Addition of novel benzylmagnesium “ate” complexes of BnR2MgLi type to 2-(thio)pyridones and related compounds

Article abstract of DOI:10.1016/j.tet.2016.12.024

Novel benzylation reagents BnR₂MgLi were obtained by mixing benzylmagnesium chloride (BnMgCl) and appropriate organolithium compounds (RLi). As BnR₂MgLi complexes are more nucleophilic than the parent Grignard compound they enabled regioselective C6-addition to electrophilic N-substituted 2-(thio)-pyridones and C4-addition to poorly reactive NH 2-(thio)pyridones in high and good yields, respectively. Thus, the application of these new reagents in efficient synthesis of 6-benzyl-3,6-dihydro- and 4-benzyl-3,4-dihydropyridin-2(1H)-ones is described. The prospect of wider application of BnR₂MgLi in 1,4-addition to other electrophiles, comprising six-membered α,β-unsaturated systems is also presented.

Full text of DOI:10.1016/j.tet.2016.12.024

Tetrahedron xxx (2016) 1e13
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Addition of novel benzylmagnesium “ate” complexes of BnR2MgLi
type to 2-(thio)pyridones and related compounds
a
,
*
a
a
a
ꢀ
ꢀ
Jacek G. Sosnicki , Tomasz Idzik , Aleksandra Borzyszkowska , Emil Wroblewski ,
Gabriela Maciejewska b, Łukasz Struk a
a West Pomeranian University of Technology, Szczecin, Faculty of Chemical Technology and Engineering, Department of Organic and Physical Chemistry, Al.
ꢀ
Piastow 42, Szczecin, 71-065, Poland
b
_
ꢀ
Faculty of Chemistry, Wrocław University of Technology, Wybrzeze Wyspianskiego 27, 50-370, Wrocław, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Novel benzylation reagents BnR2MgLi were obtained by mixing benzylmagnesium chloride (BnMgCl)
and appropriate organolithium compounds (RLi). As BnR2MgLi complexes are more nucleophilic than the
parent Grignard compound they enabled regioselective C6-addition to electrophilic N-substituted 2-
(thio)-pyridones and C4-addition to poorly reactive NH 2-(thio)pyridones in high and good yields,
respectively. Thus, the application of these new reagents in efficient synthesis of 6-benzyl-3,6-dihydro-
and 4-benzyl-3,4-dihydropyridin-2(1H)-ones is described. The prospect of wider application of
Received 18 October 2016
Received in revised form
23 November 2016
Accepted 12 December 2016
Available online xxx
BnR2MgLi in 1,4-addition to other electrophiles, comprising six-membered
also presented.
a,b-unsaturated systems is
Keywords:
Nucleophilic addition
Nitrogen heterocycles
Regioselectivity
© 2016 Elsevier Ltd. All rights reserved.
Organomagnesium compounds
Organolithium compounds
1. Introduction
complexes were obtained first by Wittig and co-workers, already in
1951,8 their wider use in the synthesis, mainly in halogen-
magnesium exchange and in deprotonation reactions,2,7 has been
developed over the last two decades, while their nucleophilic
properties toward addition to C]C double bonds have been rarely
studied.9
Organomagnesium compounds of the general formula RMgX,
called Grignard reagents,1 have made an outstanding career2 since
first reported more than a century ago.3 Although they are
considered as reactive nucleophiles, their use in the reaction with
less reactive electrophiles is still limited. Moreover, such a reaction
is often accompanied by the formation of undesired by-products or
thermal decomposition of RMgX. To overcome these drawbacks,
especially in order to improve the reactivity of Grignard com-
pounds, a few methodologies have been developed in the past
decades. Amongst them the most important are methods based on
the use of additives such as: LiCl,4 N-heterocyclic carbene ligands
(NHC),5 coordinating solvents and ammonium salts,6 which change
the coordination sphere around magnesium. However, other
methods involving various combinations of Grignard reagents with
alkali metals, especially with organolithium reagents, that lead to
“ate” complexes of the type R3MgLi, seem to be also very prom-
ising.7 It is worth emphasizing that although the bimetallic “ate”
During our investigation on the applications of magnesiates in
general synthesis, we found that apart from their use in function-
alisation of 2-methoxypyridines via CeMg bond formation,10 some
“ate” complexes became more nucleophilic towards addition to 2-
(thio)pyridones, in relation to their parent Grignard compounds.
Thus, since 2005 we have known that the nucleophility of allyl-
magnesium chloride and its derivatives could be enhanced by
converting it to “ate” complex by addition of two equivalents of n-
BuLi.11 Allylated products obtained opened up the access to some
polycyclic alkaloids-like piperidinones.11b,11g,12 Recently, nucleo-
philic activity enhancement of vinylmagnesium chloride by its
conversion to “ate” complex using MeLi has also been proved.13
Encouraged by successful enhancement of nucleophilic activity
of allylMgCl and vinylMgCl by their conversion to the corre-
sponding allyl- and vinylmagnesiate compounds,11e13 we were
prompted to examine of nucleophilicity of BnMgCl towards addi-
tion and the possibility to improve its activity by converting it to
* Corresponding author.
E-mail address: sosnicki@zut.edu.pl (J.G. Sosnicki).
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http://dx.doi.org/10.1016/j.tet.2016.12.024
0040-4020/© 2016 Elsevier Ltd. All rights reserved.
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Please cite this article in press as: Sosnicki JG, et al., Addition of novel benzylmagnesium “ate” complexes of BnR2MgLi type to 2-(thio)pyridones
and related compounds, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.12.024

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J.G. Sosnicki et al. / Tetrahedron xxx (2016) 1e13
2
formation of two regioisomeric addition products 2 and 3, the
following conclusions can be drawn. 1) In general, the reactions
with N-substituted derivatives led to the addition product in low or
moderate yields, except for NeMe 2-thiopyridone whose applica-
tion allowed getting the main product (2g) in 90%. However, such a
high yield is restricted to the derivative with a small substituent at
the nitrogen atom because N-Bn derivative (1h) (with slightly
larger substituent) gave much lower yield (52%). This results in-
dicates that for these derivatives the steric factor more influenced
the reactivity than electronic effect. The same effect was observed
for 2-pyridones: the use of NeMe derivative (1a) led to the total
yield of 75%, while N-Bn compound (1b) gave 35% yield at the same
conditions. 2) Conduction of the reaction at a low temperature
(ꢁ80 ꢀC), in general leads to incomplete conversion of the sub-
strate. 3) BnMgCl is not reactive enough to get added to NMgCl- or
NLi-substituted derivatives because these substrates remain un-
changed. 4) The formation of 6-addition products (2) is preferred,
albeit the distribution of 4- and 6-benzyl- regioisomers depends on
the substituents present at the nitrogen atom and at the ring.
For the next step of the study we checked the influence of the
addition of two equivalents of organolithium compounds on the
nucleophility of BnMgCl, assuming the BnR2MgLi complex forma-
tion. For our first tests we used the commercially available N-
methyl-2-pyridone (1a) as an electrophile and MeLi (3.0 M in
diethoxymethane), n-BuLi (2.5 M in hexane), sec-BuLi (1.4 M in
cyclohexane) and PhLi (1.8 M in dibutylether) as organolithium
compounds. As a result we found that the use of sec-BuLi at ꢁ80 ꢀC
led to the best yield of 2a (81%, Table 2, entry 3) with high C-6
regioselectivity of addition (>99: 1) and complete conversion of the
substrate. [For comparison, the corresponding reaction with sole
Grignard reagent led to benzylated product at the ratio 93: 7 and
the total yield of 64% (Table 1).] We also observed that further
improvement in the yield could be gained by scaling up the reac-
tion. Applying an almost eight times larger scale permitted
obtaining the product 2a in 90% yield (Table 2, entry 4). In order to
save ligands we have tried to activate BnMgLi using sec-BuLi with
less than twofold molar excess (in equimolar ratio and in one and a
half-fold molar excess). These results, showed the lowering of the
yield of benzylated products of about 17% and confirmed the ne-
cessity of application of two equivalents of sec-BuLi.
Subsequently, the most effective benzyl magnesiate (Bnsec-
Bu2MgLi þ LiCl)18 was tested in the reactions with N-substituted 2-
(thio)pyridones (Scheme 1), firstly with seven substrates 1b-1h,
used earlier in the reaction with sole BnMgCl, then with other ten
2-(thio)pyridones (1k-1t). The outcome of the first group of re-
actions confirmed higher activity of benzylmagnesiate reagent in
relation to BnMgCl. The products were obtained in higher yields
and in improved regioselectivity towards 6-benzylated product.
Only N-Ph derivative 1f led to a regioisomeric ratio similar to that
obtained with BnMgCl. The other 10 substrates 1k-1t also led to the
addition products in high yields and good C-6 regioselectivity. As
far as regioselectivity is concerned, it should be also noted that in
the reaction with 4-Me substituted derivatives 3o-3q the single 6-
benzyl adduct was obtained, while in the reaction with 6-Me 2-
pyridone 1t two products were formed. One was the major 4-
benzyl derivative 3t, and the second was the minor 6-benzyl-6-
methyl-substituted derivative 2t. Formation of 2t indicated the
great tendency of the addition of benzyl magnesium “ate” complex
to 2-pyridones at C-6 positon, even if it is required to overcome the
electron donating effect of the methyl group, which is present at
this position. Besides, the reaction with N-(1-phenyl-ethyl)-2-
pyridone 1s, confirmed above observed trend of increasing
amounts of 4-benzylated regioisomer with increasing the size of N-
substituent, because in this reaction excess of 3s was formed.
The first attempt to use Bnsec-BuMgLi þ LiCl in the reaction with
Fig. 1. Benzyl functionalized piperidines as benzomorphans precursors and biologi-
cally active compounds.
“ate” complexes. For assessment of nucleophilic activity of BnMgCl
and its magnesium “ate” complexes we decided to use substituted
and unsubstituted 2-pyridones and some 2-thiopyridones, simi-
larly to those used in the previous studies. Surprisingly, on the basis
of the scientific literature we established that 2-pyridones and 2-
thiopyridones had not been hitherto subjected to an addition re-
action with benzyl Grignard reagents and their “ate” complexes.
These electrophiles seemed to be perfect models for such studies
because of their broad range of reactivity, covering the less reactive
NeH(Li) and the more reactive N-R substituted derivatives. Besides,
because the substituents attached to the ring influenced the reac-
tivity of both NH and NR species,13 the additional advantage of 2-
(thio)pyridones as electrophiles is the possibility of tailoring of
their electrophilic power.
Apart from the assessment of nucleophility of organo-
magnesium compounds, the choice of 2-pyridones and 2-thio-
pyridones as electrophiles could be important also from the syn-
thetic point of view, because the predicted 6-benzyl and or 4-
benzyl-functionalized dihydropyridin-2-ones as benzylated prod-
ucts, could be subsequently transformed into benzyl functionalized
piperidine derivatives, showing not only biological activities, but
also high synthetic usefulness, especially toward benzomorphans,
e.g. normetazocine14 (Fig. 1). As regards the biologically active de-
rivatives, benzylpiperidine moiety is known to be present in such
compounds as e.g. NMDA receptor antagonists, Ifenprodil,15 Ro 67-
8867,16 their derivatives and immunosuppressant FR90148317
(Fig. 1).
Thus, in this paper we describe the results of comparing the
nucleophilic activity of BnMgCl and novel benzyl magnesium “ate”
complexes of BnR2MgLi type in addition reaction to 2-(thio)pyr-
idones, which could lead to valuable benzyl-substituted dihy-
dropyridin(e)-2(1H)-(thi)ones.
2. Results and discussion
For the first stage in our study we checked the level of activity of
commercially available benzyl Grignard reagent (BnMgCl) in re-
actions with NMe, NBn, NPh and NH substituted 2-pyridones,
including a few 2-pyridones substituted in the ring, and with NBn,
NMe and NH substituted 2-thiopyridones. For NR derivtives, the
reactions were conducted at 0 ꢀC and at ꢁ80 ꢀC, while for NH de-
rivatives the reactions were performed only at 0 ꢀC. For NH de-
rivatives two approaches were applied. The first approach was to
use up to 3-fold excess of BnMgCl, while the second one included
preliminary conversion of NH into NLi salt followed by addition of
BnMgCl. The conditions are specified in Table 1, which also presents
the results. On the basis of the results, which revealed the
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Please cite this article in press as: Sosnicki JG, et al., Addition of novel benzylmagnesium “ate” complexes of BnR2MgLi type to 2-(thio)pyridones
and related compounds, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.12.024

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J.G. Sosnicki et al. / Tetrahedron xxx (2016) 1e13
3
Table 1
The attempts at addition of benzylmagnesium chloride to 2-(thio)pyridones 1.
Entry
1a/2/3
R1
R2
X
BnMgClb (equiv.)
Temp.[ꢀC]/
Time [h]
Conversion
of 1 [%]c
Isolated yield [%]
2: 3 (total)
2:3
ratioc
1
2
3
4
5
6
7
8
a
a
bd
bd
c
Me
Me
Bn
Bn
Bn
Bn
Bn
Bn
Ph
Me
Bn
Bn
Hi
H
H
H
H
4-Me
4-Me
5-Me
5-Cl
H
H
H
H
H
H
H
H
O
O
O
O
O
O
O
O
O
S
S
S
O
O
S
1.3
1.3
1.2
1.5
1.5h
1.5h
1.5
1.5
1.2h
1.5
1.5
1.5
2.0
3.0
3.0
1.2
0/1.5
ꢁ80/1.5
0/1.5
ꢁ80/1.5
0/1.5
ꢁ80/1.5
0/1.5
0/1.5
0/1.5
0/0.75
0/1
>99
88
97
90
62f
56f
99f
99
99
>99
>99
65
0
69: 6 (75)
59: 5 (64)
35: -e (35)
54: -e (54)
38f: 0f (38)
51f: 0f (51)
39e,f: 22e,f (61)
20: 14 (34)
38: 32 (70)
90: -e (90)
52: 0 (52)
26: 4 (30)
0
91:9
93:7
93:7
92:8
>99:1
>99:1
64:36
55:45
55:45
97:3
ek
c
d
e
fg
g
h
h
i
i
j
j
9
10
11
12
13
14
15
16
ꢁ80/3
79:21
e
0/2
Hj
0/2
0/1.7
0/1.75
0
0
~5
0
0
e
Hi
e
Hj
S
tracese
e
a
2.2 mmol of substrate was used unless stated otherwise.
2.0 M solution in THF was used unless stated otherwise.
Assigned by 1H NMR of crude reaction mixture.
2.7 mmol of substrate was used.
not isolated in pure state due to not separable by-products.
assigned by 1H NMR using an internal reference.
8.7 mmol of substrate was used.
b
c
d
e
f
g
h
i
1.0 M solution in 2-MeTHF was used.
NH 2-(thio)pyridone was initially treated with 1 eq. of BnMgCl in THF in order to change NH into NMgCl.
NH 2-(thio)pyridone was initially treated with 1 eq. of MeLi in DEE in order to change NH into NLi.
Could not be assigned.
j
k
NLi derivative (1iLi) did not lead to a positive result (Table 3, entry
1). However, applying MeLi in diethoxymethane (DEM) instead of
sec-BuLi enabled 94% conversion of the substrate and allowed
obtaining product 3i in 45% yield (Table 3, entry 3). Thus,
BnMe2MgLi þ LiCl reagent were then used in the reaction with NLi
salts of 2-pyridones 1u-x and 2-thiopyridones 1j, 1y, substituted in
the ring (Scheme 2). As a result only 4-methyl (1w) and 6-methyl
(1x) 2-pyridones were unreactive, while 5-Cl (1u) and 5-Ph (1v)
2-pyridones led to 4-benzylated products in 69% and 40% yields,
respectively. However, the most efficient were the reactions with
NLi 2-thiopyridones 2j and 2y because they led to 4-benzylated
products in about 80% yields. As far as regioselectivity is con-
cerned all reactions with NLi 2-(thio)pyridones proceeded regio-
selectively at C-4.
Table 2
The optimization of benzylation of N-substituted 2-pyridones by using novel ben-
zylmagnesium “ate” complexes. The effect of variation of organolithium reagents on
the efficiency of benzyl addition.
The results obtained in all the above reactions proved that the
nucleophility of BnMgCl could be successfully enhanced by con-
verting it into magnesium “ate” complexes using organo-lithium
compounds and that the treatment of 2-(thio)pyridones with a
suitable complex is the excellent method to obtain regioselectively
N-R substituted 6-benzylated 3,6-dihydropy-ridin(ethi)ones 2 and
NeH substituted 4-benzylated 3,4-dihydro-pyridin(ethi)ones 3.
The successful syntheses of NeH 4-benzyl-substituted isomers 3
are particularly important because these compounds cannot be
synthesized using a sole Grignard reagent. Furthermore, NH 4-
benzyl-3,4-dihydropyridin-2(1H)-ones could be potentially N-
alkylated, since several methods of N-alkylation of such com-
pounds have been described in scientific literature.19,20 This pro-
cedure may allow obtaining N-alkylated isomers 3, which are
hardly obtainable by addition to N-alkylated 2-pyridones. In order
to confirm such a possibility we have successfully tested our own
N-alkylation procedure, using selected NH derivatives, applying n-
BuLi as the base and MeI, BnBr as electrophiles. The results are
presented in Scheme 3.
Entry
RLi
(equiv.)
Temp.[ꢀC]/
Time [h]
Conversion
of 1a [%]c
Isolated yield [%]
2a: 3a (total)
2a: 3a
ratio
1a,b
2a,b
3a,b
4d,e
5a,b
6a,b
n-BuLi
n-BuLi
sec-BuLi
sec-BuLi
MeLi
0/1.5
>99
>99
>99
>99
>99
~80
71: 6 (77)
61: 0 (61)
81: 0 (81)
90: 0 (90)
74:0 (74)
(44%)f,g
92: 8c
ꢁ80/0.5
ꢁ80/0.5
¡80/1.5h
ꢁ80/0.5
ꢁ80/1.5
>99: 1c
>99: 1c
99: 1c
>99: 1c
(92: 8)g
PhLi
a
2.2 mmol of substrate was used.
b
c
d
e
f
2.0 M solution of BnMgCl in THF was used.
Assigned by 1H NMR.
19 mmol of substrate was used.
1.0 M solution of BnMgCl in 2-MeTHF was used.
Not isolated in pure state due to not separable by-products.
Assigned by GC-FID.
g
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4
J.G. Sosnicki et al. / Tetrahedron xxx (2016) 1e13
Table 3
The attempts at benzylation of NLi-substituted 2-pyridones using benzylmagnesium
“ate” complexes.
Entrya
RLi
Temp.[ꢀC]/
Time [h]
Conversion
of 1i [%]b
2i: 3i Isol yield [%]
2i: 3i
ratiob
1
2
3
sec-BuLi
0/2
22/1
0/2
22/1
0/1
~50
79
ec
e
MeLi
(in DEE)
MeLi
0: 30
0: 45
>1: 99
>1: 99
94
(in DEM)
22/2
a
4.4 mmol of substrate was used.
Assigned by 1H NMR of crude reaction mixture.
The product of addition of sec-BuLi was detected by GC-MS and NMR
b
c
spectroscopy.
dihydropyridin-2(1H)-one), which was obtained from
b,
g-unsatu-
rated d-lactam 2f by isomerisation using DBU; NH a,b-unsaturated
d
-thiolactam 8,11c which before the benzylation was converted into
NLi derivative (8Li); N-benzyl pyridin-4(1H)-one (10)21; cyclohex-
2-enone (12). All these compounds were treated with Bnsec-
Bu2MgLi þ LiCl at ꢁ80 ꢀC and with BnMgCl at 0 ꢀC and also
at ꢁ80 ꢀC without any additives.
The studies, the results, which are presented in Scheme 5,
showed that a,b-unsaturated d-lactam 6 decomposed in the reac-
tion with BnMgCl, while with benzylmagnesiate it provided 1,4-
addition product 7 in high yield, albeit at a low trans: cis (56: 44)
diasteroselectivity. The addition of Grignard compounds to
Scheme 1. Benzylation of N-substituted 2-(thio)pyridones by using benzyl-
a
magnesium “ate” complexes Bnsec-Bu2MgLi. e 2.2 mmol of substrate 1, 2.0 M solu-
tion of BnMgCl in THF and 1.4 M solution of sec-BuLi in cyclohexane were used unless
stated otherwise; ꢂ99% of substrate conversion was obtained; isolated yields are
b
given; structure of major product is presented; e 8 mmol of substrate was used; c e
d
assigned by 1H NMR of crude reaction mixture; e 1.0 M solution of BnMgCl in 2-
e
f
MeTHF was used; - 1.5 equiv. of Bnsec-Bu2MgLi þ LiCl was used; e 92: 8 mixture
g
h
of diastereoisomers; e 6: 4 mixture of diastereoisomers; e 74: 26 mixture of di-
astereoisomers (assigned from 13C inverse gated decoupled spectra);
e
80: 20
i
mixture of diastereoisomers (assigned from 13C inverse gated decoupled spectra);
not isolated in pure state due to not separable by-products.
-
j
Our next objective was to determine whether or not the appli-
cation of benzylmagnesium “ate” complex could lead to 6-benzyl-
3,3-dialkylated 3,6-dihydropyridin-2(1H)-ones in “one pot” syn-
thesis, similarly to the reactions presented earlier for allymagne-
sium “ate” complexes.11d,11g Thus, following the addition of Bnsec-
Bu2MgLi þ LiCl to N-methyl-2-pyridone (1a), more than 2-fold
excess of the electrophile was added. The results presented in
Scheme 4 show that this protocol was successful, although the
double allylation led to 3,3-diallylated product 4a with lower
regioselectivity, yielding also 3,5-diallylated product 5a.
Scheme 2. The benzylation of NLi-substituted 2-(thio)pyridones using
a
BnMe2MgLi þ LiCl. e NLi derivatives were prepared from corresponding NH sub-
Finally, we evaluated the behavior of the novel benzylmagne-
sium “ate” complex Bnsec-Bu2MgLi þ LiCl and compare it to that
of BnMgCl, in the addition reactions to six-membered electrophiles,
related to 2-(thio)pyridones (Scheme 5). As model compounds we
b
strates by adding 1 eq. of MeLi (3.0 M solution in DEM); - 4.4 mmol of substrate 1,
c
2.0 M solution of BnMgCl in THF and 3.0 M solution of MeLi in DEM were used;
-
assigned by 1H NMR of crude reaction mixture. Conversion of substrate is given in the
square brackets; d e 1.0 M solution of BnMgCl in 2-MeTHF was used; e e 12.9 mmol of
f
g
substrate was used; e 1,4 mol excess of BnMe2MgLi was used; e 1,3 mol excess of
chose:
a,
b-unsaturated
d-lactam
6
(6-benzyl-1-phenyl-5,6-
h
BnMe2MgLi was used.; e reaction was conducted 1,5 h at 0 ꢀC.
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Please cite this article in press as: Sosnicki JG, et al., Addition of novel benzylmagnesium “ate” complexes of BnR2MgLi type to 2-(thio)pyridones
and related compounds, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.12.024

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J.G. Sosnicki et al. / Tetrahedron xxx (2016) 1e13
5
to open-chain
a
,b
-unsaturated amides has already been described.9
Subsequently, the addition to N-lithiated thiolactam 8 was
studied. Open-chain -unsaturated thioamides are known to
react with Grignard reagents without additives to give 1,4-
adducts,23 however,
-unsaturated thiolactams have not been
hitherto submitted to the reactions with Grignard reagents or with
magnesiates. The results (Scheme 5) showed that in the reaction of
8Li with BnMgCl, the addition product was formed in 65% yield,
with significant preference of trans diastereoisomer (86: 14), but a
more striking observation was that the reaction with benzyl mag-
nesiate (Bnsec-Bu2MgLi þ LiCl) led to much better results, because
the product was isolated in 95% yield and the trans-diaster-
eselectivity was almost complete (>99:1).
a,b
a,b
Scheme 3. The N-alkylation of NH 4-benzyl-3,4-dihydropyridin-2(1H)-ones.
Scheme 4. The benzylation of NeMe 2-pyridone 1a by using benzyl-magnesium “ate”
complexes Bnsec-Bu2MgLi þ LiCl followed by double 3,3-alkylation.
Similarly to the above presented reactions, benzylation of N-
benzyl-4-pyridone (10) using benzyl magnesiate was again more
efficient based on yield than benzylation with BnMgCl, because it
provided product 11 in 84% yield, while treatment of the same
substrate (10) with sole BnMgCl yielded product 11 in 65%.
The last electrophile tested - cyclohex-2-enone (12), is known to
be the most reactive toward addition upon treatment with
Grignard reagents. However, 1,4-addition is highly effective in the
presence of copper (I) salts,24 otherwise, it provides mainly 1,2-
addition products.25 Surprisingly, in two attempts of addition of
BnMgCl to 12, performed without any additives, only 1,4-addition
product 13 was obtained in high yield (81e85%) (Scheme 5). The
results obtained by using benzyl magnesiate are also interesting.
The first attempt at the addition of Bnsec-BuMgLi þ LiCl led to two
1,4-addition products: one with added benzyl group (13) and the
other with attached sec-butyl group (14), (obtained as a mixture of
diastereoisomers). The second attempt, performed using PhLi
instead of sec-BuLi (for benzyl magnesiate formation) provided
benzylated product 13 in high yield (91%). Although in the latter
reactions the use of magnesiate only slightly improved the yields,
these results shed much light on the application of magnesiate as
nucleophiles. Firstly, it proved the formation of Bns-Bu2MgLi
complex at the low temperature (ꢁ80 ꢀC). This is evidenced by 1,4-
addition of sec-butyl, indicating that after mixing of sec-BuLi with
BnMgCl, sec-butyl nucleophile is no further a moiety of sec-BuLi
compound, because sec-BuLi typically undergoes 1,2-addition to
12,26 what was also confirmed by us. Secondly, these results show
that in the case of reactive electrophiles it is possible to manipulate
the ligands at the magnesium atom in order to adjust the reactivity
of the magnesiate with respect to the reactivity of the incoming
electrophile.
With respect to the ability of aryl or alkyl groups transfer to
electrophilic site, it should be noted that in the benzylation re-
actions using benzyl magnesiates the transfer of the benzyl group
from among all the ligands present at magnesium was preferred.
Similarly preferred movements of allyl and vinyl group were
observed in allylation11 and vinylation13 reaction concerning
addition of the appropriate magnesiates to C]C bonds. On the
other hand, on the basis of our previous and present studies we
could conclude that the least labile were Me and Ph groups, derived
from MeLi and PhLi, respectively. Identification of Me and Ph
groups as “dummy ligands” is highly consistent with the findings of
Ishihara and co-workers, who studied the preference of transfer of
alkyl and phenyl groups in addition to ketone C]O bonds.27 The
reasons for the preference of transfer of one group from mixed
magnesiates has not been fully explained as yet and we believe that
our further investigation in this area will be helpful to explain this
phenomenon in due course.
Scheme 5. The attempts at benzylation of some other six-membered electrophiles by
using BnMgCl and Bnsec-Bu2MgLi.
unactivated lactams are described within scientific literature,
however these reactions were successfully conducted only in the
presence of copper salts and/or using TMSCl.22 Besides, the suc-
cessful 1,4-addition to lactam 6 using benzyl magnesiate is the first
example of addition of magnesiate to a,b-unsaturated d-lactams,
while the addition of a mixture of Grignard compounds with MeLi
The structures of all compounds were elucidated with the aid of
routine 1D NMR (1H, 13C, 13C-DEPT-135) and 2D NMR experiments
(1H, 1H COSY, 13C, 1H COSY). While the structures of isomers 2 and 3
could be easily distinguished on the basis of their characteristic
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Please cite this article in press as: Sosnicki JG, et al., Addition of novel benzylmagnesium “ate” complexes of BnR2MgLi type to 2-(thio)pyridones
and related compounds, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.12.024

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J.G. Sosnicki et al. / Tetrahedron xxx (2016) 1e13
6
chemical shifts (eg. for vinyl protons) and by finding their coupling
partners, the structures of 5a as well as configurations and
preferred conformations of separable lactams 7cis and 7trans and
thiolactam 9trans were additionally assigned by a rough confor-
mational analysis of the coupling constants dependence on the
torsion angle. All NMR spectra were recorded in CDCl3 solutions,
additionally for compound 9trans perdeuterated toluene was used
in order to get better signal separation.
On the grounds of our experience gained from previously per-
formed analysis of 4,6-disubstituted lactams and thio-lactams,28
we established the cis configuration and the equato-rialy-
equatorial conformation of 4,6-dibenzyl lactams 7cis (Scheme 5)
on the basis of the coupling constants of axially oriented hydrogen
atom H-5ax (the signal at 1.34 ppm). This resonance signal is
composed of two large vicinal coupling constant (11.7 Hz), indi-
cating antiperiplanar relation of this hydrogen atom with two
axially oriented vicinal hydrogen atoms: H-4ax and H-6ax, proving
the equatorial position of both benzyl substituents. In the 1H NMR
spectrum of 7trans, the signal of H-5ax atom (resolved as ddd) with
one large (12.1 Hz) and one medium (5.6 Hz) vicinal coupling
constant, indicating that one vicinal hydrogen atom adjacent
thereto is axially and the second is equatorially oriented. Well
separated signal of H-3ax (dd, J ¼ 17.6, 11.2 Hz) helped to settle
definitively that hydrogen atom H-4 was axial, thus, H-6 was
equatorially oriented. These findings imply that the benzyl sub-
stituent at C-4 is equatorial and that at C-6 is axial.
Conformational analysis led us to the conclude that compound 9
has trans a configuration with 6-butyl substituent positioned
axially and 4-benzyl moiety located equatorially (Scheme 5). This
conclusion was supported by a broad multiplet observed in the 1H
NMR spectrum (in the region of 1.62e1.74 ppm), corresponding to
the axial hydrogen atom at C-4. Judging from cross peaks found in
1H, 1H COSY spectra this proton is coupled with two hydrogen
atoms attached at C-3, which gave the resonance signals: at
2.42 ppm as dd (J ¼ 18.3, 8.3 Hz) and at 2.85 ppm as dd (J ¼ 18.3,
4.9 Hz). The large value of vicinal coupling constant (8.3 Hz) in-
dicates the axial orientation of the first mentioned proton at C-3
and the axial orientation of its vicinal partner at C-4, thus benzyl
group at C-4 must be equatorial. Furthermore, the configuration at
C-6 was established by extraction of coupling constatnts from the
signal located at 2.89 ppm, which was assigned to CH-6 proton. This
multiplet, resolved as quintet of doublet with vicinal coupling
constant of 6.0 Hz being a result of coupling with vicinal protons of
butyl group and that of 3.2 Hz which is a result of coupling with
proton at C-5. The small value of the latter coupling proved the
equatorial position of hydrogen atom at C-6, thereby indicating the
axial orientation of the butyl group.
2 equiv. of organolithium compounds. It constitutes an efficient
benzylating reagent, capable of addition to N-substituted 2-(thio)
pyridones in high yields and high C-6 regioselectivity as well as to
the poorly reactive NeLi derivatives, yielding regioselectively C-4
benzylated product in good yields. The successful addition of
benzyl magnesiate to NeLi 2-(thio)-pyridones seemed to be the
most important result because these derivatives are resistant upon
treatment with sole benzylmagnesium chloride. Apart from the
observed higher nucleophility of benzyl magnesiate in comparison
to that of the parent Grignard reagent (BnMgCl), the simplicity of
the experimental procedure, enabling an easy access (in a few gram
scale) to 6-benzyl-3,6-dihydropyridin-2(1H)-ones and to 4-benzyl-
3,4-dihydropyridin-2(1H)-ones, which can be employed in the
synthesis of alkaloids-like compounds are equally important fea-
tures of this methodology. The scaffold synthesis of benzomorphan
derivatives using 6-benzyl derivatives is currently underway in our
group. Furthermore, successful extension of the use of the benzyl
magnesiate reagent in the addition reactions to 4-pyridone, a,b-
unsaturated (thio)lactams and cyclohex-2-enone indicates its
future potential.
4. Experimental section
4.1. General
Melting points were determined on a Boetius hot stage appa-
ratus. 1H, 13C NMR spectroscopic measurements were performed on
a Bruker DPX 400 spectrometer equipped with an 5 mm 1H/BB -
inverse probehead, operating at 400.1 and 100.6 MHz, respectively.
TMS was used as internal reference and spectra were acquired in
5 mm probes.
For resolving of multiplets in 1H NMR spectra ACD/SpecManager
program (version 12.01) was used. For detailed peak assignments,
2D spectra were acquired using standard Bruker software (COSY,
HETCOR). The standard abbreviation for multiplicities were used
(s ¼ singlet, d ¼ doublet, t ¼ triplet, q ¼ quartet, quint ¼ quintet,
m
¼
multiplet, sxt
¼
sextet, spt
¼
septet, etc.). Gas
chromatography-mass spectrometry (GC-MS) measurements were
carried out on a Hewlett-Packard instrument model HP 6890
equipped with a mass detector HP 5973 and on a Agilent 7820A GC
system equipped with a mass (Agilent 5977E MSD) and FID de-
tectors. Infrared spectra were taken with a Specord M80 instrument
and Alfa spectrometer with ATR-adapter (Bruker). The standard
abbreviation for IR band intensities description were used (s e
strong, m e medium, w e weak). HRMS analyses (ESIþ) were
performed on a Waters LCT premier XE (TOF) using acetonitrile as
solvent.
The structure of by-product 5a was configurationally the same
as that of 3,5-diallylated by-products obtained earlier by using
allylmagnesium “ate” complex.11d Compound 5a also has sub-
stituents (allyl at C5 and benzyl at C6) oriented trans to each other.
Similarly as before, this configuration was assigned on the basis of
the lack of cross-peak between CH5 vs CH6 protons in the 1H, 1H
COSY spectra, indicating that these hydrogen atoms are weakly
coupled. The refination from Lorentzian to Gaussian resolution
enhancement spectra allowed concluding that this vicinal coupling
constant is 0.9 Hz. According to the Haasnoot et al. equation29 this
value corresponds to CH5eCH6 dihedral angle of 82ꢀ and is in good
agreement with the angle of 87ꢀ present in the structure of 5a
optimized by MM2 calculations.30
Reactions in tetrahydrofuran (THF) solution were performed
under argon in flame-dried flasks and liquid components were
added from a syringe. THF was purified in argon atmosphere ac-
cording to a standard procedure prior to use. Products were puri-
fied by flash column chromatography on silica gel (63e200 mm,
Merck) using mixture of n-hexane and ethyl acetate as eluent or
dichloromethane.
4.2. Compounds and reagents
n-BuLi (2.5 M in hexane), sec-BuLi (1.4 M in cyclohexane), PhLi
(1.8 M in dibutyl ether), MeLi (3.0 M in diethoxymethane) and MeLi
(1.6 M in diethylether), BnMgCl (2.0 M in THF), BnMgCl (1.0 M in 2-
MeTHF) were purchased from Aldrich.
3. Conclusions
Compounds: 1-methylpyridin-2(1H)-one (1a), NH-pyridin-
2(1H)-one (1i), pyridine-2(1H)-thione (1j), 5-chloropyridin-2(1H)-
one (1u), 6-methylpyridin-2(1H)-one (1w) and 4-methylpyridin-
2(1H)-one (1x) and supplied from commercial sources. Compunds:
In conclusion we have demonstrated that benzylmagnesium
“ate” complex can be prepared by mixing of 1 equiv. of BnMgCl and
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and related compounds, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.12.024

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J.G. Sosnicki et al. / Tetrahedron xxx (2016) 1e13
7
5-chloro-1-benzylpyridin-2(1H)-one (1e),11g 1-phenylpyridin-
2(1H)-one (1f),31 1-methylpyridine-2(1H)-thione (1g),11c 1-
benzylpyridine-2(1H)-thione (1h),11c 4-methyl-1-phenylpyridin-
2(1H)-one (1o),31 1-allyl-4-methylpyridin-2(1H)-one (1p),11g 1-(1-
phenylethyl)-pyridin-2(1H)-one (1s),32 1-benzyl-6-methylpyridin-
127.86, 128.24,128.71,130.00,135.82, 136.93 (2 ꢃ C6H5), 168.91 (C]
O); GC-MS: (EI, 70eV): m/z ¼ 277 (3), [Mþ], 186 (100), 91 (98), 65
(17); IR (KBr pellet):
n
¼ 3028 (w), 1640 (s), 1628 (s), 1494 (w), 1472
(m), 1456 (m), 1444 (w), 1406 (w), 1368 (w), 1344 (w), 1316 (w),
1262 (m), 1188 (w), 1164 (w), 1032 (w), 968 (w), 750 (w), 726 (m),
704 (m), cmꢁ1. HRMS (ESI-TOF): calcd. for C19H20NO 278.1545
[MþH]þ; found 278.1543.
2(1H)-one
(1t),32
5-phenylpyridin-2(1H)-one
(1v),
1-
benzylpyridin-4(1H)-one (10)33 were obtained according to pro-
cedure described earlier.
4.3.3. ( )-1,6-dibenzyl-4-methyl-3,6-dihydropyridin-2(1H)-one
(2c)
4.3. Typical procedure for the addition of Bns-Bu2MgLi to N-
Substituted 2-(Thio)pyridones 1 and compounds 6, 10, 12
Yield 90%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 5: 1) gave colorless solid, m.p.
103e104 ꢀC (petroleum ether, ethyl acetate). 1H NMR (400 MHz,
A stirred solution of BnMgCl (2.0 M in THF; 2.6 mmol, 1.33 mL or
1.0 M in 2-MeTHF; 2.6 mmol, 2.66 mL) in dry THF (10 mL) in a
Schlenk flask was cooled to 0 ꢀC under argon, and s-BuLi (1.4 m in
cyclohexane; 5.3 mmol, 3.8 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 solution containing lithium benzyldi(sec-butyl)
magnesate and LiCl was then transferred by syringe to a precooled
(ꢁ80 ꢀC) solution of N-substituted 2-pyridone or 2-thiopyridone or
compounds 6, 10, 12 (2.2 mmol) in THF (25 mL) prepared in another
Schlenk flask. The resulting solution was stirred for
45 min at ꢁ80 ꢀC (TLC control). After this time, the mixture was
carefully quenched with saturated aqueous NH4Cl (5 mL), then it
was allowed to warm up to room temp. and diluted with water (ca.
10 mL). The aqueous layer was extracted with ethyl acetate
(3 ꢃ 30 mL), and the combined organic layers were dried with
MgSO4. The mixture was filtered, and the solvents were evaporated
under reduced pressure. The crude product was purified by column
chromatography on silica gel using a mixture of appropriate sol-
vents to give the desired product.
CDCl3, 23 ꢀC):
d
¼ 1.63 (s, 3 H, 4-CH3), 2.02 (d, J ¼ 21.0 Hz, 1 H, CHH-
3), 2.57 (dd, J ¼ 21.0, 1.2 Hz, 1 H,CHH-3), 2.78 (dd, J ¼ 13.4, 3.4 Hz,
1 H, 6-CHH), 2.95 (dd, J ¼ 13.4, 6.4 Hz, 1 H, 6-CHH), 3.99 (d,
J ¼ 15.4 Hz, 1 H, NCHH), 4.00e4.05 (m, 1 H, CH-6), 5.34 (ddq, J ¼ 4.6,
3.0, 1.5 Hz, 1 H, ¼CH-5), 5.64 (d, J ¼ 15.1 Hz, 1 H, NCHH), 6.99e7.06
(m, 2 H, C6H5), 7.21e7.36 (m, 8 H, 2 ꢃ C6H5) ppm. 13C NMR
(100.6 MHz, CDCl3):
d
¼ 21.60 (4-CH3), 36.84 (CH2-3), 39.26 (6-
CH2), 46.48 (NeCH2), 57.27 (CH-6), 119.37 (¼CH-5), 126.66,
127.38, 127.85, 128.07, 128.65, 130.07 (2 ꢃ C6H4), 132.46 (¼C-4),
135.97, 137.04 (2 ꢃ C6H5), 169.02 (C]O) ppm. GC-MS (EI, 70eV): m/
z ¼ 291 (<1), [Mþ], 216 (63), 200 (87), 91 (100), 65 (11). IR (ATR):
n
¼ 3063 (w), 3026 (w), 2973 (w), 2933 (w), 2887 (w), 1627 (s), 1493
(w), 1473 (m), 1453 (m), 1441 (m), 1405 (m), 1359 (w), 1340 (w),
1291 (w), 1262 (w), 1189 (w), 1152 (w), 1087 (w), 1029 (w), 963 (w),
921 (w), 803 (m), 760 (m), 736 (m), 718 (m), 698 (s), 638 (m), 608
(w), 575 (w), 568 (w), 496 (m), 439 (w), 425 (m) cmꢁ1. HRMS (ESI-
TOF): m/z [MþþH] calcd for C20H22NO, 292.1701; found 292.1692.
4.3.4. ( )-1,6-dibenzyl-5-methyl-3,6-dihydropyridin-2(1H)-one
(2d)
Yield 67%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 5: 1) gave colorless solid, m.p.
65e67 ꢀC (petroleum ether). 1H NMR (400 MHz, CDCl3, 23 ꢀC):
4.3.1. ( )-6-Benzyl-1-methyl-3,6-dihydropyridin-2(1H)-one (2a)
Yield 81%. (90% at six times larger scale). The crude product
purified by column chromatography (SiO2, n-hexane: ethyl acetate,
1: 1, then 1: 2) gave colorless solid, m.p. 94e96 ꢀC (hexane: ethyl
acetate). 1H NMR (400 MHz, CDCl3, 23 ꢀC):
d
¼ 2,08e2,17 (m, 1H,
d
¼ 1.69e1.78 (m, 4 H, CHH-3, 5-CH3), 2.57 (ddt, J ¼ 21.2, 5.4, 1.0 Hz,
CHH-3), 2.63e2.72 (m, 1 H, CHH-3), 2.88 (dd, J ¼ 13.3, 3.5 Hz, 1 H, 6-
CHH), 2.94 (dd, J ¼ 13.3, 6.5 Hz, 1 H, 6-CHH), 3.11 (s, 3 H, NCH3),
4.10e4.16 (m, 1 H, CH-6), 5.63e5.71 (m, 2 H, ¼CH-4, ¼CH-5), 7.07
(dd, J ¼ 7.6, 1.7 Hz, 2 H, C6H5), 7.20e7.29 (m, 3 H, C6H5); 13C NMR
1 H, CHH-3), 2.80 (dd, J ¼ 13.8, 3.8 Hz,1 H, 6-CHH), 3.09 (dd, J ¼ 13.8,
5.0 Hz, 1 H, 6-CHH), 3.81e3.86 (m, 1 H, CH-6), 3.88 (d, J ¼ 15.1 Hz,
1 H, NCHH), 5.38 (dquin, J ¼ 5.3, 1.6 Hz, 1 H, ¼CH-4), 5.63 (d,
J ¼ 15.1 Hz, 1 H, NCHH), 7.02e7.07 (m, 2 H, C6H5), 7.19e7.35 (m, 8 H,
(100 MHz, CDCl3)
d
¼ 31.95 (CH2-3), 33.07 (NCH3), 39.53 (6-CH2),
2 ꢃ C6H5) ppm. 13C NMR (100.6 MHz, CDCl3):
d
¼ 20.21 (5-CH3),
61.55 (CH-6), 123.80, 124.90 (¼CH-4, ¼CH-5), 126.79, 128.22,
129.96, 135,72 (C6H5), 168,51 (C]O); GC-MS (EI, 70 eV): m/z ¼ 201
(<1), [Mþ], 128 (3), 110 (100), 91 (9), 67 (18), 42 (11). IR (ATR):
32.21 (CH2-3), 36.25 (6-CH2), 46.78 (NCH2), 61.33 (CH-6), 120.31
(¼CH-4), 126.94, 127.34, 127.64, 128.12, 128.67, 130.07 (2 ꢃ C6H5),
131.75 (¼C-5), 135.63, 137.03 (2 ꢃ C6H5), 169.59 (C]O); GC-MS (EI,
70eV): m/z ¼ 291 (5), [Mþ], 200 (99), 91 (100), 65 (15). IR (ATR):
n
¼ 3027 (w), 2928 (w), 1626 (s), 1494 (m), 1453 (m), 1403 (m), 1349
(m), 1313 (w), 1260 (m), 1233 (m), 1084 (m), 1048 (m), 1029 (w),
1006 (m), 975 (w), 920 (w), 885 (w), 871 (w), 792 (w), 763 (w), 727
(s), 703 (m), 691 (s), 628 (w), 548 (w), 518 (w), 499 (m), 466 (m),
442 (m) cmꢁ1. HRMS (ESI-TOF): m/z [MþþH] calcd. for C13H16NO
202.1232; found 202.1231.
n
¼ 3061 (w), 3028 (w), 2930 (w), 2881 (w), 1640 (s), 1495 (w), 1468
(m), 1452 (m), 1409 (m), 1356 (w), 1256 (m), 1187 (w), 1151 (w),
1062 (w), 1029 (w), 971 (w), 801 (w), 756 (m), 733 (m), 699 (s), 661
(m), 495 (m), 453 (w) cmꢁ1. HRMS (ESI-TOF): m/z [MþþH] calcd for
C
20H22NO, 292.1701; found 292.1693.
4.3.2. ( )-1,6-dibenzyl-3,6-dihydropyridin-2(1H)-one (2b)
4.3.5. ( )-1,4-dibenzyl-5-methyl-3,4-dihydropyridin-2(1H)-one
(3d)
Yield 22%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 5: 1) gave colorless solid, m.p.
69e71 ꢀC (petroleum ether). 1H NMR (400 MHz, CDCl3, 23 ꢀC):
Yield 73%. (86%-six times larger scale). The crude product pu-
rified by column chromatography (SiO2, n-hexane: ethyl acetate, 1:
3, then 1: 6) gave colorless solid, m.p. 107e109 ꢀC (hexane: ethyl
acetate). 1H NMR (400 MHz, CDCl3, 23 ꢀC):
d
¼ 2.20 (dq, J ¼ 21.2,
2.7 Hz, 1 H, CHH-3), 2.79 (ddd, J ¼ 21.2, 4.9, 2.0 Hz, 1 H, CHH-3), 2.84
(dd, J ¼ 13.4, 3.7 Hz, 1 H, 6-CHH), 2.96 (dd, J ¼ 13.4, 6.8 Hz, 1 H, 6-
CHH), 4.00 (d, J ¼ 15.1 Hz,1 H, NCHH), 4.04e4.10 (m 1 H, CH-6), 5.64
(ddd, J ¼ 9.8, 4.6, 2.7 Hz, 1 H, ¼CH-5), 5.65 (d, J ¼ 15.1 Hz, 1 H,
NCHH), 5.72 (ddd, J ¼ 9.8, 4.9, 2.0 Hz, 1 H]CH-4), 7.06 (dd, J ¼ 7.4,
1.8 Hz, 2 H, C6H5), 7.22e7.36 (m, 8 H, 2 ꢃ C6H5); 13C NMR
d
¼ 1.57 (d, J ¼ 1.5 Hz, 3 H, 5-CH3), 2.33e2.40 (m, 1 H, CH-4), 2.44
(dd, J ¼ 16.1, 2.9 Hz, 1 H, CHH-3), 2.47 (dd, J ¼ 13.1, 9.3 Hz, 1 H, 4-
CHH), 2.58 (dd, J ¼ 16.1, 6.8 Hz, 1 H, CHH-3), 2.75 (dd, J ¼ 13.1,
5.7 Hz, 1 H, 4-CHH), 4.58 (d, J ¼ 14.9 Hz, 1 H, NCHH), 4.69 (d,
J ¼ 14.9 Hz, 1 H, NCHH), 5.77 (q, J ¼ 1.5 Hz, 1 H, ¼CH-6), 7.09e7.13
(m, 2 H, C6H5), 7.20 (tt, J ¼ 7.3, 1.2 Hz, 1 H, C6H5), 7.24e7.30 (m, 5 H,
C6H5), 7.31e7.35 (m, 2 H, C6H5) ppm; 13C NMR (100.6 MHz, CDCl3):
(100.6 MHz CDCl3):
57.60 (CH-6), 123.89 (¼CH-4), 125.45 (¼CH-5), 126.80, 127.46,
d
¼ 32.30 (CH2-3), 39.17 (6-CH2), 46.70 (NCH2),
d
¼ 18.51 (5-CH3), 35.69 (CH2-3), 37.83 (4-CH2), 38.95 (CH-4), 48.56
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Please cite this article in press as: Sosnicki JG, et al., Addition of novel benzylmagnesium “ate” complexes of BnR2MgLi type to 2-(thio)pyridones
and related compounds, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.12.024

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J.G. Sosnicki et al. / Tetrahedron xxx (2016) 1e13
8
(NCH2), 119.67 (C-5), 123.68 (¼CH-6), 126.28, 127.77, 128.35, 128.62,
129.24, 137.42, 139.04 (2 ꢃ C6H5), 168.09 (C]O) (one signal over-
lapped); GC-MS (EI, 70eV): m/z ¼ 291 (6), [Mþ], 200 (100), 91 (99),
70eV): m/z ¼ 263 (1), [Mþ], 172 (100), 144 (10), 91 (9), 77 (11); IR
(KBr pellet):
n
¼ 3040 (w), 2932 (w), 2868 (w), 1648 (s), 1592 (m),
1494 (m), 1458 (w), 1434 (m), 1414 (m), 1342 (w), 1296 (m), 1232
65 (15). IR (ATR):
n
¼ 3062 (w), 3028 (w), 2961 (w), 2916 (w), 1643
(w), 1162 (w), 1132 (w), 992 (w), 762 (m), 728 (m), 696 (m) cmꢁ1
.
(s), 1494 (m),1451 (m),1434 (m),1406 (m),1337 (w),1279 (m),1259
(m), 1201 (s), 1179 (m), 1029 (w), 1019 (w), 958 (m), 856 (w), 798
(w), 733 (m), 719 (m), 696 (s), 599 (w), 552 (w), 543 (m), 506 (m),
479 (w), 457 (m), 445 (m) cmꢁ1. HRMS (ESI-TOF): m/z [MþþH] calcd
for C20H22NO, 292.1701; found 292.1708.
HRMS (ESI-TOF): m/z [MþþH] calcd. for C18H18NO 264.1388; found
264.1389.
4.3.9. ( )-4-Benzyl-1-phenyl-3,4-dihydropyridin-2(1H)-one (3f)
Yield 41%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 1: 1) gave pale yellow solid,
m.p. 66e69 ꢀC (hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3,
4.3.6. ( )-1,6-dibenzyl-5-chloro-3,6-dihydropyridin-2(1H)-one
(2e)
Yield 54%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 7: 3) gave colorless solid, m.p.
71e73 ꢀC (hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3, 23 ꢀC):
23 ꢀC):
d
¼ 2.55 (dd, J ¼ 16.1, 8.8 Hz, 1 H, CHH-3), 2.69e2.82 (m, 3 H,
CHH-3, 4-CH2), 2.85e2.95 (m, 1 H, CH-4), 5.20 (dd, J ¼ 7.8, 3.9 Hz,
1 H, ¼CH-5), 6.25 (dd, J ¼ 7.8,1.7 Hz,1 H, ¼CH-6), 7.18e7.41 (m,10 H,
2 ꢃ C6H5); 13C NMR (100.6 MHz CDCl3):
d
¼ 33.83 (CH-4), 37.98
d
¼ 1.64 (dddd, J ¼ 21.3, 3.1, 2.3, 0.7 Hz, 1 H, CHH-3), 2.62 (ddd,
(CH2-3), 40.69 (4-CH2), 110.76 (¼CH-5), 125.95, 126.44, 126.97,
128.44, 129.02, 129.21 (2 ꢃ C6H5), 130.30 (¼CH-4), 138.69, 140.35
(2 ꢃ C6H5), 168.60 (C]O); GC-MS (EI, 70eV): m/z ¼ 263 (4), [Mþ],
J ¼ 21.3, 5.6, 1.5 Hz, 1 H, CHH-3), 3.04 (dd, 1 H, J ¼ 14.1, 3.1 Hz, 6-
CHH), 3.15 (dd, 1 H, J ¼ 14.1, 4.3 Hz, 6-CHH), 3.96 (d, J ¼ 15.1 Hz,
1 H, NCHH), 4.08 (dtd, 1 H, J ¼ 4.3, 3.1, 1.5 Hz, CH-6), 5.66 (d, 1H,
J ¼ 15.1 Hz, NCHH), 5.70 (dd, 1 H, J ¼ 5.6, 2.3 Hz, ¼CH-4), 7.07e7.13
(m, 2 H, C6H5), 7.24e7.38 (m, 8 H, C6H5); 13C NMR (100.6 MHz,
172 (100), 144 (11), 91 (7), 77 (13); IR (KBr pellet):
n
¼ 3056 (w),
2912 (w), 2848 (w), 1682 (s), 1596 (m), 1496 (m), 1456 (w), 1396
(m), 1354 (w), 1330 (w), 1300 (m), 1268 (m), 1182 (w), 1142 (w),
1078 (w), 920 (w), 766 (w), 744 (m), 700 (m) cmꢁ1. HRMS (ESI-TOF):
m/z [MþþH] calcd. for C18H18NO 264.1388; found 264.1392.
CDCl3):
d
¼ 32.53 (CH2-3), 35.11 (6-CH2), 46.90 (NCH2), 61.69 (CH-
6), 122.79 (¼CH-4), 126.92 (¼C-5), 127.36, 127.77, 127.93, 128.26,
128.87, 130.29, 134.33, 136.26 (C6H5), 167.52 (C]O); GC-MS (EI,
70eV): m/z ¼ 313 (1), [Mþþ2], 311 (3), [Mþ], 222 (20), 220 (63), 91
(100), 65 (12). IR (ATR):
n
¼ 3062 (w), 3029 (w), 2931 (w), 1647 (s),
4.3.10. ( )-6-Benzyl-1-methyl-3,6-dihydropyridine-2(1H)-thione
(2g)
Yield 74%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 8: 2) gave pale yellow solid,
m.p. 80e83 ꢀC (hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3,
1495 (w), 1452 (m), 1405 (w), 1249 (m), 1187 (w), 1155 (w), 1071
(w), 1015 (w), 932 (w), 814 (w), 757 (w), 729 (w), 698 (s), 674 (m),
638 (w), 493 (m) cmꢁ1. HRMS (ESI-TOF): calcd. for C19H19ClNO
312.1155 [MþH]þ; found 312.1158.
23 ꢀC):
d
¼ 2.57 (br. d, J ¼ 22.5 Hz, 1 H, CHH-3), 2.93 (dd, J ¼ 13.7,
4.3.7. ( )-1,4-dibenzyl-5-chloro-3,4-dihydropyridin-2(1H)-one
(3e)
Yield 23%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 7: 3) gave white solid, m.p.
78e80 ꢀC (hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3, 23 ꢀC):
3.9 Hz,1 H, 6-CHH), 3.03 (dd, J ¼ 13.5, 6.6 Hz,1 H, 6-CHH), 3.46 (ddd,
J ¼ 22.5, 4.6, 2.4 Hz, 1 H, CHH-3), 3.57 (s, 3 H, CH3), 4.29e4.35 (m,
1 H, CH-6), 5.68e5.76 (m, 2 H, ¼CH-4, ¼CH-5), 7.04e7.08 (m, 2 H,
C6H5) 7.22e7.31 (m, 3 H, C6H5); 13C NMR (100.6 MHz CDCl3):
d
¼ 39.78 (6-CH2), 41.56 (CH2-3), 42.24 (NCH3), 64.15 (CH-6),
d
¼ 1H NMR (400 MHz, CDCl3, 23 ꢀC):
¼ 2.51e2.64 (m, 2 H, CHH-3,
d
123.86, 124.03 (2x ¼ CH), 127.17, 128.40, 129.92, 135.00, (C6H5),
197.28 (C]S); GC-MS: (EI, 70eV): m/z ¼ 217 (34), [Mþ], 126 (100),
4-CHH), 2.70e2.80 (m, 2 H, CH-4, CHH-3), 2.97 (dd, J ¼ 13.3, 4.0 Hz,
1 H, 4-CHH), 4.45 (d, J ¼ 14.9 Hz, 1 H, NCHH), 4.62 (d, J ¼ 14.9 Hz,
1 H, NCHH), 6.15 (s, 1 H, ¼CH-6), 7.15e7.19 (m, 4 H, C6H5), 7.20e7.36
91 (10); IR (KBr pellet):
n
¼ 3024 (w), 2928 (w), 1676 (w), 1526 (s),
1452 (m),1408 (m),1394 (m),1352 (s), 1244 (w),1226 (w),1126 (m),
1080 (m), 1012 (w), 808 (w), 728 (s), 704 (m), 676 (m) cmꢁ1. HRMS
(ESI-TOF): m/z [MþþH] calcd. for C13H16NS 218.1003; found
218.1002.
(m, 6 H, C6H5); 13C NMR (100.6 MHz, CDCl3):
d
¼ 35.63 (CH2-3),
37.62 (4-CH2), 41.09 (CH-4), 48.86 (NCH2), 117.14 (¼C-5), 126.12
(¼CH-6), 126.72, 127.81, 127.84, 128.46, 128.81, 129.44, 136.44,
137.44 (2 ꢃ C6H5), 166.79 (C]O); GC-MS (EI, 70eV): m/z ¼ 313 (2),
[Mþþ2], 311 (7), [Mþ], 222 (20), 220 (63), 91 (100), 65 (14); IR
(ATR):
n
¼ 3023 (w), 2933 (w), 2919 (w), 1662 (s), 1494 (w), 1457
4.3.11. ( )-1,6-dibenzyl-3,6-dihydropyridine-2(1H)-thione (2h)
Yield 70%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 8: 2) gave pale yellow solid,
m.p. 84e86 ꢀC (hexane). 1H NMR (400 MHz, Toluene-d8, 23 ꢀC):
(w), 1452 (w), 1440 (w), 1405 (m), 1367 (w), 1268 (w), 1250 (w),
1208 (m), 1198 (m), 1074 (w), 1039 (w), 1030 (w), 988 (w), 951 (m),
849 (w), 842 (m), 741 (s), 701 (s), 672 (m), 611 (w), 600 (w), 579 (w),
544 (m), 524 (m), 499 (m), 472 (w), 452 (w) cmꢁ1. HRMS (ESI-TOF):
calcd. for C19H19ClNO 312.1155 [MþH]þ; found 312.1160.
d
¼ 2.32 (dd, J ¼ 13.4, 4.2 Hz, 1 H, 6-CHH), 2.46 (dm, J ¼ 22.0 Hz, 1 H,
CHH-3), 2.53 (dd, J ¼ 13.4, 6.8 Hz, 1 H, 6-CHH), 3.56 (ddd, J ¼ 22.0,
5.4, 1.5 Hz, 1 H, CHH-3), 3.77e3.82 (m, 1 H, CH-6), 3.97 (d,
J ¼ 14.9 Hz, 1 H, NCHH), 5.11 (ddd, J ¼ 9.8, 4.9, 3.4 Hz, 1 H, ¼CH-5)
5.21 (ddd, J ¼ 9.8, 5.4, 2.0 Hz, 1 H, ¼CH-4), 6.72 (d, J ¼ 14.9 Hz, 1 H,
NCHH), 6.77e6.81 (m, 2 H, C6H5), 6.97e7.12 (m, 6 H) 7.18 (d,
4.3.8. ( )-6-Benzyl-1-phenyl-3,6-dihydropyridin-2(1H)-one (2f)
Yield 42%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 1: 1) gave pale yellow solid,
m.p. 72e74 ꢀC (hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3,
J ¼ 7.3 Hz, 2 H, C6H5); 13C NMR (100.6 MHz CDCl3):
d
¼ 39.04 (6-
23 ꢀC):
d
¼ 2.70 (dd, J ¼ 13.2, 8.5 Hz, 1 H, 6-CHH), 2.72 (ddt, J ¼ 21.7,
CH2), 42.60 (CH2-3), 54.09 (NCH2), 59.80 (CH-6), 124.59 (¼CH-4),
124.75 (¼CH-5), 127.13, 127.79, 128.12, 128.48, 128.90, 130.24,
136.03, 136.47 (2 ꢃ C6H5), 198.88 (C]S); GC-MS: (EI, 70eV): m/
z ¼ 293 (35), [Mþ], 202 (66), 168 (8), 91 (100), 65 (14); IR (KBr
3.7, 2.4 Hz, 1 H, CHH-3), 2.93 (dd, J ¼ 13.2, 3.9 Hz, 1 H, 6-CHH), 2.94
(ddd, J ¼ 21.7, 4.2, 2.7 Hz, 1 H, CHH-3), 4.58e4.65 (m, 1 H, CH-6),
5.75 (ddd, J ¼ 10.3, 3.7, 2.9 Hz, 1 H, ¼CH-4), 5.81 (ddd, J ¼ 10.3,
4.2, 2.2 Hz, 1 H, ¼CH-5), 7.07e7.11 (m, 2 H, C6H5), 7.21e7.29 (m, 3 H,
C6H5), 7.32e7.38 (m, 3 H, C6H5), 7.45e7.51 (m, 2 H, C6H5); 13C NMR
pellet):
n
¼ 3064 (w), 3032 (w), 1676 (w), 1604 (w), 1498 (s), 1452
(m), 1428 (w), 1394 (m), 1352 (s), 1316 (m), 1252 (w), 1194 (m), 1172
(m), 1160 (m), 1068 (m), 1052 (w), 968 (w), 740 (m), 720 (m), 700
(m), 684 (w) cmꢁ1. HRMS (ESI-TOF): m/z [MþþH] calcd. for
(100.6 MHz CDCl3):
d
¼ 32.86 (CH2-3), 40.68 (6-CH2), 63.04 (CH-6),
123.11 (¼CH-4), 125.26 (¼CH-5), 126.72, 127.37, 127.93, 128.29,
129.38, 129.73, 136.33, 140.93 (2 ꢃ C6H5), 167.97 (C]O); GC-MS (EI,
C
19H20NS 294.1316; found 294.1320.
ꢀ
Please cite this article in press as: Sosnicki JG, et al., Addition of novel benzylmagnesium “ate” complexes of BnR2MgLi type to 2-(thio)pyridones
and related compounds, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.12.024

ꢀ
J.G. Sosnicki et al. / Tetrahedron xxx (2016) 1e13
9
4.3.12. ( )-6-Benzyl-1-propyl-3,6-dihydropyridin-2(1H)-one (2k)
Yield 84%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 6: 4) gave oil. 1H NMR
NMR (400 MHz, CDCl3, 23 ꢀC):
d
¼ 1.24 (d, J ¼ 7.6 Hz, 3 H, 3-CH3),
2.19e2.29 (m, 1 H, CH-3), 2.84 (dd,1 H, J ¼ 13.4, 3.8 Hz, 6-CHH), 2.94
(dd, J ¼ 13.4, 7.0 Hz, 1 H, 6-CHH), 4.00 (d, J ¼ 15.4 Hz, 1 H, NCHH),
4.03e4.06 (m, 1 H, CH-6), 5.57e5.65 (m, 3 H, NCHH, ¼CH-4, ¼CH-
5), 7.04e7.08 (m, 2 H, C6H5), 7.21e7.37 (m, 8 H, C6H5); 13C NMR
(400 MHz, CDCl3, 23 ꢀC):
d
¼ 0.94 (t, 3 H, J ¼ 7.5 Hz, CH3), 1.65 (sxt,
2 H, J ¼ 7.5 Hz, CH2CH3), 2.01e2.10 (m, 1 H, CHH-3), 2.61e2.69 (m,
1 H, CHH-3), 2.81e2.95 (m, 3 H, 6-CH2, NCHH), 4.09 (dt,1 H, J ¼ 13.4,
7.5 Hz, NCHH), 4.14e4.19 (m, 1 H, CH-6), 5.65e5.72 (m, 2 H, ¼CH-
4, ¼CH-5), 7.05e7.09 (m, 2 H, C6H5), 7.22e7.28 (m, 3 H, C6H5) ppm.
(100.6 MHz, CDCl3):
d
¼ 17.86 (3-CH3), 35.26 (CH-3), 39.09 (6-CH2),
46.86 (NCH2), 57.98 (CH-6), 124.61 (¼CH-4), 126.72, 127.35, 127.70,
128.24, 128.68, 129.93, 130.47, 136.09, 137.23 (¼CH-3), 172.24 (C]
O); MS (EI, 70eV): m/z ¼ 291 (<1), [Mþ], 200 (71), 91 (100), 65 (10);
13C NMR (100.6 MHz, CDCl3):
d
¼ 11.41 (CH3), 20.69 (CH2CH3), 32.39
(CH2-3), 39.71 (6-CH2), 46.27 (NCH2), 58.80 (CH-6), 124.17, 125.22
(¼CH-4, ¼CH-5), 126.72, 128.16, 130.08, 135.80 (C6H5), 168.43 (C]
O) ppm. GC-MS (EI, 70eV): m/z ¼ 229 (<1), [Mþ], 138 (100), 96 (59),
IR (ATR):
n
¼ 3028 (w), 2930 (w), 1636 (s), 1495 (w), 1450 (m), 1342
(w), 1312 (w), 1239 (w), 1078 (w), 1029 (w), 722 (m), 697 (s), 511
(w), 492 (w), 455 (w) cmꢁ1. HRMS (ESI-TOF): calcd. for C20H22NO
292.1701 [MþH]þ; found 292.1698.
91 (12), 78 (10). IR (film):
n
¼ 3032 (w), 2964 (m), 2932 (m), 2876
(w), 1640 (s), 1496 (w), 1468 (m), 1430 (w), 1410 (w), 1318 (w), 1264
(w), 1212 (w), 1200 (w), 1164 (w), 1124 (w), 1086 (w), 1032 (w), 732
(m), 709 (s) cmꢁ1. HRMS (ESI-TOF): calcd. for C15H20NO 230.1545
[MþH]þ; found 230.1539.
4.3.16. ( )-1,6-dibenzyl-3-methyl-3,6-dihydropyridin-2(1H)-one
(2n-isomer2)
Yield 28%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 9: 1) gave colorless oil, so-
lidified on standing in refrigerator. 1H NMR (400 MHz, CDCl3,
4.3.13. ( )-6-Benzyl-1-(2-methylallyl)-3,6-dihydropyridin-2(1H)-
one (2l)
Yield 82%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 7: 6 then 6: 4) gave pale yel-
23 ꢀC):
d
¼ 0.81 (d, J ¼ 7.4 Hz, 3 H, 3-CH3), 2.86e2.98 (m, 3 H, CH-3,
6-CH2), 4.00e4.09 (m, 2 H, NCHH, CH-6), 5.53 (ddd, J ¼ 10.1, 4.2,
0.6 Hz, 1 H, ¼CH-5), 5.64e5.72 (m, 2 H, NCHH, ¼CH-4), 7.02e7.08
(m, 2 H, C6H5), 7.18e7.37 (m, 8 H, C6H5); 13C NMR (100.6 MHz,
low oil. 1H NMR (400 MHz, CDCl3, 23 ꢀC):
d
¼ 1.69 (br s, 3 H, CH3),
2.11e2.19 (m, 1 H, CHH-3), 2.68e2.77 (m, 1 H, CHH-3), 2.84 (dd, 1 H,
J ¼ 13.5, 3.9 Hz, 6-CHH), 2.89 (dd, 1 H, J ¼ 13.5, 6.6 Hz, 6-CHH), 3.40
(d, 1 H, J ¼ 15.4 Hz, NCHH), 4.07e4.14 (m, 1 H, CH-6), 4.83 (br s,
1 H, ¼CHH), 4.93 (br s, 1 H, ¼CHH), 4.96 (d, 1 H, J ¼ 15.5 Hz, NCHH),
5.67e5.76 (m, 2 H, ¼CH-4, ¼CH-5), 7.03e7.10 (m, 2 H, C6H5),
7.20e7.29 (m, 3 H, C6H5) ppm. 13C NMR (100.6 MHz, CDCl3):
CDCl3):
d
¼ 19.35 (3-CH3), 36.89 (CH-3), 40,15 (6-CH2), 46.58
(NCH2), 57.67 (CH-6), 123.80 (¼CH-5), 126.85, 127.43, 127.97, 128.27,
128.69 (C6H5), 129.04 (¼CH-4), 129.98, 136.03, 137.04 (C6H5), 172.05
(C]O); MS (EI, 70eV): m/z ¼ 291 (<1), [Mþ], 200 (64), 91 (100), 65
(9); IR (ATR):
n
¼ 3065 (w), 3027 (w), 2971 (w), 2971 (w), 2931 (w),
2873 (w), 1638 (s), 1602 (w), 1495 (w), 1464 (w), 1445 (m), 1416 (w),
1344 (w), 1325 (w), 1259 (w), 1168 (w), 1082 (w), 1028 (w), 971 (w),
764 (w), 730 (s), 698 (s), 646 (w), 604 (w), 533 (w), 494 (w), 481 (w)
cmꢁ1. HRMS (ESI-TOF): calcd. for C20H22NO 292.1701 [MþH]þ;
found 292.1702.
d
¼ 19.93 (CH3), 32.30 (CH2-3), 39.21 (6-CH2), 48.71 (NCH2), 57.32
(CH-6), 112.43 (¼CH2), 124.00, 125.46 (¼CH-4, ¼CH-5), 126.74,
128.22, 130.00, 135.97 (C6H5), 140.35 (¼C), 168.66 (C]O); GC-MS
(EI, 70eV): m/z ¼ 241 (<1), [Mþ], 150 (100), 96 (18), 91 (13), 55
(30). IR (film):
n
¼ 3028 (w), 2928 (w), 1646 (s), 1496 (w), 1462 (m),
1408 (m), 1344 (w), 1316 (w), 1254 (w), 1194 (w), 1148 (w), 902 (w),
738 (w), 702 (m) cmꢁ1. HRMS (ESI-TOF): calcd. for C16H19NO
242.1545 [MþH]þ; found 242.1551.
4.3.17. ( )-1,4-dibenzyl-3-methyl-3,4-dihydropyridin-2(1H)-one
(3n)
Yield 23%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 9: 1) gave pale yellow oil as 1:
0.9 mixture of diastereoisomers. 1H NMR (400 MHz, CDCl3, 23 ꢀC,
4.3.14. ( )-6-Benzyl-1-(3-phenylallyl)-3,6-dihydropyridin-2(1H)-
one (2m)
Yield 83%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 8: 2) gave colorless solid, m.p.
125e127 ꢀC (hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3,
~1: 1 mixture of diastereoisomers):
d
¼ 1.25 (d, J ¼ 7.1 Hz, 3 H, 3-
CH3), 1.27 (d, J ¼ 7.1 Hz, 3 H, 3-CH3), 2.31e2.45 (m, 2 H, 2 ꢃ CH-
4), 2.50e2.61 (m, 2 H, CH-3, 4-CHH), 2.67e2.80 (m, 4 H, CH-3, 4-
CHH, 4-CH2), 4.57 (d, J ¼ 14.9 Hz, 1 H, NCHH), 4.67 (s, 2 H, NCH2),
4.75 (d,1 H, J ¼ 14.9 Hz, NCHH), 4.92 (dd, J ¼ 7.7, 4.5 Hz,1 H, ¼CH-5),
4.96 (ddd, J ¼ 7.7, 5.1, 0.9 Hz, 1 H, ¼CH-5), 5.97 (d, J ¼ 7.7 Hz,
1 H, ¼CH-6), 5.98 (d, 1 H, J ¼ 7.7 Hz, ¼CH-6), 7.04e7.36 (m, 20 H,
4 ꢃ C6H5); 13C NMR (100.6 MHz CDCl3, ~1: 1 mixture of di-
23 ꢀC):
d
¼ 2.13e2.21 (m, 1 H, CHH-3), 2.69e2.77 (m, 1 H, CHH-3),
2.88 (dd, 1 H, J ¼ 13.4, 3.9 Hz, 6-CHH), 2.95 (dd, 1 H, J ¼ 13.6, 6.6 Hz,
6-CHH), 3.68 (dd,1 H, J ¼ 15.1, 7.9 Hz, NCHH), 4.21e4.28 (m, 1 H, CH-
6), 5.04 (ddd, 1 H, J ¼ 15.1, 4.8, 1.6 Hz, NCHH), 5.65e5.74 (m,
2 H, ¼CH-4, ¼CH-5), 6.20 (ddd, 1 H, J ¼ 15.9, 8.1, 4.9 Hz, NCH2CH ¼ ),
6.54 (d, 1 H, J ¼ 15.9 Hz, ¼CH-Ph), 7.08e7.10 (m, 2 H, C6H5),
7.19e7.42 (m, 8 H, 2 ꢃ C6H5) ppm. 13C NMR (100.6 MHz, CDCl3):
astereoisomers):
d
¼ 11.33 (3-CH3), 16.16 (3-CH3), 35.05 (4-CH2),
38.24, 39.76 (2 ꢃ CH-3), 40.14 (4-CH2), 40.88, 40.97 (2 ꢃ CH-4),
48.87, 48.90 (2 ꢃ NCH2), 108.77, 110.48 (2 x ¼ CH-5), 126.15, 126.24,
127.48, 127.62, 127.69, 128.27, 128.31, 128.39, 128.65, 129.00, 129.23,
137.36, 137.44, 139.02, 139.47 (4 ꢃ C6H5, 2 x ¼ CH-6), 172.15, 172.57
(2 ꢃ C]O). GC-MS (EI, 70eV): m/z ¼ 291 (1), [Mþ], 200 (99), 91
d
¼ 32.33 (CH2-3), 39.48 (6-CH2), 46.02 (NCH2), 57.91 (CH-6),123.89
[ ¼ CH-4(5)], 124.51 (NCH2CH ¼ ), 125.39 [ ¼ C(5)4], 126.45, 126.77,
127.77, 128.24, 128.60, 130.02 (2 ꢃ C6H5), 132.93 (¼CHPh), 135.85,
136.47 (2 ꢃ C6H5), 168.44 (C]O). GC-MS (EI, 70eV): m/z ¼ 303 (6),
[Mþ], 212 (97), 118 (28), 117 (100), 115 (69), 91 (52), 65 (11). IR (KBr
(100), 65 (16). IR (ATR):
n
¼ 3063 (w), 3027 (w), 2973 (w), 2930 (w),
1736 (w), 1663 (s), 1603 (w), 1495 (w), 1453 (w), 1406 (w), 1388 (m),
1239 (m),1074 (w),1029 (w), 970 (w), 850 (w), 720 (m), 696 (s), 593
(w), 556 (w), 489 (w) cmꢁ1. HRMS (ESI-TOF): calcd. for C20H22NO
292.1701 [MþH]þ; found 292.1701.
pellet):
n
¼ 3080 (w), 3040 (w), 3028 (w), 2952 (w), 2936 (w), 1634
(s), 1492 (w), 1478 (m), 1452 (w), 1410 (w), 1340 (m), 1316 (w), 1264
(w), 1194 (w), 1148 (w), 1084 (w), 976 (m), 960 (w), 754 (m), 728
(m), 698 (m) cmꢁ1. HRMS (ESI-TOF): calcd. for C21H22NO 304.1701
[MþH]þ; found 304.1706.
4.3.18. ( )-6-Benzyl-4-methyl-1-phenyl-3,6-dihydropyridin-
2(1H)-one (2o)
4.3.15. ( )-1,6-dibenzyl-3-methyl-3,6-dihydropyridin-2(1H)-one
(2n-isomer1)
Yield 90%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 1: 1) gave white solid, m.p.
135e136 ꢀC (petroleum ether). 1H NMR (400 MHz, CDCl3, 23 ꢀC):
Yield 44%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 9: 1) gave pale yellow oil. 1H
d
¼ 1.71 (s, 3 H, CH3), 2.53 (br. d, J ¼ 21.2 Hz, 1 H, CHH-3), 2.68 (dd,
ꢀ
Please cite this article in press as: Sosnicki JG, et al., Addition of novel benzylmagnesium “ate” complexes of BnR2MgLi type to 2-(thio)pyridones
and related compounds, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.12.024

ꢀ
J.G. Sosnicki et al. / Tetrahedron xxx (2016) 1e13
10
J ¼ 13.2, 7.8 Hz, 1 H, 6-CHH), 2.75 (dd, J ¼ 21.2, 2.0 Hz, 1 H, CHH-3),
2.87 (dd, J ¼ 13.1, 3.5 Hz, 1 H, 6-CHH), 4.58 (br. s., 1 H, CH-6),
5.45e5.49 (m, 1 H, ¼CH-5), 7.07 (dd, J ¼ 7.6, 1.5 Hz, 2 H, C6H5),
7.21e7.28 (m, 3 H, C6H5), 7.33e7.37 (m, 3 H, C6H5), 7.44e7.50 (m,
3.8 Hz, 1H, 6-CHH), 2.79 (ddd, J ¼ 21.2, 5.7, 1.0 Hz, 1H, CHH-3), 3.09
(dd, J ¼ 13.9, 4.6 Hz, 1H, 6-CHH), 3.93 (d, J ¼ 15.4 Hz, 1H, NCHH),
4.63e4.68 (m, 1H, CH-6), 5.76 (d, J ¼ 15.1 Hz, 1H, NCHH), 5.89 (dd,
J ¼ 5.7, 2.2 Hz, 1H, ¼CH-4), 6.99e7.02 (m, 2H, C6H5), 7.17e7.21 (m,
2H, C6H5), 7.24e7.40 (m, 11H, 3 ꢃ C6H5). 13C NMR (100.6 MHz
2 H, C6H5); 13C NMR (100.6 MHz CDCl3):
d
¼ 21.77 (CH3), 37.44
(CH2-3), 40.70 (6-CH2), 62.76 (CH-6), 119.25 (¼CH-5), 126.61,
127.28, 127.89, 128.17, 129.33, 129.83, 131.68, 136.46, 140.87
(2 ꢃ C6H5, ¼C-4), 168.28 (C]O); GC-MS (EI, 70eV): m/z ¼ 277 (>1),
[Mþ], 186 (100), 158 (7), 143 (14), 104 (10), 91 (10), 77 (11); IR (KBr
CDCl3):
d
¼ 32.70 (CH2-3), 36.79 (6-CH2), 47.08 (NeCH2), 59.23 (CH-
6), 122.05 (¼CH-4), 126.10, 127.00, 127.49, 127.59, 127.94, 128.14,
128.80, 128.84, 130.28 (C6H5), 135.52, 136.59, 136.86, 137.75
(C6H5, ¼C-5), 169.39 (C]O); GC-MS (EI, 70eV): m/z ¼ 353 (3), [Mþ],
pellet):
n
¼ 3028 (w), 2988 (w), 2924 (w), 1656 (s), 1596 (w), 1492
262 (92), 91 (100), 65 (8). IR (ATR):
n
¼ 3058 (w), 3027 (w), 2927
(m), 1448 (m), 1408 (w), 1320 (m), 1276 (m), 1172 (w), 816 (w), 768
(m), 722 (w), 698 (m) cmꢁ1. HRMS (ESI-TOF): calcd. for C19H20NO
278.1545 [MþH]þ; found 278.1543.
(w), 1734 (w), 1644 (s), 1448 (m), 1252 (m), 750 (m), 696 (s), 502
(m) cmꢁ1. HRMS (ESI-TOF): m/z [MþþH] calcd for C25H24NO,
354.1858; found 354.1853.
4.3.19. ( )-1-Allyl-6-benzyl-4-methyl-3,6-dihydropyridin-2(1H)-
one (2p)
4.3.22. ( )-6-Benzyl-1-(1-phenylethyl)-3,6-dihydropyridin-2(1H)-
one (2s)
Yield 39%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 6: 4) gave colorless oil. Only
the main isomer was assigned from the mixture of di-
Yield 91%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 7: 3 then 6: 4) gave pale yel-
low oil. 1H NMR (400 MHz, CDCl3, 23 ꢀC):
d
¼ 1.62 (q, 3 H, J ¼ 0.6 Hz,
4-CH3), 1.98 (d, 1 H, J ¼ 21.0 Hz, CHH-3), 2.50 (dd, 1 H, J ¼ 21.0,
1.5 Hz, CHH-3), 2.80 (dd, 1 H, J ¼ 13.4, 3.7 Hz, 6-CHH), 2.88 (dd, 1 H,
J ¼ 13.4, 6.5 Hz, 6-CHH), 3.51 (ddq, 1 H, J ¼ 15.4, 7.2, 0.7 Hz, NCHH),
4.09e4.16 (m, 1 H, CH-6), 4.86 (ddt, 1 H, J ¼ 15.4, 4.3, 1.7 Hz, NCHH),
5.18 (dq, 1 H, J ¼ 6.4, 1.4 Hz, ¼CHH), 5.21 (t, 1 H, J ¼ 1.2 Hz, ¼CHH),
5.37e5.42 (m, 1 H, ¼CH-5), 5.75e5.86 (m, 1 H, ¼CH), 7.01e7.06 (m,
2 H, C6H5), 7.20e7.28 (m, 3 H, C6H5) ppm. 13C NMR (100.6 MHz,
astereoisomers. 1H NMR (400 MHz, CDCl3, 23 ꢀC):
d
¼ 1.84 (d,
J ¼ 7.2 Hz, 3 H, CH3), 2.44 (ddt, J ¼ 21.0, 3.3, 2.1 Hz, 1 H, CHH-3), 2.79
(dd, J ¼ 13.0, 8.9 Hz, 1 H, 6-CHH), 2.88 (ddd, J ¼ 21.0, 5.4, 1.2 Hz, 1 H,
CHH-3), 3.00 (dd, J ¼ 13.0, 3.5 Hz, 1 H, 6-CHH), 3.80e3.86 (m, 1 H,
CH-6), 5.53 (ddd, J ¼ 9.5, 5.3, 3.3 Hz, 1 H, ¼CH-5), 5.74 (ddd, J ¼ 9.5,
5.4, 2.1 Hz, 1 H, ¼CH-4), 6.06 (q, J ¼ 7.2 Hz, 1 H, NCH), 7.02 (dd, 2 H,
J ¼ 7.5, 1.9 Hz, C6H5), 7.19e7.39 (m, 8 H, C6H5); 13C NMR (100.6 MHz
CDCl3):
d
¼ 21.59 (4-CH3), 36.84 (CH2-3), 39.64 (6-CH2), 46.30
CDCl3):
d
¼ 18.32 (CH3), 33.51 (CH2-3), 42.46 (6-CH2), 52.39 (NCH),
(NCH2), 57.71 (CH-6), 117.27 (¼CH2), 119.29 (¼CH-5), 126.64,128.08,
130.08, 132.49 (¼C-4), 133.04 (¼CH), 136.04 (C6H5), 168.61 (C]O)
ppm. GC-MS (EI, 70eV): m/z ¼ 241 (<1), [Mþ], 150 (100), 110 (29), 91
55.46 (CH-6), 123.79 (¼CH-4), 126.65 (Ph), 127.24 (¼CH-5), 127.45,
128.25, 128.57, 128.64, 129.77, 136.63, 140.34 (2 ꢃ Ph), 169.54 (C]
O); GC-MS (EI, 70eV): m/z ¼ 291 (<1), [Mþ], 200 (68), 105 (86), 96
(10), 41 (18). IR (film):
n
¼ 3060 (w), 3028 (w), 2928 (m), 1642 (s),
(100), 91 (12), 79 (13), 77 (14); IR (ATR):
n
¼ 3060 (w), 3028 (w),
1496 (w), 1466 (m), 1408 (m), 1380 (w), 1342 (w), 1294 (m), 1272
(m), 1196 (w), 1126 (w), 996 (w), 924 (w), 808 (w), 756 (w), 724 (m),
700 (m) cmꢁ1. HRMS (ESI-TOF): calcd. for C16H20NO 242.1545
[MþH]þ; found 242.1548.
2974 (w), 2934 (w), 1637 br (s), 1495 (w), 1443 (m), 1408 (w), 1375
(w), 1290 (w), 1277 (w), 1208 (w), 1175 (w), 1156 (w), 1073 (w), 1029
(w), 1003 (w), 777 (w), 748 (w), 718 (m), 695 (w), 518 br. (m) cmꢁ1
.
HRMS (ESI-TOF): calcd. for C20H22NO 292.1701 [MþH]þ; found
292.1700.
4.3.20. ( )-6-Benzyl-4-methyl-1-(2-phenyllallyl)-3,6-dihydropyri-
din-2(1H)-one (2q)
Yield 94%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 6: 4) gave colorless solid, m.p.
107e109 ꢀC (hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3,
4.3.23. ( )-4-Benzyl-1-(1-phenylethyl)-3,4-dihydropyridin-2(1H)-
one (3s)
Yield 47%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 6: 4) gave brown solid as
mixture of diastereoisomers A and B in 74: 26 ratio, m.p. 51e54 ꢀC
(petroleum ether: ethyl acetate). 1H NMR (400 MHz, CDCl3, 23 ꢀC,
23 ꢀC):
d
¼ 1.57 (s, 3 H, 4-CH3), 1.98 (br d, 1 H, J ¼ 21.0 Hz, CHH-3),
2.49 (dd, 1 H, J ¼ 21.0, 1.5 Hz, CHH-3), 2.80 (dd, 1 H, J ¼ 13.3, 3.7 Hz,
6-CHH), 2.89 (dd, 1 H, J ¼ 13.3, 6.5 Hz, 6-CHH), 3.83 (d, 1 H,
J ¼ 16.0 Hz, NCHH), 4.04e4.11 (m, 1 H, CH-6), 5.15 (quin, 1 H,
J ¼ 0.7 Hz, ¼CHH), 5.28e5.33 (m, 1 H, ¼CH-5), 5.50 (s, 1 H, ¼CHH),
5.55 (dt, 1 H, J ¼ 16.0, 1.6 Hz, NCHH), 7.01e7.05 (m, 2 H, C6H5),
7.20e7.36 (m, 6 H, C6H5), 7.42e7.48 (m, 2 H, C6H5) ppm. 13C NMR
mixture of A: B diastereoisomers ¼ 74: 26):
d
¼ 1.49 [d, J ¼ 7.1 Hz,
2,2 H, CH3, (A)],1.52 [d, J ¼ 7.1 Hz, 0.8 H, CH3, (B)], 2.37e2.48 [m,1 H,
CHH-3, (A, B)], 2.58e2.71 [m, 4 H, CHH-3, CH-4, 4-CH2, (A, B)], 5.01
[dd, J ¼ 7.9, 3.7 Hz, 0.26 H,¼CH-5, (B)], 5.05 [dd, J ¼ 7.9, 3.5 Hz,
0.74 H, ¼CH-5, (A)], 5.85 [d, J ¼ 7.9 Hz, 1 H, ¼CH-6 (A,B)], 5.98 [q,
J ¼ 7.1 Hz, 0.76 H, NCH, (A)], 6.02 [q, J ¼ 7.1 Hz, 0.24 H, NCH, (B)],
7.08e7.11 [m, 0.52 H, C6H5, (B)], 7.13e7.17 [m, 1.48 H, C6H5, (A)],
7.17e7.37 (m, 8 H, C6H5, (A, B)]; 13C NMR (100.6 MHz CDCl3):
(100.6 MHz, CDCl3):
d
¼ 21.55 (4-CH3), 36.74 (CH2-3), 39.36 (6-CH2),
46.22 (NCH2), 57.06 (CH-6), 113.92 (¼CH2), 119.22 (¼CH-5), 126.17,
126.66, 128.01, 128.10, 128.43, 130.07 (2 ꢃ C6H5), 132.24, 136.10,
138.50, 142.89 (2 ꢃ C6H5, ¼C-4, ¼C), 168.86 (C]O) ppm. GC-MS (EI,
70eV): m/z ¼ 317 (<1), [Mþ], 226 (100), 116 (15), 115 (27), 91 (22). IR
d
¼ 17.30 (A), 17.37 (B), CH3, 33.52 (A), 33.58 (B), CH-4, 37.43 (A),
(KBr pellet):
n
¼ 3080 (w), 3056 (w), 3028 (w), 2984 (w), 2928 (w),
37.75 (B), CH2-3, 40.53 (B), 40.62 (A), 4-CH2, 49.39 (A, B), NCH,
110.87 (A), 111.08 (B), ¼CH-5), 124.95 (B), 124.97 (A), ¼CH-6, 126.32
(A), 126.35 (B), 127.09 (A, B), 127.40 (A), 127.45 (B), 128.38 (A),
128.40 (B), 128.54 (A), 128.55 (B), 129.09 (B), 129.20 (A), 138.88 (A),
139.01 (B),140.50 (A),140.60 (B) 2 ꢃ C6H5,168.48 (A),168.71 (B) C]
O; GC-MS (EI, 70eV): (A, B) m/z ¼ 291 (3), [Mþ], 200 (61), 105 (88),
1634 (s), 1622 (m),1494 (w),1470 (m),1444 (m),1406 (w),1290 (w),
1256 (m), 1190 (w), 1154 (w), 968 (w), 912 (m), 800 (w), 788 (w),
756 (w), 728 (w), 716 (m), 700 (m), 640 (w) cmꢁ1. HRMS (ESI-TOF):
calcd. for C22H24NO 318.1858 [MþH]þ; found 318.1859.
4.3.21. ( )-1,6-dibenzyl-5-phenyl-3,6-dihydropyridin-2(1H)-one
(2r)
96 (100), 91 (11), 79 (12), 77 (11)). IR (ATR):
n
¼ 3057 (w), 3024 (w),
2974 (w), 2933 (w), 2915 (w), 2873 (w),1650 (s),1494 (w), 1451 (w),
1390 (m), 1294 (w), 1236 (m), 1209 (w), 1175 (w), 912 (w), 772 (w),
742 (w), 718 (m), 699 (s), 644 (w), 552 (w), 545 (w), 528 (w), 506
(w) cmꢁ1. HRMS (ESI-TOF): calcd. for C20H22NO 292.1701 [MþH]þ;
found 292.1703.
Yield 82%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 3: 1) gave colorless solid, m.p.
119e122 ꢀC (hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3,
23 ꢀC):
d
¼ 1.82 (dt, J ¼ 21.2, 2.2 Hz, 1H, CHH-3), 2.63 (dd, J ¼ 13.8,
ꢀ
Please cite this article in press as: Sosnicki JG, et al., Addition of novel benzylmagnesium “ate” complexes of BnR2MgLi type to 2-(thio)pyridones
and related compounds, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.12.024

ꢀ
J.G. Sosnicki et al. / Tetrahedron xxx (2016) 1e13
11
4.3.24. ( )-1,6-dibenzyl-6-methyl-3,6-dihydropyridin-2(1H)-one
(2t)
Yield 21%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 6: 4) gave colorless solid, m.p.
121e123 ꢀC (petroleum ether: ethyl acetate). 1H NMR (400 MHz,
chromatography (130 cm long, SiO2, n-hexane: ethyl acetate, 1: 1,
then 1: 3) gave white solid, m.p. 147e150 ꢀC (ethyl acetate/n-hex-
ane).1H NMR (400 MHz, CDCl3, 23 ꢀC):
d
¼ 1.50 (ddd, J ¼ 13.6, 12.1,
5.6 Hz, 1 H, H-5ax), 1.84 (dq, J ¼ 13.6, 2.1 Hz, 1 H, H-5eq), 2.25 (dd,
J ¼ 17.6, 11.2 Hz, 1 H, H-3ax), 2.37e2.50 (m, 2 H, CH-4ax, 4-CHH), 2.54
(dd, J ¼ 13.1, 11.1 Hz, 1 H, 6-CHH), 2.70e2.78 (m, 2 H, 4-CHH, H-3eq),
2.87 (dd, J ¼ 13.2, 3.4 Hz, 1 H, 6-CHH), 3.90e3.99 (m, 1 H, CH-6eq),
6.64 (dd, J ¼ 7.6, 1.5 Hz, 2 H, C6H5), 7.05e7.11 (m, 3 H, C6H5),
7.15e7.19 (m, 2 H, C6H5), 7.23e7.29 (m, 3 H, C6H5), 7.29e7.35 (m,
3 H, C6H5), 7.42e7.47 (m, 2 H, C6H5); 13C NMR (100.6 MHz CDCl3):
CDCl3, 23 ꢀC):
d
¼ 1.34 (s, 3 H, 6-CH3), 1.79 (dt, 1 H, J ¼ 21.9, 2.6 Hz,
CHH-3), 2.67 (dd, J ¼ 21.6, 4.5 Hz, 1 H, CHH-3), 2.67 (d, J ¼ 13.6 Hz,
1 H, 6-CHH), 3.15 (d, J ¼ 13.6 Hz, 1 H, 6-CHH), 4.27 (d, J ¼ 15.9 Hz,
1 H, NCHH), 5.45 (d, J ¼ 15.9 Hz, 1 H, NCHH), 5.53 (dd, J ¼ 10.0,
2.6 Hz, 1 H, ¼CH-5), 5.65 (ddd, J ¼ 10.0, 4.5, 2.6 Hz, 1 H, ¼CH-4),
7.05e7.08 (m, 2 H, C6H5), 7.17e7.32 (m, 8 H, C6H5); 13C NMR
d
¼ 30.10 (CH2-5), 30.78 (CH-4), 38.61 (6-CH2), 39.42 (CH2-3), 42.03
(100.6 MHz, CDCl3):
d
¼ 28.32 (CH3), 31.56 (CH2-3), 45.46 (6-CH2),
(4-CH2), 61.65 (CH-6), 126.34, 126.36, 127.27, 127.99, 128.42, 128.49,
128.93, 129.14, 129.33, 137.61, 139.23, 141.56 (3 ꢃ C6H5), 169.66 (C]
O) ppm; (EI, 70eV): m/z ¼ 355 (<1), [Mþ], 265 (24), 264 (100), 145
45.49 (NCH2), 63.28 (C-6), 122.29 (¼CH-4), 126.54, 126.62, 126.82,
127.97, 128.36 (C6H5), 130.61 (¼CH-5), 130.63, 135.87, 139.04 (C6H5),
169.68 (C]O); GC-MS (EI, 70eV): m/z ¼ 291 (<1), 200 (85), 91
(66), 127 (28), 117 (21), 115 (14), 91 (27), 77 (13). IR (ATR):
n
¼ 3067
(100), 65 (10); IR (ATR):
n
¼ 3061 (w), 3026 (w), 2982 (w), 2937 (w),
(w), 3032 (w), 2935 (w), 1644 (s), 1594 (w), 1490 (m), 1449 (w),
1429 (m), 1406 (m), 1321 (m), 1305 (w), 1246 (w), 1233 (w), 1140
(m), 1072 (w), 965 (m), 754 (s), 719 (m), 694 (s), 627 (m), 597 (w),
576 (w), 559 (m), 502 (m), 468 (m) cmꢁ1. HRMS (ESI-TOF): m/z
[MþþH] calcd for C25H26NO, 356.2014; found 356.2010.
2882 (w), 1638 (s), 1601 (w), 1493 (w), 1430 (w), 1416 (w), 1397 (m),
1358 (w), 1325 (w), 1179 (w), 1143 (m), 1072 (w), 990 (w), 929 (w),
765 (w), 735 (m), 722 (s), 699 (s), 666 (w), 546 (w), 451 (w), 410 (w)
cmꢁ1. HRMS (ESI-TOF): calcd. for C20H22NO 292.1701 [MþH]þ;
found 292.1708.
4.3.28. ( )-trans-4-Benzyl-6-butyl-piperidine-2-thione (9trans)
Yield 95%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 10: 1) gave pale yellow solid,
m.p. 105e107 ꢀC (petroleum ether).1H NMR (400 MHz, CDCl3,
4.3.25. ( )-1,4-dibenzyl-6-methyl-3,4-dihydropyridin-2(1H)-one
(3t)
Yield 59%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 6: 4) gave pale yellow oil. 1H
23 ꢀC):
d
¼ 0.89 (t, J ¼ 6.8 Hz, 3 H, CH3), 1.22e1.37 (m, 4 H, CH2, CH2-
NMR (400 MHz, CDCl3, 23 ꢀC):
d
¼ 1.84 (s, 3 H, CH3), 2.41 (dd,
5), 1.39e1.51 (m, 1 H, 6-CHH), 1.55e1.71 (m, 3 H, 6-CHH, CH2),
2.12e2.23 (m, 1 H, CH-4ax), 2.54e2.67 (m, 3 H, CH2-3, 4-CHH), 2.98
(dd, J ¼ 18.3, 4.9 Hz, 1 H, 4-CHH), 3.50 (quind, 1 H, J ¼ 6.0, 2.4 Hz,
CH-6eq), 7.10e7.17 (m, 2 H, C6H5), 7.19e7.24 (m, 1 H, C6H5),
7.27e7.32 (m, 2 H, C6H5), 8.67 (br. s, 1 H, NH); 13C NMR (100.6 MHz
J ¼ 15.4, 9.0 Hz, 1 H, CHH-3), 2.59e2.71 (m, 4 H, CHH-3, 4-CH2, CH-
4), 4.79 (d, J ¼ 16.1 Hz, 1 H, NCHH), 4.91e4.94 (m, 1 H, ¼CH-5), 4.96
(d, J ¼ 16.1 Hz, 1 H, NCHH), 7.13e7.33 (m, 10 H, C6H5); 13C NMR
(100.6 MHz CDCl3):
d
¼ 19.35 (CH3), 32.85 (CH-4), 37.61 (CH2-3),
40.60 (4-CH2), 44.58 (NCH2), 109.79 (¼CH-5), 126.30, 126.40,
126.99, 128.41, 128.62, 129.13 (C6H5), 135.74, 138.32, 139.19
(C6H5, ¼C-6), 170.60 (C]O); GC-MS (EI, 70eV): m/z ¼ 291 (3), 200
CDCl3):
d
¼ 13.89 (CH3), 22.42 (CH2-5), 27.78 (CH2), 30.79 (CH-4),
31.01 (CH2), 35.58 (CH2), 40.79 (4-CH2), 44.97 (CH2-3), 53.68 (CH-
6), 126.43, 128.55, 128.96, 138.91 (C6H5), 202.03 (C]S); GC-MS: (EI,
70eV): m/z ¼ 261 (43), [Mþ], 228 (12), 218 (32), 204 (14), 170 (100),
161 (15), 144 (16), 129 (33), 128 (98), 112 (20), 91 (46); IR (KBr
(93), 91 (100), 65 (11); IR (ATR):
n
¼ 3061 (w), 3027 (w), 2917 (w),
2850 (w), 1672 (s), 1661 (s), 1603 (w), 1495 (w), 1433 (w), 1388 (m),
1370 (m),1328 (m),1250 (w),1189 (w),1160 (w),1077 (w),1029 (w),
926 (w), 907 (w), 884 (w), 745 (w), 724 (m), 697 (s), 671 (w), 627
(w), 602 (w), 561 (w), 545 (w), 492 (m), 455 (w) cmꢁ1. HRMS (ESI-
TOF): calcd. for C20H22NO 292.1701 [MþH]þ; found 292.1704.
pellet):
(s), 1496 (w), 1452 (w), 1412 (w), 1348 (m), 1136 (m), 1088 (m), 1046
(w), 924 (w), 874 (w), 848 (w), 724 (s), 700 (m) cmꢁ1 1H NMR
(400 MHz, Toluene-d8, 23 ꢀC):
¼ 0.78 (t, J ¼ 7.5 Hz, 3 H, CH3),
n
¼ 3160 (m), 3060 (m), 2956 (m), 2928 (m), 2860 (m), 1572
.
d
0.82e1.11 (m, 7 H, 2 ꢃ CH2, CH2-5, 6-CHH), 1.12e1.23 (m, 1 H, 6-
CHH), 1.62e1.74 (m, 1 H, CH-4ax), 2.05 (dd, J ¼ 13.3, 8.2 Hz, 1 H, 4-
CHH), 2.26 (dd, J ¼ 13.3, 6.7 Hz, 1 H, 4-CHH), 2.42 (dd, J ¼ 18.3,
8.3 Hz, 1 H, CHH-3ax), 2.85 (dd, J ¼ 18.3, 4.9 Hz, 1 H, CHH-3eq), 2.89
(quind, J ¼ 6.0, 3.2 Hz, 1 H, CH-6eq), 6.86 (d, J ¼ 7.0 Hz, 2 H, C6H5),
6.99e7.04 (m, 1 H, C6H5), 7.06e7.12 (m, 2 H, C6H5); 13C NMR
4.3.26. ( )-cis-4,6-dibenzyl-1-phenylpiperidin-2-one (7cis)
Yield 38%. The crude product purified by column chromatog-
raphy (130 cm long, SiO2, n-hexane: ethyl acetate, 1: 1, then 1: 3)
gave white semisolid. 1H NMR (400 MHz, CDCl3, 23 ꢀC):
J ¼ 13.4, 11.7 Hz, 1 H, H-5ax), 1.95 (ddt, J ¼ 13.4, 4.9, 2.4 Hz, 1 H, H-
d
¼ 1.34 (dt,
5
eq), 2.09e2.21 (m, 2 H, CH-4, H-3ax), 2.31 (dd, J ¼ 13.1, 10.3 Hz, 1 H,
(100 MHz, Toluene-d8):
d
¼ 14.11 (CH3), 22.82 (CH2), 27.97 (CH2),
6-CHH), 2.47 (dd, J ¼ 13.3, 7.4 Hz, 1 H, 4-CHH), 2.54 (dt, J ¼ 15.6,
2.9 Hz, 1 H, H-3eq), 2.68 (dd, J ¼ 13.3, 5.0 Hz, 1 H, 4-CHH), 2.83 (dd,
J ¼ 13.1, 3.5 Hz, 1 H, 6-CHH), 3.92e4.01 (m, 1 H, CH-6ax), 6.99 (d,
J ¼ 6.8 Hz, 2 H, C6H5), 7.09 (d, J ¼ 7.1 Hz, 2 H, C6H5), 7.16e7.33 (m,
9 H, C6H5), 7.44 (t, J ¼ 7.8 Hz, 2 H, C6H5);13C NMR (100.6 MHz,
30.65 (CH2-5), 31.03 (CH-4), 35.58 (6-CH2), 40.82 (4-CH2), 45.66
(CH2-3), 53.27 (CH-6), 126.50, 128.64, 129.21, 139.69 (C6H5) 201.31
(C]S). HRMS (ESI-TOF): calcd. for C16H24NS 262.1629 [MþH]þ;
found 262.1625.
CDCl3):
d
¼ 33.67 (CH-4), 35.77 (CH2-5), 39.27 (CH2-3), 42.37 (4-
4.3.29. ( )-1,2-dibenzyl-2,3-dihydropyridin-4(1H)-one (11)
Yield 84%. The crude product purified by column chromatog-
raphy (SiO2, CH2Cl2: MeOH, 95: 5) gave pale yellow oil. 1H NMR
CH2), 42.39 (6-CH2), 61.01 (CH-6), 126.33, 126.56, 127.34, 128.12,
128.41, 128.47, 129.05, 129.33, 137.52, 138.73, 140.69 (3 ꢃ C6H5, two
overlapped signals), 170.63 (C]O). (EI, 70eV): m/z ¼ 355 (<1), [Mþ],
265 (25), 264 (100), 145 (66), 127 (26), 117 (20), 115 (14), 91 (28), 77
(400 MHz, CDCl3, 23 ꢀC):
d
¼ 2.22 (dt, J ¼ 16.4, 1.0 Hz, 1 H, CHH-3),
2.62 (dd, 1 H, J ¼ 16.4, 6.8 Hz, CHH-3), 2.84 (dd, J ¼ 13.3, 8.3 Hz, 1 H,
2-CHH), 3.08 (dd, J ¼ 13.3, 6.9 Hz, 1 H, 2-CHH), 3.56e3.64 (m, 1 H,
CH-2), 3.96 (d, J ¼ 15.2 Hz, 1 H, NCHH), 4.26 (d, J ¼ 15.2 Hz, 1 H,
NCHH), 5.04 (dd, 1 H, J ¼ 7.5, 1.0 Hz, ¼CH-5), 7.10 (dd, 1 H, J ¼ 7.5,
1.0 Hz, ¼CH-6), 7.11e7.15 (m, 2 H, C6H5), 7.18e7.23 (m, 2 H, C6H5),
(12); IR (ATR):
n
¼ 3061 (w), 3026 (w), 3002 (w), 2920 (w), 1649
(m), 1595 (w), 1494 (m), 1453 (w), 1320 (m), 1304 (m), 1216 (w),
1200 (w), 1029 (w), 746 (s), 695 (s), 562 (m), 505 (m) cmꢁ1. HRMS
(ESI-TOF): m/z [MþþH] calcd for C25H26NO, 356.2014; found
356.2021.
7.24e7.41 (m, 6 H, C6H5); 13C NMR (100.6 MHz CDCl3):
d
¼ 34.36 (2-
CH2), 39.15 (CH2-3), 57.78 (CH-2), 58.52 (NCH2), 97.50 (¼CH-5),
126.85, 127.50, 128.32, 129.05, 129.49, 136.48, 137.32 (2 ꢃ C6H5),
152.05 (¼CH-6), 190.41 (C]O); GC-MS (EI, 70eV): m/z ¼ 277 (6),
4.3.27. ( )-trans-4,6-dibenzyl-1-phenylpiperidin-2-one (7trans)
Yield 49%. The crude product purified by column
ꢀ
Please cite this article in press as: Sosnicki JG, et al., Addition of novel benzylmagnesium “ate” complexes of BnR2MgLi type to 2-(thio)pyridones
and related compounds, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.12.024

ꢀ
J.G. Sosnicki et al. / Tetrahedron xxx (2016) 1e13
12
[Mþ], 186 (75), 91 (100), 65 (8). IR (ATR):
n
¼ 3061 (w), 3027 (w),
d
¼ 2.63e2.71 (m, 3 H, CH-4, 4-CH2), 2.77e2.85 (m, 1 H, CHH-3),
2922 (w), 2858 (w),1630 (m),1572 (s),1494 (w),1452 (m),1412 (w),
1381 (m), 1348 (m), 1306 (w), 1198 (m), 1157 (m), 1077 (w), 1027
(w), 957 (w), 730 (m), 696 (s), 607 (w), 593 (w), 502 (m), 454 (w),
419 (w) cmꢁ1. HRMS (ESI-TOF): calcd. for C19H20NO 278.1545
[MþH]þ; found 278.1542.
2.97 (dd, J ¼ 16.6, 5.9 Hz, 1 H, CHH-3), 5.39 (dq, J ¼ 7.8, 1.8 Hz,
1 H, ¼CH-5), 6.07 (dd, J ¼ 7.8, 3.9 Hz, 1 H, ¼CH-6), 7.14e7.33 (m, 5 H,
C6H5), 9.35 (br. s., 1 H, NH); 13C NMR (100.6 MHz CDCl3):
d
¼ 32.57
(CH-4), 39.91 (4-CH2), 43.79 (CH2-3), 114.83 (¼CH-5), 123.88 (¼CH-
6), 126.51, 128.51, 129.20, 138.50 (C6H5), 199.84 (C]S); GC-MS (EI,
70eV): m/z ¼ 203 (51), [Mþ], 112 (100), 91 (19), 78 (40); IR (KBr
4.3.30. ( )-3-Benzylcyclohexanone (13)
pellet):
n
¼ 3192 br (m), 3140 (m), 3000 (m),1656 (w),1520 (s),1496
Yield 91%. The crude product was purified by distillation to give
a colorless oil, bp 67e70 ꢀC (0.01 mbar). Spectral data for this
product matched those reported previously.34 1H NMR (400 MHz,
(m), 1452 (w), 1404 (w), 1362 (m), 1312 (w), 1140 (m), 1104 (w), 936
(w), 860 (w), 808 (w), 740 (m), 704 (m) cmꢁ1. HRMS (ESI-TOF): m/z
[MþþH] calcd. for C12H14NS 204.0847; found 204.0842.
CDCl3, 23 ꢀC):
d
¼ 1.3e1.43 (m, 1 H), 1.55e1.67 (m, 1 H), 1.87 (d,
J ¼ 14.7 Hz, 1 H), 1.99e2.10 (m, 3 H), 2.25 (dddd, J ¼ 14.3, 12.0, 5.9,
0.8 Hz, 1 H), 2.31e2.41 (m, 2 H), 2.55e2.69 (m, 2 H), 7.09e7.15 (m,
2 H), 7.17e7.23 (m, 1 H), 7.25e7.31 (m, 2 H) ppm. 13C NMR
4.4.3. ( )-4-Benzyl-5-chloro-3,4-dihydropyridin-2(1H)-one (3u)
Yield 58%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 1: 1) gave white solid, m.p.
93e94 ꢀC (hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3, 23 ꢀC):
(100.6 MHz CDCl3):
(CH2), 42.98 (CH2), 47.83 (CH2),126.19,128.35,129.10,139.41 (C6H5),
d
¼ 25.10 (CH2), 30.87 (CH2), 40.88 (CH), 41.41
d
¼ 2.39 (dd, J ¼ 16.6, 2.2 Hz,1 H, CHH-3), 2.58e2.68 (m, 2 H, CHH-3,
211.67 (C]O).
4-CHH), 2.70e2.77 (m, 1 H, CH-4), 3.03 (dd, J ¼ 13.2, 3.9 Hz, 1 H, 4-
CHH), 6.20 (d, J ¼ 4.9 Hz, 1 H, ¼CH-6), 7.16e7.33 (m, 5 H,C6H5), 8.22
4.4. Typical procedure for the Benzylation of NeH substituted 2-
(Thio)pyridones 1 and compound 8
(br. s., 1 H, NH) ppm; 13C NMR (100.6 MHz CDCl3):
d
¼ 34.54 (CH2-
3), 37.42 (4-CH2), 40.85 (CH-4), 116.41 (¼C-5), 122.18 (¼CH-6),
126.72, 128.51, 129.44, 137.46 (C6H5), 169.54 (C]O); GC-MS (EI,
70eV): m/z ¼ 223 (3) [Mþ2], 221 (10) [Mþ], 132 (34), 130 (100), 129
A stirred solution of BnMgCl (2.0 M in THF; 6.16 mmol, 3.08 mL,
see Table 2 and Scheme 3) in dry THF (15 mL) in a Schlenk flask was
cooled to 0 ꢀC under argon, and MeLi (3.0 M in diethoxymethane;
12.32 mmol, 4.1 mL) was added by syringe over 5 min. The resulting
solution was stirred for 5 min at 0 ꢀC. In the second Schlenk flask
the solution of N-lithium 2-pyridone or 2-thiopyridone or com-
pound 8Li was prepared by adding by syringe a solution of MeLi
(3.0 M in diethoxymethane; 4.6 mmol, 1.53 mL) to the solution of
corresponding NH 2-(thio)pyridone or thiolactam 8 (4.4 mmol) in
(28), 91 (37), 67 (22). IR (ATR):
n
¼ 3205 br (m), 3092 br (w), 2933,
(w), 2921 (w), 1674 (m), 1655 (s), 1492 (w), 1453 (w), 1418 (w), 1376
(m), 1282 (w), 1252 (w), 1205 (m), 1139 (w), 1066 (w), 1041 (w), 967
(w), 849 (m), 788 br (m), 743 (s), 699 (s), 667 (s), 591 (m), 544 (s),
526 (m), 478 (m), 465 (m) cmꢁ1. HRMS (ESI-TOF): m/z [MþþH]
calcd for C12H13ClNO, 222.0686; found 222.0690.
4.4.4. ( )-4-Benzyl-5-phenyl-3,4-dihydropyridin-2(1H)-one (3v)
Yield 40%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 1: 2) gave white solid, m.p.
162e164 ꢀC (hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3,
THF (50e60 mL) at
0
ꢀC. The solution containing lithium
benzyldimethyl-magnesiate and LiCl (prepared in the first Schlenk
flask) was then transferred by syringe to a cooled (0 ꢀC) solution of
NLi compound (prepared in the second Schlenk flask). The resulting
solution was stirred for 60 min at 0 ꢀC and 120 min at room tem-
perature. After this time, the mixture was carefully quenched with
saturated aqueous NH4Cl (8 mL) using ice-water bath. The aqueous
layer was extracted with ethyl acetate (3 ꢃ 50 mL), and the com-
bined organic layers were dried with MgSO4. The mixture was
filtered, and the solvents were evaporated under reduced pressure.
The crude product was purified by column chromatography on
silica gel using a mixture of appropriate solvents to give the desired
product.
23 ꢀC):
d
¼ 2.51 (br d, 1 H, J ¼ 16.1 Hz, CHH-3), 2.56e2.65 (m, 2 H,
CHH-3, 4-CHH), 2.91 (dd, 1 H, J ¼ 13.8, 3.8 Hz, 4-CHH), 3.09e3.16
(m, 1 H, CH-4), 6.56 (d, 1H, J ¼ 4.6 Hz, ¼CH-6), 7.18e7.45 (m, 12 H,
2 ꢃ C6H5), 8.32 (br. s., 1H, NH) ppm. 13C NMR (100.6 MHz, CDCl3):
d
¼ 34.06 (CH2-3), 36.35 (CH-4), 37.82 (4-CH2), 121.06 (¼CH-6),
121.41 (C-5), 124.82, 126.46, 126.84, 128.48, 128.85, 129.42, 137.10,
138.65 (2 ꢃ C6H5), 170.81 (C]O) ppm; GC-MS (EI, 70eV): m/z ¼ 263
(16), [Mþ], 172 (100), 145 (14), 127 (12), 115 (15), 91 (14). IR (ATR):
n
¼ 3214 br (m), 3103 (w), 2914 (w), 1675 (s), 1639 (s), 1594 (m),
1491 (m), 1445 (m), 1384 (m), 1290 (m), 1198 (m), 1144 (w), 1020
(w), 854 (m), 784 (w), 739 (s), 691 (s), 579 (m), 501 (m) cm-1. HRMS
(ESI-TOF): m/z [MþþH] calcd for C18H18NO, 264.1388; found
264.1383.
4.4.1. ( )-4-Benzyl-3,4-dihydropyridin-2(1H)-one (3i)
Yield 45%. The crude product purified by column chromatog-
raphy (SiO2, ethyl acetate) gave white solid. Mp. 84e86 ꢀC (hexane:
ethyl acetate). 1H NMR (400 MHz, CDCl3, 23 ꢀC):
d
¼ 2.33 (dd,
4.4.5. ( )-4-Benzyl-5-chloro-3,4-dihydropyridine-2(1H)-thione
(3y)
J ¼ 16.3, 8.2 Hz, 1 H, CHH-3), 2.52 (dd, J ¼ 16.3, 6.4 Hz, 1 H, CHH-3),
2.61e2.83 (m, 3 H, CH-4, 4-CH2), 5.02 (ddd, J ¼ 7.7, 3.3, 1.0 Hz,
1 H, ¼CH-5), 6.06 (ddd, J ¼ 7.6, 4.5, 1.3 Hz, 1 H, ¼CH-6), 7.13e7.33
(m, 5 H, C6H5), 7.69 (br. s., 1 H, NH); 13C NMR (100.6 MHz CDCl3):
Yield 79%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 1: 2) gave creamy solid, m.p.
151e152 ꢀC (hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3,
d
¼ 33.71 (CH-4), 36.30 (CH2-3), 40.65 (4-CH2), 109.32 (¼CH-5),
23 ꢀC):
d
¼ 2.58 (dd, 1H, J ¼ 12.2, 10.3 Hz, 4-CHH), 2.63 (ddt, 1H,
124.28 (¼CH-6),126.38,128.43,129.15,138.91 (C6H5),171.19 (C]O);
J ¼ 10.3, 7.1, 3.1 Hz, CH-4), 2.91 (dd, 1H, J ¼ 17.5, 7.1 Hz, CHH-3), 3.00
(dd, 1H, J ¼ 12.2, 3.0 Hz, 4-CHH), 3.07 (dd, 1H, J ¼ 17.6, 3.0 Hz, CHH-
3), 6.25 (d, 1H, J ¼ 4.6 Hz, ¼CH-6), 7.19e7.27 (m, 3H, C6H5),
7.29e7.34 (m, 2H, C6H5), 9.36 (br. s., 1H, NH) ppm; 13C NMR
GC-MS (EI, 70eV): m/z ¼ 187 (2), [Mþ], 96 (100), 92 (13), 78 (11); IR
(KBr pellet):
n
¼ 3232 br (m), 3112 (w), 2908 (w), 1694 (s), 1652 (m),
1496 (w), 1452 (w), 1412 (w), 1364 (m), 1298 (w), 1152 (w), 948 (w),
776 (w), 728 (m), 716 (w), 700 (m) cmꢁ1. HRMS (ESI-TOF): m/z
[MþþH] calcd. for C12H14NO 188.1075; found 188.1071.
(100.6 MHz CDCl3):
d
¼ 36.82 (4-CH2), 40.54 (CH-4), 42.52 (CH2-3),
121.51 (¼CH-6); 122.90 (C-5), 126.83, 128.58, 129.55, 137.36 (C6H5),
197.17 (C-2); GC-MS (EI, 70 eV): m/z ¼ 239 (Mþ2) (21), 237 (Mþ)
54), 148 (38), 146 (100), 112 (29), 111 (36), 91 (54), 65 (19); IR (ATR):
4.4.2. ( )-4-Benzyl-3,4-dihydropyridine-2(1H)-thione (3j)
Yield 80%. The crude product purified by column chromatog-
raphy (SiO2, n-hexane: ethyl acetate, 5: 1) gave white solid. Mp.
59e61 ꢀC (hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3, 23 ꢀC):
n
¼ 3175 br (m), 2990 br (m), 1526 (s), 1490 (w), 1451 (w), 1414 (w),
1384 (m), 1304 (m), 1294 (m), 1250 (w), 1219 (w), 1138 (s), 1108 (m),
1056 (m), 1039 (m), 969 (w), 797 (m), 755 (m), 730 (m), 696 (s), 620
ꢀ
Please cite this article in press as: Sosnicki JG, et al., Addition of novel benzylmagnesium “ate” complexes of BnR2MgLi type to 2-(thio)pyridones
and related compounds, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.12.024

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J.G. Sosnicki et al. / Tetrahedron xxx (2016) 1e13
13
(m), 568 (s), 540 (s) cmꢁ1. HRMS (ESI-TOF): m/z [MþþH] calcd for
ꢀ
ꢀ
ꢀ
11. a) Sosnicki JG. Tetrahedron Lett. 2005;46:4295e4298;
b) Sosnicki JG. Tetrahedron Lett. 2006;47:6809e6812;
C
12H13ClNS, 238.0457; found 238.0453.
c) Sosnicki JG. Tetrahedron. 2007;63:11862e11877;
ꢀ
d) Sosnicki JG, Struk Ł. Synlett. 2009:1812e1816;
ꢀ
e) Sosnicki JG. Tetrahedron Lett. 2009;50:178e181;
Acknowledgments
ꢀ
f) Sosnicki JG. Synlett. 2009:2508e2512;
ꢀ
g) Sosnicki JG, Struk Ł, Idzik T, Maciejewska G. Tetrahedron. 2014;70:
8624e8635.
Financial support by the National Science Center (Grant N N204
219640) and by the Faculty of Chemical Technology and Engineer-
ing, West Pomeranian University of Technology, Szczecin is grate-
fully acknowledged.
ꢀ
ꢀ
ꢀ
12. Sosnicki JG, Struk Ł. Synlett. 2010:1209e1214.
13. Sosnicki JG, Dzitkowski P, Struk Ł. Eur J Org Chem. 2015:5189e5198.
14. Genisson Y, Marazano C, Das BC. J Org Chem. 1993;58:2052e2057.
15. Chenard BL, Shalaby IA, Koe BK, et al. J Med Chem. 1991;34:3085e3090.
16. Scalone M, Waldmeier P. Org Process Res Dev. 2003;7:418e425.
17. Huo H-H, Xia X-E, Zhang H-K, Huang P-Q. J Org Chem. 2013;78:455e465.
18. Next to the formula of magnesiate we introduce “LiCl” because LiCl salt is also
formed during the magnesiate preparation and has significant influence on the
reaction course. Such influence was observed in the previous studies. See for
example ref. 10b and references cited therein.
19. Salanski PKK, Young K, Mendeleev Lee. Commun. 2006;1:46e48.
20. Okano T, Fumoto M, Kusukawa T, Fujita M. Org Lett. 2002;4:1571e1573.
21. Pana A, Chiriac FL, Secu M, et al. Dalton Trans. 2015;44:14196e14199.
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2016.12.024.
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ꢀ
Please cite this article in press as: Sosnicki JG, et al., Addition of novel benzylmagnesium “ate” complexes of BnR2MgLi type to 2-(thio)pyridones
and related compounds, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.12.024