Reactions of heterocumulenes with organometallic reagents: XVII.* one-pot synthesis of alkoxy and (Alkylsulfanyl)-substituted pyrroles and 2,3-Dihydropyridines from aliphatic isothiocyanates and lithiated alkoxyallenes

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 5, pp. 659−677. © Pleiades Publishing, Ltd., 2011.

Original Russian Text © N.A. Nedolya, L. Brandsma, O.A. Tarasova, A.I. Albanov, B.A. Troﬁmov, 2011, published in Zhurnal Organicheskoi Khimii, 2011,

Vol. 47, No. 5, pp. 658−676.

Reactions of Heterocumulenes with Organometallic

Reagents: XVII.^*One-Pot Synthesis of Alkoxy

and (Alkylsulfanyl)-Substituted Pyrroles

and 2,3-Dihydropyridines from Aliphatic Isothiocyanates

and Lithiated Alkoxyallenes

N. A. Nedolya^a, L. Brandsma^b, O. A. Tarasova^a, A. I. Albanov^a, and B. A. Troﬁmov^a

^aFaworsky Irkutsk Institute bof Chemistry,Siberian Branch, Russian Academy of Sciences,

Irkutsk, 664033 Russia

e-mail: nina@irioch.irk.ru

^bUtrecht University, Netherlands

Received September 22, 2010

Abstract—A fundamentally new approach was developed to designing pyrrole and dihydropyridine rings from

available allenes and isothiocyanates involving a single preparative stage. Applying the reaction of lithiated

alkoxyallenes with aliphatic isothiocyanates we have synthesized previously unknown 1-alkyl(cycloalkyl)

pyrroles and 2,3-dihydropyridines with rare alkoxy- and alkylsulfanyl substituents. It was proved that the ﬁve-

and six-membered azaheterocycles formed as a result of competing reactions of direct intramolecular cyclization

of S-alkylated adducts of lithiated alkoxyallenes with isothiocyanates (1-aza-1,3,4-trienes) into pyrroles and of

[1,5]-sigmatropic rearrangement into conjugated 2-aza-1,3,5-trienes with subsequent closure into dihydropyridine

ring (through 6π-electrocyclization).

DOI: 10.1134/S1070428011050034

Acetylene and allene carbanions, for ages classed

among unique and most promising synthons and build-

ing blocks for the ﬁne organic synthesis [2], recently

ﬁnd developing application in the new strategy for cre-

ating C–C, C–N, C–O, and C–S bonds in the targeted

heterocyclic synthesis [3–14] including the synthesis of

fundamental nitrogen, oxygen, and sulfur heterocycles:

pyrroles, thiophenes, furans, pyridines, quinolines,

azepines, azetidines, pyrrolines, pyridazines, oxazines,

imidazoles, thietanes, oxepanes etc., in particular, owing

to the research of the authors of this study [4–11]. A spe-

cial position in the metallopropadiene series belongs to

the lithiated alkoxyallenes [ﬁrst of all, to methoxyallene

(I)] [4, 5, 9–13] due to their availability [13], high syn-

thetic versatility [4, 5, 9–14], and regiospeciﬁcity of their

generation [13]. However among diverse electrophiles

(predominantly aldehydes, ketones, alkyl halides, oxi-

ranes, more seldom, nitrones, nitriles, imides, imines and

heterocumulenes like CO₂, CS₂, PhN=C=O, PhN=S=O),

brought into reactions with polyunsaturated carbanions,

organic isothiocyanates before our studies [4–11] were

not practically explored [15].

At the same time the availability and high reactivity

of isothiocyanates with respect to nucleophiles make

them attractive starting compounds for the synthesis of

heteropolyene systems, for instance, 1-aza-1,3,4-trienes

of the type C=C=C–C=N– (which might be very active

in heterocyclization reactions) by the reaction with such

highly nucleophilic intermediates like carbanions of

alkynes or 1,2-dienes easily generated from the corre-

sponding substrates under the action of superbases [2, 13].

The systematic investigation of the reaction pair isothio-

cyanate–metalloalkyne of metallodiene that we started

in 1995 led to the development of the conceptually new

strategy of the synthesis of all the most important aza-

–––––––––––––––––––––

* For Communication XVI, see [1].

659

NEDOLYA et al.

660

and thiaheterocycles (pyrroles, pyrrolines, pyridines,

dihydropyridines, quinolines, azepines, dihydroazepines,

thietanes, thiophenes, dihydrothiophenes, thiopyrans) [4,

5], and also of carbocycles (cyclobutenes, cyclobutanes)

[8, 16] from the same precursors: adducts of metallated

dienes and alkynes with isothiocyanates.

tively low boiling point, vigorous stirring, and a strong

ﬂow of the inert gas.

As known [15, 17] and as we have established [4–11]

isothiocyanates add carbanions exclusively by the nu-

cleophilic (carbophilic) mechanism. The formation of

products of thiophilic addition in these reactions (in

contrast to the other thiocarbonyl compounds [18]) was

not observed up till now. For instance, 1-alkoxy-1-lithio-

allenes II reacted with alkyl, cycloalkyl, and heteroalkyl

isothiocyanates exothermic at low temperature (–100...

–30°C) and fast (5–15 min) giving the corresponding

lithium allenylimidothioates V in the most cases in virtu-

ally quantitative yield. Usually the isothiocyanate or its

solution in a small quantity of THF is added in one por-

tion to the cooled to –100...–90°C solution of 1-alkoxy-

1-lithioallene II generated in situ in the mixture THF–

hexane The temperature is maintained at –60...–30°C

(as a rule, about –60°C). Somewhat raised temperature

(up to –35...–30°C) is feasible in reactions with second-

ary isothiocyanates that because of the stereoelectronic

effects of the substituent react with carbanions II slower

than the primary isothiocyanates. To compensate pos-

sible losses due to the presence of water traces or other

active impurities in solvents, reagents or the atmosphere

1-lithio-1-methoxyallene (IIa) is used in slight excess

with respect to isothiocyanate (1.01–1.35 mol per 1 mol of

isothiocyanate). Moreover because it is easier to remove

from the reaction products volatile methoxyallene and/

or its alkyl derivatives (products of protolysis and alkyla-

tion of intermediate IIa) than unreacted isothiocyanate.

Thus we discovered for the ﬁrst time [4, 5] that the re-

action of lithiated alkoxyallenes II with aliphatic [methyl,

ethyl, isopropyl, sec-butyl, methoxymethyl, 2-(vinyloxy)

ethyl] and cycloaliphatic (cyclopropyl, cyclopentyl, cy-

clohexyl) isothiocyanates opened unexpectedly simple

way to previously unknown and difﬁcultly obtainable

heterosubstituted pyrroles and 2,3-dihydropyridines:

1-alkyl(cycloalkyl)-2-(alkylsulfanyl)-3-alkoxypyrroles

IIIa–IIIg, IIIi–IIIk and 6-(alkylsulfanyl)-5-alkoxy-2,3-

dihydropyridines IVa–IVd, IVf–IVk (Scheme 1) as had

been concisely reported (on single examples) in [10, 11].

Here these and new data are discussed in more detail.

We found that the deprotonation of methoxy- and

tert-butoxyallene (Ia, Ib) with butyllithium in THF–hex-

ane environment proceeded easily, fast (5–10 min) and

regiospeciﬁcally (with the formation of α-lithiated inter-

mediates II) even at very low temperature (–100…–60°C)

[4, 10]. It was previously reported on the lithiation of

alkoxyallenes with BuLi or EtLi in ether , mixtures Et₂O–

THF, Et₂O–hexane and THF–hexane at –35…–15°C

(10–25 min) [13]. It is reasonable to bring methoxyallene

(Ia) into the reaction in some excess relative to BuLi

(1.1–1.5 mol per 1 mol of BuLi) accounting for its high

volatility under experimental conditions due to its rela-

Scheme 1.

OR¹

SR⁴

R²R³CHN=C=S

BuLi

R⁴I

Δ

C

_

SR⁴

CHR²R³

IIIа^_IIIg,

IIIi^_IIIk

THF hexane

Li

IIа, IIb

SLi

CHR²R³

N

Iа, Ib

N

CHR²R³

V

VIa^_VIk

D

OR¹

SR⁴

VIIа^_VIId,

VIIf^_VIIk

OR¹

SR⁴

R²

R³

R²

R³

N

IVa^_IVd,

IVf^_IVk

I, II, R¹= Me (a), t-Bu (b); III, IV, VI, VII, R¹= R⁴= Me: R²= R³= H (a), R²= H, R³= Me (b), R²= R³= Me (c), R²=

Me, R³= Et (d), R², R³= (CH₂)_n, n = 2 (e), 4 (f); R¹= Me, R²,R³= (CH₂)₅, R⁴= Et (g); R¹= R⁴= Me: R²= H, R³= OMe

(h), R²= H, R³= CH₂OCH=CH₂(i); R¹= t-Bu, R²= R³= H, R⁴= Me (j), R⁴= Et (k).

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

REACTIONS OF HETEROCUMULENES WITH ORGANOMETALLIC REAGENTS: XVII.

661

Scheme 2.

The examination of the potential energy surface of

the reaction between methyl isothiocyanate and 1-lithio-

1-methoxyallene IIa performed by methods of various

levels in the basis 6-31G** showed that the formation

of adduct Va proceeded in one stage through a four-

center transition state [E_act74.4 (HF) and 75.3 (B3L-

YP) kJ mol⁻¹] [19].

OMe

N

OMe

N

SMe

Me

SMe

C

Me

i-

(~65%, J_CC68.4 Hz)

syn-(Z)-VIa

ant (E)-VIa

anty-(E)-VIa

(~35%, J_CC86.1 Hz)

Further alkylation of adducts V at –80...20°C (10–

30 min) by the addition to the reaction mixture of alkyl

halide, e.g., MeI or EtI taken in excess (1.4–2.8 mol per

1 mol of adduct) for the completion of the reaction occurs

exclusively at the sulfur atom and in virtually quantita-

tive yield affords previously unknown and unavailable

allenylimidothioates VI, 1-aza-1,3,4-trienes existing as

a mixture of syn-(Z) and anti-(E)-isomers with respect

to the carbon–nitrogen double bond. Their formation is

unambiguously proved by IR and NMR spectra.

anti-(E)-isomerization in the allenylimidothioate series

showed by the example of compound VIa that the most

probble mechanisms were inversion (E_act74.4 kJ mol⁻¹)

and catalyzed by nucleophile (E_ac61.6 kJ mol⁻¹) transi-

tion channels.

At storage (even at low temperature) and at heat-

ing 1-aza-1,3,4-trienes VI unexpectedly rearrange into

pyrroles III and/or 2,3-dihydropyridines IV [4]. It was

established from the experimental data that the formation

of the pyrrole III ring occurs as a result of a direct intra-

molecular cyclization of 1-aza-1,3,4-triene VI, and the

formation of the ring of dihydropyridine IV is preceded by

a sigmatropic rearrangement of 1-aza-1,3,4-triene VI into

a conjugated 2-aza-1,3,5-triene system VII followed by

the electrocyclization of the latter (Scheme 1). It should

be stressed that none of this reaction was known before

our research [4, 5, 10, 11] may be because were unknown

and unavailable proper 1-aza-1,3,4-trienes of type VI.

The vibrations of bonds C=N and C=C=C give rise in

the IR spectrum of 1-aza-1,3,4-triene VIa (Scheme 1) to

thw absorption bands at 1618 and 1946 cm^–1respectively.

The presence of geometric isomers of 1-aza-1,3,4-trienes

VI originating from the relative rigidity of the C=N bond

and the nonlinear structures containing this bond [20] is

revealed by NMR spectra: in the proton as well as carbon

spectra of compound VI all signals are doubled with

the shift from some thousandths to some ppm units. For

instance, the difference in the chemical shifts (Δδ) for

syn-(Z)- and anti-(E)-isomers of 1-aza-1,3,4-triene VIa in

the ¹H NMR spectrum attains from 0.005 to 0.160 ppm,

and in the ¹³C NMR spectrum, fromt 0.32 to 3.74 ppm

(taken from solutions in CDCl₃).

Obviously the ratio of the heterocyclic reaction

products, i.e., pyrrole III and 2,3-dihydropyridine IV,

is governed by the ratio of the rates of two competing

processes related to the thermally induced reorganization

of 1-aza-1,3,4-triene VI: the intramolecular [1,5]-cycli-

zation into pyrrole (with the formation of a new C–N

bond) and the isomerization into 2-aza-1,3,5-triene VII

(through [1,5]-H shift). It is also obvious that the kinetic

parameters of the concurrent reactions alongside the

thermodynamic characteristics of the reaction products

should be or at least may be signiﬁcantly affected by the

stereoelectronic effects of the substituents in the starting

1-aza-1,3,4-triene VI and in the long run by the structure

of the initial reagents (allene, isothiocyanate, and alkyl

halide). From the data presented in the table it is seen

that among three variables (substituents at the nitrogen,

oxygen, and sulfur atoms) the strongest effect on the ratio

of the cyclic reaction products and consequently on the

reaction route produces the substituent at the nitrogen

atom of 1-aza-1,3,4-triene VI, i.e., the structure of iso-

thiocyanate [4].

Recently the solution was found for the problem of

identiﬁcation of syn-(Z)- and anti-(E)-isomers observed in

the NMR spectra of 1-aza-1,3,4-trienes VI. By an example

of compound VIa constants J (C,C) in 1-aza-1,3,4-triene

were measured for the ﬁrst time, the ratio was determined

of syn-(Z)- and anti-(E)-isomers (C₆D₆, –10°C, 35 : 65)

(Scheme 2) [21], and the signals assignments to deﬁnite

1

geometric isomers were made in the H and ¹³C NMR

spectra. The experimental data were reliably conﬁrmed

by quantum-chemical calculations [21, 22]. It was also

established that the ratio of syn-(Z)- and anti-(E)-isomers

VIa very strongly depended on the nature of the solvent

and changed, for instance, from ~1 : 2 in C₆D₆[21] and

in CCl₄to ~1 : 1 in CDCl₃. And in proton-donor solvents

(CD₃OD) the equilibrium concentration of syn-(Z)-isomer

VIa even exceeded that of the anti-(E)-isomer. The

quantum-chemical study of the mechanism of syn-(Z)/

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

NEDOLYA et al.

662

Dependence of yield and ratio of cyclic reaction products on the structure of initial reagents : alkoxyallene (R¹OCH=C=CH₂),

isothiocyanate (R²R³CHN=C=S), and alkyl iodide (R⁴I)

Content of reaction products in the mixture, %

R¹

R²

R³

R⁴

Overall yield, %^a

pyrrole III

70–75

20–25

15

dihydropyridine IV

Me

H

Me

Et

(79)

91 (86)

89 (73)

87 (79)

80

30–25

80–75

85

Me

Et

Me

10–15

85–90

(CH₂)₂

(CH₂)₄

(CH₂)₅

H

100

0

c

d

98–100^b

75 (72)

100^e(73)

12

0

88

MeO

Me

100

Me

H

CH₂=CHOCH₂

Me

94 (70)

50

t-Bu

H

Me

Et

86 (60)

89 (73)

83

88

17

12

a

Preparative yields (nonoptimized) of the mixture of “crude” and puriﬁed products (in parentheses).

^bYield of 2-aza-1,3,5-triene VIIf in a mixture with 1−8% (depending on conditions) of 1-aza-1,3,4-triene VIf and/or pyrrole IIIf.

c

Identiﬁed in NMR spectra as a side product at the isomerization of 1-aza-1,3,4-triene VIf into 2-aza-1,3,5-triene VIIf and reorganization of

the latter into dihydroazepine at treating with t-BuOK [23].

^dIsolated in ~ 6% yield from polymerization products of 2-aza-1,3,5-triene VIIf.

e

Yield of 2-aza-1,3,5-triene VIIh.

Thus, compound VIa (Scheme 1), the ﬁrst member

of the series of methoxy-substituted 1-aza-1,3,4-trienes,

prepared from 1-lithio-1-methoxyallene (IIa), methyl

isothiocyanate, and MeI, at moderate heating (30–40°C)

and storage (under usual conditions and even in a freezer

chamber) isomerized quantitatively into pyrrole IIIa and

2,3-dihydropyridine IVa in the ratio 2.2–2.5 : 1. Some-

times the heterocyclization of 1-aza-1,3,4-triene VIa

starts spontaneously (practically at once after the removal

of solvents from the reaction mixture on a rotary evapora-

tor) and proceeds with a powerful exothermic effect that

can be avoided if the solvent is removed in the presence,

for example, of parafﬁn oil.

to 58%, and that of pyrrole IIIa decreased respectively

from 75 to 42%. Similar temperature effect on the ratio

of heterocycles IIIa and IVa was also observed at the

chromatography of azatriene VIa at different tempera-

tures: The higher the temperature of the vaporizer and the

column, the more the reaction was shifted to the side of

the formation of 2,3-dihydropyridine IVa (up to 51–59%

in the mixture with pyrrole IIIa whose content in these

cases was 41–49%). At milder temperature mode of the

chromatography the main heterocyclization product of

1-aza-1,3,4-triene VIa was always pyrrole IIIa.

1-Aza-1,3,4-triene VIb obtained from 1-lithio-1-

methoxyallene (IIa) and ethyl isothiocyanate (Scheme 1),

on the contrary, easily isomerized into 2-aza-1,3,5-triene

VIIb (by NMR data), whose 6π-electrocyclization led to

the formation of dihydropyridine IVb. Here pyrrole IIIb

was the minor cyclic product (see the table). However

also in this case it was not easy to stop the reaction at the

stage of the formation of 2-aza-1,3,5-triene VIIb. For in-

stance, 1-aza-1,3,4-triene VIb at storage in the freezer for

a week approximately to 5% converted into purrole IIIb

and nearly to 70%, into 2-aza-1,3,5-triene VIIb which

partially (by ~20%) cyclized into dihydropyridine IVb. In

the ¹H NMR spectrum of 1-aza-1,3,4-triene VIb after the

The attempt to shift the reaction to the side of forma-

tion of conjugated azatriene VIIa by adding (dropwise!)

1-aza-1,3,4-triene VIa to parafﬁn oil heated to 180–190°C

resulted in the change of the ratio of cyclic products for

beneﬁt of 2,3-dihydropyridine IVa (from 25 to 54% in

the mixture with C pyrrole IIIa). However we did not

succeed to register (even in the NMR spectra) generated in

situ thermodynamically unstable 2-aza-1,3,5-triene VIIa.

It immediately cyclized into dihydropyridine IVa. At the

addition of 1-aza-1,3,4-triene VIa to parafﬁn oil heated to

250–260°C the content of 2,3-dihydropyridine IVa grew

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REACTIONS OF HETEROCUMULENES WITH ORGANOMETALLIC REAGENTS: XVII.

663

skeleton (E_act141.9 kJ mol⁻¹). Experimentally isolated

2-aza-1,3,5-triene VIIg contained an impurity of pyrro-

lea IIIg and 1-aza-1,3,4-triene VIg. The corresponding

2,3-dihydropyridines IV in the spectra of the isomeriza-

tion products of compounds VIc, IVd, VIf were not

identiﬁed.

storage in the freezer for two weeks the main signals are

those of 2,3-dihydropyridine IVb and 2-aza-1,3,5-triene

VIIb. The intensity of signals of 1-aza-1,3,4-triene VIb

and pyrrole IIIb is negligible.

Inasmuch as 2-aza-1,3,5-trienes attract independent

interest (as linear precursors both of 2,3-dihydropyridines

[4] and, for example, of 3H-azepines and 4,5-dihydro-

3H-azepines [7]) we with especial attention investigated

the [1,5]-sigmatropic rearrangement of the synthesized

1-aza-1,3,4-trienes VI. The best result that was attained

up till now by the variation of the isomerization condi-

tions of N-ethyl-substituted azatriene was a mixture

of 1-aza-1,3,4-triene VIb and 2-aza-1,3,5-triene VIIb

(in the ratio ~3 : 2) containing traces of pyrrole IIIb and

2,3-dihydropyridine IVb. For 1-aza-1,3,4-trienes VIc,

VId, VIf the conditions were found of the isomerization

into 2-aza-1,3,5-trienes excluding or minimizing the

thermally induced competing heterocyclization reactions

of 1-aza-1,3,4-trienes VI into pyrroles III and of 2-aza-

1,3,5-trienes VII into 2,3-dihydropyridines IV. The isom-

erization process was monitored by NMR spectroscopy.

At heating (in the course of removing the solvents

on a hot water bath, at distillation, chromatography etc.)

1-aza-1,3,4-trienes VIb–VId, VIg or their mixtures with

2-aza-1,3,5-trienes VII, as was already mentioned, suf-

fer quantitative heterocyclization with the predominant

formation of 2,3-dihydropyridines IV (see the table). It

unexpectedly turned out that the polymerization and/or

tarring rate of 2-aza-1,3,5-triene VIIf was considerably

larger than its electrocyclization rate into 2,3-dihydro-

pyridine IVf. As a result the latter was isolated in 6%

yield. All attempts to minimize the thermally induced

polymerization of 2-aza-1,3,5-triene VIIf were unsuc-

cessful. The polymerization proceds with notable rate

even during th removal of solvents from the reaction

products on a rotary evaporator at 50–60°C appearing

in the growth of the viscosity of the oily substance and

in the corresponding changes in the ¹H NMR spectrum.

The same simple maintained at room temperature for

24 h practically lost the ﬂowability, and in its ¹H NMR

spectum only the unidentiﬁed signals of the polymer were

present. At the short heating (for several seconds) in the

ﬂame of spirit lamp of the mixture with a little benzene

of 2-aza-1,3,5-triene VIIf free of polymer (obtained by

solvents removal at room temperature) a sharp tempera-

ture rise from 50 to 130°C was observed with boiling of

the product (without external heating). However instead

of expected 2,3-dihydropyridine IVf, the product of the

exothermic electrocyclization of 2-aza-1,3,5-triene VIIf

in this case also polymer was obtained whose formation

was presumably related also to the low thermal stability

of compound IVf.

Short (10–15 min) heating to 65–67°C of 1-aza-

1,3,4-triene VIc obtained from 1-lithio-1-methoxyallene

(IIa) and isopropyl isothiocyanate (Scheme 1) results in

2-aza-1,3,5-triene VIIc containing an impurity of 10%

of pyrrole IIIc. At uncontrolled isomerization of 1-aza-

1,3,4-triene VIc gives usually a mixture of 15% of pyrrole

IIIc and 85% of 2,3-dihydropyridine IVc (see the table).

The isomerization of 1-aza-1,3,4-triene VId

(Scheme 1) synthesized from 1-lithio-1-methoxyallene

(IIa) and sec-butyl isothiocyanate into 2-aza-1,3,5-triene

VIId was carried out under similar conditions (~60°C,

12–15 min) and also to 90%. The impurity of pyrrole IIId

did not exceed 10%.

Materially pure 2-aza-1,3,5-triene VIIf (Scheme 1)

[99% with traces (<1%) of pyrrole IIIf] was obtained in

a quantitative yield by removing the solvents at the bath

temperature not exceeding 25°C ﬁrst on a rotary evapo-

rator and then is a vacuum of oil pump (at 1 mm Hg)

followed by the storage of the sample at –15°C (freezer

chamber) for 18 h.

In contrast to compounds VIf, VIg, derivatives of

cyclopentyl and cyclohexyl isothiocyanates respec-

tively 1-aza-1,3,4-triene VIe obtained from 1-lithio-

1-methoxyallene (IIa) and cyclopropyl isothiocyanate

(Scheme 1), on the contrary, does not isomerize into the

corresponding 2-aza-1,3,5-triene VIIe even at heating.

As a result forms exclusively 1-cyclopropylpyrrole IIIe

(see the table). The corresponding 2,3-dihydropyridine

was not identiﬁed in NMR spectra.

The transition of 1-aza-1,3,4-triene VIg obtained

by adding 1-lithio-1-methoxyallene (IIa) to cyclohexyl

isothiocyanate with the subsequent S-alkylation of the

adduct with ethyl iodide into a stable structural isomer

VIIg (Scheme 1) occurs in keeping with calculation

data (HF/6-31G**) [19] in a sigle stage by [1,5]-migra-

tion of hydrogen through the ﬂattening of the molecule

The use in the reaction with 1-lithio-1-methoxy-allene

(IIa) of methoxymethyl isothiocyanate gave an unexpect-

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

NEDOLYA et al.

664

ed result. It turned out that after the alkylation of adduct

Vh the formed 1-aza-1,3,4-triene VIh (Scheme 1) already

under the conditions of the reaction at uncommonly low

temperature (–70 × 0°C) for [1,5]sigmatropic rearrange-

ments isomerized quantitatively into 2-aza-1,3,5-triene

VIIh whose electrocyclization provided in high yield one

more representative of previously unknown and unavail-

able 6-(alkylsulfanyl)-2,3-dihydropyridines, 2-methoxy-

2,3-dihydropyridine IVh (see the table). The correspond-

ing pyrrole IIIh was not identiﬁed among the reaction

products. Moreover, dihydropyridine IVh was found to

undergo very readily the aromatization with methanol

liberation (Scheme 3) that occurred without catalyst at

room temperature (1 month, conversion of compound IVh

85%). In the presence of hydrochloric acid the quantita-

tive conversion of dihydropyridine IVh into previously

unknown 2-(methylsulfanyl)-3-methoxypyridine (VIII)

was attained in 1.5–2 h (Et₂O, ~30°C). It should be noted

that no spontaneous or thermally induced aromatization

of the other here described 2,3-dihydropyridines IV was

observed.

isothiocyanate, on the contrary, essentially facilitates the

closure of 1-aza-1,3,4-triene VIi obtained therefrom into

the pyrrole ring hence partially “inhibiting” the [1,5]-H

shift. The presence in compounds IIIi, IVi, VIi of the

highly reactive vinyloxy group essentially extends their

synthetic potential [24], in particular as monomers (it is

well known [25] that the most important application ﬁeld

for vinyl ethers is the industry of synthetic polymers).

The effect of the structure of alkoxyallene Ia, Ib on

the ratio of cyclic products proved to be less important

than the effect of isothiocyanates structure, although in

going from 1-aza-1,3,4-triene VIa obtained from methyl

isothiocyanate and 1-lithio-1-methoxy-allene (IIa) to

1-aza-1,3,4-trienes VIj, VIk prepared from methyl iso-

thiocyanate and 1-(tert-butoxy)-1-lithioallene (IIb) the

content of pyrroles in the mixture with 2,3-dihydropyri-

dines somewhat grew, from 70–75% (for pyrrole IIIa) to

83–88% (for pyrroles IIIj, IIIk) (see the table).

By an example of α-lithiated methoxyallene IIa and

methyl isothiocyanate the effect was studied on the overall

yield and the products ratio of reaction conditions [the sol-

vent nature (THF–hexane, Et₂O–hexane), the order (the

isothiocyanate addition to the solution of lithiated allene,

the solution of lithiated allene addition to the isothiocya-

nate solution) and velocity of reagents introduction (by

one portion, by small portions, dropwise) temperature

and duration of various stages of the process] and of the

workup of the reaction mixture (with water with ice,

cold water or saturated solution of ammonium chloride;

extraction of reaction products with pentane and/or ether,

drying with K₂CO₃or MgSO₄). The strong inﬂuence of

reaction conditions on its result was not observed.

Whereas the replacement of the hydrogen atom in

methyl isothiocyanate by a heteroatomic substituent

(methoxy group) favors the fast and quantitative isom-

erization of the obtained therefrom 1-aza-1,3,4-triene

VIh into 2-aza-1,3,5-triene VIIh and thus completely

“inhibiting” the pyrrole channel of compound VIh

transformation (in the case of 1-aza-1,3,4-triene VIa the

main reaction product is pyrrole IIIa, up to 75% in the

mixture with 2,3-dihydropyridine IVa) (see the table),

the analogous replacement of a hydrogen atom in the

methyl group of ethyl isothiocyanate (for vinyloxy group)

provides an opposite effect. Unlike 1-aza-1,3,4-triene

VIb whose thermally induced conversion provides as

the main product 2,3-dihydropyridine IVb [up to 80% in

the mixture with pyrrole IIIb (see the table)], the distil-

lation of 1-aza-1,3,4-triene VIi obtained from 1-lithio-1-

methoxyallene (IIa) and 2-(vinyloxy)ethyl isothiocyanate

(Scheme 1) afforded approximately equimolar mixture

of 1-[2-(binyloxy)ethyl]pyrrole IIIi and 2-[(vinyloxy)

methyl]-2,3-dihydropyridine IVi. This experiment shows

that the introduction of the vinyloxy group into the ethyl

Two most probable cyclization routes of 1-aza-1,3,4-

trienes VI into pyrroles III are postulated in [4, 11]:

through the protonated form of 3-alkoxy-1-aza-1,3,4-

triene (Scheme 4) or through the carbenoid cyclic inter-

mediate (Scheme 5).

The formation of pyrrole structures through the

protonation of 3-alkoxy-1-aza-1,3,4-triene VI recently

was conﬁrmed by calculations [19]. The most favorable

for the cyclization is the proton attack on the π-orbital

localized on the C_β–C_γcenters of the allene fragment.

This results in the activation of the p-orbital of atom

C_γand its coupling with the π-orbital of the nitrogen

atom. The calculations demonstrate that whereas

the [1,5]-H shift (VIa)→(VIIa) and the subsequent

electrocyclic rearrangement of 2-aza-1,3,5-triene VIIa

into 2,3-dihydropyridine IVa have activation energies

Scheme 3.

OMe

SMe

OMe

SMe

^_MeOH

MeO

N

VIII

IVh

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REACTIONS OF HETEROCUMULENES WITH ORGANOMETALLIC REAGENTS: XVII.

665

114.3 and 90.1 kJ mol⁻¹respectively, the formation of

the pyrrole ring IIIa through the protonated structures

A and B occurs with the activation barrier 44.9 kJ mol⁻¹

(HF/6-31G**).

the formation of σ-bond C–N and a cyclic carbine C

(Scheme 5). The activation energy of this stage for 1-aza-

1,3,4-triene VIa equals 96.2 kJ mol⁻¹[28] and is ~2 times

greater than the activation barrier (44.9 kJ mol⁻¹) [19] of

the pyrrole ring IIIa formation through the protonated

structures (Scheme 4). [1,2]-Hydride shift in intermedi-

ate C occurs with overcoming the activation barrier of

61.5 kJ mol⁻¹(transition state D). The overall heat balance

of the reaction attains 156.6 kJ mol⁻¹[28].

Obviously, the presence of an alkoxy group in 1-aza-

1,3,4-triene VI should facilitate the protonation due to the

stabilization of the carbenium center with oxygen atom

in agreement with the fact that neither from 1-lithio-1-

methylallene nor from 3-(tert-butyl)-1-lithio-allene under

identical conditions pyrroles were formed. The only

reaction products in these cases were the corresponding

2,3-dihydropyridines [26, 27] (independent of the struc-

ture of aliphatic isothiocyanate) and/or pyridines [27].

Yet this mechanism has not up till now obtained a reliable

experimental proof.

Note that in [29] quantum-chemical methods were

applied to the study of various mechanisms of the open-

ing of pyrrole ring at the thermolysis of unsubstituted

1H-pyrrole [30], and it was established that the most

preferable was the inverted mechanism of the direct

nucleophilic attack (Scheme 6).

The second hypothetical route of the [1,5]-cycliza-

tion of 1-aza-1,3,4-trienes VI into pyrroles III assumes

a direct nucleophilic attack of the nitrogen atom on the

terminal carbon atom of the allene fragment leading to

We developed a simple and convenient method of

isolation of the synthesized pyrroles and dihydropyridines

in the individual state consisting in the treatment of their

mixture ﬁrst with pentane and then with the cold ~1 M

Scheme 4.

H

OR¹

SR⁴

[1,5]-Н shift

6π-Electrocyclization

R³

R²

N

VII

OR¹

SR⁴

R³

R²

α

+

SR⁴

CHR²R³

Heating

N

CHR²R³

VI

III

IV

?

^_H⁺

OR¹

SR⁴

H

OR¹

SR⁴

H

+

H

N

CHR²R³

A

B

Scheme 5.

OMe

SMe

OMe

SMe

OMe

SMe

.

SMe

Me

H

C

H

N

.

H

SMe

H

N

Me

N

Me

C

VIa

IIIa

D

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

NEDOLYA et al.

666

Scheme 6.

505 (accelerating voltage 3 kV, emission current 100 mA,

ionizing electrons energy 70 eV, carrier gas helium).

H

All operations were carried out under nitrogen or argon

atmosphere. Cooling was performed with liquid nitrogen.

THF was puriﬁed by dispersed KOH (~50 g l⁻¹) and dis-

tillation over LiAlH₄or sodium in the presence of benzo-

phenone under the inert atmosphere. Methoxyallene (Ia)

and tert-butoxyallene (Ib) were synthesized by procedure

[13], isopropyl, sec-butyl, 2-(vinyloxy)ethyl, cyclopro-

pyl, cyclopentyl, and cyclohexyl isothiocyanates were

obtained by condensation of the corresponding triethyl-

ammonium N-monosubstituted dithiocarbamates with

acetic anhydride or acetyl chloride [4], methoxymethyl

isothiocyanate, by boiling methoxy(chloro)methane with

potassium thiocyanate in pentane [32]. Butyllithium (1.6

and 2.5 M hexane solutions) and the other reagents and

solvents used in the study were commercial products. The

individuality of initial reagents was checked by NMR

spectra. The lithiation was predominantly performed

using 1.6 M hexane solution of BuLi and only in special

cases (marked in the description of the experiment) 2.5 M

solution was applied. The yields of all reaction products

were calculated on the theoretically possible with respect

to isothiocyanate.

.

H

C

H

N

H

N

.

N

H

solution of HCl. After the separation of layers and the

removal of solvent from the organic phase pyrrole III is

obtained. Dihydropyridine IV is extracted from the water

phase after the neutralization of the latter with the concn.

solution of KOH. Compounds III and IV were isolated in

good overall yields (up to 85%). Their composition and

structure were conﬁrmed by elemental analysis, IR, ¹H,

¹³C NMR, and mass spectra [31].

Hence we demonstrated for the ﬁrst time that alkoxy-

allenes and aliphatic isothiocyanates are fundamentally

new starting compounds for the simple and convenient

synthesis of previously unknown 2-(alkylsulfanyl)-

3-alkoxypyrroles and 6-(alkylsulfanyl)-5-alkoxy-2,3-

dihydropyridine in high yield in one preparative stage.

The reported experimental data allow a conclusion that

the approach we found and the synthetic method based

thereon for preparation of versatile pyrroles and 2,3-di-

hydropyridines proceeding from isothiocyanates and

α-lithiated alkoxyallenes possess the general character

and wide preparative prospects.

Methyl-N-methyl-2-methoxybuta-2,3-dienimido-

thioate (VIa), 1-methyl-2-(methylsulfanyl)-3-methoxy-

pyrrole (IIIa), and 6-(methylsulfanyl)-5-methoxy-2,3-

dihydropyridine (IVa). a. To a solution of 104 mmol

of BuLi in 65 ml of hexane and 65 ml of THF at –90°C

was added by one portion 9.1 g (130 mmol) of allene Ia

(the reaction proceeded with powerful exothermic effect

and required efﬁcient cooling). The reaction mixture was

stirred for 10 min at –65...–60°C, cooled to –100°C and

a solution of 7.35 g (100.7 mmol) methyl isothiocya-

nate in ~20 ml of THF was added by one portion. The

temperature quickly raised to –60°C (at cooling). The

reaction mixture was stirred for 10 min at –65...–60°C

and to the formed bright yellow dispersion was added

22 g (154.9 mmol) of MeI. After warming the reaction

mixture to 0°C it was treated with 100 ml of ice water at

vigorous stirring. The reaction product was extracted into

pentane (4 × 50 ml), the extracts were thrice washed with

water and dried with K₂CO₃. The solvent was divided in

two equal parts.

EXPERIMENTAL

IR spectra were recorded on spectrophotometers

Bruker IFS-25, Perkin Elmer-283, and Specord 75-IR

from thin layers, in pellets with KBr, and in ﬁlms obtained

by evaporation of CCl₄solutions. NMR spectra were reg-

istered on spectrometers Bruker DPX-400 [400.13 (¹H)

and 100.62 MHz (¹³C)], BrukerAC-300 [300 (¹H) and 75

MHz (¹³C)], Bruker DPX-250 [250 (¹H) and 62.9 MHz

(¹³C)] from ~5–10% solutions in CDCl₃, internal refer-

ence HMDS, and Varian EM-390 [90 MHz (¹H)] for

~20% solutions in CCl₄, internal reference TMS. To prove

the structure and to provide the complete assignments of

signals in ¹H and ¹³C NMR spectra a series of 2D NMR

experiments was carried out (COSY-¹H, HSQC-¹³C, and

HMBC-¹³C) on a spectrometer Bruker AV-400. GLC

analysis was performed on a chromatograph Varian 3400

(ﬂame-ionization detector, capillary column 15 m × 0.53

mm, stationary phase DB-5 1.5 μm, carrier gas nitrogen).

Mass spectra were measured on spectrometer Jeol AX

From the ﬁrst part the solvent was removed on a rotary

evaporator at the bath temperature not exceeding 30°C.

We obtained as a residue 7.8 g (99%) of 1-aza-1,3,4-triene

VIa (mixture of E- and Z-isomers). IR spectrum (thin

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REACTIONS OF HETEROCUMULENES WITH ORGANOMETALLIC REAGENTS: XVII.

667

layer), ν, cm^–1: 436, 589, 622, 667, 699, 903, 958, 975,

998, 1050, 1088, 1140, 1173, 1211, 1267, 1310, 1396,

1435, 1448, 1459, 1547, 1618, 1946 (=C=), 2771, 2831,

2861, 2919, 2957, 3005, 3214, 3289. ¹H NMR spectrum

(90 MHz, CCl₄), δ, ppm, ratio of E- and Z-isomers ~2 :

1: 2.20 s, 2.35 s (3H, SMe), 3.17 s, 3.25 s (3H, NMe),

3.45 s (3H, OMe), 5.63 s (2H, CH₂=). ¹H NMR spectrum

(400 MHz, CDCl₃), δ, ppm, ratio of E- and Z-isomers

~1 : 1: 2.27 s, 2.43 s (3H, SMe), 3.327 s, 3.331 s (3H,

NMe), 3.46 s, 3.51 s (3H, OMe), 5.69 s, 5.74 s (2H,

CH₂=). ¹³C NMR spectrum (100 MHz, CDCl₃), δ, ppm:

12.84, 15.13 (SMe), 40.86, 41.38 (NMe), 55.86, 56.18

(OMe), 93.06, 93.56 (CH₂=), 128.21, 131.95 (O–C=),

158.43, 160.08 (C=N), 198.81, 200.52 (=C=). ¹³C NMR

spectrum (100 MHz, C₆D₆, –10°C), δ, ppm, E-isomer:

13.48 (SMe), 41.97 (NMe), 56.37 (OMe), 94.52 (CH₂=),

129.14 (O–C=), 155.72 (C=N), 199.60 (=C=); Z-isomer:

14.96 (SMe), 40.77 (NMe), 56.50 (OMe), 93.56 (CH₂=),

132.27 (O–C=), 161.66 (C=N), 200.27 (=C=).

81, 73, 53, 42, 39. Found, %: C 53.54; H 7.36; N 8.41;

S 20.13. C₇H₁₁NOS. Calculated, %: C 53.47; H 7.05;

N 8.91; S 20.39. M 157.23.

The “acidic” water layer was treated with concn. KOH,

extracted with ether (4 × 50 ml), the solution was dried

with K₂CO₃and on removing the solvent under a reduced

pressure 2,3-dihydropyridine IVa was obtained. Yield 1.8

g (23%), nearly colorless ﬂuid, bp 90–93°C (2 mm Hg),

n_D²⁰1.5444. IR spectrum (thin layer), ν, cm^–1: 540, 690,

790, 800, 960–970, 1025, 1050, 1100, 1170, 1210, 1250,

1310, 1350, 1400–1430–1450, 1570, 1640, 1690, 2830,

2900, 2930, 3000, 3070, 3140. ¹H NMR spectrum (400

MHz, CDCl₃), δ, ppm: 2.19 m (2H, 3-CH₂), 2.26 s (3H,

SMe), 3.56 m (2H, NCH₂), 3.58 s (3H, OMe), 5.10 t

3

(1H, 4-CH=, J 4.7 Hz). ¹³C NMR spectrum (J mod,

100 MHz, CDCl₃), δ, ppm: 11.42 (SMe), 21.14 (3-CH₂),

48.12 (NCH₂), 54.48 (OMe), 98.83 (4-CH=), 147.85

(5-C=), 161.67 (6-C=). Mass spectrum, m/z (I_rel, %):

157 (100) [M]^+·, 142, 124, 114, 95, 80, 69, 55, 41, 39,

27, 26, 18. Found, %: C 53.22; H 7.40; N 8.65; S 20.15.

C₇H₁₁NOS. Calculated, %: C 53.47; H 7.05; N 8.91;

S 20.39. M 157.23.

To the second part of the organic fraction 40 ml of

parafﬁn oil was added, and the solvent was removed on

the rotary evaporator at the bath temperature 60–70°C.

The residue was distilled in a vacuum to obtain 6.25 g

(79%) of the mixture of pyrrole IIIa and 2,3-dihydropyri-

dine IVa in the ratio ~7 : 3 (according to ¹H NMR and

GLC data), bp 115–117°C (15 mm Hg), n_D²⁰1.5515. The

distillate was dissolved in 50 ml of pentane, the solvent

was vigorously shaken with cold (0°C) 1 M hydrochlo-

ric acid (20% excess), and the layers were separated.

The water layer was extracted with pentane (4 × 50 ml),

the combined organic fraction was treated with a small

quantity of concn. solution of KOH (till neutral reaction),

the layers were separated. The organic fraction was dried

with K₂CO₃, the solvents were removed under a reduced

pressure to obtain in the residue pyrrole IIIa. Yield 4.2 g

(53%), content of the main substance 99% (by GLC data),

colorless ﬂuid, bp 84–85°C (2 mm Hg), n_D²⁰1.5470. At

room temperature and on cooling pyrrole IIIa crystal-

lized. IR spectrum (ﬁlm), ν, cm^–1: 700, 970, 1100, 1320,

1370, 1400, 1410, 1460, 1550, 2830, 2920–2940, 3000,

bTo a solution of 112 mmol of BuLi in 70 ml of hexane

and 80 ml of THF while stirring at –90°C was added in

one portion cooled solution of 9.1 g (130 mmol) of al-

lene Ia in 20 ml of THF. The reaction mixture was stirred

for 5 min at –65...–60°C, cooled to –90°C and quickly

was added thereto the solution of 7.35 g (100.7 mmol)

of methyl isothiocyanate in 20 ml of THF. The reaction

mixture was stirred for 5 min at –60°C, 22 g (154.9 mmol)

of MeI was added, and the cooling was removed. After

natural warming to 5°C the mixture was heated for 1 h

at 30–40°C, then it was cooled and treated with the satu-

rated water solution of NH₄Cl (at vigorous stirring). The

reaction products were extracted into ether (4 × 50 ml),

the extracts were dried with MgSO₄, the solvents were

removed on a rotary evaporator at the bath temperature

30–40°C; the last drops of solvent were removed at the

bath temperature ~70°C and cooling of the collector with

liquid nitrogen.After removing the water bath the residue

(13.25 g, 84%) unexpectedly started to boil (a vigorous

exothermic reaction began), it was quickly cooled with

liquid nitrogen. Analysis of crude product by GLC and

NMR methods showed that it contained pyrrole IIIa

(67%) and 2,3-dihydropyridine IVa (20%). By distillation

in a vacuum 9.52 g (60%) of a mixture of compounds IIIa

and IVa was isolated, bp ~75°C (~0.5 mm Hg), content

of main substances 91% (by GLC data). The products

1

3100–3120. H NMR spectrum (400 MHz, CDCl₃), δ,

ppm: 2.14 s (3H, SMe), 3.59 s (3H, NMe), 3.79 s (3H,

OMe), 5.82 d (1H, 4-CH=, ³J 3.2 Hz), 6.53 d (1H, 5-CH=,

³J 3.2 Hz). ¹³C NMR spectrum (J mod,100 MHz, CDCl₃),

δ, ppm: 20.32 (SMe), 33.83 (NMe), 58.09 (OMe), 94.32

(4-CH=), 106.19 (2-C=), 120.99 (5-CH=), 151.29 (3-

C=). For correct assignment of signals in the ¹³C NMR

spectrum 2D HMBC NMR experiment was performed.

Mass spectrum, m/z (I_rel, %): 157 (100) [M]^+·, 142, 98,

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

NEDOLYA et al.

668

(2H, NCH₂), 5.67 s, 5.74 s (2H, CH₂=). ¹³C NMR spec-

trum (100 MHz, CDCl₃), δ, ppm: 11.18, 13.44 (SMe),

13.50, 14.61 (Me), 46.44, 46.85 (NCH₂), 54.15, 54.44

(OMe), 91.34, 91.70 (CH₂=), 126.13, 126.75 (O–C=),

154.60, 156.49 (C=N), 197.00, 198.49 (=C=).

were separated with the use of dilute hydrochloric acid

as described above.

c. To a solution of 10 g (137 mmol) methyl isothio-

cyanate in 50 ml of THF cooled to −50°C was added

with a syringe in three portions a solution of 1-lithio-1-

methoxyallene (IIa) prepared in another ﬂask in a nitro-

gen ﬂow from 120 mmol of BuLi in 75 ml of hexane and

9 g (128.6 mmol) of allene Ia in 50 ml of THF at −80°C.

The solution turned into a bright yellow dispersion. The

reaction mixture was allowed to warm to –35°C and 20 g

(140.8 mmol) of MeI was added. After 30 min (when

the temperature rose to 15°C) to the reaction mixture

(transparent dark-brown solution) was poured in 150 ml

of ice water. The reaction products were extracted into

pentane (2 × 50 ml), the extracts were dried with K₂CO₃.

The solvents were removed at a reduced pressure, the

residue (17.5 g, 93%) was distilled in a vacuum. We

obtained 12.4 g (66%) of a mixture of pyrrole IIIa and

2,3-dihydropyridine IVa in a ratio 3.3 : 1. The products

were separated with the use of dilute hydrochloric acid

as described above.

b. To a solution of 104 mmol of BuLi in 65 ml of

hexane and 80 ml of THF at –100°C was added 9 g

(128.6 mmol) of allene Ia in 10 ml of THF. The tem-

perature rose to –50°C. The reaction mixture was stirred

for 10 min at –55...–50°C, cooled to–100°C, and 9 g

(103.4 mmol) of ethyl isothiocyanate was added. After

the warming of the mixture to –55°C to the formed bright

yellow dispersion was added 21.6 g (152.1 mmol) of MeI.

At 0°C the reaction mixture was treated with 150 ml of

cold water at vigorous stirring. The reaction products

were extracted into pentane (2 × 50 ml), extracts were

dried with K₂CO₃, then solvents were removed on the

rotary evaporator at the bath temperature 60–70°C. Yield

of reaction products 16.1 g (91%), content of the main

products 98%: 21% of pyrrole IIIb, 77% of 2,3-dihy-

dropyridine IVb (by GLC data). No signals of azatrienes

VIb and VIIb were observed in the ¹H NMR spectrum.

After separation of the reaction products like described

above and the removal of the solvent from the organic

fraction we obtained 3.65 g (21%) of pyrrole IIIb, content

of the main substance 97% (by GLC data), light ﬂuid,

bp 82–83°C (1 mm Hg), n_D²⁰1.5322. IR spectrum (thin

layer), ν, cm^–1: 470, 600, 650, 700, 800, 940, 960, 980,

1035, 1080, 1090, 1110, 1170, 1220, 1250, 1330, 1380,

1400, 1450, 1460, 1540, 1640, 1680, 1710, 2830, 2940,

2975, 3100, 3120. ¹H NMR spectrum (400 MHz, CDCl₃),

Methyl-2-methoxy-N-ethylbuta-2,3-dienimi-

dothioate (VIb), 1-(methylsulfanyl)-2-methoxy-

N-ethyl-idenebuta-1,3-dien-1-amine (VIIb),

2-(methylsulfanyl)-3-methoxy-1-ethylpyrrole (IIIb),

2-methyl-6-(methylsulfanyl)-5-methoxy-2,3-dihydro-

pyridine (IVb). a. To a solution of 59.2 mmol of BuLi in

37 ml of hexane and 50 ml of THF at –100°C was added

4.5 g (64.3 mmol) of allene Ia. The temperature rose to

–75°C. The reaction mixture was stirred for 10 min at

–80...–75°C, cooled to –95°C, and 4.35 g (50 mmol)

of ethyl isothiocyanate was added. The temperature

rose to –65°C. The reaction mixture was stirred for

15 min at –65...–60°C (golden-yellow dispersion), 16 g

(112.7 mmol) of MeI was added, the temperature was

allowed to rise to 10°C, then the mixture was cooled to

–10°C , and 80 ml of water solution of NH₄Cl was added

at vigorous stirring. The reaction products were extracted

into ether (3 × 20 ml), the extracts were washed with wa-

ter (3 × 10 ml), and dried with MgSO₄. On removing the

solvents at a reduced pressure and the bath temperature

20–30°C 8.6 g (100%) of thick brown ﬂuid was obtained,

n_D²⁰1.4982 (mixture of 93% of 1-aza-1,3,4-triene VIb,

6% of 2-aza-1,3,5-triene VIIb, and 1% of pyrrole IIIb

according to ¹H NMR data). ¹H NMR spectrum of 1-aza-

1,3,4-triene VIb (mixture of E- and Z-isomers) (400 MHz,

CDCl₃), δ, ppm: 1.22 t, 1.30 t (3H, NCH₂CH₃, ³J 7.2 Hz),

2.29 s, 2.43 s (3H, SMe), 3.46 s, 3.52 s (3H, OMe), 3.56 m

3

δ, ppm: 1.33 t (3H, NCH₂CH₃, J 7.2 Hz), 2.14 s (3H,

SMe), 3.77 s (3H, OMe), 3.97 q (2H, NCH₂, ³J 7.2 Hz),

5.84 d (1H, 4-CH=, ³J 3.2 Hz), 6.57 d (1H, 5-CH=, ³J 3.2

Hz). ¹³C NMR spectrum (100 MHz, CDCl₃), δ, ppm:

16.92 (Me), 20.64 (SMe), 41.72 (NCH₂), 58.32 (OMe),

95.04 (4-CH=), 105.00 (2-C=), 119.40 (5-CH=), 151.64

(3-C=). Found, %: C 56.23; H 7.40; N 8.09; S 18.58. C₈H-

₁₃NOS. Calculated, %: C 56.10; H 7.65; N 8.18; S 18.72.

From the “acidic” layer 11.56 g (65%) of 2,3-dihy-

dropyridine IVb was isolated, content of the main sub-

stance 98% (by GLC data), light ﬂuid. After distillation

in a vacuum 9 g (53%) of compound IVb was obtained,

content of the main substance 99% (by GLC data), bp

20

91–92°C (1 mm Hg), n_D1.5376. IR spectrum (thin

layer), ν, cm^–1: 550, 640, 690, 710, 780, 890, 920, 960,

995, 1010, 1030, 1040, 1060, 1100, 1140, 1170, 1185,

1200, 1240, 1265, 1290, 1300, 1340, 1370, 1400, 1420,

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669

1445, 1450, 1570, 1640, 2830, 2870, 2920, 2960, 3000,

3060, 3130. H NMR spectrum (400 MHz, CDCl₃), δ,

of compound VIIc (300 MHz, CDCl₃), δ, ppm: 1.78 s,

1.96 s [6H, (CH₃)₂C=], 2.06 C (3H, SMe), 3.52 s (3H,

OMe), 4.78 d.d (1H, CH₂=, J 10.8, J 2.0 Hz), 5.06

d.d (1H, CH₂=, ³J 17.1, ²J 2.0 Hz), 5.80 d.d (1H, CH=,

³J 17.1, 10.8 Hz).

1

ppm: 1.29 d (3H, 2-Me, ³J 6.8 Hz), 1.96, 2.00, 2.03 d.d.d

(2H, 3-CH₂, ³J 17.6, 3.8, ²J 12.01 Hz), 2.29 s (3H, SMe),

3.58 m (1H, NCH), 3.58 s (3H, OMe), 5.02 d.d (1H,

4-CH=, ³J 5.4, 3.8 Hz). ¹³C NMR spectrum (100 MHz,

CDCl₃), δ, ppm: 11.43 (SMe), 21.98 (3-CH₂), 28.58 (Me),

53.68 (NCH), 54.68 (OMe), 98.09 (4-CH=), 147.98 (5-

C=), 160.01 (6-C=). Found, %: C 55.57; H 7.74; N 7.81;

S 18.79. C₈H₁₃NOS. Calculated, %: C 56.10; H 7.65;

N 8.18; S 18.72.

3

2

After 3 min of evacuation at 60°C the reaction product

contained 70% of 2-aza-1,3,5-triene VIIc, 30% of noni-

somerized 1-aza-1,3,4-triene VIc, and traces of pyrrole

IIIc. Short heating of the reaction products by the burner

ﬂame resulted in a mixture of pyrrole IIIc and 2,3-dihy-

dropyridine IVc in the ratio ~1 : 9.

Methyl-N-isopropyl-2-methoxybuta-2,3-dienimi-

dothioate (VIc), 1-(methylsulfanyl)-N-(1-methyl-

ethylidene)-2-methoxybuta-1,3-dien-1-amine (VIIc),

1-isopropyl-2-(methylsulfanyl)-3-methoxypyrrole

(IIIc), and 2,2-dimethyl-6-(methylsulfanyl)-5-

methoxy-2,3-dihydropyridine (IVc). a. To a solution

of 64 mmol of BuLi in 40 ml of hexane and 70 ml of

THF at –100°C was added 6 g (85.7 mmol) of allene

Ia, the mixture was stirred for 10 min at –70...–60°C,

cooled again to –100°C, and 5.05 g (50 mmol) of iso-

propyl isothiocyanate was added (the temperature rose

to –30°C). The reaction mixture was stirred for 15 min

at –35...–30°C, cooled to –80°C, and 16 g (112.7 mmol)

of MeI was added (the temperature rose to 20°C within

25 min). The mixture was cooled to –80°C, and 100 ml

of saturated water solution of NH₄Cl was added at vig-

orous stirring. The reaction products were extracted into

ether (3 × 50 ml), the extracts were washed with water

(3 × 30 ml), and dried with MgSO₄. The solvents were

removed on the rotary evaporator at room temperature

to obtain 1-aza-1,3,4-triene VIc (mixture of E- and

b. To a solution of 104 mmol of BuLi in 65 ml of

hexane and 80 ml of THF at –100°C was added 9.69 g

(138.4 mmol) of allene Ia, the temperature was allowed

to rise to −50°C (within 5–7 min), the mixture was cooled

again to –100°C, and 10.3 g (102 mmol) of isopropyl

isothiocyanate was added (the temperature rose to –10°C).

The mixture was cooled to –50°C, 22.8 g (160.6 mmol)

of MeI was added (the temperature rose to 5°C within

10 min), the reaction mixture was again cooled to–30°C

and it was treated with cold water at vigorous stirring.

The reaction products were extracted with pentane (2 ×

50 ml) and ether (2 × 50 ml), the extracts were dried

with K₂CO₃. The solvents were removed on a rotary

evaporator to obtain 17.64 g (94%) of 2-aza-1,3,5-triene

VIIc with an impurity of pyrrole IIIc (by the data of

¹H NMR). ¹H NMR spectrum (400 MHz, CDCl₃), δ, ppm:

1.89 s, 2.07 s [6H, (CH₃)₂C=], 2.17 s (3H, SMe), 3.63 s

(3H, OMe), 4.90 d.d (1H, CH₂=, ³J 10.8, ²J 2.0 Hz), 5.18

d.d (1H, CH₂=, ³J 17.1, ²J 2.0 Hz), 5.91 d.d (1H, CH=,

³J 17.1, 10.8 Hz). ¹³C NMR spectrum (100 MHz, CDCl₃),

δ, ppm: 12.50 (SMe), 20.92, 27.53 [(CH₃)₂C=], 58.15

(OMe), 109.42 (CH₂=), 126.24 (CH=), 134.00 (S−C=),

137.82 (O−C=), 173.68 (C=N).

1

Z-isomers). H NMR spectrum (400 MHz, CDCl₃), δ,

ppm, major isomer: 1.18 d [6H, CH(CH₃)₂, ³J 6.3 Hz],

2.41 s (3H, SMe), 3.50 s (3H, OMe), 3.92 septet (1H,

NCH, ³J 6.3 Hz), 5.71 s (2H, CH₂=); minor isomer: 1.11

d [6H, CH(CH₃)₂, ³J 6.1 Hz], 2.27 s (3H, SMe), 3.42 s

(3H, OMe), 3.97 septet (1H, NCH, ³J 6.1 Hz), 5.65 s (2H,

CH₂=); isomers ratio ~1.3 : 1.

c. To a solution of 104 mmol of BuLi in 65 ml of

hexane and 80 ml of THF at –100°C was added 9.4 g

(134.3 mmol) of allene Ia, the temperature was allowed

to rise to −60°C, the mixture was cooled again to –100°C,

and 10.4 g (103 mmol) of isopropyl isothiocyanate was

added (the temperature rose to –50°C). The reaction mix-

ture was stirred for 15 min at –65 × –60°C (light-brown

dispersion), the cooling was removed, and at –30°C 20.6 g

(145.1 mmol) of MeI was added. The temperature rose

to 5°C. The reaction mixture was stirred at this tempera-

ture for 15 min and treated with cold water. The reaction

products were extracted with pentane (2 × 50 ml) and

ether (2 × 50 ml), the extracts were dried with K₂CO₃.

On removing the solvents on the rotary evaporator 17 g

On removing the main part of solvents on the rotary

evaporator at room temperature the reaction product

was evacuated for 5 min at the bath temperature ~60°C,

and then for 15 min in a vacuum of an oil pump (7 mm

Hg). We obtained 9.06 g (98%) of light-brown ﬂuid

1

liquid containing according to H NMR data, 89% of

2-aza-1,3,5-triene VIIc and 11% of pyrrolea IIIc. 1-Aza-

1,3,4-triene VIc and 2,3-dihydropyridine IVc were not

1

identiﬁed in the reaction products. H NMR spectrum

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

NEDOLYA et al.

670

(89%) of brown ﬂuid was obtained containing according

to the H NMR data predominantly 2-aza-1,3,5-triene

(methylsulfanyl)-2-methoxybuta-1,3-dien-1-amine

(VIId), 1-(sec-butyl)-2-(methylsulfanyl)-3-methoxy-

pyrrole (IIId) and 2-methyl-6-(methylsulfanyl)-5-

methoxy-2-ethyl-2,3-dihydropyridine (IVd). a. To

a solution of 64 mmol of BuLi in 40 ml of hexane and

70 ml of THF at –100°C was added 6.1 g (87.1 mmol)

of allene Ia, the mixture was stirred for 10 min at –70...

–60°C, cooled again to –100°C, and 5.75 g (50 mmol) of

sec-butyl isothiocyanate was added (the temperature rose

to –30°C). The reaction mixture was stirred for 15 min

at –35 × –30°C, cooled to –80°C, and 16 g (112.7 mmol)

of MeI was added. The temperature rose to 20°C within

25 min. On cooling to –80°C 100 ml of saturated water

solution of NH₄Cl was added at vigorous stirring. The

reaction products were extracted into ether (3 × 50 ml),

extracts were washed with water (3 × 30 ml), and dried

with MgSO₄. On removing the main amount of solvent

on the rotary evaporator at room temperature the reac-

tion product was subjected to a vacuum for 12 min

more at the bath temperature ~60°C, then for 15 min to

a vacuum of an oil pump (8 mm Hg) to get 9.76 g (98%)

of broun mobile liquid containing according to ¹H NMR

data 89% of 2-aza-1,3,5-triene VIId and 11% of pyrrole

IIId. ¹H NMR spectrum of compound VIId (400 MHz,

CDCl₃), δ, ppm: 1.17 t (3H, CH₂CH₃, ³J 7.4 Hz), 1.86 s

(3H, Me), 2.06 s (3H, SMe), 2.42 q (2H, CH₂CH₃,

³J 7.4 Hz), 3.63 s (3H, OMe), 4.86 d.d (1H, CH₂=, ³J 10.8,

1

VIIc with an impurity of pyrrole IIIc. The vacuum dis-

tillation furnished 14 g (73%) of products of the same

composition with the admixture of 2,3-dihydropyridine

1

IVc (according to the H NMR data), bp 80–83°C (0.5

mm Hg). The distillate was heated for several seconds

in the ﬂame of a burner to ~100°C, then the exothermic

heterocyclization started. A mixture was obtained of

practically pure 2,3-dihydropyridine IVc (main compo-

nent) and pyrrole IIIc (according to the ¹H NMR data);

overall content 96% (by GLC data). The products were

separated with the help of hydrochloric acid as described

above. From the organic fraction 2 g (11%) of pyrrolea

IIIc was isolated, content of the main substance 98% (by

GLC data), bp ~80°C (0.5 mm Hg), mp 34°C (EtOH). IR

spectrum (KBr), ν, cm^–1: 590, 620, 650, 735, 870, 955,

960, 1035, 1065, 1100, 1130, 1170, 1230, 1260, 1330,

1360, 1400, 1410, 1460, 1540, 2830, 2870, 2930, 2965,

1

3110, 3120. H NMR spectrum (300 MHz, CDCl₃), δ,

ppm: 1.33 d [6H, CH(CH₃)₂, ³J 6.8 Hz], 2.12 s (3H, SMe),

3

3.75 s (3H, OMe), 4.70 septet (1H, NCH, J 6.8 Hz),

3

5.85 d (1H, 4-CH=, J 3.3 Hz), 6.60 d (1H, 5-CH=,

³J 3.3 Hz). ¹³C NMR spectrum (75 MHz, CDCl₃), δ,

ppm: 20.36 (SMe), 23.21 [CH(CH₃)₂], 46.32 (NCH),

57.60 (OMe), 94.30 (4-CH=), 105.00 (2-C=), 115.68

(5-CH=), 150.84 (3-C=). Found, %: C 58.31; H 8.52;

N 7.45; S 17.30. C₉H₁₅NOS. Calculated, %: C 58.34;

H 8.16; N 7.56; S 17.31.

²J 1.8 Hz), 5.16 d.d (1H, CH₂=, J 17.2, J 1.8 Hz),

5.89 d.d (1H, CH=, ³J 17.2, 10.8 Hz). ¹³C NMR spectrum

(J mod, 100 MHz, CDCl₃), δ, ppm: 10.46 (CH₂CH₃),

12.61 (SMe), 19.91 (Me), 34.12 (CH₂CH₃), 58.31 (OMe),

109.37 (CH₂=), 126.33 (CH=), 134.25 (S–C=), 137.52

(O–C=), 177.74 (C=N). The correct assignment of the

signals in the ¹³C NMR spectrum was done with the help

of 2D HMBC NMR experiment.

3

2

From the “acidic” fraction 2,3-dihydropyridine IVc

was obtained, after distillation 7.7 g (40%), content of

the main substance 96% (by GLC data), bp ~115°C

(15 mm Hg), n_D²⁰1.5260. IR spectrum (thin layer), ν,

cm^–1: 480, 555, 600, 690, 720, 750, 790, 870, 890,

950, 960, 1000, 1030, 1070, 1125, 1170, 1190, 1220,

1240, 1250, 1300, 1340, 1350, 1370, 1400, 1420, 1450,

1460, 1580, 1650, 2830, 2860, 2930, 2970, 3000, 3060,

b. To a solution of 67.5 mmol of BuLi in 27 ml hexane

(2.5 M solution) and 70 ml of THF at –100°C was added

6 g (85.6 mmol) of allene Ia, the mixture was stirred for

10 min at –70...–60°C, cooled again to –90°C, and 5.76 g

(50 mmol) of sec-butyl isothiocyanate in 5 ml of THF

was added (the temperature rose to –30°C). The reaction

mixture was stirred for 30 min at –35...–30°C, cooled to

–80°C, and 15 g (105.7 mmol) of MeI was added. The

temperature rose to 18°C in 30 min. On cooling to –80°C

100 ml of saturated water solution of NH₄Cl was added

at vigorous stirring. The reaction products were extracted

into ether (3 × 50 ml), extracts were washed with water

(2 × 30 ml), and dried with MgSO₄. The solvents were

removed ﬁrst on a rotary evaporator, and then in a vacuum

1

3140. H NMR spectrum (400 MHz, CDCl₃), δ, ppm:

1.17 s [6H, 2-C(CH₃)₂], 2.20 s (3H, SMe), 2.20 d (2H,

3-CH₂, ³J 4.8 Hz), 3.55 s (3H, OMe), 4.88 t (1H, 4-CH=,

³J 4.8 Hz). ¹³C NMR spectrum (J mod, 100 MHz, CDCl₃),

δ, ppm: 10.94 (SMe), 28.13 [2-C(CH₃)₂], 33.44 (3-CH₂),

54.11 (OMe), 54.95 [2-C(CH₃)₂], 96.16 (4-CH=), 146.57

(5-C=), 157.27 (6-C=). Found, %: C 58.53; H 8.19;

N 7.50; S 17.12. C₉H₁₅NOS. Calculated, %: C 58.34;

H 8.16; N 7.56; S 17.31.

Methyl-N-(sec-butyl)-2-methoxybuta-2,3-dien-

imidothioate (VId), N-(1-methylpropylidene)-1-

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REACTIONS OF HETEROCUMULENES WITH ORGANOMETALLIC REAGENTS: XVII.

671

fraction, 0.35 g, bp 84–86°C (<1 mm Hg), contained

according to ¹H NMR data 60% of 2,3-dihydropyridine

IVd. II fraction (main), 4.03 g (43%), light-yellow mobile

ﬂuid, bp 86–88°C (<1 mm Hg), n_D²⁴1.5220, contained

according to ¹H NMR data pure 2,3-dihydropyridine IVd.

IR spectrum (thin layer), ν, cm^–1: 457, 475, 505, 536,

568, 580, 607, 619, 696, 719, 753, 795, 853, 877, 903,

916, 964, 998, 1011, 1025, 1035, 1053, 1081, 1105, 1133,

1151, 1184, 1204, 1230, 1246, 1284, 1300, 1311, 1341,

1367, 1410, 1430, 1452, 1461, 1586, 1649, 2834, 2877,

2924, 2965, 3063, 3153. ¹H NMR spectrum (400 MHz,

CDCl₃), δ, ppm: 0.90 t (3H, CH₂CH₃, ³J 7.4 Hz), 1.08 C

of an oil pump (1 mm Hg) at the bath temperature not

exceeding 25°C to obtain 9.46 g (95%) of light-brown

mobile liquid containing according to ¹H NMR data 65%

of 1-aza-1,3,4-triene VId (mixture of E- and Z-isomers),

33% of 2-aza-1,3,5-triene VIId, 2% of pyrrole IIId, and

traces of s-BuN=C=S (identiﬁed by the multiplet band

1

at 2103 cm^–1in the IR spectrum). H NMR spectrum

of 1-aza-1,3,4-triene VId (400 MHz, CDCl₃), δ, ppm:

3

0.78 t, 0.83 t (3H, NCHCH₂CH₃, J 7.4 Hz), 1.08 d,

1.13 d (3H, NCHCH₃, ³J 6.2 Hz), 1.48 m, 1.57 m (2H,

NCHCH₂CH₃), 2.27 s, 2.41 C (3H, SMe), 3.44 s, 3.50 s

(3H, OMe), 3.66 m (1H, NCHCH₃), 5.64 s, 5.71 s (2H,

CH₂=); isomers ratio 1.2 : 1.

3

(3H, 2-Me), 1.55 q (2H, CH₂CH₃, J 7.4 Hz), 2.08,

2.27 d.d (2H, 3-CH₂, ³J 5.5, 4.0, ²J 17.2 Hz), 2.24 s (3H,

To 9.16 g of reaction products 10 ml of toluene was

added, the mixture was slowly heated at stirring till boil-

ing (at virtually absent exothermic effect) and reﬂuxed for

30 min. Toluene was removed in a vacuum (1 mm Hg)

to obtain 8.36 g (87%) of dark-brown liquid containing

15% of pyrrole IIId and 85% of 2,3-dihydropyridine

IVd. The reaction products (8.16 g) were separated with

the use of dilute hydrochloric acid as described above.

From the organic fraction 1.49 g (16%) of pyrrole IIId

was isolated (dark viscous ﬂuid). By chromatography

on Al₂O₃[eluents petroleum ether (bp 40–70°C), then

a mixture petroleum ether–Et₂O, 10 : 1] 0.44 g of a frac-

tion was isolated containing according to ¹H NMR data

85% of pyrrole IIId, and 0.47 g of pure pyrrole IIId,

n_D²⁵1.5257. Yield 9%. IR spectrum (thin layer), ν, cm^–1:

470, 488, 596, 623, 649, 667, 710, 803, 846, 899, 922,

950, 967, 994, 1014, 1036, 1079, 1098, 1180, 1198, 1225,

1284, 1308, 1330, 1379, 1397, 1410, 1462, 1486, 1547,

1599, 1659, 2829, 2876, 2932, 2968, 3112. ¹H NMR spec-

trum (400 MHz, CDCl₃), δ, ppm: 0.79 t (3H, CH₂CH₃,

³J 7.4 Hz), 1.35 d (3H, NCHCH₃, ³J 6.8 Hz), 1.71 q (2H,

CH₂CH₃, ³J 7.4 Hz), 2.15 s (3H, SMe), 3.80 s (3H, OMe),

4.49 sextet (1H, NCHCH₃, ³J 6.8 Hz), 5.89 d (1H, 4-CH=,

³J 3.3 Hz), 6.59 d (1H, 5-CH=, ³J 3.3 Hz). ¹³C NMR spec-

trum (J mod, 100 MHz, CDCl₃), δ, ppm: 10.74 (CH₂CH₃),

20.83 (SMe), 21.82 (NCHCH₃), 30.64 (CH₂CH₃), 52.42

(NCH), 58.01 (OMe), 94.66 (4-CH=), 105.81 (2-C=),

116.33 (5-CH=), 150.91 (3-C=). The correct assignment

of the signals in the ¹³C NMR spectrum was done with the

help of 2D HMBC NMR experiment. Found, %: C 60.45;

H 8.39; N 7.15; S 15.90. C₁₀H₁₇NOS. Calculated, %:

C 60.26; H 8.60; N 7.03; S 16.09.

3

SMe), 3.58 s (3H, OMe), 4.88 d.d (1H, 4-CH=, J 5.5,

4.0 Hz). ¹³C NMR spectrum (J mod, 100 MHz, CDCl₃),

δ, ppm: 8.66 (2-CH₂CH₃), 11.41 (SMe), 24.70 (2-Me),

31.41 (3-CH₂), 34.74 (2-CH₂CH₃), 54.57 (OMe), 57.84

(2-C), 96.52 (4-CH=), 146.91 (5-C=), 157.30 (6-C=).

The correct assignment of the signals in the ¹³C NMR

spectrum was done with the help of 2D HMBC and HSQC

NMR experiments. Found, %: C 60.59; H 8.44; N 6.88;

S 15.79. C₁₀H₁₇NOS. Calculated, %: C 60.26; H 8.60;

N 7.03; S 16.09.

2-(Methylsulfanyl)-3-methoxy-1-cyclopropylpyr-

role (IIIe). To a solution of 64 mmol of BuLi in 40 ml

of hexane and 60 ml of THF at –100°C was added 5.5

g (78.5 mmol) of allene Ia, the reaction mixture was

stirred for 10 min at –65 × –60°C, cooled to –100°C,

and 4.95 g (50 mmol) of cyclopropyl isothiocyanate was

added. The reaction mixture was stirred for 20 min at

–35...–30°C, cooled to –70°C, and 12 g (84.5 mmol) of

MeI was added, the cooling bath was removed, and the

reaction mixture was stirred for 30 min, cooled to –80°C,

and treated with a saturated water solution of NH₄Cl.

The reaction products were extracted into ether, extracts

were washed with water, and dried with MgSO₄. On

removing the solvents at a reduced pressure and heating

we obtained 7.31 g (80%) of pyrrole IIIe, content of the

main substance 95% (by GLC data). ¹H NMR spectrum

(90 MHz, CCl₄), δ, ppm: 0.88 m [4H, (CH₂)₂], 2.18 s

(3H, SMe), 3.20 m (1H, NCH), 3.67 s (3H, OMe), 5.65 d

(1H, 4-CH=, ³J 3.3 Hz), 6.40 d (1H, 5-CH=, ³J 3.3 Hz).

Found, %: C 58.70; H 7.03; N 7.88; S 17.21. C₉H₁₃NOS.

Calculated, %: C 58.98; H 7.15; N 7.64; S 17.50.

1-(Methylsulfanyl)-2-methoxy-N-(cyclopent-

ylidene)buta-1,3-dien-1-amine (VIIf), 2-(methyl-

sulfanyl)-3-methoxy-1-cyclopentylpyrrole (IIIf),

From the “acidic” fraction 5.89 g (63%) of 2,3-dihy-

dropyridine IVd was isolated, dark brown mobile ﬂuid.

The distillation in a vacuum provided two fractions. I

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

NEDOLYA et al.

672

7-(methylsulfanyl)-8-methoxy-6-azaspiro-[4.5]deca-

6,8-diene (IVf). To a solution of 67.5 mmol of BuLi in

27 ml of hexane (2.5 M solution) and 70 ml of THF at

–100°C was added 6 g (85.6 mmol) of allene Ia, the reac-

tion mixture was stirred for 10 min at –70...–60°C, cooled

to –90°C, and 6.36 g (50 mmol) of cyclopentyl isothio-

cyanate in 5 ml of THF was added (the temperature rose

to –30°C). The reaction mixture was stirred for 30 min

at –35 × –30°C, cooled to –80°C, and 16.6 g (117 mmol)

of MeI was added. The temperature rose to 18°C within

30 min. The mixture was cooled to –80°C, and 100 ml

of saturated aqueous NH₄Cl was added at vigorous stir-

ring. The reaction products were extracted into ether (2 ×

50 ml), extracts were washed with water 2 times, and

dried with MgSO₄. The solvents were removed at the

bath temperature not exceeding 25°C ﬁrst on the rotary

evaporator at 10–20 mm Hg, then in a vacuum of an oil

pump (1 mm Hg) to get 10.57 g (100%) of brown mobile

liquid that after 18 h storage at –15°C contained accord-

ing to ¹H NMR data 2-aza-1,3,5-triene VIIf (99%) with

traces (<1%) of pyrrole IIIf. IR spectrum (thin layer), ν,

cm^–1: 552, 581, 609, 645, 692, 723, 754, 848, 892, 958,

976, 988, 1050, 1123, 1166, 1187, 1236, 1256, 1287,

1311, 1344, 1419, 1437, 1452, 1546, 1565, 1606, 1667,

2826, 2871, 2928, 2959, 3095. ¹H NMR spectrum (400

MHz, CDCl₃), δ, ppm: 1.83 m (4H, 3',4'-CH₂), 2.09 s

(3H, SMe), 2.22 m, 2.51 m (4H, 2',5'-CH₂), 3.63 s (3H,

OMe), 4.91 d.d (1H, CH₂=, ³J 10.9, ²J 1.8 Hz), 5.19 d.d

3.68 s (3H, OMe), 4.80 m (1H, NCH), 5.89 d (1H, 4-CH=,

³J 3.3 Hz), 6.66 d (1H, 5-CH=, ³J 3.3 Hz).

From the “acidic” water 4 g of insoluble solid dark-

brown polymer was isolated and 3.58 g of brown viscous

ﬂuid which was subjected to column chromatography

on Al₂O₃(eluent a mixture of petroleum ether –Et₂O,

3 : 1) to isolate 0.99 g of fraction containing 60% of

2,3-dihydropyridine IVf (red-orange mobile ﬂuid) and

0.09 g of 2,3-dihydropyridine IVf (light-yellow ﬂuid,

n_D²⁵1.5434), content of the main substance 90% (accord-

ing to ¹H NMR data). Yield 6%. IR spectrum (thin layer),

cm^–1: 417, 559, 583, 646, 697, 722, 795, 920, 962, 984,

1037, 1062, 1087, 1104, 1123, 1150, 1180, 1222, 1243,

1295, 1314, 1341, 1410, 1449, 1462, 1582, 1632, 1646,

1

1659, 2883, 2868, 2992, 2954, 3061, 3143. H NMR

spectrum (400 MHz, CDCl₃), δ, ppm: 1.59 m (4H, 3',4'-

CH₂), 1.74 m, 1.80 m (4H, 2',5'-CH₂), 2.23 s (3H, SMe),

2.27 d (2H, 3-CH₂, ³J 4.6 Hz), 3.57 s (3H, OMe), 4.94 t

(1H, 4-CH=, ³J 4.6 Hz). ¹³C (J mod, 100 MHz, CDCl₃),

δ, ppm: 11.31 (SMe), 23.67 (3',4'-CH₂), 31.84 (3-CH₂),

39.37 (2',5'-CH₂), 54.50 (OMe), 66.59 (2-C), 97.35 (4-

CH=), 147.59 (5-C=), 157.40 (6-C=). The correct assign-

ment of signals in the ¹H NMR spectrum was performed

with the help of 2D COSY NMR experiment.

2-Methoxy-N-cyclohexylidene-1-(ethyl-sulfanyl)

buta-1,3-dien-1-amine (VIIg), 3-methoxy-1-cyclo-

hexyl-2-(ethylsulfanyl)pyrrole (IIIg) and 3-methoxy-

2-(ethylsulfanyl)-1-azaspiro[5.5]-undeca-1,3-diene

(IVg). To a solution of 52.8 mmol BuLi in 33 ml of

hexane and 60 ml of THF at –90°C was added 5.4 g

(77.1 mmol) of allene Ia. After warming to –40°C the

reaction mixture was cooled to –100°C, and 7.2 g (51.1

mmol) of cyclohexyl isothiocyanate was added. The

temperature was allowed to rise to −35°C (bright yel-

low dispersion), then the reaction mixture was cooled

to −50°C, and 11 g (70.5 mmol) of EtI was added. After

the temperature rose to 5°C the reaction mixture was

treated with 50 ml of cold water at vigorous stirring. The

reaction products were extracted into pentane (3 × 50 ml),

extracts were dried with K₂CO₃, the solvent was removed

on a rotary evaporator to obtain the residue of 9.2 g (75%)

of mobile light yellow liquid (n_D²⁰1.5575) containing

according to ¹H NMR data 2-aza-1,3,5-triene VIIg with

impurity of pyrrole IIIg and 1-aza-1,3,4-triene VIg. ¹H

NMR spectrum of 2-aza-1,3,5-triene VIIg (400 MHz,

CDCl₃), δ, ppm: 1.24 t (3H, SCH₂CH₃, ³J 7.4 Hz), 1.61,

1.87 m (6H, 3',4',5'-CH₂), 2.26, 2.44 m (4H, 2',6'-CH₂),

3

2

(1H, CH₂=, J 17.2, J 1.8 Hz), 6.02 d.d (1H, CH=,

³J 17.2, 10.9 Hz). ¹³C NMR spectrum (100 MHz, CDCl₃),

δ, ppm: 13.12 (SMe), 24.68, 24.85 (3’,4’-CH₂), 31.69,

35.84 (2’,5’-CH₂), 58.54 (OMe), 109.97 (CH₂=), 126.56

(CH=), 135.42 (S–C=), 138.47 (O–C=), 187.36 (C=N).

To 0.48 g of reaction products 10 ml of toluene was

added, the mixture was slowly heated at stirring till boil-

ing (at virtually absent exothermic effect) and reﬂuxed for

30 min. Toluene was removed in a vacuum (1 mm Hg)

to obtain 9.37 g (90%) of dark brown very viscous ﬂuid.

The reaction products (9.23 g) were separated with the

use of dilute hydrochloric acid as described above. From

the organic fraction 1.6 g was isolated of relatively mobile

brown liquid which was subjected to column chromatog-

raphy on Al₂O₃[eluents petroleum ether (bp 40–70°C),

then a mixture petroleum ether–Et₂O, 10 : 1] to separate

1.07 g of fraction containing according to ¹H NMR data

10% of pyrrole IIIf (yield 1%) and two unidentiﬁed

compounds. ¹H NMR spectrum of pyrrole IIIf (400 MHz,

CDCl₃), δ, ppm: 1.75 m [8H, (CH₂)₄], 2.12 s (3H, SMe),

3

2.59 q (2H, SCH₂CH₃, J 7.4 Hz), 3.62 s (3H, OMe),

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

REACTIONS OF HETEROCUMULENES WITH ORGANOMETALLIC REAGENTS: XVII.

673

3

2

4.89 d.d (1H, CH₂=, J 10.9, J 2.0 Hz), 5.18 d.d (1H,

dien-1-yl]imidoformiate (VIIh), 2,5-dimethoxy-6-

(methylsulfanyl)-2,3-dihydropyridine (IVh). To a

solution of 57.6 mmol of BuLi in 36 ml of hexane and

70 ml of THF at –90°C was added 5 g (71.4 mmol) of

allene Ia. The reaction mixture was stirred for 5–7 min at

–65... –60°C, cooled to –100°C, and 5.15 g (50 mmol) of

methoxymethyl isothiocyanate was added.After warming

to –70°C 20 g (138.9 mmol) of MeI was added, the reac-

tion mixture was stirred for 15 min at room temperature

and poured into 100 ml of water. The reaction products

were extracted into pentane, the extracts were dried with

K₂CO₃, the solvent was removed on a rotary evaporator to

obtain the residue of 9.4 g (100%) of light yellow liquid

3

2

3

CH₂=, J 17.2, J 2.0 Hz), 5.95 d.d (1H, CH=, J 17.2,

10.9 Hz). ¹³C NMR spectrum (J mod, 100 MHz, CDCl₃),

δ, ppm: 15.39 (SCHCH₃), 24.09 (SCH₂), 25.55 (4'-CH₂),

26.85, 27.85 (3',5'-CH₂), 31.87, 38.86 (2',6'-CH₂), 58.58

(OMe), 109.88 (CH₂=), 126.62 (CH=), 133.45 (S–C=),

138.71 (O–C=), 179.19 (C=N). The correct assignment

of the signals in the ¹³C NMR spectrum was done with

the help of 2D HMBC NMR experiment.

The heating of the reaction product at ~190°C quan-

titatively provided a mixture of pyrrole IIIg (12%) and

2,3-dihydropyridine IVg (88%) (according to ¹H NMR

and GLC), bp ~180°C (15 mm Hg). Compounds IIIg and

IVg were separated using hydrochloric acid as described

above. From the organic fraction 1.3 g (11%) of pyrrole

IIIg was isolated, bright yellow ﬂuid, bp 110–118°C

(1 mm Hg), n_D²⁰1.5332. ¹H NMR spectrum (400 MHz,

CDCl₃), δ, ppm: 1.16 t (3H, SCH₂CH₃, ³J 7.2 Hz), 1.21,

1.41 m (2H, 4'-CH₂), 1.52, 1.91 m (4H, 2',6'-CH₂), 1.71,

1

that was according to H NMR data 2-aza-1,3,5-triene

VIIh, content of the main substance 100% (by GLC

1

data). H NMR spectrum (400 MHz, CDCl₃), δ, ppm:

2.19 s (3H, SMe), 3.68 s (3H, OMe), 3.82 s (3H, OMe),

3

2

5.08 d.d (1H, CH₂=, J 10.9, J 1.8 Hz), 5.39 d.d (1H,

3

2

3

CH₂=, J 17.4, J 1.8 Hz), 6.74 d.d (1H, CH=, J 17.4,

3

10.9 Hz), 7.97 C (1H, N=CH).

1.84 m (4H, 3',5'-CH₂), 2.54 q (2H, SCH₂, J 7.2 Hz),

3.79 s (3H, OMe), 4.32 t.t (1H, NCH, ³J 11.5, 3.5 Hz),

2-Aza-1,3,5-triene VIIh was heated to ~40°C, and on

the completion of exothermic electrocyclization (self-

heating up to 150°C) the reaction product was distilled

in a vacuum. Yield of 2,3-dihydropyridine IVh 6.8 g

(73%), content of the main substance 99% (by GLC

3

5.90 d (1H, 4-CH=, J 2.9 Hz), 6.65 d (1H, 5-CH=,

³J 2.9 Hz). ¹³C NMR spectrum (100 MHz, CDCl₃), δ,

ppm: 14.40 (SCHCH₃), 25.41 (4'-CH₂), 25.79 (3',5'-CH₂),

31.04 (SCH₂), 34.38 (2',6'-CH₂), 54.26 (NCH), 57.82

(OMe), 94.15 (4-CH=), 109.03 (2-C=), 116.77 (5-CH=),

151.66 (3-C=). Found, %: C 64.92; H 8.51; N 6.27; S

13.69. C₁₃H₂₁NOS. Calculated, %: C 65.23; H 8.84; N

5.85; S 13.40.

1

data), bp 85–90°C (1 mm Hg), n_D²⁰1.5365. H NMR

spectrum (400 MHz, CDCl₃), δ, ppm: 2.21–2.40 m (2H,

3-CH₂), 2.31 s (3H, SMe), 3.55 s (3H, 5-OMe), 3.58 s

3

(3H, 2-OMe), 4.61 d.d (1H, 2-CH, J 13.6, 6.3 Hz),

5.02 d.d (1H, 4-CH=, ³J 6.3, 2.8 Hz). ¹³C NMR spectrum

(100 MHz, CDCl₃), δ, ppm: 11.56 (SMe), 26.71 (3-CH₂),

54.75 (2-OMe), 54.84 (5-OMe), 90.59 (2-CH), 97.22

(4-CH=), 148.00 (5-C=), 160.64 (6-C=). The correct

assignment of the signals in the ¹³C NMR spectrum was

done with the help of 2D HMBC NMR experiment. Mass

spectrum, m/z (I_rel, %): 187 (72) [M]^+·, 172 (100), 156,

155, 140. Found, %: C 51.62; H 7.21; N 6.91; S 16.80.

C₈H₁₃NO₂S. Calculated, %: C 51.31; H 7.00; N 7.48;

S 17.12. M 187.26.

After workup of the “acidic” layer we obtained 7.5 g

(61%) of 2,3-dihydropyridine IVg, content of the main

substance 90% (by GLC data), colorless crystals, mp

32–34°C. IR spectrum (KBr), ν, cm^–1: 470, 490, 520,

570, 610, 680, 710, 760, 800, 850, 910, 935, 950, 960,

1020, 1040, 1050, 1060, 1110, 1140, 1150, 1180, 1210,

1240, 1260, 1340, 1360, 1440, 1570, 1640, 2850, 2920,

1

2980, 3050. H NMR spectrum (400 MHz, CDCl₃), δ,

3

ppm: 1.27 t (3H, SCH₂CH₃, J 7.5 Hz), 1.37 m (6H,

3',4',5'-CH₂), 1.73 m (4H, 2',6'-CH₂), 2.16 d (2H, 3-CH₂,

3

³J 4.6 Hz), 2.90 q (2H, SCH₂, J 7.5 Hz), 3.56 s (3H,

2-(Methylsulfanyl)-3-methoxypyridine (VIII). The

solution of 1.75 g (9.36 mmol) of 2,3-dihydropyridine

IVh and 2.5 g of ~30% HCl in 25 ml of Et₂O was stirred

for 1.5 h at boiling of ether, the reaction mixture was

treated with KOH solution (till neutral reaction), the or-

ganic phase was dried with K₂CO₃, the ether was removed

under a reduced pressure. Yield 1.04 g (72%), bp 82–84°C

(1.5 mm Hg), n_D²⁰1.5742. ¹H NMR spectrum (250 MHz,

CDCl₃), δ, ppm: 2.53 s (3H, SMe), 3.88 s (3H, OMe),

OMe), 4.85 t (1H, 4-CH=, ³J 4.6 Hz). ¹³C NMR spectrum

(J mod, 100 MHz, CDCl₃), δ, ppm: 14.14 (SCH₂CH₃),

22.08 (3’,5’-CH₂), 22.53 (4’-CH₂), 26.42 (SCH₂), 32.86

(3-CH₂), 37.61 (2’,6’-CH₂), 54.59 (OMe), 56.94 (2-C),

96.19 (4-CH=), 146.84 (5-C=), 156.16 (6-C=). Found,

%: C 64.92; H 8.51; N 6.27; S 13.69. C₁₃H₂₁NOS. Cal-

culated, %: C 65.23; H 8.84; N 5.85; S 13.39.

Methyl[1-(methylsulfanyl)-2-methoxybuta-1,3-

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

NEDOLYA et al.

674

6.95 m (1H, 5-CH=), 6.96 m (1H, 4-CH=), 8.07 d.d (1H,

6-CH=, ³J 3.8, 2.3 Hz). ¹³C NMR spectrum (62.9 MHz,

CDCl₃), δ, ppm: 12.03 (SMe), 55.58 (OMe), 114.65 (4-

CH=), 119.10 (5-CH=), 140.89 (6-CH=), 149.58 (2-C=),

152.37 (3-C=). Mass spectrum, m/z (I_rel, %): 155 (100)

[M]⁺, 140, 124, 122, 108. Found, %: C 54.31; H 5.42; N

8.77; S 20.32. C₇H₉NOS. Calculated, %: C 54.17; H 5.84;

N 9.02; S 20.66. M 155.21.

(3-C=). Found, %: C 56.03; H 7.29; N 6.32; S 14.88.

C₁₀H₁₅NO₂S. Calculated, %: C 56.31; H 7.09; N 6.57;

S 15.03.

After workup of the “acidic” water layer we obtained

7.3 g (34%) of 2,3-dihydropyridine IVi, content of the

main substance in the crude product 92% (by GLC data),

bp 136–137°C (3 mm Hg), n_D²⁰1.5392; crystallized on

cooling. IR spectrum (thin layer), ν, cm^–1: 680, 700–710,

780, 800, 930, 950, 970, 1000, 1025, 1050, 1100, 1120,

1140, 1200, 1220, 1240, 1300, 1330, 1400, 1430, 1450,

1570, 1600, 1630, 2830, 2865, 2920, 2950, 3000, 3050,

1-[2-(Vinyloxy)ethyl]-2-(methylsulfanyl)-3-me-

thoxypyrrole (IIIi) and 2-[(vinyloxy)methyl]-6-

(methylsulfanyl)-5-methoxy-2,3-dihydropyridine

(IVi). To a solution of 104 mmol of BuLi in 65 ml of

hexane and 65 ml of THF at –100°C was added 9.1 g

(130 mmol) of allene Ia. The reaction mixture was stirred

for 10 min at –60°C, cooled again to –100°C, and within

several seconds 12.9 g 100 mmol) of 2-(vinyloxy)ethyl

isothiocyanate was added. The reaction mixture was

stirred for 10 min at –60°C, 27 g (190.1 mmol) of MeI

was added, and after warming to 5°C the mixture was

treated with 100 ml of ice water at vigorous stirring.

The reaction products were extracted into pentane 4 ×

50 ml), the extracts were dried with K₂CO₃, the solvent

was removed on a rotary evaporator to obtain the residue

of 20 g (94%) of reaction product, whose distillation

in a vacuum gave 15 g (70%) of light yellow ﬂuid, bp

110–120°C (0.5 mm Hg), that was according to ¹H NMR

data a mixture of pyrrole IIIi and 2,3-dihydropyridine IVi

in the ratio ~1 : 1; overall content of the reaction products

96% (by GLC data).

1

3100. H NMR spectrum (300 MHz, CDCl₃), δ, ppm:

1.98–2.26 m (2H, 3-CH₂), 2.17 s (3H, SMe), 3.50 s

(3H, OMe), 3.60 m (1H, 2-CH), 3.68 m, 3.88 m (2H,

OCH₂), 3.90 d.d (1H, CH₂=, ³J 6.5, ²J 2.0 Hz), 4.15 d.d

3

2

(1H, CH₂=, J 14.2, J 2.0 Hz), 4.98 d.d (1H, 4-CH=,

³J 3.6 Hz), 6.41 q (1H, OCH=, ³J 14.2, 6.5 Hz). ¹³C NMR

spectrum (75 MHz, CDCl₃), δ, ppm: 11.17 (SMe), 23.51

(3-CH₂), 54.32 (OMe), 56.79 (2-CH), 70.96 (OCH₂),

86.15 (CH₂=), 97.50 (4-CH=), 147.65 (5-C=), 151.60

(OCH=), 161.61 (6-C=). Found, %: C 56.19; H 7.02;

N 6.61; S 15.20. C₁₀H₁₅NO₂S. Calculated, %: C 56.31;

H 7.09; N 6.57; S 15.03.

Methyl-2-tert-butoxy-N-methylbuta-2,3-di-

enimidothioate (VIj), 3-tert-butoxy-1-methyl-2-

(methylsulfanyl)pyrrole (IIIj) and 5-tert-butoxy-6-

(methylsulfanyl)-2,3-dihydropyridine (IVj). To a solu-

tion of 104 mmol of BuLi in 65 ml of hexane and 60 ml

of THF at –100°C was added 11.75 g (104.9 mmol) of

allene Ib. The reaction mixture slowly (within 15 min)

warmed to –15°C, was cooled again to –95°C, and 7.3 g

(100 mmol) of methyl isothiocyanate was added. After

warming to –70°C the reaction mixture was again cooled

to –75°C, and 18.2 g (128.2 mmol) of MeI was added.At

–12°C the reaction mixture was treated with cold water,

the organic fraction was dried with K₂CO₃, the solvents

were removed on a rotary evaporator to obtain in the

residue 17.2 g (86%) of 1-aza-1,3,4-triene VIj. ¹H NMR

spectrum (90 MHz, CCl₄), δ, ppm: 1.30 s, 1.40 s [9H,

OC(CH₃)₃], 2.20 s, 2.45 s (3H, SMe), 3.15 s, 3.32 s (3H,

NMe), 5.50 s (2H, CH₂=).

The solution of the mixture of pyrrole IIIi and 2,3-di-

hydropyridine IVi in 30 ml of pentane was treated with

cold (1–3°C) 1 M solution of HCl, taken in the exact

amount necessary for the neutralization of 2,3-dihydro-

pyridine. Further workup was carried out as described

above. From the organic fraction 7 g (33%) of pyrrole IIIi

was isolated, bp 131–132°C (3 mm Hg), n_D²⁰1.5414. IR

spectrum (thin layer), ν, cm^–1: 700, 820, 940, 960, 1090,

1190, 1330, 1350, 1400, 1460, 1550, 1620, 1635, 2830,

2870, 2920–2940, 3000, 3100, 3120. ¹H NMR spectrum

(400 MHz, CDCl₃), δ, ppm: 2.14 s (3H, SMe), 3.76 s (3H,

OMe), 3.84 t (2H, OCH₂, ³J 5.6 Hz), 3.96 d.d (1H, CH₂=,

2

3

2

³J 6.5, J 2.1 Hz), 4.14 d.d (1H, CH₂=, J 14.3, J 2.1

Hz), 4.19 t (2H, NCH₂, ³J 5.6 Hz), 5.85 d (1H, 4-CH=,

³J 3.2 Hz), 6.34 q (1H, OCH=, ³J 14.3, 6.5 Hz), 6.65 d

(1H, 5-CH=, ³J 3.2 Hz). ¹³C NMR spectrum (100 MHz,

CDCl₃), δ, ppm: 20.58 (SMe), 45.68 (NCH₂), 57.90

(OMe), 67.45 (OCH₂), 86.94 (CH₂=), 94.88 (4-CH=),

105.31 (2-C=), 121.11 (5-CH=), 151.15 (OCH=), 151.83

The reaction product was heated and on the comple-

tion of exothermic electrocyclization (self-heating up

to 192°C) we obtained pyrrole IIIj containing 17% of

2,3-dihydropyridine IVj (according to ¹H NMR and GLC

data). Compounds IIIj and IVj were separated with the

use of hydrochloric acid as described above. From the

organic fraction 10.8 g (54%) of pyrrole IIIj was isolated,

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

REACTIONS OF HETEROCUMULENES WITH ORGANOMETALLIC REAGENTS: XVII.

675

1

content of the main substance 97% (by GLC data), bp

102–103°C (3 mm Hg), n_D²⁰1.5180. IR spectrum (thin

layer), ν, cm^–1: 690, 700, 750, 870, 960, 1000, 1050, 1170,

1220, 1240, 1250, 1300, 1340, 1360, 1390, 1530, 2870,

2930, 2970, 3100. ¹H NMR spectrum (400 MHz, CDCl₃),

δ, ppm: 1.32 s [9H, OC(CH₃)₃], 2.13 s (3H, SMe), 3.58 s

(3H, NMe), 5.81 d (1H, 4-CH=, ³J 3.2 Hz), 6.50 d (1H,

2,3-dihydropyridine IVk (according to H NMR data)

of a 88 : 12 ratio (by GLC data); yield 15.5 g (73%).

Compounds IIIk and IVk were separated with the use

of hydrochloric acid as described above. ¹H NMR spec-

trum of pyrrole IIIk (90 MHz, CCl₄), δ, ppm: 1.15 t

(3H, SCH₂CH₃, J 7.2 Hz), 1.35 s [9H, OC(CH₃)₃],

2.52 q (2H, SCH₂CH₃, J 7.2 Hz), 3.60 c (3H, NMe),

5.75 d (1H, 4-CH=, J 3.2 Hz), 6.48 d (1H, 5-CH=,

³J 3.2 Hz). H NMR spectrum of 2,3-dihydropyridine

IVk (90 MHz, CCl₄), δ, ppm: 1.10 t (3H, SCH₂CH₃,

³J 7.3 Hz), 1.20 s [9H, OC(CH₃)₃], 2.00 m (2H, 3-CH₂),

3

5-CH=, J 3.2 Hz). ¹³C NMR spectrum (100 MHz,

1

CDCl₃), δ, ppm: 19.87 (SMe), 28.78 [OC(CH₃)₃], 34.38

(NMe), 78.05 [OC(CH₃)₃], 103.33 (4-CH=), 114.04 (2-

C=), 120.92 (5-CH=), 145.27 (3-C=). Found, %: C 60.09;

H 8.69; N 6.87; S 15.99. C₁₀H₁₇NOS. Calculated, %:

C 60.26; H 8.60; N 7.03; S 16.09.

3

2.70 q (2H, SCH₂CH₃, J 7.3 Hz), 3.50 t (2H, NCH₂,

³J 7.5 Hz), 5.40 t (1H, 4-CH=, ³J 4.5 Hz).

After workup of the “acidic” water layer we obtained

1.2 g (6%) of 2,3-dihydropyridine IVj. IR spectrum (thin

layer), ν, cm^–1: 860, 920, 950, 980, 1020, 1050, 1080,

1150, 1200, 1240, 1290, 1355, 1380, 1420, 1560, 1610,

2830–2920–2940. ¹H NMR spectrum (90 MHz, CCl₄), δ,

ppm: 1.32 s [9H, OC(CH₃)₃], 2.15 s (3H, SMe), 2.25 m

(2H, 3-CH₂), 3.47 t (2H, NCH₂, ³J 7.5 Hz), 5.40 t (1H,

4-CH=, ³J 4.5 Hz). Found, %: C 60.42; H 8.38; N 7.15;

S 15.80. C₁₀H₁₇NOS. Calculated, %: C 60.26; H 8.60;

N 7.03; S 16.09.

ACKNOWLEDGMENTS

The study was carried out under the ﬁnancial support

of the Russian Foundation of Basic Research (grant no.

09-03-00890a) and of the Presidium of the Siberian

Division of the Russian Academy of Sciences (Program

of fundamental research of the Presidium of the Russian

Academy of Sciences, project 18.20).

REFERENCES

Ethyl-2-tert-butoxy-N-methylbuta-2,3-diene-

imidothioate (VIk), 3-tert-butoxy-1-methyl-2-(ethyl-

sulfanyl)pyrrole (IIIk) and 5-tert-butoxy-6-(ethyl-

sulfanyl)-2,3-dihydropyridine (IVk). To a solution of

104 mmol of BuLi in 65 ml of hexane and 80 ml of THF

at –100°C was added 11.85 g (105.8 mmol) of allene

Ib. The temperature quickly rose to –50°C. The reaction

mixture was stirred at this temperature for 10 min, cooled

to –95°C, and 7.3 g (100 mmol) of methyl isothiocyanate

was added. The temperature was allowed to rise to –50°C,

the reaction mixture was stirred for 15 min at –60...

–50°C, and 22.6 g (144.9 mmol) of EtI was added. After

relatively slow warming to 5°C the reaction mixture was

treated with 70 ml of cold water. After usual treatment

and removal of the solvent on the rotary evaporator we

obtained in residue 19 g (89%) of 1-aza-1,3,4-triene

VIk with traces of pyrrole IIIk (according to ¹H NMR

data). ¹H NMR spectrum (90 MHz, CCl₄), δ, ppm: 1.25 m

(3H, SCH₂CH₃), 1.35 s, 1.40 s [9H, OC(CH₃)₃], 2.80 q,

1.Shagun, V.A., Nedolya, N.A., Tarasova, O.A., Volost-

nykh, O.G., Kazheva, O.N., Chekhlov, A.N., Aleksan-

drov, G.G., D’ya, and Chenko, O.A., Zh. Org. Khim., 2010,

vol. 46, p. 1835.

2. Brandsma, L. and Zwikker, J.W., Sci. Synth., 2005,

vol. 8a, pp. 271, 285, 305; Carbanionen, Meth. Org. Chem.

(Houben–Weyl)., 1993, vol. E, 19d; Brandsma, L., Studies

in Organic Chemistry. 34. Preparative Acetylenic Chem-

istry, Amsterdam: Elsevier, 1988; Brandsma, L. and Ver-

kruijsse, H., Preparative Polar Organometallic Chemistry.

Berlin: Springer-Verlag, 1987, vol. 1, p. 43, p. 75; Epsz-

tein, R., Studies in Organic Chemistry. 5. Comprehensive

Carbanion Chemistry, Part B, Selectivity, Carbon–Carbon

Bond, Forming Reactions, Buncel, E. and Durst, T., Eds.,

Amsterdam: Elsevier, 1984, p. 107.

3. Katritzky,A.R., Feng, D.M., and Lang, H.Y., J. Org. Chem.,

1997, vol. 62, p. 715; de Jong, R.L.P., Verkruijsse, H.D.

and Brandsma, L., Perspectives in Organic Chemistry of

Sulfur, Zwanenburg, B. and Klunder,A.J.H., Eds.,Amster-

dam: Elsevier, 1987, p. 105; Ruitenberg, K., Synthese van

Allenylmetaal-reagentia en hun Regioselectieve Omzetting

in Functioneel Gesubstitueerde Allenen Alkynen en Enige

Heterocycli, Ph.D. Thesis of Utrecht University. Utrecht,

1983.

3

3.05 q (2H, SCH₂CH₃, J 7.3 Hz), 3.20 s, 3.30 s (3H,

NMe), 5.40 s, 5.45 s (2H, CH₂=).

The reaction product was heated and on the comple-

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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

Article Doi

Reactions of heterocumulenes with organometallic reagents: XVII.* one-pot synthesis of alkoxy and (Alkylsulfanyl)-substituted pyrroles and 2,3-Dihydropyridines from aliphatic isothiocyanates and lithiated alkoxyallenes

DOI: 10.1134/S1070428011050034

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