Allenic compounds and isothiocyanates as key building units in the synthesis of heterocycles

Article abstract of DOI:10.1055/s-2004-816005

Reaction between lithiated allenic compounds and isothiocyanates, R ¹N=C=S, in most cases gives exclusively thioimidates with the allenic structure, C=C=CC(SLi)=NR¹. These intermediates have been used in novel approaches to 2,3-dihydropyridines, pyrroles, quinolines, cyclobutanopyrrolines, and thiophene or dihydrothiophene derivatives. The procedures leading to the heterocycles with a nitrogen atom in the ring involve S-alkylation followed by simple heating or by treatment with copper(I) halide. 2-Aminothiophenes and 2-imino-2,5-dihydrothiophenes are formed by intramolecular nucleophilic attack of the thiolate moiety on the allenic system and subsequent addition of methyl iodide or protonation.

Full text of DOI:10.1055/s-2004-816005

SPECIAL TOPIC
735
Allenic Compounds and Isothiocyanates as Key Building Units in the Synthesis
of Heterocycles
A
llenic Compou
a
nds and Is
m
othiocyanates in the
b
Synthesis of
e
H
eterocyc
r
le
s
t Brandsma,a Nina A. Nedolyab
a
Julianalaan 273, 3722-GN Bilthoven, The Netherlands
E-mail: l.brandsma@wxs.nl
b
A. E. Favorsky Irkutsk Institute of Chemistry of the Russian Academy of Sciences, Siberian Branch, Favorsky Street 1, 664033 Irkutsk,
Russia
E-mail: nina@irioch.irk.ru
Received 7 February 2004
Our research dealing with reactions between metallated
acetylenes or allenes13 and thiocarbonyl compounds was
extended in 1995 to include reactions involving heterocu-
mulenes, in particular isothiocyanates.
Abstract: Reaction between lithiated allenic compounds and
isothiocyanates, R1N=C=S, in most cases gives exclusively thioim-
idates with the allenic structure, C=C=CC(SLi)=NR1. These inter-
mediates have been used in novel approaches to 2,3-
dihydropyridines, pyrroles, quinolines, cyclobutanopyrrolines, and
thiophene or dihydrothiophene derivatives. The procedures leading
to the heterocycles with a nitrogen atom in the ring involve S-alky-
lation followed by simple heating or by treatment with copper(I) ha-
lide. 2-Aminothiophenes and 2-imino-2,5-dihydrothiophenes are
formed by intramolecular nucleophilic attack of the thiolate moiety
on the allenic system and subsequent addition of methyl iodide or
protonation.
2
Generation of Allenic Lithium Compounds
Treatment of the allenic ethers and sulfur analogs,
H2C=C=CHR [R = OMe, t-BuO, OCH(Me)OEt, SMe],
with BuLi at low temperatures in hexane–THF affords the
lithium derivatives H2C=C=C(Li)R (1, Scheme 1) re-
giospecifically. Analogous intermediates are readily gen-
erated under mild conditions from acetylenes MeC≡CR
(R = alkyl, SMe or CH2NEt2).1–5 The g-lithiation of
mono-substituted allenic hydrocarbons, RCH=C=CH2,
and geminally disubstituted allenes, R2C=C=CH2, with
BuLi can be accomplished within the temperature range
–50 to –10 °C. In the case of 1,2-butadiene, however, 10–
15% a-lithiation has been observed.1,14
1
2
3
Introduction
Generation of Allenic Lithium Compounds
Formation of 2,3-Dihydropyridines or Mixtures of 2,3-Di-
hydropyridines and Pyrroles
4
5
6
7
8
Directed Synthesis of Pyrroles
Synthesis of Quinolines
Synthesis of Cyclobutanopyrrolines
Synthesis of Thiophene and Dihydrothiophene Derivatives
Concluding Remarks
Key words: thioimidates, azatrienes, 2,3-dihydropyridines, pyr-
roles, quuinolines, cyclobutanopyrrolines, 2-aminothiophenes, 2-
imino-2,5-dihydrothiophenes
3
Formation of 2,3-Dihydropyridines or Mix-
tures of Dihydropyridines and Pyrroles
1
Introduction
Reaction of intermediates 1 (Scheme 1) with alkyl
isothiocyanates, methoxymethyl isothiocyanate, 2-vinyl-
oxyethyl isothiocyanate, or cyclohexyl isothiocyanate at
temperatures below –70 °C as well as S-alkylation with
alkyl iodides proceeds smoothly. Once temperatures high-
er than 25 °C are avoided during the work-up, the expect-
ed products 2 can be isolated in a fairly pure state.15 IR
spectroscopy shows inter alia absorptions at ca. 1950
cm–1 (C=C=C) and ca. 1650 (C=N) cm–1. In the 1H NMR
spectra the signals of the methylene group (H2C=C) are
doubled, as are the other protons due to the presence of
syn- and anti-isomers.
Regioselective deprotonation using a strongly basic re-
agent is the first step in many syntheses involving allenic
compounds. Reaction of the resulting intermediate with
an electrophile in general affords a mixture of an allenic
and an acetylenic derivative.1–3 The ratio of the products
strongly depends upon the counter ion, the nature of the
electrophile, and the substituents at positions close to the
reacting centres. Also the polarity of the solvent may have
a strong influence. Solutions of lithiated allenic ethers,
H2C=C=C(Li)OR, in organic solvents give only the allen-
ic derivatives in reactions with a wide variety of electro-
philes. Several useful applications of allenic ethers in
syntheses of heterocyclic compounds have been report-
ed.4–12
If the above-mentioned precautions during the work-up
are not taken and bath temperatures during the isolation
procedure are allowed to rise to 40 °C or higher, other
products can be formed. In the case of R = OMe and
R1 = R2 = H (1a, see Table 1) a mixture consisting of
ca.70% of pyrrole 5a and ca. 30% of 2,3-dihydropyridine
4a is isolated in about 80% combined yield after dis-
tillation.15a The two components can be quantitatively
SYNTHESIS 2004, No. 5, pp 0735–0745
Advanced online publication: 09.03.2004
DOI: 10.1055/s-2004-816005; Art ID: C01104SS
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
.2
0
0
4

736
L. Brandsma, N. A. Nedolya
SPECIAL TOPIC
1. RCH2N=C=S
2. MeI
separated by treatment with dilute aqueous hydro-
chloric acid, followed by addition of potassium hy-
droxide to the acidic aqueous layer. Similar procedures
H
R
SMe
Li
using
H2C=CHOCH2CH2N=C=S,15c
EtN=C=S,
H
N
N
6
7
Me2CHN=C=S, and c-C6H11N=C=S15b lead to analogous
results. In the last three cases, however, mainly the fully
conjugated systems 3b, c, and f, respectively, are isolated;
in the case of MeOCH2N=C=S 3e is the only isolated
product; no trace of the intermediate 2e can be detected,
even when the temperature is kept below room tempera-
ture during the work-up.16a Heating at elevated tempera-
tures results in all cases in the formation of the cyclic
products. Ratios of pyrrole 5b–d, f and dihydropyridine
4b–d, f (see Table 1) are different from that obtained in
the reaction with methyl isothiocyanate. In the reactions
with MeOCH2N=C=S dihydropyridines 4e are the exclu-
sive end products.16
SMe
SMe
N
9
R
R
8
a R = H; b R = H2C=CHOCH2
Scheme 2
1. RCH2N=C=S
2. MeI
H
SMe
11
Li
H
N
10
R
The formation of the 2,3-dihydropyridines may be visual-
ized as a succession of a 1,5-hydrogen shift’s in 2, fol-
lowed by electrocyclization of 3. We have been unable to
elucidate the mechanism by which 2 are converted into
the pyrroles 5. A possible route, involving protonation of
the allenic ether system and subsequent cyclization, is
shown in Scheme 1. Attempts to influence the ratio of 4
and 5 by treating 2 with protic acids or Lewis acids (such
as lithium halides and zinc halides) failed (cf. the results
mentioned in Section 3). If intermediate 2a is added drop-
wise to hot (ca. 260 °C) paraffin oil, however, a ca. 60:40
mixture of 4a and 5a is obtained in a high yield.14
SMe
SMe
N
N
R
R
13
12
a
R = H; b R = Me
Scheme 3
Elimination of methanol from 2,3-dihydropyridines 4e, n,
and t, effected by heating or by treatment with catalytic
amounts of hydrochloric acid, results in the formation of
pyridines 14 in good yield. This method represents a novel
approach to pyridines.16 The presence of an ethoxyethoxy
group in 14j allows the easy transformation into 2-meth-
ylthio-3-pyridinol 15 (Scheme 4).16b
Dihydropyridines 4j–u are the only end products from the
reaction of lithium compounds 1j–u and isothiocyanates.
H
R
SR3
H
The formation of pyridine 16 from the dihydropyridines
9a–c, which must proceed by elimination of hydrogen,
methane, and methyl vinyl ether, respectively, is effected
by refluxing under atmospheric pressure (Scheme 5).14,17
N
1. R1R2CHN=C=S
2. R3I
H
H+
R
CHR1R2
R
Li
H
R1
SR3
H
R
N
2
R2
1
SR3
OH
R
R
H
heat or H+
- MeOH
H+, H2O
1,5-H shift
N
H
CHR1R2
R
N
SMe
MeO
N
SMe
N
SMe
R1
15
14
4
SR3
R2
R
R
R = OCH(Me)OEt
e
j
n
t
R = OMe
N
N
R = OCH(Me)OEt
R = SMe
R1 R2
SR3
SR3
N
3
R = Me
4
CHR1R2
5
Scheme 4
Scheme 1
heat
- RH
Reactions of the lithiated allenes 6 and 10 (Schemes 2
and 3) with isothiocyanates and subsequent S-methyla-
tion gives the rather stable compounds 7 and 8 or 11 and
12, respectively. For their conversion into the correspond-
ing 2,3-dihydropyridines 9 and 13 heating at elevated
temperatures is necessary.15f,17,18
SMe
SMe
R
N
N
16
9
a
b
c
R = H
R = Me
R = CH2OCH=CH2
Scheme 5
Synthesis 2004, No. 5, 735–745 © Thieme Stuttgart · New York

SPECIAL TOPIC
Allenic Compounds and Isothiocyanates in the Synthesis of Heterocycles
737
Table 1 Formation of 2,3-Dihydropyridines 4 or Mixtures of 4 and Pyrroles 5 (Scheme 1)
R
R1
R2
R3
Yieldsa of end products (%)
4
5
a
b
c
d
e
f
OMe
H
H
Me
Me
Me
Me
Me
Et
23
53
42
34
73
63b
54
15
18
33
–
OMe
H
Me
OMe
Me
H
Me
OMe
H2C=CHOCH2
OMe
OMe
H
OMe
–C=(CH2)5C–
11b
c
e
c
g
h
i
t-BuO
t-BuO
OCH(Me)OEt
OCH(Me)OEt
SMef
H
H
Me
Et
H
H
11d
85d
e
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
75
j
H
OMe
84
65
70
57
–
–
–
–
–
–
–
–
–
k
l
H
H
SMef
Me
H
Me
m
n
o
p
q
r
s
SMef
H2C=CHOCH2
SMef
H
OMe
100b
92
Meg
H
H
Meg
H
Me
80b
85
Meg
Me
H
Me
Meg
H2C=CHOCH2
68
Meg
R1R2C=(CH2)5C
Me
OMe
H
–
t
Meg
H
H
Me
Me
100b
68
–
–
h
u
CH2NEt2
a Isolated yields are based on the reagent used in the lowest molar amounts, mostly BuLi; satisfactory microanalyses were obtained.
b Undistilled.
c Qualitative experiment; no yields determined; excellent NMR spectra and satisfactory microanalyses for 4 and 5.
d Combined yield > 80%; the ratio 5/4, determined with GC, was about 8:1.
e Ratio of 4/5 was about 6:1 (GC); no yields determined; attempts to separate the components via treatment with HCl–H2O, 4 was converted
into 6-methyl-2-methylthio-5,6-dihydro-3(4H) pyridinone, which was isolated in about 30% yield.
f A mixture of MeSCH=C=CH2 and MeSC≡CMe was used.
g The lithiated allenic compound 1 was generated from MeC≡CMe and BuLi.
h The lithiated allenic compound 1 was generated by treating MeC≡CCH2NEt2 with a 1:1 mixture of BuLi and t-BuOK at temperatures below
–80 °C and subsequently adding anhydrous LiBr.
allowed to rise to –40 °C. MeNCS (8.8 g, 0.12 mol) was
added over 10 min as a solution in THF (10 mL), while
keeping the temperature of the reaction mixture between
–100 and –90 °C. After this addition, the temperature was
allowed to rise gradually (over 15 min) to –40 °C. MeI
(17.0 g, 0.20 mol, excess) was then added in one portion,
after which the temperature of the yellowish suspension
was allowed to rise to 10 °C. Ice water (100 mL) was add-
ed with vigorous stirring, after which the layers were sep-
arated and the aqueous layer extracted twice with small
3-Methoxy-1-methyl-2-(methylthio)pyrrole (5a) and
5-Methoxy-6-(methylthio)-2,3-dihydropyridine (4a)
(Scheme 1)15
a. Preparation of Methyl 2-Methoxy-N-methyl-2,3-buta-
dienimidothioate (2a)
THF (65 mL) was added with cooling below 0 °C to a so-
lution of BuLi (0.10 mol) in hexane (63 mL). Methoxy-
allene (8.4 g, 0.12 mol) was added at –80 °C over a few
seconds, after which the temperature of the solution was
Synthesis 2004, No. 5, 735–745 © Thieme Stuttgart · New York

738
L. Brandsma, N. A. Nedolya
SPECIAL TOPIC
portions of Et2O or pentane. The organic solution was tion in vacuum afforded 2,3-dihydropyridine 9a (bp 92
dried over K2CO3.
°C/2 Torr, nD20 1.5200) in 85% yield.
b. Conversion of 2,3-Butadienimidothioate (2a) into Pyr- 5-(tert-butyl)-2-(methylthio)pyridine (16, Scheme 5)15f,17
role 5a and 2,3-Dihydropyridine 4a
2,3-Dihydropyridine 9a (4.0 g) was heated under reflux
To the organic solution of 2,3-butadienimidothioate (2a) and under inert gas for 30 min. Distillation gave pyridine
20
paraffin oil (40 ml) was added and the solvent was re- 2o (by elimination of H2; bp 78-80 °C/1 Torr, nD
moved under water aspirator pressure. In the last stage of 1.5464) in 75% yield.
the evaporation procedure the temperature of the heating
bath was increased to over 70 °C in order to initiate the cy-
clization. After removal of the last traces of solvent and
the other volatile components under reduced pressure, the
4
Directed Synthesis of Pyrroles
mixture of the product and paraffin oil was subjected to a As shown in the preceding section mixtures of pyrroles
distillation in vacuo, using a 20 cm Vigreux column. A ca. and 2,3-dihydropyridines or exclusively dihydropyridines
7:3 mixture of the pyrrole 5a and 2,3-dihydropyridine 4a resulted. Several attempts have been made to influence
(bp 115-117 °C/15 Torr; nD20 1.5515) was collected in ca. the cyclization of the intermediates 2 and 7 to favor for-
80% yield. After mixing the distillate with Et2O–pentane mation of pyrroles, including treatment with catalytic
(1:1, 100 ml), the solution was vigorously shaken with a amounts of protic or Lewis acids, organonickel or -palla-
ca. 20% excess of a cold (0 °C) 1 M aqueous solution of dium compounds, and copper(I) halides. Only the latter
HCl. The acidic aqueous layer was extracted twice with appear to effectively catalyze the cyclization of allenic
small portions of pentane, subsequently treated with KOH thioimidates to pyrroles. The formation of pyrroles from
pellets (5 g), after which three extractions with Et2O were allenic thioimidates 17 prepared from allenic ethers
carried out. Both organic solutions were dried over [R = OMe or OCH(Me)OEt, Scheme 6] proceeds smooth-
K2CO3. Concentration under reduced pressure followed ly within the temperature range 10–30 °C.19,20 The sulfur
by distillation afforded pyrrole 5a and 2,3-dihydropyri- analogs (R = SMe) give only tar-like material. From aza-
dine 4a. Pyrrole 5a (bp 84-85 °C/2 Torr; nD20 1.5470) was trienes with a conjugated system of double bonds (3 or 8)
obtained in 54% yield and 2,3-dihydropyridine 4a (bp no pyrroles are formed. The cyclization of allenic com-
90-93 °C/2 Torr; nD20 1.5444) in 23% yield.
pounds 17, R = alkyl (Scheme 6) to pyrroles proceeds
sluggishly and results in low yields as the formation of
fully conjugated azatrienes 3 (Scheme 1) is a thriving
competing reaction. Successful results can be obtained
with the intermediates 19 (Scheme 6), prepared from 4,4-
dimethyl-1,2-pentadiene (6), though in the cases R1 = aryl
prolonged heating at 60–80 °C with a relatively large
amount of copper halide is necessary. Reaction times may
be shortened by using concentrated solutions of 19 in
THF.14,20
3-(tert-Butyl)-6-(methylthio)-2,3-dihydropyridine
(9a) (Scheme 2)15f,17
a. Preparation of Methyl N,5,5-Trimethyl-2,3-hexadien-
imidothioate (7a)
A solution of BuLi (0.11 mol) in hexane (69 mL) was
mixed with THF (100 mL), while the temperature was
kept below 0 °C. 4,4-Dimethyl-1,2-pentadiene (12.5 g,
0.13 mol) was added in one portion at –60 °C, after which
the temperature was allowed to rise to –15 °C. The solu-
tion was stirred for an additional 15 min at –15 °C, then a
mixture of MeNCS (7.3 g, 0.10 mol) and THF (10 mL)
was added portionwise over 5 min at –100 °C. The temp-
erature was allowed to rise to –40 °C, then MeI (21.3 g,
0.15 mol) was added. When the temperature of the light
yellow suspension had reached 10 °C, water (100 mL)
was added with vigorous stirring. The upper layer and two
extracts (pentane) were dried over K2CO3, then the sol-
vent was removed under reduced pressure. Distillation of
the remaining liquid through a short Vigreux column af-
forded 2,3-hexadienimidothioate 7a (bp ca. 85 °C/0.7
Torr, nD20 1.528) in ca. 95% yield.
Competitive cyclization, resulting (after methylation) in
the formation of 2-N,N-disubstituted aminothiophenes oc-
curs in the reactions between lithiated methoxyallene and
some aryl isothiocyanates. A few attempts have been
made to avoid this reaction, but further research is neces-
sary to optimize the pyrrole syntheses. It seems that pyr-
roles are the only or main products if the reaction between
lithiated methoxyallene and aryl isothiocyanate is carried
out with relatively large amounts of THF once the temper-
ature of this reaction and that of the subsequent S-methyl-
ation, with a large excess of methyl iodide, is kept as low
as possible. During reactions with methyl-substituted
phenyl isothiocyanates, thiophene formation was not ob-
served. The ring closure, which is assumed to take place
in the absence of an external proton donor, may be ex-
plained as shown in Section 7, Scheme 9.14,20 The very
weakly basic 2-aminothiophene derivatives can be re-
moved from the mixtures by repeated extraction with con-
centrated aqueous hydrochloric acid.14,20
b. Ring Closure of 2,3-Hexadienimidothioate 7a with For-
mation of 2,3-Dihydropyridine 9a
The distillate 7a was heated under nitrogen to 215 °C,
when an exothermic reaction started. Subsequent distilla-
Synthesis 2004, No. 5, 735–745 © Thieme Stuttgart · New York

SPECIAL TOPIC
Allenic Compounds and Isothiocyanates in the Synthesis of Heterocycles
739
more over a period of 30 min. The reaction was completed
by heating for an additional 30 min at ca. 50 °C, then a so-
lution of NH4Cl (15 g) and KCN (6 g) in water (100 mL)
was added at r.t. with vigorous stirring. After ca. 10 min
the layers were separated and the aqueous layer extracted
with Et2O. The organic solution was dried over K2CO3
and subsequently concentrated under reduced pressure.
Traces of copper compounds were removed by flash chro-
matography on Al2O3 using Et2O as eluent. After addition
of Et2NH (1 mL), the eluate was concentrated under re-
duced pressure and the remaining liquid distilled [the
amine serves to neutralize traces of acid which might ad-
here to the glass and which may cause decomposition of
the product containing the acid-sensitive OCH(Me)OEt
group]. The pyrrole 18p [R = OCH(Me)OEt, R1 = Me; bp
23
ca. 115 °C/0.7 Torr, nD 1.5154, purity ca. 100%, GC],
was obtained in 75% yield.
b. Conversion of 18p into 1-Methyl-2-methylthio-3-pyr-
rolol (21)
One drop of 30% aq HCl was added to a solution of 18p
(4.3 g, 0.02 mol) in MeOH (20 mL) cooled to –5 °C. Ini-
tially the temperature was allowed to rise to 20 °C, then
the mixture was heated for 5 min at 55 °C. The solution
was then concentrated under reduced pressure and a solu-
tion of of KOH (0.5 g) in water (50 mL) was added. Ex-
traction with Et2O, followed by drying over MgSO4 and
concentration under reduced pressure gave pure pyrrolol
21 (bp ca. 100 °C/1 Torr, nD20 1.5848, in 75% yield. The
IR spectrum showed inter alia absorptions at 1539 (C=C)
and 3341 cm–1 (OH).
Scheme 6
Pyrrole 18p having an OCH(Me)OEt group in the 3-posi-
tion readily converts into 3-hydroxypyrrole 21, in equili-
brium with very small amounts (5–10%) of the keto
tautomer (Scheme 6).21 3-Hydroxypyrroles and their
keto-enol tautomerism have been described in detail.22
The hydroxy form is favored in polar solvents where a hy-
drogen bond can form (e.g. DMSO) whereas the keto
form is favored in non-polar solvents (e.g. CDCl3), or in
polar, protic solvents such as H2O and MeOH. For deriv-
atives having an ester group at the 2-position only the enol
form is detected in CDCl3.22
The NMR spectrum of the CDCl3 solution showed the
presence of ca. 10% of the keto tautomer of 21 (in CCl4
ca. 5% was present), while in the IR spectrum absorptions
of the C=O group at 1639 and the C=C double bond at
1572 cm–1 were visible.
Analogs of 21 with R1 = Et, c-Hex, or Ph were obtained in
a similar way from pyrroles 18q–s as undistilled products.
3-Methoxy-2-methylthio-1-phenylpyrrole (18g,
Scheme 6a)14,20
3-Hydroxy-1-methyl-2-(methylthio)pyrrole (21,
Scheme 6a)21
To a solution of BuLi (0.06 mol) in hexane (37 mL) and
THF (50 mL), methoxyallene (5.6 g, 0.08 mol) was added
at –90 °C and the solution was stirred for 15 min at ca.
–70 °C, then a mixture of PhNCS (7 g, 0.052 mol) and
THF (20 mL) was added dropwise over ca. 5 min at –90
to –80 °C. the red suspension was stirred for 15 min at ca.
–60 °C, then MeI (14 g, 0.10 mol) was added at ca –75 °C.
After an additional 15 min the temperature was allowed to
rise to 5 °C, then finely powdered CuI (0.7 g) was added.
After stirring for 30 min at r.t., the mixture was heated to
50 °C, then the work-up as described in the preceding pro-
cedure was carried out and 18g [bp ca. 140°C/ca. 1 Torr;
nD20 1.6116; purity ca. 100% (GC)] was obtained in 52%
yield (5.7 g).
1-Methyl-3-(1-ethoxyethoxy)-2-(methylthio)pyrrole
[18p, R = OCH(Me)OEt, R1 = Me]
Ethoxyethoxyallene (15,36 g, 0.12 mol) was added over a
few seconds to a solution of BuLi (0.10 mol) in hexane
(63 mL) and THF (75 mL), cooled at –90 °C. After stir-
ring for 10 min at –70 °C, the solution was cooled to –100
°C and a mixture of MeNCS (7.3 g, 0.10 mol) and THF
(20 mL) was added over a few minutes. After stirring for
15 min at –65 °C, MeI (21.6 g, 0.15 mol) was added, the
temperature was allowed to rise to 10 °C, and then finely
powdered CuBr (1.3 g) was added with efficient stirring.
The temperature of the reaction mixture rose by 10 °C or
Synthesis 2004, No. 5, 735–745 © Thieme Stuttgart · New York

740
L. Brandsma, N. A. Nedolya
SPECIAL TOPIC
few electrocyclizations of all-carbon systems C=C=C–
C=C–C=C, analogous to 23Æ24 in Scheme 7 have been
reported.23c
1-(4-Fluorophenyl)-3-methoxy-2-(methylthio)pyr-
role (18o, Scheme 6a)14,20
To a solution of lithiated methoxyallene [from BuLi (0.06
mol) in hexane (38 mL), THF (100 mL) and methoxy-
allene (5.5 g, 0.08 mol)] was added 4-fluorophenyl
isothiocyanate (7.7 g, 0.05 mol) at ca. –100 °C, after
which the temperature was allowed to rise to –60 °C over
a period of 30 min. After stirring for an additional 20 min
at ca. –65 °C, MeI (40 g, 0.28 mol, large excess) was add-
ed at –60 °C. The reaction mixture was stirred for an ad-
ditional 15 min at ca. –70 °C, then the cooling bath was
removed and the temperature was allowed to rise to 10 °C.
Finely powdered CuBr (1 g) was introduced with vigorous
stirring. After stirring for 30 min at r.t., the mixture was
heated for 10 min at 50 °C. After addition of an aqueous
solution of NH4Cl and KCN (cf. preceding experiments),
the product, (bp ca. 120 °C/0.3 Torr) was isolated in 69%
yield. Upon standing at r.t. yellow crystals formed.
Using 4,4-dimethyl-1,2-pentadiene, t-BuCH=C=CH2, or
geminally disubstituted allenes, R2C=C=CH2, [R = Me or
R2C = (CH2)5C] and phenyl or substituted-aryl isothiocy-
anates a number of quinoline derivatives can be prepared
with good yields.14,18,20,24 Syntheses with 2-substituted
phenyl isothiocyanates gives 8-substituted quinolines,
while the 6-substituted derivatives are obtained when us-
ing 4-substituted phenyl isothiocyanates. Reactions with
3-substituted phenyl isothiocyanates in principle may af-
ford both 5- and 7-substituted quinolines. 7-Trifluorome-
thylquinoline is obtained as the predominant product from
the synthesis starting with 3-CF3C6H4N=C=S and 4,4-
dimethyl-1,2-pentadiene.14,20
2-tert-Butyl-5-methylthio-1-phenylpyrrole (20d,
R1 = Ph, Scheme 6b)14,20
To a solution of BuLi (0.07 mol) in THF (45 mL) and hex-
ane (45 mL) was added at –50 °C 4,4-dimethyl-1,2-penta-
diene (10 g, 0.10 mol). After stirring for an additional 20
min at –15 °C, the solution was cooled to –100 °C and a
solution of PhNCS (6.75 g, 0.05 mol) in THF (20 mL) was
added over a few seconds while keeping the temperature
of the reaction mixture below –80 °C. After an additional
10 min (at –85 °C), MeI (12 g, 0.08 mol) was added, and
the temperature was allowed to rise to 10 °C. A solution
of CuBr (5 g) and anhydrous LiBr (6 g) in THF (25 mL)
was added and the reaction mixture was heated under re-
flux for 4 h. After cooling to r.t., a solution of NH4Cl (15
g) and KCN (10 g) in water (100 mL) was added with vig-
Scheme 7
orous stirring. The aqueous phase was separated and ex- The synthesis with methoxyallene, MeOCH=C=CH2, and
tracted 3 times with Et2O.The organic layer and ethereal PhN=C=S gives a mixture of approximately equal
extracts were concentrated under reduced pressure and the amounts of 4-methyl-3-methoxy-2-(methylthio)quinoline
remaining liquid subjected to flash chromatography on and 1-phenyl-3-methoxy-2-(methylthio)pyrrole in ap-
Al2O3 in order to remove traces of copper compounds. proximately 60% combined yield.25 The compounds can
The (ethereal) eluate was concentrated under reduced be separated by treatment of an ethereal solution of the
pressure and the remaining liquid distilled through a short mixture with dilute hydrochloric acid and subsequent neu-
column. Pyrrole derivative 20d, (bp ca. 110 °C/0.7 Torr, tralization of the aqueous layer with potassium hydroxide.
nD20 1.5773) was obtained in 75% yield.
Using methylthioallene results in 2,3-bis(methyl-
thio)quinoline being obtained as the only product in a fair
yield.25
5
Synthesis of Quinolines
2-Methylthio-4-neopentylquinoline (25a,
Scheme 7)24c
The formation of 4-methyl-2-(methylthio)quinoline by
thermal rearrangement of the thioimidate obtained from
the reaction of allenylmagnesium bromide with phenyl 4,4-Dimethyl-1,2-pentadiene, (11.5 g, 0.12 mol) was add-
isothiocyanate and subsequent S-methylation was report- ed in one portion to a solution of of BuLi (0.10 mol) in
ed in a short communication.23a A similar sequence with hexane (63 mL) and THF (70 mL) cooled to –50 °C. After
Me2C=C=CHLi, PhN=C=S, and MeI (Scheme 7) afford- the addition the temperature was allowed to rise to –15 °C,
ed 4-isopropylpropyl-2-(methylthio)quinoline (25b).23a and maintained at this temperature for 30 min. The almost
Azapolyenic systems, as precursors of quinoline rings,
clear solution was cooled to –100 °C, a mixture of PhNCS
(13.5 g, 0,10 mol) and THF (20 mL) was added over 10
min, while keeping the temperature of the reaction mix-
can be constructed by reaction of allenylmagnesium bro-
mide with N-arylsubstituted chloroformamidines.23b
A
Synthesis 2004, No. 5, 735–745 © Thieme Stuttgart · New York

SPECIAL TOPIC
Allenic Compounds and Isothiocyanates in the Synthesis of Heterocycles
741
ture below –80 °C. After an additional 15 min, MeI (20 g, avoided. Explanations for the formation of cyclobutan-
0.14 mol) was added at – 80 °C and the cooling bath was opyrrolines remain speculative, as attempts to detect inter-
removed. Once the temperature reached 5 °C, water (60 mediates from the cyclizations of 28 have been
mL) was added and the solution was then extracted with unsuccessful.
Et2O. After drying over MgSO4, the organic solution was
concentrated under reduced pressure (bath temperature <
40 °C) to give 5,5-dimethyl-N-phenyl-2,3-hexadienimi-
dothioate (23a) in quantitative yield. The crude azatriene
23a was mixed with toluene (30 mL) and the solution
heated at ca. 100 °C under a reflux condenser. A strongly
Cyclobutanopyrrolines 31–33 were prepared by heating
the precursors 28 under an inert gas at approximately
230 °C. The progress of the cyclization was followed by
1H NMR spectroscopy, after disappearance of the CH=
signals the product was isolated by vacuum distillation. If
compound 28 (R = Me, R1R2C = (CH2)5C) was heated at
exothermic reaction ensued. After the reflux has subsided
approximately 280 °C for 10–15 minutes, appreciable
the solution was heated under reflux for an additional 10
amounts of 1-cyclohexyl-5-methyl-2(1H) pyridinethione
min. Removal of the toluene under reduced pressure fol-
(up to about 25% yield) could be isolated as a by-product
lowed by distillation gave quinoline 25a, (bp ca. 135 °C/
by crystallization. Its formation may be explained by as-
0.5 Torr, nD20 1.6090) in 82% yield.
suming
a
1,7-hydrogen shift in the azatriene
affording
Me2C=CHCH=C(SMe)N=C(CH2)5
H2C=C(Me)CH=CHC(SMe)=N-cyclohexyl, electrocy-
clization of the latter to the 1,2-dihydropyridine and elim-
ination of methane.27
6
Synthesis of Cyclobutanopyrrolines
As shown in Scheme 3 the azatriene 12 obtained from the
reaction between 3-methyl-1,2-butadienyllithium 10 and
methyl or ethyl isothiocyanate gives dihydropyridine 13
upon strong heating. Using 3-methyl-1,2-butadienyllithi-
um and i-propyl isothiocyanate (R1 = R2 = Me) the aza-
triene 28 (R = R1 = R2 = Me) is obtained by a similar
sequence (Scheme 8). This compound is stable at temper-
atures of at least 190 °C, but heating at about 220 °C un-
der normal pressure (reflux) surprisingly does not afford
the dihydropyridine 29, but cyclobutanopyrroline 30 as
the only product in excellent overall yield.18,26 The ana-
logs 31, 32, and 33 are obtained with good overall yields
from syntheses with geminally disubstituted allenyllithi-
ums and isopropyl or cycloalkyl isothiocyanates.14,27 The
advantage of this route over electrocyclization, for the for-
mation of 2,3-dihydropyridines, is that steric repulsion is
1,6,6-Trimethyl-3-methylthio-2-azabicyclo3.2.0]-
hept-2-ene (30, Scheme 8)26
a. Methyl N-Isopropyl-4-methyl-2,3-pentadienimidothio-
ate, Me2C=C=CHC(SMe)=NCHMe2 (27)
3-Methyl-1,2-butadiene (4.9 g, 0.07 mol) was added to a
solution of BuLi (0.05 mol) in hexane (32 mL) and THF
(70 mL) cooled at –50 °C. The mixture was stirred for 30
min at –10 to –15 °C and then cooled to –95 °C. i-PrSCN
(5.4 g, 0.05 mol) was added and the temperature was al-
lowed to rise over 20 min to –55 °C. MeI (9.8 g, 0.07 mol)
was added and the temperature was allowed to rise to 5
°C. After addition of water (50 mL), extraction with Et2O,
and drying over K2-CO3, the solvents were removed under
R
R
Li
26
1. R1R2CHN=C=S
2. MeI
R2C=C=CHC(SMe)=NCHR1R2
27
heat
R2C=CHCH=C(SMe)N=CR1R2
28
N
N
SMe
SMe
29
R = R1 = R2 = Me
31
R = Me and
R1R2C = c-hexyl
SMe
N
30
SMe
N
R = R1 = R2 = Me
32
SMe
R = Me and
R1R2C = c-pentyl
N
33
R2C = c-hexyl
and R1 = R2 = Me
Scheme 8
Synthesis 2004, No. 5, 735–745 © Thieme Stuttgart · New York

742
L. Brandsma, N. A. Nedolya
SPECIAL TOPIC
reduced pressure to afford 8.51 g (93% yield) of azatriene 280 °C for 10–15 min, appreciable amounts of 1-cyclo-
27 as a light mobile liquid.
hexyl-5-methyl-2(1H) pyridinethione (up to ca. 25%
yield) could be isolated as a by-product by crystalliz-
ation. Its formation may be explained by assuming a
b. 4-Methyl-N-(1-Methylethylidene)-1-methylthio-1,3-
pentadien-1-amine (28, R = R1 = R2 = Me)
1,7-hydrogen
shift
in
the
azatriene
affording
Me2C=CHCH=C(SMe)N=C(CH2)5
Heating of 31 for a few minutes at ca. 100 °C, followed by H2C=C(Me)CH=CHC(SMe)=Nc-hex, electrocyclization
20
distillation, gave 28 (bp ca. 85 °C/0.7 Torr, nD 1.5610) of the latter to the 1,2-dihydropyridine and elimination of
in 90% yield.
methane.27
c. 1,6,6-Trimethyl-3-methylthio-2-azabicyclo3.2.0]hept-
2-ene (30)
Azatriene 28 (R = R1 = R2 = Me) was heated in an atmo-
7
Synthesis of Thiophene and Dihydrothio-
phene Derivatives
sphere of inert gas under reflux for 15 min (internal tem- Adducts 34 obtained from intermediate 1 (Scheme 9) sug-
perature ca. 220 °C). After this period the refractive index gests the possibility of ring closure leading ultimately to
had reached its minimal value. The product 30 (bp 215 °C/ formation of thiophene derivatives. This expectation was
760 Torr, nD20 1. 5060) was isolated in 87% yield by dis- realized with successful one-pot procedures for several 3-
tillation through a very short column.
substituted 2-aminothiophenes 38 and 39. As shown in
Scheme 9 the initial cyclization product 35 has to be trans-
formed into the amide 36 ´ 37 by a proton-metal (charge)
exchange. In Section 4 we have seen that during reactions
between lithiomethoxyallene and a number of substituted-
phenyl isothiocyanates this cyclization can proceed to a
considerable extent at low temperatures in the absence of
a proton-donating agent.20 It can be completed by stirring
Cyclobutanopyrrolines 31–33 were prepared by heating
the precursors 28 under inert gas at ca. 230 °C. The
progress of the cyclization was followed by H NMR
spectroscopy After disappearance of the CH= signals the
product was isolated by vacuum distillation. If compound
28 with R = Me and R1R2C = (CH2)5C was heated at ca.
1
Table 2 Procedures for the Directed Synthesis of 3-Substituted 2-Aminothiophenes 39 (Scheme 9)20,
Methoda
R
R1
Yield (%)b
Methoda
R
R1
Yield (%)b
A
B
E
MeO
MeO
MeO
MeS
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
Me
32
61
75
67
70
70
41
46
73c
71
68
31
E
E
E
C
E
E
E
A
C
D
D
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
Me
2-FPh
2-ClPh
2-BrPh
3-ClPh
3-ClPh
4-FPh
4-ClPh
3,4-Cl2Ph
Me
66
67
69
70
79
76
63
76
61
42
60
Me
Me
E
Me
C
A
A
A
A
A
E
Et
Ph
3-MePh
4-MePh
2,6-Me2Ph
3-F3CPh
4-F3CPh
4-Me2NPh
Me
Me
Et
Me
E
a A: A solution of 34 was heated for 30 min at 40 °C, then MeI was added at 0 °C, followed by heating at 40 °C. B: To a solution of 34 (0.05
molar scale) was added at –40 °C powdered t-BuOK (1 equiv). After heating for 45 min at ca. 35–45 °C, MeI was added at –15 °C, followed
by heating. C: To a solution of 34 (0.05 molar scale) was added at –50 °C a solution of t-BuOK (1 equiv) in THF (20 mL). After heating for 30
min at 40 °C, MeI was added at 0 °C, followed by heating. D: To a solution of 34 (0.05–0.10 molar scale) was added of t-BuOK (1 equiv) in
THF (40 mL), followed by heating to 10–15 °C, addition of DMSO (30 mL), heating for 20–40 min at ca. 40 °C, addition of some excess of
MeI or Me2SO4 at 0–5 °C and stirring at r.t. E: To a solution of 34 (0.05 molar scale) were successively added at –50 °C t-BuOH (1 equiv) in
THF and t-BuOK (1 equiv) in DMSO (30 mL). After 30 min at 25 °C excess MeI was added at 0 °C, followed by heating.
b Not optimized.
c N-(2,6-Dimethylphenyl)-N-[3-methoxy-5-methyl-2(5H)-thiophenyliden]amine was obtained instead of the expected N-(2,6-dimethylphenyl)-
3-methoxy-N-methyl-2-thiophenamine.
Synthesis 2004, No. 5, 735–745 © Thieme Stuttgart · New York

SPECIAL TOPIC
Allenic Compounds and Isothiocyanates in the Synthesis of Heterocycles
743
the reaction mixture for a limited period at temperatures without external cooling. The red or purple solution of 34
above 0 °C. Subsequent addition of water or methyl io- was heated for 30 min at 40 °C, then MeI (11.4 g, 0.08
dide affords the aminothiophenes 38 or 39, respective- mol) was added at 0 °C, followed by heating at 40 °C over
ly.20,28,29 Yields are high in the cases of R1 = Ph, 3,4- 15 min. Water (50 mL) was added followed by extraction
Cl2C6H4 and 3-F3CC6H4 and moderate if R1 = 3-MeC6H4 with Et2O. The organic solution was concentrated under
and 4-MeC6H4 (method A). In variants B–E of Table 2 a reduced pressure after drying. Distillation through a short
20
solution of 34 is treated with t-BuOK prior to carrying out column gave thiophene 39 (bp ca. 120 °C/0.5 Torr, nD
the final methylation (cf. note a of this table), thus creating 1.6135) in 70% yield.
more strongly nucleophilic conditions for the ring closure
of 34.
3-Methoxy-N-phenyl-2-thiophenamine (38,
Schemes 9 and 10)29
H
R
R
R
The reaction mixture obtained by the addition of phenyl
isothiocyanate to lithiomethoxyallene (cf. preceding pro-
cedure) was allowed to reach 0 °C, then water (100 mL)
was added followed by stirring for 15 min at r.t. The ami-
nothiophene was isolated as described in the preceding
N-R1
H
H
NR1
NR1
S
S
H
LiS
34
36
35
R1N=C=S
o
20
R
procedure (bp ca. 140 C/0.6 Torr, nD 1.6333) in 79%
yield.
R
R
R
H2O
NR1
MeI
NR1
H
NR1
Me
Li
S
S
S
In analogy with the reactions in Scheme 9 the ami-
nothiophenes 41 or 42 and iminodihydrothiophenes 43
can be obtained in excellent yields from 4,4-dimethyl-1,2-
pentadienyllithium (6) and geminally disubstituted
allenyllithiums 26, respectively (Schemes 11 and 12).31,32
1
39
37
38
R = OMe; R1 = Alkyl, Ph, 2-, 3-, 4-subst.-Ph
R = Alkyl;R1 = alkyl
R = SMe; R1 = Me, Ph
Scheme 9
1. R1N=C=S
2. t-BuOK, t-BuOH,
DMSO
R1
N
S
N-Methyl- or N-phenylaminothiophenes 38 show amimo-
imino tautomerism, the first examples of this kind of
isomerism (Scheme 10). The ratio of the tautomers de-
pends upon the solvent. In CCl4–CDCl3 (1:1) and in neat
CDCl3 the very oxygen-sensitive imino form of 38
(R1 = Me) predominates (ratio imino/amino approximate-
ly 7:15, respectively. In the case of 38 (R1 = Ph), the ratio
of amino/imino is 10:7 in neat CDCl3. Replacement of
these solvents by acetone-d6 causes a strong shift toward
the amino tautomer (amino/imino 33:1). Compounds 42
having a methylthio group in the 3-position exist only in
the amino form.29,30
Li
K
40
6
MeI
H2O
R1
R1
N
H
S
N
S
Me
41
42
R1 = alkyl or aryl
Scheme 11
OMe
OMe
R1
H
N
N
S
S
R1
38
R1 = Me or Aryl
Scheme 12
Scheme 10
8
Concluding Remarks
3-Methoxy-N-methyl-N-phenyl-2-thiophenamine
(39, Method A, Scheme 9)20
Many reactions between lithiated allenic compounds and
electrophiles afford a mixture of the allenic and acetylenic
derivative.1–3 Synthetically useful selectivities of func-
tionalizations may be attained by replacing lithium by oth-
er metals, such as zinc, titanium, and aluminium.33–36
Remarkably, reactions of lithiated allenes with isothiocy-
anates in most cases afford allenic thioimidates with very
high selectivities, making these metal-metal exchanges,
A solution of lithiomethoxyallene (0.06 mol) in hexane
(37 mL) and THF (40 mL) was prepared by adding meth-
oxyallene (0.07 mol) at –80 °C to a solution of BuLi (0.06
mol) and subsequently allowing the temperature to rise to
–50 °C. The resulting solution was cooled again to ca.
–100 °C, after which a mixture of PhNCS (6.8 g, 0.05
mol) and THF (20 mL) was added over a few seconds
Synthesis 2004, No. 5, 735–745 © Thieme Stuttgart · New York

744
L. Brandsma, N. A. Nedolya
SPECIAL TOPIC
(14) Unpublished results from the author’s laboratory.
for which stochiometric amounts of halides or other deriv-
atives of these metals are required, unnecessary. The
ready access to these allenic thioimidates allows a conve-
nient approach to the heterocyclic systems mentioned in
the preceding sections. The 2,3-dihydropyridines are
scarcely studied.37–41 Some of the dihydropyridines ob-
tained in our investigations can be converted with good
yields into derivatives of pyridine that are not accessible
otherwise. Cyclobutanopyrrolines represent a new class
of compounds. Syntheses using methoxyallene or other
allenic ethers H2C=C=CHOR afford heterocyclic com-
pounds containing the OR substituent. The OCH(Me)OEt
substituent, which is introduced when using the readily
available1 H2C=C=CHOCH(Me)OEt, can be easily trans-
formed into the hydroxyl function under mildly acidic
conditions.
(15) (a) Nedolya, N. A.; Brandsma, L.; Trofimov, B. A. Zh.
Obshch. Khim. 1996, 66, 2042. (b) Nedolya, N. A.;
Brandsma, L.; Trofimov, B. A. Khim. Geterotsikl. Soedin.
1996, 917. (c) Nedolya, N. A.; Brandsma, L.; Trofimov, B.
A. Russ. Chem. Bull. 1996, 45, 2670. (d) Nedolya, N. A.;
Brandsma, L.; Trofimov, B. A. Dokl. Akad. Nauk. 1996, 350,
68. (e) Nedolya, N. A.; Brandsma, L.; Zinov’eva, V. P.;
Trofimov, B. A. Russ. J. Org. Chem. 1997, 33, 80.
(f) Nedolya, N. A.; Brandsma, L.; Trofimov, B. A. Russ. J.
Org. Chem. 1998, 34, 1494.
(16) (a) Nedolya, N. A.; Brandsma, L.; Schlyakhtina, N. I.;
Fedorov, S. V.; Klyba, L. V. Zh. Org. Khim. 2002, 38, 957.
(b) Nedolya, N. A.; Schlyakhtina, N. I.; Klyba, L. V.;
Ushakov, I. A.; Fedorov, S. V.; Brandsma, L. Tetrahedron
Lett. 2002, 43, 9679. (c) Nedolya, N. A.; Brandsma, L.;
Schlyakhtina, N. I.; Fedorov, S. V. Khim. Geterotsikl.
Soedin. 2002, 707.
(17) Nedolya, N. A.; Brandsma, L.; de Lang, R.-J.; Trofimov, B.
A. Russ. J. Org. Chem. 1997, 33, 580.
(18) Brandsma, L.; Nedolya, N. A.; Verkruijsse, H. D.; Owen, N.
L.; Du, Li.; Trofimov, B. A. Tetrahedron Lett. 1997, 38,
6905.
(19) Nedolya, N. A.; Brandsma, L.; Verkruijsse, H. D.; Tarasova,
O. A.; Trofimov, B. A. Tetrahedron Lett. 1998, 39, 2409.
(20) Nedolya, N. A. Dissertation; Utrecht University: The
Netherlands, 1999.
(21) Brandsma, L.; Nedolya, N. A.; Trofimov, B. A. Russ. Chem.
Bull. 2000, 49, 1634.
Although isocyanates seem less versatile ‘partners’ for
metallated allenes than their thio analogs (isothiocyan-
ates), our preliminary investigations suggest that they can
be also successfully used in the synthesis of heteroatomic
open-chain and cyclic compounds. Thus, reactions of
lithiated allenes with alkyl or aryl isocyanates give easy
access to 2,3-dienamides,42,43 their cyclization products,
the 2-(5H)-furanylidenamines,43 and 2-O-silylated quino-
lines.44 These and the above-mentioned research are in
progress.45
(22) McNab, H.; Monahan, L. C. The Synthesis Reactivity and
Physical Properties of Substituted Pyrroles, In the Series
The Chemistry of Heterocyclic Compounds, Part 2; Taylor,
E. C., Ed.; John Wiley & Sons: New York, 1992, 525.
(23) (a) Darnault, G.; Saquet, M.; Thuiller, A. Chem. Ind.
(London) 1983, 391. (b) Ried, W.; Weidemann, P. Chem.
Ber. 1971, 104, 3329. (c) Reischl, W.; Okamura, W. H. J.
Am. Chem. Soc. 1982, 104, 6115.
Several acetylenic compounds from which allenic carban-
ions can be generated have been incorporated in the reac-
tions with isothiocyanates, leading to new families of
functionalized pyrroles, dihydropyridines, quinolines, thi-
etanes, cyclobutenes, etc.20,46
(24) (a) Brandsma, L.; Nedolya, N. A.; de Lang, R.-J.; Trofimov,
B. A. Russ. Chem. Bull. 1996, 45, 2873. (b) Brandsma, L.;
Nedolya, N. A.; de Lang, R.-J.; Trofimov, B. A. Chem.
Heterocycl. Compd. (N.Y., NY, U. S.) 1997, 33, 491.
(c) Nedolya, N. A.; Brandsma, L.; de Lang, R.-J.; Trofimov,
B. A. Russ. J. Org. Chem. 1997, 33, 1361.
(25) Nedolya, N. A.; Brandsma, L.; Tarasova, O. A.; Klyba, L.
V.; Sinegovskaya, L. M.; Trofimov, B. A. Russ. J. Org.
Chem. 1999, 35, 928.
(26) (a) Brandsma, L.; Nedolya, N. A.; van der Kerk, A. C. H. T.
M.; Heerma, W.; Lutz, E. T. H. G.; de Lang, R.-J.; Afonin,
A. V.; Trofimov, B. A. Russ. Chem. Bull. 1997, 46, 832.
(b) Nedolya, N. A.; Brandsma, L.; van der Kerk, A. C. H. T.
M.; Heerma, W.; Lutz, E. T. H. G.; Afonin, A. V.; de Lang,
R.-J.; Trofimov, B. A. Russ. J. Org. Chem. 1997, 33, 1359.
(c) Brandsma, L.; Nedolya, N. A.; Heerma, W.; van der
Kerk, A. C. H. T. M.; Lutz, E. T. H. G.; de Lang, R.-J.;
Afonin, A. V.; Trofimov, B. A. Chem. Heterocycl. Compd.
(N.Y., NY, U.S.) 1997, 33, 493.
(27) Nedolya, N. A.; Brandsma, L.; Trofimov, B. A. Khim.
Geterotsikl. Soedin. 2002, 1396.
(28) Brandsma, L.; Nedolya, N. A.; Tarasova, O. A.; Klyba, L.
V.; Sinegovskaya, L. M.; Trofimov, B. A. Dokl. Akad. Nauk.
1997, 357, 350.
(29) Brandsma, L.; Tarasova, O. A.; Vvedensky, V. Yu.; de Jong,
R. L. P.; Verkruijsse, H. D.; Klyba, L. V.; Nedolya, N. A.;
Trofimov, B. A. Russ. J. Org. Chem. 1999, 35, 1228.
(30) Brandsma, L.; Vvedensky, V. Yu.; Nedolya, N. A.;
Tarasova, O. A.; Trofimov, B. A. Tetrahedron Lett. 1998,
39, 2433.
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(3) Epsztein, R. In Comprehensive Carbanion Chemistry. Part
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