Structural reorganization of (allyl-, benzyl-, and propargylsulfanyl)- substituted 2-aza-1,3,5-trienes in t-BuOK/THF/DMSO: Access to rare functionalized 2-thiazolines

Article abstract of DOI:10.1016/j.tetlet.2014.03.015

Treatment of (allyl-, benzyl-, and propargylsulfanyl)-substituted 2-aza-1,3,5-trienes, which are readily accessible from lithiated methoxyallene, isopropyl isothiocyanate, and allyl, benzyl, or propargyl bromide, respectively, with t-BuOK in THF/DMSO resu

Full text of DOI:10.1016/j.tetlet.2014.03.015

Tetrahedron Letters 55 (2014) 2495–2498
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Structural reorganization of (allyl-, benzyl-, and propargylsulfanyl)
-substituted 2-aza-1,3,5-trienes in t-BuOK/THF/DMSO: access to rare
functionalized 2-thiazolines
⇑
Nina A. Nedolya , Ol’ga A. Tarasova, Alexander I. Albanov, Boris A. Trofimov
A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1 Favorsky St., Irkutsk 664033, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Treatment of (allyl-, benzyl-, and propargylsulfanyl)-substituted 2-aza-1,3,5-trienes, which are readily
accessible from lithiated methoxyallene, isopropyl isothiocyanate, and allyl, benzyl, or propargyl bro-
mide, respectively, with t-BuOK in THF/DMSO resulted in the unexpected formation of 2-thiazoline deriv-
atives along with seven-membered azaheterocycles [in the case of (allyl- and benzylsulfanyl)-substituted
2-aza-1,3,5-trienes]. An unprecedented structural reorganization of the azatrienes into 2-thiazolines pre-
Received 30 September 2013
Revised 26 February 2014
Accepted 4 March 2014
Available online 12 March 2014
sumably occurs via
a-deprotonation of the substituents at the sulfur atom followed by intramolecular
Keywords:
[1,5]-cyclization. Deprotonation of the ketimine fragment of the same molecule followed by [1,7]-electro-
cyclization resulted in azepine ring formation.
Methoxyallene
Isothiocyanates
2-Aza-1,3,5-trienes
Deprotonation
2-Thiazolines
Azepines
Ó 2014 Elsevier Ltd. All rights reserved.
We have shown that (alkylsulfanyl)-substituted conjugated
2-aza-1,3,5-trienes [H2C@CH–C(R)@C(SAlk)–N@CR2] prepared in
one preparative step from readily accessible allenes or alkynes,
isothiocyanates, and alkylating agents, according to procedures
developed by us,1 can serve as direct precursors of a new series
of azacycloheptadienes and azacycloheptatrienes.2–4 The process
comprises an unprecedented structural reorganization of
2-aza-1,3,5-trienes 1 into seven-membered azaheterocycles under
the action of t-BuOK (1.2–1.5 equiv) in dry THF (0 °C, 10 min3a or
15 °C, 30 min4b), or THF/DMSO (ca. ꢀ30 °C, 30 min)3,4 according
to Scheme 1 (via in situ generation and [1,7]-azaelectrocyclization
of azatrienyl anions A), and represents a novel, simple, and
synthetically attractive approach to both dihydroazepines 2 and
azepines 3.
R"
R'
t-BuOK
R
R
R"
R'
R"
R
+
THF or
N
N
N
SAlk
R'
SAlk
THF DMSO
/
2
1
3
t-BuOK
−AlkS
H2O
R"
R'
K
R"
R'
R"
R
R
R
N
B
N
C
N
A
R'
SAlk
SAlk
SAlk
R = OAlk, OAll, OCH(Me)OAlk, Ar, HetAr; R', R" = H, Alk, (CH ) , n = 3 5
−
2 n
Scheme 1.
would not allow prediction of the result of their interaction with
We have also found that the ratio of 4,5-dihydro-3H-azepines 2
and 3H-azepines 3 is strongly influenced by the structure and nat-
ure of the substituents on both the azomethine and butadiene
parts of the 2-aza-1,3,5-trienes 1 as well as at the sulfur atom.
In the light of these results, we have studied the reaction of
t-BuOK with conjugated azatrienic systems bearing unusual base-
sensitive substituents at the sulfur atom, namely, (allyl-, benzyl-,
and propargylsulfanyl)-substituted 2-aza-1,3,5-trienes 1a–d. The
presence of these substituents in the structure of substrates 1a–d
t-BuOK, which brings additional intrigue into this study.
2-Aza-1,3,5-trienes 1a–d were prepared from
a-lithiated
methoxyallene, isopropyl, sec-butyl, or cyclohexyl isothiocyanate
and allyl, benzyl, or propargyl bromide, respectively, (via the
one-pot synthesis of 1-aza-1,3,4-trienes 4a–d in yields of 87–
98%, and their thermally induced sigmatropic rearrangement)
(Scheme 2).
The isomerization of 1-aza-1,3,4-trienes 4a–d into the target 2-
aza-1,3,5-trienes 1a–d was completed by heating under reduced
pressure [on a rotary evaporator at 55–60 °C for 10 min followed
by vacuum treatment at 50–58 °C (1 mmHg) for 5–15 min]. This
⇑
Corresponding author. Tel.: +7 3952 425585; fax: +7 3952 419346.
E-mail address: nina@irioch.irk.ru (N.A. Nedolya).
http://dx.doi.org/10.1016/j.tetlet.2014.03.015
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

2496
N. A. Nedolya et al. / Tetrahedron Letters 55 (2014) 2495–2498
R1
OMe
X
Me
Me
Δ
N
R2
t-BuOK
N
2a
Me
S
1. BuLi,
THF/DMSO
S
R3
[1,5]-H shift
N
THF/hexane
OMe
∼ −30 оС, 30 min
Me
Me
2. R1R2CHN=C=S
3. R3CH2Br
S
OMe
N
OMe
OMe
S
R3
OMe
1a d
−
+
C
1a
t-BuOK
C
S
N
4a d
−
R1
N
Me
Me
MeO
+
7
3a
R2
OMe
S
Me
Me
H2O
Δ
Me
Me
Me
Me
K
R3
N
N
N
N
[1,5]-heterocyclization
R1 R2
S
S
S
MeO
MeO
Me
5a−d
OMe
E
F
D
R1 = R2 = Me, R3 = CH=CH2 ( ), Ph ( ); R1 = Me, R2 = Et, R3 = C
CH ( );
a
b
c
R1,R2 = (CH2)5, R3 = C
CH (d)
Scheme 4.
Scheme 2.
tert-butoxide yielding, instead of the expected 2-(allylsulfanyl)-3-
methoxy-6-methyl-4,5-dihydro-3H-azepine (2a), a product that
was identified by extensive NMR studies as 5-[(Z)-ethylidene]-2-
(1-methoxyallyl)-4,4-dimethyl-1,3-thiazole (7) (yield ꢁ18%), along
with 3H-azepine 3a (yield ꢁ7%) (Scheme 4).6
was accompanied by competitive intramolecular [1,5]-heterocycli-
zation of 4 into pyrroles 5 (8–13% as mixtures with 1; a trace
amount in the case of 4d) (Scheme 2), the conversion of 1-aza-
1,3,4-trienes 4 being 100%. The total yield of compounds 1 and 5
is almost quantitative (94–99%).
Also, the corresponding pyrrole 5a, which was present in the
starting 2-aza-1,3,5-triene 1a (as a side product of its synthesis),
was isolated (yield ꢁ13%), the conversion of the 2-aza-1,3,5-triene
1a being 100% (according to 1H NMR).
Notably, parallel formation of pyrroles (as by-products) during
sigmatropic rearrangement of 1-aza-1,3,4-trienes takes place only
in the case of alkoxy-substituted derivatives.1,3,5 Attempts to iso-
late 2-aza-1,3,5-trienes from the mixture with pyrroles by com-
mon techniques proved to be unsuccessful. During distillation in
vacuo they cyclized into 2,3-dihydropyridines,1,5 but upon chro-
matographic separation on a column with Al2O3 or SiO2, complete
decomposition occurred. This is why, in the reaction with t-BuOK,
2-aza-1,3,5-trienes 1 contaminated with pyrroles 5 were used.
It should be recalled, that treatment of the (methylsulfanyl)-
substituted analog of 2-aza-1,3,5-trienes 1a–d (azatriene 1e) with
t-BuOK (1.2 equiv) under unusually mild reaction conditions [THF/
DMSO (5/1, v/v), ꢀ30 to ꢀ25 °C, 30 min]3a led to simultaneous syn-
thesis of 3-methoxy-7-methyl-2-(methylsulfanyl)-4,5-dihydro-
3H-azepine (2e) and 6-methoxy-2-methyl-3H-azepine (3a) in
yields of 33% and 38%, respectively (Scheme 3).
1-Isopropyl-3-methoxy-2-(methylsulfanyl)pyrrole (5e) and
5-methoxy-2,2-dimethyl-6-(methylsulfanyl)-2,3-dihydropyridine
(6) were identified (1H NMR) as side products of the 2-aza-1,3,
5-triene 1e synthesis.3a
To our surprise, (allylsulfanyl)-substituted 2-aza-1,3,5-triene
1a, in contrast to (methylsulfanyl)-substituted analog 1e
(Scheme 3),3a,3c under similar conditions, reacted with potassium
Such a result arises from the fact that, in contrast to (meth-
ylsulfanyl)-substituted 2-aza-1,3,5-triene 1e (Scheme 3),3a,3c along
with the ketimine fragment, the substituent at the sulfur atom,
that is, the allyl group, participates in the reaction with t-BuOK.
Formation of 3H-azepine 3a is thought to proceed via a similar
mechanism to that depicted in Scheme 1 [through deprotonation
of a methyl group from the ketimine moiety (N@CMe2) of the 2-
aza-1,3,5-trienic system 1a (via intermediates A–C)]. Final elimina-
tion of the sulfide-anion (CH2@CHCH2Sꢀ) from cyclic anion C under
the reaction conditions affords 3H-azepine 3a.
However, the unexpected structural transformation of 2-aza-
1,3,5-triene 1a into 4,5-dihydro-1,3-thiazole 7 likely involves the
competitive deprotonation of the allylsulfanyl substituent upon
treatment with t-BuOK, and proceeds according to Scheme 4 (via
intermediates D–F). Activation of the SCH2 moiety with a vinyl
group makes its protons acidic enough for easy deprotonation.
Metallation of (benzylsulfanyl)-substituted 2-aza-1,3,5-triene
1b with t-BuOK under very similar reaction conditions afforded a
new thiazole derivative, 2-[(Z)-1-methoxyprop-1-enyl]-4,4-di-
methyl-5-phenyl-4,5-dihydro-1,3-thiazole (8), along with the
expected products, 2-(benzylsulfanyl)-3-methoxy-7-methyl-4,5-
dihydro-3H-azepine (2b) and 3H-azepine 3a (Scheme 5).
The yields of compounds 2b, 3a, and 8 were ꢁ23, 5, and 20%,
respectively (calculated from the 1H NMR spectrum of the reaction
mixture, purified from tar-like products by column
chromatography).
Deprotonation at the ketimine fragment, accompanied by spon-
taneous [1,7]-electrocyclization of the carbanion A to give the aza-
cycloheptadienyl anion C and final protolysis or elimination of the
sulfide anion (PhCH2Sꢀ), leads to 4,5-dihydro-3H-azepine 2b and
3H-azepine 3a, respectively (Scheme 5). Competitive deprotonation
of the benzylsulfanyl substituent, that is, the SCH2 moiety activated
with a phenyl group, results in the formation of 4,5-dihydro-1,
3-thiazole 8. This reaction most likely proceeds through intermedi-
ates G–I (Scheme 5).
The presence of pyrrole 5b among the reaction products is
caused by the above-mentioned competitive heterocyclization of
the 1-aza-1,3,4-triene 4b, which occurs during its isomerization
into the 2-aza-1,3,5-triene 1b (Scheme 2).
OMe
SMe
N
Me Me
OMe
5e
(~10%)
SMe
Me
~65 o
C
C
+
N
15 min
Me
Me
SMe
4e
OMe
Me
N
Me
Me
N
6
SMe
(~10%)
1. BuLi,
THF/hexane
2. i-PrN=C=S
OMe
1e
3. MeI
OMe
C
t-BuOK
THF/DMSO
∼ −30 оС, 30 min
OMe
OMe
3a (~38%)
+
N
N
SMe
Me
Me
2e (~33%)
It should be noted that participation of the allylsulfanyl and
benzylsulfanyl groups in the process of deprotonation of the
Scheme 3.

N. A. Nedolya et al. / Tetrahedron Letters 55 (2014) 2495–2498
2497
OMe
K
OMe
X
+
OMe
OMe
OMe
Me
Et
N
2c
t-BuOK
N
3b
Et
S
Et
N
N
N
Me
Me
H2O
THF/DMSO
Me
S
S
S
N
Ph
Ph
Ph
A
Me
∼ −30 оС, 30 min
B
C
−PhCH2S
OMe
S
N
Et
OMe
t-BuOK
Me
Me
Ph
Me
C
OMe
1c
S
9a
+
MeO
t-BuOK
N
2b
N
3a
t-BuOK
Me
S
Me
Ph
Me
Me
Ph
THF DMSO
N
/
H2O
∼ −30 оС, 30 min
Me
Et
S
Me
Me
Et
K
OMe
N
N
N
Et
C
N
1b
Me
MeO
S
S
S
S
t-BuOK
MeO
MeO
8
OMe
J
K
L
Me
Me
Ph
H2O
N
K
Me
Me
Me
Ph
Scheme 6.
N
N
S
Me
Ph
S
S
MeO
MeO
OMe
G
H
I
t-BuOK
THF/DMSO
N
N
Scheme 5.
Me
C
ca. −30 oC,
S
S
OMe
9b
OMe
15 min
1d
2-aza-1,3,5-trienes 1a,b under the investigated conditions was not
anticipated since allyl and benzyl sulfides are usually metallated
by BuLi7 or lithium amides.7a,8 To the best of our knowledge, the
use of t-BuOK for abstraction of allylic or benzylic protons has
not yet been described. Moreover, unsymmetrically substituted
allylic anions are ambident, which can react with electrophiles at
Scheme 7.
t-BuOK
OMe
S
R1 R2
5c',5d'
)
OMe
THF/DMSO
Me
S
∼ −30 оС, 15−30 min
N
two positions (
a- and c-), the selectivity of such reactions not
N
being predictable.9 In our case, only the product derived from the
R1 R2
a-carbanion was obtained.
5c,d
1
R1 = Me, R2 = Et ( , ); R ,R2 = (CH2)5 ( ,
The singularity of the discussed reactions lies in the fact that in
c c'
d d'
the process of structural reorganization of the 2-aza-1,3,5-triene
1b into 4,5-dihydro-1,3-thiazole 8, an unprecedented low-temper-
ature (ca. ꢀ30 °C) isomerization of the 1-methoxyallyl group into a
1-methoxyprop-1-enyl group occurs. According to our10 and the
literature11 data, allyl–propenyl isomerization in a number of allyl
ethers, even in the presence of a strong base, usually takes place
under harsh conditions (at temperatures above 100 °C, within sev-
eral hours), and is generally very sensitive not only to the reaction
parameters (solvent, base, ratio of reagents, temperature, time,
etc.), but also to the allyl ether structure. Interestingly, in the case
of thiazole 7, similar isomerization of the 1-methoxyallyl group did
not take place. At the same time, and typical for allyl sulfides, base-
catalyzed12 isomerization into propenyl sulfides was found to
occur at low temperatures during the synthesis of thiazole 7 and
appears in the transformation of the 5-vinyl group, as a part of
an allyl sulfide fragment (intermediate E), into 5-(ethylidene)
group (via intermediate F) (Scheme 4). While, 2-(allylsulfanyl)-
1H-pyrrole 5a, which was also present in the reaction mixture,
did not show any tendency to isomerize into 2-(prop-1-enylsulfa-
nyl)-1H-pyrrole.
Scheme 8.
types of base-induced isomerization, namely allyl–propenyl and
acetylene–allene, also occurring at low temperatures (Scheme 6).
Starting from (propargylsulfanyl)-substituted 2-aza-1,3,5-tri-
ene 1d, which possesses an imino cyclohexanone moiety, spirocy-
clic 4,5-dihydro-1,3-thiazole 9b was obtained under similar
reaction conditions (15 min) in 23% isolated yield (Scheme 7), the
conversion of 2-aza-1,3,5-triene 1d being ꢁ100%.
1-(sec-Butyl)- and 1-cyclohexyl-3-methoxy-2-(propargylsulfa-
nyl)-1H-pyrroles (5c and 5d, respectively), that were present in
the starting compounds 1c,d in small amounts (ꢁ8 and ꢁ4%), upon
reaction with t-BuOK isomerized into 2-(prop-1-ynylsulfanyl)-1H-
15
pyrroles 5c0 and 5d0 (Scheme 8).
4,5-Dihydro-1,3-thiazoles 7–9 and other heterocycles were iso-
lated from their mixtures by column chromatography and were
characterized by spectral and elemental analysis data.
In conclusion, the discovered reaction of competitive mild
deprotonation of allyl-, benzyl-, and propargylsulfanyl substituents
in 2-aza-1,3,5-trienes [N-(buta-1,3-dienyl)ketimines] under the ac-
tion of the t-BuOK/THF/DMSO not only significantly broadens
knowledge about the metallation reactions of azatrienic systems
having several reaction centers, but can also be the basis for a novel
approach to the simple synthesis of new classes of multifunctional
2-thiazolines, known representatives of which are used widely in
medicine and pharmacology.16 Further studies on the scope and
generality of this novel methodology for thiazole ring construction,
as well as optimization of the reaction conditions are in progress.
Elimination of sulfur-centered (allyl- and benzylsulfanyl)-an-
ions from (allyl- and benzylsulfanyl)-substituted azacyclohepta-
dienyl-anions, type C (Schemes 1 and 5), leading to azepine 3a, is
also unknown.
A really surprising result was obtained when (propargylsulfa-
nyl)-substituted 2-aza-1,3,5-triene 1c13 was involved in the reac-
tion with t-BuOK under conditions that are typical for
dihydroazepine/azepine synthesis.3,4 In this case, the reaction pro-
ceeded efficiently with high selectivity, and instead of the expected
4,5-dihydro-3H-azepine 2c and 3H-azepine 3b, gave 5-ethenylid-
ene-4-ethyl-2-[(Z)-1-methoxyprop-1-enyl]-4-methyl-4,5-dihydro-
1,3-thiazole (9a) as the only product in ꢁ60% yield (crude) and
ꢁ46% (after double purification) (Scheme 6).14
Acknowledgments
The authors are grateful for the financial support from the
Russian Foundation for Basic Research (Grant No. 13-03-00691a)
and the Presidium of the Russian Academy of Sciences (Project
No. 8.17).
A possible mechanism for the reaction is suggested in Scheme 6.
Structural reorganization of 2-aza-1,3,5-triene 1c into thiazole 9a
probably proceeds through intermediates J–L, and includes two

2498
N. A. Nedolya et al. / Tetrahedron Letters 55 (2014) 2495–2498
an additional 25 min. Next, the mixture was cooled to ꢀ80 °C and propargyl
Supplementary data
bromide (5.7 g, 47.9 mmol) was added in one portion, after which the cooling
bath was removed. After stirring for 65 min at room temperature, H2O (40 mL)
was added to the mixture and cooled to ꢀ60 °C. After separation of the layers,
the products were extracted from the aqueous fraction with Et2O (3 ꢂ 40 mL).
The combined organic fractions were washed with H2O (3 ꢂ 30 mL), dried
(MgSO4), and concentrated under reduced pressure (at ꢁ1 mmHg) to give a
very dark mobile liquid consisting of 1-aza-1,3,4-triene 4c and 2-aza-1,3,5-
triene 1c as a mixture in the ratio 1:2 (by NMR). Yield: 8.11 g (94%).
Supplementary data (experimental section, characterization of
all compounds) associated with this article can be found, in the on-
line version, at http://dx.doi.org/10.1016/j.tetlet.2014.03.015.
References and notes
2-Methoxy-N-(1-methylpropylidene)-1-(prop-2-ynylsulfanyl)buta-1,3-dien-1-
amine (2-aza-1,3,5-triene 1c). The complete isomerization of 1-aza-1,3,4-triene
4c into 2-aza-1,3,5-triene 1c was effected by vacuum treatment of a sample
(8.0 g, 35.9 mmol) at 56–58 °C (1 mmHg) for 15 min. The residue (7.64 g, 96%)
consisted of 2-aza-1,3,5-triene 1c (ꢁ92%) and pyrrole 5c (ꢁ8%) (by 1H NMR).
1H NMR (400.13 MHz, CDCl3, ppm): d = 5.87 (1H, dd, 3Jtrans 17.2 Hz, 3Jcis 10.9 Hz,
1. (a) Nedolya, N. A. Novel Chemistry Based on Isothiocyanates and Polar
Organometallics Thesis; Utrecht University: Utrecht, The Netherlands, 1999;
(b) Brandsma, L.; Nedolya, N. A.; Tarasova, O. A.; Trofimov, B. A. Chem.
Heterocycl. Compd. (Engl. Transl.) 2000, 36, 1241–1260; (c) Brandsma, L. Eur. J.
Org. Chem. 2001, 4569–4581; (d) Brandsma, L.; Nedolya, N. A. Synthesis 2004,
735–745; (e) Nedolya, N. A. Chem. Heterocycl. Compd. (Engl. Transl.) 2008, 44,
1165–1219.
3
3
2
CH@), 5.23 and 4.95 (2H, both dd, Jtrans 17.2 Hz, Jcis 10.9 Hz, Jgem 1.8 Hz,
CH2@), 3.64 (3H, s, OCH3), 3.35 (2H, d, 4J 2.7 Hz, SCH2), 2.43 (2H, q, 3J 7.4 Hz,
CH2CH3), 2.15 (1H, t, 4J 2.7 Hz, HC„), 1.91 (3H, s, CH3C@), 1.17 (3H, t, 3J 7.4 Hz,
CH2CH3). 13C NMR (100.62 MHz, CDCl3, ppm): d = 179.08 (C@N), 138.53 (@C–
O), 126.58 (@C–S), 126.33 (CH@), 110.90 (CH2@), 80.93 (C„), 70.57 (HC„),
58.90 (OCH3), 34.59 (SCH2), 20.69 (CH3C@), 17.71 (CH2), 10.46 (CH2CH3). IR
(cm–1): 3293 („CH), 2969, 2933, 2876, 2828, 2272, 1645, 1607, 1565, 1545,
1460, 1438, 1398, 1367, 1332, 1258, 1237, 1187, 1155, 1067, 1047, 977, 953,
893, 788, 707, 644.
2. Nedolya, N. A.; Trofimov, B. A. Chem. Heterocycl. Compd. (Engl. Transl.) 2013, 49,
152–176.
3. (a) Nedolya, N. A.; Dmitrieva, L. L.; Albanov, A. I.; Klyba, L. V.; Tarasova, O. A.;
Ushakov, I. A. Russ. J. Org. Chem. 2006, 42, 465–468; (b) Nedolya, N. A.; Tarasova,
O. A.; Albanov, A. I.; Volostnykh, O. G.; Brandsma, L.; Trofimov, B. A. Mendeleev
Commun. 2008, 18, 164–166; (c) Nedolya, N. A.; Tarasova, O. A.; Volostnykh, O.
G.; Albanov, A. I.; Trofimov, B. A. J. Organomet. Chem. 2011, 696, 3359–3368.
4. (a) Nedolya, N. A.; Tarasova, O. A.; Volostnykh, O. G.; Albanov, A. I. Chem.
Heterocycl. Compd. (Engl. Transl.) 2008, 44, 1113–1116; (b) Nedolya, N. A.;
Tarasova, O. A.; Albanov, A. I.; Klyba, L. V.; Trofimov, B. A. Russ. J. Gen. Chem.
(Engl. Transl.) 2009, 79, 1041–1044; (c) Nedolya, N. A.; Tarasova, O. A.;
Volostnykh, O. G.; Albanov, A. I.; Klyba, L. V.; Trofimov, B. A. Synthesis 2011,
2192–2204; (d) Nedolya, N. A.; Volostnykh, O. G.; Tarasova, O. A.; Albanov, A. I.;
Trofimov, B. A. Russ. Chem. Bull. Int. Ed. 2011, 60, 2617–2620.
5. Nedolya, N. A.; Brandsma, L.; Tarasova, O. A.; Albanov, A. I.; Trofimov, B. A. Russ.
J. Org. Chem. (Engl. Transl.) 2011, 47, 659–677.
6. Nedolya, N. A.; Tarasova, O. A.; Volostnykh, O. G.; Albanov, A. I.; Trofimov, B. A.
Chem. Heterocycl. Compd. (Engl. Transl.) 2012, 47, 1430–1435.
7. (a) Brandsma, L. Preparative Polar Organometallic Chemistry In ; Springer:
Berlin, 1990; Vol. 2, pp 107–110, 118; (b) Piffl, M.; Weston, J.; Günther, W.;
Anders, E. J. Org. Chem. 2000, 65, 5942–5950; (c) Arroyo, Y.; Meana, Á.;
Rodríguez, J. F.; Santos, M.; Sanz-Tejedor, M. A.; García-Ruano, J. L. J. Org. Chem.
2005, 70, 3914–3920.
8. (a) Reich, H. J.; Willis, W. W., Jr. J. Org. Chem. 1980, 45, 5227–5229; (b) Cabiddu,
S.; Floris, C.; Melis, S.; Sotgiu, F. Phosphorus, Sulfur Relat. Elem. 1984, 19, 61–64;
(c) Nakamura, S.; Nakagawa, R.; Watanabe, Y.; Toru, T. J. Am. Chem. Soc. 2000,
122, 11340–11347.
9. Katritzky, A. R.; Piffl, M.; Lang, H.; Anders, E. Chem. Rev. 1999, 99, 665.
10. (a) Trofimov, B. A.; Oparina, L. A.; Lavrov, V. I.; Parshina, L. N. Zh. Org. Khim.
1990, 26, 725–729; (b) Dmitrieva, L. L.; Nikitina, L. P.; Albanov, A. I.; Nedolya, N.
A. Russ. J. Org. Chem. 2005, 41, 1430–1444.
11. (a) DeWolfe, R. H.; Young, W. G. Chem. Rev. 1956, 56, 753–901; (b) Tarbell, D. S.;
Lovett, W. E. J. Am. Chem. Soc. 1956, 78, 2259–2264; (c) Simons, D. M.; Verbanc,
J. J. J. Polym. Sci. 1960, 44, 303–311; (d) Prosser, T. J. J. Am. Chem. Soc. 1961, 83,
1701–1704; (e) Price, C. C.; Snyder, W. H. J. Am. Chem. Soc. 1961, 83, 1773; (f)
Price, C. C.; Snyder, W. H. J. Org. Chem. 1962, 27, 4639–4641; (g) Crivello, J. V.;
Kaur, S. J. Macromol. Sci., Pure Appl. Chem. 1998, A35, 411–426; (h)
Vansteenkiste, S.; Matthijs, G.; Schacht, E.; De Schrijver, F. C.; Van Damme,
M.; Vermeersch, J. Macromolecules 1999, 32, 55–59.
14. Treatment of 2-Aza-1,3,5-triene 1c with t-BuOK. To a stirred solution of the
product mixture (7.58 g, 34 mmol) containing ꢁ92% of 2-aza-1,3,5-triene 1c
and ꢁ8% of pyrrole 5c in THF (51 mL), DMSO (11 mL) and t-BuOK (4.25 g,
37.9 mmol) were added sequentially at ꢀ60 °C. The mixture was stirred for
30 min while the temperature was kept between ꢀ35 °C and ꢀ30 °C, and was
then cooled to ꢀ70 °C, and H2O (40 mL) was added. After separation of the
layers, the products were extracted from the aqueous fraction with Et2O
(4 ꢂ 40 mL). The combined organic fractions were washed with H2O
(3 ꢂ 50 mL) and dried (MgSO4). Flash column chromatography of the
solution on alumina (2 cm layer) followed by concentration under reduced
pressure gave 6.54 g (86%) of a dark-brown mobile liquid consisting of 4,5-
dihydro-1,3-thiazole 9a (ꢁ74%), pyrrole 5c0 (ꢁ10%), and an unidentified
product (ꢁ16%) (by 1H and 13C NMR). 4,5-Dihydro-1,3-thiazole 9a was
separated by column chromatography (neutral alumina, hexane) in a yield of
3.2 g (ꢁ46%). Pyrrole 5c0 was identified by NMR in the mixture with thiazole 9a
in one of the small fractions.
5-Ethenylidene-4-ethyl-2-[(Z)-1-methoxyprop-1-enyl]-4-methyl-4,5-dihydro-1,3-
thiazole (9a). Brownish viscous liquid, n2D3 1.5481. 1H NMR (400.13 MHz, CDCl3,
ppm): d = 5.74 (1H, q, 3J 6.9 Hz, CH3CH@), 5.12 and 5.10 (1H, d, 2J 10.2 Hz,
CH2@C@), 3.68 (3H, s, OCH3), 1.91 and 1.64 (2H, dq, 3J 7.4 Hz, 2J 13.6 Hz,
CH2CH3), 1.77 (3H, d, 3J 6.9 Hz, CH3CH@), 1.42 (3H, s, CH3-4), 0.86 (3H, t, 3J
7.4 Hz, CH2CH3). 13C NMR (100.62 MHz, CDCl3, ppm): d = 198.04 (@C@), 158.36
(C@N), 149.54 (@C–O), 119.41 (CH3CH@), 109.43 (@C–S), 85.01 [C(C2H5)CH3],
83.52 (CH2@C@), 59.78 (OCH3), 34.83 (CH2CH3), 27.76 (CH3CH=), 11.03 (CH3- ),
4
8.71 (CH2CH3). IR (cm–1): 3043, 2971, 2932, 2878, 2854, 2841, 1954, 1652,
1604, 1457, 1446, 1435, 1377, 1367, 1329, 1308, 1290, 1241, 1222, 1201, 1192,
1154, 1137, 1113, 1097, 1072, 1041, 1000, 977, 929, 896, 891, 864, 824, 812,
786, 711, 687, 681. Anal. Calcd for C12H17NOS: C, 64.53; H, 7.67; N, 6.27; S,
14.36. Found: C, 64.40; H, 7.75; N, 6.47; S, 14.10.
15. 1-(sec-Butyl)-3-methoxy-2-(prop-1-ynylsulfanyl)-1H-pyrrole (5c0). 1H NMR
(400.13 MHz, CDCl3, ppm): d = 6.65 (1H, d, 3J 3.3 Hz, H-5), 5.89 (1H, d, 3J
3.3 Hz, H-4), 4.52 (1H, tq, 3J 6.8 Hz, J 7.1 Hz, CHCH3), 3.82 (3H, s, OCH3), 1.84
and 1.77 (2H, both m, CH2CH3), 1.82 (3H, s, CH3C„), 1.38 (3H, d, 3J 6.8 Hz,
CHCH3), 0.82 (3H, t, 3J 7.4 Hz, CH2CH3). 13C NMR (100.62 MHz, CDCl3, ppm):
d = 151.23 (C-3), 118.00 (C-5), 102.48 (C-2), 95.06 (C-4), 67.90 (CH3C„), 58.34
(OCH3), 55.53 (SC„), 53.27 (NCH), 30.60 (CH2CH3), 21.70 (CHCH3), 10.77
(CH2CH3), 4.76 (CH3C„).
12. Tarbell, D. S.; McCall, M. A. J. Am. Chem. Soc. 1952, 74, 48–56.
13. Prop-2-ynyl N-(sec-butyl)-2-methoxybuta-2,3-dienimidothioate (4c). To
a
vigorously stirred solution of methoxyallene (4.61 g, 65.8 mmol) in THF
(40 mL) was added BuLi (40.8 mmol, 25.5 mL of a ꢁ1.6 M solution in hexane)
at ꢀ100 °C under argon. The temperature was allowed to rise to ꢀ30 °C, after
which the solution was cooled to ꢀ80 °C and sec-butyl isothiocyanate (4.45 g,
38.7 mmol) was added in one portion. The temperature of the reaction mixture
was allowed to rise to ca. ꢀ30 °C, and was maintained at ꢀ33 °C to ꢀ25 °C for
16. Martins, M. A. P.; Frizzo, C. P.; Moreira, D. N.; Buriol, L.; Machado, P. Chem. Rev.
2009, 109, 4140–4182.