Regioselective Synthesis of 6-Vinyl-3,6-dihydropyridine-2(1H)-ones through Simple Addition of a Vinylmagnesium "ate" Complex to 2-Pyridones

Article abstract of DOI:10.1002/ejoc.201500605

A highly nucleophilic vinylation reagent, lithium vinyldimethylmagnesate (vinylMe₂MgLi), is obtained by mixing vinylmagnesium chloride (1 equiv.) and MeLi (in diethoxymethane; 2 equiv.). The application of this new reagent in the completely regioselective synthesis of 6-vinyl-3,6-dihydro-1H-pyridin-2(1H)-ones by simple 1,6-additions to 2-pyridones is described. Examination of the scope and limitations of the addition revealed the influence on the efficiency of the 6-vinylation reaction of substituents on the nitrogen atom and on the 2-pyridone ring. The vinyl "ate" complex (lithium vinyldimethylmagnesate) formed directly by mixing vinylMgCl and MeLi is, unlike a simple Grignard reagent, nucleophilic enough that it undergoes addition to N-substituted 2-pyridones.

Full text of DOI:10.1002/ejoc.201500605

FULL PAPER
DOI: 10.1002/ejoc.201500605
Regioselective Synthesis of 6-Vinyl-3,6-dihydropyridine-2(1H)-ones through
Simple Addition of a Vinylmagnesium “Ate” Complex to 2-Pyridones
[a]
[a]
[a]
´
Jacek G. Sosnicki,* Przemysław Dzitkowski, and Łukasz Struk
Dedicated to Professor Jürgen Liebscher on the occasion of his 70th birthday
Keywords: Nucleophilic addition / Nitrogen heterocycles / Lactams / Magnesium / Substituent effects
A highly nucleophilic vinylation reagent, lithium vinyldi-
methylmagnesate (vinylMe2MgLi), is obtained by mixing
vinylmagnesium chloride (1 equiv.) and MeLi (in diethoxy-
methane; 2 equiv.). The application of this new reagent in the
completely regioselective synthesis of 6-vinyl-3,6-dihydro-
1H-pyridin-2(1H)-ones by simple 1,6-additions to 2-pyr-
idones is described. Examination of the scope and limitations
of the addition revealed the influence on the efficiency of the
6-vinylation reaction of substituents on the nitrogen atom
and on the 2-pyridone ring.
As a result of our recent work aimed at the synthesis of
functionalized piperidin-2(1H)-(thi)ones, we have reported
on the nucleophilic properties of lithium allyldi-n-butylmag-
nesates ([allylnBu2Mg]Li [1a]), which are prepared simply
by mixing allylmagnesium chloride (1) (or 2-methylallyl-
magnesium chloride or 3,3-dimethylallylmagnesium brom-
ide) and n-butyllithium in a 1:2 molar ratio at 0 °C in THF
solution (Scheme 1).[7] The magnesium “ate” complexes
that are formed allowed the fairly regioselective introduc-
tion of an allyl substituent into a 2-(thio)pyridone. This
gave 6-allyl-3,6-dihydropyridin-2(1H)-(thi)ones (A) or 4-
allyl-3,4-dihydropyridin-2(1H)-(thi)ones (B), depending on
Introduction
Functionalized piperidin-2(1H)-ones have become im-
portant since it was recognized that compounds of this class
show a wide range of pharmacological activities,[1] includ-
ing anticancer,[1a] antidiabetic,[1b] and anti-HIV[1c] activities.
It has also been shown that such compounds can act as
neurokinin-2 receptor antagonists,[1d] glycosidase inhibi-
tors,[1e] and fibrinogen receptor antagonists,[1f] among other
roles. In addition to their applications as biologically active
compounds, they have been used as building blocks for the
synthesis of a wide range of naturally occurring alkaloids,[2]
and also of potential pharmaceuticals based on a piperidine
skeleton,[3] and their commonly used precursors.[4]
Among the variety of approaches to the synthesis of
functionalized piperidin-2(1H)-ones that have been re-
ported, the nucleophilic addition of organometallic species
to 2-pyridones [pyridin-2(1H)-ones] is fundamentally im-
portant, because of the high availability of the substrates
and the possibility of synthesizing functionalized dihydro-
pyridin-2(1H)-ones, which are capable of undergoing fur-
ther transformations.[5] However, it should be emphasized
that unactivated 2-pyridones react effectively only with
organolithium[5a–5c,5f,5g] reagents; it has been shown that
they are inert towards Grignard reagents, and in order to
overcome this lack of reactivity, the 2-pyridones must be
transformed into highly electrophilic pyridinium salts by O-
silylation.[6]
[a] West Pomeranian University of Technology, Szczecin, Institute
of Chemistry and Environmental Protection,
Al. Piastów 42, Szczecin 71-065, Poland
E-mail: sosnicki@zut.edu.pl
Scheme 1. The addition of allylmagnesates to 2-(thio)pyridones
and further transformations (previous work), and the addition of
vinyl magnesates to 2-pyridones (this work).
http://www.wtiich.zut.edu.pl
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500605.
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J. G. Sos´nicki, P. Dzitkowski, Ł. Struk
FULL PAPER
whether NR- or NH-substituted pyridin(e)-2(1H)-(thi)ones than the compounds shown in Scheme 2. A simple route to
and allyl(2-methylallyl)di-n-butylmagnesate or 3,3-dimeth- 6-vinyl-3,6-dihydropyridin-2(1H)-ones would also be valu-
ylallyldi-n-butylmagnesate were used. Furthermore, the able because the 6-vinylpiperidine moiety is found in certain
variable regioselectivity of the addition of allyl moieties en- naturally occurring compounds, including (Ϯ)-pinidine,[19]
abled us to obtain substituted 3,6,9,9a-tetrahydroquin- (+)-caulophyllumine B,[20] (+)-dienomycin C,[21] and galbul-
olizin-4-ones[8] (C) and trans-4a,5,8,8a-tetrahydro-2H-iso- imima alkaloids[22] (himbeline and himbacine), and also in
quinolin-1-ones[9] (D) by using ring-closing metathesis some synthetic derivatives showing e.g., anticancer[15b] and
(Scheme 1). It should be noted that with the exception of antibacterial[23] activity. Thus, in this paper we describe the
the above-mentioned lithium allylmagnesates, which are results of the first attempts to activate vinylmagnesium
monoanionic allylmagnesium compounds,[10] and which be- chloride by its conversion into “ate” complexes of type
long to the relatively new and useful family of “ate” com- R3MgLi by the addition of organolithium reagents, and the
plexes,[11] no further examples of the addition of magnesates application of these “ate” complexes in nucleophilic ad-
to pyridin-2(1H)-ones have been reported. Furthermore, al- dition to 2-pyridones, which in turn enables easy access to
though the first preparation of vinylmagnesium “ate” com- 6-vinyl-3,6-dihydropyridin-2-ones.
plexes from vinyl iodides by iodine–magnesium exchange
using iPrnBu2MgLi as an exchange reagent has been re-
ported by Oshima and coworkers,[12] the preparation of vin-
ylmagnesates directly from Grignard reagents has not been
Results and Discussion
described to date.
For our first tests, we used commercially available N-
Encouraged by the successful use of allylmagnesates in methyl-2-pyridone. Treatment with vinylmagnesium chlor-
the functionalization of piperidin-2(1H)-ones, we were ide (2; 1.6 m solution in THF) alone at 0 °C gave only traces
prompted to check whether it would be possible to intro- of 6-vinyl-3,6-dihydropyridine-2(1H)-one (4a) but with a
duce a vinyl substituent into a piperidin-2(1H)-one ring by high consumption of the substrate; this reagent showed a
using a vinylmagnesate reagent. This is not only an interest- complete lack of reactivity at –80 °C (Table 1, entries 1 and
ing issue from the point of view of the fundamental chemis- 2). However, when vinylmagnesium chloride was converted
try of magnesium “ate” complexes. It could also be attract- into magnesate 2a by the addition of 2 equiv. nBuLi, this
ive from a synthetic point of view, because 6-vinyl-substi- reagent yielded 4a in up to 49% isolated yield, although the
tuted piperidin-2(1H)-ones and piperidines could be further substrate conversion was still unsatisfactory (Table 1, en-
functionalized in many ways by reaction of the vinyl moiety tries 3–6). Subsequent optimization of the reaction condi-
by ring-closing[13] or cross[14] metathesis reactions, Heck re- tions involved testing other commercially available lithium
action,[15] reduction,[16] cleavage by ozonolysis,[17] or other reagents, and adjusting the temperature and reaction time.
transformations.[18] A few examples of transformations of MeLi [3 m in DEM (diethoxymethane)] was the best choice
6-vinylpiperidin-2-ones into other piperidine derivatives are among the organolithium reagents tested, and it was advan-
shown in Scheme 2. Furthermore, the anticipated products tageous to change the temperature from –80 to 0 °C during
of the vinylation reaction, vinyldihydropyridin-2(1H)-ones, the reaction (Table 1, entries 7–9). Furthermore, by using
in addition to the exocyclic C=C double bond (vinyl moi- 1.4 equiv. of lithium dimethylvinylmagnesate, and increas-
ety) would also contain a C=C double bond inside the ring. ing the scale of the reaction by a factor of three (up to
This would allow additional transformations, and these 6.9 mmol of 3a), we were able to obtain 4a in a best isolated
products seem to be even more valuable building blocks yield of 79% (Table 1, entry 9). It should be noted that in
all attempts, only the 6-vinyl-substituted product (i.e., 4a)
1
was formed, as shown by H NMR spectroscopic analysis
of the crude reaction mixtures (the 4-vinyl isomer, which
could potentially also be formed, was not detected). The
choice of MeLi for the activation of vinylmagnesium chlor-
ide was also justified from a practical point of view, as its
use led to a minimum number of by-products, as observed
by 1H NMR spectroscopy and GC–MS analysis of the
crude reaction mixtures (see footnote in Table 1). In the
light of the above results, it should be mentioned that the
activation of aryl and alkyl Grignard reagents towards
Michael addition to α,β-unsaturated NH amides by treat-
ment with MeLi (in diethyl ether) has been reported ear-
lier.[24]
Next, we were driven to check the level of influence of
diethoxymethane (DEM; introduced into the reaction envi-
ronment together with MeLi) on the product yield. When
we ran the reaction using a diethyl ether solution of MeLi
(1.6 m), another commercially available reagent, the yield
Scheme 2. Examples of the application of 6-vinylpiperidin-2-ones
in the synthesis of functionalized piperidin-2-ones and piperidines.
RCM = ring-closing metathesis; CM = cross metathesis.
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Synthesis of 6-Vinyl-3,6-dihydropyridine-2(1H)-ones
Table 1. Optimization of reaction conditions for the 6-vinylation of
3a. The effect of varying the organolithium reagents on the effi-
ciency of the vinyl addition.
Entry
2
RLi (equiv.)
T [°C]/
t [min.]
3a[a]
Conv. [%][b] Yield [%][c]
4
equiv.
1
2
3
4
5
1.3
1.3
1.2
1.2
1.4
–
–
0/90
–80/90
0/30
–80/30
–80/60
–80Ǟ23/15
0/45
–80/90
–80Ǟ23/15
0/30
–80/60
–80Ǟ23/15
0/45
as above
as above
as above
88
0
95
44
87
(2)1
0
nBuLi[d] (2.4)
nBuLi[d] (2.4)
nBuLi[d] (2.8)
31 (34)1
(18)1
49 (54)1
6
7
2.0
1.2
nBuLi[d] (4.0)
93
93
48
MeLi[e] (2.4)
(59)2
8
9
10
11
12
13
1.4
1.4
1.4
1.2
1.2
1.2
MeLi[e] (2.8)
MeLi[e] (2.8)
MeLi[h] (2.8)
Ͼ99
Ͼ99
Ͼ99
81
93
95
(68)2[f]
79[f,g]
60[g]
sec-BuLi[i] (2.4) as above
tert-BuLi[k] (2.4) as above
(36)1[j]
(22)1[j]
(44)1[m]
PhLi[l] (2.4)
as above
[a] 2.3 mmol of 3a (1.0 equiv.) was used unless otherwise stated.
[b] Conversion of 3a [%] estimated by 1H NMR spectroscopic
analysis of the crude reaction mixture. [c] Isolated yield [%], yield
1
estimated by H NMR spectroscopy using an internal reference is
given in parentheses. The number of determinations is given in the
upper index. [d] 2.5 m n-hexane solution. [e] 3 m diethoxymethane
solution. [f] The minimum number of by-products was observed by
1H NMR spectroscopy and GC–MS analysis of the crude reaction
mixture. [g] The reaction scale was increased threefold (6.9 mmol of
3a). [h] 1.6 m diethyl ether solution. [i] 1.4 m cyclohexane solution.
[j] The product of addition of the organolithium to 2a was detected
by GC–MS (m/z = 167), among other by-products. [k] 1.7 m pent-
ane solution. [l] 1.8 m dibutyl ether solution. [m] Biphenyl was de-
tected by GC–MS as the main by-product.
decreased significantly by 19%. This indicates that DEM is
a better cosolvent, and that it is responsible for an ad-
ditional activation effect (Table 1, entry 10).
Having established optimal reaction conditions, we went
on to evaluate the scope and limitations of the vinylation
reaction in terms of substituted 2-pyridones. First, we ex-
amined 2-pyridones bearing various substituents on the
nitrogen atom only, and then we tested derivatives with
various substituents on both the nitrogen atom and the
ring. The results of the first part of the study are presented
in Scheme 3 (Part A). We found that the optimized protocol
described above permits the 6-vinylation of N-substituted
2-pyridones; the N-Li 2-pyridone derived from N-H sub-
strate 3k remained intact. However, among the N-substi-
tuted 2-pyridones tested, only the derivatives with an N-
phenyl group (3h) and with less bulky N-alkyl groups (3a–
Scheme 3. Scope of the addition of vinylMgMe2Li + LiCl to substi-
tuted 2-pyridones. [a] Conditions are as follows: i) THF, 5 min at
0 °C; ii) 60 min at –80 °C, then warming at room temp. over
15 min, then 45 min at 0 °C. [b] High mass product detected by
GC–MS analysis of the crude reaction mixture. [c] complex mixture
observed by 1H NMR spectroscopy. [d] Product not isolated.
[e] Through N-Li salt.
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3g) gave satisfactory yields. Derivatives with N-phenylsulf- sponding products (i.e., 4r–4t) were obtained in good yields,
onyl (3j) and N-(3-phenylallyl) (3l) substituents gave only and no self-condensed by-products were formed. This ob-
traces of the products or underwent degradation.
servation is very important, because in the light of the ob-
N-Benzyl- (3c) and N-allyl-substituted (3d) 2-pyridones served competition between the nucleophilic and basic be-
constitute a separate group; they gave the products in lower haviour of vinylmagnesate 2a, the influence of the ring sub-
yields (4c, 28%; and 4d, 27%, respectively) due to the com- stituent enables a shift of the reactivity of 2-pyridones
petitive formation of benzyl and allyl anions, which led to towards nucleophilic addition.
self-addition products. These undesirable by-products were
The lack of success in the addition reactions of 2-pyrid-
1
detected by H NMR spectroscopy and GC–MS analysis ones with bulky nitrogen substituents can be attributed to
of the crude reaction mixtures. Their presence was con- steric hindrance between the nucleophile and the large
firmed by the successful isolation of one such by-product nitrogen substituents. The experimentally observed relation-
(i.e., 5d; Scheme 4), whose purity was high enough to per- ship between the structures of N-alkyl and N-aryl 2-pyrid-
mit its structural analysis by 1H and 13C NMR spec- ones and their reactivity towards addition can be rational-
troscopy and HRMS (ESI-TOF).
ized in terms of classical frontier molecular orbital (FMO)
theory.[25] LUMO energies were calculated using the PM3
method[26] for acceptors 3 for the prepared N-Me (3a) and
N-Ph substituted (3h, 3o, 3w) derivatives, and also for theo-
retical structures 3Ta–3Td similar to those obtained (N-
alkyl or alkenyl) but with an N-Me group (Figure 1). The
structures were simplified for the calculations in order to
avoid interruption of the calculations at local energy min-
ima due to N-alkyl-chain rotation. The results showed that
the LUMO energies change in parallel to the experimentally
observed reactivities of the acceptors. Derivatives with 3-Ph
and 3-Cl substituents have LUMOs with significantly lower
energies compared to the LUMO of 3a, which makes them
more reactive towards addition (Figure 1, structures 3Ta,
3Tb, and 3a, respectively). The presence of a methyl substit-
uent on the ring slightly increases the energy of LUMO,
thus decreasing the reactivity (Figure 1, structures 3Tc and
3Td). The same substituent effect was observed in the N-
Ph series. The highest reactivity was noted for 5-Cl-substi-
tuted 2-pyridone 3w, whose LUMO energy had the lowest
Scheme 4. Formation of by-product 5d by competitive formation
of a stabilized allyl anion and subsequent addition.
The above observations imply that the nucleophilic be- value; 4-Me derivative 3o led to the lowest yield and conver-
haviour of vinylmagnesate 2a, which leads to the addition sion. These tentative results may indicate that orbital over-
products, competes with its behaviour as a base, manifested lap is the main factor that controls the reactivity of 3. How-
by proton abstraction from the N-CH moiety, and enabling ever, more detailed calculations need to be carried out to
self-addition through the formation of a stabilized anion. support this hypothesis.
The above results show that the behaviour of 2a is in dis-
tinct contrast to the reactivity of allyldi-n-butylmagnesate
(1a), which yielded the addition product exclusively in its
reactions with the corresponding N-allyl-2-pyridone (i.e.,
3d).[8d]
The results obtained from the second set of reactions
(Scheme 3, B) indicate that the substituents on the 2-pyr-
idone ring have a substantial influence on the yield of the
6-vinylation products (i.e., 4), compared to the yields ob-
tained for the ring-unsubstituted analogues. Judging by the
conversion of the substrates and the yield of the products
(i.e., 4), it is clear that a 4-Me group decreases the reactivity
of the 2-pyridone ring, whereas a 3-Me group does not in-
fluence the reactivity. 3-Cl, 3-Ph, and 3-PhS substituents
Figure 1. PM3-calculated energies of LUMO orbitals of selected
N-Me and N-Ph 2-pyridones arranged in order of decreasing en-
make the 2-pyridone ring more reactive towards addition,
except for 3-Cl, N-H substituted derivative 3v, which, simi-
larly to unsubstituted N-H 2-pyridone 3k, remained intact.
ergy values for the two types of N-substituent.
It is not trivial to explain the regioselectivity of the ad-
The influence of substituents on the 2-pyridone ring on the dition of vinylmagnesium “ate” complexes to N-alkyl or N-
reactivity towards addition is the most pronounced for N- aryl 2-pyridones; it requires detailed high-level calculations
allyl (3r and 3s) and N-benzyl (3t) substrates; the corre- within e.g., FMO theory or another theory. Without using
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Synthesis of 6-Vinyl-3,6-dihydropyridine-2(1H)-ones
calculations, our current idea to explain the complete 1,6- vinylMgCl in THF (Figure 2, part a) and of 1:1 and 1:2
regioselectivity in the addition reactions involves the exis- molar mixtures of vinylMgCl (in THF) and MeLi (in
tence of a polarized transition state, in which the amide DEM) (Figure 2, c and d, respectively) clearly indicated
functionality of the 2-pyridone interacts with the vinyl- that there was an interaction between vinylMgCl and MeLi,
magnesate in the manner shown in Scheme 5. The pos- especially in a 1:2 molar ratio. [The highest chemical shift
tulated existence of such a complex, with a charge-driven differences were observed for the 1:2 molar ratio mixture: δ
1
orientation of the two components, is based on the assump- ≈ 0.5 ppm in the H NMR spectra, and δ ≈ 5.8 ppm (C=)
tion that the magnesate could be regarded as a contact or in the 13C NMR spectra.] Additional experiments showed
separated ion pair,[11b] and that the 2-pyridone is polarized only a weak interaction between vinylMgCl and diethoxy-
due to the presence of an amide functionality.[27] The pro- methane (DEM).
posed interaction may result in a decrease of the electron
Finally, we checked the possibility of functionalizing 2-
density in the pyridone ring, which would increase its reac- pyridones by the addition of vinyl magnesate prepared by
tivity towards the addition of the vinyl nucleophile. More Oshima’s Mg–I exchange method. Thus, β-styrylmagnesate
importantly, it seems that this proposed interaction is cru- 7, prepared from easily available β-iodostyrene[28] (6) using
cial for obtaining complete 1,6-regioselectivity in the ad- iPrMe2MgLi as an exchange reagent (instead of the
dition reaction. This explanation may be confirmed by the iPrnBu2MgLi used in Oshima’s original method), was
failure of the reaction between N-methyl 2-pyridone and treated with 2-pyridone 3a, and gave product 8 in 46%
standard vinylmagnesium chloride, which has a different yield, together with by-product 9 (11% yield; Scheme 6). It
electron distribution compared to the vinylmagnesate. The should be noted that undesired product 9 was formed as
final point is the fact that N-lithiated pyridones (which the result of alkylation of 8 by isopropyl iodide, which was
could be regarded as nitrogen-electron-rich variants of 2- released during the exchange process (Scheme 6). [The ease
pyridone) do not react on treatment with vinylmagnesate.
of alkylation of 3,6-dihydropyridin-2(1H)-one by alkyl iod-
Scheme 5. The electrostatic interaction between vinylmagnesate 2a
and N-alkyl (or phenyl) substituted 2-pyridones as the potential
reason for the total 1,6-regioselectivity.
Scheme 6. Attempted use of magnesate derived from styryl iodide
by the I–Mg exchange method. The cis-configuration of product 9
was assigned from 1H,1H NOESY spectra (see Supporting Infor-
mation). i) THF, 5 min at –10 °C; ii) 60 min at –80 °C then warm-
Next, we studied the activation of vinylMgCl by MeLi
(in DEM) by 1H and 13C NMR spectroscopy, performed at
22 °C in a coaxial probe using CD3COCD3 as an external
1
lock and reference (Figure 2). The H and 13C spectra of ing at room temp. over 15 min, then 60 min at 0 °C.
Figure 2. The additive effect of MeLi (c, d) and DEM (b) on 1H (400 MHz; left) and 13C (100 MHz; right) NMR spectra of vinylmagne-
sium chloride in THF (a) at 22 °C using CD3COCD3 as external lock and reference.
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J. G. Sos´nicki, P. Dzitkowski, Ł. Struk
FULL PAPER
ides using magnesates has already been reported by us.][7c]
These results indicate that the direct styrylation of 2-pyrid-
ones using magnesates obtained by the exchange method is
also a promising prospect, but the reaction conditions
should be optimized to minimize formation of the alkylated
by-product.
ethyl acetate, 1:10) to give 4a (79%) as a pale yellow oil that dark-
ened on standing. H NMR (400 MHz, CDCl3, 23 °C): δ = 2.92–
1
3.00 (m, 5 H, CH2-3, NCH3), 4.28 (dq, J = 8.1, 3.9 Hz, 1 H, CH-
6), 5.18–5.26 (m, 2 H, =CH2), 5.53–5.6 (ddd, J = 17.0, 9.8, 8.1 Hz,
1 H, =CH), 5.62–5.68 (m, 1 H, =CH-5), 5.77 (dtd, J = 10.0, 3.5,
1.3 Hz, 1 H, =CH-4) ppm. 13C NMR (100.6 MHz CDCl3): δ =
31.76 (CH2-3), 32.28 (NCH3), 64.19 (CH-6), 117.22 (=CH2), 122.20
(=CH-4), 124.39 (=CH-5), 136.61 (=CH), 167.41 (C-2) ppm. GC–
MS (EI, 70 eV): m/z (%) = 137 (29) [M]+, 137 (80), 110 (100), 79
Conclusions
(50), 68 (20). IR (film): ν = 3084 (w), 3048 (w), 2932, 1660 (s), 1484
˜
(m), 1398 (m), 1312 (m), 1244 (w), 1120 (w), 1064 (w), 988 (w), 932
(m), 716 (w), 664 (w) cm–1. HRMS (ESI-TOF): calcd. for C8H12NO
[M + H]+ 138.0919; found 138.0911.
We have demonstrated that lithium vinyldimethyl-
magnesate can be formed directly by mixing of 1 equiv. of
vinylMgCl and 2 equiv. of MeLi. The vinyl “ate” complex,
although less nucleophilic than the corresponding allyl-
magnesate, is capable of addition to N-substituted 2-pyrid-
ones regioselectively through C-6(sp3)–C-vinyl(sp2) bond
formation. The presence on the 2-pyridone ring of substitu-
ents such as 3-Cl, 3-Ph, and 3-PhS enhances the reactivity
of the 2-pyridone towards the addition reaction, helping to
overcome the undesired basic properties of the vinyl
magnesate, and thus improving the yields of the 6-vinyl-3,6-
dihydropyridin-2(1H)-one addition products. We postulate
(؎)-1-Propyl-6-vinyl-3,6-dihydropyridin-2(1H)-one (4b): The crude
product was purified by column chromatography (SiO2, n-hexane/
ethyl acetate, 1:7) to give 4b (77%) as a pale yellow oil that dark-
ened on standing. 1H NMR (400 MHz, CDCl3, 23 °C): δ = 0.89 (t,
J = 7.5 Hz, 3 H, CH3), 1.53–1.65 (m, 2 H, CH2), 2.88 (ddd, J =
13.4, 8.9, 6.0 Hz, 1 H, NCHH), 2.94–3.00 (m, 2 H, CH2-3), 3.82
(ddd, J = 13.4, 9.1, 6.8 Hz, NCHH), 4.35 (dq, J = 7.8, 3.6 Hz, 1
H, CH-6), 5.15–5.24 (m, 2 H, =CH2), 5.60 (ddd, J = 17.1, 9.9,
8.1 Hz, 1 H, =CH), 5.63–5.68 (m, 1 H, =CH-5), 5.77 (dddd, J =
10.0, 4.2, 3.2, 1.2 Hz, 1 H, =CH-4) ppm. 13C NMR (100.6 MHz
that the LUMO energy of the 2-pyridones, which is depend- CDCl3): δ = 11.35 (CH3), 20.35 (CH2), 32.19 (CH2-3), 46.10
(NCH2), 61.96 (CH-6), 116.74 (=CH2), 122.43 (=CH-4), 124.70
(=CH-5), 136.91 (=CH), 167.25 (C=O) ppm. GC–MS (EI, 70 eV):
m/z (%) = 165 (27) [M]+, 164 (100), 150 (13), 148 (16), 138 (31),
136 (28), 122 (18), 107 (61), 96 (58), 94 (20), 80 (32), 79 (76), 77
ent on the type of substituents on the 2-pyridone ring, is
the main factor influencing the reactivity of the addition of
lithium dimethylvinylmagnesate. The observed direction of
activation can be used to design new reactive acceptors. The
possible extension of the above reactions to magnesates ob-
tained by an Mg–I exchange process indicates the great po-
tential of these reactions. We are currently studying how the
substituted vinylmagnesates obtained from Grignard rea-
gents as well as by the Mg–I exchange process can be ap-
plied in addition reactions to 2-pyridones and to other ac-
ceptors.
(30), 67 (15), 53 (12), 41 (28), 39 (24). IR (film): ν = 3084 (w), 3048
˜
(w), 2964 (s), 2932 (m), 2876 (m), 1642 (s), 1466 (s), 1432 (m), 1410
(s), 1320 (m), 1262 (m), 1206 (m), 1168 (w), 1124 (w), 1080 (m),
990 (m), 926 (m), 714 (m), 664 cm–1. HRMS (ESI-TOF): calcd. for
C10H16NO [M + H]+ 166.1232; found 166.1228.
(؎)-1-Benzyl-6-vinyl-3,6-dihydropyridin-2(1H)-one (4c): The crude
product was purified by column chromatography (SiO2, n-hexane/
ethyl acetate, 1:10) to give 4c (28%) as a pale yellow oil that dark-
1
ened on standing. H NMR (400 MHz, CDCl3, 23 °C): δ = 3.05–
3.10 (m, 2 H, CH2-3), 3.83 (d, J = 14.9 Hz, 1 H, NCHH), 4.23 (dq,
J = 8.0, 3.9 Hz, 1 H, CH-6), 5.17 (dt, J = 17.0, 0.8 Hz, 1 H,
=CHH), 5.22 (d, J = 10.0 Hz, 1 H, =CHH), 5.55–5.65 (m, 3 H,
NCHH, =CH-5, =CH), 5.78 (dddd, J = 9.9, 4.0, 3.2, 1.2 Hz, 1 H,
=CH-4), 7.21–7.34 (m, 5 H, C6H5) ppm. 13C NMR (100.6 MHz
CDCl3): δ = 32.09 (CH2-3), 46.20 (NCH2), 60.55 (CH-6), 117.62
(=CH2), 122.24 (=CH-4), 124.75 (=CH-5), 127.36, 128.09, 128.62
(C6H5), 136.30 (=CH), 136.88 (C6H5), 167.57 (C=O) ppm. GC–
MS (EI, 70 eV): m/z (%) = 213 (45) [M]+, 132 (20), 106 (30), 91
Experimental Section
Typical Procedure for the Synthesis of 6-Vinyl-3,6-dihydropyridine-
2(1H)-ones 4: A stirred solution of vinylMgCl (1.6 m in THF;
9.7 mmol, 6 mL) in dry THF (18 mL) in a Schlenk flask was cooled
to 0 °C under argon, and MeLi (3.0 m in DEM; 19.5 mmol,
6.5 mL) was added by syringe over 3 min. The resulting solution
was stirred for 5 min, and then it was cooled to –80 °C. The solu-
tion containing lithium vinyldimethylmagnesate was then transfer-
red by syringe to a precooled (–80 °C) solution of 2-pyridone (3;
6.9 mmol) in THF (40 mL) in another Schlenk flask. The resulting
solution was stirred for 60 min at –80 °C. After this time, the mix-
ture was removed from the bath and allowed to warm up for
15 min, and then the flask was put into an ice-water bath (0 °C)
for 45 min. The mixture was carefully quenched with saturated
aqueous NH4Cl (15 mL), then it was allowed to warm up to room
temp., and diluted with water (ca. 20 mL). The aqueous layer was
extracted with ethyl acetate (2ϫ 40 mL), and the combined organic
layers were dried with MgSO4. The mixture was filtered, and the
solvents were evaporated under reduced pressure. The crude prod-
uct was purified by column chromatography on silica gel using a
mixture of n-hexane and ethyl acetate as eluent to give the desired
product.
(100), 80 (20), 79 (32), 77 (17), 65 (24). IR (film): ν = 3028 (w),
˜
2928 (w), 1644 (s), 1496 (w), 1452 (s), 1408 (m), 1356 (w), 1318
(m), 1252 (m), 1182 (w), 1148 (w), 1072 (w), 1028 (w), 990 (w), 962
(w), 930 (w), 772 (w), 702 (m), 668 cm–1. HRMS (ESI-TOF): calcd.
for C14H15NNaO [M + Na]+ 236.1051; found 236.1051.
(؎)-1-Allyl-6-vinyl-3,6-dihydropyridin-2(H)-one (4d): The crude
product was purified by column chromatography (SiO2, n-hexane/
ethyl acetate, 1:7) to give 4d (27%) as a pale yellow oil that dark-
1
ened on standing. H NMR (400 MHz, CDCl3, 23 °C): δ = 2.98–
3.02 (m, 2 H, CH2-3), 3.40 (dd, J = 15.4, 7.6 Hz, 1 H, NCHH),
4.36 (dq, J = 8.1, 3.4 Hz, 1 H, CH-6), 4.75 (ddt, J = 15.4, 4.1,
1.7, Hz, 1 H, NCHH), 5.10–5.23 (m, 4 H, 2 =CH2), 5.58 (ddd, J =
17.3, 9.7, 8.1 Hz, 1 H, =CH), 5.67 (dquint, J = 10.0, 2.1 Hz, 1
H, =CH-5), 5.71–5.81 (m, 2 H, =CH-4, =CH) ppm. 13C NMR
(؎)-1-Methyl-6-vinyl-3,6-dihydropyridin-2(1H)-one (4a): The crude (100.6 MHz CDCl3): δ = 32.06 (CH2-3), 45.94 (NCH2), 60.93 (CH-
product was purified by column chromatography (SiO2, n-hexane/ 6), 117.27, 117.38 (2 =CH2), 122.32 (=CH-4), 124.67 (=CH-5),
5194
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5189–5198

Synthesis of 6-Vinyl-3,6-dihydropyridine-2(1H)-ones
132.59, 136.47 (2 =CH), 167.17 (C=O) ppm. GC–MS (EI, 70 eV):
(w), 1648 (s), 1464 (m), 1410 (m), 1360 (w), 1320 (m), 1280 (m),
m/z (%) = 162 (74) [M]+, 148 (40), 136 (56), 134 (40), 120 (31), 106 1188 (w), 1154 (w), 1120 (s), 1070 (w), 994 (w), 930 (w), 716 (w),
(16), 96 (65), 80 (44), 79 (100), 77 (35), 67 (26), 53 (15), 41 (64), 39 664 (w) cm–1. HRMS (ESI-TOF): calcd. for C10H16NO2 [M + H]+
(44). IR (film): ν = 3084 (w), 3048 (w), 2980 (w), 2924 (w), 1658 182.1181; found 182.1177.
˜
(s), 1460 (s), 1408 (s), 1318 (m), 1264 (m), 1194 (w), 1120 (w), 992
(؎)-1-Phenyl-6-vinyl-3,6-dihydropyridin-2(1H)-one (4h): The crude
(m), 926 (m), 716 (m) cm–1. HRMS (ESI-TOF): calcd. for
C10H14NO [M + H]+ 164.1075; found 164.1077.
product was purified by column chromatography (SiO2, n-hexane/
ethyl acetate, 1:20) to give 4h (66%) as a yellow oil that darkened
on standing. 1H NMR (400 MHz, CDCl3, 23 °C): δ = 3.09–3.23
(m, 2 H, CH2-3), 4.71 (dq, J = 7.6, 3.6 Hz, 1 H, CH-6), 4.97 (dt, J
= 16.9, 0.8 Hz, 1 H, =CHH), 5.03 (br. d, J = 10.0 Hz, 1 H, =CHH),
5.68 (ddd, J = 17.0, 9.9, 8.3 Hz, 1 H, =CH), 5.81 (ddt, J = 10.0,
4.0, 2.1 Hz, 1 H, =CH-5), 5.91 (dddd, J = 10.0, 4.0, 3.2, 1.0 Hz, 1
H, =CH-4), 7.18–7.23 (m, 2 H, C6H5), 7.29 (tt, J = 7.6, 1.2 Hz, 1
H, C6H5), 7.36–7.42 (m, 2 H, C6H5) ppm. 13C NMR (100.6 MHz
CDCl3): δ = 32.70 (CH2-3), 65.46 (CH-6), 117.33 (=CH2), 122.52
(=CH-4), 125.08 (=CH-5), 127.38, 127.99, 129.14 (C6H5), 136.31
(=CH), 140.98 (C6H5), 167.53 (C=O) ppm. GC–MS (EI, 70 eV):
m/z = 199 (100) [M]+, 198 (59), 172 (71), 170 (29), 156 (22), 144
(22), 130 (26), 119 (14), 104 (18), 91 (17), 80 (57), 79 (82), 77 (70),
(؎)-1-But-3-enyl-6-vinyl-3,6-dihydropyridin-2(1H)-one (4e): The
crude product was purified by column chromatography (SiO2, n-
hexane/ethyl acetate, 1:8) to give 4e (68%) as a pale yellow oil that
darkened on standing. 1H NMR (400 MHz, CDCl3, 23 °C): δ =
2.26–2.42 (m, 2 H, CH2), 2.90–3.04 (m, 3 H, CH2-3, NCHH), 3.93
(ddd, J = 13.5, 8.5, 6.4 Hz, 1 H, NCHH), 4.36 (dq, J = 7.6, 3.6 Hz,
1 H, CH-6), 5.02 (dm, J ≈ 10.0 Hz, 1 H, =CHH), 5.07 (dq, J =
17.1, 1.7 Hz, 1 H, =CHH), 5.17–5.24 (m, 2 H, =CH2), 5.55–5.67
(m, 2 H, =CH-5, =CH), 5.73–5.84 (m, 2 H, =CH-4, =CH) ppm.
13C NMR (100.6 MHz CDCl3): δ = 31.70 (CH2), 32.15 (CH2-3),
43.98 (NCH2), 62.32 (CH-6), 116.66, 116.92 (2 =CH2), 122.37
(=CH-4), 124.59 (=CH-5), 135.32, 136.82 (2 =CH), 167.33 (C=O)
ppm. GC–MS (EI, 70 eV): m/z (%) = 177 (8) [M]+, 176 (22), 136
(100), 107 (94), 94 (19), 79 (51), 77 (25), 41 (13), 39 (17). IR (film):
51 (28), 39 (19). IR (film): ν = 3048 (w), 1654 (s), 1596 (m), 1496
˜
(m), 1428 (m), 1402 (s), 1290 (m), 1282 (m), 1240 (w), 1168 (w),
1144 (m), 1074 (w), 986 (m), 926 (m), 832 (w), 762 (m), 696 (s)
cm–1. HRMS (ESI-TOF): calcd. for C13H13NNaO [M + Na]+
222.0895; found 222.0899.
ν = 3080 (w), 3048 (w), 2976 (w), 2932 (w), 1646 (s), 1466 (m),
˜
1410 (m), 1320 (w), 1246 (w), 1192 (w), 1124 (w), 1086 (w), 992
(m), 918 (m), 714 (m) cm–1. HRMS (ESI-TOF): calcd. for
C11H16NO [M + H]+ 178.1232; found 178.1240.
(؎)-4-Methyl-1-propyl-6-vinyl-3,6-dihydropyridin-2(1H)-one (4m):
The crude product was purified by column chromatography (SiO2,
n-hexane/ethyl acetate, 1:2) to give 4w (51%) as a yellow oil. 1H
NMR (400 MHz, CDCl3, 23 °C): δ = 0.88 (t, J = 7.4 Hz, 3 H,
CH3), 1.51–1.63 (m, 2 H, CH2), 1.73 (s, 3 H, 4-CH3), 2.77–2.95 (m,
3 H, CH2-3, NCHH), 3.81 (ddd, J = 13.4, 9.0, 6.8 Hz, 1 H,
NCHH), 4.28 (br. dquint, J = 4.2 Hz, ca. 2.8 Hz, 1 H, CH-6), 5.11–
5.19 (m, 2 H, -CH2), 5.35 (br. s, 1 H, CH-5), 5.55 (ddd, J = 17.0,
9.8, 8.2 Hz, 1 H, =CH) ppm. 13C NMR (100.6 MHz CDCl3): δ
= 11.35 (CH3), 20.35 (CH2), 21.80 (4-CH3), 36.83 (CH2-3), 45.85
(NCH2), 61.91 (CH-6), 116.18 (=CH2), 118.87 (=CH-5), 130.75
(=C-4), 137.49 (=CH-5), 167.43 (C=O) ppm. GC–MS (EI, 70 eV):
m/z (%) = 179 (44) [M]+, 178 (98), 164 (54), 162 (32), 152 (81), 150
(53), 136 (31), 122 (35), 121 (41), 110 (100), 108 (21), 94 (33), 93
(؎)-1-Pent-4-enyl-6-vinyl-3,6-dihydropyridin-2(1H)-one (4f): The
crude product was purified by column chromatography (SiO2, n-
hexane/ethyl acetate, 1:10) to give 4f (64%) as a yellow oil that
darkened on standing. 1H NMR (400 MHz, CDCl3, 23 °C): δ =
1.67 (quint, J = 7.3 Hz, 2 H, CH2), 2.06 (q, J = 7.6 Hz, 2 H, CH2),
2.89–3.03 (m, 3 H, CH2-3, NCHH), 3.84 (dt, J = 13.6, 7.8 Hz, 1
H, NCHH), 4.34 (dq, J = 7.6, 3.6 Hz, 1 H, CH-6), 4.97 (ddt, J =
10.1, 2.0, 1.2 Hz, 1 H, =CHH), 5.03 (dq, J = 17.2, 1.8 Hz, 1 H,
=CHH), 5.16–5.23 (m, 2 H, =CH2), 5.59 (ddd, J = 17.1, 9.8,
8.1 Hz, 1 H, =CH), 5.65 (ddt, J = 10.0, 4.1, 1.8 Hz, 1 H, =CH-5),
5.75–5.86 (m, 2 H, =CH, =CH-4) ppm. 13C NMR (100.6 MHz
CDCl3): δ = 26.23 (CH2), 31.07 (CH2), 32.18 (CH2-3), 44.11
(NCH2), 62.07 (CH-6), 114.91, 116.87 (2 =CH2), 122.43 (=CH-4),
124.66 (=CH-5), 136.88, 137.91 (2 =CH), 167.24 (C=O) ppm. GC–
MS (EI, 70 eV): m/z (%) = 191 (15) [M]+, 190 (83), 176 (25), 162
(25), 148 (28), 136 (82), 122 (53), 107 (88), 96 (59), 79 (100), 77
(37), 79 (57), 77 (34), 67 (17), 53 (14), 41 (26). IR (film): ν = 2968
˜
(m), 2932 (m), 2876 (w), 1654 (s), 1466 (m), 1408 (m), 1380 (w),
1292 (m), 1262 (m), 1204 (w), 1136 (w), 990 (w), 926 (w), 832 cm–1.
HRMS (ESI-TOF): calcd. for C11H18NO [M + H]+ 180.1388;
found 180.1396.
(42), 67 (31), 53 (22), 41 (65), 39 (42). IR (film): ν = 3080 (w), 3048
˜
(w), 2976 (w), 2928 (m), 1648 (s), 1466 (m), 1410 (m), 1320 (m),
1280 (m), 1244 (w), 1184 (w), 1124 (w), 990 (m), 916 (m), 714 (m)
cm–1. HRMS (ESI-TOF): calcd. for C12H18NO [M + H]+ 192.1388;
found 192.1382.
(؎)-5-Chloro-1-propyl-6-vinyl-3,6-dihydropyridin-2(1H)-one
(4n):
The crude product was purified by column chromatography (SiO2,
n-hexane/ethyl acetate, 1:20) to give 4n (70%) as a yellow oil. 1H
NMR (400 MHz, CDCl3, 23 °C): δ = 0.90 (t, J = 7.4 Hz, 3 H,
(؎)-1-(2-Methoxyethyl)-6-vinyl-3,6-dihydropyridin-2(1H)-one (4g): CH3), 1.53–1.64 (m, 2 H, CH2), 2.81 (ddd, J = 13.6, 8.6, 6.4 Hz, 1
The crude product was purified by column chromatography (SiO2,
H, NCHH), 3.05 (dd, J = 3.9, 2.9 Hz, 2 H, CH2-3), 3.84 (ddd, J =
n-hexane/ethyl acetate, 1:20) to give 4g (40%) as a yellow oil. 1H 13.6, 8.7, 7.2 Hz, 1 H, NCHH), 4.25 (dm, J = 7.8 Hz, 1 H, CH-6),
NMR (400 MHz, CDCl3, 23 °C): δ = 2.90–3.05 (m, 2 H, CH2-3), 5.30–5.37 (m, 2 H, =CH2), 5.66 (ddd, J = 16.9, 10.0, 7.8 Hz, 1 H,
3.12 (ddd, J = 14.0, 8.5, 4.8 Hz, 1 H, NCHH), 3.33 (s, 3 H, OCH3),
=CH), 5.88 (t, J = 3.9 Hz, 1 H, CH-4) ppm. 13C NMR (100.6 MHz
3.52 (dt, J = 10.0, 4.6 Hz, 1 H, OCHH), 3.61 (ddd, J = 10.0, 8.3, CDCl3): δ = 11.26 (CH3), 20.36 (CH2), 32.91 (CH2-3), 46.44
4.6 Hz, 1 H, OCHH), 4.05 (dt, J = 14.0, 4.6 Hz, 1 H, NCHH), 4.56 (NCH2), 65.65 (CH-6), 119.60 (=CH2), 120.74 (=CH-4), 127.15 (C-
(dq, J = 8.0, 3.9 Hz, 1 H, CH-6), 5.16–5.25 (m, 2 H, =CH2), 5.58
(ddd, J = 17.0, 10.0, 8.0 Hz, 1 H, =CH), 5.66 (dddd, J = 10.0, 3.9,
5), 133.97 (=CH), 165.97 (C=O) ppm. GC–MS (EI, 70 eV): m/z
(%) = 201 (6) [M + 2], 200 (37) [M + 1], 199 (20) [M]+, 198 (100),
2.4, 1.5 Hz, 1 H, =CH-5), 5.76 (dddd, J = 10.0, 4.2, 3.2, 1.2 Hz, 1 184 (16), 172 (27), 164 (31), 156 (14), 143 (25), 141 (37), 130 (39),
H, =CH-4) ppm. 13C NMR (100.6 MHz CDCl3): δ = 32.16 (CH2- 113 (38), 79 (84), 77 (54), 51 (14), 39 (15). IR (film): ν = 3084 (w),
˜
3), 44.02 (NCH2), 58.89 (CH3), 63.25 (CH-6), 70.93 (OCH2),
3064 (w), 2968 (s), 2936 (m), 2876 (m), 1658 (br. s), 1460 (m), 1430
117.12 (=CH2), 122.04 (=CH-4), 124.89 (=CH-5), 136.72 (=CH), (m), 1408 (s), 1380 (w), 1302 (w), 1250 (s), 1200 (m), 1124 (m),
167.56 (C=O) ppm. GC–MS (EI, 70 eV): m/z (%) = 181 (15) [M]+, 1084 (w), 1014 (m), 986 (w), 930 (m), 874 (w), 812 (m), 796 (w),
180 (89), 149 (32), 148 (45), 136 (28), 122 (48), 107 (100), 94 (25),
79 (69), 77 (32). IR (film): ν = 3048 (w), 2980 (w), 2932 (w), 2896
776 (w), 694 (w) cm–1. HRMS (ESI-TOF): calcd. for
C10H14ClNNaO [M + Na]+ 222.0662; found 222.0699.
˜
Eur. J. Org. Chem. 2015, 5189–5198
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5195

J. G. Sos´nicki, P. Dzitkowski, Ł. Struk
(؎)-4-Methyl-1-phenyl-6-vinyl-3,6-dihydropyridin-2(1H)-one (4o): J = 15.8, 7.2, 0.6 Hz, 1 H, NCHH), 4.80 (dsxt, J = 7.0, 1.1, Hz, 1
FULL PAPER
The crude product was purified by column chromatography (SiO2,
H, CH-6), 4.90 (ddt, J = 15.8, 3.9, 1.9 Hz, 1 H, NCHH), 5.08–5.16
(m, 2 H, =CH2), 5.18–5.25 (m, 2 H, =CH2), 5.65 (ddd, J = 17.0,
n-hexane/ethyl acetate, 1:7) to give 4o (32%) as a red-orange oil.
1H NMR (400 MHz, CDCl3, 23 °C): δ = 1.82 (s, 3 H, CH3), 2.99 10.1, 7.0 Hz, 1 H, =CH), 5.77–5.88 (m, 1 H, =CH), 6.07 (dd, J =
(ddt, J = 21.5, 2.7, 0.7 Hz, 1 H, CHH-3), 3.12 (dspt, J = 21.5,
1.1 Hz, 1 H, CHH-3), 4.64 (br. s, 1 H, CH-6), 4.92 (dt, J = 17.0,
5.4, 2.7 Hz, 1 H, =CH-4), 7.28–7.38 (m, 5 H, C6H5) ppm. 13C
NMR (100.6 MHz CDCl3): δ = 33.01 (CH2-3), 46.39 (NCH2),
0.8 Hz, 1 H, =CHH), 4.99 (d, J = 10.0 Hz, 1 H, =CHH), 5.48–5.52 61.90 (CH-6), 117.15, 117.40 (2 =CH2), 120.41 (=CH-4), 126.07,
(m, 1 H, =CH-5), 5.64 (ddd, J = 17.0, 10.0, 8.2 Hz, 1 H, =CH),
127.92, 128.62 (C6H5), 132.83, 134.30 (2 CH), 136.63, 137.69 (C-5,
7.17–7.21 (m, 2 H, C6H5), 7.25–7.30 (m, 1 H, C6H5), 7.35–7.41 (m,
C6H5), 168.00 (C=O) ppm. GC–MS (EI, 70 eV): m/z (%) = 239
2 H, C6H5) ppm. 13C NMR (100.6 MHz CDCl3): δ = 21.91 (CH3), (90) [M]+, 238 (88), 224 (22), 212 (69), 210 (25), 196 (25), 171 (72),
37.36 (CH2-3), 65.36 (CH-6), 116.74 (=CH2), 119.23 (=CH-5), 156 (61), 155 (87), 141 (95), 128 (75), 115 (100), 91 (38), 77 (22),
127.29, 127.98, 129.10 (C6H5), 130.93 (=C-4), 136.88 (=CH), 41 (25). IR (film): ν = 3080 (w), 2980 (w), 2920 (w), 1658 (s), 1496
˜
140.95 (C5H6), 167.73 (C=O) ppm. GC–MS (EI, 70 eV): m/z = 213
(w), 1464 (m), 1408 (m), 1260 (m), 1184 (w), 1122 (w), 990 (w), 926
(100) [M]+, 212 (30), 198 (37), 186 (72), 170 (24), 158 (11), 143 (19), (m), 824 (w), 758 (s), 698 (m) cm–1. HRMS (ESI-TOF): calcd. for
130 (23), 104 (16), 94 (34), 91 (19), 79 (80), 77 (62), 51 (17). IR
C16H18NO [M + H]+ 240.1388; found 240.1395.
(film): ν = 3064 (w), 2976 (w), 2912 (w), 1660 (s), 1596 (m), 1494
˜
(؎)-1-Benzyl-5-chloro-6-vinyl-3,6-dihydropyridin-2(1H)-one
The crude product was purified by column chromatography (SiO2,
n-hexane/ethyl acetate, 1:1) to give 4t (83%) as an orange oil. H
NMR (400 MHz, CDCl3, 23 °C): δ = 3.16 (dd, J = 3.7, 3.0 Hz, 2
(4t):
(s), 1428 (s), 1402 (s), 1280 (s), 1240 (w), 1176 (m), 1072 (w), 988
(w), 924 (m), 832 (w), 762 (m), 696 (s) cm–1. HRMS (ESI-TOF):
calcd. for C14H15NNaO [M + Na]+ 236.1051; found 236.1046.
1
(؎)-1-Allyl-5-methyl-6-vinyl-3,6-dihydropyridin-2(1H)-one (4q): The H, CH2-3), 3.78 (d, J = 15.1 Hz, 1 H, NCHH), 4.14 (dt, J = 8.0,
crude product was purified by column chromatography (SiO2, n-
hexane/ethyl acetate, 1:5) to give 4q (27%) as a pale yellow oil. H
2.8 Hz, 1 H, CH-6), 5.31 (d, J = 16.9 Hz, 1 H, =CHH), 5.42 (d, J
= 10.0 Hz, 1 H, =CHH), 5.55 (d, J = 15.1 Hz, 1 H, NCHH), 5.66
1
NMR (400 MHz, CDCl3, 23 °C): δ = 1.72 (q, J = 1.6 Hz, 3 H, (ddd, J = 16.9, 10.0, 8.1 Hz, 1 H, =CH), 5.89 (t, J = 3.9 Hz, 1 H,
CH3), 2.93–2.98 (m, 2 H, CH2-3), 3.35 (dd, J = 15.4, 7.4 Hz, 1 H,
NCHH), 4.03 (dt, J = 8.3, 2.7 Hz, 1 H, CH-6), 4.76 (ddt, J = 15.4,
=CH-4), 7.23 (br. d, J ≈ 6.8 Hz, 2 H, C6H5), 7.26–7.37 (m, 3 H,
C6H5) ppm. 13C NMR (100.6 MHz CDCl3): δ = 32.79 (CH2-3),
4.0, 1.8 Hz, 1 H, NCHH), 5.09–5.29 (m, 4 H, 2 =CH2), 5.48–5.50 46.60 (NCH2), 64.26 (CH-6), 120.54 (=CH-4), 120.58 (=CH2),
(m, 1 H, =CH-4), 5.53 (ddd, J = 17.1, 10.0, 8.8 Hz, 1 H, =CH),
127.22 (=C-5), 127.66, 128.08, 128.78 (C6H5), 133.53 (=CH),
5.70–5.80 (m, 1 H, =CH) ppm. 13C NMR (100.6 MHz CDCl3): δ 136.19 (C6H5), 166.12 (C=O) ppm. GC–MS (EI, 70 eV): m/z (%)
= 19.73 (CH3), 32.24 (CH2-3), 45.94 (NCH2), 64.77 (CH-6), 117.30 = 249 (6) [M + 2]+, 248 (5) [M + 1]+, 247 (21) [M]+, 212 (74), 184
(=CH2), 118.02 (=CH-4), 118.21 (=CH2), 131.07 (=C-5), 132.78, (56), 132 (26), 117 (14), 106 (32), 91 (100), 79 (43), 77 (32), 65 (29),
135.73 (2 =CH), 167.57 (C=O) ppm. GC–MS (EI, 70 eV): m/z = 51 (12), 39 (12). IR (film): ν = 3060 (w), 3032 (w), 2928 (w), 1656
˜
177 (32) [M]+, 176 (43), 162 (52), 150 (55), 153 (21), 134 (25), 110
(56), 93 (30), 91 (21), 79 (100), 77 (33), 41 (39), 39 (24). IR (film):
˜
(s), 1496 (w), 1450 (m), 1408 (m), 1356 (w), 1328 (w), 1246 (m),
1156 (w), 1074 (w), 1016 (w), 936 (w), 816 (w), 704 (s) cm–1. HRMS
ν = 3080 (w), 2976 (w), 2916 (w), 1660 (s), 1462 (m), 1410 (m), (ESI-TOF): calcd. for C14H15ClNO [M + H]+ 248.0842; found
1302 (m), 1258 (m), 1172 (w), 1122 (w), 1066 (m), 992 (m), 926 248.0838.
(m), 798 (w), 736 (w) cm–1. HRMS (ESI-TOF): calcd. for
(؎)-1-But-3-enyl-5-phenylsulfanyl-6-vinyl-3,6-dihydropyridin-2(1H)-
one (4u): The crude product was purified by column chromatog-
C11H16NNO [M + H]+ 178.1232; found 178.1240.
(؎)-1-Allyl-5-chloro-6-vinyl-3,6-dihydropyridin-2(1H)-one (4r): The
crude product was purified by column chromatography (SiO2, n-
hexane/ethyl acetate, 1:1) to give 4r (72%) as a yellow oil. 1H NMR
raphy (SiO2, n-hexane/ethyl acetate, 1:7) to give 4u (81%) as a yel-
low oil that darkened on standing. 1H NMR (400 MHz, CDCl3,
23 °C): δ = 2.15–2.22 (m, 2 H, CH2), 2.74 (dt, J = 13.7, 7.2 Hz, 1
(400 MHz, CDCl3, 23 °C): δ = 3.09 (dd, J = 3.9, 3.2 Hz, 2 H, CH2- H, NCHH), 3.03 (dt, J = 21.2, 2.7 Hz, 1 H, CHH-3), 3.13 (ddd, J
3), 3.34 (dd, J = 15.4, 7.7 Hz, 1 H, NCHH), 4.27 (dt, J = 8.0, = 21.2, 5.6, 1.7 Hz, 1 H, CHH-3), 4.00 (ddd, J = 13.7, 7.8, 6.8 Hz,
2.8 Hz, 1 H, CH-6), 4.78 (ddt, J = 15.4, 4.3, 1.7 Hz, 1 H, NCHH), 1 H, NCHH), 4.13 (ddt, J = 5.6, 2.7, 1.2 Hz, 1 H, CH-6), 4.93–
5.17 (dq, J = 17.1, 1.4 Hz, 1 H, =CHH), 5.22 (dq, J = 10.0, 1.3 Hz,
1 H, =CHH), 5.32 (dt, J = 16.9, 0.9 Hz, 1 H, =CHH), 5.38 (d, J
5.02 (m, 2 H, =CH2), 5.10 (dt, J = 17.0, 0.9 Hz, 1 H, =CHH), 5.23
(d, J = 10.0 Hz, 1 H, =CHH), 5.66 (ddt, J = 17.1, 10.0, 6.8 Hz, 1
= 10.0 Hz, 1 H, =CHH), 5.64 (ddd, J = 16.9, 9.9, 7.9 Hz, 1 H, H, =CH), 5.73 (ddd, J = 17.1, 10.0, 6.8 Hz, 1 H, =CH), 6.09 (dd,
=CH), 5.74 (dddd, J = 17.1, 10.1, 7.8, 4.4 Hz, 1 H, =CH), 5.89 (t,
J = 5.4, 2.7 Hz, 1 H, =CH-4), 7.26–7.40 (m, 5 H, C6H5) ppm. 13C
J = 3.9 Hz, 1 H, =CH-4) ppm. 13C NMR (100.6 MHz CDCl3): δ NMR (100.6 MHz CDCl3): δ = 31.89 (CH2), 33.91 (CH2-3), 44.60
= 32.78 (CH2-3), 46.22 (NCH2), 64.47 (CH-6), 118.18, 120.21 (2 (NCH2), 63.56 (CH-6), 116.82, 117.34 (2 =CH2), 127.51 (C6H5),
=CH2), 120.58 (=CH-4), 127.23 (=C-5), 132.09, 133.61 (2 =CH), 128.25 (=CH-4), 129.31 (C6H5), 130.58 (C-5), 130.70 (C6H5),
165.81 (C=O) ppm. GC–MS (EI, 70 eV): m/z (%) = 199 (5) [M +
2]+, 198 (9) [M + 1]+, 197 (17) [M]+, 196 (26), 182 (18), 170 (25),
162 (58), 134 (16), 130 (23), 113 (13), 79 (100), 77 (54), 51 (17), 41
133.30 (C6H5), 134.11, 135.00 (2 =CH), 167.37 (C=O) ppm. GC–
MS (EI, 70 eV): m/z (%) = 285 (42) [M]+, 284 (55), 244 (100), 230
(15), 216 (12), 187 (65), 176 (27), 154 (14), 111 (25), 109 (21), 106
(39). IR (film): ν = 3084 (w), 2984 (w), 2924 (w), 1660 (s), 1456
(26), 77 (25). IR (film): ν = 3072 (w), 2980 (w), 2936 (w), 1658 (s),
˜
˜
(m), 1408 (m), 1320 (w), 1248 (m), 1184 (w), 1122 (w), 1016 (w),
992 (w), 930 (m), 814 (w), 712 (w) cm–1. HRMS (ESI-TOF): calcd.
for C10H12ClNNaO [M + Na]+ 220.0505; found 220.0510.
1582 (w), 1468 (m), 1440 (m), 1406 (m), 1248 (m), 994 (w), 920
(m), 816 (w), 746 (m), 692 (m) cm–1. HRMS (ESI-TOF): calcd. for
C17H20NOS [M + H]+ 286.1266; found 286.1274.
(؎)-1-Allyl-5-phenyl-6-vinyl-3,6-dihydropyridin-2(1H)-one (4s): The
crude product was purified by column chromatography (SiO2, n-
hexane/ethyl acetate, 1:1) to give 4s (85%) as a yellow oil. 1H NMR
(؎)-5-Chloro-1-phenyl-6-vinyl-3,6-dihydropyridin-2(1H)-one (4w):
The crude product was purified by column chromatography (SiO2,
n-hexane/ethyl acetate, 1:7) to give 4w (84%) as a thick brown oil.
(400 MHz, CDCl3, 23 °C): δ = 3.12 (dt, J = 21.2, 2.7 Hz, 1 H, 1H NMR (400 MHz, CDCl3, 23 °C): δ = 3.16–3.31 (m, 2 H, CH2-
CHH-3), 3.21 (ddd, J = 21.2, 5.4, 1.7 Hz, 1 H, CHH-3), 3.42 (ddq, 3), 4.59 (dm, J = 7.8 Hz, 1 H, CH-6), 5.11 (d, J = 17.1 Hz, 1 H,
5196
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Eur. J. Org. Chem. 2015, 5189–5198

Synthesis of 6-Vinyl-3,6-dihydropyridine-2(1H)-ones
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=CHH), 5.24 (d, J = 10.0 Hz, 1 H, =CHH), 5.75 (ddd, J = 16.9,
10.0, 7.8 Hz, 1 H, =CH), 6.01 (dd, J = 5.1, 3.2 Hz, 1 H, =CH-4),
7.19–7.24 (m, 2 H, C6H5), 7.28–7.33 (m, 1 H, C6H5), 7.37–7.43 (m,
2 H, C6H5) ppm. 13C NMR (100.6 MHz CDCl3): δ = 33.42 (CH2-
3), 69.28 (CH-6), 120.18 (=CH2), 120.80 (=CH-4), 127.54 (=C-5),
127.71, 127.84, 129.28 (C6H5), 133.47 (=CH), 140.43 (C6H5),
166.19 (C=O) ppm. GC–MS (EI, 70 eV): m/z (%) = 235 (26) [M +
2]+, 234 (18) [M + 1]+, 233 (78) [M]+, 206 (36), 198 (21), 143 (24),
[4]
119 (18), 115 (17), 79 (100), 77 (74), 51 (23). IR (film): ν = 3064
˜
(w), 1660 (s), 1596 (w), 1496 (m), 1422 (m), 1402 (s), 1326 (w), 1274
(m), 1256 (m), 1232 (w), 1148 (w), 1074 (w), 1040 (w), 1016 (w),
988 (w), 932 (w), 836 (w), 796 (w), 754 (m), 696 (m) cm–1. HRMS
(ESI-TOF): calcd. for C13H13ClNO [M + H]+ 234.0686; found
234.0688.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, analysis data, and NMR spectra.
Acknowledgments
Financial support from the Polish National Science Center (grant
number N204 219640) and from the Faculty of Chemical Technol-
ogy and Engineering, West Pomeranian University of Technology,
Szczecin is gratefully acknowledged.
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Received: May 12, 2015
Published Online: July 14, 2015
5198
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Eur. J. Org. Chem. 2015, 5189–5198