(Propargylsulfanyl)-2-aza-1,3,5-trienes as a direct source for novel family of highly functionalized 4,5-dihydro-1,3-thiazoles

Article abstract of DOI:10.1016/j.tet.2016.12.064

A novel, simple approach to 2-(1-alkoxyprop-1-enyl)-5-ethenylidene-4,5-dihydro-1,3-thiazoles has been disclosed through the reaction of (propargylsulfanyl)-2-aza-1,3,5-trienes (readily available from alkoxyallenes, isothiocyanates, and propargyl bromide) with potassium or sodium tert-butoxide (1.1–1.4 equiv) under mild conditions [DMSO/THF (～1:4–5), ca.??30?°C, 15–30?min]. The process proceeds through deprotonation of an activated SCH₂group, followed by intramolecular [1,5]-ring-closure. Unlike alkyl-, benzyl-, and allylsulfanyl-analogues, the exclusive or competitive formation of seven-membered azaheterocycles was not observed.

Full text of DOI:10.1016/j.tet.2016.12.064

Accepted Manuscript
(Propargylsulfanyl)-2-aza-1,3,5-trienes as a direct source for novel family of highly
functionalized 4,5-dihydro-1,3-thiazoles
Nina A. Nedolya, Ol'ga A. Tarasova, Alexander I. Albanov, Lyudmila V. Klyba, Boris
A. Trofimov
PII:
S0040-4020(16)31361-8
10.1016/j.tet.2016.12.064
TET 28356
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 5 May 2016
Revised Date: 19 December 2016
Accepted Date: 23 December 2016
Please cite this article as: Nedolya NA, Tarasova OA, Albanov AI, Klyba LV, Trofimov BA,
(Propargylsulfanyl)-2-aza-1,3,5-trienes as a direct source for novel family of highly functionalized 4,5-
dihydro-1,3-thiazoles, Tetrahedron (2017), doi: 10.1016/j.tet.2016.12.064.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract
(Propargylsulfanyl)-2-aza-1,3,5-trienes as a
direct source for novel family of highly func-
tionalized 4,5-dihydro-1,3-thiazoles
Leave this area blank for abstract info.
Nina A. Nedolya*, Ol'ga A. Tarasova, Alexander I. Albanov, Lyudmila V. Klyba, Boris A. Trofimov*
Departmental address here

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
(Propargylsulfanyl)-2-aza-1,3,5-trienes as a direct source for novel family of
highly functionalized 4,5-dihydro-1,3-thiazoles
Nina A. Nedolya*, Ol'ga A. Tarasova, Alexander I. Albanov, Lyudmila V. Klyba, Boris A. Trofimov*
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 1 Favorsky Street, Irkutsk 664033, Russian Federation
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A novel, simple approach to 2-(1-alkoxyprop-1-enyl)-5-ethenylidene-4,5-dihydro-1,3-thiazoles
has been disclosed through the reaction of (propargylsulfanyl)-2-aza-1,3,5-trienes (readily avail-
able from alkoxyallenes, isothiocyanates, and propargyl bromide) with potassium or sodium
tert-butoxide (1.1–1.4 equiv) under mild conditions [DMSO/THF (~1:4–5), ca. –30 °C, 15–30
min]. The process proceeds through deprotonation of an activated SCH2 group, followed by
intramolecular [1,5]-ring-closure. Unlike alkyl-, benzyl-, and allylsulfanyl-analogues, the exclu-
sive or competitive formation of seven-membered azaheterocycles was not observed.
Available online
Keywords:
5-Ethenylidene-4,5-dihydro-1,3-thiazoles
(Propargylsulfanyl)-2-aza-1,3,5-trienes
Alkoxyallenes
Isothiocyanates
Propargyl bromide
2016 Elsevier Ltd. All rights reserved
.
1. Introduction
(methoxyprop-1-enyl)-5-vinyl-4,5-dihydro-1,3-thiazoles 5 and 6,
respectively (Scheme 1).6
Thiazoles and their derivatives, including 2-thiazolines (4,5-
dihydro-1,3-thiazoles), are an important class of heterocyclic
compounds that have found application in wide range of fields
ranging from medicine and pharmacology to thin and general
organic synthesis and industry.1,2 Besides, The 2-thiazoline cycle
is the a privileged structural motif found in many natural prod-
ucts and pharmaceuticals, such as thiopeptide antibiotics, cyto-
toxic alkaloids, etc.,3 as well as in aroma and flavors.3a,4 There-
fore, thiazole derivatives attract considerable interest, which war-
rants the continued development of synthetic methods to access
these species.1,5
Our own interest in the synthesis of thiazole derivatives syn-
thesis stems from our recently reported short communications on
the novel approach to 4,5-dihydro-1,3-thiazole ring assembly
from methoxyallene, isopropyl isothiocyanate, and benzyl or
allyl bromide (through synthesis and structural reorganizations of
corresponding azatrienes).6 We have found, that conjugated 2-
aza-1,3,5-trienes 1, H2C=CHC(OR1)=C(SCH2R4)N=CR2R3,
which under heating undergo cyclization to yield stable 2,3-
dihydropyridines,7 and, upon treatment with potassium tert-
butoxide, they give seven-membered azaheterocycles (dihydro-
azepines and azepines),8 for example, into compounds 2, 3a, and
4, respectively (Scheme 1), can serve as the direct precursors of
fully substituted 4,5-dihydro-1,3-thiazoles, if alkylsulfanyl sub-
stituent is replaced with benzyl- or allylsulfanyl one.9 In this
case, 2-aza-1,3,5-trienes 1b (R = Ph) and 1c (R = CH2=CH), un-
der the reaction conditions similar to those yielding seven-
membered azaheterocycles synthesis8b [t-BuOK (1.2−1.4 equiv),
DMSO/THF (~1:5), ca. –30 °C, 30 min], were transformed into
previously unknown 2-(methoxyprop-1-enyl)-5-phenyl- and 2-
Scheme 1. Synthesis and structural transformations of (methyl-, benzyl-, and
allylsulfanyl)-2-aza-1,3,5-trienes
1 in the presence of potassium tert-
butoxide: a novel approach to dihydroazepines 3, azepine 4, and 4,5-dihydro-
1,3-thiazoles 5 and 6.
In both cases the reaction was not completely chemoselective.
From the (benzylsulfanyl)-2-aza-1,3,5-triene 1b, along with 5-
phenyl-4,5-dihydro-1,3-thiazole 5, 4,5-dihydro-3H-azepine 3b
and 3H-azepine 4 were obtained in yield of 20, 23, and 5%, re-
spectively.6a,6b However, (allylsulfanyl)-2-aza-1,3,5-triene 1c
afforded 5-vinyl-4,5-dihydro-1,3-thiazole derivative 6 (yield
~18%) together with 3H-azepine 4 (yield ~7%)6b,6c with no sign
of 4,5-dihydro-3H-azepine (Scheme 1).
It was previously reported,8 that the formation of seven-
membered azaheterocycles requires deprotonation at the ketimine
fragment, followed by [1,7]-electrocyclization of the carbanion A
to the azacycloheptadienyl anion B (Scheme 2, Path A). The lat-

2
Tetrahedron
ter undergoes either protolysis on aqueous workup or elimina-
pyrroles 9 by the standard practices, because during the vacuum
ACCEPTED MANUSCRIPT
tion of the sulfide anion (MeS–, PhCH2S– or CH2=CHCH2S–) to
give 4,5-dihydro-3H-azepines 3 and 3H-azepine 4, respectively.
Competitive deprotonation of the benzylsulfanyl or allylsulfanyl
substituent, i.e., SCH2 moiety activated with phenyl or vinyl
group, results in the formation of 4,5-dihydro-1,3-thiazoles 5 and
6. The reaction most likely proceeds through anions C–D
(Scheme 2, Path B).6b
distillation they cyclized to 2,3-dihydropyridines,7b,7c and upon
chromatographic separation on a column with Al2O3 or SiO2 they
decomposed. This is why, in further reactions with superbases, 2-
aza-1,3,5-trienes 7, contaminated with pyrroles 9, were used.
Scheme 3. Synthesis of (propargylsulfanyl)-2-aza-1,3,5-trienes 7.
We have also studied the configuration of (propargylsulfanyl)-
2-aza-1,3,5-trienes on example of the compound 7a (Fig. 1). The
homo- and heteronuclear 1H–1H COSY, 1H–1H NOESY, and 1H–
13C HMBC 2D experiments provided additional support for the
proposed structure. SCH2C≡CH group is in (Z)-configuration
relatively to the group MeO at C=C bond.
Scheme 2. Plausible mechanisms of reorganization of 2-aza-1,3,5-trienes 1b
and 1c to 4,5-dihydro-3H-azepine 3, 3H-azepine 4, and 4,5-dihydro-1,3-
thiazoles 5 and 6 in the presence of potassium tert-butoxide.
Therefore, the unprecedented base-driven transformation of 2-
aza-1,3,5-trienes 1b and 1c into 4,5-dihydro-1,3-thiazoles can
have a great synthetic potential if applied to new representatives
of alkoxyallene/isothiocyanate-based 2-aza-1,3,5-trienes contain-
ing sulfasubstituent with activated methylene group at the sulfur
atom.
In this paper, we demonstrate a novel synthetic approach to a
new class of 4,5-dihydro-1,3-thiazole derivatives, namely 2-(1-
alkoxyprop-1-enyl)-5-ethenylidene-4,5-dihydro-1,3-thiazoles.
Fig. 1. Configuration of (propargylsulfanyl)-2-aza-1,3,5-triene 7a, according
to NMR data.
Treatment of (propargylsulfanyl)-2-aza-1,3,5-trienes 7 with
potassium tert-butoxide under conditions typical for dihydroaze-
pine/azepine synthesis8 [DMSO/THF (1:4.3–4.8), ca. –30 °C, 30
min] provided really surprising results. In this case, instead of
expected 3H-azepines 10 or 11, the only observed products were
5-ethenylidene-4,5-dihydro-1,3-thiazoles 12a−i in the isolated
yield of 5−58% (Table 1).
2. Results and discussion
We started our work with the preparation of a series of (pro-
pargylsulfanyl)-2-aza-1,3,5-trienes 7 from α-lithiated alkoxy-
allenes7,8a,10 (methoxy-, ethoxy-, n-butoxy-, and 1-ethoxyethoxy
allenes), isothiocyanates (isopropyl, sec-butyl, cyclopentyl, cy-
clohexyl, and cycloheptyl isothiocyanates), and propargyl bro-
mide by a one-pot synthesis of 1-aza-1,3,4-trienes 8 and subse-
quent thermally induced [1,5]-sigmatropic rearrangement
(Scheme 3).
As can be seen from the Table 1, the dependence of the 4,5-
dihydro-1,3-thiazoles 12 yields from the structure of the substitu-
ents in both butadiene and ketimine parts of the 2-aza-1,3,5-triene
molecule is evident, but a general pattern “stereo-electronic effect
vs yield” is not clearly visible.
After aqueous workup, followed by evaporation of solvents
under reduced pressure at ~35 °C, along with 1-aza-1,3,4-trienes
8, 2-aza-1,3,5-trienes 7 and some amounts (mainly traces) of
pyrroles 9 (as side products resulted from competitive intramo-
lecular [1,5]-heterocyclization of compounds 8) were identified
(by 1H NMR) in crude products (Scheme 3). The isomerization of
1-aza-1,3,4-trienes 8 into the target 2-aza-1,3,5-trienes 7 was
completed by vacuum treatment of the products mixture at 50−60
°C (1–2 mmHg) for 5–15 min. The content of pyrroles 9 in a
mixture with 2-aza-1,3,5-trienes 7 increased up to <1−8%. The
conversion of 1-aza-1,3,4-trienes 8 was ~100%. Total yields of
compounds 7 and 9 were ranging from good to excellent
(80−97%). It should be noted that due to high reactivity of 2-aza-
1,3,5-trienes 7 it was impossible to get rid of the impurities of
The use of sodium tert-butoxide (instead of potassium tert-
butoxide) in the reaction with 2-aza-1,3,5-trienes 7a and 7d gave
4,5-dihydro-1,3-thiazoles 12a and 12d in isolated yields that are
comparable with those obtained with t-BuOK (Table 1, entries 1
and 2, 5 and 6). The concurrent formation of seven-membered
azaheterocycles in the reaction of (propargylsulfanyl)-2-aza-
1,3,5-trienes 7 even with the strong base t-BuOK was not ob-
served, i.e., under the studied conditions the reaction involving
deprotonation on the ketimine fragment does not occur. Addi-
tional evidence of a higher reactivity of propargylsulfanyl group
toward investigated bases compared with substituent in the
ketimine fragment was obtained when the reaction of

3
ACCEPTED MANUSCRIPT
Table 1
Synthesis of 4,5-dihydro-1,3-thiazoles 12 through structural reorganization of (propargylsulfanyl)-2-aza-1,3,5-trienes 7 upon treatment with sodium or
potassium tert-butoxide
Entry
1
Substrate
Base
Producta
Yieldb (%)
56
t-BuONa
12a
12a
12b
7a
7a
7b
7c
t-BuOK
t-BuOK
t-BuOK
58c
2
3
43
4
5
5
12c
12d
25
t-BuONa
t-BuOK
7d
6
7
8
23d
37c
24e
12d
12e
7d
7e
7f
t-BuOK
t-BuOK
12f

4
Tetrahedron
ACCEPTED MANUSCRIPT
9
t-BuONa
42
48
43
12g
7g
N
Me
Me
.
S
10
11
t-BuONa
t-BuONa
O
EtO
12h
12i
7h
7i
a Exclusively or mainly (Z)-isomers.
b Isolated yield, after column chromatography.
c A mixture of (Z)- and (E)-isomers in a ratio of ~88:12 (by 1H NMR).
d For 15 min.
e A mixture of (Z)- and (E)-isomers in a ratio of ~80:20 (by 1H NMR).
(methylsulfanyl)-2-aza-1,3,5-triene 1a (Schemes 1 and 2), not
having competitive reaction center at the sulfur atom, with sodi-
um tert-butoxide (1.0–1.5 equiv, THF, 0 °С, 10 min) was carried
out. No product formation was observed by 1H NMR.
yield, structure, and ratio of the products, on the example of the
2-aza-1,3,5-triene 7a. The results are summarized in the Table 2.
Under the standard reaction conditions [DMSO/THF (~1:4),
ca. −30 °C, 30 min], the main reaction product of 2-aza-1,3,5-
triene 7a as with t-BuOK, and t-BuONa was the 4,5-dihydro-1,3-
thiazole 12a [with t-BuONa – (Z)-isomer; with t-BuOK – a mix-
ture of (Z)- and (E)-isomers in a ratio of ~88:12 (Table 2, entries
1 and 2). In the absence of DMSO, the corresponding 4,5-
dihydro-1,3-thiazole 12a was obtained only in the reaction of 2-
aza-1,3,5-triene 7a with t-BuOK. The isolated yield of 12a was
41% (Table 2, entry 3). However, with t-BuONa (without
DMSO), under similar conditions, the reaction does not take
place (Table 2, entry 4). At the same time, (propargylsulfanyl)-2-
aza-1,3,5-triene 7a isomerizes to (propa-1,2-dienylsulfanyl)-2-
aza-1,3,5-triene 7a' on ~54% (by 1H NMR). When the reaction of
compound 7a with t-BuOK in THF (without DMSO) was carried
out at 0 °C for 10 min, a mixture of (Z)- and (E)-isomers of 4,5-
dihydro-1,3-thiazole 12a was obtained in a ratio of ~72:28 and in
57% total yield (Table 2, entry 5). Similarly, with t-BuONa (also
without DMSO) at ~0 °C for 10 min, only (Z)-isomer of 4,5-
dihydro-1,3-thiazole 12a was isolated in 43% yield (Table 2,
entry 6).
This means that sodium tert-butoxide is the base that is not
strong enough for deprotonation of ketimines. Our attempt to
deprotonate (benzylsulfanyl)-2-aza-1,3,5-triene 1b with sodium
tert-butoxide under the conditions that were used for (propargyl-
sulfanyl)-analogues (DMSO/THF, ca. –30 °C, 30 min) also
failed. Neither dihydrothiazole 5 nor azepine derivatives 3b and 4
(Schemes 1 and 2) were found as the expected reaction products.
Only an unreacted 2-aza-1,3,5-triene 1b was identified by NMR.
High efficiency of t-BuONa as base for deprotonating base for
(propargylsulfanyl)-2-aza-1,3,5-trienes was additionally illustrat-
ed by the synthesis of 4,5-dihydro-1,3-thiazoles 12g, 12h, and
12i in isolated yields of 42, 48, and 43%, respectively (Table 1,
entries 9–11). It should be also noted that in the presence of t-
BuONa, 5-ethynyl-4,5-dihydro-1,3-thiazoles 13a, 13d, and 13g,
unisomerized precursors of 5-ethenylidene-4,5-dihydro-1,3-
thiazoles 12a, 12d, and 12g, were identified among the reaction
products by the NMR and/or mass spectrometry.
The reaction of 2-aza-1,3,5-triene 7d with t-BuOK gives an
example of the effect of the reaction time on the conversion of
compound 7d and the yield of compound 12d. It is established
that quantitative conversion of 2-aza-1,3,5-triene is reached in
10–15 min (instead of 30 min) at −30 °C, the yield of 4,5-
dihydro-1,3-thiazole 12d being 23%. When the reaction time was
shortened to 5 min, the reaction mixture, along with 4,5-dihydro-
1,3-thiazole 12d (~78%), contained unreacted 2-aza-1,3,5-triene
A mixture of (Z)- and (E)-isomers of 4,5-dihydro-1,3-
thiazoles 12e and 12f in a ratio of ~88:12 and ~80:20 (by H
NMR) was also obtained in the reaction of 2-aza-1,3,5-trienes 7e
and 7f, respectively, with t-BuOK in DMSO/THF at ca. –30 °C
for 30 min (Table 1, entries 7 and 8).
1
Exclusive (Z)-configuration of the products obtained in the
presence of t-BuONa, is probably, due to the formation of a more
stable (than with bulkier potassium counter-ion) intermediate,
wherein sodium cation is coordinated both to a terminal carbani-
on center, and with an electron lone pare of the oxygen atom
(from alkoxy group), thereby fixing the (Z)-configuration (Fig.
2).
1
7d (~22%) (by H NMR). Compound 12d was isolated in 18%
yield. Replacement of t-BuOK by t-BuONa (1.3 equiv, −30 °C,
30 min) did not reveal any obvious advantages of one base over
another. In both cases, the preparative yield of the desired prod-
uct remained at the level of 23−25%.
We have also controlled the influence of the deprotonation
conditions (solvent, base, temperature, and reaction time) on the

5
ACCEPTED MANUSCRIPT
Table 2
Influence of the deprotonation conditions on the yield, structure, and ratio of products in the reaction of (propargylsulfanyl)-2-aza-1,3,5-
triene 7a with sodium or potassium tert-butoxide
Base
Solvent (mL)
DMSO THF
Deprotonation
Products ratioa (yield)b (%)
Entry
Azatriene
7a
(mmol)
Base
(mmol)
T (°C)
Time
(min)
(Z)-isomer 12a
(E)-isomer 12a'
–32 to –30
1
13.5
13.6
8.8
t-BuOK
15.6
15.6
10.4
10.3
10.4
10.3
5
5
0
0
0
0
22
22
15
15
15
15
30
30
30
30
10
10
~88 (58)c
~100 (56)
~100 (41)
0
~12
0
2
t-BuONa
t-BuOK
t-BuONa
t-BuOK
t-BuONa
–33 to –29
–35 to –30
–33 to –30
0
3
trace
0
4d
8.8
5
8.8
~72 (57)c
~28
0
6
8.8
–5 to 0
~100 (43)
a After flash chromatography on Al2O3 (by 1H NMR).
b Isolated yield, after column chromatography.
c Total yield of (Z)- and (E)-isomers.
d Mixture of starting azatriene 7a (46%) and its (propa-1,2-dienylsulfanyl)-derivative 7a' (54%) (by 1H NMR).
R2
R3
30 to 5 min, and a second stage of the reaction (with MeI) was
carried out at 35–42 °C for 75 min (Table 3, entry 5). In this case,
the ratio of the compounds 12a/14/15 was ~30:61:9 (by H
NMR). The formation of N-methylated derivative 16 (Scheme 4)
was not observed. This means that the rate of methylation of both
the carbon atoms (C1' and C3') of the substituent at C2-position of
the anionic intermediate F is much higher than that of also ex-
pected N-methylation.
N
H2C
Na+
1
.
S
O
R1
Fig. 2.
The structural reorganization of the 2-aza-1,3,5-trienes 7 to
4,5-dihydro-1,3-thiazoles 12 probably proceeds through anionic
species E and F (Scheme 4). Propargyl–allenyl isomerization can
occur both as before and after cyclization of the intermediate E.11
Along with the NMR spectra, structures 12a, 14, and 15 were
supported by electron ionization mass-spectra (70 eV). Surpris-
ingly, small changes in the structure of the substituent at the C2-
position of 4,5-dihydro-1,3-thiazole cycle in compounds 12a, 14,
and 15 had an unexpectedly strong impact on the character of
fragmentation of their molecular ions with participation of this
substituent. In all cases, fragmentation of the molecular ion in-
cludes cleavage of the C1'−C2 bond. But in the case of com-
pounds 12a and 14, this cleavage leads to the formation of cati-
ons [M – C7H8NS]+ with m/z 71 (Irel. 12%) and 85 (Irel. 100%),
respectively (Fig. 3).
Scheme 4. Plausible mechanisms of reorganization of 2-aza-1,3,5-trienes 7 to
4,5-dihydro-1,3-thiazoles 12 in the presence of sodium or potassium tert-
butoxide.
The proposed reaction mechanism (Scheme 4) has received
experimental support. Thus, treatment of 2-aza-1,3,5-triene 7a at
first with t-BuOK and then with methyl iodide, along with 4,5-
dihydro-1,3-thiazole 12a, gave two new 4,5-dihydro-1,3-thiazole
derivatives, namely compounds 14 and 15 (Scheme 4, Table 3).
As can be seen from the Table 3, the ratio of products depends
on the reaction conditions. For instance, with sodium counter-ion
methylation of mesomeric anion F does not take place (Table 3,
entry 1). In the reaction of azatriene 7a with t-BuOK, the highest
content (70%) of the products of C-methylation was achieved
when the ratio of DMSO/THF was increased from ~0.2:1 to 0.7:1
(v/v) but the reaction time, on the contrary, was decreased from
Fig. 3. Electron ionization mass-spectra (70 eV) of compounds 12a, 14, and
15.
Moreover, for the compound 14 it is main channel of primary
fragmentation of M+•. While cleavage of the C1'−C2 bond in the
compound 15 leads to the release of the substituent from С2-

6
Tetrahedron
ACCEPTED MANUSCRIPT
Table 3
Results of the experiments on methylation of the intermediates in the reaction of (propargylsulfanyl)-2-aza-1,3,5-triene 7a upon treatment with
sodium or potassium tert-butoxide
Base
Deprotonation
MeI
Products ratioa (yield)b (%)
Entry Azatriene
DMSO/
7a(mmol)
THF (mL)
Base
(mmol)
T (°C)
Time (mmol)
(min)
T (°C)
Time
(min)
12a
14
15
1
2
13.3
13.3
t-BuONa
t-BuOK
15.6
15.6
5/22
5/22
–32 to –25
–33 to –25
30
30
35.2
37.3
–60 to 23
–60 to 23
50
72
~100 (57)c
0
0
33–40
r.t.
30
over-
night
19.7
~49 (25)
~65 (35)
~38 (19)
~27 (16)
~13 (7)
~8 (4)
d
e
3
4
5
8.4
8.4
7.9
t-BuOK
t-BuOK
t-BuOK
9.9
9.9
9.3
6/28
6/28
7/10
–60 to –30
–60 to –40
–33 to –25
35.2
35.2
33.8
–30 to 19
–40 to –33
–30 to 10
35–42
60
60
10
75
~77 (43)
~23 (13)
0
5
~30 (7)
~61 (15)
~9 (2)
a After flash chromatography on Al2O3 (by 1H NMR).
b Yields calculated from 1H NMR spectra of the products, isolated by column chromatography as a mixture.
c Isolated yield.
d The time of rising the temperature from –60 to –30 °C.
e The time of rising the temperature from –60 to –40 °C.
position as [C5H9O]• radical and to the appearance of [C7H8NS]+
ion with m/z 138 (Irel. 14%). Lengthening of the alkyl part of a
substituent at the C2-position led to the appearance of the second
channel of fragmentation of this substituent (Fig. 3, compound
15, ion [M – Et]+, m/z 194).
agreement with the structure of the products. Pyrroles 9, 9', and
9'' were mostly identified in NMR spectra of the products mix-
tures; some of them were concentrated in small fractions and
characterized by NMR.
3. Conclusion
However, the decay of 4,5-dihydro-1,3-thiazole ring under
electron ionization is general for all investigated compounds and
runs mainly with pairwise cleavage of С2–S/C4–N bonds and
with consequent formation of cation-radicals of nitrile, [RCN]+•
In conclusion, we have shed new light on the reactivity and
synthetic potential of 2-aza-1,3,5-trienic systems readily accessi-
ble from allenic or acetylenic carbanions, isothiocyanates, and
alkylating agents. In particular, we have shown that (propargyl-
sulfanyl)-2-aza-1,3,5-trienes in the presence of potassium or so-
dium tert-butoxide undergo an unprecedented structural reorgani-
zation leading to the construction of 4,5-dihydro-1,3-thiazole (2-
thiazoline) ring. Most importantly, on the base of the found reac-
tion, we have developed a simple approach to a new class of mul-
tifunctional 2-thiazolines, namely 2-(1-alkoxyprop-1-enyl)-5-
ethenylidene-4,5-dihydro-1,3-thiazoles, that are not available by
other means. Obviously, the synthetic potential of the discovered
reaction of selective mild deprotonation of (propargylsulfanyl)-2-
aza-1,3,5-trienes leading to 2-thiazolines with rare substituents is
certainly not limited to the described examples. This protocol
expands the range of synthetically available 2-thiazolines as
building blocks and might be useful in the synthesis of bioactive
products.
[R
=
MeCH=C(OMe) (12a), CH2=CHC(OMe)Me (14),
EtCH=C(OMe) (15)], and probably of 4-methylpent-1-yne-3-
thione, [Me2CHC(=S)C≡CH]+•, with m/z 112 (Fig. 3). The peak
intensity of the latter ion was maximal for the compounds 12a
and 15 and for all compounds the intensity of this peak was near-
ly twice the intensity of the [RCN]+• ion peak.
2-(Propargylsulfanyl)-1H-pyrroles 9, that were present in the
starting compounds 7 in small amount (from trace to ~8%, by 1H
NMR), upon the reaction of the latter with potassium tert-
butoxide isomerized to 2-(prop-1-ynylsulfanyl)-1H-pyrroles 9''.
Whereas, with t-BuONa pyrroles 9 isomerizes to 2-(propa-1,2-
dienylsulfanyl)-1H-pyrroles 9' (Scheme 5).
Currently, study of the scope and generality of the found nov-
el methodology for dihydrothiazole ring construction as well as
optimization of the reaction conditions are in progress.
4. Experimental Section
Scheme 5. Isomerization of 2-(propargylsulfanyl)-1H-pyrroles 9 into 2-
(propa-1,2-dienylsulfanyl)- and 2-(prop-1-ynylsulfanyl)-derivatives 9' and
9'', respectively, upon treatment with sodium or potassium tert-butoxide.
4.1. General Comments
1H (400.13 MHz), 13C (100.62 MHz), and 15N (40.55 MHz)
NMR spectra were recorded with Bruker DPX-400 and Bruker
AV-400 spectrometers in CDCl3 at r.t., referenced to HMDS (for
1H), CDCl3 (for 13C), and MeNO2 (for 15N) as internal standards.
Assignments of spectra were carried out using 2D experiments.
IR spectra were measured neat on a Bruker Vertex-70 infrared
All the above mentioned compounds are novel. were synthe-
sized by us for the first time. 4,5-Dihydro-1,3-thiazoles 12 were
isolated by column chromatography and adequately characterized
by spectral [NMR (1H, 13C, 15N, COSY, NOESY, HSQC,
HMBC), IR, MS] and elemental analysis data which are in good

7
spectrophotometer. The mass spectra (EI, 70 eV; CI, gas-reactant
– methane) were obtained with a Agilent 5975С instrument. The
microanalyses were performed with a Flash EA 1112 Series ele-
mental analyzer. Full spectral data for all novel compounds are
given below, few previously characterized compounds gave spec-
tra consistent with the literature. Alkoxyallenes12 and isothiocya-
nates,13 were prepared according to the reported procedures. n-
BuLi (1.6 M and 2.5 M solution in hexane), propargyl bromide,
t-BuONa, t-BuOK, and solvents are commercially available. All
solvents were purified according to standard procedures. All re-
actions involving n-BuLi and sodium or potassium tert-butoxide
were carried out under anhydrous conditions and under argon
atmosphere (with n-BuLi). For all reactions at low temperatures,
a cooling bath with liquid N2 was used. Reaction courses and
product mixtures were routinely monitored by thin-layer chroma-
tography using precoated silica gel 60 F254 aluminum plates and
visualized by exposure to I2 vapour.
Me2C=N); δC (100.6 MHz, CDCl3) 175.1 (C=N), 138.9
ACCEPTED MANUSCRIPT
(=C−O), 132.0 (=C−S), 126.1 (CH2=CH), 110.9 (CH2=CH), 80.6
(C≡), 70.4 (HC≡), 58.7 (OMe), 28.0, 21.6 (Me2C=N), 17.6
(SCH2). The homo- and heteronuclear H−1H COSY, H−1H
NOESY, and 1H−13C HMBC 2D experiments provided additional
support for the proposed structure of the compound 7a.
1
1
4.2.1.2. 1-Isopropyl-3-methoxy-2-(prop-2-ynylsulfanyl)-1H-
pyrrole (9a) (tentative assignment). δH (400 MHz, CDCl3) 6.70
(1 H, d, 3J 3.3 Hz, 5-H), 5.90 (1 H, d, 3J 3.3 Hz, 4-H), 4.88−4.81
(1 H, m, NCH), 3.79 (3 H, s, OMe), 3.26 (2 H, d, J 2.6 Hz,
SCH2), 2.20 (1 H, t, J 2.6 Hz, HC≡), 1.37 (6 H, d, J 6.8 Hz,
4
4
3
Me2CH).
4.2.2. Synthesis of 2-aza-1,3,5-triene 7b. Following the general
procedure,
a
mixture of prop-2-ynyl N-(sec-butyl)-2-
methoxybuta-2,3-dienimidothioate (1-aza-1,3,4-triene 8b) and 2-
aza-1,3,5-triene 7b in a ratio of ~1:2 (by 1H NMR) was obtained
from methoxyallene (4.61 g, 65.9 mmol), n-BuLi (25.5 mL, 40.8
mmol), s-BuNCS (4.45 g, 38.7 mmol), and propargyl bromide
(5.70 g, 47.9 mmol) in THF (40 mL). Vacuum treatment of crude
product at 56−58 °C (~1 mmHg) for 15 min gave 2-aza-1,3,5-
triene 7b contaminated with pyrrole 9b (~8%) (by 1H NMR).
4.2. General Procedure for the Synthesis of 2-Aza-1,3,5-
trienes 7a–i
To a vigorously stirred solution of alkoxyallene (47–86 mmol)
in THF (40–50 mL), n-BuLi (41−55 mmol, 16.5–22 mL of ~2.5
M a solution in hexane or 25.5 mL of ~1.6 M a solution in hex-
ane for 7b) was added at ca. –100 °C under argon. After stirring
for an additional 5–10 min at ca. –60 to –50 °C, the solution was
cooled to –80 °C, and isothiocyanate (39–50 mmol) or its mix-
ture with THF (3–4 mL) was added in one portion. The tempera-
ture was allowed to rise to ca. –30 °C, and the mixture was
stirred at this temperature for an additional 20–25 min. The mix-
ture was then cooled to –80 °C, and propargyl bromide (48–71
mmol) was added in one portion, after which the cooling bath
was removed. After stirring for 45–65 min at r.t., the mixture was
cooled to –60 °C, and then treated with H2O (40 mL) or saturated
aqueous solution of NH4Cl (40 mL). The layers were separated,
and the aqueous phase was extracted with Et2O (2–3×30–40 mL).
The organic layers were combined, washed with H2O (2–3×30–
50 mL), dried (MgSO4), and concentrated at a bath temperature
of ~35 °C under reduced pressure (on a rotary evaporator, then at
~1–2 mmHg) to give a residue consisting of corresponding 1-aza-
1,3,4-triene 8 as a mixture of the syn- and anti-isomers in admix-
4.2.2.1.
(1Z)-2-Methoxy-N-(1-methylpropylidene)-1-(prop-2-
ynylsulfanyl)buta-1,3-dien-1-amine (7b).6b Brown mobile liquid
(7.74 g, 90%); purity ~92%; ν(neat) 3293 (s) (HC≡) cm–1; δH
3
3
(400 MHz, CDCl3) 5.87 (1 H, dd, Jtrans 17.2, Jcis 10.9 Hz,
CH2=CH), 5.23, 4.95 (2 H, both dd, Jtrans 17.2, Jcis 10.9, Jgem
1.8 Hz, CH2=CH), 3.64 (3 H, s, OMe), 3.35 (2 H, d, J 2.7 Hz,
SCH2), 2.43 (2 H, q, J 7.4 Hz, MeСН2), 2.15 (1 H, t, J 2.7 Hz,
3
3
2
4
3
4
3
HC≡), 1.91 (3 H, s, MeС=), 1.17 (3 H, t, J 7.4 Hz, MeСН2); δC
(100.6 MHz, CDCl3) 179.0 (C=N), 138.4 (=C−O), 126.5 (=C−S),
126.2 (CH2=CH), 110.8 (CH2=CH), 80.8 (C≡), 70.5 (HC≡), 58.8
(OMe), 34.5 (MeСН2), 20.6 (MeС=), 17.6 (SCH2), 10.4
(MeСН2).
4.2.3. Synthesis of 2-aza-1,3,5-triene 7c. Following the general
procedure, 2-aza-1,3,5-triene 7c was obtained from methoxy-
allene (4.68 g, 66.9 mmol), n-BuLi (18 mL, 45.0 mmol), cyclo-
C5H9NCS (5.09 g, 40.1 mmol), and propargyl bromide (5.80 g,
48.7 mmol) in THF (40 mL).
1
ture with 2-aza-1,3,5-triene 7 and pyrrole 9 (by H NMR). The
4.2.3.1.
(1Z)-N-Cyclopentyliden-2-methoxy-1-(prop-2-
complete isomerization of 1-aza-1,3,4-trienes 8 into 2-aza-1,3,5-
trienes 7 was effected by vacuum treatment of the crude products
at 50–60 °C (1–2 mmHg) for 5–15 min. Yields (based on isothio-
cyanate) and characteristic data of 2-aza-1,3,5-trienes 7a–i are
reported below. 2-Aza-1,3,5-trienes were used in the next step
without further purification, i.e., in a mixture with small amount
of pyrrole 9.
ynylsulfanyl)buta-1,3-dien-1-amine (7c). Dark viscous liquid
(8.49 g, 90%); ν(neat) 3292 (s) (HC≡) cm–1; δH (400 MHz,
3
3
CDCl3) 6.00 (1 H, dd, Jtrans 17.2, Jcis 10.9 Hz, CH2=CH), 5.25,
4.98 (2 H, both dd, Jtrans 17.2, 3Jcis 10.9, 2Jgem 1.8 Hz, CH2=CH),
3
4
3.63 (3 H, s, OMe), 3.37 (2 H, d, J 2.6 Hz, SСН2), 2.32−2.19,
1.86−1.78 (4 H, both m, 2',5'-H), 2.16 (1 H, t, J 2.6 Hz, HC≡),
1.72−1.67, 1.67−1.53 (4 H, both m, 3',4'-H); δC (100.6 MHz,
CDCl3) 188.6 (C=N), 139.5 (=C−O), 133.4 (=C−S), 126.4
(CH2=CH), 111.3 (CH2=CH), 80.9 (C≡), 70.7 (HC≡), 58.9
(OMe), 36.1, 31.9 (2',5'-C), 24.6, 24.1 (3',4'-C), 17.9 (SCH2).
4
4.2.1. Synthesis of 2-aza-1,3,5-triene 7a. Following the general
procedure, a mixture of prop-2-ynyl N-isopropyl-2-methoxybuta-
2,3-dienimidothioate (1-aza-1,3,4-triene 8a), 2-aza-1,3,5-triene
1
7a, and pyrrole 9a in a ratio of ~43:55:2 (by H NMR) was ob-
4.2.4. Synthesis of 2-aza-1,3,5-triene 7d. Following the general
mixture of prop-2-ynyl N-cyclohexyl-2-
methoxybuta-2,3-dienimidothioate (1-aza-1,3,4-triene 8d), 2-aza-
tained from methoxyallene (6.00 g, 85.7 mmol), n-BuLi (22 mL,
55.0 mmol), i-PrNCS (5.06 g, 50.1 mmol), and propargyl bro-
mide (8.50 g, 71.4 mmol) in THF (50 mL). Vacuum treatment of
crude product at 52–58 °C for 12 min on a rotary evaporator and
then for 5 min at ~1 mmHg gave 2-aza-1,3,5-triene 7a contami-
nated with pyrrole 9a (~7%) (by 1H NMR).
procedure,
a
1
1,3,5-triene 7d, and pyrrole 9d in a ratio of ~55:43:2 (by H
NMR) was obtained from methoxyallene (5.00 g, 71.4 mmol), n-
BuLi (18 mL, 45.0 mmol), cyclo-C6H11NCS (5.65 g, 40.1
mmol)/THF (4 mL), and propargyl bromide (6.00 g, 50.4 mmol)
in THF (40 mL). Vacuum treatment of crude product at 52–60 °C
(~1 mmHg) for 8 min gave 2-aza-1,3,5-triene 7d contaminated
with pyrrole 9d (~4%) (by 1H NMR).
4.2.1.1. (1Z)-2-Methoxy-N-(1-methylethylidene)-1-(prop-2-
ynylsulfanyl)buta-1,3-dien-1-amine (7a). Dark-brown mobile
liquid (10.16 g, 97%); purity ~93%; ν(neat) 3291 (s) (HC≡) cm–1;
3
3
δH (400 MHz, CDCl3) 5.89 (1 H, dd, Jtrans 17.2, Jcis 10.9 Hz,
3
3
2
4.2.4.1.
(1Z)-N-Cyclohexyliden-2-methoxy-1-(prop-2-
CH2=CH), 5.24, 4.96 (2 H, both dd, Jtrans 17.2, Jcis 10.9, Jgem
ynylsulfanyl)buta-1,3-dien-1-amine (7d).6b Dark mobile liquid
(9.02 g, 90%); purity ~96%; ν(neat) 3293 (s) (HC≡) cm–1; δH
4
1.9 Hz, CH2=CH), 3.64 (3 H, s, OMe), 3.36 (2 H, d, J 2.6 Hz,
4
SСН2), 2.18 (1 H, t, J 2.6 Hz, HC≡), 2.17, 1.93 (6 H, both s,

8
Tetrahedron
ACCEPTED MANUSCRIPT
3
3
(400 MHz, CDCl3) 5.93 (1 H, dd, Jtrans 17.2, Jcis 10.9 Hz,
4.2.7. Synthesis of 2-aza-1,3,5-triene 7g. Following the general
3
3
2
CH2=CH), 5.24, 4.96 (2 H, both dd, Jtrans 17.2, Jcis 10.9, Jgem
2.0 Hz, CH2=CH), 3.64 (3 H, s, OMe), 3.36 (2 H, d, J 2.6 Hz,
procedure, prop-2-ynyl 2-(1-ethoxyethoxy)-N-isopropylbuta-2,3-
dienimidothioate (1-aza-1,3,4-triene 8g) was obtained from 1-(1-
ethoxyethoxy)allene (7.00 g, 54.7 mmol), n-BuLi (22 mL, 55.0
mmol), i-PrNCS (5.06 g, 50.1 mmol), and propargyl bromide
(7.14 g, 60.0 mmol) in THF (50 mL). Vacuum treatment of crude
product at 54−60 °C (~1 mmHg) for 13 min gave 2-aza-1,3,5-
triene 7g with trace of pyrrole 9g (by 1H NMR).
4
SCH2), 2.48−2.42, 2.32−2.28 (4 H, both m, 2',6'-H), 2.18 (1 H, t,
4J 2.6 Hz, HC≡), 1.85−1.77 (2 H, m, 4'-H), 1.72−1.62 (4 H, m,
3',5'-H); δC (100.6 MHz, CDCl3) 180.7 (C=N), 139.5 (=C−O),
131.6 (=C−S), 126.5 (CH2=CH), 111.2 (CH2=CH), 80.8 (C≡),
70.8 (HC≡), 59.1 (OMe), 39.0, 32.2, 27.7, 26.8, 25.6
(2',3',4',5',6'-C), 17.9 (SCH2).
4.2.7.1. (1Z)-2-(1-Ethoxyethoxy)-N-(1-methylethylidene)-1-(prop-
2-ynylsulfanyl)buta-1,3-dien-1-amine (7g). Dark-brown mobile
liquid (11.25 g, 84%); ν(neat) 3289 (s) (HC≡) cm–1; δH (400
4.2.4.2.
1-Cyclohexyl-3-methoxy-2-(prop-2-ynylsulfanyl)-1H-
pyrrole (9d) (tentative assignment). δH (400 MHz, CDCl3) 6.72 (1
H, d, 3J 3.2 Hz, 5-H), 5.91 (1 H, d, 3J 3.2 Hz, 4-H), 4.50−4.36 (1
H, m, NCH), 3.82 (3 H, s, OMe), 3.27 (2 H, d, 4J 2.6 Hz, SCH2),
3
3
MHz, CDCl3) 6.00 (1 H, dd, Jtrans 17.2, Jcis 11.1 Hz, CH2=CH),
3
3
2
5.37, 4.98 (2 H, both dd, Jtrans 17.2, Jcis 11.1, Jgem 1.8 Hz,
CH2=CH), 5.22 (1 H, q, 3J 5.3 Hz, OCHO), 3.90, 3.60 (2 H, both
dq, 2J 9.3, 3J 7.1 Hz, OCH2Me), 3.36, 3.33 (2 H, both dd, 2J 17.0,
4J 2.5 Hz, SCH2), 2.18, 1.93 (6 H, both s, Me2C=), 2.16 (1 H, t, 4J
4
2.20 (1 H, t, J 2.6 Hz, HC≡), 2.00−1.14 (10 H, m, 2',3',4',5',6'-
H); δC (100.6 MHz, CDCl3) 152.3 (3-C), 118.1 (5-C), 102.5 (2-
C), 94.3 (4-C), 80.5 (C≡), 71.4 (HC≡), 58.0 (OMe), 54.6 (NCH),
34.6 (2',6'-C), 25.9 (3',5'-C), 25.8 (4'-C), 25.6 (SCH2).
3
3
2.6 Hz, HC≡), 1.45 (3 H, d, J 5.3 Hz, OCHMe), 1.18 (3 H, t, J
7.1 Hz, OCH2Me); δC (100.6 MHz, CDCl3) 175.1 (C=N), 136.6
(=C−O), 132.6 (=C−S), 128.1 (CH2=CH), 112.0 (CH2=CH),
102.2 (OCHO), 80.8 (C≡), 70.5 (HC≡), 64.5 (OCH2Me), 28.2,
22.1 (Me2C=), 21.1 (OCHMe), 18.0 (SCH2), 15.4 (OCH2Me).
4.2.5. Synthesis of 2-aza-1,3,5-triene 7e. Following the general
procedure,
prop-2-ynyl
N-(sec-butyl)-2-ethoxybuta-2,3-
dienimidothioate (1-aza-1,3,4-triene 8e) was obtained from eth-
oxyallene (5.00 g, 59.5 mmol), n-BuLi (16.5 mL, 41.2 mmol), s-
BuNCS (4.61 g, 40.1 mmol), and propargyl bromide (5.95 g,
50.0 mmol) in THF (40 mL). Vacuum treatment of crude product
at 54−60 °C (~2 mmHg) for 15 min gave 2-aza-1,3,5-triene 7e
4.2.8. Synthesis of 2-aza-1,3,5-triene 7h. Following the general
procedure, prop-2-ynyl N-cyclohexyl-2-(1-ethoxyethoxy)buta-
2,3-dienimidothioate (1-aza-1,3,4-triene 8h) was obtained from
1-(1-ethoxyethoxy)allene (6.41 g, 50.1 mmol), n-BuLi (20 mL,
50.0 mmol), cyclo-C6H11NCS (5.85 g, 40.1 mmol)/THF (3 mL),
and propargyl bromide (6.54 g, 55.0 mmol) in THF (40 mL).
Vacuum treatment of crude product at 50–60 °C (~1 mmHg) for
10 min gave 2-aza-1,3,5-triene 7h contaminated with pyrrole 9h
(~7%) (by 1H NMR).
1
contaminated with contaminated with pyrrole 9e (~6%) (by H
NMR).
4.2.5.1.
(1Z)-2-Ethoxy-N-(1-methylpropylidene)-1-(prop-2-
ynylsulfanyl)buta-1,3-dien-1-amine (7e). Dark-brown liquid
(7.67 g, 81%); purity ~94%; ν(neat) 3293 (s) (HC≡) cm–1; δH
3
3
(400 MHz, CDCl3) 5.89 (1 H, dd, Jtrans 17.2, Jcis 11.0 Hz,
3
3
2
CH2=CH), 5.22, 4.92 (2 H, both dd, Jtrans 17.2, Jcis 11.0, Jgem
4.2.8.1.
(1Z)-N-Cyclohexyliden-2-(1-ethoxyethoxy)-1-(prop-2-
1.9 Hz, CH2=CH), 3.85 (2 H, q, 3J 7.0 Hz, OСН2Me), 3.34 (2 H,
ynylsulfanyl)buta-1,3-dien-1-amine (7h). Dark-brown viscous
4
3
d, J 2.6 Hz, SСН2), 2.42 (2 H, q, J 7.3 Hz, MeСН2C=), 2.14 (1
H, t, J 2.6 Hz, HC≡), 1.91 (3 H, s, MeC=), 1.34 (3 H, t, J 7.0
Hz, OСН2Me), 1.17 (3 H, t, J 7.3 Hz, MeСН2C=); δC (100.6
MHz, CDCl3) 179.0 (C=N), 137.3 (=C−O), 132.6 (=C−S), 126.7
(CH2=CH), 110.5 (CH2=CH), 80.8 (C≡), 70.4 (HC≡), 66.8
(OСН2Me), 34.5 (MeСН2C=), 20.6 (MeС=), 17.6 (SCH2), 15.5
(OСН2Me), 10.4 (MeСН2C=).
liquid (11.75 g, 96%); purity ~93%; ν(neat) 3290 (s) (HC≡) cm–1;
δH (400 MHz, CDCl3) 6.04 (1 H, dd, Jtrans 17.2, Jcis 11.1 Hz,
4
3
3
3
3
3 3 2
CH2=CH), 5.37, 4.97 (2 H, both dd, Jtrans 17.2, Jcis 11.1, Jgem
1.3 Hz, CH2=CH), 5.23 (1 H, q, 3J 5.2 Hz, OCHO), 3.89, 3.60 (2
H, both dq, 2J 9.2, 3J 7.1 Hz, OCH2Me), 3.35, 3.33 (2 H, both dd,
2J 16.7, J 2.6 Hz, SСН2), 2.49−2.43, 2.33−2.27 (4 H, both m,
4
4
3
2',6'-H), 2.17 (1 H, t, J 2.6 Hz, HС≡), 1.45 (3 H, d, J 5.2 Hz,
OCHMe), 1.86−1.78, 1.74−1.60, 1.40−1.32 (6 H, all m, 3',4',5'-
H), 1.17 (3 H, t, J 7.1 Hz, OCH2Me); δC (100.6 MHz, CDCl3)
180.5 (C=N), 137.0 (=C−O), 132.0 (=C−S), 128.4 (CH2=CH),
112.0 (CH2=CH), 102.3 (OCHO), 80.7 (С≡), 70.8 (HС≡), 64.4
(OCH2Me), 38.9 (6'-C), 32.4 (2'-C), 27.6 (5'-C), 26.7 (3'-C), 25.5
(4'-C), 21.2 (OCHMe), 18.2 (SСН2), 15.4 (OCH2Me).
4.2.6. Synthesis of 2-aza-1,3,5-triene 7f. Following the general
3
procedure,
prop-2-ynyl
2-butoxy-N-isopropylbuta-2,3-
dienimidothioate (1-aza-1,3,4-triene 8f) was obtained from n-
butoxyallene (5.23 g, 46.7 mmol), n-BuLi (16.5 mL, 41.2 mmol),
i-PrNCS (4.05 g, 40.1 mmol), and propargyl bromide (5.95 g,
50.0 mmol) in THF (40 mL). Vacuum treatment of crude product
at 52−60 °C (~2 mmHg) for 15 min gave 2-aza-1,3,5-triene 7f
with trace of pyrrole 9f (by 1H NMR).
4.2.9. Synthesis of 2-aza-1,3,5-triene 7i. Following the general
procedure, prop-2-ynyl N-cycloheptyl-2-(1-ethoxyethoxy)buta-
2,3-dienimidothioate (1-aza-1,3,4-triene 8i) was obtained from 1-
(1-ethoxyethoxy)allene (6.41 g, 50.1 mmol), n-BuLi (20 mL,
50.0 mmol), cyclo-C7H13NCS (6.21 g, 40.1 mmol)/THF (3 mL),
and propargyl bromide (6.54 g, 55.0 mmol) in THF (40 mL).
Vacuum treatment of crude product at 50−60 °C (~1 mmHg) for
10 min gave 2-aza-1,3,5-triene 7i.
4.2.6.1.
(1Z)-2-Butoxy-N-(1-methylethylidene)-1-(prop-2-
ynylsulfanyl)buta-1,3-dien-1-amine (7f). Dark-brown mobile
liquid (8.09 g, 80%); ν(neat) 3295 (s) (HC≡) cm–1; δH (400 MHz,
3
3
CDCl3) 5.91 (1 H, dd, Jtrans 17.2, Jcis 11.0 Hz, CH2=CH), 5.23,
3
4.94 (2 H, both d, Jtrans 17.2, 3Jcis 11.0 Hz, CH2=CH), 3.77 (2 H,
3
4
t, J 6.5 Hz, OCH2Pr), 3.35 (2 H, d, J 2.3 Hz, SСН2), 1.98, 1.22
(6 H, both s, Me2C=), 1.75−1.65 (2 H, m, OCH2CH2Et),
4.2.9.1. (1Z)-N-Cycloheptyliden-2-(1-ethoxyethoxy)-1-(prop-2-
ynylsulfanyl)buta-1,3-dien-1-amine (7i). Dark-brown mobile
liquid (12.44 g, 97%); ν(neat) 3291 (s) (HC≡) cm–1; δH (400
4
1.53−1.44 [2 H, m, O(CH2)2CH2Me], 1.20 (1 H, t, J 2.3 Hz,
3
HC≡), 0.95 [3 H, t, J 7.5 Hz, O(CH2)3Me]; δC (100.6 MHz,
3
3
CDCl3) 175.2 (C=N), 138.0 (=C−O), 132.3 (=C−S), 126.7
(CH2=CH), 110.8 (CH2=CH), 80.8 (C≡), 71.0 (OCH2Pr), 70.3
(HC≡), 32.2 (OCH2CH2Et), 28.2, 21.8 (Me2C=), 19.2
[O(CH2)2CH2Me], 17.7 (SCH2), 13.9 [O(CH2)3Me]. The hetero-
MHz, CDCl3) 6.08 (1 H, dd, Jtrans 17.2, Jcis 11.0 Hz, CH2=CH),
3 3 2
5.36, 4.97 (2 H, both dd, Jtrans 17.2, Jcis 11.0, Jgem 1.5 Hz,
CH2=CH), 5.22 (1 H, q, 3J 5.3 Hz, OCHO), 3.90, 3.61 (2 H, both
dq, 2J 9.2, 3J 7.1 Hz, OCH2Me), 3.37, 3.35 (2 H, both dd, 2J 16.8,
4J 2.6 Hz, SСН2), 2.65−2.63, 2.49−2.44 (4 H, both m, 2',7'-H),
1
1
nuclear H−13C HMBC and H−13C HSQC 2D experiments pro-
4
vided additional support for the proposed structure.
2.18 (1 H, t, J 2.6 Hz, HС≡), 1.77−1.53 (8 H, m, 3',4',5',6'-H),
1.45 (3 H, d, 3J 5.3 Hz, OCHMe), 1.18 (3 H, t, 3J 7.1 Hz,

9
OCH2Me); δC (100.6 MHz, CDCl3) 184.1 (C=N), 136.2 (=C−O),
131.8 (=C−S), 128.4 (CH2=CH), 111.9 (CH2=CH), 102.2
(OCHO), 80.8 (С≡), 71.0 (HС≡), 64.4 (OCH2Me), 40.4, 34.7
(2',7'-C), 30.6, 29.8 (4',5'-C), 26.7, 24.7 (3',6'-C), 21.2 (OCHMe),
18.1 (SСН2), 15.4 (OCH2Me).
(w), 921 (s), 866 (m), 826 (w), 713 (w), 683 (w), 604 (w), 576
ACCEPTED MANUSCRIPT
(w), 492 (w) cm–1; δH (400 MHz, CDCl3) 5.75 (1 H, q, 3J 7.1 Hz,
MeСН=), 5.12 (2 H, s, CH2=C=), 3.68 (3 H, s, OMe), 1.77 (3 H,
d, J 7.1 Hz, MeСН=), 1.45 (6 H, s, Me2C); δC (100.6 MHz,
CDCl3) 198.0 (=C=), 157.6 (C=N), 149.5 (=C−O), 119.5
(MeСН=), 111.0 (5-C), 83.6 (CH2=C=), 81.2 (4-C), 59.7 (OMe),
28.4 (Me2C), 11.0 (MeСН=); δN (40.5 MHz, MeNO2) −60.1. The
3
4.3. Reaction of 2-Aza-1,3,5-trienes 7 with Sodium or Potassi-
um tert-Butoxide: Synthesis of 4,5-Dihydro-1,3-thiazoles 12;
General Procedure
1H−1H NOESY, H−13C HSQC, and H−13C HMBC 2D experi-
ments provided additional support for the proposed structure. Me
group is in (Z)-configuration relatively to the group MeO at C=C
bond; m/z (EI, 70 eV)6d 210 ([M+1]+, 23), 209 ([M]+, 56), 194
(48), 179 (5), 178 (6), 139 (6), 130 (6), 124 (22), 113 (11), 112
(100), 109 (7), 108 (8), 97 (58), 82 (12), 79 (23), 77 (15), 71 (12),
70 (15), 69 (12), 68 (7), 65 (11), 59 (12), 58 (24), 56 (12), 55
(15), 53 (16%).
1
1
To a stirred solution of the product mixture (~9–42 mmol), con-
taining 2-aza-1,3,5-triene 7 (~92−99%) and pyrrole 9 (from trac-
es to ~8%) in THF (15−65 mL), DMSO (5−15 mL) and t-BuONa
(~16−47 mmol) (Method A) or t-BuOK (~10−38 mmol) (Method
B) were added sequentially at −60 °C. The mixture was stirred
for 30 min (or for 15 min for compound 7d) while the tempera-
ture was kept between −35 and −27 °C, and was then cooled to
ca. −60 °C, and H2O (20−50 mL) was added. After separation of
the layers, the products were extracted from the aqueous fraction
with Et2O (2−4×30−40 mL). The combined organic fractions
were washed with H2O (3×50 mL), dried (MgSO4), and concen-
trated under reduced pressure at a bath temperature of ~35 °C (on
rotary evaporator, then at ~1 mmHg) to give the crude product,
which was purified by flash chromatography on neutral alumina
(2 cm layer) followed by separation by column chromatography
(neutral alumina, hexane, then hexane/Et2O) to give the title
compound 12. In the absence of DMSO, reaction of 2-aza-1,3,5-
triene 7a with t-BuOK was carried out at 0 °C for 10 min (Meth-
od C).
4.3.1.2.
5-Ethenylidene-2-[(E)-1-methoxyprop-1-enyl]-4,4-
dimethyl-4,5-dihydro-1,3-thiazole (12a') (tentative assignment).
δH (400 MHz, CDCl3) 5.11 (2 H, s, CH2=C=), 5.03 (1 H, q, 3J 7.3
Hz, MeСН=), 3.56 (3 H, s, OMe), 1.93 (3 H, d, 3J 7.3 Hz,
MeСН=), 1.45 (6 H, s, Me2C); δC (100.6 MHz, CDCl3) 198.0
(=C=), 157.4 (C=N), 147.7 (=C−O), 110.6 (5-C), 102.3
(MeСН=), 83.4 (CH2=C=), 77.3 (4-C), 55.3 (OMe), 29.6 (Me2C),
12.2 (MeСН=).
4.3.1.3. 5-Ethynyl-2-[(Z)-1-methoxyprop-1-enyl]-4,4-dimethyl-
4,5-dihydro-1,3-thiazole (13a) (tentative assignment).6d m/z (CI,
CH4) 210 ([M+H]+, 100), 209 ([M]+, 6), 208 (11), 194 (8), 113
(46%); m/z (EI, 70 eV) 210 ([M+1]+, 18), 209 ([M]+, 33), 194
(100), 139 (31), 138 (7), 130 (31), 124 (45), 112 (8), 111 (9), 109
(12), 108 (13), 100 (11), 98 (7), 97 (17), 96 (8), 94 (10), 82 (12),
80 (7), 79 (12), 77 (14), 71 (15), 70 (9), 69 (15), 68 (10), 65 (6),
56 (11), 55 (14), 53 (10%).
4.3.1. Synthesis of 4,5-dihydro-1,3-thiazole 12a. Following the
general procedure (Method A), 4,5-dihydro-1,3-thiazole 12a [as
1
(Z)-isomer] contaminated with pyrrole 9a (~8%) (by H NMR)
was obtained from 2-aza-1,3,5-triene 7a (3.06 g, 13.6 mmol) and
t-BuONa (1.50 g, 15.6 mmol, 1.15 equiv) in THF (22 mL) and
DMSO (5 mL) at ca. −30 °C for 30 min in yield of 92% (2.60 g),
after rough separation on alumina. Further purification (alumina,
hexane, hexane/Et2O, 10:1) gave compound 12a (1.60 g, 56%).
Compound 13a was identified in crude product by MS (EI and
CI).
4.3.1.4.
1-Isopropyl-3-methoxy-2-(prop-1-ynylsulfanyl)-1H-
pyrrole (9a'') (tentative assignment). δH (400 MHz, CDCl3) 6.70
(1 H, d, 3J 3.3 Hz, 5-H), 5.88 (1 H, d, 3J 3.3 Hz, 4-H), 4.76 (1 H,
3
septet, J 6.6 Hz, NCH), 3.80 (3 H, s, OMe), 1.83 (3 H, s,
MeC≡), 1.41 (6 H, d, 3J 6.6 Hz, Me2CH).
4.3.2. Synthesis of 4,5-dihydro-1,3-thiazole 12b. Following the
general procedure (Method B), a mixture of 4,5-dihydro-1,3-
thiazole 12b (~74%), pyrrole 9b'' (~10%), and unidentified
Following the general procedure (Method B), 4,5-dihydro-1,3-
thiazole 12a [as a mixture of (Z)- and (E)-isomers, 12a-(Z) and
12a'-(E), in a ratio of ~88:12] contaminated with pyrrole 9a''
1
products (~16%) (by H NMR) was obtained from 2-aza-1,3,5-
1
(~9%) (by H NMR) was obtained from 2-aza-1,3,5-triene 7a
triene 7b (7.58 g, 31.3 mmol) and t-BuOK (4.25 g, 37.9 mmol,
1.21 equiv) in THF (51 mL) and DMSO (11 mL) at ca. −30 °C
for 30 min in yield of 94% (6.54 g), after rough separation on
alumina. Further purification (alumina, hexane) gave compound
12b. Pyrrole 9b'' was identified by 1H NMR in the mixture with
thiazole 12b in one of the small fractions.
(3.04 g, 13.5 mmol) and t-BuOK (1.75 g, 15.6 mmol, 1.15
ewuiv) in THF (22 mL) and DMSO (5 mL) at ca. −30 °C for 30
min in yield of 94% (2.65 g), after rough separation on alumina.
Further purification (alumina, hexane, hexane/Et2O, 10:1) gave
compound 12a [as a mixture of (Z)- and (E)-isomers] (1.64 g,
58%).
4.3.2.1. 5-Ethenylidene-4-ethyl-2-[(Z)-1-methoxyprop-1-enyl]-4-
methyl-4,5-dihydro-1,3-thiazole (12b).6b Brownish liquid (2.98 g,
43%); nD23 1.5481; [Found: С, 64.40; Н, 7.75; N, 6.47; S, 14.10.
C12H17NOS requires С, 64.53; Н, 7.67; N, 6.27; S, 14.36%];
ν(neat) 3043 (w), 2971 (s), 2932 (s), 2878 (m), 2854 (m), 2841
(m), 1954 (w) (=C=), 1652 (m), 1604 (s), 1457 (m), 1446 (m),
1435 (sh), 1377 (m), 1367 (w), 1329 (m), 1308 (m), 1290 (w),
1241 (m), 1222 (m), 1201 (m), 1192 (sh), 1154 (m), 1137 (m),
1113 (m), 1097 (sh), 1072 (s), 1041 (m), 1000 (w), 977 (m), 929
(s), 891 (w), 864 (m), 824 (m), 812 (m), 787 (w), 711 (w), 687
(w), 681 (w) cm–1; δH (400 MHz, CDCl3) 5.74 (1 H, q, 3J 6.9 Hz,
Following the general procedure (Method C), 4,5-dihydro-1,3-
thiazole 12a [as a mixture of (Z)- and (E)-isomers, 12a-(Z)
(~66%) and 12a'-(E) (~26%)] contaminated with pyrrole 9a''
1
(~8%) (by H NMR) was obtained from 2-aza-1,3,5-triene 7a
(2.00 g, 8.8 mmol) and t-BuOK (1.16 g, 10.4 mmol, 1.18 equiv)
in THF (15 mL) at 0 °C for 10 min in yield of 67% (1.24 g). Fur-
ther purification (alumina, hexane) gave a mixture of compounds
12a-(Z), 12a'-(E), and 9a'' in calculated yield of 41, 16, and 6%,
respectively (by 1H NMR).
4.3.1.1.
5-Ethenylidene-2-[(Z)-1-methoxyprop-1-enyl]-4,4-
2
MeСН=), 5.13, 5.09 (2 H, both d, J 10.2 Hz, CH2=C=), 3.68 (3
dimethyl-4,5-dihydro-1,3-thiazole (12a). Dark-brown mobile
liquid (1.64 g, 58%); [Found: С, 63.24; Н, 7.35; N, 6.50; S,
15.18. C11H15NOS requires С, 63.12; Н, 7.22; N, 6.69; S,
15.32%]; ν(neat) 3041 (w), 2974 (s), 2928 (s), 2852 (m), 1953
(w) (=C=), 1652 (m), 1602 (s), 1543 (m), 1448 (s), 1376 (w),
1363 (w), 1320 (s), 1249 (m), 1218 (w), 1157 (m), 1068 (s), 971
H, s, OMe), 1.90, 1.64 (2 H, both dq, 2J 13.6, 3J 7.4 Hz, MeСН2),
1.77 (3 H, d, 3J 6.9 Hz, MeСН=), 1.42 (3 H, s, Me), 0.86 (3 H, t,
3J 7.4 Hz, MeСН2); δC (100.6 MHz, CDCl3) 197.9 (=C=), 158.2
(C=N), 149.4 (=C−O), 119.3 (MeСН=), 109.3 (5-C), 84.8 (4-C),
83.4 (CH2=C=), 59.6 (OMe), 34.7 (MeСН2), 27.6 (MeСН=), 10.9

10
Tetrahedron
ACCEPTED MANUSCRIPT
(Me), 8.6 (MeСН2); m/z (EI, 70 eV)6d 223 ([M]+, 13), 208 (6),
(alumina, hexane, hexane/Et2O, 10:1) gave compound 12d (23%,
196 (6), 195 (13), 194 (100), 179 (6), 178 (5), 138 (15), 126 (7),
125 (12), 111 (39), 98 (10), 97 (8), 93 (17), 91 (8), 77 (9), 71 (8),
70 (10), 69 (6), 65 (5), 55 (10), 53 (7%).
1.05 g). Pyrrole 9d'' was isolated (alumina, hexane/Et2O, 10:1) in
a mixture with thiazole derivative 12d in a ratio of 67:33 (by 1H
NMR). 2-(Propa-1,2-dienylsulfanyl)pyrrole 9d' was identified in
1H NMR spectrum of this fraction in trace amounts.
4.3.2.2.
1-(sec-Butyl)-3-methoxy-2-(prop-1-ynylsulfanyl)-1H-
pyrrole (9b'') (tentative assignment).6b δH 3(400 MHz, CDCl3)
4.3.4.1. 4-Ethenylidene-2-[(Z)-1-methoxyprop-1-enyl]-3-thia-1-
azaspiro[4.5]dec-1-ene (12d). Yellow-orange mobile liquid (2.12
g, 25%); nD23.5 1.5697;6b [Found: С, 67.30; H, 7.44; N, 5.64; S,
12.70. C14H19NOS requires С, 67.43; Н, 7.68; N, 5.62; S,
12.86%]; ν(neat) 3042 (w), 2932 (s), 2854 (m), 1955 (w) (=C=),
1652 (m), 1603 (s), 1458 (sh), 1447 (s), 1378 (w), 1361 (w),
1327 (m), 1308 (m), 1280 (w), 1264 (w), 1233 (s), 1222 (sh),
1188 (w), 1153 (m), 1143 (w), 1113 (sh), 1088 (s), 1069 (s),
1032 (w), 986 (m), 954 (s), 936 (w), 914 (m), 904 (m), 857 (s),
831 (w), 805 (m), 780 (w), 719 (m), 693 (w), 666 (w), 654 (w),
629 (w), 572 (w), 516 (w), 505 (w), 490 (w) cm–1; δH (400 MHz,
CDCl3) 5.72 (1 H, q, 3J 7.0 Hz, MeСН=), 5.11 (2 H, s, CH2=C=),
3.70 (3 H, s, OMe), 1.87−1.79, 1.72−1.62, 1.58−1.51, 1.41−1.31
(10 H, all m, 2',3',4',5',6'-H), 1.76 (3 H, d, 3J 7.0 Hz, MeСН=); δC
(100.6 MHz, CDCl3) 198.5 (=C=), 156.2 (C=N), 149.5 (=C−O),
118.8 (MeСН=), 111.2 (5-C), 84.0 (4-C), 83.4 (CH2=C=), 59.5
(OMe), 38.1 (2',6'-C), 25.6 (4'-C), 23.1 (3',5'-C), 10.8 (MeСН=);
m/z (EI, 70 eV)6d 250 ([M+1]+, 15), 249 ([M]+, 55), 235 (12), 234
(100), 178 (7), 164 (10), 152 (31), 151 (17), 137 (16), 136 (6),
124 (25), 123 (14), 119 (22), 117 (10), 111 (11), 110 (8), 109 (7),
97 (9), 91 (34), 81 (12), 79 (13), 77 (10), 71 (10), 70 (15), 69 (7),
65 (7), 56 (6), 55 (13), 53 (10%).
3
6.65 (1 H, d, J 3.3 Hz, 5-H), 5.89 (1 H, d, J 3.3 Hz, 4-H), 4.52
(1 H, tq, 3J 7.1, 3J 6.8 Hz, NCHEt), 3.82 (3 H, s, OMe),
1.91−1.77, 1.82−1.72 (2 H, both m, MeCH2), 1.82 (3 H, s,
MeC≡), 1.38 (3 H, d, 3J 6.8 Hz, NCHMe), 0.82 (3 H, t, 3J 7.4 Hz,
MeCH2); δC (100.6 MHz, CDCl3) 151.2 (3-C), 118.0 (5-C), 102.5
(2-C), 95.1 (4-C), 67.9 (MeC≡), 58.3 (OMe), 55.5 (≡C−S), 53.3
(NCH), 30.6 (MeCH2), 21.7 (MeCH), 10.8 (MeCH2), 4.8
(MeC≡).
4.3.3. Synthesis of 4,5-dihydro-1,3-thiazole 12c. Following the
general procedure (Method B), a mixture of 4,5-dihydro-1,3-
thiazole 12c and unidentified resinous product was obtained from
2-aza-1,3,5-triene 7c (4.80 g, 18.8 mmol) and t-BuOK (2.50 g,
22.3 mmol, 1.19 equiv) in THF (30 mL) and DMSO (7 mL) at
ca. −30 °C for 30 min in yield of 81% (3.58 g), after rough sepa-
ration on alumina. Further purification (alumina, hexane, hex-
ane/Et2O, 10:1, 3:1) gave compound 12c.
4.3.3.1. 4-Ethenylidene-2-[(Z)-1-methoxyprop-1-enyl]-3-thia-1-
azaspiro[4.4]non-1-ene (12c). Yellow-brown mobile liquid (0.22
g, 5%); nD29 1.5696; [Found: C, 66.51; H, 7.11; N, 5.88; S, 13.50.
С13H17NOS requires C, 66.34; H, 7.28; N, 5.95; S, 13.63%];
ν(neat) 3041 (w), 2959 (s), 2870 (m), 1954 (w) (=C=), 1652 (m),
1601 (s), 1500 (w), 1464 (sh), 1447 (m), 1438 (m), 1394 (w),
1378 (w), 1365 (w), 1346 (m), 1329 (m), 1308 (m), 1246 (m),
1222 (m), 1205 (sh), 1185 (m), 1142 (m), 1115 (m), 1088 (sh),
1068 (s), 1030 (w), 1001 (m), 962 (w), 946 (w), 921 (s), 866 (m),
834 (w), 812 (w), 716 (w), 677 (w), 562 (w), 499 (w) cm–1; δH
(400 MHz, CDCl3) 5.74 (1 H, q, J 7.0 Hz, MeСН=), 5.13 (2 H,
s, CH2=C=), 3.68 (3 H, s, OMe), 2.13−2.01, 1.94−1.78 (8 H, both
m, 2',3',4',5'-H), 1.76 (3 H, d, J 7.0 Hz, MeСН=); δC (100.6
MHz, CDCl3) 198.0 (=C=), 157.2 (C=N), 149.4 (=C−O), 119.0
(MeСН=), 111.2 (5-C), 90.6 (4-C), 83.5 (CH2=C=), 59.6 (OMe),
41.7 (2',5'-C), 25.1 (3',4'-C), 10.9 (MeСН=); m/z (EI, 70 eV)6d
236 ([M+1]+, 7), 235 ([M]+, 13), 220 (100), 166 (6), 150 (7), 138
(16), 137 (13), 123 (9), 110 (21), 105 (12), 97 (8), 79 (6), 71 (6),
70 (16), 67 (14), 56 (6), 55 (7), 53 (5%).
4.3.4.2.
4-Ethynyl-2-[(Z)-1-methoxyprop-1-enyl]-3-thia-1-
azaspiro[4.5]dec-1-ene (13d) (tentative assignment). Red-orange
mobile liquid (0.22 g, 3%, calculated from H NMR); δH (400
1
3
4
MHz, CDCl3) 5.78 (1 H, q, J 7.2 Hz, MeСН=), 4.17 (1 H, d, J
2.5 Hz, SCH), 3.68 (3 H, s, OMe), 2.49 (1 H, d, 4J 2.5 Hz, HC≡),
3
2.42−0.91 (10 H, m, 2',3',4',5',6'-H), 1.76 (3 H, d, J 7.2 Hz,
3
MeСН=); δH (400 MHz, CDCl3) 158.8 (C=N), 149.8 (=C−O),
120.0 (MeСН=), 82.6 (4-C), 80.1 (C≡), 75.2 (HC≡), 59.5 (OMe),
46.8 (5-C), 34.7, 33.3 (2',6'-C), 25.6 (4'-C), 23.6, 23.1 (3',5'-C),
11.0 (MeСН=); m/z (CI, CH4)6d 250 ([M+H]+, 100), 249 ([M]+,
10), 248 (28), 234 (6), 153 (38%); m/z (EI, 70 eV)6d 250 ([M+1]+,
10), 249 ([M]+, 27), 235 (14), 234 (100), 179 (21), 178 (6), 164
(24), 148 (6), 130 (28), 109 (6), 98 (6), 97 (5), 91 (11), 82 (5), 81
(17), 79 (10), 71 (7), 67 (15), 56 (5), 55 (10), 54 (7), 53 (8%).
3
4.3.4.3. Cyclohexyl-3-methoxy-2-(propa-1,2-dienylsulfanyl)-1H-
pyrrole (9d') (tentative assignment). δH (400 MHz, CDCl3) 6.68
(1 H, d, 3J 3.3 Hz, 5-H), 5.88 (1 H, d, 3J 3.3 Hz, 4-H), 5.58 (1 H,
t, 4J 6.3 Hz, SCH=), 4.82 (2 H, d, 4J 6.3 Hz, CH2=C=), 4.29−4.25
(1 H, m, NCH), 3.79 (3 H, s, OMe), 1.98−1.18 (10 H, m,
2',3',4',5',6'-H).
4.3.4. Synthesis of 4,5-dihydro-1,3-thiazole 12d. Following the
general procedure (Method A), 4,5-dihydro-1,3-thiazole 12d con-
taminated with traces of pyrroles 9d and 9d' was obtained from
2-aza-1,3,5-triene 7d (8.82 g, 34.0 mmol) and t-BuONa (3.75 g,
39.1 mmol, 1.15 equiv) in THF (54 mL) and DMSO (12 mL) at
ca. −30 °C for 30 min in yield of 86% (7.26 g), after rough sepa-
ration on alumina. After separation with a ~10% solution of HCl,
two fractions, 4.73 g (56%) (consisting of 4,5-dihydro-1,3-
thiazole 12d contaminated with pyrroles 9d and 9d') and 1.36 g
(16%) [consisting of 4,5-dihydro-1,3-thiazole 12d, 5-ethynyl-4,5-
4.3.4.4.
1-Cyclohexyl-3-methoxy-2-(prop-1-ynylsulfanyl)-1H-
pyrrole (9d'') (tentative assignment).6b δH (400 MHz, CDCl3)
3
3
6.69 (1 H, d, J 3.2 Hz, 5-H), 5.87 (1 H, d, J 3.2 Hz, 4-H),
4.35−4.29 (1 H, m, NCH), 3.81 (3 H, s, OMe), 2.04−1.22 (10 H,
m, 2',3',4',5',6'-H), 1.82 (3 H, s, MeC≡).
1
dihydro-1,3-thiazole 13d, and unidentified compounds (by H
NMR)], were obtained. Further purification of the first fraction
(4.73 g, alumina, hexane, hexane/Et2O, 10:1) gave compound
12d (2.12 g, 25%). Compound 13d (with some impurities) was
isolated from the second fraction (1.36 g, alumina, hexane/Et2O,
10:1).
4.3.5. Synthesis of 4,5-dihydro-1,3-thiazole 12e. Following the
general procedure (Method B), 4,5-dihydro-1,3-thiazole [as a
mixture of (Z)- and (E)-isomers, 12e and 12e'] with traces of
1
pyrrole 9e'' and unidentified compounds (by H NMR) was ob-
tained from 2-aza-1,3,5-triene 7e (7.60 g, 30.1 mmol) and t-
BuOK (3.82 g, 34.1 mmol, 1.13 equiv) in THF (48 mL) and
DMSO (10 mL) at ca. –30 °C for 30 min in yield of 65% (4.62
g), after rough separation on alumina. Further purification (alu-
mina, hexane) gave two fractions, 2.93 g of a mixture of 4,5-
dihydro-1,3-thiazole (~90%) [as a mixture of (Z)- and (E)-
isomers, 12e and 12e', in a ratio of ~88:12] and pyrrole 9e''
Following the general procedure (Method B), a mixture of 4,5-
dihydro-1,3-thiazole 12d (~86%) and pyrrole 9d'' (~14%) (by 1H
NMR) was obtained from 2-aza-1,3,5-triene 7d (4.84 g, 18.7
mmol) and t-BuOK (2.83 g, 25.3 mmol, 1.35 equiv) in THF (26
mL) and DMSO (6 mL) at ca. –30 °C for 15 min in yield of 62%
(2.87 g), after rough separation on alumina. Further purification

11
(~10%) (by 1H NMR) and 0.03 g of 4,5-dihydro-1,3-thiazole [as
a mixture of (Z)- and (E)-isomers in a ratio of ~13:87] with trace
(OCH2Pr), 31.9 (OCH2CH2Et), 28.5 (Me2C), 19.1
ACCEPTED MANUSCRIPT
[O(CH2)2CH2Me], 13.8 [O(CH2)3Me], 11.1 (MeСН=); m/z (EI,
70 eV) 251 ([M]+, 34), 236 (7), 208 (13), 194 (52), 179 (14), 112
(100), 111 (60), 97 (60), 79 (23), 77 (15), 69 (14), 58 (32%).
of
1-(sec-butyl)-3-ethoxy-2-(prop-1-ynylsulfanyl)-1H-pyrrole
(9e'').
4.3.5.1. 5-Ethenylidene-2-[(Z)-1-ethoxyprop-1-enyl]-4-ethyl-4-
methyl-4,5-dihydro-1,3-thiazole (12e). Red-orange liquid (2.64 g,
37%); [Found: С, 65.67; H, 8.15; N, 5.77; S, 13.70. C13H19NOS
requires С, 65.78; Н, 8.07; N, 5.90; S, 13.51%]; ν(neat) 3042
(w), 2973 (s), 2928 (s), 2878 (m), 1954 (w) (=C=), 1650 (m),
1604 (s), 1550 (m), 1476 (sh), 1456 (m), 1443 (m), 1396 (w),
1377 (m), 1366 (m), 1310 (m), 1290 (w), 1240 (m), 1221 (m),
1201 (w), 1155 (m), 1137 (m), 1109 (m), 1088 (m), 1065 (s),
1042 (m), 1001 (w), 966 (m), 957 (m), 940 (m), 926 (s), 866 (m),
821 (w), 806 (w), 714 (w), 679 (w), 664 (w), 654 (w), 619 (w),
596 (w), 509 (w), 490 (w) cm–1; δH (400 MHz, CDCl3) 5.79 (1 H,
4.3.6.2.
2-[(E)-1-Butoxyprop-1-enyl]-5-ethenylidene-4,4-
dimethyl-4,5-dihydro-1,3-thiazole (12f') (tentative assignment).
δH (400 MHz, CDCl3) 5.09 (2 H, s, CH2=C=), 5.05 (1 H, q, 3J 7.3
3
3
Hz, MeСН=), 3.67 (2 H, t, J 6.4 Hz, OCH2Pr), 1.93 (3 H, d, J
7.3 Hz, MeСН=), 1.69−1.62 (2 H, m, OCH2CH2Et), 1.50−1.44 [2
H, m, O(CH2)2CH2Me], 1.45 (6 H, s, Me2C), 0.95 [3 H, t, J 7.2
Hz, O(CH2)3Me]; δC (100.6 MHz, CDCl3) 210.8 (=C=), 158.0
(C=N), 147.1 (=C−O), 117.4 (MeСН=), 110.8 (5-C), 83.2
(CH2=C=), 81.6 (4-C), 71.2 (OCH2Pr), 31.5 (OCH2CH2Et), 28.7
(Me2C), 19.2 [O(CH2)2CH2Me], 13.8 [O(CH2)3Me], 12.3
(MeСН=).
3
3
2
q, J 7.1 Hz, MeСН=), 5.12, 5.10 (2 H, both d, J 10.5 Hz,
4.3.7. Synthesis of 4,5-dihydro-1,3-thiazole 12g. Following the
general procedure (Method A), 4,5-dihydro-1,3-thiazole 12g [as
(Z)-isomer] contaminated with 3-(1-ethoxyethoxy)-1-isopropyl-
2-(propa-1,2-dienylsulfanyl)-1H-pyrrole (9g') (~7%) (by 1H
NMR) was obtained from 2-aza-1,3,5-triene 7g (11.19 g, 41.9
mmol) and t-BuONa (4.47 g, 46.6 mmol, 1.11 equiv) in THF (65
mL) and DMSO (15 mL) at ca. –30 °C for 30 min in yield of
45% (5.04 g), after purification on alumina. Second isolated frac-
tion, 0.22 g, consisted 2-[(Z)-1-(1-ethoxyethoxy)prop-1-enyl]-5-
ethynyl-4,4-dimethyl-4,5-dihydro-1,3-thiazole (13g) and uniden-
tified products (by 1H NMR).
2
CH2=C=), 3.92, 3.87 (2 H, dq, J 9.7, 3J 7.1 Hz, OСН2Me), 1.88,
2
3
3
1.64 (2 H, both dq, J 13.7, J 7.3 Hz, MeСН2), 1.76 (3 H, d, J
3
7.1 Hz, MeСН=), 1.41 (3 H, s, Me), 1.28 (3 H, t, J 7.1 Hz,
OСН2Me), 0.85 (3 H, t, J 7.3 Hz, MeСН2); δC (100.6 MHz,
3
CDCl3) 197.9 (=C=), 159.0 (C=N), 147.9 (=C−O), 118.8
(MeСН=), 109.4 (5-C), 84.9 (4-C), 83.4 (CH2=C=), 67.7
(OСН2Me), 34.8 (MeСН2), 27.7 (Me), 15.2 (OСН2Me), 11.1
(MeСН=), 8.6 (MeСН2); m/z (EI, 70 eV) 237 ([M]+, 14), 222
(26), 208 (100), 179 (11), 126 (11), 125 (15), 111 (47), 93 (25),
77 (11), 70 (11), 55 (13%).
4.3.5.2. 5-Ethenylidene-2-[(E)-1-ethoxyprop-1-enyl]-4-ethyl-4-
methyl-4,5-dihydro-1,3-thiazole (12e') (tentative assignment). δH
(400 MHz, CDCl3) 5.10, 5.08 (2 H, both d, 2J 10.4 Hz, CH2=C=),
5.07 (1 H, q, 3J 7.3 Hz, MeСН=), 3.74 (2 H, q, 3J 7.1 Hz,
4.3.7.1. 5-Ethenylidene-2-[(Z)-1-(1-ethoxyethoxy)prop-1-enyl]-
4,4-dimethyl-4,5-dihydro-1,3-thiazole (12g). Red-brown mobile
liquid (4.70 g, 42%); [Found: С, 62.94; H, 7.80; N, 5.15; S,
11.78. C14H21NO2S requires С, 62.89; Н, 7.92; N, 5.24; S,
11.99%]; ν(neat) 3048 (w), 2976 (s), 2931 (s), 2871 (sh), 1954
(sh) (=C=), 1648 (m), 1602 (s), 1529 (w), 1481 (w), 1445 (m),
1379 (s), 1358 (m), 1343 (w), 1320 (m), 1313 (m), 1251 (m),
1225 (m), 1178 (sh), 1154 (s), 1144 (sh), 1100 (m), 1071 (m),
1044 (m), 1027 (s), 989 (m), 964 (m), 948 (m), 919 (m), 908 (m),
865 (m), 834 (m), 812 (m), 742 (sh), 722 (m), 677 (m), 663 (m),
626 (w), 606 (w), 577 (w), 493 (w) cm–1; δH (400 MHz, CDCl3)
5.78 (1 H, q, 3J 7.0 Hz, MeСН=), 5.23 (1 H, q, 3J 5.1 Hz,
3
OСН2Me), 1.93 (3 H, d, J 7.3 Hz, MeСН=), 1.88, 1.66 (2 H,
both dq, 2J 13.7, 3J 7.2 Hz, MeСН2), 1.42 (3 H, s, Me), 1.30 (3 H,
t, 3J 7.1 Hz, OСН2Me), 0.89 (3 H, t, 3J 7.2 Hz, MeСН2).
4.3.6. Synthesis of 4,5-dihydro-1,3-thiazole 12f. Following the
general procedure (Method B), 4,5-dihydro-1,3-thiazole 12f con-
taminated with pyrrole 9f'' was obtained from 2-aza-1,3,5-triene
7f (8.02 g, 31.9 mmol) and t-BuOK (3.82 g, 34.1 mmol, 1.07
equiv) in THF (45 mL) and DMSO (10 mL) at ca. –30 °C for 30
min in yield of 72% (5.76 g), after rough separation on alumina
(hexane/Et2O, 3:1). Further purification (alumina, hexane) gave
two fractions, 2.15 g of a mixture of 4,5-dihydro-1,3-thiazole
(~87%) [consisting of (Z)- and (E)-isomers, 12f-(Z) and 12f'-(E),
in a ratio of ~4:1] and pyrrole 9f'' (~13%) (by 1H NMR) and 0.07
g consisting of 4,5-dihydro-1,3-thiazole [as a mixture of (Z)- and
(E)-isomers in a ratio of ~1:4] and 3-butoxy-1-isopropyl-2-(prop-
2
OCHO), 5.12 (2 H, s, CH2=C=), 3.84, 3.60 (2 H, both dq, J 9.5,
3
3J 7.2 Hz, OCH2Me), 1.81 (3 H, d, J 7.0 Hz, MeСН=), 1.44,
1.43 (6 H, both s, Me2C), 1.40 (3 H, d, 3J 5.1 Hz, OCHMe), 1.17
3
(3 H, t, J 7.2 Hz, OCH2Me); δC (100.6 MHz, CDCl3) 197.9
(=C=), 158.0 (C=N), 145.9 (=C−O), 120.7 (MeСН=), 111.1 (5-
C), 101.2 (OCHO), 83.6 (CH2=C=), 81.2 (4-C), 63.8 (OCH2Me),
28.5, 28.4 (Me2C), 20.8 (OCHMe), 15.2 (OCH2Me), 11.6
1
1
1-ynylsulfanyl)-1H-pyrrole (9f'') in a ratio of ~78:22 (by H
(MeСН=). The heteronuclear H–13C HSQC 2D experiment pro-
NMR).
vided additional support for the proposed structure; m/z (EI, 70
eV) 267 ([M]+, 5), 238 (6), 210 (9), 195 (91), 180 (25), 112
(100), 111 (52), 97 (61), 79 (28), 77 (22), 73 (86), 69 (61), 57
(42%).
4.3.6.1.
2-[(Z)-1-Butoxyprop-1-enyl]-5-ethenylidene-4,4-
dimethyl-4,5-dihydro-1,3-thiazole (12f). Red-orange liquid (1.93
g, 24%); [Found: С, 66.64; H, 8.51; N, 5.38; S, 12.70.
C14H21NOS requires С, 66.89; Н, 8.42; N, 5.57; S, 12.76%];
ν(neat) 3042 (w), 3026 (w), 2971 (s), 2932 (s), 2872 (s), 1954
(w) (=C=), 1650 (m), 1603 (s), 1550 (m), 1460 (m), 1436 (m),
1397 (w), 1377 (m), 1357 (m), 1325 (s), 1312 (sh), 1250 (s),
1225 (s), 1204 (m), 1155 (s), 1113 (m), 1093 (m), 1070 (s), 1045
(sh), 1012 (w), 988 (w), 968 (m), 959 (sh), 944 (sh), 919 (s), 865
(s), 811 (w), 741 (w), 713 (m), 693 (w), 679 (w), 665 (w), 618
(w), 605 (w), 575 (w), 493 (w) cm–1; δH (400 MHz, CDCl3) 5.78
(1 H, q, 3J 7.1 Hz, MeСН=), 5.11 (2 H, s, CH2=C=), 3.81 (2 H, t,
3J 6.8 Hz, OCH2Pr), 1.75 (3 H, d, 3J 7.1 Hz, MeСН=), 1.69−1.62
(2 H, m, OCH2CH2Et), 1.48−1.40 [2 H, m, O(CH2)2CH2Me],
4.3.7.2.
2-[(Z)-1-(1-Ethoxyethoxy)prop-1-enyl]-5-ethynyl-4,4-
dimethyl-4,5-dihydro-1,3-thiazole (13g) (tentative assignment).
3
δH (400 MHz, CDCl3) 5.80, 5.78 (1 H, q, J 7.0 Hz, MeСН=),
3
4
5.17 (1 H, q, J 5.1 Hz, OCHO), 4.24, 4.22 (1 H, d, J 2.6 Hz,
2
3
SCH), 3.93, 3.78 (2 H, dq, J 9.5, J 7.1 Hz, OCH2Me), 2.48 (1
4
3
H, d, J 2.6 Hz, HC≡), 1.79 (3 H, d, J 7.0 Hz, MeСН=), 1.43,
3
3
1.42 (3 H, d, J 5.1 Hz, OCHMe), 1.22, 1.18 (3 H, t, J 7.1 Hz,
OCH2Me), 1.10, 1.08 (6 H, both s, Me2C).
4.3.8. Synthesis of 4,5-dihydro-1,3-thiazole 12h. Following the
general procedure (Method A), 4,5-dihydro-1,3-thiazole 12h con-
1
taminated with pyrrole 9h' (~11%) (by H NMR) was obtained
3
1.44 (6 H, s, Me2C), 0.93 [3 H, t, J 7.2 Hz, O(CH2)3Me]; δC
(100.6 MHz, CDCl3) 198.1 (=C=), 158.5 (C=N), 148.4 (=C−O),
118.2 (MeСН=), 111.2 (5-C), 83.5 (CH2=C=), 81.2 (4-C), 72.0
from 2-aza-1,3,5-triene 7h (11.62 g, 35.2 mmol) and t-BuONa
(4.04 g, 42.1 mmol, 1.20 equiv) in THF (61 mL) and DMSO (14

12
Tetrahedron
mL) at ca. −30 °C for 30 min in yield of 54% (5.84 g), after
then MeI (4.8 g, 33.8 mmol) was added at −30 °C. The cooling
ACCEPTED MANUSCRIPT
purification on alumina (hexane).
bath was removed, and when the temperature was reached 10 °C
(in 10 min), the reaction mixture was warmed at 35−42 °C for 75
min. After treatment with water (20 mL), separation of the layers,
the products were extracted from the aqueous fraction with Et2O
(2×20 mL). The combined organic fractions were washed with
H2O (3×40 mL) and dried (MgSO4). Concentration of the solu-
tion on rotary evaporator followed by flash column chromatog-
raphy of the solution of the residue (1.35 g of dark-brown liquid)
in hexane on alumina (2 cm layer) gave 0.50 g of mobile liquid
consisting of 4,5-dihydro-1,3-thiazoles 12a (~27%), 14 (~55%),
and 15 (~8%) and pyrrole 9a'' (~10%) (by 1H NMR). Calculated
4.3.8.1. 4-Ethenylidene-2-[(Z)-1-(1-ethoxyethoxy)prop-1-enyl]-3-
thia-1-azaspiro[4.5]dec-1-ene (12h). Brown mobile liquid (5.20
g, 48%); [Found: С, 66.58; H, 8.10; N, 4.64; S, 10.23.
C17H25NO2S requires C, 66.41; H, 8.20; N, 4.56; S, 10.43%];
ν(neat) 3047 (w), 2977 (s), 2932 (s), 2856 (s), 1956 (w) (=C=),
1646 (m), 1602 (s), 1523 (w), 1506 (sh), 1481 (w), 1446 (s),
1397 (sh), 1380 (m), 1345 (w), 1318 (w), 1280 (w), 1263 (w),
1250 (w), 1234 (w), 1216 (w), 1178 (w), 1143 (w), 1101 (w),
1084 (w), 1043 (sh), 1026 (m), 984 (m), 966 (m), 948 (m), 905
(w), 858 (m), 806 (w), 728 (m), 660 (m), 623 (w), 571 (w), 491
(w) cm–1; δH (400 MHz, CDCl3) 5.71 (1 H, q, 3J 7.0 Hz,
MeСН=), 5.37 (1 H, q, 3J 5.3 Hz, OCHO), 5.12 (2 H, s,
1
from H NMR spectrum the yields of compounds 12a, 14, 15,
and 9a'' are ~7, 15, 2, and 3%, respectively.
2
3
СН2=C=), 3.87, 3.62 (2 H, dq, J 9.4, J 7.1 Hz, OCH2Me),
4.4.1. 5-Ethenylidene-2-(1-methoxy-1-methylallyl)-4,4-dimethyl-
3
1.93−1.78, 1.58−1.50 (4 H, both m, 2',6'-H), 1.82 (3 H, d, J 7.0
4,5-dihydro-1,3-thiazole (14) (tentative assignment). δH (400
3
3
Hz, MeСН=), 1.77−1.67, 1.39−1.35 (2 H, both m, 4'-H),
MHz, CDCl3) 5.94 (1 H, dd, Jtrans 17.4, Jcis 10.8 Hz, CH2=CH),
3
3
1.73−1.64 (4 H, m, 3',5'-H), 1.41 (3 H, d, J 5.3 Hz, OCHMe),
5.38, 5.28 [2 H, both d, Jtrans 17.4, 3Jcis 10.8 Hz, CH2=CH], 5.10
1.19 (3 H, t, 3J 7.1 Hz, OCH2Me); δC (100.6 MHz, CDCl3) 198.4
(=C=), 156.4 (C=N), 146.3 (=C−O), 121.6 (MeСН=), 111.4 (5-
C), 101.2 (OCHO), 84.3 (4-C), 83.7 (СН2=C=), 63.7 (OCH2Me),
38.5, 38.2 (2',6'-C), 25.7 (4'-C), 23.2, 23.1 (3',5'-C), 20.9 (OCH-
(2 H, s, CH2=C=), 3.26 (3 H, s, OMe), 1.53 [3 H, s, C(Me)O],
1.41, 1.39 (6 H, both s, Me2C); δC (100.6 MHz, CDCl3) 197.9
(=C=), 168.8 (C=N), 138.8 (CH2=CH), 116.2 (CH2=CH), 110.9
(5-C), 94.7 [C(Me)O], 83.4 (CH2=C=), 81.2 (4-C), 51.3 (OMe),
28.4, 28.2 (Me2C), 22.1 (Me); m/z (EI, 70 eV) 223 ([M]+, 21),
208 (5), 193 (24), 112 (44), 111 (20), 97 (20), 85 (100), 79 (7),
77 (5), 58 (10), 55 (36), 53 (7%).
1
Me), 15.4 (OCH2Me), 11.7 (MeСН=). The heteronuclear H−13C
HSQC 2D experiment provided additional support for the pro-
posed structure; m/z (EI, 70 eV) 321 ([M]+, 5), 292 (21), 264
(58), 249 (21), 248 (22), 234 (14), 232 (12), 220 (21), 192 (33),
165 (14), 151 (17), 134 (23), 105 (20), 91 (38), 83 (51), 73 (100),
55 (69%).
4.4.2. 5-Ethenylidene-2-(1-methoxybut-1-enyl)-4,4-dimethyl-4,5-
dihydro-1,3-thiazole (15) (tentative assignment). δH (400 MHz,
CDCl3) 5.69 (1 H, t, 3J 7.6 Hz, EtCH=), 3.67 (3 H, s, OMe), 2.25
3
3
4.3.9. Synthesis of 4,5-dihydro-1,3-thiazole 12i. Following the
general procedure (Method A), 4,5-dihydro-1,3-thiazole 12i was
obtained from 2-aza-1,3,5-triene 7i (12.30 g, 38.3 mmol) and t-
BuONa (4.28 g, 44.6 mmol, 1.16 equiv) in THF (65 mL) and
DMSO (15 mL) at ca. −30 °C for 30 min in yield of 44% (5.46
g), after purification on alumina (hexane, 10:1 hexane/Et2O).
(2 H, quintet, J 7.6 Hz, MeCH2CH=), 1.03 (3 H, t, J 7.6 Hz,
MeCH2CH=). Signals of Me2C and CH2=C= groups are masked
by more intensive signals from other compounds; m/z (EI, 70 eV)
223 ([M]+, 52), 208 (49), 194 (13), 138 (14), 112 (100), 111 (58),
97 (66), 96 (14), 79 (20), 77 (11), 70 (14), 69 (16), 59 (10), 58
(31), 55 (18), 53 (13%).
4.3.9.1. 4-Ethenylidene-2-[(Z)-1-(1-ethoxyethoxy)prop-1-enyl]-3-
thia-1-azaspiro[4.6]undec-1-ene (12i). Red-brown mobile liquid
(5.46 g, 44%); [Found: C, 67.45; H, 8.59; N, 4.21; S, 10.11.
C18H27NO2S requires C, 67.25; H, 8.47; N, 4.36; S, 9.97%];
ν(neat) 3047 (w), 2977 (s), 2928 (s), 2857 (s), 1953 (w) (=C=),
1648 (m), 1603 (s), 1481 (sh), 1458 (m), 1444 (m), 1379 (m),
1358 (w), 1343 (w), 1324 (w), 1312 (sh), 1284 (sh), 1238 (w),
1219 (w), 1175 (m), 1144 (m), 1100 (w), 1071 (w), 1042 (sh),
1027 (s), 964 (m), 947 (m), 925 (m), 863 (m), 845 (sh), 827 (w),
808 (w), 768 (w), 754 (w), 721 (m), 673 (w), 660 (m), 628 (w),
600 (w), 568 (w), 499 (w) cm–1; δH (400 MHz, CDCl3) 5.72 (1 H,
Corresponding Authors
*E-mail: nina@irioch.irk.ru
*E-mail: boris_trofimov@irioch.irk.ru
Acknowledgements
The reported study was performed using the equipment of Baikal
Analytical Center for collective use SB RAS.
3
3
q, J 7.1 Hz, MeСН=), 5.30 (1 H, q, J 5.2 Hz, OCHO), 5.14 (2
2
H, s, СН2=C=), 3.86, 3.61 (2 H, dq, J 9.2, 3J 7.1 Hz, OCH2Me),
Supplementary data
3
1.95−1.87 (4 H, m, 2',7'-H), 1.80 (3 H, d, J 7.1 Hz, MeСН=),
3
Supplementary data (copies of H and 13C NMR spectra for se-
lected products) associated with this article can be found in
the online version, at
1
1.74−1.50 (8 H, m, 3',4',5',6'-H), 1.39 (3 H, d, J 5.2 Hz, OCH-
3
Me), 1.16 (3 H, t, J 7.1 Hz, OCH2Me); δC (100.6 MHz, CDCl3)
198.6 (=C=), 156.8 (C=N), 146.1 (=C−O), 121.1 (MeСН=),
112.2 (5-C), 101.1 (OCHO), 87.2 (4-C), 83.4 (СН2=C=), 63.7
(OCH2Me), 40.34, 40.28 (2',7'-C), 30.2 (3',6'-C), 23.1, 22.9 (4',5'-
C), 20.8 (OCHMe), 15.3 (OCH2Me), 11.6 (MeСН=); m/z (EI, 70
eV) ([M+1]+, 11), 276 (6), 249 (100), 234 (36), 105 (14), 91 (26),
73 (65), 45 (59%).
References and notes
1. (a) Wu, Y.-J. Top Heterocycl. Chem. 2012, 29, 307–328; (b) Koutentis,
P. A.; Ioannidou, H. A. In Science of Synthesis, Knowledge Updates;
Blank, I., Wuest, M., Yeretzian, Ch., Eds.; Thieme: Stuttgart, Germa-
ny, 2010; pp 267–391; (c) Siddiqui, N.; Arya, S. K.; Ahsan, W.; Azad,
B. Int. J. Drug Dev. Res. 2011, 3, 156–164 (and references therein); (d)
Davyt, D.; Serra, G. Marine Drugs 2010, 8, 2755–2780; (e) Kashyap,
Sh. J.; Garg, V. K.; Sharma, P. K.; Kumar, N.; Dudhe, R.; Gupta, J. K.
Med. Chem. Res. 2012, 21, 2123–2132 (and references therein); (f)
Siddiqui, N.; Arya, S. K.; Ahsan, W.; Azad, B. Int. J. Drug Dev. Res.
2011, 3, 55–67; (g) Zagade, A. A.; Senthilkumar, G. P. Pharma Chem.
2011, 3, 523–537; (h) Siddiqui, N.; Arshad, M. F.; Ahsan, W.; Alam,
M. Sh. Int. J. Pharm. Sci. Drug Res. 2009, 1, 136–143; (i) De Souza,
4.4. Treatment of 2-Aza-1,3,5-triene 7a with Potassium tert-
Butoxide Followed by the Reaction with MeI
To a stirred solution of the product mixture (1.80 g, 8.6 mmol)
containing 2-aza-1,3,5-triene 7a (~92%) and pyrrole 9a (~8%) in
THF (10 mL) and DMSO (7 mL) t-BuOK (1.04 g, 9.3 mmol,
1.08 equiv) was added at −35 °C. The mixture was stirred for 5
min while the temperature was kept between −33 °C and −25 °C,

13
M. V. N. J. Sulfur Chem. 2005, 26, 429–449; (j) Dondoni, A.; Marra,
A. Chem. Rev. 2004, 104, 2557–2600.
ACCEPTED MANUSCRIPT
2. (a) Gaumont, A.-C.; Gulea, M.; Levillain, J. Chem. Rev. 2009, 109,
1371–1401; (b) Sansinenea, E.; Ortiz, A. Mini-Rev. Org. Chem. 2009,
6, 120–127; (c) Faghih, R.; Gfesser, G. A.; Lynch, C. L.; Gopalakrish-
nan, M.; Gopalakrishnan, S.; Malysz, J.; Gubbins, E. J.; El Kouhen, R.;
Li, J.; Sarris, K. A.; Michmerhuizen, M. J.; Wang, Y. WO Patent 2008
002 956, 2008; Chem. Abstr. 2008, 148, 121698; (d) Bigot, A.; Carry,
J.-C.; Mignani, S. WO Patent 2003 040 115, 2003; Chem. Abstr. 2003,
138, 368886; (e) Yamakuchi, M.; Matsunaga, H.; Tokuda, R.; Ishizu-
ka, T.; Nakajima, M.; Kunieda, T. Tetrahedron Lett. 2005, 46, 4019–
4022; (f) Abrunhosa, I.; Delain-Bioton, L.; Gaumont, A.-C.; Gulea,
M.; Masson, S. Tetrahedron 2004, 60, 9263–9272; (g) Shaojiang, S.;
Taunton, J. Org. Lett. 2005, 7, 299–301; (h) Liu, L.; Li, J.; Wang, M.;
Du, F.; Qin, Z.; Fu, B. Tetrahedron: Asymmetry 2011, 22, 550–557.
3. (a) Bagley, M. C.; Dale, J. W.; Merritt, E. A.; Xiong, X. Chem. Rev.
2005, 105, 685–714 (and references therein); (b) Higashibayashi, S.;
Kohno, M.; Goto, T.; Suzuki, K.; Mori, T.; Hashimoto, K.; Nakata, M.
Tetrahedron Lett. 2004, 45, 3707–3712; (c) Ino, A.; Hasegawa, Y.;
Murabayashi, A. Tetrahedron 1999, 55, 10283–10294; (d) Ino, A.;
Murabayashi, A. Tetrahedron 2001, 57, 1897–1902; (e) Cañedo, L.
M.; de la Fuente, J. A.; Gesto, C.; Ferreiro, M. J.; Jiménez, C.; Rigue-
ra, R. Tetrahedron Lett. 1999, 40, 6841–6844; (f) Hayashi, K.; Sato,
C.; Hiki, S.; Kumagai, T.; Tamai, S.; Abe, T.; Nagao, Y. Tetrahedron
Lett. 1999, 40, 3761–3764.
4. Adams, A.; De Kimpe, N. Chem. Rev. 2006, 106, 2299–2319.
5. (a) Liu, H.; Thomas, E. J. Tetrahedron Lett. 2013, 54, 3150–3153; (b)
Hoveyda, H. R.; Karunaratne, V.; Orvig, C. Tetrahedron 1992, 48,
5219–5226; (c) Mislin, G. L.; Burger, A.; Abdallah, M. A. Tetrahe-
dron 2004, 60, 12139–12145; (d) Abrunhosa, I.; Gulea, M.; Levillain,
J.; Masson, S. Tetrahedron: Asymmetry 2001, 12, 2851–2859; (e)
Rivault, F.; Schons, V.; Liébert, C.; Burger, A.; Sakr, E.; Abdallah, M.
A.; Schalk, I. J.; Mislin, G. L. A. Tetrahedron 2006, 62, 2247–2254.
6. (a) Nedolya, N. A.; Tarasova, O. A.; Albanov, A. I.; Trofimov, B. A.
Russ. J. Org. Chem. 2013, 49, 1491–1496; (b) Nedolya, N. A.; Tara-
sova, O. A.; Albanov, A. I.; Trofimov, B. A. Tetrahedron Lett. 2014,
55, 2495–2498; (c) Nedolya, N. A.; Tarasova, O. A.; Volostnykh, O.
G.; Albanov, A. I.; Trofimov, B. A. Chem. Heterocycl. Compd. 2012,
47, 1430–1435; (d) Klyba, L. V.; Nedolya, N. A.; Tarasova, O. A.;
Sanzheeva, E. R. Russ. J. Org. Chem. 2015, 51, 541−551.
7. (a) Brandsma, L.; Nedolya, N. A.; Tarasova, O. A.; Trofimov, B. A.
Chem. Heterocycl. Compd. 2000, 36, 1241–1260; (b) Brandsma, L.;
Nedolya, N. A. Synthesis 2004, 735–745; (c) Brandsma, L. Eur. J.
Org. Chem. 2001, 4569−4581; (d) Nedolya, N. A.; Brandsma, L.; Tar-
asova, O. A.; Albanov, A. I.; Trofimov, B. A. Russ. J. Org. Chem.
2011, 47, 659–677.
8. (a) Nedolya, N. A.; Tarasova, O. A.; Volostnykh, O. G.; Albanov, A.
I.; Trofimov, B. A. J. Organomet. Chem. 2011, 696, 3359–3368; (b)
Nedolya, N. A.; Trofimov, B. A. Chem. Heterocycl. Compd. 2013, 49,
152–176.
9. Nedolya, N. A.; Tarasova, O. A.; Albanov, A. I.; Trofimov, B. A. Syn-
thesis 2015, 47, 3593–3610.
10. (a) Brasholz, M.; Reissig, H.-U.; Zimmer, R. Acc. Chem. Res. 2009,
42, 45–56; (b) Lechel, T.; Reissig, H.-U. Pure Appl. Chem. 2010, 82,
1835–1844; (c) Zimmer, R.; Reissig, H.-U. Chem. Soc. Rev. 2014, 43,
2888–2903; (d) Reissig, H.-U.; Zimmer, R. In Multicomponent
Reactions in Organic Synthesis; Zhu, J., Wang, Q., Wang, M.-X., Eds.;
Wiley-VCH: Weinheim, 2015; pp 301–332.
11. (a) Wotiz, J. H. In Chemistry of Acetylenes; Viehe, H., Ed.; Marcel
Dekker: New York, 1969; Ch. 7, pp 365–424; (b) Kobychev, V. B.;
Vitkovskaya, N. M.; Klyba, N. S.; Trofimov, B. A. Russ. Chem. Bull.,
Int.Ed. 2002, 51, 774–782; (c) Hubert, A. J.; Reimlinger, H. J. Chem.
Soc. (C) 1968, 606–608; (d) Benneche, T.; Undheim, K. Acta Chem.
Scand. 1983, B37, 115–119; (e) Li, Y.; Chen, J.; Qiu, R.; Wang, X.;
Long, J.; Zhu, L.; Au, C.-T.; Xu, X. Tetrahedron Lett. 2015, 56, 5504–
5507.
12. (a) Hoff, S.; Brandsma, L.; Arens, J. F. Rec. Trav. Chim. Pays-Bas
1968, 87, 916–924; (b) Brandsma, L. Best Synthetic Methods: Synthe-
sis of Acetylenes, Allenes and Cumulenes: Methods and Techniques;
Elsevier: Amsterdam, 2004.
13. Trofimov, B. A.; Nedolya, N. A.; Gerasimova, V. V.; Voronkov, M. G.
Sulfur Lett. 1988, 8, 73–78.