Synthesis of 3-(alk-2-yn-1-yl)-1,3-oxazolidines using copper-containing catalysts

Article abstract of DOI:10.1007/s10593-014-1527-y

A selective method for the synthesis of 3-(alk-2-yn-1-yl)-1,3-oxazolidines has been developed by the reaction of bis(oxazolidin-3-yl)methanes with terminal acetylenes with copper-containing catalysts. The reaction of terminal acetylenes with optically active bis((4R)-4-ethyl-1,3-oxazolidin-yl)methane led to the formation of (4R)-3-(2-alkynyl)-4-ethyl-1,3-oxazolidines.

Full text of DOI:10.1007/s10593-014-1527-y

Chemistry of Heterocyclic Compounds, Vol. 50, No. 5, August, 2014 (Russian Original Vol. 50, No. 5, May, 2014)
SYNTHESIS OF 3-(ALK-2-YN-1-YL)-1,3-OXAZOLIDINES
USING COPPER-CONTAINING CATALYSTS
G. P. Khabibullina1*, V. M. Yanybin1, A. G. Ibragimov1, and U. M. Dzhemilev1
A selective method for the synthesis of 3-(alk-2-yn-1-yl)-1,3-oxazolidines has been developed by the
reaction of bis(oxazolidin-3-yl)methanes with terminal acetylenes with copper-containing catalysts. The
reaction of terminal acetylenes with optically active bis((4R)-4-ethyl-1,3-oxazolidin-yl)methane led to
the formation of (4R)-3-(2-alkynyl)-4-ethyl-1,3-oxazolidines.
Keywords: 3-(alk-2-yn-1-yl)-1,3-oxazolidines, bis(1,3-oxazolidin-3-yl)methane, 3,8-dioxa-1,6-diazabi-
cyclo[4.4.1]undecane, terminal acetylenes, catalysis.
One of the most widely known and used methods for the synthesis of propargylamines [1-4] is the
Mannich three-component condensation of terminal acetylenes with amines under the influence of Cu(I) [5-9],
Zn, Ni, Au(I), Au(III), Ag(I), Fe(III), In (III), and Hg salts, bimetallic Cu–Ru(II) systems, heterogeneous
catalysts, for example, Cu-zeolite, Ni-Y-zeolite, LDH-AuCl4, silver and copper nanoparticles, and copper
catalysts on Al2O3 and SiO2 [10]. Microwave [11] and ultrasound irradiation [12] are used to activate the three-
component condensation mentioned above in the presence of Cu(I) salts. In addition, propargylamines are
obtained by the reaction of metal acetylides with C=N electrophiles in anhydrous conditions at low temperatures
[5]. The interest in polyfunctional propargylamines is explained by their wide use as universal precursors in fine
organic synthesis [13-15] and also their use as biologically active compounds [16-25].
We have shown previously [26, 27] that it is possible to synthesize propargylamines by catalytic
aminomethylation of terminal acetylenes with gem-diamines. With a continuation of the study of this reaction
and also with objective of developing an effective method for the synthesis of 3-(alk-2-yn-1-yl)-1,3-ox-
azolidines, we have studied the aminomethylation of the terminal acetylenes 1a-c with bis(oxazolidin-3-yl)-
methanes 2a-d. The latter were chosen because of the wide use of derivatives of oxazolidines in stereospecific
organic synthesis [28-32].
We found that bis(oxazolidin-3-yl)methane (2a), obtained by method [33], was in a 1:4 mixture with
3,8-dioxa-1,6-diazabicyclo[4.4.1]undecane (3a), which is in agreement with other studies [34]. The reaction of
terminal acetylenes 1a-c with bis(oxazolidin-3-yl)methanes 2a-d was carried out in conditions optimal for the
aminomethylation of acetylenes with gem-diamines (5 mol% CuCl, 80C, 6 h) [26, 27]. Under these conditions,
the mixture of compounds 2a and 3a in reaction with 1-pentyne 1a, 1-hexyne (1b), and phenylacetylene (1c) led
to the selective formation of 3-(hex-2-yn-1-yl)-, 3-(hept-2-yn-1-yl)-, and 3-(3-phenylprop-2-yn-1-yl)-
1,3-oxazolidines (4a-c) in 58, 71, and 81 yields, respectively.
_______
*To whom correspondence should be addressed, e-mail: ink@anrb.ru.
1Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Oktyabrya Ave., Ufa 450075,
Russia.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 788-796, May, 2014. Original
article submitted February 15, 2014; revision submitted April 4, 2014.
726
0009-3122/14/5005-0726©2014 Springer Science+Business Media New York

In the presence of other Cu-containing catalysts (CuCl2, CuBr, CuI, CuSO4, Cu(CH3CO2)2,
.
CuCl2 2H2O–Al2O3) the yields of 3-(hept-2-yn-1-yl)-1,3-oxazolidine (4b) ranged from 24-72% (Table 1). The
results obtained indicated that in the reaction with the acetylenes 1a-c in the presence of copper catalyst, the
isomer 2a interacts with the formation of 3-(alk-2-yn-1-yl)-1,3-oxazolidines 4a-c. It is possible that the high
selectivity of the formation of compounds 4a-c is explained by the shift of the equilibrium of the regioisomers
2a+3a under the reaction conditions towards compound 2a which is more reactive with the acetylenes. A similar
isomerization 3a → 2a was observed in other studies [34] (conditions: 80-90C, 1.5 h, toluene). According to
the paper [34], the isomerization occurs through the stage of formation of the imine as determined by 13C NMR
spectra (164 ppm).
R2
R1
R2
O
O
R1
OH
N
N
R1
R1
1.5 equiv. CH2O
O
N
N
+
O
PhH, , 6 h
R1
R2
R2
NH2
2a–d
R2
3a–c
HC
R3
O
R1
1a–c
–
HN
5 mol% [Cu]
PhMe, 80°C, 6 h
R2
2a, 3a, 4a–c R1 = R2 = H;
R3
2b, 3b, 5a–c R1 = Me, R2 = H;
2c, 3c, 6a–c R1 = H, R2 = Et;
O
R1
N
4–6 a R3 = n-Pr, b R3 = n-Bu, c R3 = Ph;
2d, 7 R1 = Ph, R2 = H; 7 R3 = Ph
R2
4–6 a–c, 7
It might be suggested [35, 36] that in the conditions of aminomethylation of acetylenes, the first step is
the coordination of the bis(oxazolidin-3-yl)methane molecule to the central atom of the catalyst [37], followed
by nucleophilic addition of the acetylene to the carbocation formed, leading to the formation of the molecule of
the 3-(alk-2-yn-1-yl)-1,3-oxazolidine.
O
+
N
CH2
O
O
O
O
Cu+
N
N+
Cu
H
R
N
N
Cu
O
N
O
R
O
NH
+
–Cu+
N
It should be noted that we did not succeed in obtaining 3-(alk-2-yn-1-yl)-1,3-oxazolidines from the
three-component condensation of terminal acetylenes with formaldehyde (or paraform) and 1,3-oxazolidine,
obtained in situ, with CuCl as catalyst.
To broaden the scope of the method developed, and also the synthesis of new 3-(alk-2-yn-1-yl)-
1,3-oxazolidines, we have studied the reaction of methyl-, ethyl-, and phenyl-substituted bis(oxazolidin-
3-yl)methanes 2b-d with terminal acetylenes in the presence of CuCl catalyst. The ratio of products 2:3 in the
727

TABLE 1. Effect of Catalyst on the Yield of 3-(Hept-2-yn-1-yl)-
1,3-oxazolidine (4b)*
Experiment No.
Catalyst
СuCl
CuBr
CuI
CuCl2
CuCl2·2Н2О – Al2O3
CuSO4
Yield, %
1
2
3
4
5
6
7
71
56
43
50
24
54
72
Cu(OAc)2
_______
*Molar ratios of compound 2a : 1-hexyne (2b) : catalyst = 1:1:0.05,
PhMe, 80C, 6 h, argon atmosphere.
reaction of substituted ethanolamines (amino-2-propanol, R-(-)-2-amino-1-butanol, and 2-amnio-1-phenyl-
ethanol) with formaldehyde depended on the substituent in the initial ethanolamine. As a result, mixtures of
compounds 2b+3b (ratio 4:1), 2c+3c (ratio 9:1), whereas with 2-amino-1-phenylethanol only compound 2d was
obtained with a yield of 55%.
The synthesized bis(5-methyl-1,3-oxazolidin-yl)methane (2b) and bis(4-ethyl-1,3-oxazolidin-3-yl)-
methane (2c) were isolated by column chromatography in pure form. The terminal acetylenes reacted with
mixture of compounds 2b+3b or 2c+3c or with individual bis(oxazolidin-3-yl)methanes 2b,c formed
exclusively 3-(alk-2-yn-1-yl)-1,3-oxazolidines 5,6 a-c.
1
In the H NMR spectra of compounds 2c,d, the protons of the CH2 groups, which lie between the
nitrogen and oxygen atoms, appear in the form AB system with coupling constants of 6.0 and 5.6 Hz,
respectively, characteristic of bis(oxazolidin-3-yl)methanes, whereas the coupling constants for 3,8-dioxa-1,6-di-
azabicyclo[4.4.1]undecanes 3c,d are >10 Hz [34]. The hydrogen atoms on the substituted carbon atom C-4 in
compound 2c and C-5 in compound 2d appear as triplets at 2.79 and 5.01, respectively (J = 6.0 Hz).
We have established that the aliphatic acetylenes 1a,b react with methyl- and ethyl-substituted
bis(oxazolidin-3-yl)methanes 2b,c, but do not react with bis(5-phenyl-1,3-oxazolidin-3-yl)methane (2d). The
latter reacts only with phenylacetylene (1c) to give 5-phenyl-3-(3-phenylprop-2-yn-1-yl)-1,3-oxazolidine (7).
Propargylamines containing optically active substituents are effective intermediates in the synthesis of
biologically active and natural compounds. However, methods for their synthesis are few and complex [29, 30].
We have proposed an effective method for the synthesis of optically active (4R)-3-(hex-2-yn-1-yl)-, (4R)-3-(hept-
2-yn-1-yl)-, and (4R)-3-(phenylprop-2-yn-1-yl)-1,3-oxazolidines (6a-c) by the reaction of terminal acetylenes
1a-c with optically active bis((4R)-4-ethyl-1,3-oxazolidin-3-yl)methane (2c). The reaction gave rise to (4R)-3-(alk-
2-yn-1-yl)-4-ethyl-1,3-oxazolidines 6a-c with yields of 24-83%.
Because of the presence of the asymmetric center C-4, in compounds 6a-c the germinal methylene
protons 5-CH2 in the oxazolidine ring and the methylene group CH2CH3 in the ethyl substituent are non-
1
equivalent. In the H NMR spectra, the diastereotopic protons of the 5-CH2 methylene group appear as a
multiplet and a triplet or two triplets with J = 7.5 Hz, and the protons of CHCH2CH3 as two multiplets.
CH
2 equiv. 2a + (CH2)5
CH
CH
5 mol% CuCl
O
(CH2)5
PhH, 80°C, 6 h
N
8
728

To elucidate the possibility of the synthesis of bis(1,3-oxazolidin-3-yl)-substituted diynes, we carried
out the reaction of bis(oxazolidin-3-yl)methane 2a with 1,8-nonadiyne in a ratio of 2a : 1,8-nonadiyne :
CuCl = 2:1:0.05 (reaction conditions: 80C, 6h, argon atmosphere). Under these conditions 3-(deca-2,9-diyn-
1-yl)-1,3-oxazolidine (8) was obtained in 33% yield. Substituted bis(oxazolidin-3-yl)methanes 2b-d did not
react with 1,8-nonadiyne at all.
The mass spectra of the propargylamines 4-6 a-c, 8 contain intense peaks for the [M-H]+ ions, which are
characteristic for mass spectra of higher amines [38]. It is probable that this is connected with the electronic
factors of the amino groups, whereas in the spectrum of 5-phenyl-3-(3-phenylprop-2-yn-1-yl)-1,3-oxazolidine (7)
the molecular ion [M]+ with mass m/z 263 was observed with peaks of maximum intensity at 115 [PhC≡CCH2]+
and 104 [PhCHCH2]+ due to the aromatic rings influence. The fragment ions [PhC≡CCH2]+ (m/z 115) with
maximum intensity are characteristic for 3-(3-phenylprop-2-yn-1-yl)-1,3-oxazolidines 4-6.
So we have developed a new selective method for the synthesis of 3-(alk-2-yn-1-yl)-1,3-oxazolidines by
the reaction of bis(oxazolidin-3-yl)methanes with terminal acetylenes in the presence of copper-containing
catalysts. The reactions of terminal acetylenes with optically active bis((4R)-4-ethyl-1,3-oxazolidin-3-yl)-
methanes led to the retention of the configuration of the chiral center with the formation of optically active (4R)-
3-(hex-2-yn-1-yl)-, (4R)-3-(hept-2-yn-1-yl)-, and (4R)-4-ethyl-3-(3-phenylprop-2-yn-1-yl)-1,3-oxazolidines in 24-
83 % yields.
EXPERIMENTAL
1
IR spectra of nujol mulls were recorded with a Bruker Vertex 70v spectrometer. H and 13C NMR
spectra were recorded with Bruker Avance 400 (400 and 100 MHz, respectively, for compounds 4, 5 a-c, 7, 8)
and Bruker Avance 500 spectrometers (500 and 125 MHz, respectively, for compounds 2c,d, 6a-c). The solvent
was CDCl3, the residual signals (7.26 ppm) of which were used as internal standard. 15N NMR spectra were
recorded with a Bruker Avance 500 (50 MHz) spectrometer with urea (77.0 ppm) as internal standard. Analysis
of the reaction products was carried by GLC with a Chrom-5 chromatograph with a flame ionization detector,
SE-30 (5%) stationary phase on Chromaton N-AW-HMDS carrier packed steel column, 2400×3 mm,
programmer temperature 50-270C, 8C/min, helium carrier gas). Analysis by GC-MS was carried out on a
Shimadzu GC 2010 chromatograph with a GCMS-QP2010 Ultra (Shimadzu, Japan) mass spectrometric
detector, and a Supelco 5ms column (60 m×0.25mm×0.25µm). Carrier gas was helium, the temperature of the
injector and interface 260C, ion source 200C. Method of ionization EI (70 eV). Mass spectra of compounds 7,
8 were recorded on an Autoflex MALDITOF/TOF spectrometer (Bruker, Germany) with α-cyano-
4-hydroxycinnamic and 2,5-dihydrobenzoic acids as matrix (samples were prepared as dried drops in
chloroform, 1:10). Elemental analyses were carried out with a Karlo Erba 1106 apparatus. Special angles of
rotation were measured with a Perkin-Elmer 341 polarimeter. Melting points were measured with a PHMK
80/2617 apparatus. The compounds prepared were purified by chromatography on KSK silica gel (50-160 µm).
TLC was carried out on Sorbfil plates with detection in an iodine chamber.
Bis(1,3-oxazolidin-3-yl)methane (2a) and 3,8-dioxa-1,6-diazabicyclo[4.4.1]undecane (3a) were
prepared by the method described in paper [33]. A mixture of monoethanolamine (6 ml, 0.10 mol) and paraform
(3.0 g, 0.10 mol) in PhH (100 ml) were heated in flask with a Dean-Stark condenser for 30 min. Then more
paraform (1.5 g, 0.05 mol) was added, and the mixture was refluxed in the flask until water was no longer lost
from the Dean and Stark condenser. The reaction mixture was filtered off, and the solvent was evaporated on a
rotary evaporator. The colorless viscous liquid obtained consisted of a 1:4 mixture of compounds 2a and 3a.
Yield 9.5 g (60%). The physicochemical and spectral characteristics of compounds 2a and 3a corresponded to
the literature values [34].
729

Bis(5-methyl-1,3-oxazolidin-3-yl)methane (2b) and 6,9-dimethyl-3,8-dioxa-1,6-diazabicyclo-
[4.4.1]undecane (3b) were obtained analogously by the method described above [33]. A colorless liquid,
consisting of a 4:1 mixture of compounds 2b and 3b, was obtained from 1-amino-2-propanol (3.80 g,
0.050 mol) and paraform (2.25 g, 0.075 mol). Yield 4.90 g (53%). Compound 2b was isolated by column
chromatography (Rf 0.20, 2:1 CCl4EtOAc). The physicochemical and spectroscopic properties of compound
2b corresponded to the literature values [34].
Bis((4R)-4-ethyl-1,3-oxazolidin-3-yl)methane (2c) was obtained analogously to the method described
above [33]. A colorless liquid consisting of a 9:1 mixture of compounds 2c and 3c was obtained from R-(-)-2-ami-
no-1-butanol (4.7 ml, 0.05 mol). Yield 4.5 g (42%). Compound 2c was isolated by column chromatography
18
1
(Rf 0.40, 2:1 hexaneEtOAc). [α]D -41.7 (c 4.05, CHCl3). H NMR spectrum, δ, ppm (J, Hz): 0.79 (6Н, t,
J = 7.5, CH2СН3); 1.18-1.25 (2Н, m) and 1.36-1.42 (2Н, m, СН2СН3); 2.79 (2Н, t, J = 6.0, 4-СН); 3.13-3.16
(2Н, m) and 3.79 (2Н, t, J = 6.5, 5-СН2); 3.18 (2Н, s, NCH2N); 4.12 (2Н, d, J = 6.0) and 4.42 (2Н, d, J = 6.0,
2-СН2). 13H NMR spectrum, δ, ppm: 10.8 (СН2СН3); 26.6 (СН2СН3); 63.1 (C-4); 69.2 (С-5); 75.5 (NСH2N);
84.2 (С-2). 15N NMR spectrum, δ, ppm: 73.1. Found, %: С 61.59; Н 10.40; N 13.12. С11Н22N2О2. Calculated,
%: С 61.65; Н 10.35; N 13.07.
Bis(5-phenyl-1,3-oxazolidin-3-yl)methane (2d) was prepared by the method described above [33]
from 2-amino-1-phenylethanol (0.690 g, 5.0 mmol) and paraform (0.225 g, 7.5 mmol). Yield 0.860 g, (55%),
1
white crystals, mp 67-68°С. Rf 0.25 (hexane−СН2Сl2EtOAc, 2:2:1). H NMR spectrum, δ, ppm (J, Hz):
2.94-2.99 (2Н, m) and 3.57-3.67 (2Н, m, 4-СН2); 3.61 (2Н, s, NСH2N); 4.77 (2Н, d, J = 5.6) and 4.79 (2Н, d,
J = 5.6, 2-СН2); 5.01 (2Н, t, J = 6.0, 5-СН); 7.35-7.44 (10Н, m, H Ph). 13H NMR spectrum, δ, ppm: 59.0 (С-4);
74.8 (NСH2N); 76.3 (C-5); 86.1 (С-2); 125.6 (C Ph); 127.5 (C Ph); 128.6 (C Ph); 142.3 (C Ph). Found, %:
С 73.48; Н 7.23; N 9.12. С19Н22N2О2. Calculated, %: С 73.52; Н 7.14; N 9.02.
Synthesis of 3-(Alk-2-yn-1-yl)-1,3-oxazolidines 4-6 a-c, 7. Compounds 4-6 a-c, 7 were prepared by
the method described in papers [26, 27]. A mixture of bis(oxazolidin-3-yl)methane (1 mmol) 2a-d (compounds
2a-c were used as a mixture with the isomeric 3,8-dioxa-1,6-diazabicyclo[4.4.1]undecane 3a-c), terminal
acetylene 1a-c (1 mmol) and catalyst (0.05 mmol) in PhMe (3 ml) was stirred in an atmosphere of argon at 80C
for 6 h. The catalyst was separated from the reaction mixture, the solvent was evaporated, and the reaction
mixture was purified by column chromatography.
3-(Hex-2-yn-1-yl)-1,3-oxazolidine (4a). Yield 0.09 g, (58%), соlorless oil, Rf 0.22 (2:1 CCl4-EtOAc).
IR spectrum, ν, cm-1: 1056 (C–O–C); 1450 (CH2), 2253 (C≡C); 2932 (CH3). 1H NMR spectrum, δ, ppm (J, Hz):
0.98 (3Н, t, J = 7.2, СН3); 1.53 (2Н, sextet, J = 7.2, СН2СН3); 2.17 (2Н, t, J = 7.2, СН2СН2СН3); 3.06 (2Н, t,
J = 6.8, 4-СН2); 3.36 (2Н, s, NCH2C≡C); 3.80 (2Н, t, J = 6.8, 5-СН2); 4.37 (2Н, s, 2-СН2). 13C NMR spectrum,
δ, ppm: 13.5 (СH3); 20.7 (СН2СН2СН3); 22.2 (СН2СН3); 42.9 (NCH2C≡C); 51.3 (С-4); 63.6 (С-5); 76.1
(NCH2C≡C); 84.3 (NCH2C≡C); 85.9 (С-2). Mass spectrum, m/z (Irel, %): 152 [M-Н]+ (100), 123 [M-Н-C2Н5]+
(28), 110 [M-C3Н7]+ (31), 72 [C2H4NCH2O]+ (62). Found, %: С 70.47; Н 9.95; N 9.21. С9Н15NО. Calculated,
%: С 70.55; Н 9.87; N 9.14.
3-(Hept-2-yn-1-yl)-1,3-oxazolidine (4b). Yield 0.12 g (71%), соlorless oil, Rf 0.22 (2:1 CCl4–EtOAc).
IR spectrum, ν, сm-1: 1058 (C–O–C), 1458 (CH2), 2250 (C≡C), 2930 (CH2). 1H NMR spectrum, δ, ppm (J, Hz):
0.93 (3Н, t, J = 7.2, СН3); 1.39-1.45 (2Н, m, СН2СН3); 1.45-1.52 (2Н, m, СН2СН2СН3); 2.18-2.22 (2Н, m,
С≡ССН2СН2); 3.07 (2Н, t, J = 6.8, 4-СН2); 3.37 (2Н, s, NCH2C≡C); 3.80 (2Н, t, J = 6.8, 5-СН2); 4.38 (2Н, s,
13
2-СН2). C NMR spectrum, δ, ppm: 13.6 (СH3); 18.4 (С≡ССН2СН2); 21.9 (СН2СН3); 30.8 (СН2СН2СН3); 42.8
(NCH2C≡C); 51.3 (С-4); 63.6 (С-5); 75.9 (NCH2C≡C); 84.5 (NCH2C≡C); 85.9 (С-2). Mass spectrum, m/z (Irel, %):
166 [M-Н]+ (100), 137 [M-Н-C2Н5]+ (22), 110 [M-C4Н9]+ (31), 72 [C2H4NCH2O]+ (33). Found, %: С 71.89;
Н 10.17; N 8.35. С10Н17NО. Calculated, %: С 71.81; Н 10.25; N 8.37.
3-(3-Phenylprop-2-yn-1-yl)-1,3-oxazolidine (4c). Yield 0.15 g (81%), соlorless oil, nD 1.3657 (at
1
28C), Rf 0.23 (2:2:1 hexane–CH2Cl2–EtOAc). H NMR spectrum, δ, ppm (J, Hz): 3.05 (2Н, t, J = 6.8, 4-СН2);
3.54-3.57 (2Н, m, NCH2C≡C); 3.76 (2Н, t, J = 6.8, 5-СН2); 4.36-4.40 (2Н, m, 2-СН2); 7.22-7.25 (3Н, m, H Ph);
7.37-7.41 (2Н, m, H Ph). 13C NMR spectrum, δ, ppm: 43.2 (NCH2C≡C); 51.4 (С-4); 63.7 (С-5); 84.0
730

(NCH2C≡C); 85.6 (NCH2C≡C); 86.0 (С-2); 122.9 (C Ph); 128.2 (C Ph); 128.3 (C Ph); 131.7 (C Ph). Mass
spectrum, m/z (Irel, %): 186 [M-Н]+ (42), 156 [M-CH2О]+ (81), 115 [PhC≡CCH2]+ (100), 102 [PhC≡CH]+ (17),
89 [CPh]+ (64). Found, %: С 76.91; Н 7.06; N 7.55. С12Н13NО. Calculated, %: С 76.98; Н 7.00; N 7.48.
3-(Hex-2-yn-1-yl)-5-methyl-1,3-oxazolidine (5a). Yield 0.09 g (45%), light-yellow transparent oil,
Rf 0.40 (2:1 hexane–EtOAc). IR spectrum, ν, сm-1: 1076 (C–O–C), 1457 (CH2), 2250 (C≡C), 2932 (CH2).
1H NMR spectrum, δ, ppm (J, Hz): 0.91-0.94 (3Н, m, CH2CH2СН3); 1.15-1.21 (3Н, m, 5-СН3); 1.43-1.49 (2Н,
m, СН2СН2СН3); 2.11-2.12 (2Н, m, СН2СН2СН3); 2.44-2.48 (1Н, m) and 3.11-3.16 (1Н, m, 4-СН2); 3.33 (2Н,
13
d, J = 2.0, NCH2C≡C); 4.08-4.12 (1Н, m, 5-СН); 4.33 (2Н, d, J = 2.4, 2-СН2). C NMR spectrum, δ, ppm: 13.4
(CH2CH2СH3); 19.9 (5-СН3); 20.6 (СН2СН2СН3); 22.1 (СН2СН2СН3); 42.8 (NCH2C≡C); 58.2 (С-4); 71.8 (С-5);
75.9 (NCH2C≡C); 84.5 (NCH2C≡C); 85.2 (С-2). Mass spectrum, m/z (Irel, %): 166 [M-Н]+ (37), 123 [M-Н-C3H7]+
(100), 95 [NCH2С≡CC3Н7]+ (63). Found, %: С 71.77; Н 10.32; N 8.42. С10Н17NО. Calculated, %: С 71.81;
Н 10.25; N 8.37.
3-(Hept-2-yn-1-yl)-5-methyl-1,3-oxazolidine (5b). Yield 0.14 g (70%), light-yellow oil, Rf 0.38 (2:1
1
hexane–EtOAc). H NMR spectrum, δ, ppm (J, Hz): 0.83 (3Н, t, J = 7.2, СН2СН3); 1.17-1.19 (3Н, m, 5-СН3);
1.30-1.35 (2Н, m, СН2СН2СН3); 1.37-1.40 (2Н, m, СН2СН2СН3); 2.12 (2Н, m, С≡ССН2СН2); 2.42-2.47 (1Н,
m) and 3.09-3.16 (1Н, m, 4-СН2); 3.30-3.31 (2Н, m, NCH2C≡C); 4.01-4.10 (1Н, m, 5-СН); 4.31-4.32 (2Н, m,
2-СН2). 13C NMR spectrum, δ, ppm: 13.5 (СН2СH3); 18.3 (5-СН3); 19.9 (С≡ССН2СН2); 21.8 (СН2СН3); 30.7
(СН2СН2СН3); 42.8 (NCH2C≡C); 58.2 (С-4); 71.8 (С-5); 76.7 (NCH2C≡C); 84.4 (NCH2C≡C); 85.2 (С-2). Mass
spectrum, m/z (Irel, %): 180 [M-Н]+ (45), 137 [M-Н-C3H7]+ (53), 95 [CH2С≡CC4Н9]+ (100). Found, %: С 72.79;
Н 10.61; N 7.78. С11Н19NО. Calculated, %: С 72.88; Н 10.56; N 7.73.
5-Methyl-3-(3-phenylprop-2-yn-1-yl)-1,3-oxazolidine (5c). Yield 0.06 g (28%), light-yellow oil,
1
Rf 0.45 (2:1 hexane–EtOAc). H NMR spectrum, δ, ppm (J, Hz): 1.29 (3Н, d, J = 6.0, СН3); 2.61 (1Н, dd,
J = 12.0, J = 7.2) and 3.27 (1Н, dd, J = 12.0, J = 7.2, 4-СН2); 3.65 (2Н, s, NCH2C≡C); 4.21 (1Н, m, 5-СН);
4.48 (2Н, s, 2-СН2); 7.30-7.31 (3Н, m, H Ph); 7.52-7.55 (2Н, m, H Ph). 13C NMR spectrum, δ, ppm: 20.1
(СН3); 43.4 (NCH2C≡C); 58.4 (С-4); 72.0 (С-5); 84.2 (NCH2C≡C); 85.3 (NCH2C≡C); 85.4 (С-2); 122.9 (C Ph);
128.3 (C Ph); 131.7 (C Ph); 132.2 (C Ph). Mass spectrum, m/z (Irel, %): 200 [M-Н]+ (8), 157 [M-CH3СНО]+
(29), 115 [PhC≡CCH2]+ (100). Found, %: С 77.52; Н 7.45; N 7.02. С13Н15NО. Calculated, %: С 77.58; Н 7.51;
N 6.96.
(4R)-4-Ethyl-3-(hex-2-yn-1-yl)-1,3-oxazolidine (6a). Yield 0.13g (72%), light-yellow oil, Rf 0.56 (2:1
21
1
hexane–EtOAc), [α]D -7.8 (c 0.40, CHCl3). H NMR spectrum, δ, ppm (J, Hz): 0.96 (3Н, t, J = 7.5,
4-СН2СН3); 0.99 (3Н, t, J = 7.5, СН2СН2СН3); 1.41 (1Н, quin, J = 7.0) and 1.64 (1Н, quin, J = 7.0, 4-CH2СН3);
1.54-1.56 (2Н, m, СН2CH2СН3); 2.18 (2Н, t, J = 7.0, CH2CH2СН3); 2.99 (1Н, quin, J = 7.0, 4-СН); 3.40-3.43
13
(1Н, m) and 4.06 (1Н, t, J = 7.5, 5-СН2); 3.43 (2Н, s, NCH2C≡C); 4.44 (2Н, s, 2-СН2). C NMR spectrum, δ,
ppm: 11.0 (4-СН2СН3); 13.5 (СН2СН2СН3); 20.7 (CH2CH2СН3); 22.2 (CH2CH2СН3); 25.9 (4-CH2СН3); 42.5
(NCH2C≡C); 63.8 (С-4); 70.3 (С-5); 76.9 (NCH2C≡C); 85.0 (NCH2C≡C); 85.3 (С-2). Mass spectrum, m/z (Irel,
%): 180 [M-Н]+ (38), 152 [M-C2Н5]+ (100), 124 [M-C4Н9]+ (45). Found, %: С 72.95; Н 10.61; N 7.66.
С11Н19NО. Calculated, %: С 72.88; Н 10.56; N 7.73.
(4R)-4-Ethyl-3-(hept-2-yn-1-yl)-1,3-oxazolidine (6b). Yield 0.17 g (83%), dark-yellow oil, Rf 0.50
20
1
(2:1 hexane–EtOAc). [α]D -7.3 (c 2.39, CHCl3). H NMR spectrum, δ, ppm (J, Hz): 0.90 (3H, t, J = 7.5,
CH2CH2CH3); 0.94 (3H, t, J = 7.5, 4-CH2CH3); 1.31-1.37 (1H, m) and 1.57-1.64 (1H, m, 4-CH2CH3); 1.38-1.44
(2H, m, CH2CH2CH3); 1.45-1.51 (2H, m, CH2CH2CH3); 2.18 (2H, t, J = 7.0, C≡CCH2CH2); 2.94 (1H, q,
J = 7.0, 4-CH); 3.36-3.39 (1H, m) and 4.02 (1H, t, J = 7.5, 5-CH2); 3.37 (2H, s, NCH2C≡C); 4.40 (2H, s,
2-CH2). 13C NMR spectrum, δ, ppm: 10.9 (4-CH2CH3); 13.6 (CH2CH2CH3); 18.4 (C≡CCH2CH2); 21.9
(CH2CH2CH3); 26.1 (4-CH2CH3); 30.8 (CH2CH2CH3); 42.5 (NCH2C≡C); 63.7(C-4); 70.2 (C-5); 75.8
(NCH2C≡C); 84.4 (NCH2C≡C); 85.4 (C-2). 15N NMR spectrum, δ, ppm: 65.1. Mass spectrum, m/z (Irel, %): 194
[M-H]+ (6), 166 [M-C2H5]+ (100), 138 [M-C4H9]+ (50). Found, %: C 73.87; H 10.79; N 7.24. C12H21NO.
Calculated, %: C 73.80; H 10.84; N 7.17.
731

(4R)-4-Ethyl-3-(3-phenylprop-2-yn-1-yl)-1,3-oxazolidine (6c). Yield 0.05 g (24%), light-yellow oil,
18
1
Rf 0.53 (2:1 hexane–EtOAc), [α]D -2.3 (c 1.01, CHCl3). H NMR spectrum, δ, ppm (J, Hz): 1.01 (3Н, t,
J = 7.5, СН2СН3); 1.41-1.49 (1Н, m) and 1.64-1.73 (1Н, m, CH2СН3); 3.09 (1Н, quin, J = 7.0, 4-СН); 3.45 (1Н,
t, J = 7.5) and 4.12 (1Н, t, J = 7.5, 5-СН2); 3.69 (2Н, s, NCH2C≡C); 4.50 (1Н, d, J = 5.3) and 4.53 (1Н, d,
J = 5.3, 2-СН2); 7.32-7.33 (3Н, m, H Ph); 7.44-7.46 (2Н, m, H Ph). 13C NMR spectrum, δ, ppm: 11.0
(СН2СН3); 26.1 (CH2СН3); 43.0 (NCH2C≡C); 64.0 (C-4); 70.4 (C-5); 84.0 (NCH2С≡С); 84.5 (NCH2С≡С); 85.5
(C-2); 122.9 (C Ph); 128.2 (C Ph); 128.3 (C Ph); 131.7 (C Ph). 15N NMR spectrum, δ, ppm: 65.1. Mass
spectrum, m/z (Irel, %): 214 [M-Н]+ (55), 186 [M-CHСН3]+ (100), 115 [PhC≡CCH2]+ (100). Found, %: С 78.18;
Н 7.91; N 6.56. С14Н17NО. Calculated, %: С 78.10; Н 7.96; N 6.51.
5-Phenyl-3-(3-phenylprop-2-yn-1-yl)-1,3-oxazolidine (7). Yield 0.09 g (60%), light-yellow oil,
1
Rf 0.50 (2:1:2 hexane–CCl4–EtOAc). H NMR spectrum, δ, ppm (J, Hz): 2.41 (1Н, s) and 2.96-3.02 (1Н, m,
4-СН2); 3.77 (2Н, s, NCH2C≡C); 4.77 (2Н, m, 2-СН2); 5.13 (1Н, t, J = 7.2, 5-СН); 7.22-7.52 (10Н, m, H Ph).
13C NMR spectrum, δ, ppm: 43.5 (NCH2C≡C); 61.4 (С-4); 77.4 (С-5); 83.4 (NCH2C≡C); 85.3 (NCH2C≡C);
86.9 (С-2); 122.9 (С Ph); 125.6 (С Ph); 127.2 (C Ph); 127.3 (C Ph); 128.1 (C Ph); 131.8 (C Ph); 141.8 (C Ph).
Mass spectrum (EI), m/z (Irel, %): 263 [M]+ (65), 115 [PhC≡CCH2]+ (100), 104 [PhCНCH2]+ (100). Mass
spectrum (MALDI–TOF/TOF), m/z: 264.318 [M+Н]+. Found, %: С 82.03; Н 6.56; N 5.28. С18Н17NО.
Calculated, %: С 82.10; Н 6.51; N 5.32.
3-(Deca-2,9-diyn-1-yl)-1,3-oxazolane (8) was prepared by the described method [26, 27] from a
mixture of bis(1,3-oxazolidin-3-yl)methane (2a) (0.32 g, 2 mmol) and 3,8-dioxa-1,6-diazabicyclo[4.4.1]unde-
cane (3a), 1,8-nonadiyne (0.12 g, 1 mmol), and CuCl (5 mg, 0.05 mmol) in PhMe (3 ml). The reaction mixture
was stirred in an atmosphere of argon at 80C for 6h, the catalyst was then separated, the solvent was
evaporated, and the product was purified by column chromatography. Yield 0.10 g (33%), light-yellow oil.
1H NMR spectrum, δ, ppm (J, Hz): 1.41-1.54 (6Н, m, CH2(CH2)3CH2C≡CН); 1.95 (1Н, t, J = 2.6, C≡CН);
2.18-2.21 (4Н, m, CH2(CH2)3CH2C≡CН); 3.07 (2Н, t, J = 6.8, 4-СН2); 3.35-3.37 (2Н, m, NCH2C≡C); 3.80 (2Н,
t, J = 6.8, 5-СН2); 4.37 (2Н, s, 2-СН2). 13C NMR spectrum, δ, ppm: 18.3 (СH2C≡CH); 18.6 (NCH2С≡CCH2);
27.9 ((СH2)2CH2(CH2)2); 28.0 (NCH2С≡CCH2CH2); 28.2 (СH2СH2C≡CH); 42.8 (NCH2C≡C); 51.2 (C-4); 63.6
(C-5); 68.3 (C≡CН); 76.1 (NCH2C≡C); 84.2 (C≡CН); 85.1 (C-2); 85.9 (NCH2C≡C). Mass spectrum (EI,
70 eV), m/z (Irel, %): 204 [M-Н]+ (28), 119 [C≡C(CH2)5C≡CН]+ (23), 72 [NC3H6O]+ (100). Mass spectrum
(MALDI–TOF/TOF), m/z: 206.445 [M+Н]+. Found, %: С 75.98; Н 9.30; N 6.87. С13Н19NО. Calculated, %:
С 76.06; Н 9.33; N 6.82.
This work was supported by the Federal Agency for Science and Innovation (grant from the President of
the Russian Federation NSh02136.2014.3), the Russian Foundation for Basic Research (projects 14-03-00240-a,
13-03-12027ofi_m, and 14-03-97032-p_Povolzh'e_a), and the Government of the Russian Federation (stipends
from the President of the Russian Federation for young scientists and aspirants (SP-2161.2012.4)).
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