): d=166.8, 152.1, 151.1, 149.1, 136.8,
134.8, 129.3, 128.6, 126.0, 124.8, 52.3; IR (ATR): n=3057,
2928, 2853, 2361, 2341, 1728, 1595, 1543, 1479, 1306, 1294,
1123, 1091, 1011, 853, 835, 790, 769 cmÀ1; MS (APCI): m/z
(%)=248.0 [M+H]+ (100), 215.0 (1), 214.0 (9), 154.1 (1);
HR-MS
C13H10ClNO2: 248.0478.
(TOF-ESI+):
m/z=248.0478,
calcd.
for
Methyl 4-(naphthalene-1-yl)nicotinate (15i): Elution:
hexane/EtOAc 7:3; Method A: yield: 78 mg (60%); Method
1
B: yield: 130 mg (43%); yellowish oil; H NMR (500 MHz,
CDCl3): d=9.24 (s, 1H), 8.83 (d, J=5.0 Hz, 1H), 7.95–7.89
(m, 2H), 7.57–7.47 (m, 2H), 7.44–7.39 (m, 2H), 7.37 (d, J=
4.9 Hz, 1H), 7.32 (dd, J=7.0, 1.1 Hz, 1H), 3.46 (s, 3H);
13C NMR (126 MHz, CDCl3): d=166.2, 152.2, 151.2, 149.5,
136.7, 133.2, 131.0, 128.6, 128.4, 127.2, 126.5, 126.2, 126.0,
125.6, 125.0, 124.8, 52.1; IR (ATR): n=3053, 2952, 2924,
2852, 1728, 1588, 1541, 1431, 1407, 1393, 1274, 1219, 1191,
1123, 1102, 1022, 960, 803, 788 cmÀ1; MS (APCI): m/z (%)=
234.1 [M+H]+ (100), 232.0 (8), 228.0 (13), 214.1 (5), 204.0
(7), 168.0 (1); HR-MS (TOF-ESI+): m/z=264.1024, calcd.
for C17H13NO2: 264.1025.
Methyl 4-(4-bromophenyl)nicotinate (15d): Elution with
hexane/EtOAc 7:3; Method A: yield: 61 mg (20%); Method
1
B: yield: 149 mg (51%); yellow amorphous solid; H NMR
(500 MHz, CDCl3): d=9.12 (s, 1H), 8.80 (d, J=4.9 Hz, 1H),
7.64–7.59 (m, 2H), 7.51 (d, J=4.9 Hz, 1H), 7.24–7.21 (m,
2H), 3.79 (s, 3H); 13C NMR (125 MHz, CDCl3): d=165.1,
148.1, 147.8, 136.0, 131.9, 129.6, 127.1, 126.2, 124.2, 118.5,
52.9; IR (ATR): n=3511, 3436, 3050, 2943, 1917, 1727, 1592,
1572, 1542, 1499, 1477, 1453, 1431, 1314, 1306, 1294, 1268,
1123, 1074, 1061, 1027, 956, 834, 789, 762 cmÀ1; MS (APCI):
m/z (%)=293.9 [M+H]+ (100), 292.9 (11), 292.0 (68), 214.1
(14), 126.1 (5); HR-MS (TOF-ESI+): m/z=291.9974, calcd.
for C13H10BrNO2: 291.9973.
Methyl 4-(4-methoxyphenyl)nicotinate (15j): Elution with
hexane/EtOAc 7:3; Method A: yield: 85 mg (51%); Method
1
B: yield: 148 mg (38%); yellowish oil; H NMR (500 MHz,
CDCl3): d=8.99 (s, 1H), 8.70 (s, 1H), 7.34–7.22 (m, 3H),
7.01–6.93 (m, 2H), 3.87 (s, 3H), 3.75 (s, 3H); 13C NMR
(126 MHz, CDCl3): d=167.5, 160.0, 151.8, 150.7, 149.6,
130.5, 129.4, 129.4, 124.8, 113.9, 55.3, 52.3; IR (ATR): n=
3003, 2950, 2839, 2547, 1728, 1610, 1588, 1518, 1481, 1436,
1290, 1250, 1180, 1112, 1042, 1023, 830, 805, 789 cmÀ1; MS
(APCI): m/z (%)=244.0 [M+H]+ (100), 229.0 (5), 228.0
(5); HR-MS (TOF-ESI+): m/z=244.0974, calcd. for
C14H13NO3: 244.0974.
Methyl 4-(4-nitrophenyl)nicotinate (15e): Elution with
hexane/EtOAc 7:3; Method A: yield: 23 mg (13%); yellow-
1
ish oil; H NMR (500 MHz, CDCl3): d=9.19 (s, 1H), 8.82
(d, J=5.0 Hz, 1H), 8.32 (d, J=8.7 Hz, 2H), 7.49 (d, J=
8.7 Hz, 2H), 7.29 (d, J=5.0 Hz, 1H), 3.77 (s, 3H); 13C NMR
(125 MHz, CDCl3): d=166.0, 152.5, 151.5, 148.5, 147.8,
145.2, 129.0, 128.6, 125.3, 124.6, 123.5, 114.2, 52.5; IR
(ATR): n=2956, 2921, 2850, 1828, 1796, 1726, 1702, 1644,
1592, 1547, 1508, 1460, 1437, 1412, 1344, 1315, 1300, 1256,
Methyl 4-(3-methoxyphenyl)nicotinate (15k): Elution:
hexane/EtOAc 7:3; Method A: yield: 79 mg (70%); Method
B: yield: 59 mg (32%); yellowish oil; H NMR (500 MHz,
CDCl3): d=9.00 (s, 1H), 8.70 (d, J=5.1 Hz, 1H), 7.51–7.13
(m, 2H), 7.01–6.69 (m, 3H), 3.82 (s, 3H), 3.71 (s, 3H);
13C NMR (126 MHz, CDCl3): d=167.1, 159.4, 151.8, 150.6,
149.7, 139.6, 129.3, 126.4, 124.7, 120.3, 113.9, 113.6, 55.2,
52.2; IR (ATR): n=2924, 2853, 1731, 1586, 1545, 1475, 1434,
1404, 1286, 1264, 1221, 1175, 1114, 1051, 1030, 843, 825, 780,
724, 698 cmÀ1; MS (APCI): m/z (%)=244.1 [M+H]+ (100),
1
1242, 1204, 1174, 1147, 1117, 1075, 1066, 1034, 1011 cmÀ1
;
MS (APCI): m/z (%)=259.0 [M+H]+ (100), 213.0 (3),
160.0 (2), 142.9 (2); HR-MS (TOF-ESI+): m/z=259.0723,
calcd. for C13H10N2O4: 259.0713.
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229.1 (17), 201.1 (11), 186.1 (6), 143.1 (13); HR-MS (TOF-
ESI+): m/z=244.0974, calcd. for C14H13NO3: 244.0968.
Dimethyl 4-phenylpyridine-2,3-dicarboxylate (15l): Elu-
tion with hexane/EtOAc 6:4; Method A: yield: 28 mg
(18%); with 1 equiv. of DBU at room temperature: yield:
150 mg (95%); yellow amorphous solid; 1H NMR
(500 MHz, CDCl3): d=8.77 (d, J=4.9 Hz, 1H), 7.49 (d, J=
4.9 Hz, 1H), 7.46–7.43 (m, 3H), 7.41–7.38 (m, 2H), 4.01 (s,
3H), 3.73 (s, 3H); 13C NMR (126 MHz, CDCl3): d=167.5,
165.1, 149.7, 149.1, 145.3, 136.7, 131.0, 129.1, 128.7, 128.1,
127.2, 53.3; IR (ATR): n=3649, 3281, 3064, 2927, 2857,
2365, 1732, 1720, 2596, 1578, 1544, 1500, 1456, 1441, 1431,
1408, 1325, 1317, 1265, 1231, 1207, 1186, 1176, 1160, 1146,
1134, 1113, 1093, 1077, 1067, 1023, 1001, 981, 968, 956, 926,
870, 857, 834, 812, 780, 776, 767, 749, 735, 723, 704,
670 cmÀ1; MS (APCI): m/z (%)=272.1 [M+H]+ (100),
240.0 (13), 273.0 (14); HR-MS (TOF-ESI+): m/z=272.0926,
calcd. for C15H13NO4: 272.0917.
H]+ (100), 258.0 (5), 230.1 (4), 214.1 (9), 181.1 (2); HR-MS
(TOF-ESI+): m/z=290.1188, calcd. for C19H15NO2: 290.1176.
Methyl 4-(4-fluorophenyl)nicotinate (15u): Elution with
hexane/EtOAc 7:3; Method B: 103 mg (44%); white amor-
1
phous solid; H NMR (500 MHz, CDCl3): d=9.05 (s, 1H),
8.73 (d, J=5.2 Hz, 1H), 7.38–7.22 (m, 3H), 7.18–7.08 (m,
2H), 3.74 (s, 3H); 13C NMR (126 MHz, CDCl3): d=166.9,
162.9 (d, J=248.5 Hz), 152.0, 151.0, 149.2, 134.4 (d, J=
3.6 Hz), 129.8 (d, J=8.3 Hz), 126.2, 124.9, 115.4 (d, J=
21.8 Hz), 52.3; IR (ATR): n=3060, 2958, 1727, 1589, 1514,
1482, 1434, 1297, 1215, 1121, 958, 841, 812, 792 cmÀ1; MS
(APCI): m/z (%)=232.0 [M+H]+ (100), 202.2 (2), 171.9
(1), 161.9 (1); HR-MS (TOF-ESI+): m/z=232.0782, calcd.
for C13H10FNO2: 232.0774.
Procedure for Cyclization of Methyl Carbamates 13b
and 13v to Dihydropyridines 16
An oven-dried flask was flushed with argon and loaded with
methyl carbamate 13 (4.000 mmol). AgBF4 (79 mg,
0.400 mmol) was weighed directly into the flask under an
argon atmosphere and mixture was dissolved in dry benzene
(40 mL). (TFP)AuCl (97 mg, 0.200 mmol) was added into
the flask and the reaction mixture was stirred at room tem-
perature for 2.5 h. The reaction mixture was then filtered
through a thin layer of silica gel, washed with EtOAc and
the remaining solvents were evaporated. The residue was
separated on a silica gel column eluting with the mobile
phases given below.
Dimethyl 4-phenyl-1,6-dihydropyridine-1,3-dicarboxylate
(16b): Elution with hexane/EtOAc 8:2; yellowish oil; yield:
255 mg (81%); 1H NMR (500 MHz, CDCl3): d=7.95 (bs,
1H), 7.32–7.25 (m, 3H), 7.17–7.10 (m, 2H), 5.49 (bs, 1H),
4.45 (d, J=4.4 Hz, 2H), 3.88 (s, 3H), 3.56 (s, 3H).
Ethyl 2-methyl-4-phenylnicotinate (15m): Elution with
hexane/EtOAc 8:2; Method A: yield: 74 mg (55%); yellow-
1
ish oil; H NMR (500 MHz, CDCl3): d=8.57 (d, J=5.1 Hz,
1H), 7.47–7.34 (m, 5H), 7.17 (d, J=5.1 Hz, 1H), 4.12 (q, J=
7.1 Hz, 2H), 2.65 (s, 3H), 1.01 (t, J=7.1 Hz, 3H); 13C NMR
(126 MHz, CDCl3): d=168.6, 155.5, 149.5, 148.0, 138.4,
128.5, 128.5, 127.9, 121.6, 61.4, 22.8, 13.6; IR (ATR): n=
2980, 2925, 1724, 1578, 1549, 1445, 1265, 1139, 1097, 1072,
1014, 841, 861, 700 cmÀ1; MS (APCI): m/z (%)=242.1 [M+
H]+ (41), 214.1 (100), 196.1 (5), 170.1 (5), 141.1 (2); HR-MS
(TOF-ESI+): m/z=242.1187, calcd. for C15H15NO2: 242.1176.
Methyl 4-phenyl-2-propylnicotinate (15n): Elution with
hexane/EtOAc 8:2; Method A: yield: 24 mg (10%); yellow-
1
ish oil; H NMR (500 MHz, CDCl3): d=8.62 (d, J=5.1 Hz,
1H), 7.50–7.33 (m, 5H), 7.17 (d, J=5.1 Hz, 1H), 3.64 (s,
3H), 2.89–2.80 (m, 2H), 1.90–1.75 (m, 2H), 1.01 (t, J=
7.4 Hz, 3H); 13C NMR (126 MHz, CDCl3): d=169.3, 159.3,
149.8, 147.9, 138.4, 128.6, 128.6, 128.2, 127.8, 121.5, 52.2,
38.3, 23.1, 14.1; IR (ATR): n=2964, 2845, 1725, 1597, 1500,
Dimethyl 4-(4-fluorophenyl)-1,6-dihydropyridine-1,3-di-
carboxylate (16v): Elution with hexane/EtOAc 7:3; yellow
1
oil; yield: 993 mg (85%); H NMR (500 MHz, CDCl3): d=
7.97 (bs, 1H), 7.16–7.04 (m, 2H), 7.02–6.92 (m, 2H), 5.46
(bs, 1H), 4.45 (d, J=4.4 Hz, 2H), 3.89 (s, 3H), 3.59 (s, 3H);
13C NMR (126 MHz, CDCl3): d=165.5, 161.9 (d, J=
245.7 Hz), 151.4 (d, J=133.2 Hz), 137.3, 135.7 (d, J=
3.4 Hz), 134.5, 128.3 (d, J=8.0 Hz), 117.4, 114.5 (d, J=
21.5 Hz), 110.4, 53.9, 51.1, 43.7; IR (ATR): n=2954, 2359,
1709, 1637, 1585, 1509, 1437, 1398, 1437, 1398, 1362, 1219,
1130, 1082, 1047, 965, 841, 764 cmÀ1; MS (APCI): m/z (%)=
292.2 [M+H]+ (100), 250.3 (9), 232.1 (32), 188.2 (2); HR-
MS (TOF-ESI+): m/z=292.0986, calcd. for C15H14FNO4:
292.0980.
1445, 1340, 1265, 1160, 1102, 865, 799, 726, 696, 677 cmÀ1
;
MS (APCI): m/z (%)=256.1 [M+H]+ (100), 244.1 (9),
224.2 (8), 212.1 (6), 169.1 (3), 154.1 (2); HR-MS (TOF-
ESI+): m/z=256.1338, calcd. for C16H17NO2: 256.1332.
Methyl 2,4-diphenylnicotinate (15o): Elution with hexane/
EtOAc 9:1; Method A: yield: 50 mg (18%); yellowish oil;
1H NMR (500 MHz, CDCl3): d=8.77 (d, J=5.1 Hz, 1H),
7.70–7.56 (m, 2H), 7.52–7.34 (m, 8H), 7.31 (d, J=5.1 Hz,
1H), 3.49 (s, 3H); 13C NMR (126 MHz, CDCl3): d=168.9,
156.8, 149.9, 148.6, 139.6, 138.0, 128.8, 128.7, 128.6, 128.4,
128.3, 128.2, 127.9, 122.7, 52.2; IR (ATR): n=3056, 2926,
2854, 1731, 1569, 1458, 1439, 1397, 1286, 1252, 1127, 1062,
806, 759, 745, 669 cmÀ1; MS (APCI): m/z (%)=290.2 [M+
H]+ (100), 258.1 (26), 230.1 (22), 202.1 (1); HR-MS (TOF-
ESI+): m/z=290.1186, calcd. for C19H15NO2: 290.1176.
Methyl 4-([1,1’-biphenyl]-4-yl)nicotinate (15t): Elution
with hexane/EtOAc 7:3; Method B: yield: 170 mg (51%);
brown oil; 1H NMR (500 MHz, CDCl3): d=9.06 (s, 1H),
8.75 (d, J=5.1 Hz, 1H), 7.78–7.54 (m, 4H), 7.58–7.14 (m,
6H), 3.76 (s, 3H); 13C NMR (126 MHz, CDCl3): d=167.2,
151.9, 150.9, 149.7, 141.5, 140.4, 137.4, 128.8, 128.5, 127.6,
127.1, 127.0, 126.5, 124.8, 52.1; IR (ATR): n=3030, 2952,
1731, 1587, 1478, 1434, 1403, 1288, 1270, 1215, 1119, 1052,
1007, 835, 774, 715 cmÀ1; MS (APCI): m/z (%)=290.2 [M+
Dimethyl 4-(4-Fluorophenyl)-1,4,5,6-tetrahydro-
pyridine-1,3-dicarboxylate (17)
Dihydropyridine 16v (90 mg, 0.309 mmol) was dissolved in
a two-necked flask in MeOH (5 mL). 10% Pd/C (17 mg,
0.015 mmol) was added to the solution and the atmosphere
above the solvent was evacuated and changed to H2. The re-
action mixture was stirred under a hydrogen-filled balloon
overnight, then filtered through celite and evaporated with
1 g of silica gel. The residue was separated on a silica gel
column eluting with mobile phase hexane/EtOAc 8:2 to give
a yellowish oil; yield: 51 mg (56%). 1H NMR (500 MHz,
CDCl3): d=8.32 (s, 1H), 7.16–7.03 (m, 2H), 7.02–6.89 (m,
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2H), 4.05–3.81 (m, 5H), 3.65 (s, 3H), 3.01 (td, J=13.1,
3.3 Hz, 1H), 2.07–1.96 (m, 1H), 1.89 (dd, J=13.6, 3.0 Hz,
1H); 13C NMR (126 MHz, CDCl3): d=167.1, 161.5 (d, J=
244.5 Hz), 153.2, 139.4 (d, J=3.0 Hz), 136.6, 128.9 (d, J=
8.0 Hz), 115.1 (d, J=21.3 Hz), 109.0, 53.7, 51.4, 37.8, 35.5,
29.0; IR (ATR): n=3117, 3015, 2955, 2934, 2342, 1730, 7394,
1629, 1603, 1505, 1445, 1435, 1386, 1285, 1241, 1121, 1188,
1171, 1130, 1099, 1061, 998, 845, 828, 768, 740 cmÀ1; MS
(APCI): m/z (%)=294.1 [M+H]+ (12), 262.1 (10), 198.1
(100), 154.1 (6), 138.0 (5), 122.0 (5), 94.1 (18); HRMS
(TOF-ESI+): m/z=294.1140, calcd. for C15H16FNO4:
294.1136.
ren, Chem. Rev. 2008, 108, 3326–3350; c) S. P. Nolan,
Acc. Chem. Res. 2011, 44, 91–100; d) Z. B. Zhu, S. F.
Kirsch, Chem. Commun. 2013, 49, 2272–2283; e) R.
Dorel, A. M. Echavarren, Chem. Rev. 2015, 115, 9028–
9072.
[3] For recent examples, see: a) G. Abbiati, A. Arcadi, G.
Bianchi, S. Di Giuseppe, F. Marinelli, E. Rossi, J. Org.
Chem. 2003, 68, 6959–6966; b) M. H. Suhre, M. Reif,
S. F. Kirsch, Org. Lett. 2005, 7, 3925–3927; c) S. Couty,
C. Meyer, J. Cossy, Angew. Chem. 2006, 118, 6878–
6882; Angew. Chem. Int. Ed. 2006, 45, 6726–6730;
d) B. D. Sherry, L. Maus, B. N. Laforteza, F. D. Toste, J.
Am. Chem. Soc. 2006, 128, 8132–8133; e) C. Jiang, M.
Xu, S. Wang, H. Wang, Z. J. Yao, J. Org. Chem. 2010,
75, 4323–4325; f) L. E. Brown, P. Dai, J. A. Porco Jr,
S. E. Schaus, Org. Lett. 2011, 13, 4228–4231; g) F. J.
FaÇanꢁs, T. Arto, A. Mendoza, F. Rodrꢀguez, Org. Lett.
2011, 13, 4184–4187; h) T. Harschneck, S. F. Kirsch, J.
Org. Chem. 2011, 76, 2145–2156; i) K. Wittstein, K.
Kumar, H. Waldmann, Angew. Chem. 2011, 123, 9242–
9246; Angew. Chem. Int. Ed. 2011, 50, 9076–9080; j) H.
Yin, F. Kong, S. Wang, Z. J. Yao, Tetrahedron Lett.
2012, 53, 7078–7082; k) K. Goutham, D. Ashok Kumar,
S. Suresh, B. Sridhar, R. Narender, G. V. Karunakar, J.
Org. Chem. 2015, 80, 11162–11168.
Ethyl 1-(4-Methylphenylsulfonyl)-2-methyl-4-phenyl-
1,6-dihydropyridine-3-carboxylate (18)
By the general method for cyclization of sulfonamides to di-
hydropyridines, and elution with hexane/EtOAc 7:3 to fur-
nish a yellow oil; yield:98 mg (46%). 1H NMR (500 MHz,
CDCl3): d=7.67–7.62 (m, 2H), 7.19–7.11 (m, 5H); 6.76–6.73
(m, 2H); 5.42 (t, J=4.7 Hz, 1H), 4.41 (d, J=4.7 Hz, 2H),
3.82 (q, J=7.1 Hz, 2H), 2.50 (s, 3H); 2.26 (s, 3H), 0.70 (t,
J=7.1 Hz, 3H); 13C NMR: d=166.7, 143.8, 143.3, 138.6,
137.3, 136.5, 129.3, 127.8, 127.2, 127.1, 126.3, 124.7, 117.6,
60.6, 45.8, 21.3, 20.3, 13.3; IR (ATR): n=2929, 2362, 1717,
1636, 1597, 1579, 1493, 1445, 1352, 1254, 1184, 1164, 1085,
1042, 1017, 908, 881, 862, 844, 813, 782, 762, 713, 700,
667 cmÀ1; MS (APCI): m/z (%)=398.5 (100) [M+H]+,
352.1 (8), 242.1 (3).
ˇ
˚ ˇ
ˇ
[4] E. Matousovꢁ, A. Ruzicka, J. Kunes, J. Krꢁlovꢁ, M.
Pour, Chem. Commun. 2011, 47, 9390–9392.
[5] For other examples of dihydropyridine preparation,
see: a) H. Kim, C. Lee, J. Am. Chem. Soc. 2006, 128,
6336–6337; b) S. Cacchi, G. Fabrizi, E. Filisti, Org. Lett.
2008, 10, 2629–2632; c) M. A. P. Martins, M. Rossatto,
C. P. Frizzo, E. Scapin, L. Buriol, N. Zanatta, H. G. Bo-
nacorso, Tetrahedron Lett. 2013, 54, 847–849; d) X. Xin,
D. Wang, F. Wu, X. Li, B. Wan, J. Org. Chem. 2013, 78,
4065–4074; e) H. Mizoguchi, R. Watanabe, S. Minami,
H. Oikawa, H. Oguri, Org. Biomol. Chem. 2015, 13,
5955–5963; f) E. M. P. Silva, P. A. M. M. Varandas,
A. M. S. Silva, Synthesis 2013, 45, 3053–3089; g) D. Te-
jedor, L. Cotos, G. Mꢂndez-Abt, F. Garcꢀa-Tellado, J.
Org. Chem. 2014, 79, 10655–10661.
Methyl 1-(4-Methoxyphenylsulfonyl)-4-phenyl-1,6-
dihydropyridine-3-carboxylate-5-d1 (14b-d1).
[(IPr)Au(MeCN)]BF4 (14 mg, 0.019 mmol) was added to
a solution of 12b (150 mg, 0.389 mmol) in CH2Cl2/HFIP-d1
(3:1, 2 mL) and the reaction mixture was stirred at room
temperature for 1 h. The reaction mixture was then filtered
1
through celite and evaporated to dryness. H NMR experi-
ments with CH2Br2 as an internal standard showed a 78%
NMR yield of dihydropyridine 14b-d1; 73% incorporation of
D.
[6] A. Saito, T. Konishi, Y. Hanzawa, Org. Lett. 2010, 12,
372–374.
[7] S. Undeela, S. Thadkapally, J. B. Nanubolu, K. K. Sin-
garapu, R. S. Menon, Chem. Commun. 2015, 51, 13748–
13751.
[8] E. Herrero-Gómez, C. Nieto-Oberhuber, S. López, J.
Benet-Buchholz, A. M. Echavarren, Angew. Chem.
2006, 118, 5581–5585; Angew. Chem. Int. Ed. 2006, 45,
5455–5459.
Acknowledgements
This work was supported by the Czech Science Foundation
(project No. 15-07332S) and by Charles University in Prague
(project Nos. SVV 260 291 and GAUK 567112).
References
[9] G. Pavan Kumar, D. Rambabu, M. V. Basaves-
AHCTUNGTRENNwGUN ara Rao, M. Pal, J. Chem. 2013, ID 916960.
[1] P. Mauleon, F. D. Toste, in: Modern gold Catalyzed
Synthesis, 1st edn., (Eds.: A. S. K. Hashmi, F. D. Toste),
Wiley-VCH, Weinheim, 2012, pp 75–130.
[2] For reviews, see: a) A. S. K. Hashmi, Chem. Rev. 2007,
107, 3180–3211; b) E. Jimꢂnez-NfflÇez, A. M. Echavar-
[10] J. C. Pastre, C. R. D. Correia, Org. Lett. 2006, 8, 1657–
1660.
[11] An analogous oxocarbenium ion has been proposed by
Toste, see for example, ref.[3d]
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12 Substrate Control in the Gold(I)-Catalyzed Cyclization of b-
Propargylamino Acrylic Esters and Further Transformations
of the Resultant Dihydropyridines
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Jirꢀ Mikusek, Petr Matous, Eliska Matousovꢁ,
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Martin Janousek, Jirꢀ Kunes, Milan Pour*
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