Aromatization of 2,2,5-trialkyl-substituted 2,5-dihydrofurans and factors affecting their stabilization

Article abstract of DOI:10.1007/s10593-018-2277-z

[Figure not available: see fulltext.] We demonstrate that the synthesis of 5-methoxy-2,2,5-trialkyl-substituted 2,5-dihydrofurans containing unprotected hydroxymethyl group at the C-2 position involves aromatization via fragmentation involving С–С bond cleavage, resulting in the formation of 2,5-disubstituted furans and carbonyl compounds. 2,5-Dihydrofurans bearing an ester group at the С-2 position were stable. It was found that 2,2,5-trialkyl-substituted 2,5-dihydrofurans containing a hydroxymethyl or carbonyl group in the side chain could aromatize through auto-oxidation, which was facilitated by adjacent functional groups (sulfo- or pivaloyl groups).

Full text of DOI:10.1007/s10593-018-2277-z

DOI 10.1007/s10593-018-2277-z
Chemistry of Heterocyclic Compounds 2018, 54(4), 403–410
Aromatization of 2,2,5-trialkyl-substituted 2,5-dihydrofurans
and factors affecting their stabilization
Bulat T. Sharipov1*, Anna N. Davidova1, Farid A. Valeev1
1 Ufa Institute of Chemistry, Ufa Research Center of the Russian Academy of Sciences,
71 Oktyabrya Ave., Ufa 450054, Russia; e-mail: sinvmet@anrb.ru
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2018, 54(4), 403–410
Submitted January 25, 2018
Accepted May 13, 2018
We demonstrate that the synthesis of 5-methoxy-2,2,5-trialkyl-substituted 2,5-dihydrofurans containing unprotected hydroxymethyl
group at the C-2 position involves aromatization via fragmentation involving С–С bond cleavage, resulting in the formation of
2,5-disubstituted furans and carbonyl compounds. 2,5-Dihydrofurans bearing an ester group at the С-2 position were stable. It was found
that 2,2,5-trialkyl-substituted 2,5-dihydrofurans containing a hydroxymethyl or carbonyl group in the side chain could aromatize through
auto-oxidation, which was facilitated by adjacent functional groups (sulfo- or pivaloyl groups).
Keywords: 2,5-dihydrofurans, 2,5-disubstituted furans, aromatization, auto-oxidation, fragmentation.
Marine organisms offer a rich source of terpenoids that
exhibit a broad range of specific biological effects, as well
as contain unique molecular structures. A remarkable
example of eunicellane type metabolites isolated from soft
corals of Eleutherobia genus is the diterpenoid
eleutherobin (1),1a which has become a progenitor for a
whole class of eleuthesides that can be considered to
include also the sarcodictyines A (2) and B (3) (Fig. 1).1b
The biological properties of eleutherobin were studied in
vitro, revealing cytotoxic activity, mechanistically related
to that of the well-known anticancer drug taxol, against cell
cultures of breast, kidney, ovarian, and lung cancer.2 Those
studies indicated that eleutherobin is a potent inhibitor of
cancer cells with IC50 values of 10–15 nM. It is also
important to note that eleutherobin was shown to compete
with taxol as an agent stabilizing microtubule poly-
merization. The selective action of eleutherobin on
malignant tumors was determined using a panel of 60
cancer cell types. The toxic properties were shown to
exceed the average cytotoxicity by one hundred times.2
One of the issues to be solved during the synthesis of
eleuthesides is the construction of 2,5-dihydrofuran nucleus
by introducing an oxygen bridge between the C-4 and C-7
atoms of the 10-membered ring3 or by an alternate
intramolecular cyclization in a 10-membered ring of pre-
cursors already containing the С ring (Fig. 1).4 The
complications arising in that case are characteristic for the
synthesis of many natural compounds containing a
2,5-dihydrofuran ring in their molecules.4b,5
In the previous work6 we accomplished the synthesis of
compound 4 containing the С ring of eleuthesides. The
attempt to hydrolyze the pivaloyl group in ester 4 to
alcohol 5 was accompanied by aromatization and formation
of furan 6 in 82% yield (Scheme 1). The hydrolysis of
acetate 7 proceeded along analogous route, leading to the
formation of furan 9 through elimination of hydroxymethyl
group in the intermediate 8.
Figure 1. Diterpenoids isolated from marine organisms:
eleutherobine 1 and sarcodictyins А (2) and B (3).
0009-3122/18/54(4)-0403©2018 Springer Science+Business Media, LLC
403

Chemistry of Heterocyclic Compounds 2018, 54(4), 403–410
Scheme 1
PivO
to functionalized trialkyl-substituted 2,5-dihydrofurans was
found by treatment of alcohol 13 with СH2(CH2SH)2.10
This alcohol can be obtained by methylation of
levoglucosenone (12) with methyl-magnesium iodide.6 The
use of BF3·Et2O, TiCl4, SnCl4, ZnCl2, p-TsOH, CF3SO3H,
or 70% HClO4 as catalysts resulted in moderate yields of
product 14 that did not exceed 29%. The best results were
obtained by using TMSOTf in СH2Cl2. The yields of
dithiane 14 deteriorated when the dilution was insufficient
or excessive. The best result achieved with TMSOTf was
49% yield at 0.1 M concentration of substrate, while the
yield was only 39% in the absence of solvent. The
application of TВSOTf as a milder reagent allowed to
obtain the dithiane 14 in 54% yield. (Scheme 4).
HO
t-BuO2C
82%
Me
Me
MeONa
O
Me
O
O
MeOH
rt, 12 h
6
t-BuO2C
t-BuO2C
4
5
AcO
Me
HO
Me
MeONa
O
Me
O
MeO
O
MeO
TrO
70%
MeOH
rt, 3 h
9
TrO
7
TrO
8
Scheme 4
During an earlier synthesis of eleutheside – an analog of
sarcodictyin А – we also found that the hydrolysis of
acetate group in compound 10 was accompanied by
aromatization with the formation of furan 11 (Scheme 2).7
A similar process occurred upon alkaline hydrolysis of
sarcodictyin С8 during attempted synthesis of
eleutherobin.5 The analogous result obtained in simpler
cases points to the fact that 5-methoxy-2,2,5-trialkyl-
substituted 2,5-dihydrofurans containing a free hydroxy
group at the α-position tend to readily undergo aromatization
under alkaline conditions, which is accompanied by С–С bond
cleavage. It should be noted that trialkyl-substituted
2,5-dihydrofurans can be obtained under mildly basic
conditions, even though there is a lack of data in those
studies about their stability.3,9
The molecular structure of alcohol 14 was determined
on the basis of its Н and 13С NMR spectra. The signals of
1
carbon atoms bearing hydrogen atoms in the structure of
compound 14 were assigned by considering the data from
1H–1H COSY and 1H–13С HSQC experiments. The
presence of 2,5-dihydrofuran ring was deduced from the
crosspeaks of 2-СH atom with methyl and thioacetal
Scheme 2
(СHS2) groups in H–13С HMBC spectra. The observed
1
NOE values between the methyl group protons and the
hydroxymethyl group protons in the structure of compound
14 pointed to 2S,5S-configuration, thus the methyl and
hydroxymethyl groups in the dihydrofuran ring were
deduced to be in a syn-relationship.
The primary hydroxy group in dithiane 14 was in one
example protected by reaction with pivaloyl chloride,
providing the ester 15. In another case, the dithiane 14 was
converted to bromide 16 by treatment with СBr4 in the
presence of PPh3 (Scheme 5). The removal of 1,3-dithiane
protective group and preparation of aldehydes 17 and 18
was achieved by treating the compounds 15 and 16 with
MeI in the presence of СаСО3.11 Aldehyde 17 was found to
be unstable and completely transformed into the furan 19
after keeping for one week. The storage of aldehyde 18 for
a weak did not produce detectable lebels of decomposition
products.
The preparation of hydroxy derivatives from aldehyde
18 was accomplished by the addition of 4-TBS-oxy-
butylmagnesium bromide 20. The reaction proceeded with
the formation of stable compounds – the secondary
alcohols 21a,b, accompanied by the hydroxymethyl
derivative 22 as a minor product. However, the alcohol 24,
obtained by hydrolysis of acetates 23a,b, underwent
The formation of type В furans apparently can be
explained by retro-aldol fragmentation, accompanied by
1,2-shift of double bond after the initial deprotonation of
the free hydroxy group in compound А. The formed
alkoxide ion was converted into stable products – furan В and
aldehyde С through a mechanism consisting of С(2)–С(6)
bond cleavage, 1,2-shift of double bond, and elimination of
methoxide anion (Scheme 3).
Scheme 3
Me MeO–
MeO
O
– MeOH
– MeO–
O
2
R1
Me
R2
+
6
O
O
R1
5
H
C
R2
B
A
Our further efforts were aimed at studying the possi-
bilities for С–С bond cleavage and the stability of similar
structures, in order to identify 2,5-dihydrofurans that may
be more stable towards aromatization. A short route leading
404

Chemistry of Heterocyclic Compounds 2018, 54(4), 403–410
Scheme 5
Keeping for
1 week at rt
Me
PivO
PivO
O
Me3CCOCl, Py
MeI, CaCO3
Me
PivO
O
S
S
O
Me
63%
0°C, 30 min
74%
MeCN, H2O
rt, 72 h
Me
HO
CHO
O
S
S
15
17
19
70%
S
14
Me
Br
O
CBr4, PPh3
MeI, CaCO3
Me
Br
O
CH2Cl2, 40°C, 4 h
78%
MeCN, H2O
74%
CHO
S
16
18
Scheme 6
fragmentation to furan 25 and aldehyde 26 during
separation on silica gel column (Scheme 6).
In order to verify this interpretation, we performed a
series of experiments to study the effect of oxygen on
compounds 17 and 24. Thus, storing the aldehyde 17 in the
form of a thin film under air atmosphere resulted in its
complete decomposition to furan 19 over less than 24 h.
Complete fragmentation of aldehyde 17 could be also
achieved by bubbling of air through its toluene solution for
a week, while under argon atmosphere the aldehyde 17
remained unchanged for a long time, confirming the
occurrence of auto-oxidation. Analogous reactivity was
also observed in the case of dihydrofuran 24, therefore
compounds of this type must be kept under oxygen-free
conditions in order to avoid auto-oxidation and
aromatization.
Aromatization of 2,5-dihydrofurans 17 and 24
proceeded with the formation of analogous fragmentation
products as in the case of the aforementioned 2,5-
dihydrofurans 4, 7, 10. The only difference was that the
structures of compounds 7, 10 lacked a methoxy group at
the С-5 atom and fragmentation was not caused by reaction
with bases. Besides that, achieving complete destruction
required prolonged time, indicating another reaction
mechanism for the formation of furans.
It is quite likely that the limiting step in the first reaction
step leading to the aromatization of 2,5-dihydrofurans 17
and 24 was the oxidation of furan ring to the intermediate
product D by air oxygen (Scheme 7). The tendency of
similar furan structures to readily undergo oxidation with
air oxygen is well known.12 The intermediate product D
was further transformed into the furan 25 and aldehyde 26
by a retro-aldol fragmentation. The propensity of furans 17
and 24 for facile fragmentation, in contrast to the bromides
18, 21a,b, and 22, can be best explained by the influence of
adjacent functional groups (sulfo- and pivaloyl groups),
which are involved in hydrogen bonding with the proton at
the С-2 carbon atom, enabling easy oxidation of furans to
the intermediate product D.
The easy access to 2,2,5-trialkyl-substituted 2,5-dihydro-
furans containing an ester group at the position 2, as well as
the stability of such compounds was confirmed in a study
were 2,5-dihydrofurans bearing similar functional groups
were synthesized.13 In addition, we also converted the
aldehydes 17 and 18 to carboxy derivatives. The oxidation
of aldehydes 17 and 18 to carboxylic acids was achieved by
using NaClO2 and the obtained carboxylic acids were
converted without isolation into the respective methyl
esters 27 and 28. The alkyl bromide derivative 28 was used
for the incorporation of alkoxy substituent into the dihydro-
furan ring. Thus, refluxing of bromide 28 in benzene
solution in the presence of DBU allowed to obtain the
dehydrobromination product 29, which was further
oxidized with МCPBA in methanol, producing the methyl
ketals 30а,b (Scheme 8). All of the obtained esters 27, 28
and 30а,b were found to be quite stable compounds.
Scheme 7
It should be noted that the aromatization reaction
conditions for the obtained compounds were not systema-
tically explored. In any case, we cannot exclude the
405

Chemistry of Heterocyclic Compounds 2018, 54(4), 403–410
Scheme 8
possibility of aromatization for 2,5-dihydrofurans, which
under certain conditions were found to be stable. For
example, the products of [4+3] addition,14 Diels–Alder
adducts,15 and some other 2,5-dihydrofurans16 have been
shown to undergo С–С bond cleavage under various
conditions, leading to the formation of furans.
Thus, we have shown that 5-methoxy-2,2,5-trialkyl-
substituted 2,5-dihydrofurans containing an unprotected
hydroxy group at the α-position tend to undergo aromati-
zation by С–С bond cleavage, leading to the formation of
2,5-disubstituted furans and carbonyl compounds. Auto-
oxidation is possible in the case of 2,2,5-trialkyl-substituted
2,5-dihydrofurans, resulting in the formation of analogous
aromatization products.
t-Butyl 2-(5-methylfuran-2-yl)acetate (6). A solution
of ester 4 (0.57 g, 1.84 mmol) in MeOH (10 ml) was
cooled to 0°С and treated by the addition of MeONa
(0.30 g, 5.51 mmol). The reaction mixture was stirred at
room temperature for 12 h, then neutralized with AcOH,
diluted with EtOAc (30 ml), the precipitate was collected
by filtration and washed with EtOAc. The filtrate was
evaporated at reduced pressure, the residue was separated
by column chromatography, using petroleum ether –
EtOAc system with gradient from 100:1 to 25:1 as the
eluent. Yield 0.30 g (82%), oil, Rf 0.52 (hexane‒EtOAc,
50:1). IR spectrum, ν, cm‒1: 3108, 2981, 1736, 1642, 1565,
1477, 1393, 1244, 1147, 1048, 733. 1H NMR spectrum, δ, ppm
(J, Hz): 1.48 (9Н, s, С(СН3)3); 2.28 (3Н, s, СН3); 3.53 (2Н,
s, СН2); 5.90 (1Н, d, J = 1.9. Н-4); 6.06 (1Н, d, J = 1.9,
Н-3). 13C NMR spectrum, δ, ppm: 13.5 (CH3); 28.0 (CH3);
35.4 (СH2); 81.1 (CCH3); 106.3 (C-4); 108.3 (C-3); 149.4
(C-5); 151.6 (C-2); 167.4 (CO). Mass spectrum, m/z (Irel, %):
196 [M]+ (100). Found, %: С 67.36; Н 8.25. С11Н16О3.
Calculated, %: С 67.32; Н 8.22.
Experimental
IR spectra were recorded on Shimadzu IRPrestige-21 or
Bruker Tensor 27 FT-IR spectrometers for samples
1
prepared as thin films or Nujol mulls. Н and 13С NMR
spectra were acquired on a Bruker AM-300 spectrometer
(300 and 75 MHz, respectively, compounds 6, 17) and
Bruker Avance III 500 MHz spectrometer (500 and 125
MHz, respectively, compounds 15, 16, 18, 19, 21a,b, 22,
23a,b, 27, 28) in CDCl3 (the use of other solvents is
indicated in each specific case). Residual solvent signals
2-Methyl-5-(trityloxymethyl)furan (9) was obtained
analogously from acetate 7 (0.30 g, 1.51 mmol) and
MeONa (0.163 g, 3.02 mmol). The reaction mixture was
stirred at room temperature for 3 h. Yield 0.16 g (70%), oil,
Rf 0.52 (hexane–EtOAc, 50:1). IR spectrum, ν, cm‒1: 2975,
1
1
1
were used as internal standards. H–1H COSY, H–1H
2855, 1445, 1155, 1041, 770. H NMR spectrum, δ, ppm
1
1
NOESY, H–13C HMBC, and H–13C HSQC experiments
were performed on a Bruker Avance III 500 MHz
instrument (compounds 11, 14, 30a, 30b). Mass spectra
were recorded on a Shimadzu LCMS-2010 EV single
quadrupole system in positive and negative ion modes at
capillary voltages of 4.5 and –3.5 kV, respectively,
electrospray ionization, eluent MeCN–Н2О. A sample of
compound 18 was prepared in СHCl3. Elemental analysis
was performed on a Eurovector EuroEA2000 automatic
СНNS(O)-analyzer. Bromine content was determined
quantitatively by the Schoeniger method, while silicon was
determined according to the methodology of Gelman.17 The
specific optical rotation was measured on a PerkinElmer
341 polarimeter. Melting points were determined on a
Boetius apparatus using RNMK-05 visual observation
adapter. Sorbfil PTSKh-AF-A plates (Sorbpolymer,
Krasnodar, Russia) were used for TLC analysis. Macherey–
Nagel silica gel 60 (0.063–0.2 mm particle size) was used
for column chromatography.
(J, Hz): 2.31 (3Н, s, С(СН3)3); 4.02 (2Н, s, СН2О); 5.92
(1Н, d, J = 2.8, Н-3); 6.13 (1Н, d, J = 2.8, Н-4); 7.10–7.70
(15Н, m, H Ph). 13C NMR spectrum, δ, ppm: 13.5 (CH3);
56.4 (СH2); 87.0 (CPh3); 107.5 (C-3); 108.2 (C-4); 127.2,
127.8, 128.7, 143.6 (С Ph); 141.3 (C-2); 159.3 (C-5). Mass
spectrum, m/z (Irel, %): 354 [M]– (100). Found, %: С 84.69;
Н 6.27. С25Н22О2. Calculated, %: С 84.72; Н 6.26.
2-{(1R,5R,6S)-6-[(Z)-3-(t-Butyldimethylsilyloxy)-
2-(5-methylfuran-2-yl)prop-1-enyl]-5-methylcyclohex-
3-enyl}acetaldehyde (11) was obtained analogously from
acetate 10 (0.030 g, 0.065 mmol) and MeONa (0.007 g,
(0.13 mmol). The reaction mixture was stirred at room
temperature for 5 h. Yield 0.019 g (74%), oil, [α]D20 ‒26.9°
(c 0.5, CHCl3), Rf 0.52 (hexane–EtOAc, 10:1). IR spectrum,
ν, cm‒1: 2928, 1726, 1361, 1254, 1133, 1047, 837, 776.
1H NMR spectrum (C6D6), δ, ppm (J, Hz): 0.03 (6Н, s,
СН3); 0.93 (3Н, d, J = 7.5, СН3); 0.95 (9Н, s, С(СН3)3);
1.69–1.76 (2H, m, 2-CH2); 1.79 (1H, ddd, J = 17.7, J = 5.5,
J = 1.0, CH2СHO); 2.05 (3Н, s, СН3); 2.30 (1H, ddd,
406

Chemistry of Heterocyclic Compounds 2018, 54(4), 403–410
J = 17.7, J = 8.3, J =1.0, CH2СHO); 2.39–2.47 (1Н, m, 1-CН);
s, СН3); 1.72–1.82 (1Н, m, 5'-CН2); 1.97–2.05 (1Н, m,
5'-СН2); 2.78–2.84 (4Н, m, 4',6'-СН2); 3.94 (1Н, dd,
J = 11.7, J = 3.7, СН2О); 4.22 (1Н, s, 2'-СН); 4.23 (1Н,
dd, J = 11.7, J = 3.5, СН2О); 5.01–5.07 (1Н, m, 2-СН
Fur); 5.77 (1Н, d, J = 5.9, Н-4 Fur); 5.86 (1Н, dd, J = 5.9,
J = 2.2, Н-3 Fur). 13C NMR spectrum, δ, ppm: 25.3 (CH3);
25.7 (C-5'); 27.2 (CH3); 30.3, 30.7 (C-4',6'); 38.7 (C(CH3)3);
58.3 (C-2'); 65.3 (СH2О); 85.1 (C-2); 92.1 (C-5); 127.5
(C-4); 132.9 (C-3); 178.3 (CO). Mass spectrum, m/z (Irel, %):
317.10 [M+H]+ (100). Found, %: С 56.97; Н 7.60; S 20.18.
С15Н24О3S2. Calculated, %: С 56.93; Н 7.64; S 20.26.
2.48–2.55 (1Н, m, 5-CН); 3.51 (1H, dt, J = 11.7, J = 3.6,
6-CH); 4.38 (1H, dd, J = 13.2, J = 1.5, 3'-CH2); 4.41 (1H,
dd, J = 13.2, J = 1.5, 3'-CH2); 5.41 (1H, d, J = 9.9, 4-CH);
5.60 (1H, ddd, J = 9.9, J = 4.8, J = 2.6, 3-CH); 5.70 (1H, d,
J = 11.7, 1'-CH); 5.78 (1H, dt, J = 3.2, J = 1.0, H-4 Fur);
6.16 (1H, d, J = 3.2, H-3 Fur); 9.34 (1H, s, CHO).
13C NMR spectrum (C6D6), δ, ppm: –5.5 (CH3); –5.5 (CH3);
13.1 (CH3); 18.1 (С(CH3)3); 18.7 (CH3); 25.7 (CH3); 28.2
(C-2); 32.9 (C-1); 35.0 (C-5); 39.7 (C-6); 48.1 (CH2СHO);
65.1 (C-3'); 106.8 (С-4 Fur); 109.0 (С-3 Fur); 123.4 (C-1');
125.3 (C-3); 128.0 (C-2'); 131.7 (C-4); 132.1 (С-5 Fur);
151.0 (С-2 Fur); 200.1 (CO). Mass spectrum, m/z (Irel, %):
388 [M]+ (100). Found, %: С 71.13; Н 9.33; Si 7.20.
С23Н36О3Si. Calculated, %: С 71.09; Н 9.34; Si 7.23.
[(2S,5S)-5-(1,3-Dithian-2-yl)-5-methyl-2,5-dihydro-
furan-2-yl]methanol (14). Method I. A solution of alcohol
13 (4.30 g, 30.3 mmol) in CH2Cl2 (300 ml) was cooled to
‒10°С and treated by dropwise addition of 1,3-propanedithiol
(9.2 ml, 90.8 mmol) and TMSOTf (5.5 ml, 30.3 mmol).
The reaction mixture was heated to room temperature and
stirred for 1 h, then diluted with MeOH (100 ml) and left
overnight at the same temperature. The mixture was further
treated with Et3N (8.5 ml, 60.5 mmol). The solvent was
removed by evaporation at reduced pressure, the residue
was separated by column chromatography, using petroleum
ether – EtOAc system with gradient from 3:1 to 1:1 as
eluent.
(2S,5S)-5-(Bromomethyl)-2-(1,3-dithian-2-yl)-2-methyl-
2,5-dihydrofuran (16). A solution of alcohol 14 (1.90 g,
8.18 mmol) and CBr4 (2.85 g, 8.59 mmol) in СH2Cl2
(50 ml) was stirred and treated by the addition of PPh3
(2.36 g, 9.00 mmol). The reaction mixture was then stirred
at 40°С for 4 h. The solvent was evaporated at reduced
pressure, the dry residue was treated with Et2O (50 ml), the
solids were collected by filtration and washed with Et2O.
The filtrate was evaporated at reduced pressure, the residue
was separated by column chromatography, using petroleum
ether – EtOAc system with gradient from 10:1 to 5:1 as
eluent. Yield 1.88 g (78%), yellowish crystals, mp 86–88°С,
20
[α]D ‒124.8° (c 1.0, CHCl3), Rf 0.24 (hexane–EtOAc,
10:1). IR spectrum, ν, cm‒1: 2927, 1445, 1083, 743.
1H NMR spectrum, δ, ppm (J, Hz): 1.54 (3Н, s, СН3); 1.78–
1.88 (1Н, m, 5'-СН2); 2.07 (1Н, dd, J = 14.1, J = 3.6,
5'-СН2); 2.83–2.89 (4Н, m, 4',6'-СН2); 3.32 (1Н, dd,
J = 10.2, J = 6.6, СН2Br); 3.48 (1Н, dd, J = 10.2, J = 4.0,
СН2Br); 4.26 (1Н, s, 2'-СН); 5.13–5.16 (1Н, m, 5-СН Fur);
5.94 (1Н, dd, J = 6.1, J =0.9, Н-3 Fur); 5.97 (1Н, dd,
J = 6.1, J = 2.0, Н-4 Fur). 13C NMR spectrum, δ, ppm:
25.5 (CH3); 25.7 (C-5'); 30.4, 30.7 (C-4',6'); 35.1 (СH2Br);
58.2 (C-2'); 85.7 (C-5); 92.9 (C-2); 128.7 (C-4); 133.4
(C-3). Mass spectrum, m/z (Irel, %): 295 [M(79Br)+H]+
(100), 297 [M(81Br)+H]+ (100). Found, %: С 40.73;
Н 5.08; Br 27.00; S 21.68. C10H15BrOS2. Calculated, %:
С 40.68; Н 5.12; Br 27.06; S 21.72.
Method II. TВSOTf (6.9 ml, 30.3 mmol) was used
instead of TMSOTf. Yield 3.4 g (49%, Method I), 3.8 g
20
(54%, Method II), oil, [α]D ‒102.8° (c 1.0, CHCl3),
Rf 0.32 (hexane–EtOAc, 1:1). IR spectrum, ν, cm‒1: 2973,
1734, 1445, 1173, 1042, 935, 789. 1H NMR spectrum, δ, ppm
(J, Hz): 1.51 (3Н, s, СН3); 1.76–1.88 (1Н, m, 5'-СН2); 2.03–
2.09 (1Н, m, 5'-СН2); 2.84–2.88 (4Н, m, 4',6'-СН2); 3.54
(1Н, dd, J = 11.8, J = 4.8, СН2О); 3.70 (1Н, dd, J = 11.8,
J = 3.4, СН2О); 4.28 (1Н, s, 2'-СН); 4.99–5.03 (1Н, m,
2-СН); 5.83 (1Н, dd, J = 6.1, J = 1.3, Н-4 Fur); 5.93 (1Н,
dd, J = 6.1, J = 2.3, Н-3 Fur). 13C NMR spectrum, δ, ppm:
25.8 (C-5', CH3); 30.5, 30.8 (C-4',6'); 58.4 (C-2'); 64.9
(СH2О); 87.8 (C-2); 92.1 (C-5); 127.8 (C-4); 133.2 (C-3).
Mass spectrum, m/z (Irel, %): 232 [M]+ (100). Found, %:
С 51.69; Н 6.99; S 27.51. С10Н16О2S2. Calculated, %:
С 51.69; Н 6.94; S 27.60.
[(2S,5S)-5-Methyl-5-formyl-2,5-dihydrofuran-2-yl]methyl-
2,2-dimethylpropanoate (17). A solution of 2,2-di-
methylpropanoate 15 (3.90 g, 12.3 mmol) in 5:1 mixture of
MeCN–H2O (40 ml) was treated with CaCO3 (3.7 g,
36.9 mmol) and MeI (15.4 ml, 0.25 mol). The reaction
mixture was stirred at room temperature for 72 h and then
treated with saturated NaCl solution. The reaction products
were extracted with EtOAc, the extract was dried over
anhydrous MgSO4, evaporated at reduced pressure, the
residue was separated by column chromatography, using
petroleum ether – EtOAc system with gradient from 10:1 to
[(2S,5S)-5-(1,3-Dithian-2-yl)-5-methyl-2,5-dihydro-
furan-2-yl]methyl-2,2-dimethylpropanoate (15). A solution
of dithiane 14 (1.35 g, 5.81 mmol) in pyridine (15 ml) was
cooled to 0°С and treated by dropwise addition of
Me3CCOCl (1.43 ml, 11.63 mmol). The mixture was
stirred at room temperature for 30 min, then diluted with
water. The reaction products were extracted with EtOAc,
the extract was dried over anhydrous MgSO4, evaporated at
reduced pressure, and the residue was separated by column
chromatography using petroleum ether – EtOAc system
with gradient from 10:1 to 3:1 as eluent. Yield 1.37 g (74%),
20
3:1 as eluent. Yield 1.9 g (70%), oil, [α]D ‒1.3° (c 1.0,
CHCl3), Rf 0.22 (hexane–EtOAc, 3:1). IR spectrum, ν, cm‒1:
2975, 1734, 1457, 1368, 1282, 1152, 1033, 963, 758.
1H NMR spectrum, δ, ppm (J, Hz): 1.20 (9Н, s, С(СН3)3);
1.42 (3Н, s, СН3); 4.08 (1Н, dd, J = 11.7, J = 3.6, СН2О);
4.28 (1Н, dd, J = 11.7, J = 4.2, СН2О); 5.13–5.23 (1Н, m,
2-СН Fur); 5.69 (1Н, dd, J = 5.8, J = 1.9, Н-3 Fur); 5.96
(1Н, d, J = 5.8, Н-4 Fur); 9.54 (1Н, s, CHO). 13C NMR
spectrum, δ, ppm: 21.1 (CH3); 27.2 (CH3); 38.8 (C(CH3)3);
65.3 (СH2О); 85.9 (C-2); 94.7 (C-5); 129.6, 130.2 (C-3,4);
20
white crystals, mp 65–67°С, [α]D ‒134.3° (c 1.0, CHCl3),
Rf 0.36 (hexane–EtOAc, 5:1). IR spectrum, ν, cm‒1: 2976,
1
2252, 1725, 1480, 1282, 1161, 1096, 910, 732. H NMR
spectrum, δ, ppm (J, Hz): 1.12 (9Н, s, C(СН3)3); 1.47 (3Н,
407

Chemistry of Heterocyclic Compounds 2018, 54(4), 403–410
178.4 (CO); 200.2 (CHO). Mass spectrum, m/z (Irel, %): 227
(С(CH3)3); 22.9 (С-3'); 24.2 (CH3); 25.9 (CH3); 31.7, 32.7
(С-2',4'); 35.7 (СН2Br); 63.1 (СH2О); 77.3 (С-1'); 85.5
(C-5); 94.4 (C-2); 128.4 (C-4); 132.8 (C-3). Mass
spectrum, m/z (Irel, %): 393 [M(79Br)+H]+ (100), 395
[M(81Br)+H]+ (100). Found, %: С 51.93; Н 8.40; Br 20.26;
Si 7.10. C17H33BrO3Si. Calculated, %: С 51.90; Н 8.45;
Br 20.31; Si 7.14.
[M+H]+ (100). Found, %: С 63.79; Н 7.98. С12Н18О4.
Calculated, %: С 63.70; Н 8.02.
(2S,5S)-5-(Bromomethyl)-2-methyl-2,5-dihydrofuran-
2-carbaldehyde (18) was obtained analogously from
bromide 16 (1.88 g). Yield 0.97 g (74%), oil, [α]D20‒554.2°
(c 1.0, CHCl3), Rf 0.28 (hexane–EtOAc, 3:1). IR spectrum,
ν, cm‒1: 2931, 1732, 1346, 1087, 1019, 732. H NMR
Compound 21b. Yield 1.40 g (73%), oil, [α]D20 ‒102.3°
1
1
spectrum, δ, ppm (J, Hz): 1.45 (3Н, s, СН3); 3.40 (1Н, dd,
J = 10.4, J = 6.0, СН2Br); 3.50 (1Н, dd, J = 10.4, J = 4.5,
СН2Br); 5.22–5.28 (1Н, m, 5-СН); 5.76 (1Н, dd, J = 6.0,
J = 2.2, Н-4 Fur); 6.04 (1Н, dd, J = 6.0, J = 1.3, Н-3 Fur);
9.53 (1Н, s, CНO). 13C NMR spectrum, δ, ppm: 21.1
(CH3); 35.2 (СH2Br); 86.3 (C-5); 95.2 (C-2); 130.0 (C-4);
131.3 (C-3); 199.7 (CHO). Mass spectrum, m/z (Irel, %):
463 [2M+Cl+H2O]– (100). Found, %: С 41.06; Н 4.38;
Br 38.91. C7H9BrO2. Calculated, %: С 41.00; Н 4.42;
Br 38.97.
(c 1.0, CHCl3), Rf 0.77 (hexane–EtOAc, 5:1). H NMR
spectrum, δ, ppm (J, Hz): 0.01 (6Н, s, 2СН3); 0.88 (9Н, s,
C(СН3)3); 1.30–1.63 (6Н, m, 2',3',4'-CН2); 1.32 (3Н, s,
СН3); 2.10 (1Н, br. s, ОН); 3.32 (1Н, dd, J = 10.1, J = 6.4,
СН2Br); 3.45 (1Н, dd, J = 10.1, J = 4.4, СН2Br); 3.46–
3.54 (1Н, m, 1'-CН); 3.55–3.66 (2Н, m, СН2О); 4.98–5.03
(1Н, m, 5-CН Fur); 5.83–5.95 (2Н, m, Н-3,4 Fur). 13C NMR
spectrum, δ, ppm: –5.3 (CH3); 18.3 (С(CH3)3); 21.3 (CH3);
22.9 (С-3'); 25.9 (CH3); 31.3, 32.7 (С-2',4'); 35.6 (СН2Br);
63.2 (СH2О); 76.9 (С-1'); 84.6 (C-5); 94.1 (C-2); 128.4
(C-4); 134.1 (C-3). Mass spectrum, m/z (Irel, %): 393
[M(79Br)+H]+ (100), 395 [M(81Br)+H]+ (100). Found, %:
С 51.96; Н 8.41; Br 20.25; Si 7.08. C17H33BrO3Si.
Calculated, %: С 51.90; Н 8.45; Br 20.31; Si 7.14.
(5-Methylfuran-2-yl)methyl-2,2-dimethylpropanoate (19)
was obtained by maintaining aldehyde 17 (0.49 g) for one
week under air atmosphere at room temperature. Yield
0.27 g (63%), oil, Rf 0.52 (hexane–EtOAc, 50:1). IR
spectrum, ν, cm‒1: 2973, 1731, 1481, 1280, 1145, 928, 787.
1H NMR spectrum, δ, ppm (J, Hz): 1.19 (9Н, s,
С(СН3)3); 2.28 (3Н, s, СН3); 4.98 (2Н, s, СН2О); 5.92 (1Н,
s, Н-4 Fur); 6.25 (1Н, s, Н-3 Fur). 13C NMR spectrum, δ,
ppm: 13.5 (CH3); 27.0 (CH3); 38.7 (C(CH3)3); 58.3
(СH2О); 106.4 (C-4); 111.1 (C-3); 148.0 (C-5); 152.8
(C-2); 178.2 (CO). Mass spectrum, m/z (Irel, %): 196.10
[M]– (100). Found, %: С 67.38; Н 8.20. С11Н16О3.
Calculated, %: С 67.32; Н 8.22.
20
Compound 22. Yield 0.17 g (17%), oil, [α]D ‒136.2°
(c 1.0, CHCl3), Rf 0.22 (hexane–EtOAc, 3:1). IR spectrum,
1
ν, cm‒1: 3420, 2928, 1355, 1054, 732. H NMR spectrum,
δ, ppm (J, Hz): 1.33 (3Н, s, СН3); 2.30 (1Н, br. s, ОН); 3.32
(1Н, dd, J = 10.2, J = 6.1, СН2Br); 3.43 (1Н, dd, J = 10.2,
J = 5.0, СН2Br); 3.48 (1Н, d, J = 11.6, СН2O); 3.52 (1Н, d,
J = 11.6, СН2О); 5.03–5.09 (1Н, m, 5-CН Fur); 5.82 (1Н,
dd, J = 6.1, J = 2.1, Н-4 Fur); 5.90 (1Н, d, J = 6.1,
Н-3 Fur). 13C NMR spectrum, δ, ppm: 23.4 (CH3); 35.7
(СH2Br); 68.4 (СН2О); 85.4 (C-5); 91.9 (C-2); 128.5 (C-4);
133.6 (C-3). Mass spectrum, m/z (Irel, %): 129.05
[M–Br+2H]+ (100). Found, %: С 40.54; Н 5.40; Br 38.53.
C7H11BrO2. Calculated, %: С 40.60; Н 5.35; Br 38.59.
(1S)-5-(t-Butyldimethylsilyloxy)-1-[(2S,5S)-2-methyl-5-
(phenylsulfonylmethyl)-2,5-dihydrofuran-2-yl]pentylace-
tate (23а) and (1S)-5-(t-butyldimethylsilyloxy)-1-[(2S,5R)-
2-methyl-5-(phenylsulfonylmethyl)-2,5-dihydrofuran-2-yl]-
pentylacetate (23b) (3:1 mixture of isomers). A solution
containing a mixture of alcohols 21а,b (0.50 g, 1.27 mmol)
in anhydrous pyridine (5 ml) was treated by the addition of
Ac2O (0.6 ml, 6.35 mmol) and a catalytic amount of
DMAP. The mixture was left overnight at room temperature,
then diluted with MeOH (5 ml) and 30 min later with 5%
НCl solution (10 ml). The aqueous layer was extracted with
EtOAc, the organic layers were combined, washed with
saturated NaCl solution and dried over anhydrous MgSO4.
The solvent was removed by evaporation at reduced
pressure, the residue was separated by column chromato-
graphy using petroleum ether – EtOAc system with
gradient from 10:1 to 3:1 as eluent. The acetates were
obtained in 0.45 g (81%) yield. The obtained acetates were
subsequently dissolved in DMF (10 ml), treated by the addition
of PhSO2Na (0.51 g, 3.10 mmol), KI (0.171 g, 1.03 mmol),
and Bu4NI (0.004 g, 0.01 mmol). The reaction mixture was
stirred while heating at 60°С over the course of 5 h. The
mixture was then diluted with water, the aqueous phase
was extracted with EtOAc, the organic layers were
(1S)-1-[(2S,5S)-5-(Bromomethyl)-2-methyl-2,5-dihydro-
furan-2-yl]-5-[(t-butyldimethylsilyl)oxy]pentan-1-ol
(21а) and (1R)-1-[(2S,5S)-5-(bromomethyl)-2-methyl-
2,5-dihydrofuran-2-yl]-5-[(t-butyldimethylsilyl)oxy]pen-
tan-1-ol (21b) (3:1 mixture of isomers) and [(2S,5S)-5-
(bromomethyl)-2-methyl-2,5-dihydrofuran-2-yl]methanol
(22). A solution of aldehyde 18 (1.00 g, 4.88 mmol) in
CH2Cl2 (30 ml) was stirred and cooled to 0°С under argon
atmosphere, then treated by slow dropise addition of TBSO
(CH2)4MgBr (20) as 0.6 M solution in THF (16.4 ml,
9.76 mmol). The reaction mixture was treated after 10 min
with 3% NH4Cl solution, the reaction products were
extracted with CH2Cl2 and the extract was dried over
anhydrous MgSO4. The solvent was evaporated at reduced
pressure, the residue was separated by column
chromatography, using petroleum ether – EtOAc system
with gradient from 10:1 to 3:1 as eluent.
20
Compound 21а. Yield 1.40 g (73%), oil, [α]D ‒80.2°
(c 1.0, CHCl3), Rf 0.73 (hexane–EtOAc, 5:1). IR spectrum,
1
ν, cm‒1: 3445, 2929, 1734, 1255, 1097, 836, 775. H NMR
spectrum, δ, ppm (J, Hz): 0.03 (6Н, s, 2СН3); 0.88 (9Н, s,
С(СН3)3); 1.25–1.42 (2Н, m, 3'-СН2); 1.35 (3Н, s, СН3);
1.47–1.65 (4Н, m, 2',4'-СН2); 2.13 (1Н, br. s, ОН); 3.32 (1Н,
dd, J = 10.1, J = 6.3, СН2Br); 3.44 (1Н, dd, J = 10.1,
J = 4.8, СН2Br); 3.49 (1Н, d, J = 10.1, 1'-СН); 3.58–3.63
(2Н, m, СН2О); 5.02–5.08 (1Н, m, 5-СН Fur); 5.86 (1Н,
dd, J = 6.1, J = 1.9, Н-4 Fur); 5.91 (1Н, d, J = 6.1, Н-3
Fur). 13C NMR spectrum, δ, ppm: ‒5.3 (CH3); 18.3
408

Chemistry of Heterocyclic Compounds 2018, 54(4), 403–410
combined, washed with saturated NaCl solution, water, and
128.5, 128.8 (C-2,3,5,6 Ph); 133.7 (C-4 Ph); 138.3
(C-1 Ph); 140.1 (C-5); 153.6 (C-2). Mass spectrum, m/z
(Irel, %): 236 [M]– (100). Found, %: С 60.93; Н 5.15;
S 13.53. С12Н12О3S. Calculated, %: С 61.00; Н 5.12; S 13.57.
Compound 26. Yield 0.061 g (70%). The spectral
characteristics of compound 26 were identical to those
reported in the literature.18
dried over anhydrous MgSO4. The solvent was removed by
evaporation at reduced pressure, the residue was separated
by column chromatography, using petroleum ether –
EtOAc system with gradient from 5:1 to 2:1 as eluent. The
overall yield was 0.45 g (88%).
Mixture of compounds 23a,b. Oil, Rf 0.5 (hexane–
EtOAc, 3:1). IR spectrum, ν, cm–1: 2930, 1742, 1237, 1096,
837, 775. Mass spectrum, m/z (Irel, %): 497 [M+H]+ (100).
Found, %: С 60.56; Н 8.16; S 6.32, Si 5.54. С25Н40О6SSi.
Calculated, %: С 60.45; Н 8.12; S 6.45, Si 5.65.
Methyl (2S,5S)-2-methyl-5-{[(2,2-dimethylpropanoyl)-
oxy]methyl}-2,5-dihydrofuran-2-carboxylate (27).
A
solution of aldehyde 17 (0.500 g, 1.58 mmol) in 3:1
mixture of MeOH‒Н2О (10 ml) was cooled to 0°С and
treated by the addition of DMSO (1.11 ml, 15.80 mmol),
80% NaClO2 (0.715 g, 6.32 mmol), and NaH2PO4·2Н2О
(0.739 g, 4.74 mmol). The reaction mixture was stirred at
0°С for 1 h, then treated with Na2SO3 (0.610 g, 4.74 mmol)
and further stirred for 10 min. The mixture was then diluted
with acetone (30 ml), the precipitate was collected by
filtration, washed with acetone, and the filtrate was
evaporated at reduced pressure. The obtained crude acid
was further dissolved in anhydrous MeCN (10 ml), then
treated at room temperature by the addition of MeI (0.6 ml,
9.48 mmol) and heat-dried K2CO3 (0.65 g, 4.74 mmol).
The reaction mixture was filtered after 5 h and the solids
were washed with Еt2O. The combined organic layers were
evaporated at reduced pressure, the residue was separated by
column chromatography, using petroleum ether – EtOAc
system with gradient from 10:1 to 3:1 as eluent. Yield
Compound 23а (from mixture with compound 23b).
1H NMR spectrum, δ, ppm (J, Hz): 0.00 (6Н, s, СН3); 0.84
(9Н, s, СН3); 1.13 (3Н, s, СН3); 1.20–1.65 (6Н, m,
2',3',4'-CН2); 2.00 (3Н, s, СН3); 3.19 (1Н, dd, J = 14.3,
J = 6.8, СН2S); 3.38 (1Н, dd, J = 14.3, J = 6.0, СН2S);
3.48–3.58 (2Н, m, 5'-CН2); 4.74–4.98 (1Н, m, 1'-CН); 5.15–
5.20 (1Н, m, Н-5 Fur); 5.73 (1Н, dd, J = 6.1, J = 2.1,
Н-4 Fur); 5.86 (1Н, d, J = 6.1, Н-3 Fur); 7.43–7.92 (5Н, m,
Н Ph). 13C NMR spectrum, δ, ppm: –5.36 (CH3); 18.29
(СCH3); 20.95 (CH3); 21.95 (CH3); 22.29 (С-3'); 25.88
(CH3); 29.52 (С-2'); 32.43 (С-4'); 61.49 (СН2S); 62.76
(СH2О); 76.81 (С-1'); 79.44 (C-5); 91.71 (C-2); 127.69
(C-2,6 Ph); 128.19 (C-3,5 Ph); 129.05 (C-4); 129.18 (C-4 Ph);
133.40 (C-1 Ph); 133.63 (C-3); 170.36 (СО).
Compound 23b (from mixture with compound 23а).
1H NMR spectrum, δ, ppm (J, Hz): 0.00 (6Н, s, СН3); 0.84
(9Н, s, СН3); 1.15 (3Н, s, СН3); 1.20–1.65 (6Н, m,
2',3',4'-CН2); 1.99 (3Н, s, СН3); 3.10–3.20 (1Н, m, СН2S);
3.48–3.58 (1Н, m, CН2S); 3.52–3.63 (2Н, m, 5'-CН2); 4.61–
4.65 (1Н, m, 1'-CН); 5.08–5.12 (1Н, m, Н-5 Fur); 5.65–
5.68 (1Н, m, Н-4 Fur); 5.81–5.84 (1Н, m, Н-3 Fur); 7.43–
7.92 (5Н, m, Н Ph). 13C NMR spectrum, δ, ppm: –5.33
(CH3); 18.29 (СCH3); 21.01 (CH3); 22.08 (CH3); 22.16
(С-3'); 25.88 (CH3); 29.16 (С-2'); 32.14 (С-4'); 61.94
(СН2S); 62.80 (СH2О); 77.11 (С-1'); 80.41 (C-5); 95.34
(C-2); 126.28 (C-2,6 Ph); 129.02 (C-4); 128.21 (C-3,5 Ph);
129.09 (C-4 Ph); 132.84 (C-3); 133.78 (C-1 Ph); 171.12
(СО).
20
0.396 g (70%), oil, [α]D ‒167° (c 1.0, CHCl3), Rf 0.34
(hexane–EtOAc, 5:1). IR spectrum, ν, cm‒1: 2954, 2921,
1
1730, 1457, 1281, 1154, 1108, 762. H NMR spectrum,
δ, ppm (J, Hz): 1.17 (9Н, s, C(СН3)3); 1.55 (3Н, s, СН3);
3.69 (3Н, s, OСН3); 4.06 (1Н, dd, J = 11.9, J = 3.8,
СН2O); 4.30 (1Н, dd, J = 11.8, J = 3.8, СН2O); 5.11–5.16
(1Н, m, 5-CH); 5.82 (1Н, d, J = 6.0, Н-3 Fur); 5.88 (1Н,
dd, J = 6.0, J =2.3, Н-4 Fur). 13C NMR spectrum, δ, ppm:
24.7 (CH3); 27.2 (CH3); 29.6 (C(CH3)3); 52.3 (CH3); 65.1
(СH2O); 85.2 (C-5); 87.4 (C-2); 128.3 (C-3); 131.9 (C-4);
173.4 (CO); 178.3 (CO). Mass spectrum, m/z (Irel, %): 256
[M]+ (100). Found, %: С 60.98; Н 7.93. С13Н20О5.
Calculated, %: С 60.92; Н 7.87.
2-Methyl-5-[(phenylsulfonyl)methyl]furan (25) and
5-[(t-butyldimethylsilyl)oxy]pentanal (26). A solution of
the acetate 23a,b (0.200 g, 0.40 mmol) in MeOH (5 ml)
was cooled to 0°С and treated by the addition of MeONa
(0.044 g, 0.80 mmol). The reaction mixture was stirred at
room temperature for 1 h, then neutralized with AcOH,
diluted with EtOAc (30 ml), the precipitate was collected
by filtration and washed with EtOAc. The filtrate was
evaporated at reduced pressure. The hydrolysis product
underwent fragmentation during the chromatographic
separation using 5:1 petroleum ether – EtOAc as eluent,
resulting in the isolation of furan 25 and aldehyde 26.
Methyl (2S,5S)-5-(bromomethyl)-2-methyl-2,5-dihydro-
furan-2-carboxylate (28) was obtained analogously from
aldehyde 18 (0.90 g, 4.39 mmol). Yield 0.85 g (82%), oil,
[α]D20 ‒239° (c 1.0, CHCl3), Rf 0.21 (hexane–EtOAc, 10:1).
IR spectrum, ν, cm‒1: 2954, 1734, 1263, 1116, 1019, 773.
1H NMR spectrum, δ, ppm (J, Hz): 1.57 (3Н, s, СН3); 3.35
(1Н, dd, J = 10.4, J = 6.1, СН2Br); 3.49 (1Н, dd, J = 10.4,
J = 3.9, СН2Br); 3.69 (3Н, s, OСН3); 5.15–5.21 (1Н, m,
5-CН Fur); 5.90 (1Н, d, J = 6.0, Н-3 Fur); 5.95 (1Н, dd,
J = 6.0, J =1.3, Н-4 Fur). 13C NMR spectrum, δ, ppm: 24.6
(CH3); 34.8 (СH2Br); 52.4 (OCH3); 85.6 (C-5); 90.9 (C-2);
129.4 (C-4); 132.3 (C-3); 173.1 (CO). Mass spectrum, m/z
(Irel, %): 234 [M(79Br)]+ (100), 236 [M(81Br)]+ (100).
Found, %: С 40.82; Н 4.78; Br 34.03. С8Н11BrО3.
Calculated, %: С 40.88; Н 4.72; Br 33.99.
Compound 25. Yield 0.085 g (89%), oil, Rf 0.55
(hexane–EtOAc, 3:1). IR spectrum, ν, cm‒1: 3134, 2975,
1
2855, 1445, 1150, 1020, 765. H NMR spectrum, δ, ppm
(J, Hz): 2.10 (3Н, s, СН3); 4.32 (2Н, s, СН2); 5.87 (1Н, d,
J = 3.0, Н-3); 6.11 (1Н, d, J = 6.0, J = 1.3, Н-4); 7.48 (2Н,
dd, J = 7.8, J = 7.5, Н-3,5 Ph); 7.61 (2Н, d, J = 7.5, Н-2,6 Ph);
7.71 (1Н, dd, J = 7.8, J = 7.5, Н-4 Ph). 13C NMR spectrum,
δ, ppm: 13.4 (CH3); 56.1 (СH2S); 107.1 (C-3); 113.0 (C-4);
Methyl (2S,5R)-5-(hydroxymethyl)-2-methyl-5-methoxy-
2,5-dihydrofuran-2-carboxylate (30а) and methyl
(2S,5S)-5-(hydroxymethyl)-2-methyl-5-methoxy-2,5-di-
hydrofuran-2-carboxylate (30b). A mixture of bromide
409

Chemistry of Heterocyclic Compounds 2018, 54(4), 403–410
28 (0.400 g, 1.70 mmol) and DBU (0.780 g, 5.10 mmol) in
Spectral analyses were performed on the equipment of
Collective Use Center ''Chemistry'' at the Ufa Institute of
Chemistry, Ufa Research Center of the Russian Academy of
Sciences.
anhydrous benzene (10 ml) was refluxed under argon
atmosphere for 3 h. Benzene was then removed by
evaporation at reduced pressure, the residue was dissolved
in МеОН, the reaction mixture was cooled to 0°С and
treated with MCPBA (0.290 g, 1.70 mmol) for 10 min. The
reaction mixture was then quenched with saturated Na2SO3
solution (10 ml). The aqueous phase was extracted with
EtOAc, the organic layers were combined, washed with
saturated NaCl solution, and dried over anhydrous MgSO4.
The solvent was removed by distillation at reduced
pressure and the residue was separated by column
chromatography using petroleum ether – EtOAc system
with gradient from 3:1 to 1:1 as eluent.
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Chem. 2015, 51, 1408. [Zh. Org. Khim. 2015, 51, 1440.]
7. (a) Sharipov, B. T.; Pershin, A. A.; Valeev, F. A. Mendeleev
Commun. 2017, 27, 119. (b) Sharipov, B. T.; Pershin, A. A.;
Salikhov, Sh. M.; Valeev, F. A. Russ. J. Org. Chem. 2016, 52,
721. [Zh. Org. Khim. 2016, 52, 732.]
Compound 30а. Yield 0.140 g (41%), oil, [α]D20 ‒84.9°
(c 1.0, CHCl3), Rf 0.45 (hexane–EtOAc, 1:1). IR spectrum,
1
ν, cm‒1: 2958, 1733, 1263, 1116, 1010, 773. H NMR
spectrum, δ, ppm (J, Hz): 1.66 (3Н, s, СН3); 3.21 (3Н, s,
ОСН3); 3.65 (1Н, d, J = 11.7, СН2О); 3.77 (1Н, d,
J = 11.7, СН2О); 3.76 (3Н, s, ОСН3); 5.73 (1Н, d, J = 5.8,
Н-3); 6.17 (1Н, d, J = 5.8, Н-4). 13C NMR spectrum,
δ, ppm: 23.1 (CH3); 50.3 (CH3); 53.2 (CH3); 65.9 (СH2О);
89.2 (C-2); 117.1 (C-5); 128.2 (C-4); 135.6 (C-3); 174.2
(CO). Mass spectrum, m/z (Irel, %): 202 [M]+ (100).
Found, %: С 53.46; Н 7.04. С9Н14О5. Calculated, %:
С 53.46; Н 6.98.
8. D'Ambrosio, M.; Guerriero, A.; Pietra, F. Helv. Chem. Acta
1988, 71, 964.
9. Chandrasekhar, S.; Narsihmulu, Ch.; Jagadeshwar, V.;
Shameem, S. ARKIVOC 2005, (iii), 92.
Compound 30b. Yield 0.096 g (28%), oil. [α]D20 ‒51.4°
(c 1.0, CHCl3). Rf 0.4 (hexane–EtOAc, 1:1). IR spectrum,
1
ν, cm‒1: 2958, 1730, 1263, 1116, 1010, 773. H NMR
10. Krohn, K.; Heins, H. J. Carbohydr. Chem. 1991, 10, 917.
11. Clarke, P. A.; Cridland, A. P. Org. Lett. 2005, 7, 4221.
12. (a) Kim, K. H.; Lee, H. S.; Kim, S. H.; Lee, K. Y.; Lee, J.-E.;
Kim, J. N. Bull. Korean Chem. Soc. 2009, 30, 1012. (b) Jahn, U.;
Rudakov, D.; Jones, P. G. Tetrahedron 2012, 68, 447.
(c) Lourie, L. F.; Serguchev, Y. A.; Ponomarenko, M. V.;
Rusanov, E. B.; Vovk, M. V.; Ignat'ev, N. V. Tetrahedron
2013, 69, 833.
spectrum, δ, ppm (J, Hz): 1.53 (3Н, s, СН3); 3.17 (3Н, s,
ОСН3); 3.56 (1Н, d, J = 11.6, СН2О); 3.71 (1Н, d,
J = 11.6, СН2О); 3.75 (3Н, s, ОСН3); 5.79 (1Н, d, J = 5.8,
Н-3); 6.30 (1Н, d, J = 5.8, Н-4). 13C NMR spectrum,
δ, ppm: 25.6 (CH3); 50.4 (CH3); 53.2 (CH3); 66.8 (СH2О);
89.4 (C-2); 115.0 (C-5); 127.2 (C-4); 136.3 (C-3); 172.2
(CO). Mass spectrum, m/z (Irel, %): 202 [M]+ (100).
Found, %: С 53.49; Н 7.02. С9Н14О5. Calculated, %:
С 53.46; Н 6.98.
13. Xu, Q.; Weeresakare, M.; Rainier, J. D. Tetrahedron 2001, 57,
8029.
14. (a) Gao, X.; Harmata, M. Tetrahedron 2013, 69, 7675.
(b) Mann, J.; Wilde, P. D.; Finch, M. W. Tetrahedron 1987,
43, 5431.
Supplementary information file containing NMR spectra
of all synthesized compounds is available at the journal
website at http://link.springer.com/journal/10593.
15. (a) Araújo, N.; Gil, M. V.; Román, E.; Serrano, J. A.
Tetrahedron: Asymmetry 2009, 20, 1999. (b) McNally, J. J.;
Press, J. B. J. Org. Chem. 1991, 56, 245.
16. Wu, Y.-K.; Dunbar, C. R.; McDonald, R.; Ferguson, M. J.;
West, F. G. J. Am. Chem. Soc. 2014, 136, 14903.
This work was performed according to State contract
(АААА-А17-117011910022-5) and with financial support
from the Russian Foundation for Basic Research (grant 17-
43-020166 r_a) and the President of Russian Federation
award for young scientists (SP-1934.2015.4).
17. Gelman, N. E. Methods of Quantitative Organic Elemental
Microanalysis [in Russian]; Khimiya: Moscow, 1987, p. 165.
18. (a) Wohland, M.; Maier M. E. Synlett 2011, 1523. (b) Evans, D. M.;
Murphy, P. J. Chem. Commun. 2011, 47, 3225.
410