A new synthesis of bicyclic N,O- and N,S-enaminals by the anionic cyclization of alk-4-ynals with amino alcohols and amino thiols

Article abstract of DOI:10.1007/s11172-014-0445-6

A reaction of alk-4-ynals with aliphatic amino alcohols or 2-aminoethanethiol in the system DMSO - KOH gives bicyclic N,O- and N,S-enaminals: 6-methylidenehexahydro-2H-pyrrolo[2,1-b][1,3]oxazines, 5-methylidenehexahydropyrrolo[2,1-b]oxazoles, or 5-methyl-

Full text of DOI:10.1007/s11172-014-0445-6

Russian Chemical Bulletin, International Edition, Vol. 63, No. 2, pp. 409—415, February, 2014
409
A new synthesis of bicyclic N,Oꢀ and N,Sꢀenaminals by the anionic cyclization
of alkꢀ4ꢀynals with amino alcohols and amino thiols*
V. D. Gvozdev, K. N. Shavrin, and O. M. Nefedov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 532. Eꢀmail: vgvozdev2006@yandex.ru
A reaction of alkꢀ4ꢀynals with aliphatic amino alcohols or 2ꢀaminoethanethiol in the sysꢀ
tem DMSO—KOH gives bicyclic N,Oꢀ and N,Sꢀenaminals: 6ꢀmethylidenehexahydroꢀ2Hꢀ
pyrrolo[2,1ꢀb][1,3]oxazines, 5ꢀmethylidenehexahydropyrrolo[2,1ꢀb]oxazoles, or 5ꢀmethylꢀ
idenehexahydropyrrolo[2,1ꢀb]thiazoles. The reaction proceeds through the formation of equiꢀ
librium mixtures of the corresponding imines and monocyclic aminals with subsequent 5ꢀexoꢀ
digꢀcyclization catalyzed by the superbasic system DMSO—KOH.
Key words: alkꢀ4ꢀynals, aminoalkanols, 2ꢀaminoethanethiol, hexahydroꢀ2Hꢀpyrrolo[2,1ꢀb]ꢀ
[1,3]oxazines, hexahydropyrrolo[2,1ꢀb]oxazoles, hexahydropyrrolo[2,1ꢀb]thiazoles, 1,3ꢀoxꢀ
azinanes, hydroamination, anionic cyclization, dimethyl sulfoxide, potassium hydroxide.
Earlier, we have suggested1,2 an original method for
the preparation of bicyclic N,Nꢀenaminals, viz., 6ꢀ(arylꢀ
methylidene)octahydropyrrolo[1,2ꢀa]pyrimidines and
5ꢀ(arylmethylidene)hexahydropyrrolo[1,2ꢀa]imidazoles,
based on the reaction of 1ꢀ(alkꢀ1ꢀynyl)ꢀ1ꢀchlorocycloꢀ
propanes with lithium derivatives of aliphatic diamines.
Later, it was shown3,4 that an anionic cyclization of alkꢀ4ꢀynꢀ
als with aliphatic 1,2ꢀ and 1,3ꢀdiamines in a KOH—DMSO
system is more convenient and general approach to these
compounds. At the same time, N,Oꢀ and N,Sꢀanalogs of
these enaminals are comparatively little studied heteroꢀ
cyclic structures. To date, only 5ꢀmethylidenehexahydroꢀ
pyrrolo[2,1ꢀb]oxazoles with two fused fiveꢀmembered rings
were obtained. They were synthesized by methods based
on either the reaction of tetrahydropyrrolo[2,1ꢀb]oxazolꢀ
5(6H)ꢀones with organolithium reagents5—7 or on the reꢀ
actions of aminoalkanols with diketones8,9 or ꢀoxoꢀ
alkynes9 having an activated triple bond. Compounds of
this series exhibit antiinflammatory and antinociceptive
activity,10,11 whereas the presence in their structure of
highly reactive 2ꢀmethylidenepyrrolidine12 and bicyclic
N,Oꢀaminal13 fragments is of considerable synthetic inꢀ
terest. In particular, their characteristic reactions are reꢀ
duction with the simultaneous selective oxazole ring openꢀ
ing,8,14 hydrolysis with the formation of cyclopentanone
structures5 or dicarbonyl compounds.15
apparently, results from the absence of convenient general
approaches to these types of compounds. We suggested
that these N,Oꢀ and N,Sꢀenaminals, as well as 5ꢀmethꢀ
ylidenehexahydropyrrolo[2,1ꢀb]oxazoles, can be obtained
similarly to N,Nꢀenaminals by the reaction of the correꢀ
sponding alkꢀ4ꢀynals with amino alcohols and amino thiꢀ
ols in the superbasic16,17 system DMSO—KOH.
Results and Discussion
In the course of the present studies, it was found that a
sequential addition of aldehydes 1a,b,d and powdered
KOH to the solutions of amino alcohols 2a—c in DMSO
(the molar ratio aldehyde : amine : KOH = 1 : 1 : 5) leads
to the corresponding N,Oꢀenaminals 3a—e in 42—82%
yields (Scheme 1, Table 1). The highest yields were obꢀ
tained when 2,2ꢀdisubstituted aldehydes 1a,b were used.
The products 3a—d with ~90% purity were isolated by the
dilution of the reaction mixtures with a 10ꢀfold amount of
water with subsequent extraction of the aqueous phases
with dichloromethane. The crystalline compound 3b was
additionally purified by recrystallization from hexane,
while the products 3a,c—e, which are dense liquids, were
isolated by column chromatography on neutral Al2O3.
The reaction of aldehyde 1c having no substituents at
ꢀposition to the carbonyl group did not lead to the correꢀ
sponding enaminals 3 neither with 3ꢀaminopropanol (2a),
nor with (1ꢀaminomethylcyclopropyl)methanol (2c), givꢀ
ing mixtures of unidentifiable compounds. It is probable
that this results from the side processes involving relatively
acidic hydrogen atoms in the corresponding imino alcoꢀ
At the same time, there is no data on the related
6ꢀmethylidenehexahydroꢀ2Hꢀpyrrolo[2,1ꢀb][1,3]oxazines
and 5ꢀmethylidenehexahydropyrrolo[2,1ꢀb]thiazoles, that,
* On the occasion of the 80th anniversary of the N. D. Zelinsky
Institute of Organic Chemistry of the Russian Academy of Sciences.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 0409—0415, February, 2014.
1066ꢀ5285/14/6302ꢀ0409 © 2014 Springer Science+Business Media, Inc.

410
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Gvozdev et al.
Scheme 1
Yield of compound 3: 82% (a), 72% (b), 78% (c), 68% (d), 42% (e).
1: R1 = Ph, R2 = R3 = Me (a)
3—5: R1 = Ph, R2 = R3 = Me, R4 = R5 = H (a)
4, 5: R1 = Ph,
R
R
R
1 = 2ꢀthienyl, R2 = R3 = Me (b)
1 = Ph, R2 = R3 = H (c)
R1 = Ph, R2 = R3 = R4 = R5 = Me (b)
R2 = R3 = R4 = R5 = H (f)
R1 = Ph, R2 = R3 = Me, R4 + R5 = (CH2)2 (c)
R1 = 2ꢀthienyl, R2 = R3 = Me, R4 = R5 = H (d)
R1 = 4ꢀF3CC6H4, R2 = R3 = R4 = R5 = H (e)
R1 = Ph, R2 = R3 = H,
R4 + R5 = (CH2)2 (g)
1 = 4ꢀF3CC6H4, R2 = R3 = H (d)
2: R4 = R5 = H (a), R4 = R5 = Me (b)
R
4 + R5 = (CH2)2 (c)
hols 4f,g, which proceed significantly faster than the intraꢀ
molecular hydroamination of the triple bond. However,
the reaction of aldehyde 1d bearing a 4ꢀtrifluoromethylꢀ
phenyl substituent at the triple bond with 3ꢀaminopropanꢀ
ol 2a led to the product 3e in 42% yield. In this case, it was
shown that compound 3e was formed only when an
equimolar ratio of the starting reactants was used, whereas
an excess of 3ꢀaminopropanol led to the complete resinifiꢀ
cation of the reaction mixture. Apparently, this is explained
by the strong polarization of the triple bond due to the
–Iꢀeffect of the trifluoromethyl group, that facilitates its
hydroamination and promotes the side processes of the
addition of 3ꢀaminopropoxide anion formed from the exꢀ
cess of 3ꢀaminopropanol by the action of KOH in DMSO.
The structure of the amino alcohol used considerably
influences the rate of this process. Thus, in the case of
3ꢀaminopropanol 2a and (1ꢀaminomethylcyclopropyl)ꢀ
methanol 2c, the reaction with all the aldehydes 1 reached
completion within 2 h, whereas a similar process with
3ꢀaminoꢀ2,2ꢀdimethylpropanꢀ1ꢀol (2b) proceeds considꢀ
erably slower and requires stirring for 24 h at room temꢀ
perature to be complete. Most likely, this is due to the
stronger steric influence of the dimethylmethylene fragꢀ
ment as compared to the methylene or cyclopropaneꢀ1,1ꢀ
diyl one. Note that this reaction, like the reaction of alkꢀ
4ꢀynals with 1,3ꢀdiaminopropane and its derivatives studꢀ
ied earlier,4 is highly stereoselective and leads to the corꢀ
responding 6ꢀmethylidenehexahydroꢀ2Hꢀpyrrolo[2,1ꢀb]ꢀ
[1,3]oxazines 3a—e as the individual Eꢀisomers.
Like the reaction of alkꢀ4ꢀynals with 1,2ꢀdiaminoꢀ
ethane catalyzed by the system KOH—DMSO and deꢀ
scribed by us earlier,4 similar reactions of aldehydes 1a,b
with 2ꢀaminoethanol (6) proceed less stereoselectively and
lead to the corresponding products 7a,b as mixtures of
Eꢀ and Zꢀisomers in the ratios 3.5 : 1 and 7.5 : 1, respecꢀ
tively (Scheme 2). The isomers were identified using the
Scheme 2
Yield of compound 7: 75 (a), 64% (b).
1, 7: R1 = Ph (a), 2ꢀthienyl (b)

Bicyclic N,Oꢀ and N,Sꢀenaminals
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 2, February, 2014
411
2D NOESY NMR spectra based on the analysis of the
interactions of the protons at the double bond and the
protons of the methylidene fragment at position 6. Apparꢀ
ently, a decrease in the stereoselectivity in the reactions of
alkꢀ4ꢀynals with 2ꢀaminoethanol 6 as compared to the
similar transformations involving 3ꢀaminopropanols (2)
results from the considerably lower steric effect of the fiveꢀ
membered ring formed as compared to the sixꢀmembered one.
In order to involve N,Sꢀbinucleophiles in such cyclizaꢀ
tions, we carried out the reaction of aldehydes 1a,e with
2ꢀaminoethanethiol in DMSO with subsequent treatment
of the reaction mixture with KOH. For this, we added
1 equiv. of triethylamine to the solution of the equimolar
amounts of commercially available 2ꢀaminoethanethiol
hydrochloride 8 and the corresponding aldehyde 1a,e in
DMSO, that led to the rapid quantitative formation of the
corresponding thiazolidines 9 (Scheme 3). Thus, the reacꢀ
tion of aldehyde 1a with compound 8 reached completion
within 30 min and after aqueous treatment of the reaction
mixture, extraction with dichloromethane, washing the
organic phases with water, and evaporation of the solvent,
thiazolidine 9a was isolated in 90% yield and more than
95% purity.
however, in this case the content of Zꢀisomer was signifiꢀ
cantly lower (see Table 1), that, most likely, is explained
by the larger steric effect of the thiazolidine ring as comꢀ
pared to the oxazolidine one.
To obtain the data on the intermediate products emergꢀ
ing in the course of the reactions of alkꢀ4ꢀynals 1 with
amino alcohols, we carried out more detailed studies of
their progress in DMSOꢀd6 with the monitoring the comꢀ
position of the reaction mixture by 1H NMR spectroꢀ
scopy. The spectra recorded 10 min after mixing the soluꢀ
tions of the equimolar amounts of aldehyde 1a and amino
alcohols 2a or 2b showed the complete absence of the
signals for the starting aldehyde, whereas the linear imines
4a or 4b, respectively, were the major products with conꢀ
tent exceeding 90%. When these reaction mixtures were
allowed to stand at room temperature, a slow formation of
cyclic aminals 5a and 5b was observed, the content of
which after 1 h was 33 and 45%, respectively, whereas
after 18 h it was 54% (4a : 5a = 1 : 1.2) and 86% (4b : 5b =
= 1 : 6) and did not change during further standing.
Similarly to the processes involving aliphatic diamines
studied by us earlier,4 the products 4 and 5 were obtained
as the equilibrium mixtures, that was shown by 1H NMR
spectroscopy at different temperatures. Thus, heating the
mixture obtained by the reaction of aldehyde 1a with
3ꢀaminopropanol 2a to 50 C led to the change of the ratio
of components 4a and 5a from 1 : 1.2 to 1 : 0.45, which
A subsequent addition of the excess of powdered KOH
to the reaction mixtures obtained by the reaction of aldeꢀ
hydes 1a,e with 2ꢀaminoethanethiol hydrochloride 8 in
the presence of triethylamine led to the previously unꢀ
known 5ꢀbenzylidenehexahydropyrrolo[2,1ꢀb]thiazoles
10a,b in 30—32% yields (see Scheme 3). These products,
like structurally similar hexahydropyrrolo[2,1ꢀb]oxazolꢀ
es 7a,b, were formed as mixtures of Eꢀ and Zꢀisomers,
Table 1. Reaction of alkꢀ4ꢀynals 1a—e with amino alcohols 2
and 6 and 2ꢀaminoethanethiol hydrochloride 8 in DMSO in the
presence of KOHa
Aldehyde Amino alcohol
(thiol)
t/h*
Product
Yield
(%)
Scheme 3
1a
1a
1a
1b
1c
1c
1d
1a
1e
1a
1e
2a
2b
2c
2a
2a
2с
2a
6
2
24
2
2
2
2
2
2
2
3a
3b
3c
3d
82b
72c
78b
68b
—
d
—
—
d
—
3e
42b
75b
64b
32g
30b
7a (3.5 : 1)e
7b (7.5 : 1)e
10a (14 : 1)e
10b (16 : 1)e
6
8f
8f
6
6
Note: t is the reaction time.
a The molar ratio alkynal : amino alcohol : KOH = 1 : 1 : 5.
b The yield of the product isolated by column chromatography.
c The yield of the product isolated by recrystallization from
hexane.
d A complete resinification of the reaction mixture was observed.
e The ratio of isomers was determined using 1H NMR spectra of
the isolated products.
Yield of compound 10: 32 (a), 30% (b).
f An equimolar amount of triethylamine was added to the reacꢀ
tion mixture.
R
R
1 = R2 = Me (1a, 9a, 10a)
1 + R2 = (CH2)5 (1e, 9b, 10b)
g The yield of the product isolated by microdistillation in vacuo.

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Gvozdev et al.
4500 V). Masses were scanned in the range of m/z from 50 to
3000 Da, using an external or an internal calibration (Electroꢀ
spray Calibrant Solution, Fluka). Solutions of compounds in
returned to the initial proportion within 10 h after cooling
to 23 C. A similar experiment with a mixture of comꢀ
pounds 4b and 5b led to a reversible increase in the content
of the linear product 4b from 14% (4b : 5b = 1 : 6) to 45%
(4b : 5b = 1 : 1.2). A comparative analysis of the spectra
obtained at different temperatures allowed us to unambigꢀ
uously assign the signals observed to compounds 4a,b and
5a,b without separation of the mixtures.
When an excess of freshly powdered KOH was added
to the solution of compound 4a in DMSOꢀd6, the 1H NMR
spectrum of the reaction mixture recorded after 5 min
showed, besides the signals for the starting compound, the
presence of the signals for the products 5a and 3a (the
ratio 4a : 5a : 3a = 1 : 0.22 : 0.20). Further stirring the reꢀ
action mixture at room temperature for 30 min led to
the change in the ratio of components 4a : 5a : 3a to
1 : 0.45 : 0.50, with the reaction reaching completion 2 h
after the beginning. Taking into account that in the abꢀ
sence of KOH only ~33% of imino alcohol 4a isomerizes
to oxazinane 5a within 1 h (see above), a conclusion can
be drawn that the addition of KOH slightly accelerates
this reaction, with its rate and the rate of subsequent transꢀ
formation of oxazinane 5a to bicyclic enaminal 3a being
comparable.
Slightly different behavior was observed in the case of
the reaction of compound 4b with KOH in DMSOꢀd6.
The spectrum of the reaction mixture obtained after
10 min, besides the signals for the starting compound, also
contained the signals for the products 5b (the ratio 4b : 5b
= 1 : 0.4) and 3b (trace amount). Further stirring the reacꢀ
tion mixture at room temperature for 3 h led to the change
in the ratio of components 4b : 5b : 3b to 1 : 3 : 0.8, indiꢀ
cating significantly more rapid formation of oxazinane 5b
than its transformation to the final enaminal 3b.
In conclusion, we accomplished a oneꢀpot synthesis of
6ꢀmethylidenehexahydroꢀ2Hꢀpyrrolo[2,1ꢀb][1,3]oxazines,
5ꢀmethylidenehexahydropyrrolo[2,1ꢀb]oxazoles, and
5ꢀmethylidenehexahydropyrrolo[2,1ꢀb]thiazoles by the reꢀ
action of available alkꢀ4ꢀynals with amino alcohols and
2ꢀaminoethanethiol in the presence of KOH. The reacꢀ
tion proceeds with the formation of three new C—heteroꢀ
atom bonds. The compounds obtained seem promising for
the medicinal chemistry.
acetonitrile were injected using a syringe, the flow rate 3 L min–1
.
Nebulizer gas was nitrogen (4 L min–1), the interface temperaꢀ
ture was 180 C.
The starting alkynals 1a,b,e were synthesized from the corꢀ
responding propargylic chlorides (1ꢀchloroꢀ3ꢀphenylpropꢀ2ꢀyne,
1ꢀchloroꢀ3ꢀ(2ꢀthienyl)propꢀ2ꢀyne) and aldehydes (isobutyric
aldehyde and cyclohexanecarbaldehyde) according to the proꢀ
cedures described in the work.4 Alkynals 1c,d were obtained by
the crossꢀcoupling of the corresponding iodoarenes (iodobenꢀ
zene, 4ꢀiodobenzotrifluoride) with pentꢀ4ꢀyneꢀ1ꢀol upon treatꢀ
ment with a mixture of Pd(PPh3)2Cl2—CuI in anhydrous triethylꢀ
amine18 with subsequent oxidation of forming acetylenic alcoꢀ
hols with pyridinium chlorochromate in dichloromethane (the
overall yield on the two steps was 68% for 1c, 75% for 1d). The
spectral data of the compounds obtained agree with those pubꢀ
lished earlier (see Ref. 19 for 1c, Ref. 20 for 1d).
3ꢀAminoꢀ2,2ꢀdimethylpropanꢀ1ꢀol (2b). Anhydrous K2CO3
(138 g, 1 mol) was added to a solution of ethyl cyanoacetate
(28.2 g, 0.25 mol) and iodomethane (60.2 g, 0.6 mol) in anhyꢀ
drous acetone (300 mL) and the mixture obtained was refluxed
with stirring, monitoring the reaction progress by 1H NMR specꢀ
tra. After the reaction reached completion (~15—30 h), the reꢀ
action mixture was filtered, a precipitate was washed with aceꢀ
tone (400 mL) on the filter, the solvent was evaporated. The
residue was distilled in vacuo to isolate a colorless liquid (23.5 g,
75%) with b.p. 80—82 C (15 Torr), which according to the 1H NMR
spectra was a pure ethyl 2ꢀcyanoꢀ2ꢀmethylpropanoate.
The product obtained was slowly added to a suspension of
LiAlH4 (15.2 g, 0.4 mol) in anhydrous THF (200 mL), the mixꢀ
ture formed was refluxed for 1 h, followed by a careful dropwise
addition of water until hydrogen evolution ceased and an even
white color persisted. A precipitate formed was filtered off,
washed with THF (500 mL), the solvent from the organic phases
was evaporated. The precipitate was additionally washed with
a mixture of THF—dichloromethane (10 times), evaporating the
solvent after each washing and reusing it. The residue obtained
was distilled in vacuo to isolate a colorless compound (12.7 g,
56% calculated on the starting ethyl cyanoacetate) solidifying in
the condenser (b.p. 93—95 C (12 Torr)), which according to the
NMR spectra was a pure amino alcohol 2b. 1H NMR, : 0.82
(s, 6 H, 2 Me); 2.63 (s, 2 H, CH2NH2); 2.69 (br.s, 3 H, OH,
NH2); 3.41 (s, 2 H, CH2OH). 13C NMR, : 22.2 (2 Me); 35.3
(C(CH3)2); 51.7 (CH2NH2); 71.8 (CH2OH).
(1ꢀAminomethylcyclopropyl)methanol (2c) was obtained simꢀ
ilarly using 1,2ꢀdibromoethane (1 equiv. with respect to ethyl
cyanoacetate) instead of iodomethane. Compound 2c was isoꢀ
lated by distillation in vacuo (b.p. 68—70 C (1 Torr)). The yield
calculated on the starting ethyl cyanoacetate was 62%. 1H NMR,
: 0.21—0.39 (m, 4 H, 2 CH2, cycloꢀC3); 2.64 (s, 2 H, CH2NH2);
2.71 (br.s, 3 H, OH, NH2); 3.42 (s, 2 H, CH2OH). 13C NMR,
: 8.8 (2 CH2, cycloꢀC3); 23.7 (C(1), cycloꢀC3); 48.5 (CH2NH2);
68.8 (CH2OH).
Experimental
The starting compounds and the products obtained were anꢀ
alyzed by GC on a Hewlett—Packard 5890 Series II instrument
with an HPꢀ1 capillary column (30 m×0.153 mm) and an
Hewlett—Packard 3396A automated integrator. 1H and 13C NMR
spectra were recorded on a Bruker ACꢀ200p spectrometer in
CDCl3, using SiMe4 as an internal standard. Mass spectra were
obtained on a Finnigan DSQ II GLCꢀMS spectrometer. High
resolution mass spectra were recorded on a Bruker micrOTOF II
instrument with electrospray ionization (ESI). The measureꢀ
ments were performed on the positive ions (capillary voltage
Bicyclic N,Oꢀaminals 3a—e and 9a,b (general procedure).
A solution of aldehyde 1 (1 mmol) in DMSO (3 mL) was added
to a solution of the corresponding amino alcohol 2 or 6 (1 mmol)
in anhydrous DMSO (3 mL) with stirring. The mixture was stirred
for 30 min at room temperature, followed by addition of freshly
powdered KOH (280 mg, 5 mmol), the suspension obtained was
stirred until the reaction reached completion (monitoring by

Bicyclic N,Oꢀ and N,Sꢀenaminals
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 2, February, 2014
413
GLC or 1H NMR spectroscopy, the reaction time is given in
Table 1). Then, the reaction mixture was quenched with water
(30 mL) and CH2Cl2 (30 mL), the organic layer was separated,
the aqueous phase was extracted with CH2Cl2 (3×10 mL). The
combined organic layers were washed with water (4 times), dried
with anhydrous K2CO3, the solvent was evaporated. The prodꢀ
uct was isolated from the residue by recrystallization or column
chromatography (see Table 1).
(C(2), C(3)); 16.7 (C(1,3´)); 22.0 (Me); 26.7 (Me); 38.3 (C(8´));
43.5 (C(7´)); 50.5 (C(4´)); 74.4 (C(2´)); 95.3, 97.1 (C(8a´),
PhCH=); 122.9, 126.1, 128.1 (Ph); 139.7 (C(1), Ph); 147.5
(PhCH=C). MS, m/z (Irel (%)): 269 [M]+ (100), 268 [M – H]+ (19).
(E)ꢀ8,8ꢀDimethylꢀ6ꢀ(2ꢀthienylmethylidene)hexahydroꢀ2Hꢀ
pyrrolo[2,1ꢀb][1,3]oxazine (3d) was obtained from aldehyde 1b
and 3ꢀaminopropanol 2a and isolated in 68% yield by chromatoꢀ
graphy on neutral Al2O3 (eluent hexane—diethyl ether, 8 : 1).
1H NMR, : 1.11 (s, 6 H, 2 Me); 1.32 (m, 1 H, NCH2CHHCH2O);
1.97 (m, 1 H, NCH2CHHCH2O); 2.56 (dd, 1 H, =CCHH,
2J = 16.2 Hz, 4J = 1.7 Hz); 2.67 (dd, 1 H, =CCHH, 2J = 16.2 Hz,
(E)ꢀ6ꢀBenzylideneꢀ8,8ꢀdimethylhexahydroꢀ2Hꢀpyrrolo[2,1ꢀb]ꢀ
[1,3]oxazine (3a) was obtained from aldehyde 1a and 3ꢀaminoꢀ
propanol 2a and isolated in 82% yield by chromatography on
neutral Al2O3 (eluent hexane—diethyl ether, 10 : 1). Found (%):
C, 78.72; H, 8.85; N, 5.63. C16H21NO. Calculated (%): C, 78.97;
H, 8.70; N, 5.76. 1H NMR, : 1.10 (s, 3 H, Me); 1.13
(s, 3 H, Me); 1.33 (m, 1 H, NCH2CHHCH2O); 1.97 (m, 1 H,
NCH2CHHCH2O); 2.60 (dd, 1 H, =CCHH, 2J = 15.8 Hz, 4J =
= 1.7 Hz); 2.79 (dd, 1 H, =CCHH, 2J = 15.8 Hz, 4J = 2.1 Hz);
2
4J = 2.1 Hz); 3.11 (ddd, 1 H, NCHHCH2CH2O, J = 13.2 Hz,
3
3J = 12.4 Hz, J = 3.3 Hz); 3.67 (ddd, 1 H, NCH2CH2CHHO,
3J = 12.4 Hz, 3J = 11.4 Hz, 3J = 2.3 Hz); 3.69 (dddd, 1 H,
NCHHCH2CH2O, 2J = 13.2 Hz, 3J = 4.7 Hz, 3J = 1.7 Hz,
4J = 1.7 Hz); 4.11 (dddd, 1 H, NCH2CH2CHHO, 2J = 11.4 Hz,
3J = 4.7 Hz, 3J = 1.7 Hz, 4J = 1.7 Hz); 4.18 (s, 1 H, NCHO);
3
3
3.13 (ddd, 1 H, NCHHCH2CH2O, 2J = 13.2 Hz, J = 12.4 Hz,
5.56 (br.s, 1 H, CH=CN); 6.67 (dd, 1 H, thienyl, J = 3.4 Hz,
3
3
3
3J = 3.3 Hz); 3.68 (ddd, 1 H, NCH2CH2CHHO, J = 12.4 Hz,
4J = 1.2 Hz); 6.93 (dd, 1 H, thienyl, J = 5.2 Hz, J = 3.4 Hz);
6.97 (dd, 1 H, thienyl, 3J = 5.2 Hz, 4J = 1.2 Hz). 13C NMR,
: 22.0 (Me); 23.0 (C(3)); 26.9 (Me); 38.5 (C(8)); 42.8, 43.6 (C(4),
C(7)); 67.2 (C(2)); 89.6, 97.9 (C(8a), CH=CN); 119.7, 120.4,
126.9 (C(1), C(4), C(5), thienyl); 143.9, 146.6 (C(2), thienyl;
CH=CN). MS, m/z (Irel (%)): 249 [M]+ (100). MS (ESI), found:
m/z 250.1257, calculated for C14H19NOS, [M + H]+: m/z
250.1260.
3J = 11.4 Hz, 3J = 2.3 Hz); 3.77 (dddd, 1 H, NCHHCH2CH2O,
2J = 13.2 Hz, 3J = 4.7 Hz, 3J = 1.7 Hz, 4J = 1.7 Hz); 4.14 (dddd,
1 H, NCH2CH2CHHO, 2J = 11.4 Hz, 3J = 4.7 Hz, 3J = 1.7 Hz,
4J = 1.7 Hz); 4.18 (s, 1 H, NCHO); 5.81 (br.s, 1 H, PhCH=);
7.01 (br.t, 1 H, Ph, J = 6.8 Hz); 7.15—7.32 (m, 4 H, Ph). 13C NMR,
: 22.0 (Me); 23.1 (C(3)); 26.7 (Me); 38.4 (C(8)); 42.9, 43.5
(C(4), C(7)); 67.3 (C(2)); 95.3, 97.5 (C(8a), PhCH=); 123.1,
126.3, 128.3 (Ph); 139.8 (C(1), Ph); 147.1 (PhCH=C). MS, m/z
(Irel (%)): 243 [M]+ (100), 242 [M – H]+ (55).
(E)ꢀ6ꢀ(4ꢀTrifluoromethylbenzylidene)hexahydroꢀ2Hꢀpyrrolo
[2,1ꢀb][1,3]oxazine (3e) was obtained from aldehyde 1d and
3ꢀaminopropanol 2a and isolated in 42% yield by chromatoꢀ
graphy on neutral Al2O3 (eluent hexane—diethyl ether, 10 : 1).
Found (%): C, 63.85; H, 5.45; N, 5.03. C15H16F3NO. Calculatꢀ
ed (%): C, 63.60; H, 5.69; N, 4.94. 1H NMR, : 1.28—1.41 (m, 1 H,
NCH2CHHCH2O); 1.81—2.24 (m, 3 H, NCH2CHHCH2O,
=CCH2CHH); 2.68—3.10 (m, 2 H, =CCH2); 3.45 (ddd, 1 H,
NCHHCH2CH2O, 2J = 13.2 Hz, 3J = 13.2 Hz, 3J = 3.4 Hz);
3.75 (ddd, 1 H, NCH2CH2CHHO, 3J = 12.4 Hz, 3J = 12.4 Hz,
3J = 2.2 Hz); 3.78 (m, 1 H, NCHHCH2CH2O); 4.07 (m, 1 H,
NCH2CH2CHHO); 4.79 (dd, 1 H, NCHO, J = 5.6 Hz, J = 2.2 Hz);
5.30 (br.s, 1 H, 4ꢀF3CC6H4CH=); 7.24 (br.d, 2 H, Ph, J = 8.2 Hz);
7.46 (br.d, 2 H, Ph, J = 8.2 Hz). 13C NMR, : 22.9 (C(3)); 28.4,
28.4 (C(7), C(8)); 42.4 (C(4)); 67.3 (C(2)); 91.3, 93.8 (C(8a),
4ꢀF3CC6H4CH=); 124.0 (q, C(4), Ph, JCF = 32 Hz); 125.0 (q, CF3,
JCF = 270 Hz); 125.2 (q, C(3), C(5), Ph, JCF = 3.7 Hz); 125.8
(C(2), C(6), Ph); 143.6 (C(1), Ph); 149.7 (4ꢀF3CC6H4CH=C).
MS, m/z (Irel (%)): 283 [M]+ (100), 282 [M – H]+ (45).
5ꢀBenzylideneꢀ7,7ꢀdimethylhexahydropyrrolo[2,1ꢀb]oxazole
(7a) was obtained from aldehyde 1a and 2ꢀaminoethanol 6 as
a mixture of Eꢀ and Zꢀisomers (the ratio 3.5 : 1) and isolated in
75% yield by chromatography on neutral Al2O3 (eluent hexꢀ
ane—diethyl ether, 10 : 1). MS, m/z (Irel (%)): 229 [M]+ (100),
228 [M – H]+ (18). MS (ESI), found: m/z 230.1534, calculated
for C15H19NO, [M + H]+: m/z 230.1539.
(E)ꢀ6ꢀBenzylideneꢀ3,3,8,8ꢀtetramethylhexahydroꢀ2Hꢀpyrroloꢀ
[2,1ꢀb][1,3]oxazine (3b) was obtained from aldehyde 1a and
3ꢀaminoꢀ2,2ꢀdimethylpropanol 2b and isolated in 72% yield by
recrystallization from hexane. 1H NMR, : 0.86 (s, 3 H, Me);
1.11 (s, 3 H, Me); 1.13 (s, 3 H, Me); 1.16 (s, 3 H, Me); 2.60 (dd,
1 H, =CCHH, 2J = 15.6 Hz, 4J = 1.6 Hz); 2.81 (d, 1 H,
NCHHCH2CH2O, J = 13.0 Hz); 2.85 (dd, 1 H, =CCHH,
2J = 15.6 Hz, 4J = 2.0 Hz); 3.39 (d, 1 H, NCH2CH2CHHO,
2
J = 11.1 Hz); 3.42 (dd, 1 H, NCHHCH2CH2O, J = 13.0 Hz,
4J = 2.0 Hz); 3.66 (dd, 1 H, NCH2CH2CHHO, 2J = 11.1 Hz,
4J = 2.0 Hz); 4.07 (s, 1 H, NCHO); 5.26 (br.s, 1 H, PhCH=);
7.00 (br.t, 1 H, Ph, J = 6.8 Hz); 7.12—7.32 (m, 4 H, Ph). 13C NMR,
: 22.2 (Me); 23.8 (Me); 24.0 (Me); 26.4 (Me); 31.0 (C(3)); 38.5
(C(8)); 43.6 (C(7)); 54.3 (C(4)); 77.7 (C(2)); 94.4, 97.3 (C(8a),
PhCH=); 122.9, 126.2, 128.3 (Ph); 140.0 (C(1), Ph); 147.4
(PhCH=C). MS, m/z (Irel (%)): 271 [M+] (100), 270 [M+ – H]
(22). MS (ESI), found: m/z 272.2007; calculated for C18H25NO,
[M + H]+: m/z 272.2009.
(E)ꢀ6´ꢀBenzylideneꢀ8´,8´ꢀdimethylhexahydrospiro[cycloꢀ
propaneꢀ1,3´ꢀpyrrolo[2,1ꢀb][1,3]oxazine] (3c) was obtained
from aldehyde 1a and [1ꢀ(aminomethyl)cyclopropyl]methanol
2c and isolated in 72% yield by chromatography on neutral Al2O3
(eluent hexane—diethyl ether, 8 : 1). Found (%): C, 80.43;
H, 8.49; N, 5.36. C18H23NO. Calculated (%): C, 80.26; H, 8.61;
N, 5.20. 1H NMR, : 0.25—0.50 (m, 2 H, cycloꢀC3); 0.60—0.89
(m, 2 H, cycloꢀC3); 1.83 (s, 3 H, Me); 1.25 (s, 3 H, Me); 2.68
(br.d, 1 H, =CCHH, J = 15.7 Hz); 2.95 (dd, 1 H, =CCHH,
2J = 15.7 Hz, 4J = 1.7 Hz); 3.11 (d, 1 H, NCHHCH2CH2O,
J = 13.3 Hz); 3.29 (dd, 1 H, NCH2CH2CHHO, 2J = 11.4 Hz,
4J = 1.6 Hz); 3.55 (d, 1 H, NCHHCH2CH2O, J = 13.3 Hz); 4.08
Isomer Eꢀ7a. 1H NMR, : 1.18 (s, 3 H, Me); 1.19 (s, 3 H,
2
4
Me); 2.70 (dd, 1 H, =CCHH, J = 15.6 Hz, J = 2.0 Hz); 2.79
(dd, 1 H, =CCHH, 2J = 15.6 Hz, 4J = 2.2 Hz); 3.40 (ddd, 1 H,
NCHH, 2J = 10.6 Hz, 3J = 7.7 Hz, 3J = 6.2 Hz); 3.49 (ddd, 1 H,
NCHH, 2J = 10.6 Hz, 3J = 7.7 Hz, 3J = 5.7 Hz); 3.82 (ddd, 1 H,
OCHH, 2J = 7.7 Hz, 3J = 7.7 Hz, 3J = 5.7 Hz); 3.96 (ddd, 1 H,
OCHH, 2J = 7.7 Hz, 3J = 7.7 Hz, 3J = 6.2 Hz); 4.48 (s, 1 H,
NCHO); 5.68 (br.s, 1 H, PhCH=); 7.10 (br.t, 1 H, Ph, J = 6.8 Hz);
7.19—7.37 (m, 4 H, Ph). 13C NMR, : 22.1 (Me); 26.6 (Me);
4
(dd, 1 H, NCH2CH2CHHO, 2J = 11.4 Hz, J = 1.6 Hz); 4.29
(s, 1 H, NCHO); 5.33 (br.s, 1 H, PhCH=); 7.07 (br.t, 1 H, Ph,
J = 6.8 Hz); 7.20—7.40 (m, 4 H, Ph). 13C NMR, : 5.1, 13.6

414
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 2, February, 2014
Gvozdev et al.
39.1 (C(7)); 43.8 (C(6)); 51.3 (C(3)); 65.5 (C(2)); 102.2, 102.4
(C(7a), PhCH=); 123.9, 126.7, 128.1 (Ph); 138.6 (C(1), Ph);
152.1 (PhCH=C).
H, 7.80; N, 5.71. MS, m/z (Irel (%)): 245 [M]+ (100), 244
[M – H]+ (25).
Isomer Eꢀ10a. 1H NMR, : 1.25 (s, 3 H, Me); 1.32 (s, 3 H,
Me); 2.62 (d, 1 H, C=CCHH, J = 15.7 Hz); 2.85—3.27 (m, 3 H,
NHCHHCH2S); 2.93 (dd, 1 H, C=CCHH, 2J = 15.7 Hz,
4J = 1.8 Hz); 4.04—4.17 (m, 1 H, NHCH2CHHS); 4.68 (s, 1 H,
SCHNH); 5.70 (br.s, 1 H, PhCH=); 7.03—7.35 (m, 5 H, Ph).
13C NMR, : 25.6 (Me); 28.8 (Me); 31.7 (C(2)); 39.3 (C(7));
43.0 (C(6)); 53.5 (C(3)); 84.4 (C(7a)); 101.3 (PhCH=); 124.2,
126.9, 128.3 (Ph); 138.7 (C(1), Ph); 149.9 (PhCH=C).
Isomer Zꢀ7a. 1H NMR, : 1.20 (s, 3 H, Me); 1.22 (s, 3 H,
Me); 2.30 (d, 1 H, =CCHH, 2J = 15.0 Hz); 2.70 (dd, 1 H,
2
4
=CCHH, J = 15.0 Hz, J = 2.2 Hz); 3.11 (ddd, 1 H, NCHH,
2J = 10.9 Hz, 3J = 7.5 Hz, 3J = 5.8 Hz); 3.31—3.45 (m, 1 H,
NCHH); 3.73 (ddd, 1 H, OCHH, 2J = 7.8 Hz, 3J = 7.8 Hz, 3J =
= 5.7 Hz); 3.75—3.85 (m, 1 H, OCHH); 4.50 (s, 1 H, NCHO);
5.68 (d, 1 H, PhCH=, 4J = 2.2 Hz); 7.20—7.55 (m, 5 H, Ph).
13C NMR, : 22.0 (Me); 26.1 (Me); 37.9 (C(7)); 45.1 (C(6));
52.4 (C(3)); 65.5 (C(2)); 101.8, 104.3 (C(7a), PhCH=); 124.2,
127.3, 127.8 (Ph); 137.5 (C(1), Ph); 151.2 (PhCH=C).
1
Isomer Zꢀ10a. H NMR, : 1.30 (s, 3 H, Me); 1.32 (s, 3 H,
Me); 2.17 (d, 1 H, C=CCHH, J = 14.3 Hz); 2.73—2.84 (m, 3 H,
NHCHHCH2S); 3.12 (d, 1 H, C=CCHH, J = 14.3 Hz); 3.72—3.87
(m, 1 H, NHCH2CHHS); 4.75 (s, 1 H, SCHNH); 5.38 (br.s,
1 H, PhCH=); 7.03—7.73 (m, 5 H, Ph).
5´ꢀBenzylidenetetrahydroꢀ2´Hꢀspiro(cyclohexaneꢀ1,7´ꢀpyrꢀ
rolo[2,1ꢀb]thiazole) (10b) was obtained from aldehyde 1e as
a mixture of Eꢀ and Zꢀisomers (the ratio 16 : 1) and isolated in
30% yield by chromatography on neutral Al2O3 (eluent hexꢀ
ane—dichloromethane, 5 : 1). MS, m/z (Irel (%)): 285 [M]+ (100).
MS (ESI), found: m/z 285.1540, 286.1612, calculated for C18H23NS,
[M]+: m/z 285.1546, [M + H]+: m/z 286.1624.
Isomer Eꢀ10b. 1H NMR, : 1.20—1.80 (m, 10 H, 5 CH2,
cycloꢀC6); 2.68 (d, 1 H, C=CCHH, J = 16.0 Hz); 2.81 (dd, 1 H,
C=CCHH, 2J = 16.0 Hz, 4J = 2.5 Hz); 2.80—3.23 (m, 3 H,
NHCHHCH2S); 4.02—4.14 (m, 1 H, NHCH2CHHS); 4.81
(s, 1 H, SCHNH); 5.67 (br.s, 1 H, PhCH=); 7.00—7.30 (m, 5 H,
Ph). 13C NMR, : 23.0, 24.2, 26.0, 30.9, 35.8, 36.9 (C(2), C(3),
C(4), C(5), C(6), C(2´)); 40.6 (C(1,7´)); 42.9 (C(6´)); 53.1
(C(3´)); 82.8 (C(7a´)); 101.1 (PhCH=); 124.0, 126.8, 128.3 (Ph);
138.7 (C(1), Ph); 149.4 (PhCH=C).
7,7ꢀDimethylꢀ5ꢀ(2ꢀthienylmethylidene)hexahydropyrroloꢀ
[2,1ꢀb]oxazole (7b) was obtained from aldehyde 1b and 2ꢀaminoꢀ
ethanol 6 as a mixture of Eꢀ and Zꢀisomers (the ratio 7.5 : 1) and
isolated in 64% yield by chromatography on neutral Al2O3 (eluꢀ
ent hexane—diethyl ether, 8 : 1). Found (%): C, 66.56; H, 7.05;
N, 5.84. C17H13NOS. Calculated (%): C, 66.34; H, 7.28; N, 5.95.
MS, m/z (Irel (%)): 235 [M]+ (100), 234 [M – H]+ (17).
Isomer Eꢀ7b. 1H NMR, : 1.18 (s, 3 H, Me); 1.19 (s, 3 H,
Me); 2.64 (br.s, 2 H, =CCH2); 3.37—3.54 (m, 2 H, NCH2); 3.78
(ddd, 1 H, OCHH, 2J = 7.7 Hz, 3J = 7.7 Hz, 3J = 5.6 Hz); 3.92
(ddd, 1 H, OCHH, 2J = 7.7 Hz, 3J = 7.7 Hz, 3J = 6.5 Hz); 4.43
(s, 1 H, NCHO); 5.88 (br.s, 1 H, CH=CN); 6.74 (dd, 1 H,
thienyl, 3J = 3.5 Hz, 4J = 1.2 Hz); 6.96 (dd, 1 H, thienyl, 3J = 5.1 Hz,
3
4
3J = 3.5 Hz); 7.06 (dd, 1 H, thienyl, J = 5.1 Hz, J = 1.2 Hz).
13C NMR, : 22.5 (Me); 27.4 (Me); 39.2 (C(7)); 44.0 (C(6));
51.7 (C(3)); 65.4 (C(2)); 96.6, 103.4 (C(7a), CH=CN); 121.3,
122.2, 127.0 (C(1), C(4), C(5), thienyl); 142.7, 152.1 (C(2), thiꢀ
enyl and CH=CN).
Isomer Zꢀ7b. 1H NMR, : 1.11 (s, 3 H, Me); 1.31 (s, 3 H,
Me); 2.59 (br.s, 2 H, =CCH2); 3.23 (ddd, 1 H, NCHH, 2J =
= 10.8 Hz, 3J = 7.0 Hz, 3J = 5.8 Hz); 3.45—3.60 (m, 1 H, NCHH);
3.80—4.08 (m, 2 H, OCH2); 4.47 (s, 1 H, NCHO); 5.69 (br.s,
1 H, CH=CN); 6.74 (dd, 1 H, thienyl, 3J = 3.5 Hz, 4J = 1.2 Hz);
6.92 (dd, 1 H, thienyl, 3J = 5.1 Hz, 3J = 3.5 Hz); 7.11 (dd, 1 H,
thienyl, 3J = 5.1 Hz, 4J = 1.2 Hz). 13C NMR, : 22.3 (Me); 28.4
(Me); 38.9 (C(7)); 45.0 (C(6)); 53.0 (C(3)); 65.4 (C(2)); 97.9,
104.6 (C(7a), CH=CN); 121.3, 122.1, 126.7 (C(1), C(4), C(5),
thienyl); 140.9, 150.7 (C(2), thienyl and CH=CN).
5ꢀBenzylidenehexahydropyrrolo[2,1ꢀb]thiazoles 10a,b (genꢀ
eral procedure). Triethylamine (100 mg, 1 mmol) was added to
a solution of 2ꢀaminoethanethiol hydrochloride 8 (115 mg,
1 mmol) and the starting aldehyde 1 (1 mmol) in anhydrous DMSO
(3 mL) with stirring. The mixture was stirred for 30 min at room
temperature, followed by addition of freshly powdered KOH
(280 mg, 5 mmol) and the stirring was continued for 6 h until the
reaction was complete (monitoring by GLC or 1H NMR spectroꢀ
scopy). Then, the mixture was treated with water (30 mL) and
CH2Cl2 (30 mL), the organic layer was separated, the aqueous
layer was additionally extracted with CH2Cl2 (3×10 mL). The
combined organic layers were washed with water (4 times), dried
with anhydrous K2CO3, the solvent was evaporated. The target
products 10a,b were isolated from the residue by microdistillaꢀ
tion in vacuo or column chromatography (see Table 1).
Isomer Zꢀ10b. 1H NMR, : 1.20—1.80 (m, 10 H, 5 CH2,
cycloꢀC6); 2.31 (d, 1 H, C=CCHH, J = 14.7 Hz); 2.74 (d, 1 H,
C=CCHH, J = 14.7 Hz); 2.80—3.23 (m, 3 H, NHCHHCHHS);
3.69—3.80 (m, 1 H, NHCH2CHHS); 4.87 (s, 1 H, SCHNH);
5.34 (br.s, 1 H, PhCH=); 7.00—7.30 (m, 5 H, Ph).
2ꢀ(2ꢀMethylꢀ5ꢀphenylpentꢀ4ꢀynꢀ2ꢀyl)thiazolidine (9a). Triꢀ
ethylamine (100 mg, 1 mmol) was added to a solution of
2ꢀaminoethanethiol hydrochloride 8 (115 mg, 1 mmol) and alꢀ
dehyde 1a (185 mg, 1 mmol) in anhydrous DMSO (3 mL) with
stirring. The mixture was stirred for 30 min at room temperature
and treated with water (30 mL) and CH2Cl2 (30 mL), the organꢀ
ic layer was separated, the aqueous layer was extracted with
CH2Cl2 (3×10 mL). The combined organic layers were washed
with water (4 times), dried with anhydrous K2CO3, the solvent
was evaporated to obtain compound 9a (220 mg, 90%) as a dense
light yellow liquid. Found (%): C, 73.11; H, 7.95; N, 5.96.
C15H19NS. Calculated (%): C, 73.42; H, 7.80; N, 5.71. 1H NMR,
: 1.18 (s, 3 H, Me); 1.21 (s, 3 H, Me); 1.78 (br.s, 1 H, NH); 2.50
(d, 1 H, CCCHH, J = 16.6 Hz); 2.61 (d, 1 H, CCCHH,
J = 16.6 Hz); 2.67—2.82 (m, 1 H, NHCHH); 2.85—3.05 (m, 2 H,
NHCHHCHHS); 3.50—3.64 (m, 1 H, SCHH); 4.63 (s, 1 H,
SCHNH); 7.35—7.50 (m, 5 H, Ph). 13C NMR, : 24.2 (Me);
24.7 (Me); 31.2 (CCCH2); 35.0 (SCH2); 37.7 (C(CH3)2); 53.0
(NCH2); 81.2 (SCHN); 83.0, 87.5 (CC); 123.8 (C(1), Ph);
127.7, 128.4, 131.6 (Ph).
5ꢀBenzylideneꢀ7,7ꢀdimethylhexahydropyrrolo[2,1ꢀb]thiazole
(10a) was obtained from aldehyde 1a as a mixture of Eꢀ and
Zꢀisomers (the ratio 14 : 1) and isolated in 32% yield by microꢀ
distillation in vacuo (tbath = 150—160 C (1 Torr)). Found (%):
C, 73.52; H, 7.62; N, 5.87. C15H19NS. Calculated (%): C, 73.42;
Reaction of aldehyde 1a with amino alcohols 2a,b in DMSOꢀd6.
A solution of aldehyde 1a (47 mg, 0.25 mmol) in DMSOꢀd6
(0.5 mL) was added to a solution of amino alcohol 2a or 2b
(0.25 mmol) in anhydrous DMSOꢀd6 (0.5 mL). Some (~0.4 mL)
of the solution obtained was placed into an NMR tube to moniꢀ

Bicyclic N,Oꢀ and N,Sꢀenaminals
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 2, February, 2014
415
tor the reaction progress and the composition of the forming
products by regular recording 1H NMR spectra.
of Organic Synthesis and Creation of Compounds with
Valuable Applied Properties").
The solutions of compounds 4a and 4b in DMSOꢀd6 obꢀ
tained by the condensation of aldehyde 1a with amino alcohols
2a or 2b for 5 min were stirred with freshly powdered KOH
(70 mg, 1.25 mmol) at room temperature, monitoring the reacꢀ
tion progress by 1H NMR spectroscopy. The ratio of the starting
compounds, forming oxazinanes 5a,b and aminals 3a,b was deꢀ
termined based on the ratio of integral intensities of the imine
and the aminal protons. Compounds 4a,b and 5a,b were characꢀ
terized without isolation from the reaction mixtures.
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1999, 64, 1979.
2ꢀ(2ꢀMethylꢀ5ꢀphenylpentꢀ4ꢀynꢀ2ꢀyl)ꢀ1,3ꢀoxazinane (5a).
1H NMR, : 0.98 (s, 6 H, 2 Me); 1.17—1.28 (m, 1 H,
NCH2CHHCH2O); 1.48—1.60 (m, 1 H, NCH2CHHCH2O);
2
2.37 (s, 2 H, CCCH2); 2.73 (ddd, 1 H, NCHH, J = 12.6 Hz,
3
3J = 12.6 Hz, J = 3.2 Hz); 2.98—3.11 (m, 1 H, NCHH); 3.68
(ddd, 1 H, OCHH, 2J = 12.0 Hz, 3J = 12.0 Hz, 3J = 2.5 Hz);
3.84 (NCHO); 3.97—4.09 (m, 1 H, OCHH); 7.30—7.42 (m, 5 H,
Ph). 13C NMR, : 22.1 (Me); 22.6 (Me); 27.0, 28.9 (CCCH2
and C(5), cycloꢀC4NO); 37.8 (C(CH3)2); 44.2 (C(4), cycloꢀ
C4NO); 67.4 (C(6), cycloꢀC4NO); 82.0, 88.0 (CC); 93.0 (C(2),
cycloꢀC4NO); 123.4 (C(1), Ph); 127.8, 128.5, 131.2 (Ph).
3ꢀ(2,2ꢀDimethylꢀ5ꢀphenylpentꢀ4ꢀynylidenamino)ꢀ2,2ꢀdimethꢀ
ylpropanꢀ1ꢀol (4b). 1H NMR, : 0.78 (s, 6 H, 2 Me); 1.13 (s, 6 H,
2 Me); 2.53 (s, 2 H, CCCH2); 3.16 (d, 2 H, NCH2, J = 1.2 Hz);
3.18 (s, 2 H, CH2OH); 3.35 (br.s, 1 H, OH); 7.28—7.40 (m, 5 H,
Ph); 7.56 (t, 1 H, CH=N, J = 1.2 Hz). 13C NMR, : 22.7 (2 Me);
24.5 (2 Me); 29.8 (CCCH2); 36.5 (NCH2C(CH3)2CH2O); 39.2
(CH2C(CH3)2); 68.0, 68.6 (NCH2C(CH3)2CH2O); 82.1, 88.1
(CC); 123.2 (C(1), Ph); 127.9, 128.5, 131.2 (Ph); 169.4 (CH=N).
5,5ꢀDimethylꢀ2ꢀ(2ꢀmethylꢀ5ꢀphenylpentꢀ4ꢀynꢀ2ꢀyl)ꢀ1,3ꢀoxꢀ
1
azinane (5b). H NMR, : 0.65 (s, 3 H, Me); 0.99 (s, 3 H, Me);
1.02 (s, 3 H, Me); 1.03 (s, 3 H, Me); 2.41 (s, 2 H, CCCH2);
2.52 (d, 1 H, NCHH, J = 13.2 Hz); 2.62 (dd, 1 H, NCHH,
14. S. CalvetꢀVitale, C. VanucciꢀBacqué, M. FargeauꢀBellasꢀ
soued, G. Lhommet, Tetrahedron, 2005, 61, 7774.
15. C. A. Busacca, A. I. Meyers, J. Chem. Soc., Perkin Trans. 1,
1991, 10, 2299.
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76, 507.
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V. B. Kobychev, B. A. Trofimov, Russ. Chem. Bull. (Int. Ed.),
2013, 62, 26 [Izv. Akad. Nauk, Ser. Khim., 2013, 27].
18. K. M. Gericke, D. I. Chai, M. Lautens, Tetrahedron, 2008,
64, 6002.
19. R. Jana, J. A. Tunge, Org. Lett., 2009, 11, 971.
20. K. Tanaka, Y. Hagiwara, K. Noguchi, Angew. Chem., Int.
Ed., 2005, 44, 7260.
4
3J = 13.2 Hz, J = 2.4 Hz); 3.23 (br.s, 1 H, NH); 3.27 (d, 1 H,
OCHH, J = 10.9 Hz); 3.52 (dd, 1 H, OCHH, 3J = 10.9 Hz,
4J = 2.4 Hz); 3.75 (NCHO); 7.30—7.43 (m, 5 H, Ph). 13C NMR,
: 22.3 (Me); 22.5 (Me); 22.8 (Me); 23.7 (Me); 28.8 (CCCH2);
28.9 (C(5), cycloꢀC4NO); 37.5 (C(CH3)2); 55.7 (C(4), cycloꢀ
C4NO); 77.2 (C(6), cycloꢀC4NO); 81.9, 88.6 (CC); 92.7 (C(2),
cycloꢀC4NO); 123.4 (C(1), Ph); 127.8, 128.5, 131.2 (Ph).
This work was financially supported by the Council on
Grants at the President of the Russian Federation (Proꢀ
gram of State Support for Leading Scientific Schools of
the Russian Federation, Grant NShꢀ604.2012.3) and the
Presidium of the Russian Academy of Sciences (Program
for Basic Research "Development of Methods for Prepaꢀ
ration of Chemical Compounds and Development of New
Materials", Subprogram "Development of Methodology
Received November 29, 2013;
in revised form December 23, 2013